StemCell Therapy

Historically, most large-scale immunogenomic studies those exploring the association between genes and disease were conducted with a bias toward individuals of European ancestry. Corey T. Watson, assistant professor in the University of Louisville Department of Biochemistry and Molecular Genetics, is leading a call to actively diversify the genetic resources he and fellow immunogenomics researchers use in their work to advance genomic medicine more equitably.

Watson, along with UofL post-doctoral fellow Oscar Rodriguez, and visiting fellow Yana Safonova, are part of an international group of researchers who say the narrow studies limit their ability to identify variation in human adaptive immune responses across populations.

We need to better understand how genetics influences immune system function by studying population cohorts that better represent the diversity observed across the globe if we are to fully understand disease susceptibility, as well as design more tailored treatments and preventative measures, Watson said.

In an article published in Nature Methods, Diversity in immunogenomics: the value and the challenge, the group advocates for resources used in immunogenomics research to actively include and specifically identify additional populations and minority groups. They say such diversity will make their research more relevant and help in understanding population and ancestry-specific gene-associated disease, leading to improvements in patient care.

As scientists, we have a say in which populations are investigated. Therefore, it is critical for us to be actively inclusive of individuals representative of the world we live in. This is especially critical for genes that are as diverse and clinically relevant as those that encode antibodies and T cell receptors, Rodriguez said.

Watsons research focuses on immune function and molecular genetics. His team is studying a specific area of the genetic code that controls antibody function to better understand how differences in an individuals genes determine their susceptibility to certain diseases or immune responses to vaccines.

In collaboration with Melissa Smith, assistant professor in the Department of Biochemistry and Molecular Genetics, the team is conducting the largest sequencing efforts of the antibody gene regions in humans and in animal models, Watson said.

Specifically in humans, we are working to build catalogs of genetic variation in samples from multiple ethnic backgrounds and are engaged in projects that seek to understand how this genetic variation influences the immune response in infection, vaccination and other disease contexts, he said.

Watson is involved in efforts to improve the resources and data standards for antibody and T cell receptor genes for immunogenomics researchers around the world.

The article in Nature Methods was co-authored by researchers from the United States, Canada, Norway, France, Sweden, the United Kingdom, Russia, Saudi Arabia, Israel, South Africa, Nigeria, Chile, Peru, China, Japan, Taiwan and French Polynesia with expertise in biomedical and translational research, population and public health genetics, health disparities and computational biology as well as immunogenomics.

Continued here:
UofL researchers lead the call to increase genetic diversity in immunogenomics - uoflnews.com

NEW YORK Foundation Medicine and Flatiron Health announced this week that Foundations comprehensive genomic profiling tests will be available to order through Flatiron's OncoEMR platform. The integration will allow clinicians to electronically order, track, and receive Foundations test through OncoEMR, the companies said. Both Flatiron and Foundation are planning further integrations with the others comprehensive genomic profiling tests and electronic medical record systems, respectively.

Myriad Genetics this week said it has completed the sale of its Myriad RBM unit which specializes in providing laboratory research services to pharmaceutical companies to IQVIA subsidiary Q2 Solutions. When Myriad announced its intent to sell this business unit in May, it did not disclose the deal's financial details.

GenetronHealth said this week that it has entered a new partnership with the World Economic Forum under its Health and Healthcare Platform, where it is contributing its research insights, technologies, and industry experience. The platform's overall goal is to ensure worldwide equal access to the highest standards of health and healthcare.Genetroniscurrentlyparticipating in a sub-project,dubbedMoving Genomics to the Clinic, which seeks to promote the use of genetic testing in routine clinical practices by proving its utility and efficacy.

AccessHope, a City of Hope subsidiary, said this week that it has partnered with the Dana-Farber Cancer Institute to bring the latest cancer care expertise to patients and oncologists in the community. By partnering withAccessHope, Dana-Farber's experts will support oncologistswiththe latest advances in oncology,includingpersonalized treatments, clinical trials, promising investigational medications, and molecular testing. Patients in Massachusetts, Maine, New Hampshire, Vermont, Connecticut, Rhode Island, New York,and New Jersey, as well asthosein other parts of the country,can access these services through their employee benefits programs. City of Hope and Northwestern University's Robert H. Lurie Comprehensive Cancer Center are also foundational members ofAccessHope.

Molecular breath analysis startup Deep Breath Intelligencesaid this week that it has entered a collaboration with Lwenstein Medical, a sleep and respiratory medicine firm based inRheinland-Pfalz, Germany.Rotkreuz, Switzerland-based DBI said that it is applying artificial intelligence to identify breath biomarkers related to obstructive sleep apnea syndrome. DBIsaid ithas initiated a study on OSASin collaboration with Lwenstein Medical,using participantsbreath samples and applying DBIs patterned analytical algorithms to provide results.

Enable Biosciences said this week it is partnering with the California Department of Public Health to survey state residents for the presence of antibodies against SARS-CoV-2. As part of the program, more than 200,000 households in California will be invited to submit dried blood samples collected at home using kits developed by Enable Bio andtheCDPH. The samples will then be tested by Enable Bio for the presence of antibodies against SARS-CoV-2 to distinguish antibody response fromviralinfection versusresponse fromvaccination. Test results will provide information about the spread of COVID-19 in California and the uptake of vaccines for the disease, South San Francisco, California-based Enable Bio said. The project is a collaboration betweenthe company,theCDPH, Stanford University, and Gauss Surgical. The first survey period concluded June 15 with the second and third enrollment periods slated tobeginat the start of 2022.

NeoGensaid this week that it has extended itsglobalanimal genomicspartnership withGencove. Thepartnership allowsNeoGento offerGencove'sSkimSeeklow-pass sequencing technology to customers in the agricultural sector, including those in the bovine, canine,poultry, and swine industries. UsingGencove'ssequencingimputationplatform,NeoGensaid it can deliver increased genomics data with improved accuracy and flexibility.

Bioceptsaid this week ithas been added to the Russell Microcap Index. Michael Nall, Biocept's president and CEO,called the nodexceptionally exciting, as a driver ofawarenessfor the cancer liquid biopsy firm within thelargerglobal investment community.

Immunoviasaid this week that its American subsidiary hasreceived a CLIA Certificate of Registration,which isan important step in the accreditation of its laboratory in Marlborough, Massachusetts, and a prerequisite to receiving clinical laboratory licensure fromtheMassachusetts Department of Public Health. Clinical laboratory licensure is required beforeImmunoviacan begin testing patients with itsImmrayPanCan-d test, the firm said.According to the Centers for Medicare and Medicaid Services, a Certificate of Registration allows a laboratory toconduct moderate and/or high complexity testing until it is inspected to determine its compliance with the CLIA regulations.

In Brief This Week is a selection of news items that may be of interest to our readers but had not previously appeared onGenomeWeb.

Original post:
In Brief This Week: Foundation Medicine, Myriad Genetics, Genetron Health, and More - GenomeWeb

Flies have discriminating taste. Like a gourmet perusing a menu, they spend much of their time seeking sweet nutritious calories and avoiding bitter, potentially toxic food. But what happens in their brains when they make these food choices?

Yale researchers discovered an interesting way to find out. They tricked them.

In a study that could also help illuminate how people make food choices, the researchers gave hungry fruit flies the choice between sweet, nutritious food laced with bitter quinine and a less sweet, but not bitter, food containing fewer calories. Then, using neuroimaging, they tracked neural activity in their brains as they made these tough choices.

So which won? Calories or better taste?

It depends on how hungry they are, said Michael Nitabach,professor of cellular and molecular physiology, genetics, and neuroscience at Yale School of Medicine and senior author of the study.The hungrier they are, the more likely they will tolerate bitter taste to obtain more calories.

But the real answer to how flies make these decisions is a little more complex, according to the study published July 5 in the journal Nature Communications.

According to the research team, led by Preeti Sareen, associate research scientist at Yale, flies relay sensory information to a portion of their brain called the fan-shaped body, where signals are integrated, triggering what amounts to the insect version of an executive decision. The researchers found that patterns of neuronal activity in the fan-shaped body change adaptively when novel food choices are introduced, which dictates the flys decision over what food to eat.

But researchers went a step further. And things got even stranger. They found they could change a flys choice by manipulating neurons in areas of the brain that feed into the fan-shaped body. For example, when they caused a decrease in activity in the neurons involved in metabolism, they found that it made hungry flies choose the lower calorie food.

It is one big feedback loop, not just top-down decision making, Nitabach said.

And this is where there are connections to food choices of humans, he said. Neural activity in both a flys brain and a humans brain are regulated by the secretion of neuropeptides and the neurotransmitter dopamine, which in humans helps regulate sensations of reward. Changes in this network may alter how the brain responds to different types of food. In other words, neurochemistry may sometimes dictate food choices we think we are making consciously.

The study provides a template to understand how it is that things like hunger and internal emotional states influence our behavior, Nitabach said.

Sareen and Li Yan McCurdy, a graduate student at Yale School of Medicine, are co-authors of the paper.

Read more from the original source:
More filling? Tastes great? How flies, and maybe people, choose their food - Yale News

Introduction

Fragile X syndrome (FXS), OMIM # 300624, is a X-linked inherited genetic disease classified as a triplet repeat condition. FXS is the most common cause of inherited intellectual disability and autism in the world. It has a prevalence of 1 in 5000 men and 1 in 8000 women. Affected individuals are characterized by intellectual disability, autism, language deficit, typical facies, and macroorchidism.1,2

Alterations in the FMR1 gene with locus Xq27.3 are causative of Fragile X Syndrome and other disorders. This gene harbors a CGG repeat within the 5 untranslated region and, depending on the number of repetitions, 4 types of alleles are defined with different clinical manifestations:3 Normal alleles, which have up to 44 CGG repeats; grey zone or intermediate alleles that contain between 45 and 54 repeats; premutation (PM) alleles with between 55 and 200 repeats; and full mutation (FM) alleles, with more than 200 repeats. In most cases, this is due to an expansion of the CGG triplet from one generation to the next.4

The Fragile Mental Retardation Protein (FMRP) is coded by the FMR1 gene. The absence of FMRP expression is usually secondary to the methylation of the FMR1 gene that occurs when more than 200 CGG repeats are present in the 5UTR region; this can also be explained by a point mutation in the coding region for FMR1 or a deletion that includes this gene, but these changes have only been reported in a few cases. The absence of FMRP is related to the classic FXS phenotype.5,6

FMRP expression is slightly lower in the carriers of a PM allele. Lower levels of FMRP are found particularly in the upper premutation (PM) range however, they typically do not present the classic FXS syndrome phenotype.7 Furthermore, they have elevated FMR1 mRNA levels between 2 to 8 times normal levels, which also leads to RNA toxicity. These elevated levels of mRNA are a risk for a number of medical conditions that are not explained by decreased FMRP.2,4,8

FMRP has roles in chromatin dynamics, RNA binding, mRNA transport, and mRNA translation9,10 and for certain subgroups of cerebral transcripts.11

This protein is involved in the regulation of RNA stability, subcellular transport and translation of neural mRNAs that codify proteins involved in synapsis development, neural plasticity and brain development.8

In addition, FMRP interacts with at least 180 proteins expressed in the brain and connective tissue. This interactome comprises known FMRP-binding proteins, including the ribosomal proteins FXR1P, NUFIP2, Caprin-1, and other novel FMRP-interacting candidate proteins located in different subcellular compartments, including CARF, LARP1, LEO1, NOG2, G3BP1, NONO, NPM1, SKIP, SND1, SQSTM1 and TRIM28. This interactome suggests that, besides its known functions, FMRP is involved in transcription, RNA metabolism, ribonucleoprotein stress granule formation, translation, DNA damage response, chromatin dynamics, cell cycle regulation, ribosome biogenesis, miRNA biogenesis and mitochondrial organization.9

Several studies have shown that in the absence of FMRP, a wide range of neural mRNAs are affected, boosting neural protein synthesis, which results in dendritic spine dysmorphogenesis and glutamate/GABA imbalance, which in turn produce variations in neural excitation/inhibition, phenomena that are present in FXS. Dendritic spine dysmorphogenesis plays a role in the intellectual deficits and behavioral problems, due to the weak synaptic connections found in this syndrome.12,13

Fragile X syndrome (FXS) has incomplete penetrance and variable expressivity and biological sex is a decisive factor of the phenotype. Full mutation of the FMR1 gene has a 100% penetrance of intellectual disability in males and 60% in females. Other characteristics associated with FXS Appear with varying frequencies in affected individuals. Autism spectrum disorder (ASD) symptoms appear during early childhood in 50% to 60% of males and 20% of females with FXS.1417

Physical features include elongated face, large and prominent ears (7578% of affected males), mandibular prognathism (80% of adult men), hyperlaxity and macroorchidism (95% of adult men). Other characteristics also vary in their frequency of presentation: seizures (23%), strabismus (8%), and cardiac abnormalities such as abnormal aortic root dimensions (18%) and mitral valve prolapse (55%). In general, the female phenotype is less severe and less specific.4,18

The variation in the phenotype of monogenic diseases is common,19,20 it is explained by a combination of genetic, environmental, and lifestyle factors,21 and FXS is not an exception.

Here, we present a review of the knowledge about the molecular factors involved in the variable expressivity of FXS.

The presence of a full mutation in FMR1 is associated with the hypermethylation of a CpG island located in the promoter of the FMR1 gene. Methylation of DNA regions (mDNA) is one of the main epigenetic modifications related to transcription regulation.22 A CpG island is located proximal to the CGG repeat tract, which is expanded in FXS. Hypermethylation of the CpG island generates transcriptional silencing of the FMR1 gene.23 As a consequence, the Fragile Mental Retardation Protein (FMRP), codified by the FMR1 gene, is not produced24 and in turn, the absence or low expression of FMRP causes FXS.

CGG tract repetition expansion in the untranslated region (UTR) of exon 1 in the FMR1 gene generates instability of that region during the replication process, inducing size mosaicism, which is defined as the presence of premutation and mutation alleles in several cells.25

In males with FXS caused by full mutation, the detection of FMR1 mRNA levels in peripheral blood lymphocytes is common. This phenomenon is due to both size mosaicism and mDNA in the CpG island and nearby regions that vary between cells and tissues.26 Furthermore, longitudinal studies in women with FXS have shown that levels of mRNA transcribed from FMR1 decrease significantly with age.23 Complicating even more the behavior of mDNA and FXS, it has been found that in premutation alleles, a considerable number of cells have mDNA.27 The variation between methylation states of the CpG island and nearby regions among different cells and tissue of the same person is known as methylation mosaicism.28 It is estimated that around 50% of people with FXS have this type of mosaicism.29 In cells where mutated alleles are not methylated, they are transcriptionally active and can be expressed.30 However, in these cells there is no FMRP synthesis since mRNA with CGG expansion greater than 200 repeats is not translated efficiently in ribosomes.31,32

The absence or low levels of FMRP is a decisive factor for FXS development, as several studies have aimed to discover the relationship between protein levels and phenotypic characteristics of the patients. Since the late 1990s, correlations between FMRP levels and the neurological phenotype of FXS have been established.29,33,34 The first studies about this topic established the standard levels of FMRP in peripheral blood leucocytes through immunoblotting. When comparing protein levels with the allele type and the presence of size mosaicism, it was demonstrated that people with the lowest FMRP levels were males with FM. Males with size mosaicism and females with FM had slightly higher levels of FMRP than males with FM.33,35,36 Via multiple regression models, it was found that FMRP levels were significantly correlated with the intelligence quotient (IQ) of the patients in the study.33 However, studies did not identify the same relation between FMRP levels and behavioral symptoms.34,37 More recent evidence supports a partial overlap between the pathogenic mechanisms that lead to FXS and ASD.38 Lower FMRP levels have been documented in samples of individuals with FXS and ASD compared to patients with FXS only.29,34 The relation between FMRP levels and IQ in males and females with different expansions in CGG repeats was studied recently.39 This last study has two important advantages compared with previous studies: firstly, the use of fluorescence resonance energy transfer (FRET), which has a higher sensibility when measuring protein levels, and also FMRP levels were measured in dermal fibroblasts. Unlike leucocytes, fibroblasts derive from the ectoderm, the same germ layer from which nervous system cells originate. Researchers found a strong and positive relation between FMRP levels and cognitive skills in patients with levels below 30% of the standard levels in controls. Interestingly, above this level, there was a higher dependence between low FMRP levels and low IQ.39

In parallel with the aforementioned studies, researchers reported the incidence of size and methylation mosaicism in cognitive impairment severity.4042 The classic definition of premutation alleles behavior as non-methylated alleles, and mutated alleles as methylated or partially methylated ones in order to categorize premutation carriers and patients with FXS has been extended progressively to include a detailed classification that takes into account the existence of size and methylation mosaicisms.

Regarding size mosaicisms, different combinations have been described, including patients with some FM cells and other cells with PM. Indeed, patients with FM, PM, grey zone alleles and even alleles with normal size have been reported.40 The presence of size mosaicisms with PM and FM alleles is related with a less severe phenotype and a higher risk of developing fragile X-associated tremor/ataxia syndrome (FXTAS).43

When exploring the possible relation between size mosaicisms and the intellectual functioning of patients with FXS disregarding sex, it was found that patients with FM/PM had better intellectual functioning and less maladaptive behavior, compared with FM-affected individuals.42 Interestingly, the same study found that ASD features and maladaptive behaviors were similar between FM-only and PM/FM mosaics within each sex, after controlling for overall intellectual functioning. A limitation of this study is that they used venous blood and real time PCR and Southern blot analysis to quantify the level of methylation.

Recently, methylation mosaicism has been taken into account as an important variable in phenotype traits. The most frequent mosaicism found in males is the presence of FM-methylated alleles and non-methylated FM and PM alleles (combination of size and methylation mosaicism).25,44 However, in patients with FM and not PM mosaicisms, methylated alleles do not express mRNA, while non-methylated alleles do. An aspect that highlights the importance of detecting the presence of this kind of mosaicism is the influence on phenotype severity. Additionally, according to some case reports, the presence of synthesized mRNA from PM and FM alleles increases the odds of developing the FXTAS phenotype.45,46 The final consequence of methylation mosaicism is the cells reduced ability to express FMR1 mRNA, measure mRNA and determine if there is a relation with phenotypic traits. When analyzing mRNA levels between males and females, it was found that females had higher levels. Also, in females, higher levels of FMR1 mRNA were related positively with age but not with intellectual functioning and autistic features. Males with FM that express FMR1 mRNA had significantly higher ADOS calibrated severity scores, when compared with males with fully methylated FM. Interestingly, no differences were found regarding intellectual functioning.41 Likewise, when contrasting FMR1 mRNA levels and scores on the Aberrant Behavior Checklist-Community-FXS version (ABC-CfX) it was found that in males with FM, higher values of FMR1 mRNA were related with elevated irritability and lower health-related quality of life scores.47 This association was not found in males with PM/FM, suggesting that for improved genotype/phenotype associations, it is essential to take into consideration not only sex but also size and methylation mosaicism.

Recent investigations explored simultaneously how FMR1 mRNA levels of FMRP are related to phenotypic alterations in males with PM and FM.48 In a study composed of 14 cases of patients with PM or PM and FM mosaicism and mental illnesses such as bipolar disorder, schizophrenia and psychosis, among others, low levels of FMRP and increased FMR1 mRNA were evident in these patients. This combination of characteristics in patients with FM, decreased FMRP, PM and increased FMR1 mRNA represents a dual mechanism of clinical significance that may generate characteristics of both FXS and FXTAS.48 In a clinic-based ascertained group of patients with FXS of both gender, a significant difference was found between FXS with ASD and low levels of FMRP when comparing concentrations of the protein in patients with FXS without ASD.29 They found that the mean full scale IQ and adaptive skills composite scores were significantly lower in males than in females (p = 0.016 and p = 0.001, respectively, MannWhitney). Additionally, all individuals with moderate or severe ID were males. Not surprisingly, ASD was present more frequently in males with FXS (46% vs 20% females). This association was not found in males with PM/FM, suggesting that for improved genotype/phenotype associations is essential to take into consideration not only sex but size and methylation mosaicism.29

There is a small proportion of FXS patients without expansions in the CGG-repeat tract. In this group, the condition is caused by missense or nonsense mutations,5,16 or deletions in FMR1.1,6 Patients with these mutations have similar physical, cognitive and behavioral characteristics to FXS patients. With the increasing availability of diagnostic methods based on next-generation sequencing and comparative genomic hybridization, a higher rate of diagnosis of mutations causing FMR1 function loss is expected. This will allow a clear delimitation of the phenotype caused by the loss of the protein in the absence of CGG tract expansions.

For many monogenic diseases it is known that, besides the allelic variance, the effect of modifier genes has an important role in incomplete penetrance and variable expressivity. The identification of modifier genes that affect the phenotype in monogenic diseases has many challenges that complicate their description. A genetic variant can modify the effect in the phenotype of another variant in many ways, including epistasis and genetic interactions.49,50

In studies using FXS murine models, important new evidence was acquired in order to establish the importance of potential modifier genes and their impact on FXS phenotype development. The knockout mouse model for FXS was generated in the last decade of the XX century. Fmr1 KO mice had learning deficits, abnormal synaptic connections, seizures, hyperactivity and macroorchidism.51,52 When describing the mouse phenotype in detail, it was evident that abnormal phenotypic characteristics depend, at least in some proportion, on their genetic background.53

During the identification of modifier genes in the FXS phenotype, a large proportion of the research has aimed towards the susceptibility to developing certain clinical behavioral characteristics, such as aggression, ASD and seizures.34,5459 All of the studies use a similar methodological design: they arrange groups of people with or without a specific phenotypic trait and establish the frequency of specific variants in modifier gene candidates.

The possibility that Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) gene may modulate the epilepsy phenotype in FXS patients has also been investigated. The replacement of a methionine for a valine in the 66th position of the BDNF protein interferes with normal intracellular traffic and BDNF dependent secretory activity in cortical neurons.60 This polymorphism has been related to cerebral anatomy alterations61 and neuropsychiatric disorders.62,63 In a sample of 27 males with FXS from Finland, it was found that all the patients with epilepsy (15%) had the Met66 allele, whereas the prevalence of this allele is 20% in the normal population. Research suggests that the Met66 allele in BDNF interacting with FM in FMR1 may partially explain the higher incidence of seizures in patients with FXS.56 In a more recent study with a higher number of males with FXS (77 patients), the results were not replicated and there was no association between seizures and Val66Met polymorphism.58 These results show the importance of validating studies about modifier genes in different populations.

In research about genes that affect mood and aggression, such as the serotonin transporter (5-HTTLPR), the monoamine oxidase A (MAOA-VNTR) and COMT, conflicting results were found. All of those genes are involved in regulatory pathways for different neurotransmitters, and their variants have been associated with the development of behavioral phenotypes in different contexts other than FXS. In one group of 50 males with FXS, the relationship of 5-HTTLPR and MAOA-VNTR polymorphisms with the frequency/severity of aggressive/destructive, self-injurious and stereotypic behaviors was studied. It was found that the high-transcribing long (L/L) genotype in 5-HTTLPR was related with a higher frequency of aggressive/destructive and stereotypic behavior, while patients with the short (S/S) genotype had less aggression. The MAOA-VNTR genotype had no effect on behavior.55 On the other hand, in a study of 64 males with FXS where the COMT gene was also included, the results of the previous study were not replicated. There was no association between behavioral characteristics and either 5-HTTL PR (serotonin) or MAOA genotypes. Nevertheless, the A/A genotype in COMT that modifies dopamine levels was associated with greater interest and pleasure in the environment, and with less risk of property destruction, stereotyped behavior and compulsive behavior.54 The authors of the study suggest that the non-reproducibility of the results regarding MAOA-VNTR can be explained by differences in the prevalence of aggressive and stereotyped behavior among the studied populations or by differences in the measurements used to characterize each behavior.

The importance of identifying potential modifier genes was explored in a clinical trial. The researchers investigated the relation between polymorphisms in several genes and the response of sertraline in 51 children. They found that BDNF, MAOA, 5-HTTLPR, Cytochrome P450 2C19 and 2D6 polymorphisms had significant correlations with treatment response.64

Currently the knowledge about molecular causes of the variable phenotype in patients with FXS include characteristics associated with the FMR1 gene itself and to secondary, modifying gene effects.

Regarding FMR1, when the diagnosis is established, the type of mutation causing FXS is identified: CGG repeat tract expansion vs pathological variant causing loss of function in FMR1.

When the CGG is identified, is it expected that about half of the patients have size or methylation mosaicism or both.29 The presence of any of those mosaicisms determines the expression or not of FMR1 mRNA and FMRP. The quantity of FMRP is directly related with IQ.34,37,39 While the presence of size mosaicism is related with better intellectual functioning and less maladaptive behavior,29,42 elevated concentrations of FMR1 mRNA in patients with FM have been associated with a higher risk of developing FXTAS45,46,48 and with the severity of behavioral symptoms.47

The search for modifier genes affecting the phenotype has been carried out using the candidate genes strategy. Because high impact clinical manifestations in FXS are related with neurologic phenotypes, the studied candidate genes are involved in CNS development and the appearance of seizures (BNDF)56,6062 and associated with mood and aggression (5-HTTLPR, MAOA-VNTR y COMT).54,55 Recent research has been done with small groups of patients and there are no conclusive results about the importance of these variants in modifier genes.

Scientific and clinical evidence about molecular causes of variable expressivity in FXS is growing quickly. It is evident that aspects of the mutation type in FMR1 and the behavior of the CGG repeat tract are relevant in the presentation of the condition. Research about modifier genes is still emerging. There are important limitations such as sample size and comparability of different studies, mainly due to smaller groups of selected patients and the use of different tools for measuring the phenotypes.

Independent cohorts of patients with FXS across different continents have shown evidence that mosaicism, FMR1 mRNA or FMRP quantification are associated with the severity of the phenotype. However, this information cannot currently be used effectively in the integral management of patients. When intervention strategies become available in order to prevent the development of FXTAS, or when certain molecules can regulate levels of FMRP expression to measure FMR1 mRNA and FMRP, they could be crucial for selecting patients and identifying the best therapeutic intervention.

In clinical trials there is an important window of opportunity. Identifying mosaicism, measuring transcription/translation activity of FMR1 and stratifying patients by modifier genotypes29,65 will permit the identification of subgroups of patients with greater potential to respond to specific treatments.

The authors report no conflicts of interest in this work.

1. Coffee B, Keith K, Albizua I, et al. Incidence of Fragile X syndrome by newborn screening for methylated FMR1 DNA. Am J Hum Genet. 2009;85(4):503514. doi:10.1016/j.ajhg.2009.09.007

2. Saldarriaga W, Tassone F, Gonzlez-Teshima LY, Forero-Forero JV, Ayala-Zapata S. Fragile X Syndrome. Colomb Med. 2014;190198. doi:10.25100/cm.v45i4.1810

3. Bagni C, Tassone F, Neri G, Fragile HR. X syndrome: causes, diagnosis, mechanisms, and therapeutics. J Clin Invest. 2012;122(12):43144322. doi:10.1172/JCI63141

4. Salcedo-Arellano MJ, Dufour B, McLennan Y, Martinez-Cerdeno V, Hagerman R. Fragile X syndrome and associated disorders: clinical aspects and pathology. Neurobiol Dis. 2020;136:104740. doi:10.1016/j.nbd.2020.104740

5. Sitzmann AF, Hagelstrom RT, Tassone F, Hagerman RJ, Butler MG. Rare FMR1 gene mutations causing fragile X syndrome: a review. Am J Med Genet Part A. 2018;176(1):1118. doi:10.1002/ajmg.a.38504

6. Coffee B, Ikeda M, Budimirovic DB, Hjelm LN, Kaufmann WE, Warren ST. Mosaic FMR1 deletion causes fragile X syndrome and can lead to molecular misdiagnosis: a case report and review of the literature. Am J Med Genet Part A. 2008;146A(10):13581367. doi:10.1002/ajmg.a.32261

7. Tassanakijpanich N, Hagerman RJ, Worachotekamjorn J. Fragile X premutation and associated health conditions: a review. Clin Genet. 2021;99(6):751760. doi:10.1111/cge.13924

8. Hagerman RJ, Berry-Kravis E, Hazlett HC, et al. Fragile X syndrome. Nat Rev Dis Prim. 2017. doi:10.1038/nrdp.2017.65

9. Taha MS, Haghighi F, Stefanski A, et al. Novel FMRP interaction networks linked to cellular stress. FEBS J. 2021;288(3):837860. doi:10.1111/febs.15443

10. Siomi H, Siomi MC, Nussbaum RL, Dreyfuss G. The protein product of the fragile X gene, FMR1, has characteristics of an RNA-binding protein. Cell. 1993;74(2):291298. doi:10.1016/0092-8674(93)90420-U

11. Ashley CT Jr, Wilkinson KD, Reines D, Warren ST. FMR1 protein contains conserved RNP-family domains and demonstrates selective RNA binding. Science (80-). 1993;262(5133):563566. doi:10.1126/science.7692601

12. Bear MF, Huber KM, Warren ST. The mGluR theory of fragile X mental retardation. Trends Neurosci. 2004;27(7):370377. doi:10.1016/j.tins.2004.04.009

13. Gatto CL, Broadie K. Genetic controls balancing excitatory and inhibitory synaptogenesis in neurodevelopmental disorder models. Front Synaptic Neurosci. 2010. doi:10.3389/fnsyn.2010.00004

14. Budimirovic DB, Haas-Givler B, Blitz R, et al. Consensus of the fragile X clinical and research consortium on clinical practices: autism Spectrum Disorder in Fragile X Syndrome. 2014;115.

15. Budimirovic DB, Subramanian M. Neurobiology of Autism and Intellectual Disability: fragile X Syndrome. 2 ed. In: Johnston M, Adams H, Fatemi A, editors. London: Oxford University Press;2016.doi:10.1093/med/9780199937837.001.0001

16. Saldarriaga W, Payn-Gmez C, Gonzlez-Teshima LY, Rosa L, Tassone F, Hagerman RJ. Double genetic hit: fragile X syndrome and partial deletion of protein patched homolog 1 antisense as cause of severe autism spectrum disorder. J Dev Behav Pediatr. 2020;41(9):724728. doi:10.1097/DBP.0000000000000850

17. Sherman SL, Kidd SA, Riley C, et al. Forward: a registry and longitudinal clinical database to study fragile X syndrome. Pediatrics. 2017;139(Supplement 3):S183S193. doi:10.1542/peds.2016-1159E

18. Loehr JP, Synhorst DP, Wolfe RR, Hagerman RJ. Aortic root dilatation and mitral valve prolapse in the fragile X syndrome. Am J Med Genet. 1986;23(12):189194. doi:10.1002/ajmg.1320230113

19. Rahit KMTH, Tarailo-Graovac M. Genetic modifiers and rare mendelian disease. Genes (Basel). 2020;11(3):239. doi:10.3390/genes11030239

20. Li D, Yu J, Gu F, et al. The roles of two novel FBN1 gene mutations in the genotypephenotype correlations of marfan syndrome and ectopia lentis patients with marfanoid habitus. Genet Test. 2008;12(2):325330. doi:10.1089/gte.2008.0002

21. Fahed AC, Wang M, Homburger JR, et al. Polygenic background modifies penetrance of monogenic variants for tier 1 genomic conditions. Nat Commun. 2020;11(1). doi:10.1038/s41467-020-17374-3

22. Kim M, Costello J. DNA methylation: an epigenetic mark of cellular memory. Exp Mol Med. 2017;49(4):e322e322. doi:10.1038/emm.2017.10

23. Kraan CM, Baker EK, Arpone M, et al. Dna methylation at birth predicts intellectual functioning and autism features in children with fragile x syndrome. Int J Mol Sci. 2020;21(20):7735. doi:10.3390/ijms21207735

24. Pieretti M, Zhang F, Fu YH, et al. Absence of expression of the FMR-1 gene in fragile X syndrome. Cell. 1991;66(4):817822. doi:10.1016/0092-8674(91)90125-I

25. Nolin SL, Glicksman A, Houck GE, Brown WT, Dobkin CS. Mosaicism in fragile X affected males. Am J Med Genet. 1994;51(4):509512. doi:10.1002/ajmg.1320510444

26. Stger R, Genereux DP, Hagerman RJ, Hagerman PJ, Tassone F, Laird CD. Testing the FMR1 promoter for mosaicism in dna methylation among cpg sites, strands, and cells in FMR1-expressing males with fragile x syndrome. PLoS One. 2011;6(8):e23648. doi:10.1371/journal.pone.0023648

27. Pretto DI, Mendoza-Morales G, Lo J, et al. CGG allele size somatic mosaicism and methylation in FMR1 premutation alleles. J Med Genet. 2014;51(5):309318. doi:10.1136/jmedgenet-2013-102021

28. Jiraanont P, Kumar M, Tang H-T, et al. Size and methylation mosaicism in males with Fragile X syndrome. Expert Rev Mol Diagn. 2017;17(11):10231032. doi:10.1080/14737159.2017.1377612

29. Budimirovic DB, Schlageter A, Filipovic-Sadic S, et al. A genotype-phenotype study of high-resolution FMR1 nucleic acid and protein analyses in fragile X patients with neurobehavioral assessments. Brain Sci. 2020;10(10):694. doi:10.3390/brainsci10100694

30. Tassone F, Hagerman RJ, Loesch DZ, Lachiewicz A, Taylor AK, Hagerman PJ. Fragile X males with unmethylated, full mutation trinucleotide repeat expansions have elevated levels of FMR1 messenger RNA. Am J Med Genet. 2000;94(3):232236. doi:10.1002/1096-8628(20000918)94:3<232::aid-ajmg9>3.0.CO;2-H

31. Dolskiy AA, Yarushkin AA, Grishchenko IV, et al. miRNA expression and interaction with the 3UTR of FMR1 in FRAXopathy pathogenesis. Non-Coding RNA Res. 2021;6(1):17. doi:10.1016/j.ncrna.2020.11.006

32. Primerano B, Tassone F, Hagerman RJ, Hagerman P, Amaldi F, Bagni C. Reduced FMR1 mRNA translation efficiency in fragile X patients with premutations. RNA. 2002;8(12):14821488. doi:10.1017/S1355838202020642

33. Kaufmann WE, Abrams MT, Chen W, Reiss AL. Genotype, molecular phenotype, and cognitive phenotype: correlations in fragile X syndrome. Am J Med Genet. 1999. doi:10.1002/(SICI)1096-8628(19990402)83:4<286::aid-ajmg10>3.0.CO;2-H

34. Loesch DZ, Bui QM, Dissanayake C, et al. Molecular and cognitive predictors of the continuum of autistic behaviours in fragile X. Neurosci Biobehav Rev. 2007. doi:10.1016/j.neubiorev.2006.09.007

35. Backes M, Gen B, Schreck J, Doerfler W, Lehmkuhl G, Von Gontard A. Cognitive and behavioral profile of fragile X boys: correlations to molecular data. Am J Med Genet. 2000;95(2):150156. doi:10.1002/1096-8628(20001113)95:2<50::aid-ajmg11><50::aid-ajmg11>3.0.CO;2-1

36. Tassone F, Hagerman RJ, Ikl DN, et al. FMRP expression as a potential prognostic indicator in fragile X syndrome. Am J Med Genet. 1999;84(3):250261. doi:10.1002/(SICI)1096-8628(19990528)84:3<250::aid-ajmg17>3.0.CO;2-4

37. Hall S, DeBernardis M, Reiss A. Social escape behaviors in children with fragile X syndrome. J Autism Dev Disord. 2006;36(7):935947. doi:10.1007/s10803-006-0132-z

38. Bagni C, Zukin RS, Synaptic A. Perspective of Fragile X syndrome and autism spectrum disorders. Neuron. 2019. doi:10.1016/j.neuron.2019.02.041

39. Kim K, Hessl D, Randol JL, et al. Association between IQ and FMR1 protein (FMRP) across the spectrum of CGG repeat expansions. PLoS One. 2019;14(12):e0226811. doi:10.1371/journal.pone.0226811

40. Aliaga SM, Slater HR, Francis D, et al. Identification of males with cryptic fragile x alleles by methylation-Specific quantitative melt analysis. Clin Chem. 2016;62(2):343352. doi:10.1373/clinchem.2015.244681

41. Baker EK, Arpone M, Aliaga SM, et al. Incomplete silencing of full mutation alleles in males with fragile X syndrome is associated with autistic features. Mol Autism. 2019;10(1). doi:10.1186/s13229-019-0271-7

42. Baker EK, Arpone M, Vera SA, et al. Intellectual functioning and behavioural features associated with mosaicism in fragile X syndrome. J Neurodev Disord. 2019;11(1). doi:10.1186/s11689-019-9288-7

43. Kraan CM, Godler DE, Amor DJ. Epigenetics of fragile X syndrome and fragile X-related disorders. Dev Med Child Neurol. 2019;61(2):121127. doi:10.1111/dmcn.13985

44. Rousseau F, Heitz D, Biancalana V, et al. Direct diagnosis by DNA analysis of the fragile X syndrome of mental retardation. Obstet Gynecol Surv. 1992;47(5):306308. doi:10.1097/00006254-199205000-00008

45. Loesch DZ, Sherwell S, Kinsella G, et al. Fragile X-associated tremor/ataxia phenotype in a male carrier of unmethylated full mutation in the FMR1 gene. Clin Genet. 2012;82(1):8892. doi:10.1111/j.1399-0004.2011.01675.x

46. Santa Mara L, Pugin A, Alliende MA, et al. FXTAS in an unmethylated mosaic male with fragile X syndrome from Chile. Clin Genet. 2014;86(4):378382. doi:10.1111/cge.12278

47. Baker EK, Arpone M, Kraan C, et al. FMR1 mRNA from full mutation alleles is associated with ABC-CFX scores in males with fragile X syndrome. Sci Rep. 2020;10(1). doi:10.1038/s41598-020-68465-6

48. Schneider A, Winarni TI, Cabal-Herrera AM, et al. Elevated FMR1-mRNA and lowered FMRP a double-hit mechanism for psychiatric features in men with FMR1 premutations. Transl Psychiatry. 2020;10(1). doi:10.1038/s41398-020-00863-w

49. Dipple KM, McCabe ERB. Phenotypes of patients with Simple mendelian disorders are complex traits: thresholds, modifiers, and systems dynamics. Am J Hum Genet. 2000;66(6):17291735. doi:10.1086/302938

50. Schffer AA. Digenic inheritance in medical genetics. J Med Genet. 2013;50(10):641652. doi:10.1136/jmedgenet-2013-101713

51. Mineur YS, Sluyter F, De Wit S, Oostra BA, Crusio WE. Behavioral and neuroanatomical characterization of the Fmr1 knockout mouse. Hippocampus. 2002;12(1):3946. doi:10.1002/hipo.10005

52. Bakker CE, Verheij C; The Dutch-Belgian Fragile X Consorthium, et al. Fmr1 knockout mice: a model to study fragile X mental retardation. Cell. 1994. doi:10.1016/0092-8674(94)90569-X

53. Errijgers V, Kooy RF. Genetic modifiers in mice: the example of the fragile X mouse model. Cytogenet Genome Res. 2004;105(24):448454. doi:10.1159/000078218

54. Crawford H, Scerif G, Wilde L, et al. Genetic modifiers in rare disorders: the case of fragile X syndrome. Eur J Hum Genet. 2021;29(1):173183. doi:10.1038/s41431-020-00711-x

55. Hessl D, Tassone F, Cordeiro L, et al. Brief report: aggression and stereotypic behavior in males with fragile X syndrome - Moderating secondary genes in a single gene disorder. J Autism Dev Disord. 2008;38(1):184189. doi:10.1007/s10803-007-0365-5

56. Louhivuori V, Arvio M, Soronen P, Oksanen V, Paunio T, Castrn ML. The Val66Met polymorphism in the BDNF gene is associated with epilepsy in fragile X syndrome. Epilepsy Res. 2009;85(1):114117. doi:10.1016/j.eplepsyres.2009.01.005

57. Stepniak B, Kstner A, Poggi G, et al. Accumulated common variants in the broader fragile X gene family modulate autistic phenotypes. EMBO Mol Med. 2015;7(12):15651579. doi:10.15252/emmm.201505696

58. Tondo M, Poo P, Naud M, et al. Predisposition to epilepsy in fragile X syndrome: does the Val66Met polymorphism in the BDNF gene play a role? Epilepsy Behav. 2011;22(3):581583. doi:10.1016/j.yebeh.2011.08.003

59. Wassink TH, Hazlett HC, Davis LK, Reiss AL, Piven J. Testing for association of the monoamine oxidase a promoter polymorphism with brain structure volumes in both autism and the fragile X syndrome. J Neurodev Disord. 2014;6(1). doi:10.1186/1866-1955-6-6

60. Chen ZY, Patel PD, Sant G, et al. Variant Brain-Derived Neurotrophic Factor (BDNF) (Met66) alters the intracellular trafficking and activity-dependent secretion of wild-type BDNF in neurosecretory cells and cortical neurons. J Neurosci. 2004;24(18):44014411. doi:10.1523/JNEUROSCI.0348-04.2004

61. Szeszko PR, Lipsky R, Mentschel C, et al. Brain-derived neurotrophic factor val66met polymorphism and volume of the hippocampal formation. Mol Psychiatry. 2005;10(7):631636. doi:10.1038/sj.mp.4001656

62. Chen ZY, Jing D, Bath KG, et al. Genetic variant BDNF (Val66Met) polymorphism alters anxiety-related behavior. Science (80-). 2006;314(5796):140143. doi:10.1126/science.1129663

63. Gratacs M, Gonzlez JR, Mercader JM, de Cid R, Urretavizcaya M, Estivill X. Brain-derived neurotrophic factor Val66Met and psychiatric disorders: meta-analysis of case-control studies confirm association to substance-related disorders, eating disorders, and schizophrenia. Biol Psychiatry. 2007;61(7):911922. doi:10.1016/j.biopsych.2006.08.025

See the original post here:
Genetic mapping of subsets of patients with fragile X syndro | TACG - Dove Medical Press

Danielle Lloyd recently revealed that she is expecting a baby girl after using a controversial sex-selection guide called The Babydust Method.

The mum-of-four shares Archie, 10, Harry, nine, and George, seven, with her ex-husband, footballer Jamie OHara, and Ronnie, three, with current husband Michael O'Neill.

She came across the guide, written and researched by Kathryn Taylor - who has a degree in Microbiology, Immunology, and Molecular Genetics from UCLA - and followed it in hopes of having a girl.

Danielle revealed she followed the book to a T, explaining to OK! magazine : "I tried it previously and I got pregnant but I had a miscarriage. So this time I was trying for a few months and nothing happened.

"When I got the negative result I felt really upset about it and Michael said, 'Come on, lets leave trying now and do the gender selection.'

"I had come to terms with the fact that we werent going to try any more and then two or three days later I found out I was pregnant."

The author, Kathryn, based her Babydust Method after Missionary Sister Dr Lonie McSweeney's 2011 study.

99 couples in Nigeria monitored their ovulation and then had intercourse with the exact timing and number of times placed depending on what sex they wanted their child to be.

For families that wanted a girl, sex could only happen only once, exactly two to three days before ovulation.

And if the couple wanted a boy, intercourse was meant to happen twice, as close to ovulation as possible.

Women chart their luteinising hormone twice a day and use ovulation predictor kits for three months before they want to conceive a child so that they could recognise patterns in their cycle.

The luteinising hormone surges at around day 14 in the menstrual cycle and ovulation, which is when an egg is released from the ovary.

Kathryn had taken to her Facebook to warn followers that she isn't a doctor but simply wanted to help people better understand the method.

She explained: "I have to mention, I am not a doctor, and I cannot guarantee you'll conceive the sex of your choice.

"All I can do is help you better understand how to implement the method, and give you encouragement along the way."

Do you enjoy reading about celebrities? Sign up for all the best celeb news from the Mirror here .

Doctors have been sceptical about the method, explaining how the chances of getting a boy or girl are usually 50-50.

"There are some scientific ideas on how to improve your chances to get a boy and girl," Dr. Elena Trukhacheva, President and Medical Director of Reproductive Medicine Institute in Chicago, Ill., told Refinery29.

"But in real life, its 50-50. These ideas are not going to take you farther than 50-50, and its not going to work for some couples."

It is important to note that no exact method can promise the desired results.

Do you have a story to sell? Get in touch with us at webcelebs@trinitymirror.com or call us direct 0207 29 33033.

Read the original here:
What is The Babydust Method? Danielle Lloyd swears method helped her conceive girl - The Mirror

Datar Cancer Genetics

NASHIK, India (PRWEB) July 04, 2021

"This association will assist patients within the Iylon system to avail genomic solutions offered by the Datar group. Our passion and commitment to deliver best-in-class, genomic-based personalized cancer treatment recommendations has resulted in developing an unparalleled range of blood and tissue-based diagnostics for clinicians and patients," said Dr Vineet Datta, Executive Director, Datar Cancer Genetics. "This partnership will support clinicians to interpret genomic information and facilitate personalized cancer treatment through comprehensive interrogation of cancer genomics."

Iylons clinical advisors are globally renowned experts in Precision Oncology and together with Iylons own in-house experts and Datars diagnostic tools, patients can look forward to best chance at being cancer-free.

About Iylon Precision Oncology

Iylon Precision Oncology has partnered with pioneers in the field of Oncology to review clinical and genomic information and provide individualized, evidence-based optimal treatment plan for each patient. This flagship service is geared towards top global experts in Radiology, Pathology, Molecular Oncology, Medical Oncology, and Cancer Genomics, team up to discuss and offer their recommendations. Iylons virtual consultations will provide personalized, evidence-based, optimal precision treatment recommendations for cancer patients.

About Datar Cancer Genetics

Datar Cancer Genetics is a leading cancer research corporation specializing in non-invasive techniques for better diagnosis, treatment decisions, and management of cancer. Datar Cancer Genetics has a state of art, College of American Pathologists (CAP), CLIA, ISO15189, ISO9001 and ISO27001 accredited molecular genomic facility at India with a staff strength over 250, in addition to a state-of-the-art lab facility in the United Kingdom. Our team of scientists, clinicians and experts, based out of the United Kingdom, Germany and India, help facilitate our technologies for better cancer management

Contact: Dr Vineet Datta - drvineetdatta@datarpgx.com

Website datarpgx.com

Contact: Dr. Padmaja Ganapathy - contact@iylon.com

Websitehttp://www.iylon.com

Share article on social media or email:

See more here:
Datar Cancer Genetics joins hands with US based Iylon Precision Oncology to offer personalized Precision Oncology cancer treatment solutions - PR Web

Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers. Its poor prognosis is predominantly due to the fact that most patients remain asymptomatic until the disease reaches an advanced stage, alongside the lack of early markers and screening strategies. A better understanding of PDAC risk factors is essential for the identification of groups at high risk in the population. Genome-wide association studies (GWAS) have been a powerful tool for detecting genetic variants associated with complex traits, including pancreatic cancer. By exploiting functional and GWAS data, we investigated the associations between polymorphisms affecting gene function in the pancreas (expression quantitative trait loci, eQTLs) and PDAC risk. In a two-phase approach, we analysed 13 713 PDAC cases and 43 784 controls and identified a genome-wide significant association between the A allele of the rs2035875 polymorphism and increased PDAC risk (P=7.1410 -10). This allele is known to be associated with increased expression in the pancreas of the keratin genes KRT8 and KRT18, whose increased levels have been reported to correlate with various tumor cell characteristics. Additionally, the A allele of the rs789744 variant was associated with decreased risk of developing PDAC (P=3.5610 -6). This SNP is situated in the SRGAP1 gene and the A allele is associated with higher expression of the gene, which in turn inactivates the cyclin-dependent protein 42 (CDC42) gene expression, thus decreasing the risk of PDAC. In conclusion, we present here a functional-based novel PDAC risk locus and an additional strong candidate supported by significant associations and plausible biological mechanisms. The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Read more:
Associations between pancreatic expression quantitative traits and risk of pancreatic ductal adenocarcinoma. - Physician's Weekly

"We believe CEA will be fuelled by the diversity of crops. We need to focus on products for consumers and food producers, looking forward to other stable crops we can produce. We have to break the perception of what can be grown and what cannot be grown in CEA as we believe it's the future of growing crops, sustainably and locally," says Jaime Guerrero with consultancy firm Accenture.

Last week he joined the Indoor AgTech panel on the pathway to competitive production. During the panel, it became clear that several growers are looking into ways to diversify their crops.

Unusual cropsThe panel session, lead by Jaime Guerrero with Accenture, was joined by growers, such as David Freidenberg the CEO of Saffron Tech (Israel) and David Soo the CEO of Australian Vanilla Plantation (AU), that are already growing unusual products. Also, other growers are looking to find a unique position in the market, but not specifically with rare products.

Mark Tester, Co-Founder and CSO of Red Sea Farms (UAE), said that genetics is absolutely essential in order to improve plants and make them profitable in the long run. Red Sea Farms is turning salt-tolerant plants into salt-tolerant plants crops. Currently, the company is growing tomatoes but is moving into cucumbers soon as, Mark shared.

According to Sam Norton, founder of Heron Farms (US), many CEA companies were running into the same problems in the beginning but didnt tell. "We wont be going away from leafy greens as fast as predicted, I think its leveraging the whole CEA community."

The panelists

David Soo added that when talking about rare spices, the market has to look at where the costs come through. With vanilla, its the number of crops that go into a cubic meter. Resulting in 20% more cubic meters in the Vanilla Dome Greenhouse in comparison to a regular greenhouse. "Its important to get the right yield density- and volume for each cubic meter you have to manage.

Overall, David Freidenberg thinks that its going to be a lot of AI, machine learning using data to succeed in vertical farming. We have to leverage the knowledge we have today, implementing it into this business.

Growing vanilla in a hybrid solutionDavid Soo said that "Vanilla is the second spice in the world. However, naturally grown (open field) vanilla only satisfies 2% of the world's demand." As a result of a brainstorming session during a dinner, David said to have come up with his 'Vanilla Dome greenhouse' which is a hybrid-growing solution, where high volumes of vanilla are produced.

According to David, every dome greenhouse holds 200 vines that are growing to 20m. The company targets to grow 4km of vines of which 1 tonne of beans can be yielded, two harvests a year.

Saltwater as a resourceHeron Farms is a saltwater farm, combining seawater and carbon dioxide into a useful product, helophytes. "We brought the system indoors by growing vertically, controlling the photoperiod and the salinity of the irrigation water," noted Sam Norton.

It's solving two major environmental problems; excess carbon dioxide and excess seawater. As a result of combining these, the farm has multiple outputs; food, fresh water and salt. "We're not reinventing any models, but we're following the models that have worked already," Sam affirmed.

In order for the tomato plants to grow, the salinity tolerance of plants is increased. "We're using molecular genetics, biology to accelerate salt-tolerant plants in CEA," noted Mark Tester.

At Red Sea Farms salt-tolerant tomato plants are grown in a CEA greenhouse using saltwater resources. Their produce is sold around Saudi Arabia, whereas, according to Ryan Lefers, the company is planning to expand throughout Saudi Arabia and plans to enter the UAE.

Challenging the saffron marketSaffron Tech is growing saffron in vertical farms, to challenge the traditional agriculture market. Allowing for more sustainable growth of saffron year-round at a solid price. Normally, saffron is very expensive in terms of labor and its fragility given its stems that can easily break. "We'll start to launch our first commercial vertical farm soon, ready for sales to retailers," says David Freidenberg.

The shape of the dome works more efficiently than a rectangular as there's better airflow and humidity. David Soo adds, "All we have to do is help it along with a few fans. We can grow tropical plants in subtropical areas."

For more information:

Australian Vanilla PlantationDavid Soo, CEOdsoo@vanillaplantation.com.au

AccentureJaime Guerrerowww.accenture.com

Red Sea FarmsMark Tester, Co-Founder and CSO https://redseafarms.com

SaffronTechDavid Freidenberg, CEO http://www.saffron-tech.ag

Read this article:
Mapping a pathway to competitive production - hortidaily.com - hortidaily.com

Straits Research Latest 2021 Report: The Global Genomics Report represents a comprehensive study on the Genomics industry including current trends and status.

The report can help to understand the market in-depth and strategize for business expansion accordingly in the future. In the strategic analysis process, it gives insights from marketing channel and market positioning to potential growth strategies, providing in-depth analysis for new entrants or exists competitors in the Genomics Market now and in the future.

The genomics market was valued at USD 17,500 million in 2019 and is expected to grow with a CAGR of 8.0% during the forecast period, 20202029.

Aimed to offers the most segmented consumption and sales data of downstream consumption fields and competitive landscape in various regions and countries around the globe, this report analyses the latest market data from the primary and secondary authoritative sources also.

Genomics is the science of studying an organisms genomes and its interaction with a variety of signals. The field of genomics has seen substantial growth in terms of technological advancements that have encourageda better understanding of genomes and their immediate environment and techniques.

Conventional genome editing technologies are inefficient, time-consuming, labor-intensive, and have limited capacity. However, the advent of CRISPR / Cas9 nuclease, ZFN, and TALEN gene-editing technologies is positioned to solve these issues by facilitating easy and accurate editing of genomes.

Market Key Drivers, Restraints, and Opportunities:

On the contrary, technological advancements are expected to open lucrative opportunities for the market players in the future.

Cumulative Impact of COVID-19 on Genomics Market:

COVID-19 is a unique global public health emergency that has affected almost every industry in the world, and the long-term effects are predicted to influence the industry growth during the estimated period. Our ongoing research amplifies our research framework to ensure the enclosure of underlying COVID-19 issues and potential paths forward.

The report delivers insights on COVID-19 considering the changes in consumer behavior and demand, purchasing patterns, re-routing of the supply chain, dynamics of present market forces, and the significant involvements of governments. The updated study offers market insights, industry analysis, estimations, and forecasts, considering the COVID-19 impact on the market.

Global Genomics Market is Segmented Based Segmentation and Region.

By Product- Instruments and Software, Consumables and Reagents.By Services- Core Genomics Services, DNA Sequencing services, Biomarker Translation Services, Computational Services.By Application- Functional Genomics, Mutational Analysis, Microarray Analysis, Epigenetics.By End-User- Clinical and Research Laboratories, Academics and Government Institutes, Hospitals and Clinics, Pharmaceutical and Biotechnology Companies

Reasons to Buy this Report:

Company Profiles of Genomics Market:

The report profoundly explores the recent significant developments by the leading vendors and innovation profiles in the Global Genomics Market, including 23andMe, Agilent Technologies, Thermo Fisher Scientific, Inc., Bio-Rad Laboratories, Hoffmann-La Roche Ltd., Myriad Genetics, Inc., Foundation Medicine, Inc., Danaher, Pacific Biosciences, Illumina, Inc., Stratos Genomics, Inc., Qiagen, Oxford Nanopore Technologies, BGI

Table of Contents of Genomics Market:

Study Coverage: It includes key vendors covered, key market segments, the scope of products offered in the global Flanged Heaters market, years considered, and study objectives. Additionally, it touches on the segmentation study offered in the report on the basis of the market segments.

Executive Summary: It gives an overview of key studies of industry, market growth rate, competitive landscape, key restraints, market drivers, key trends, and industry issues, swot analysis, and macroscopic indicators of the market.

Production by Region: Here, the report offers information regarding to import and export details, production, revenue, market sales, and key vendors of all regional markets studied.

Profile of Manufacturers: Every vendor profiled in this section is studied on the basis of SWOT analysis, their products, market production, value, capacity, and other vital factors.

About Us:

StraitsResearch.com is a leading market research and market intelligence organization, specializing in research, analytics, and advisory services along with providing business insights & market research reports.

Contact Us:

Email: sales@straitsresearch.comAddress: 825 3rd Avenue, New York, NY, USA, 10022Tel: +1 6464807505, +44 203 318 2846Website: https://straitsresearch.com/

List of Similar Industry Reports:

Human Genetics Market: Information by Type (Cytogenetics, Prenatal Genetics, Molecular Genetics), End-Users (Research Center, Hospital, Forensic Laboratories), Region Forecast Till 2029 | Straits Research

https://straitsresearch.com/report/human-genetics-market/

Genome Editing Market: Information by Product (CRISPR, TALEN, ZFN), Application (Cell Line Engineering, Animal Genetic Engineering), End-User, and Region Forecast till 2029 | Straits Research

https://straitsresearch.com/report/genome-editing-market/

View post:
Global Genomics Market | Rising Incidence of Chronic and Genetic Diseases are Key Factors to Grow Market During 2021-2029 | 23andMe, Agilent...

Danielle Lloyd is finally expecting a baby girl after having four sons.

The 37 year old mum is expecting her fifth child and revealed she used a method called The Babydust Method in a bid to try and encourage a natural sex selection.

Danielle, who is married to husband Michael O'Neill with whom she shares 3-year-old Ronnie, as well as sons, Archie, 10, Harry, nine, and George, seven, with ex-husband Jamie OHara, has been open in the past about her plans to travel abroad to undergo IVF using sex selection.

However Covid and travel restrictions put an end to the couple's plans to undergo IVF in a bid to finally have their much longed for daughter and Danielle instead put her faith in a famed natural sex selection method.

Danielle revealed she had followed the book "to a T" for several months and after having a miscarriage last year finally got pregnant again, finding out it was a girl last month.

The Babydust Method, a guide to conceiving a girl or a boy, was written by Kathryn Taylor, who devised the method and successfully used it to have a son in 2012, followed by a girl in 2014.

Kathryn, who has a degree in Microbiology, Immunology, and Molecular Genetics from the University of California, Los Angeles, then released the now famous book of her method in 2016.

Boasting a success rate of 94%, the method uses both the timing and frequency of sex to sway the odds in favour of having a boy or girl.

Women are instructed to use ovulation predictor kits for three months to fully familiarise themselves with their cycle.

Then in the lead-up to ovulation, when an egg is released from the ovary, women use the ovulation predictor kits to test twice a day.

When the two lines on the test strips are equally dark or darker than the control line it indicates you will ovulate 24 hours later.

If you are trying for a girl, you should only have sex once, two to three days before ovulation, and at no other times throughout the cycle.

If you're hoping for a boy you should wait until 24 hours after the first darkest (also known as peak) test and again after 24 hours but at no other times during the cycle.

There are a number of other tips you can use to increase your odds of conceiving a girl - though it should be noted that there are no scientific researches proving these to be right!

Shallow penetration is the more optimal type of penetration for conceiving a girl. Male sperm cells are actually the faster swimmers, so the shallower penetration means it gives the female sperm cells an opportunity to get to the egg as well.

Missionary position is the best position to try for conceiving a girl.

It's rumoured that male sperm cells are heat averse, and that by having a hot bath before having sex to conceive may slow the male swimmers down and allow the female cells race to the egg to fertilise it! It could be a nice way to bring some romance to what can sometimes be the monotony of trying to conceive on certain days and times. Make it a romantic bath for two!

We do need the male orgasm to release the sperm, as it's his sperm that dictates whether the baby conceived will be boy or girl, and some experts claim that a female orgasm releases a certain alkaline secretion. This allows the male sperm to apparently survive longer due to the fact that the male sperm cells need this secretion to survive.

No orgasm, no alkaline secretion and thus creating a hostile environment for the male sperm cells.

If you are trying to conceive a girl, think about eating foods that are high in calcium to aid your chances.- so eggs, milk, yogurts.

It's also said a diet that is high in fruit and vegetables such as spinach, broccoli, bananas may help to conceive a girl, and a vegetarian diet is one that is rumoured to be very good in terms of conceiving a girl.

Steer clear of Alkaline rich foods such as Apples and Avocados however, as alkaline is said to help the male swimmers along by creating a more welcome space for them.

Eat Acidic rich foods in days leading up to Ovulation to ensure you've created the best environment for the female sperm cells to swim into. Apparently, male sperm cells aren't as good at surviving in acidic environments, so you can alter the pH of your vagina with the help of chocolate and fizzy drinks!

Remember to cut out the salt to boost your chances of conceiving a girl. Put down the olives, step away from the cheese and put that pack of crisps back in the cupboard because eating high salt foods may help your chances of conceiving a boy, and not the girl you want.

Stick with the fruit and veg and foods that are high in calcium in the lead up to ovulation to give your female sperm cells a better opportunity of reaching the egg first.

Remember though, these are just suggestions and you should have fun trying to conceive your much wanted baby!

Read more:
The Babydust Method Danielle Lloyd used to conceive a girl after four sons and how it works - RSVP Live

KENILWORTH, N.J.--(BUSINESS WIRE)--Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced that the company plans to voluntarily withdraw the U.S. accelerated approval indication for KEYTRUDA for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 [combined positive score (CPS 1)] as determined by a U.S. Food and Drug Administration (FDA)-approved test, with disease progression on or after two or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, human epidermal growth factor receptor 2 (HER2)/neu-targeted therapy.

The decision was made in consultation with the FDA following the April 29 Oncologic Drugs Advisory Committee evaluation of this third-line gastric cancer indication for KEYTRUDA as a monotherapy because it failed to meet its post-marketing requirement of demonstrating an overall survival benefit in a Phase 3 study. As agreed with the FDA, Merck will initiate the withdrawal in six months. Patients being treated with KEYTRUDA for metastatic gastric cancer in the third- or further-line setting should discuss their care with their health care provider. This decision does not affect other indications for KEYTRUDA.

While there remains an unmet need for heavily pre-treated patients with advanced gastric cancer, we recognize that the treatment landscape has evolved and we respect the FDAs efforts to continually evaluate accelerated approvals, said Dr. Scot Ebbinghaus, vice president, clinical research, Merck Research Laboratories. Our research with KEYTRUDA has contributed to recent advances in the treatment of gastric cancer, and we are continuing to advance studies to help more patients with this disease.

KEYTRUDA will continue to play an important role in the treatment of certain patients with gastric cancer:

These indications are approved under accelerated approval based on tumor response rate and durability of response; continued approval for these indications may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Mercks clinical program in gastric cancer includes the first-line Phase 3 studies KEYNOTE-811, KEYNOTE-859 and LEAP-015, as well as KEYNOTE-585 in the neoadjuvant and adjuvant treatment setting.

About KEYTRUDA (pembrolizumab) Injection, 100 mg

KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the bodys immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck has the industrys largest immuno-oncology clinical research program. There are currently more than 1,500 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

Selected KEYTRUDA (pembrolizumab) Indications in the U.S.

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.

KEYTRUDA is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection.

Non-Small Cell Lung Cancer

KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) 1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is stage III where patients are not candidates for surgical resection or definitive chemoradiation, or metastatic.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS 1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

Head and Neck Squamous Cell Cancer

KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.

Classical Hodgkin Lymphoma

KEYTRUDA is indicated for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL).

KEYTRUDA is indicated for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy.

Primary Mediastinal Large B-Cell Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy. KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.

Urothelial Carcinoma

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 (CPS 10), as determined by an FDA-approved test, or in patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

KEYTRUDA is indicated for the treatment of patients with locally advanced or mUC who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

KEYTRUDA is indicated for the treatment of patients with Bacillus Calmette-Guerin-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.

Microsatellite Instability-High or Mismatch Repair Deficient Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options.

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.

Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC).

Gastric Cancer

KEYTRUDA, in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent locally advanced or metastatic gastric or GEJ adenocarcinoma whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test, with disease progression on or after two or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, HER2/neu-targeted therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Esophageal Cancer

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic esophageal or GEJ (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma that is not amenable to surgical resection or definitive chemoradiation either:

Cervical Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Hepatocellular Carcinoma

KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Merkel Cell Carcinoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Renal Cell Carcinoma

KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of patients with advanced renal cell carcinoma.

Tumor Mutational Burden-High Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [10 mutations/megabase] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.

Cutaneous Squamous Cell Carcinoma

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) that is not curable by surgery or radiation.

Triple-Negative Breast Cancer

KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of patients with locally recurrent unresectable or metastatic triple-negative breast cancer (TNBC) whose tumors express PD-L1 (CPS 10) as determined by an FDA-approved test. This indication is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Selected Important Safety Information for KEYTRUDASevere and Fatal Immune-Mediated Adverse Reactions

KEYTRUDA is a monoclonal antibody that belongs to a class of drugs that bind to either the programmed death receptor-1 (PD-1) or the programmed death ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, can affect more than one body system simultaneously, and can occur at any time after starting treatment or after discontinuation of treatment. Important immune-mediated adverse reactions listed here may not include all possible severe and fatal immune-mediated adverse reactions.

Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Early identification and management are essential to ensure safe use of antiPD-1/PD-L1 treatments. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

Withhold or permanently discontinue KEYTRUDA depending on severity of the immune-mediated adverse reaction. In general, if KEYTRUDA requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose adverse reactions are not controlled with corticosteroid therapy.

Immune-Mediated Pneumonitis

KEYTRUDA can cause immune-mediated pneumonitis. The incidence is higher in patients who have received prior thoracic radiation. Immune-mediated pneumonitis occurred in 3.4% (94/2799) of patients receiving KEYTRUDA, including fatal (0.1%), Grade 4 (0.3%), Grade 3 (0.9%), and Grade 2 (1.3%) reactions. Systemic corticosteroids were required in 67% (63/94) of patients. Pneumonitis led to permanent discontinuation of KEYTRUDA in 1.3% (36) and withholding in 0.9% (26) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence. Pneumonitis resolved in 59% of the 94 patients.

Pneumonitis occurred in 8% (31/389) of adult patients with cHL receiving KEYTRUDA as a single agent, including Grades 3-4 in 2.3% of patients. Patients received high-dose corticosteroids for a median duration of 10 days (range: 2 days to 53 months). Pneumonitis rates were similar in patients with and without prior thoracic radiation. Pneumonitis led to discontinuation of KEYTRUDA in 5.4% (21) of patients. Of the patients who developed pneumonitis, 42% interrupted KEYTRUDA, 68% discontinued KEYTRUDA, and 77% had resolution.

Immune-Mediated Colitis

KEYTRUDA can cause immune-mediated colitis, which may present with diarrhea. Cytomegalovirus infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (1.1%), and Grade 2 (0.4%) reactions. Systemic corticosteroids were required in 69% (33/48); additional immunosuppressant therapy was required in 4.2% of patients. Colitis led to permanent discontinuation of KEYTRUDA in 0.5% (15) and withholding in 0.5% (13) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence. Colitis resolved in 85% of the 48 patients.

Hepatotoxicity and Immune-Mediated Hepatitis

KEYTRUDA as a Single Agent

KEYTRUDA can cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in 0.7% (19/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.4%), and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 68% (13/19) of patients; additional immunosuppressant therapy was required in 11% of patients. Hepatitis led to permanent discontinuation of KEYTRUDA in 0.2% (6) and withholding in 0.3% (9) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, none had recurrence. Hepatitis resolved in 79% of the 19 patients.

KEYTRUDA with Axitinib

KEYTRUDA in combination with axitinib can cause hepatic toxicity. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider monitoring more frequently as compared to when the drugs are administered as single agents. For elevated liver enzymes, interrupt KEYTRUDA and axitinib, and consider administering corticosteroids as needed. With the combination of KEYTRUDA and axitinib, Grades 3 and 4 increased alanine aminotransferase (ALT) (20%) and increased aspartate aminotransferase (AST) (13%) were seen, at a higher frequency compared to KEYTRUDA alone. Fifty-nine percent of the patients with increased ALT received systemic corticosteroids. In patients with ALT 3 times upper limit of normal (ULN) (Grades 2-4, n=116), ALT resolved to Grades 0-1 in 94%. Among the 92 patients who were rechallenged with either KEYTRUDA (n=3) or axitinib (n=34) administered as a single agent or with both (n=55), recurrence of ALT 3 times ULN was observed in 1 patient receiving KEYTRUDA, 16 patients receiving axitinib, and 24 patients receiving both. All patients with a recurrence of ALT 3 ULN subsequently recovered from the event.

Immune-Mediated Endocrinopathies

Adrenal Insufficiency

KEYTRUDA can cause primary or secondary adrenal insufficiency. For Grade 2 or higher, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold KEYTRUDA depending on severity. Adrenal insufficiency occurred in 0.8% (22/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.3%), and Grade 2 (0.3%) reactions. Systemic corticosteroids were required in 77% (17/22) of patients; of these, the majority remained on systemic corticosteroids. Adrenal insufficiency led to permanent discontinuation of KEYTRUDA in <0.1% (1) and withholding in 0.3% (8) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement.

Hypophysitis

KEYTRUDA can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism. Initiate hormone replacement as indicated. Withhold or permanently discontinue KEYTRUDA depending on severity. Hypophysitis occurred in 0.6% (17/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.3%), and Grade 2 (0.2%) reactions. Systemic corticosteroids were required in 94% (16/17) of patients; of these, the majority remained on systemic corticosteroids. Hypophysitis led to permanent discontinuation of KEYTRUDA in 0.1% (4) and withholding in 0.3% (7) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement.

Thyroid Disorders

KEYTRUDA can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated. Withhold or permanently discontinue KEYTRUDA depending on severity. Thyroiditis occurred in 0.6% (16/2799) of patients receiving KEYTRUDA, including Grade 2 (0.3%). None discontinued, but KEYTRUDA was withheld in <0.1% (1) of patients.

Hyperthyroidism occurred in 3.4% (96/2799) of patients receiving KEYTRUDA, including Grade 3 (0.1%) and Grade 2 (0.8%). It led to permanent discontinuation of KEYTRUDA in <0.1% (2) and withholding in 0.3% (7) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement. Hypothyroidism occurred in 8% (237/2799) of patients receiving KEYTRUDA, including Grade 3 (0.1%) and Grade 2 (6.2%). It led to permanent discontinuation of KEYTRUDA in <0.1% (1) and withholding in 0.5% (14) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement. The majority of patients with hypothyroidism required long-term thyroid hormone replacement. The incidence of new or worsening hypothyroidism was higher in 1185 patients with HNSCC, occurring in 16% of patients receiving KEYTRUDA as a single agent or in combination with platinum and FU, including Grade 3 (0.3%) hypothyroidism. The incidence of new or worsening hypothyroidism was higher in 389 adult patients with cHL (17%) receiving KEYTRUDA as a single agent, including Grade 1 (6.2%) and Grade 2 (10.8%) hypothyroidism.

Type 1 Diabetes Mellitus (DM), Which Can Present With Diabetic Ketoacidosis

Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Withhold KEYTRUDA depending on severity. Type 1 DM occurred in 0.2% (6/2799) of patients receiving KEYTRUDA. It led to permanent discontinuation in <0.1% (1) and withholding of KEYTRUDA in <0.1% (1) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement.

Immune-Mediated Nephritis With Renal Dysfunction

KEYTRUDA can cause immune-mediated nephritis. Immune-mediated nephritis occurred in 0.3% (9/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.1%), and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 89% (8/9) of patients. Nephritis led to permanent discontinuation of KEYTRUDA in 0.1% (3) and withholding in 0.1% (3) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, none had recurrence. Nephritis resolved in 56% of the 9 patients.

Immune-Mediated Dermatologic Adverse Reactions

KEYTRUDA can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson syndrome, drug rash with eosinophilia and systemic symptoms, and toxic epidermal necrolysis, has occurred with antiPD-1/PD-L1 treatments. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate nonexfoliative rashes. Withhold or permanently discontinue KEYTRUDA depending on severity. Immune-mediated dermatologic adverse reactions occurred in 1.4% (38/2799) of patients receiving KEYTRUDA, including Grade 3 (1%) and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 40% (15/38) of patients. These reactions led to permanent discontinuation in 0.1% (2) and withholding of KEYTRUDA in 0.6% (16) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 6% had recurrence. The reactions resolved in 79% of the 38 patients.

Other Immune-Mediated Adverse Reactions

The following clinically significant immune-mediated adverse reactions occurred at an incidence of <1% (unless otherwise noted) in patients who received KEYTRUDA or were reported with the use of other antiPD-1/PD-L1 treatments. Severe or fatal cases have been reported for some of these adverse reactions. Cardiac/Vascular: Myocarditis, pericarditis, vasculitis; Nervous System: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barr syndrome, nerve paresis, autoimmune neuropathy; Ocular: Uveitis, iritis and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment, including blindness, can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss; Gastrointestinal: Pancreatitis, to include increases in serum amylase and lipase levels, gastritis, duodenitis; Musculoskeletal and Connective Tissue: Myositis/polymyositis rhabdomyolysis (and associated sequelae, including renal failure), arthritis (1.5%), polymyalgia rheumatica; Endocrine: Hypoparathyroidism; Hematologic/Immune: Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection.

Infusion-Related Reactions

KEYTRUDA can cause severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis, which have been reported in 0.2% of 2799 patients receiving KEYTRUDA. Monitor for signs and symptoms of infusion-related reactions. Interrupt or slow the rate of infusion for Grade 1 or Grade 2 reactions. For Grade 3 or Grade 4 reactions, stop infusion and permanently discontinue KEYTRUDA.

Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Fatal and other serious complications can occur in patients who receive allogeneic HSCT before or after antiPD-1/PD-L1 treatment. Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute and chronic GVHD, hepatic veno-occlusive disease after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between antiPD-1/PD-L1 treatment and allogeneic HSCT. Follow patients closely for evidence of these complications and intervene promptly. Consider the benefit vs risks of using antiPD-1/PD-L1 treatments prior to or after an allogeneic HSCT.

Increased Mortality in Patients With Multiple Myeloma

In trials in patients with multiple myeloma, the addition of KEYTRUDA to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of these patients with an antiPD-1/PD-L1 treatment in this combination is not recommended outside of controlled trials.

Embryofetal Toxicity

Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. Advise women of this potential risk. In females of reproductive potential, verify pregnancy status prior to initiating KEYTRUDA and advise them to use effective contraception during treatment and for 4 months after the last dose.

Adverse Reactions

In KEYNOTE-006, KEYTRUDA was discontinued due to adverse reactions in 9% of 555 patients with advanced melanoma; adverse reactions leading to permanent discontinuation in more than one patient were colitis (1.4%), autoimmune hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and cardiac failure (0.4%). The most common adverse reactions (20%) with KEYTRUDA were fatigue (28%), diarrhea (26%), rash (24%), and nausea (21%).

In KEYNOTE-054, KEYTRUDA was permanently discontinued due to adverse reactions in 14% of 509 patients; the most common (1%) were pneumonitis (1.4%), colitis (1.2%), and diarrhea (1%). Serious adverse reactions occurred in 25% of patients receiving KEYTRUDA. The most common adverse reaction (20%) with KEYTRUDA was diarrhea (28%).

In KEYNOTE-189, when KEYTRUDA was administered with pemetrexed and platinum chemotherapy in metastatic nonsquamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 20% of 405 patients. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA were pneumonitis (3%) and acute kidney injury (2%). The most common adverse reactions (20%) with KEYTRUDA were nausea (56%), fatigue (56%), constipation (35%), diarrhea (31%), decreased appetite (28%), rash (25%), vomiting (24%), cough (21%), dyspnea (21%), and pyrexia (20%).

In KEYNOTE-407, when KEYTRUDA was administered with carboplatin and either paclitaxel or paclitaxel protein-bound in metastatic squamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 15% of 101 patients. The most frequent serious adverse reactions reported in at least 2% of patients were febrile neutropenia, pneumonia, and urinary tract infection. Adverse reactions observed in KEYNOTE-407 were similar to those observed in KEYNOTE-189 with the exception that increased incidences of alopecia (47% vs 36%) and peripheral neuropathy (31% vs 25%) were observed in the KEYTRUDA and chemotherapy arm compared to the placebo and chemotherapy arm in KEYNOTE-407.

In KEYNOTE-042, KEYTRUDA was discontinued due to adverse reactions in 19% of 636 patients with advanced NSCLC; the most common were pneumonitis (3%), death due to unknown cause (1.6%), and pneumonia (1.4%). The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia (7%), pneumonitis (3.9%), pulmonary embolism (2.4%), and pleural effusion (2.2%). The most common adverse reaction (20%) was fatigue (25%).

In KEYNOTE-010, KEYTRUDA monotherapy was discontinued due to adverse reactions in 8% of 682 patients with metastatic NSCLC; the most common was pneumonitis (1.8%). The most common adverse reactions (20%) were decreased appetite (25%), fatigue (25%), dyspnea (23%), and nausea (20%).

Visit link:
Merck Provides Update on KEYTRUDA (pembrolizumab) Indication in Third-Line Gastric Cancer in the US - Business Wire

Highlights the broader potential of Orchards ex vivo HSC gene therapy platform approach in new and larger indications

Reinforces Pharmings commitment to the HAE community and utilizes its relevant clinical expertise and global commercialization infrastructure

Companies to host joint investor call at 8:00 a.m. EDT / 2:00 p.m. CEST

BOSTON, LONDON and LEIDEN, The Netherlands, July 01, 2021 (GLOBE NEWSWIRE) -- Orchard Therapeutics(Nasdaq: ORTX), a global gene therapy leader, and Pharming Group N.V. (Euronext Amsterdam: PHARM/Nasdaq: PHAR), a global, commercial stage biopharmaceutical company, today announced a strategic collaboration to research, develop, manufacture and commercialize OTL-105, a newly disclosed investigational ex vivo autologous hematopoietic stem cell (HSC) gene therapy for the treatment of hereditary angioedema (HAE), a life-threatening rare disorder that causes recurring swelling attacks in the face, throat, extremities and abdomen.

OTL-105 is an investigational HSC gene therapy designed to increase C1 esterase inhibitor (C1-INH) in HAE patient serum to prevent hereditary angioedema attacks. OTL-105 inserts one or more functional copies of the SERPING1 gene into patients own HSCs ex vivo which are then transplanted back into the patient for potential durable C1-INH production. In preclinical studies, to date, OTL-105 demonstrated high levels of SERPING1 gene expression via lentiviral-mediated transduction in multiple cell lines and primary human CD34+ HSCs. Furthermore, the program achieved production of functional C1-INH protein, as measured by a clinically validated assay.

Under the terms of the collaboration, Pharming has been granted worldwide rights to OTL-105 and will be responsible for clinical development, regulatory filings, and commercialization of the investigational gene therapy, including associated costs. Orchard will lead the completion of IND-enabling activities and oversee manufacturing of OTL-105 during pre-clinical and clinical development, which will be funded by Pharming. In addition, both companies will explore the application of non-toxic conditioning regimen for use with OTL-105 administration.

Orchard will receive an upfront payment of $17.5 million comprising $10 million in cash and a $7.5 million equity investment from Pharming at a premium to Orchard's recent share price. Orchard is also eligible to receive up to $189.5 million in development, regulatory and sales milestones as well as mid-single to low double-digit royalty payments on future worldwide sales.

Given the combination of our expertise in HSC gene therapy with Pharmings long-standing legacy and experience, we have the potential to reinvent the treatment paradigm for HAE by providing people living with this life-threatening disorder a sustained therapy with a single administration, said Bobby Gaspar, M.D., Ph.D., chief executive officer of Orchard Therapeutics. This collaboration demonstrates the promise of the HSC gene therapy platform and how it can be applied to new therapeutic areas with larger patient populations. We believe the HSC gene therapy pipeline we are building could continue to be a source of future partnerships in areas where the biology supports our approach.

Pharming has been committed to the HAE community for more than two decades, said Sijmen de Vries M.D., MBA, chief executive officer of Pharming. We have partnered with Orchard Therapeutics, a leader in the development of autologous HSC gene therapy, to develop a potentially curative treatment for HAE. Based on Pharmings experience in HAE, we believe that HSC gene therapy has the potential for the highest probability of success. This confidence is based on the durability of effect and safety observed in approved treatments from Orchards HSC gene therapy portfolio and positive clinical data in several other programs. This a significant first step in developing a potentially transformative one-time treatment for HAE.

Great progress has been made in HAE treatment over the last 15 years.However, HAE remains a severe, debilitating disease with an ongoing burden of angioedema attacks or chronic medication use, said Dr. MarcRiedl, professor of medicine and clinical director of the U.S. Hereditary Angioedema Association Center at the University of California, San Diego.This promising work toward treatment with the potential for durable long-term clinical benefit is encouraging and signifies an ongoing commitment to the HAE community.I look forward to these efforts to identify and carefully advance a potential cure for HAE.

The HAE market is expected to generate ~$2 billion in sales in 2021, currently growing at 8% per annum. This represents a significant commercial opportunity for Pharming Group and Orchard Therapeutics.

Webcast Link:https://webcast.openbriefing.com/pharming-jul21/

Access code:470719

About HAE Hereditary angioedema (HAE) is a rare genetic disorder. The condition is caused by a deficiency of the C1 esterase inhibitor protein, which is normally present in blood and helps control inflammation (swelling) and parts of the immune system. Deficient C1 inhibitor does not adequately perform its regulatory function and, as a result, a biochemical imbalance can occur and produce unwanted peptides that induce the capillaries to release fluids into surrounding tissue, thereby causing swelling or edema.

HAE is characterized by spontaneous and recurrent episodes of swelling (edema attacks) of the skin in different parts of the body, as well as in the airways and internal organs. Edema of the skin usually affects the extremities, the face, and the genitals. Patients suffering from this kind of edema often withdraw from their social lives because of the disfiguration, discomfort and pain these symptoms may cause. Almost all HAE patients suffer from bouts of severe abdominal pain, nausea, vomiting and diarrhea caused by swelling of the intestinal wall.

Edema of the throat, nose or tongue is particularly dangerous and potentially life-threatening as it can lead to obstruction of the airway passages. Although there is currently no known cure for HAE, it is possible to treat the symptoms associated with angioedema attacks. HAE affects about 1 in 10,000 to 1 in 50,000 people worldwide. Experts believe a lot of patients are still seeking the right diagnosis: although HAE is (in principle) easy to diagnose, it is frequently identified very late or not discovered at all. The reason HAE is often misdiagnosed is because the symptoms are similar to those of many other common conditions such as allergies or appendicitis. By the time it is diagnosed correctly, the patient has often been through a long ordeal.

About Pharming Group N.V.Pharming Group N.V. is a global, commercial stage biopharmaceutical company developing innovative protein replacement therapies and precision medicines for the treatment of rare diseases and unmet medical needs.

The flagship of our portfolio is our recombinant human C1 esterase inhibitor (rhC1INH) franchise. C1INH is a naturally occurring protein that down regulates the complement and contact cascades in order to control inflammation in affected tissues.

Our lead product, RUCONEST, is the first and only plasma-free rhC1INH protein replacement therapy. It is approved for the treatment of acute hereditary angioedema (HAE) attacks. We are commercializing RUCONEST in the United States, the European Union and the United Kingdom through our own sales and marketing organization, and the rest of the world through our distribution network.

In addition, we are investigating the clinical efficacy of rhC1INH in the treatment of further indications, including pre-eclampsia, acute kidney injury, and severe pneumonia as a result of COVID-19 infections.

Furthermore, we are leveraging our transgenic manufacturing technology to develop next-generation protein replacement therapies, most notably for Pompe disease, which is currently in preclinical development.

About Orchard TherapeuticsOrchard Therapeutics is a global gene therapy leader dedicated to transforming the lives of people affected by severe diseases through the development of innovative, potentially curative gene therapies. Our ex vivo autologous gene therapy approach harnesses the power of genetically modified blood stem cells and seeks to correct the underlying cause of disease in a single administration. In 2018, Orchard acquired GSKs rare disease gene therapy portfolio, which originated from a pioneering collaboration between GSK and theSan Raffaele Telethon Institute for Gene Therapy in Milan, Italy. Orchard now has one of the deepest and most advanced gene therapy product candidate pipelines in the industry spanning multiple therapeutic areas where the disease burden on children, families and caregivers is immense and current treatment options are limited or do not exist.

Orchard has its global headquarters in London and U.S. headquarters in Boston. For more information, please visit http://www.orchard-tx.com, and follow us on Twitter and LinkedIn.

Availability of Other Information About Orchard TherapeuticsInvestors and others should note that Orchard communicates with its investors and the public using the company website (www.orchard-tx.com), the investor relations website (ir.orchard-tx.com), and on social media (Twitter andLinkedIn), including but not limited to investor presentations and investor fact sheets,U.S. Securities and Exchange Commissionfilings, press releases, public conference calls and webcasts. The information that Orchard posts on these channels and websites could be deemed to be material information. As a result, Orchard encourages investors, the media, and others interested in Orchard to review the information that is posted on these channels, including the investor relations website, on a regular basis. This list of channels may be updated from time to time on Orchards investor relations website and may include additional social media channels. The contents of Orchards website or these channels, or any other website that may be accessed from its website or these channels, shall not be deemed incorporated by reference in any filing under the Securities Act of 1933.

Orchard Therapeutics Forward-looking StatementsThis press release contains certain forward-looking statements about Orchards strategy, future plans and prospects, which are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include express or implied statements relating to, among other things, Orchards business strategy and goals, the therapeutic potential of Orchards product candidates, including the product candidate or candidates referred to in this release, and the possibility of future milestone or royalty payments. These statements are neither promises nor guarantees and are subject to a variety of risks and uncertainties, many of which are beyond Orchards control, which could cause actual results to differ materially from those contemplated in these forward-looking statements. In particular, these risks and uncertainties include, without limitation: the risk that prior results, such as signals of safety, activity or durability of effect, observed from preclinical studies or clinical trials will not be replicated or will not continue in ongoing or future studies or trials involving Orchards product candidates, will be insufficient to support regulatory submissions or marketing approval in the US or EU, as applicable, or that long-term adverse safety findings may be discovered; the risk that any one or more of Orchards product candidates, including the product candidates referred to in this release, will not be approved, successfully developed or commercialized; the risk of cessation or delay of any of Orchards ongoing or planned clinical trials; the risk that Orchard may not successfully recruit or enroll a sufficient number of patients for its clinical trials; the delay of any of Orchards regulatory submissions; the failure to obtain marketing approval from the applicable regulatory authorities for any of Orchards product candidates or the receipt of restricted marketing approvals; the inability or risk of delays in Orchards ability to commercialize its product candidates, if approved, or Libmeldy in the EU; the risk that the market opportunity for Libmeldy, or any of Orchards product candidates, may be lower than estimated; the risk that certain milestones may never be achieved or royalty payments may never be earned and paid; and the severity of the impact of the COVID-19 pandemic on Orchards business, including on clinical development, its supply chain and commercial programs. Given these uncertainties, the reader is advised not to place any undue reliance on such forward-looking statements.

Other risks and uncertainties faced by Orchard include those identified under the heading "Risk Factors" in Orchards Quarterly Report on Form 10-Q for the quarter endedMarch 31, 2021, as filed with theU.S. Securities and Exchange Commission(SEC), as well as subsequent filings and reports filed with theSEC. The forward-looking statements contained in this press release reflect Orchards views as of the date hereof, and Orchard does not assume and specifically disclaims any obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as may be required by law.

Pharming Group N.V. Forward-looking Statements This press release contains forward-looking statements, including with respect to timing and progress of Pharmings preclinical studies and clinical trials of its product candidates, Pharmings clinical and commercial prospects, Pharmings ability to overcome the challenges posed by the COVID-19 pandemic to the conduct of its business, and Pharmings expectations regarding its projected working capital requirements and cash resources, which statements are subject to a number of risks, uncertainties and assumptions, including, but not limited to the scope, progress and expansion of Pharmings clinical trials and ramifications for the cost thereof; and clinical, scientific, regulatory and technical developments. In light of these risks and uncertainties, and other risks and uncertainties that are described in Pharmings 2020 Annual Report and the Annual Report on Form 20-F for the year ended December 31, 2020 filed with the U.S. Securities and Exchange Commission, the events and circumstances discussed in such forward-looking statements may not occur, and Pharmings actual results could differ materially and adversely from those anticipated or implied thereby. Any forward-looking statements speak only as of the date of this press release and are based on information available to Pharming as of the date of this release.

Inside InformationThis press release relates to the disclosure of information that qualifies, or may have qualified, as inside information within the meaning of Article 7(1) of the EU Market Abuse Regulation.

Orchard Therapeutics Contacts

InvestorsRenee LeckDirector, Investor Relations+1 862-242-0764Renee.Leck@orchard-tx.com

MediaBenjamin NavonDirector, Corporate Communications+1 857-248-9454Benjamin.Navon@orchard-tx.com

Pharming Group N.V. Contacts

CompanyPharming Group, Leiden, The NetherlandsSijmen de Vries, CEO+31 71 524 7400

InvestorsSusanne EmbletonInvestor Relations Manager+31 71 524 7400investor@pharming.com

Media FTI Consulting, London, UKVictoria Foster Mitchell/Alex Shaw +44 203 727 1000

LifeSpring Life Sciences Communication, Amsterdam, The NetherlandsLeon Melens+31 6 53 81 64 27pharming@lifespring.nl

Read more:
Orchard Therapeutics and Pharming Group Announce Collaboration to Develop and Commercialize ex vivo autologous HSC Gene - GlobeNewswire

According to the latest report by IMARC Group, titled Saudi Arabia Health Insurance Market: Industry Trends, Share, Size, Growth, Opportunity and Forecast 2021-2026, the saudi arabia health insurance market reached a value of around US$ 6 Billion in 2020. Looking forward, IMARC Group expects the Saudi Arabia health insurance market to exhibit strong growth during the next five years.

We are regularly tracking the direct effect of COVID-19 on the market, along with the indirect influence of associated industries. These observations will be integrated into the report.

Request Free Report Sample:

https://www.imarcgroup.com/saudi-arabia-health-insurance-market/requestsample

Health insurance refers to a type of insurance coverage that wholly or partially covers the medical and surgical expenses of an insured individual. It reimburses the medical and surgical expenses incurred for the treatment of injuries or illness to the insurer or pays for the same to the care provider directly. The insurer must develop a routine premium structure to pay for the opted insurance plan to avail numerous benefits at an affordable price point. Health insurance can also include additional services like diagnosis, medical check-ups, dental care, psychiatric care, treatment for chronic ailments, emergency transportation, and in-patient and daycare management.

Saudi Arabia Health Insurance Market 2021-2026 Competitive Analysis and Segmentation:

Competitive Landscape With Key Players:

The competitive landscape of the saudi arabia health insurance market has been studied in the report with the detailed profiles of the key players operating in the market.

Key Market Segmentation:

The report has segmented the saudi arabia health insurance market on the basis of type and service provider.

Breakup by Type:

Breakup by Service Provider:

Explore Full Report with TOC & List of Figure: https://www.imarcgroup.com/saudi-arabia-health-insurance-market

Key highlights of the report:

If you need specific information that is not currently within the scope of the report, we will provide it to you as a part of the customization.

Browse Related Reports:

India Facility Management Market: https://www.imarcgroup.com/india-facility-management-market

Gardening Equipment Market: https://www.imarcgroup.com/gardening-equipment-market

Eucalyptus Essential Oil Market: https://www.imarcgroup.com/eucalyptus-essential-oil-market

Fall Protection Equipment Market: https://www.imarcgroup.com/fall-protection-equipment-market

UAE Health Insurance Market: https://www.imarcgroup.com/uae-health-insurance-market

Baler Market: https://www.imarcgroup.com/baler-market

Bone Densitometer Market: https://www.imarcgroup.com/bone-densitometer-market

Hearing Aid Market: https://www.imarcgroup.com/hearing-aid-market

Stem Cell Banking Market: https://www.imarcgroup.com/stem-cell-banking-market

Endoscopy Devices Market: https://www.imarcgroup.com/endoscopy-devices-market

About Us

IMARC Group is a leading market research company that offers management strategy and market research worldwide. We partner with clients in all sectors and regions to identify their highest-value opportunities, address their most critical challenges, and transform their businesses.

IMARCs information products include major market, scientific, economic and technological developments for business leaders in pharmaceutical, industrial, and high technology organizations. Market forecasts and industry analysis for biotechnology, advanced materials, pharmaceuticals, food and beverage, travel and tourism, nanotechnology and novel processing methods are at the top of the companys expertise.

Contact US:

IMARC Group30 N Gould St, Ste RSheridan, WY 82801, USAEmail: sales@imarcgroup.comAmericas: +1-631-791-1145 | Europe & Africa: +44-753-713-2163 | Asia: +91-120-433-0800

Read the original:
Saudi Arabia Health Insurance Market Size, Share, Competitive Analysis and Growth by 2026 The Manomet Current - The Manomet Current

There are a number of reasons you might consider donating your eggs. For some, the choice is monetary, as you may be well-compensated for your donation. For others, its the act of helping a couple have a baby. And it can certainly be both.

Whatever your motivation, the egg donation process is relatively straightforward and takes place over a 2-month period, according to the Center for Reproductive Health & Gynecology. Once you pass the initial application and legal hurdles, youll use medications to prepare your eggs for the egg procedure.

Keep reading to learn more about the egg donation process, including the possible risks and some tips for ways to prepare yourself before, during, and after the procedure.

Egg donation involves a donor who provides eggs to a recipient for the purpose of getting pregnant. Sometimes this recipient is the intended parent, and other times, it may be a surrogate who will carry a pregnancy for the intended parents.

A 2017 study showed that typically, between 5 to 24 eggs will be retrieved per cycle. The number of eggs retrieved is based on how many you produce and any specific guidelines the clinic follows.

Compensation for egg donation varies by area and fertility clinic. ConceiveAbilities, which has offices across the United States, shares that donor compensation begins at $8,000 per donation. This amount can go up based on various factors specific to each clinic.

The egg donor will receive various injectable medications throughout their menstrual cycle. These medications stimulate your ovaries to produce multiple eggs. Specific medications may include:

First, you will receive a dose of human chorionic gonadotropin (hCG), which is sometimes called a trigger shot. A doctor will remove the eggs in a procedure called egg retrieval. This is performed using a special needle attached to a transvaginal ultrasound device. The needle is passed through your vaginal wall and into your ovary. The eggs are suctioned (aspirated) out and sent to an embryologist for evaluation before fertilization.

Here is a step-by-step overview of the entire process:

Next, the eggs can either be frozen or mixed together with the intended fathers sperm to create embryos. The embryos are then transferred and implanted into the uterus of the birth parent or surrogate.

Yes. Egg donation when closely supervised by a medical professional is generally a safe process and does not carry any long-term health risks. This includes fertility issues, provided you dont develop complications.

A 2015 research review showed that most young adult females have around 400,000 eggs. So, taking even up to 24 eggs per donation cycle for several cycles will leave many to spare for the future.

However, there are some short-term risks to be aware of during the donation cycle. These risks include:

Its not easy to predict the discomfort you may experience before, during, and after the retrieval process. Many factors may contribute to pain, including your personal tolerance level, your bodys reaction to the different medications, as well as any complications you may experience.

Symptoms you may have after the egg retrieval include:

The good news is that you can expect your discomfort to improve as soon as the day or a few days after the retrieval procedure.

Your doctor will advise you about over-the-counter (OTC) medications you can take for pain, such as acetaminophen or ibuprofen. A heating pad may also help ease abdominal discomfort.

If you develop a fever, heavy bleeding, or any other symptoms of infection, call your doctor as soon as possible.

Preparing your body for egg donation is similar to preparing your body for the in vitro fertilization process. First, youll want to take good care of yourself by following a healthy lifestyle.

Fertility clinics, like the CNY Fertility Center, recommend paying special attention to the following areas for 3 months before retrieval for the best quality eggs:

Its also a good idea to create a support network for yourself. Egg donation can be challenging both physically and emotionally, so having trusted friends or family members nearby can help. Your support network can also help if you need transportation to and from appointments or any other assistance during the process.

Above all else: Ask questions. A 2020 survey of egg donors revealed that 55 percent of women did not feel they were well educated on the long-term risks of donation. Your doctor or fertility clinic can give you specific advice and resources to both understand and lower your risk of complications.

There are both state and federal regulations surrounding egg donation. Specifics vary depending on your state, so be sure to check with your clinic for any specific information that applies where you live.

Children born through egg donation are not considered your legal children, despite their genetic relation to you. The intended parent is listed as the guardian on any legal documents, like the birth certificate.

These details should be clearly stated in any contracts that you sign before the physical process begins. Working with lawyers to come up with an egg donation legal agreement can help protect you and ensure youll be fairly compensated.

Areas covered by the egg donation contract may include:

Be sure to ask yourself how much (if any) involvement you would want after your donation. Your rights are protected once you sign your agreement. And as the donor, you should have your own attorney. Tulip Fertility says that this does not come as a cost to you. Instead, the intended parents should cover these fees.

The egg donation process involves various physical, emotional, and potentially legal challenges. Along with doing your own research, reach out to a local fertility clinic for more specifics about your location and your personal situation.

Theres a lot to consider, but donating your eggs can be incredibly rewarding and financially empowering. Once you understand the risks and rewards, you can make the right choice for yourself and your future.

See the rest here:
Egg Donation Process: From Application to Recovery - Healthline

Researchers have been studying and working with mRNA vaccines for decades. Interest in these vaccines has grown since they can be developed in a laboratory using readily available materials for low-cost manufacture and safe administration. This means that the process can be standardized and scaled up, which make vaccine development faster than traditional methods of making vaccines.

As soon as the necessary information about the virus that causes COVID-19 was available, scientists began designing the mRNA instructions for cells to build the unique spike protein into an mRNA vaccine.

For most emerging virus vaccines, the main obstacle is not the effectiveness of conventional approaches but the need for more rapid development and large-scale deployment.

How mRNA vaccines work

Messenger ribonucleic acid (mRNA) vaccines are a novel technology that stimulates the bodys own immune response. These vaccines contain information from mRNA, including the blueprint or code of a specific virus trait (virus antigen). The information enables the body to produce this antigen on its own: mRNA transfers the information for the production of the antigen to our cell machinery that makes proteins. Cells in our body then present the antigen on their surface and thus trigger the desired specific immune response. When the body comes into contact with the virus, the immune system recognizes the specific antigen and can fight the virus and thus the infection quickly and in a targeted manner.

mRNA vaccines are safe because they are not made with pathogen particles or inactivated pathogens; therefore, they are non-infectious. RNA does not integrate itself into the host genome and the RNA strand in the vaccine is degraded once the protein is made.

Due to the high yields of in vitro transcription reactions, mRNA vaccines have the potential for rapid, inexpensive and scalable manufacturing.

mRNA vaccines can be used for infectious diseases, particularly for viruses, that cause both acute (Influenza, Ebola, Zika, etc.) and chronic (HIV-1, herpes simplex virus, etc.) infections.

Cancer vaccines can be designed to target tumor-associated antigens that are preferentially expressed in cancerous cells, for example, blood cancers, melanoma, glioblastoma (brain cancer), renal cell carcinoma, prostate cancer, etc. Most cancer vaccines are therapeutic, rather than prophylactic, and seek to stimulate cell-mediated responses, such as those from CTLs, that are capable of clearing or reducing tumor burden.

Four of the vaccine candidates currently in clinical trials to prevent COVID-19 are mRNA vaccines: mRNA-1273 (Moderna), BNT-162 (BioNTech), CVnCoV (CureVac), and LNP-nCoVsaRNA (Imperial College London).

Types of RNA vaccine

Protection by Patent

Patent Rights play an important role in encouraging investment on research of new technologies. The patent system is designed to support innovation and, at the same time, offer a mechanism to ensure that such innovations are accessible to society. Published patents and patent applications are an important source of technical and legal information.

Scientists have studied the use of mRNA as a novel therapeutic since the early 1990s. The first patent family identified was published in 1990. However, it was not until 2005 that a group of researchers from the University of Pennsylvania published findings on mRNA technology that have since been deemed critical to the development of mRNA-based therapies. US Securities and Exchange Commission filings, highlighted by Knowledge Ecology International, reveal a series of sublicenses for mRNA-related patents that stem from the University of Pennsylvania to both Moderna and BioNTech. The 2017 filings indicate that the University of Pennsylvania exclusively licensed their patents to mRNA RiboTherapeutics, which then sublicensed them to its affiliate CellScript. CellScript proceeded to sublicense the patents to Moderna and BioNTech; however, the patent numbers are redacted in all the filings, making it difficult to determine which are relevant to the production of COVID-19 vaccines.

Another key aspect of an mRNA vaccine platform is the ability to deliver the mRNA to a cell using a lipid nanoparticle. Some early work on lipid nanoparticles was done jointly by the University of British Columbia and Arbutus Biopharmaceuticals in 1998. US Securities and Exchange Commission filings show that patents relating to this early technology were solely assigned to the University of British Columbia and then licensed back to Arbutus.

Patent-filing activity grew dramatically over the past 5 years for both infectious disease and cancer indications. The number of applications for infectious disease indications surpassed those for cancer over the past 3 years, which could reflect increased interest in vaccines following epidemic outbreaks of MERS-CoV, Ebola virus and Zika virus. In August 2019, Moderna received FDA Fast Track Designation for an investigational Zika virus vaccine (mRNA-1893) currently being evaluated in a phase I study.

According to PATENTSCOPE WIPO, from 2012 to 2021, 1,834 patent applications related with mRNA have been published. The main filing countries are the following:

The applicants who have filed the most patent application are listed below:

The present IP landscape includes foundational patents in modified mRNA technologies and delivery technologies that are essential for mRNA therapeutics and vaccines, including their application in specific unmet needs in infectious diseases, cancer (immuno-oncology), and rare and cardiometabolic diseases, among others.

Compulsory licenses

Compulsory licensing is when a government allows someone else to produce a patented product or process without the consent of the patent owner or plans to use the patent-protected invention itself. It is one of the flexibilities in the field of patent protection included in the WTOs agreement on Intellectual Property Trade-Related Aspects of Intellectual Property Rights (TRIPS) Agreement.

To explain the public policy objectives for a compulsory licensing mechanism, countries refer to striking a balance between the interest of patentees and that of third parties, public interest, and/or society; preventing abuses that may result from the exercise of exclusive rights; and promoting the public interest at large, such as in situations of public interest and emergency motivated by considerations of public health, nutrition, and national security. Some possible grounds for compulsory licensing are suggested in Article 5A of the Paris Convention (e.g., abuse of patent rights, including failure of the patent holder to work the invention) and in Article 31 of the TRIPS Agreement (e.g., national emergency and public noncommercial use).

Compulsory licenses are thus not limited to public health emergencies or other urgent situations, as is sometimes mistakenly believed. A range of grounds have been set out in national laws, such as:

In Mexico, compulsory licenses can be granted based on articles 146-153 of the Federal Law for the Protection of Industrial Property, which states they can be granted for non-working the patent and national emergency or circumstances of extreme urgency:

In cases of serious diseases, the General Health Council will declare priority attention, ex officio or at the request of national institutions specialized in said disease that are accredited before it, in which the causes of emergency or national security are justified. Once the declaration issued by the Council has been published in the Official Gazette, pharmaceutical companies may request the granting of a license of public utility to the Institute, which will grant it, after hearing the parties and the opinion of the Council, within a period not exceeding ninety days from the date of submission of the respective application

The Emergency Use Authorization (EUA) authority allows FDA to help strengthen the nations public health protections against chemical, biological, radiological, and nuclear (CBRN) threats including infectious diseases, by facilitating the availability and use of medical countermeasures (MCMs) needed during public health emergencies, such as the current COVID19 pandemic.

Under an Emergency Use Authorization, FDA may allow the use of unapproved medical products -or unapproved uses of approved medical products- in an emergency to diagnose, treat, or prevent serious or life-threatening diseases or conditions when certain statutory criteria have been met, including that there are no adequate, approved, and available alternatives. Taking into consideration input from the FDA, manufacturers decide whether and when to submit an Emergency Use Authorization request to FDA. Once submitted, FDA will evaluate the Emergency Use Authorization request and determine whether the relevant statutory criteria are met, taking into account the totality of the scientific evidence about the vaccine that is available to FDA.

There are no specific guidelines from the FDA or European Medicines Agency (EMA) for mRNA vaccine products. However, the increasing number of clinical trials conducted under EMA and FDA oversight indicate that regulators have accepted the approaches proposed by various organizations to demonstrate that products are safe and acceptable for testing in humans. Because mRNA falls into the broad vaccine category of genetic immunogens, many of the guiding principles that have been defined for DNA vaccines and gene therapy vectors can likely be applied to mRNA with some adaptations to reflect the unique features of mRNA.

Emergency use of vaccines in Mexico

The Federal Commission for the Protection against Sanitary Risks (COFEPRIS) is the health authority responsible for protecting the Mexican population from the risks that may arise from the consumption or use of medicines and medical devices, as well as from those derived from the consumption of food and of other products that we use on a daily basis, while also issuing import and export permits for these products.

The Mexican Government published on March 30, 2020 the agreement declaring a health emergency due to force majeure, the disease epidemic generated by the SARS-CoV2 virus (COVID-19). Furthermore, on November 11, 2020, it published an Agreement instructing the Ministry of Health and the Federal Commission for the Protection against Sanitary Risks to carry out the following actions:

CONCLUSIONS

Unwarranted restrictions on competition, whether resulting from the abuse of a dominant position resulting from intellectual property rights or other factors, or from anti-competitive agreements, can be addressed through competition law enforcement. Regarding innovation, a key concern is merger control, where competition authorities must ensure that mergers do not threaten R&D pipelines.

Incremental innovation can improve the safety, therapeutic effect or method of delivery of an existing medicine or vaccine. Whether such inventions merit the granting of a patent is judged on a case-by-case basis.

Regulation should promote access to medical technologies of proven quality, safety and efficacy and should not unnecessarily delay the market entry of products.

Challenges for regulatory systems that impact access include lack of political support and adequate resources, a focus on regulating products without effective oversight of the whole supply chain, poorly developed systems for post-marketing surveillance, and different standards for locally produced versus imported products.

In this area, both regulatory and IP tools can be used in a complementary way to combat substandard and falsified products.

Continue reading here:
Patent protection of mRNA vaccines and regulatory authorization - Lexology

Good morning and welcome, health colleagues, to the second European Alliance for Personalised Medicine (EAPM) update of the week as it stands, more than 150 people have now registered for our upcoming EAPM Slovenian EU Presidency conference on 1 July, so now is the time to join them and book your place before its too late,and we also have an update on the European Parliaments draft report on strengthening Europe in the fight against cancer,writes EAPM Executive Director Dr. Denis Horgan.

EAPM conference approaches - a reminder yet again...

The EAPM conference will act as a bridging event between the EU Presidencies ofPortugalandSlovenia.The conference is divided into sessions which cover the follows areas: Session 1: Generating alignment in the regulation of Personalized Medicine: RWE and Citizen Trus;Session 2: Beating Prostate Cancer and Lung Cancer - The Role of the EU Beating Cancer: Updating EU Council Conclusions on ScreeningSession 3: Health Literacy - Understanding Ownership and Privacy of Genetic Data and finallynot least,Session 4: Securing patient Access to Advanced Molecular Diagnostics.

Each session will comprise panel discussions as well as Q&A sessions to allow the best possible involvement of all participants, so now is the time to registerhere, and download your agendahere.

Battling cancer Parliaments key draft report

As mentioned in previous updates, the European Parliament has set up a special committee on beating cancer. It has published its first draft report on the EU Beating Cancer Plan on the last day, which has included a number of items which the EAPM has advocated for in the last months representing key issues representing themulti-stakeholder nature of its membership.

Subdivided into numerous articles, article 66 in the report is of particular attention to EAPM members, saying as it does that huge advances in biology have revealed that cancer is an umbrella term for more than 200 diseases, and that precision or personalised medicine can be made available through the drug targeting of various mutations.

The report also considers that precision or personalised medicine, consisting of a treatment choice based on individual tumour biomarkers, is a promising way to improve cancer treatment, and encourages member states to promote the implementation of regional molecular genetics platforms and facilitate equal and rapid access to personalised treatment for patients.

In addition, article 48 in the draft report calls on the Commission to promote, and on member states to strengthen, the role of general practitioners, paediatricians and primary care professionals, given their importance in patient referral to diagnostic tests and oncology specialists, as well as during cancertreatment and follow-up care; calls for the development of multidisciplinary decision-making in the framework of dedicated concertation meetings bringing together various cancer specialists.

According to article 61, the provisional agreement on the Health Technology Assessment (HTA) Regulation reached by the European Parliament and the Council on 22 June 2021 is welcomed, to harmonize access to innovative cancer diagnosis and treatments.

Perhaps most importantly, article 87 sees an urgent need for a European charter of the rights of cancer patients; calls for this charter to define the rights of cancer patients at every stage of their care pathway, i.e. access to prevention, initial diagnosis and throughout their treatment, and for it to apply equally to all EU citizens, regardless of the country or region in which they live.

In addition, article 105 looks to the Cancer Diagnostic and Treatment for All flagship and puts a spotlight on the need for the use of the next generation sequencing technology for quick and efficient genetic profiles of tumour cells, allowing researchers and clinicians to share cancer profiles and apply the same or similar diagnostic and therapeutic approaches to patients with comparable cancer profiles.

EAPM looks forward with enthusiasm to all forward progress being made in the fight against cancer. In this context, EAPM is working on two publications with its experts on NGS and RWE which will provide additional input/guidance to the European politicians which EAPM is working with.

HTA political agreement

The Commission welcomes the political agreement on the Health Technology Assessment (HTA) Regulation reached by the European Parliament and the Council on 23 June. The Regulation will improve the availability of innovative health technologies such as innovative medicines and certain medical devices for EU patients, ensure efficient use of resources and strengthen the quality of HTA across the EU. Examples of health technologies include medicinal products, medical equipment and diagnostics. It will also facilitate business predictability, reduce duplication of efforts for HTA bodies and industry and ensure the long-term sustainability of EU HTA co-operation.

Welcoming the agreement, Commissioner for Health and Food Safety Stella Kyriakides made the following statement: I am very pleased that the European Parliament and the Council have reached a long-awaited political agreement on the Health Technology AssessmentRegulation. The Regulation will be a significant step forward to enable joint scientific assessments of promising treatments and medical devices at EU level.

Progress on vaccinations welcomed, but further effort urged

The European Council welcomes the good progress on vaccination and the overall improvement in the epidemiological situation, while stressing the need to continue vaccination efforts and to be vigilant and co-ordinated with regard to developments, particularly the emergence and spread of variants.

According to the draft European Council conclusions for the June 24-25 meeting, the Council stated that it reaffirms the EUs commitment to international solidarity in response to the pandemic.

All producing countries and manufacturers should actively contribute to efforts to increase worldwide supply of COVID-19 vaccines, raw material, treatments and therapeutics, and coordinate action in case of bottlenecks in supply and distribution, the draft text declares.

The conclusions also reference recent agreements on travel within the EU, stating that member countries would apply these measures in a manner that ensures the full return to free movement as soon as the public health situation allows. The Council also plans to welcome the decision to set up a special session for the World Health Assembly to discuss a pandemic treaty, with the EU saying that it will continue to work toward a goal of a treaty.

WHO, WIPO and the WTO agree on intensified co-operation to tackle COVID-19 pandemic

On 15 June, the directors general of WHO, WIPO and the WTO met in a spirit of co-operation and solidarity to map out further collaboration to tackle the COVID-19 pandemic and the pressing global challenges at the intersection of public health, intellectual property and trade.Acutely conscious of the shared responsibility to communities across the world as they confront a health crisis of unprecedented severity and scale, the organizations pledged to bring the full extent of the expertise and resources of the respective institutions to bear in ending the COVID-19 pandemic and improving the health and well-being of all people, everywhere around the globe.

Commitment to universal, equitable access to COVID-19 vaccines, therapeutics, diagnostics, and other health technologies was underscored a commitment anchored in the understanding that this is an urgent moral imperative in need of immediate practical action.In this spirit, there was an agreement to build further on the long-standing commitment to WHO-WIPO-WTO Trilateral Cooperation that aims to support and assist all countries as they seek to assess and implement sustainable and integrated solutions to public health challenges.

Within this existing cooperative framework, it was agreed to enhance and focus our support in the context of the pandemic through two specific initiatives - the three agencies will collaborate on the organization of practical, capacity-building workshops to enhance the flow of updated information on current developments in the pandemic and responses to achieve equitable access to COVID-19 health technologies. The aim of these workshops is to strengthen the capacity of policymakers and experts in member governments to address the pandemic accordingly.The first workshop in the series will be a workshop on technology transfer and licensing, scheduled for September.

Long COVID concerns

More than 2 million adults in England have experienced coronavirus symptoms lasting over 12 weeks, such as respiratory problems and fatigue, government data suggests. It is double the previous estimate for long Covid. The research by the React-2 study, which has not yet been peer-reviewed, found that 37.7% of those who had symptomatic Covid experienced at least one symptom lasting 12 weeks or more, while 14.8% had three or more persistent symptoms. The scale of the problem is quite alarming, said Professor Kevin McConway, emeritus professor of applied statistics at the Open University. It comes as more than 16,000 new confirmed Covid cases were reported in the UK on Wednesday (23 June), the highest daily figure since early February. The newest figures showed another 19 people had died within 28 days of testing positive for Covid-19, bringing the UK total to 128,027. While death figures remain relatively low, the sharp rise in reported cases would appear to make it less likely that ministers will scrap most remaining Covid restrictions before the current four-week delay ends on 19 July.

Switzerland to re-open

While countries such as the UK delay their planned lifting of restrictions (as it stands, until 19 July in the case of the UK), Switzerland has announced an even more wide-ranging lifting of restrictions than previously planned. Citizens will no longer be required to work from home; they wont have to wear masks or social distance at cultural and sporting events; and mass events can go ahead without restrictions on numbers or the need for masks if theres a requirement for coronavirus certificates.

And that is all from EAPM for this week have a lovely weekend, stay safe and well, and dont forget to registerhere, and download your agendahere,for the EAPM EU Presidency conference on 1 July.

Go here to see the original:
EAPM: Presidency bridging conference a great success, HTA compromise agreed and data on the agenda - EU Reporter

Dr. Michael DiGiorno

By Dan Murphy

With most Westchester residents vaccinated, and with COVID-19 positivity rates at less than 1%, Dr. Michael DiGiorno, Medical Director of St. Johns Medical Group, is encouraging patients and our readers to return to their pre-COVID routine of getting tested, including getting their annual physicals, screening colonoscopies, bone density testing and mammograms.

Its important not to let your health lapse because of the pandemic any longer. At least come in and have an annual physical and ensure that your health screening tests are up to date. It is an extraordinarily safe time for patients to come in and catch up with their health care needs, and we are here to help them through the testing process.

Part of our challenge during the COVID-19 pandemic was to make sure that we stayed open, and that we continued to deliver care to Yonkers and the surrounding communities. We thought it was crucial to maintain a presence in the community during a very difficult time, and if you had an underlying medical condition, or had a medical question or needed a prescription refill, we were open for in person and telemedicine appointments. We concentrated on the safety of our physicians and staff and made sure we were all protected, and we did so quite successfully, said Dr. DiGiorno.

Now we are moving towards a return to normalcy. People are vaccinated and we can accommodate more patients in person. We are maintaining processes in place, including using masks and enhanced cleaning to ensure optimal safety. We provide a very safe, clean environment, so now is the time to pivot and focus on health care maintenance.

Our physicians and staff are available and understand that not everyone has the same level of comfort. If you have any specific concerns, let us know and we will work to ensure your return is a positive experience. In addition to primary care, our specialty physicians are on-site and available to address your gastroenterology, nephrology, physical medicine, vascular, podiatric and pain management needs.

Dr. DiGiorno stressed that, unfortunately, underlying health conditions dont wait for the pandemic to pass. We do see some patients, with diabetes who have strayed and have weight gain because of a lack of activity. As a result, their diabetes has become poorly controlled. Similarly, we are seeing patients with chronic hypertension, which was once well-controlled, now require additional therapy. We understand whygyms were closed, our diets and routines were interrupted, and we were told to stay home, and it all took a toll on our health.

Now is the time to get people back on track, with basic testing, and diabetes and blood pressure treatments and screenings. While we have seen some slippage with chronic conditions in some patients, we want that to be the exception and not the rule.

So go back for your basic labs, physicals, and colonoscopies. The environment is safe and clean and accessible. They will expedite your appointment and connect you to your primary care physician. If you do not have a physician, St. Johns has lots of options and it all starts with a phone call.

We understand what our community, and the world has been through. There is no judgement here. Our goal is to achieve wellness, so dont be afraid to see a physician. We just want everyone to get well again, and move forward as a community said Dr. DiGiorno.

Michael DiGiorno, DO, MHSA, FASN, is the Vice-President, Medical Operations, and the Chief of Nephrology at St. Johns Riverside Hospital, and the Medical Director of the St. Johns Medical Group practice.

To make an appointment or contact a member of St. Johns Riverside Hospital, or St. Johns Medical Group call 914.964.4DOC.

View original post here:
Dr. Michael DiGiorno, Director of St. John's Medical Group: Now is the Time to Catch up with Preventative Health Care, Testing - Yonkers Times

Just like other devices we rely on, medical devices can improve our quality of life so long as they are maintained to work properly. When they are not or not maintained or serviced in line with FDA approval there can be huge health care and cybersecurity risks.

In the brief on a just-released FDA discussion paper, William Maisel, notes,Many medical devices are reusable and need preventative maintenance and repair during their useful life; therefore, proper servicing is critical to their continued safe and effective use.Maisel, M.D., is the director of the Office of Product Evaluation and Quality in FDAs Center for Devices and Radiological Health.Who could possibly disagree with such a statement? Lawyers.

Thats right, the tort bar is prioritizing profit over patient safety. For shame. (No, Im not surprised either.)

Quality is the glue that holds together our health care technology ecosystem. Whether its a medicine for high blood pressure, a COVID-19 vaccine or a medical device such as an implantable stent or a room-size MRI machine, the FDAs mission rests upon a triad of trust safety, effectiveness and quality. And the bedrock upon which quality rests isGood Manufacturing Practices. Who could be against that? Lawyers.

Considerthe recent spate of suggested state and federal legislationon what is called Right-to-Repair. At first glance, it seems like a good idea. Why not make it easier for consumers to fix their broken electronics, without having to pay a costly sum to the original manufacturer? But, as HL Mencken reminds us, for every complex problem there is an answer that is clear, simple, and wrong. The reality is that Right-to-Repair presents many dangerous unintended consequences. The No.1 problem is that it compromises patient safety.

The core of Right-to-Repair laws is to require innovative technology companies to make product repair information, replacement parts and tools readily available to consumers and third-party repair shops. Should that be the case for devices such as Automated External Defibrillators and hospital ventilators? What about electrocardiograph (ECG) machines? Can physicians and patients be confident in non-FDA compliant vendors without the advanced training and technical ability to properly repair and recalibrate life-saving machines? Who could argue that anyone can do it? Lawyers.

Why? Because when things go wrong, when medical devices fail, when patients and their families suffer the consequences, when associated health care costs skyrocket it seems lawyers see opportunity. And they aim their lightening lances of litigation at the deepest pockets the original manufacturers.

It seems the tort bar is creating a problem they can exploit for profit.

But wait, it gets worse. By allowing third parties without any FDA competence to repair regulated, complicated medical devices, Right-to-Repair also opens the door to breaches in cybersecurity.

According to the FDA, cybersecurity is a widespread issue affecting medical devices connected to the Internet, networks, and other devices. Cybersecurity is the process of preventing unauthorized access, modification, misuse or denial of use, or the unauthorized use of information that is stored, accessed, or transferred from a medical device to an external recipient.

In the just-released FDA discussion paper that I referenced above, Strengthening Cybersecurity Practices Associated with Servicing Medical Devices: Challenges and Opportunities, the agency asks, How can entities that service medical devices contribute to strengthening the cybersecurity of medical devices?

According to the discussion paper, FDA defines service to be the repair and/or preventive or routine maintenance of one or more parts in a finished device, after distribution, for purposes of returning it to the safety and performance specifications established by the original equipment manufacturer (OEM) and to meet its original intended use.

In other words, the first step in advancing medical device cybersecurity is to limit and ensure that those who control repairs and maintenance of these highly sophisticated pieces of health care technology are regulated FDA manufacturers.

On July 27, the FDA is holding a public meeting on this topic. It couldnt be timelier. The proper servicing and security of medical devices and other health care technologies mustnt be subsumed for profit.

Peter J.Pitts, a former FDA Associate Commissioner, is president of the Center for Medicine in the Public Interest and a visiting professor at the University of Paris School of Medicine.

Visit link:
The major health care and cybersecurity risk of 'Right-to-Repair' laws | TheHill - The Hill

Researchers from the University of Leeds and the University of Sheffield have discovered a key mechanism in preventing the escalation of blockages caused by blood clots.

A blood clot forms a pulmonary embolism or blockage, cutting off blood flow to major blood vessels in the lungs. In many cases, the blockage is caused by fragments that have broken away from a blood clot elsewhere in the body, such as a deep vein thrombosis in one of the legs. The fragments are transported to the lungs via the blood stream. Now, researchers have discovered that the protein fibrin plays a key role in stabilising the original clot to prevent bits of clot from breaking loose.

The findings from the research, which was funded by the British Heart Foundation, have been published in the scientific journal PNAS.

The research team used animal studies involving mice to investigate a key chemical building block of the clotting protein fibrin, known as -chain cross links. The scientists found that the -chain cross links give the fibrin its stability through enhanced resistance to rupture and clot fragmentation.

The study examined clot behaviour in mice that were genetically modified so they could not produce the stabilising -chain cross links in the fibrin, and compared them with mice that could.

The results revealed that the clots without the -chain cross links were more unstable and more likely to fragment and produced more associated embolisms.

Dr Cdric Duval, the studys lead author and lecturer in the School of Medicine at Leeds, said: What we believe is happening is that, without the -chain cross links, the fibrin is not strong enough to hold the clot in place against the forces generated in the body from muscle movement and from blood flow.

Professor Robert Arins, also from the School of Medicine at Leeds, who supervised the research, said: The findings reveal the importance of the -chain cross links. These are the structural supports in the fibrin that keep the clot in place.

By identifying the structural dynamics of this mechanism, we have identified new targets for drugs that could be developed to stop fragments of a thrombosis breaking away to cause an embolism in the lungs.

This is a disease that is a major cause of disability and death around the world.

The research findings confirm the long-held suspicion by Professor Arins that the structure of fibrin plays a role in the fragmentation of clots but, until now, there was no scientific evidence.

He said: I have always thought that the remarkable elasticity of fibrin, which has been described as like rubber or spider silk, would be important to prevent clot fragmentation and thus thromboembolic disease.

I was astounded to see the level of differences in pulmonary embolism that resulted from a genetic mutation that resulted in reduced elastic recovery of the fibres. So, when I saw the results, it definitely was a wow moment and I also had the I told you so feeling.

Recommended Related Articles

Here is the original post:
Discovery could inform new preventive treatment for blood clots - Health Europa

Pancreatic cancer accounts for 3% of all new cancer diagnoses, but is the fourth leading cause of cancer death in the United States.5 Therefore, it is imperative that we, as a community, focus our efforts on learning more about precancerous conditions within the pancreas and the early identification of cancers; pancreatic cysts are an ideal target. There are 2 key components to remember with regard to pancreatic cysts: accurate identification and evidence-based longitudinal surveillance. Unfortunately, an ongoing issue for this patient population is that many are never appropriately identified or followed. However, even when identified, many patients are not referred to a pancreatic center of excellence, a gastroenterologist who focuses on the pancreas, or a surgeon with experience in pancreatic cysts. As a result, these patients can re-present years later with a pancreatic cancer.

Our institution, Saint Barnabas Medical Center, an RWJBarnabas Health Facility, in conjunction with the Rutgers Cancer Institute of New Jersey, has made efforts to focus on preventative care. Specifically, we have recently focused our attention on pancreatic cysts and partnered

with Eon to develop and implement a platform called Essential Patient Management (EPM) Pancreas to identify patients with a pancreatic abnormality, and then, longitudinally follow them using an innovative and modern cloud-based platform that includes automatic patient and physician reminders.

Through the adoption of Eon EPM Pancreas, patients who now undergo either ultrasound, computed tomography, or magnetic resonance imaging in our Emergency Department, inpatient setting, or outpatient imaging facility, will be automatically identified if they are found to have an abnormality within their pancreas. The patient will then be contacted by one of our preventative medicine nurse navigators with a phone call and a letter; they will also be offered consultation with our pancreatic care team. Additionally, the patients ordering physician will also be contacted with a letter and a call. This algorithm links all parties together and lets them know about the pancreatic abnormality that may harbor precancerous potential. This automatic identification and population of cyst factors into the cloud-based platform accomplishes the first key component to remember with these cysts.

The second component is accomplished through individual risk stratification. The pancreatic cyst size, tempo of growth, pancreatic duct caliber, mural nodularity, evidence of pancreatitis, tumor markers, pancreatic cyst fluid aspirate for carcinoembryonic and amylase levels, and, at times, genetic mutations are added to the Eon EPM dashboard. Putting these factors together, along with national and international guidelines, we determine how to best manage and follow a particular patient. Previously, this has been done by using an Excel spreadsheet. However, now, with the EPM platform, we can advance healthcare and manage patients electronically; the cloud-based system embeds into our institutions electronic medical record (EMR) system, and with that, all the aforementioned factors can be seen immediately at the time of consultation. Moreover, we have extrapolated the method of a tumor board into our pancreatic cyst clinic and we now have a weekly pancreatic multidisciplinary conference where we discuss our patients with pancreatic cysts, thus providing them with a multidisciplinary/team approach.

Eon EPM offers the most powerful Pancreas solution that uses best-in-class technology to identify incidental pancreatic abnormalities, and longitudinally track patients who require serial surveillance. Eon EPM uses sophisticated proprietary models, referred to as Computational Linguistics data science models, to positively identify incidentally found pancreatic abnormalities with 93.9% accuracy; this high accuracy rate means fewer missed patients and less coordinator effort. Moreover, EPM can integrate with any facilitys EMR and IT system, and through Robotic Process Automation, it automates many mundane and repetitive tasks.

Eon EPM Pancreas detects incidental pancreatic abnormalities noted in radiology reports, extracts pertinent information from these reports such as pancreatic cyst characteristics, enters all information into one dashboard for serial surveillance, ensures patients are tracked and followed according to evidence-based guidelines, segments and prioritizes patients based on risk stratification, and triggers follow-up.

In summary, there are 2 overarching goals of this program. The first is to improve the quality in identifying patients with pancreatic cysts and longitudinally following them to ensure that they do not fall through the cracks within the community in which they are being served. The second goal is to offer patients surgery only when it is indicated because the great majority of pancreatic cysts only require lifetime surveillancenot an operation. If we can identify high-risk pancreatic cysts and surgically remove them prior to the development of pancreas cancer and prevent other patients from having an unnecessary operation, we believe that to be a massive improvement in how patients are being cared for. I have no doubt that Eon EPM Pancreas Solution will change the landscape for patients with pancreatic cysts and tumors, and have a true impact on survival from pancreatic-related diseases.

Russell Langan, M.D., is chief of Surgical Oncology and Hepatopancreatobiliary Surgery at Saint Barnabas Medical Center (SBMC), an RWJBarnabas Health facility, and surgical oncologist at Rutgers Cancer Institute of New Jersey.

Link:
RWJBarnabas Health Pioneers Innovative Pancreatic Cyst Surveillance Program - OncLive