StemCell Therapy

CLEVELAND Anyone who has driven on the shoreway near downtown has come just a few feet away from a series of brick buildings that, in some cases, are just feet away from the road.

What many people dont know is that just a few feet from all those passing cars is a company helping doctors fight cancer insight a nondescript but wide open building.

Thats actually what were were looking for, said GenomOncology CEO Brad Wertz talking about the companys new space.

He says GenomOncology was looking for a place where they could build a modern, start-up type office space.

From the street, First Energy Stadium is to the north, with the Flats, Warehouse District, and Public Square a short walk away in other directions.

You start with a cool, comfortable, enjoyable place to work that we believe is highly productive, highly collaborative and you build out from there based on what youre in the mood for, said Wertz.

Wertz says the space is home base for Cleveland-based employees, a place to visit for the few employees who work remote, and allows the company to host clients in from out of town, after the coronavirus passes.

Thats all important for a bio-technology company looking to attract all kinds of workers. Additional space on other floors gives the company options to expand in the future.

GenomOncology Chief Technology Officer Ian Maurer says the demand for their work continues to increase as they help more doctors.

How do we take DNA data for cancer and process it, analyze it, and understand what the variances mean, said Maurer explaining the work GenomOncology does.

He says more research is revealing more about the human body, helping doctors fight cancer more effectively. Since theres more information to keep track of, GenomOncology has created software that helps doctors find the right specialized treatment based on the best knowledge of the day.

Were not about replacing pathologists, said Maurer. Were about making them better. Were about democratizing this information, this knowledge so everyone across the country can give the best care to their patients.

All just a few feet off the shoreway.

Have you ever noticed something interesting in Northeast Ohio and wondered, Heywhats going on there?

Us, too. We love learning more about what shapes the world around us -- the buildings, the spaces and the ways we move between them.

Next time you're wondering about some building, project or piece of land, send me an email at Kevin.Barry@wews.com and I'll look into it for a possible story.

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Biotechnology company just feet away from the shoreway helping doctors diagnose and treat cancer - News 5 Cleveland

BOSTON & TORONTO--(BUSINESS WIRE)--Virna Therapeutics announces that they are partnering with University of Toronto to in-license neutralizing antibodies, to treat COVID-19. The discovery was made in the laboratory of Sachdev Sidhu, PhD., a professor of Molecular Genetics at the University of Torontos Donnelly Centre for Cellular and Biomolecular Research and founder of the Toronto Recombinant Antibody Centre.

The speed and scale of the COVID-19 pandemic has revealed the urgent need for better methods for developing and testing novel therapeutics. The crisis has presented severe challenges to global health but has also provided an opportunity to integrate advanced methods. The speed with which SARS-CoV-2 neutralizing antibodies were produced and validated highlights the robustness of the Donnelly Centre antibody engineering platform and its ability to address urgent health challenges like COVID-19, says Brenda Andrews, Director of the Donnelly Centre. "The partnership with Virna Therapeutics is the latest in a string of industry collaborations allowing our investigators to translate their discoveries into new therapies."

The founders of Virna Therapeutics include Dr. Sachdev Sidhu (Chief Scientific Officer), leader of the discovery and development process, Suresh K. Jain, PhD. (President and Chief Executive Officer), a Boston-based serial biotech entrepreneur with a track record of success in building world-class organizations and teams, and Pier Paolo Pandolfi, MD., PhD., FRCP, a famed cancer molecular geneticist and RNA therapy expert.

Virna Therapeutics has a three-pronged strategy to target the COVID-19 virus: (1) neutralizing antibodies that will prevent the virus from entering host cells, (2) CRISPR/Cas13d-based and LNA-based technologies for the treatment and prevention of RNA virus infection and (3) novel protease inhibitors that will prevent replication and release from host cells.

Virna has prioritized developing potent and highly selective neutralizing antibodies against spike proteins and plans to clinically test these leads within the next three to four months says Dr. Jain. We aim to become the worlds leading expert in the development of novel, best-in-class, anti-viral therapies based on synthetic antibodies, small molecules and RNA medicine.

Dr. Sidhu adds, Besides antibodies against spike protein, we also have several antibodies that target additional epitopes on the spike protein and are exploring those in functional assays. We are confident that the targeting of the key epitope will be a very effective therapy, but we still have a long-term interest in achieving a complete understanding of the various epitopes that can be recruited for therapy.

About University of Toronto

Founded in 1827, the University of Toronto is Canadas leading institution of discovery and knowledge. Located at U of T, the Donnelly Centre is a research institute where scientists from diverse fields make discoveries to improve health. It houses the Toronto Recombinant Antibody Centre (TRAC), which produces a variety of antibodies to support academic collaborations, industry partnerships and to help seed promising start-up companies. U of Ts Innovations & Partnership Office (IPO) is responsible for the negotiation and licensing of biologics from the university and represents U of T in its commercial transactions with VIRNA. For more information about the Donnelly Centre, visit us at thedonnellycentre.utoronto.ca or follow us on LinkedIn and Twitter.

About VirnaVirna Therapeutics Inc. is a privately held biotech company specializing in multi-pronged discovery technologies. While Virna is researching multiple approaches for treating infectious diseases, their validated synthetic antibody technology is a powerful platform enabling efficient generation of fully-human monoclonal antibodies. The company is headquartered in Boston, Massachusetts and has a registered office in Montreal; http://www.virnatherapeutics.com

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Virna Therapeutics and University of Toronto Announce Licensing of Neutralizing Monoclonal Antibodies to Treat COVID-19 - Business Wire

With top White House officials indicating a coronavirus vaccine may be available by January 2021, scientists and vaccine experts outside the Trump administration are cautious but optimistic that a vaccine could be delivered on such an accelerated timeline.

Experts interviewed by ABC warned that developing a vaccine within a 12-month time frame could mean throwing normal scientific standards out the window, but added that a vaccine could be available by the new year if everything goes perfectly.

While President Donald Trump has been bullish in his promise to have a "vaccine by the end of the year," his top advisors have taken a more measured approach, saying a January deadline is a best-case scenario. Last week, Dr. Anthony Fauci, the nation's top infectious disease doctor, said, "we want to go quickly, but we want to make sure it's safe and it's effective."

Since the start of the U.S. epidemic, Fauci has been estimating a vaccine is 12 to 18 months away. But the prior record for vaccine development -- the mumps vaccine -- took four years, meaning Fauci's early estimates drew skepticism among many vaccine experts.

But with the growing sense of urgency as the death toll mounted dramatically in March and April, vaccine developers collapsed the normal development timelines by running concurrent studies that would normally be conducted in a stepwise approach. Meanwhile, drug companies are already scaling up production without even knowing which vaccine is likely to work.

"It is not impossible," said Paul Duprex, PhD, Director of the Center for Vaccine Research and professor of microbiology and molecular genetics at the University of Pittsburgh. "It's of course very aggressive -- but it is possible."

"You'd have to be lucky," said Dr. Paul Offit, co-inventor of the rotavirus vaccine, who sits on the Food and Drug Administration's vaccine advisory committee. "It would be remarkable, but not completely ridiculous."

The first box of the vaccine candidate to be used in Phase I / II trial, at the Clinical Biomanufacturing Facility (CBF) in Oxford, Britain, April 2, 2020.

Dr. Paul Goepfert, professor of medicine at the University of Alabama at Birmingham (UAB) and an expert in vaccine design, said a vaccine by January would only be possible "if everything works out perfectly."

To have a new vaccine by January, experts said a study would need to be conducted in parts of the world where the pandemic is still raging. This would help ensure a big enough group of patients were exposed, and then protected, from the virus.

Then, one of the vaccines currently being developed would have to show positive results, which isn't a guarantee. That vaccine would also have to prove safe, without any dangerous side effects. Finally, vaccine makers would have to be ready with hundreds of millions of doses as soon as data is in hand.

"It is possible but not likely," Goepfert said.

"It's difficult to set exact timelines," said Rinke Bos, principal scientist and immunologist for Johnson and Johnson - one of the companies advancing a COVID-19 vaccine. There are several complicating factors that could easily delay the timeline beyond 18 months, including the fact that the studies will need to be conducted in places where the virus is still circulating.

"Those are quite complicated discussions," she said. "It's very difficult to say something about a timeline."

Right now there are more than 100 vaccines being studied, and at least eight of those have already progressed outside the laboratory and into human studies, according to the World Health Organization. The furthest along include candidates from the University of Oxford, Pfizer, Moderna Therapeutics, Inovio Pharmaceuticals and China's CanSino Biologics.

Many of these vaccines use different technology -- some brand-new to vaccine science -- and experts still don't know which is the most likely to work.

Meanwhile, the White House's Operation Warp Speed has resulted in a handful of vaccine candidates that might work against the novel coronavirus -- although those will also need further study.

Right now, many of the vaccines already tested in people have been accelerated far beyond the normal, methodical timelines. Instead of moving from animal studies in a laboratory to a carefully tiered Phase I, II and III system of in-human study, some of these studies are being conducted simultaneously -- with some even skipping normal animal studies.

Under normal circumstances, it would be too expensive for drug developers and too risky for human volunteers to run these types of studies concurrently. But vaccine developers are deviating from the normal rule book because of the sheer devastation of the global pandemic.

A researcher works on coronavirus vaccine development at the Walter Reed Army Institute of Research in Silver Spring, Md., April 28, 2020.

"We as scientists are rather linear individuals," said Duprex. "There are huge financial reasons for that." Now, he said, "there are people taking risks, doing something that might not lead to fruition."

The scientific challenges are unprecedented, considering how little is known about the novel coronavirus that has killed more than 250,000 people across the globe.

For example, said Offit, most vaccines work by triggering an immune response inside the body without making a person sick. But for this novel coronavirus, scientists still haven't had time to adequately study the body's immune response to infection -- meaning we don't know whether an immune system response necessarily protects against a future infection.

And rushing development could mean that important safety issues are missed.

"Most vaccines have been pretty safe, but there have been problems in the past," said Goepfert.

And the downside of immunizing millions of people with a rushed, unsafe vaccine could have long-ranging consequences.

"Vaccines are so, so important for public health," Duprex said. If something goes wrong the general public will extrapolate that vaccines are unsafe."

"Time is critical, of course, but safety is critical," said Duprex. "In the middle of this fast approach, we absolutely cannot compromise on safety."

Tune into ABC at 1 p.m. ET and ABC News Live at 4 p.m. ET every weekday for special coverage of the novel coronavirus with the full ABC News team, including the latest news, context and analysis.

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Is it possible to have a safe coronavirus vaccine by New Years Eve? - ABC News

The global spread of COVID-19 has forced us to become familiar with terminology from contact tracing to social distancing most of us didnt know a few months ago. Now, if the hunch of many scientists is correct, we are about to hear a lot about genome sequencing, too.

In search of a genetic explanation for why the novel coronavirus affects some people much more severely than others, the federal government has invested $20 million into a national project to sequence and analyze the genomes of 10,000 Canadians who have had COVID-19.

The project, part of a larger $40 million investment in the Canadian COVID Genomics Network, will be managed by CGEn, a federally funded national platform for genome sequencing, a complex process that, among other things, can help spot DNA mutations in individuals or groups that predispose them to certain illnesses.

There seems to be a genetic component to this virus. You can see that in the individuals who have had the same level of exposure to the virus but respond very differently, says Lisa Strug, associate director of The Centre for Applied Genomics (TCAG) at The Hospital for Sick Children (SickKids) and an associate professor in the department of statistical sciences in the University of Torontos Faculty of Arts & Science.

That points to this idea that our genetics could impact our response to the virus and how some people can fight it off and some cant. So, we need to know what are the genetic variations that are determining this variable response?

Strug, who is scientific lead of the CGEn sequencing project, says published studies have already examined so-called heritability.

Researchers have looked at whether some of the symptoms being seen with COVID-19 run in families, she says. Some families are experiencing the virus in the same way they all have mild symptoms, or all have very severe experiences. So it appears that there is some hereditary component. And thats another piece of evidence pointing to genetics.

Strug will work with scientists at CGEn nodes at U of T and SickKids, McGill University and at the University of British Columbia. CGEn will collect blood samples from 10,000 patients from across the country, of all ages and genders, who have COVID-19. The researchers will then extract the DNA from the samples, sequence and analyze it with sophisticated computing and statistical techniques and put all the clinical and genetic information in a protected database so researchers around the world can use it in their COVID-19 projects. A similar project is being conducted in the United Kingdom, which will involve about 20,000 patients.

The large sample size is essential because there are likely different factors that contribute to the response to COVID-19 infection in different individuals and at different ages, and the more data we have, the greater the ability researchers will have to identify these, says Strug. There is a huge benefit in not just looking at one patient at a time, but across the population and across all genes.

How will this information benefit research into the novel coronavirus? Strug says the results will be useful in identifying who is the most susceptible to COVID-19 and in understanding which genes scientists should be targeting when developing drugs to treat the virus and, ideally, a vaccine that will help control it.

There is also another major benefit of starting this massive, two year-long project immediately: data that can be used to protect ourselves from future illnesses.

U of Ts StephenScherer,the lead principal investigator of CGEn,says the genetic information gleaned from the project can be used to help guard against future outbreaks (photo courtesy of SickKids)

This is Canadas first time doing a large-scale project like this, says Stephen Scherer, TCAGs director and a University Professor of molecular genetics at U of T. When global society moves past the COVID-19 pandemic, there will be another one. All this genetic information will be extremely useful for that point in the future.

Were about to get an excellent genetic cross-section of the Canadian population. This virus has been destructive, but it is also forcing us to create new knowledge that we will be able to leverage for years to come.

For example, knowledge gained from the SARS epidemic of the early 2000s has been useful during the current outbreak, according to Strug and Scherer. Thats because of the similarities between the two coronaviruses.

That has helped the global research community be able to respond quickly to this new virus, says Strug.

That said, genetic sequencing must deal with a huge amount of data. The numbers are staggering the human genome contains three billion base chemical units that code for about 25,000 to 35,000 genes, and this project will sequence 10,000 genomes.

This is very big data analysis, Strug says.

Both scientists note that computing technology used for sequencing is far more advanced than even a decade ago. The technology has become so sophisticated and affordable that we can propose to look at entire DNA sequences, says Scherer. In 2003, for SARS 1, we couldnt do this.

Scherer, who is the lead principal investigator of CGEn, a senior scientist at SickKids and director of U of Ts McLaughlin Centre, says hes impressed with how the global research community has pivoted to focus on solving the COVID-19 puzzle.

Its amazing how scientists around the world have come together on this, he says. Just at U of T, there are researchers working on COVID-19 who I would have never predicted would be. I would say that 75 per cent of the people Im talking with every day, now, are not the same people I was talking with eight weeks ago. But they have a specific technology or some useful knowledge that links in.

Thats how scientific research needs to work to be effective: By bringing in a wide breadth of perspectives and specialists, cracking COVID-19 could become this generations moonshot.

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U of T researchers help lead national effort to explore role of genes in COVID-19 - News@UofT

DetailsCategory: Proteins and PeptidesPublished on Tuesday, 26 May 2020 18:19Hits: 273

Pegzilarginase Showed Durable Clinical Response at 56 Week Analysis

All Patients Demonstrated a Marked and Sustained Reduction in Plasma Arginine

Favorable Safety Profile, Consistent with Previously Reported Results

AUSTIN, TX, USA I May 26, 2020 I Aeglea BioTherapeutics, Inc. (NASDAQ:AGLE), a clinical-stage biotechnology company developing a new generation of human enzyme therapeutics as innovative solutions for rare and other high-burden diseases, today announced a new 56 week analysis on Arginase 1 Deficiency (ARG1-D) patients who have been treated with pegzilarginase from the Companys completed Phase 1/2 clinical trial and the ongoing Phase 2 open-label extension study. The data were shared yesterday in a virtual, late-breaking oral presentation at the 6th Congress of the European Academy of Neurology.

Arginase 1 Deficiency is a devastating disease that is frequently under diagnosed or misdiagnosed as more common neurological conditions, such as cerebral palsy, due to lack of awareness of this rare condition, said George Diaz, M.D., Ph.D., division chief of medical genetics in theDivision of Medical Genetics and Genomics and Department of Genetics and Genomic Sciences at theIcahn School of MedicineatMount Sinai, New York, NY. Because of the conditions progressive nature, it is essential that patients be diagnosed early, and there is an urgent need for a therapy that addresses the underlying cause of the disease and improves clinical manifestations.

The results of this long-term data demonstrate that treatment with pegzilarginase resulted in a durable clinical response, which is a critical factor in effectively treating a life-long, progressive condition, said Ravi M. Rao, M.B Ch.B PhD, chief medical officer of Aeglea. We are also pleased to see that the lowering of arginine levels observed in the 20 week analysis were maintained through the 56 week analysis. These results align with the primary endpoint of PEACE, our ongoing pivotal Phase 3 clinical trial, and together with the durable clinical response bolsters our belief that pegzilarginase has the potential to be an impactful treatment for people living with Arginase 1 Deficiency.

The presentation, titled 1 Year Data from First in Human Study of Pegzilarginase for the Treatment of Arginase 1 Deficiency (ARG1-D), includes data on 13 patients treated with pegzilarginase who completed the 56 week treatment period (8 weeks Part 2 repeat dosing + 48 weeks open-label extension).

Highlights from the 56 week analysis include:

The presentation is available for download on the Presentations & Events section of the Companys website.

About the Phase 1/2 and Open-Label Extension Trial

The Phase 1/2, multicenter, single arm, open-label extension study of pegzilarginase enrolled patients aged 2 years and older with Arginase 1 Deficiency in the United States, Canada, and Europe. The trial investigates single ascending doses (Part 1), repeated weekly dosing for eight weeks (Part 2). The trial enrolled 16 adult and pediatric patients and 14 patients rolled over to the open-label extension. The primary endpoint of the trial is safety and tolerability of intravenous administration of pegzilarginase in patients with Arginase 1 Deficiency. The trial also evaluated the pharmacokinetic and pharmacodynamic effects of repeated doses of pegzilarginase on plasma arginine levels, and evaluation of clinical outcomes using several mobility assessments.

Please visit http://www.clinicaltrials.gov for more information.

About Pegzilarginase in Arginase 1 Deficiency

Pegzilarginase is an enhanced human arginase that enzymatically lowers levels of the amino acid arginine. Aeglea is developing pegzilarginase for the treatment of patients with Arginase 1 Deficiency (ARG1-D), a rare debilitating disease presenting in childhood with persistent hyperargininemia, severe progressive neurological abnormalities and early mortality. Pegzilarginase is intended for use as an enzyme therapy to reduce elevated blood arginine levels in patients with ARG1-D. Aegleas Phase 1/2 and Phase 2 open-label extension data for pegzilarginase in patients with ARG1-D demonstrated clinical improvements and sustained lowering of plasma arginine. The Companys single, global pivotal Phase 3 PEACE trial is designed to assess the effects of treatment with pegzilarginase versus placebo over 24 weeks with a primary endpoint of plasma arginine reduction.

About Aeglea BioTherapeuticsAeglea BioTherapeutics is a clinical-stage biotechnology company redefining the potential of human enzyme therapeutics to benefit people with rare and other high burden diseases. Aeglea's lead product candidate, pegzilarginase, is in a pivotal Phase 3 trial for the treatment of Arginase 1 Deficiency and has received both Rare Pediatric Disease and Breakthrough Therapy Designation. The Company received approval of its Clinical Trial Application (CTA) for ACN00177 for the treatment of Homocystinuria by the United Kingdoms Medicines and Healthcare Products Regulatory Agency (MHRA). Aeglea has an active discovery platform, with the most advanced program for Cystinuria. For more information, please visit http://aegleabio.com.

SOURCE: Aeglea BioTherapeutics

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Aeglea BioTherapeutics Announces 1-Year Data for Pegzilarginase in Patients with Arginase 1 Deficiency at the 6th Congress of the European Academy of...

Ordering takeout or delivery during a pandemic, you cant help but wonder just how safe food that hasnt been prepared in your own home might be especially when delivered by a stranger.

There are no reported cases of COVID-19 being spread through food, and we know that the chance of transmission through food is very low. Thats reassuring, but its still easy to feel anxious about an interaction that was mundane in pre-pandemic times. We spoke to health and food experts for best practices when handling takeout during a pandemic.

The short answer is no. Food that has been cooked is very likely to be safe to eat. When a meal is moved from the kitchen straight into a takeout container, those chances become even lower.

Heres the scientific answer:

This virus is very different than the types of viruses commonly being spread through food, explains Jennifer Ronholm, assistant professor of agricultural and environmental science at McGill University. COVID-19 is an enveloped virus, meaning it is surrounded by a phospholipid, protein and glycoprotein membrane. These membranes are critical to the virus it simply cannot infect you if its membrane isnt mostly intact.

However, these viral membranes are very sensitive to desiccation, heat, enzymes, pH and detergents, she adds. Which means enveloped viruses succumb to the elements relatively quickly when compared to non-enveloped viruses, like norovirus, which are known to spread easily using food as a vector.

When it comes to the delivery process itself, the individual most at risk is the delivery person, who interacts with both the restaurant and the customer. COVID-19 is transmitted through respiratory droplets, i.e. if someone coughs, sneezes or breathes while handling food though the risk of it spreading via packaging is low.

As such, you should opt for contactless payment when possible, whether paying electronically or leaving cash outside your door in an envelope; asking for contactless delivery; remaining physically distanced from the delivery person; and washing your hands after handling the delivery.

A useful practice is to assume your delivery person is infected and treat the surface of your package as though it has been contaminated in order to get into a new rhythm.

After you receive the package, remove the box of food and throw away the bag. Open the box, wash your hands and dish the food onto a plate. Then throw away the box. Wash your hands again and eat. If youre dealing with uncooked food or groceries, for example, fruits or vegetables, give them a good wash or wipe-down.

If youre picking up takeout, maintain a two-metre distance from other patrons and do not go out if you are sick or living with someone who is.

Reheating leftovers is okay, as isrefrigerating food.

Coronavirus is a virus not a bacterium so it does not grow outside of the human body, says William Navarre, associate professor of molecular genetics at the University of Toronto. If I put 1,000 virus particles on a piece of food and come back a day later? Still 1,000 viruses. If I put 1,000 bacteria [like salmonella or listeria] on a piece of food? By the next day, Ill have over a million bacteria. So while refrigeration of food is a great thing, its irrelevant for COVID-19. In fact, it may keep the virus active for longer than if it were sitting at room temperature.

If you suspect your food is contaminated, toss it out.

When thousands gathered in close proximity in Torontos Trinity Bellwoods Park on May 23, Bloordale restaurant Seoul Shakers announced it would no longer make park deliveries due to the risk not just to those delivering, but those in the park.

In Wuhan, China, where the outbreak wreaked havoc for months, many delivery drivers wore protective gear, including full-body suits, gloves, goggles and masks and were provided with sanitizer by their employers. They also had temperature checks twice daily.

Restaurants and delivery services are also adapting to safety measures in Canada, but to a lesser degree. DoorDash is offering its delivery drivers hand sanitizer and gloves through online delivery, while Uber Eats is working to provide delivery people with sanitization materials.

The risk to delivery people depends not only on the restaurant but on the customer. Its important to evaluate how much danger you might be placing your delivery person in when you place an order. Where are you located? Are you sick or living with someone who is? Can you manage a contactless process? Its important to weigh the risk to both parties. (And dont forget to tip.)

While restaurant kitchens should always operate in accordance with provincial occupational health and safety rules, they must now follow additional public health measures, as per the chief medical officer of health: washing hands often, sanitizing between each transaction and delivery, wearing masks and gloves where possible, sneezing or coughing into sleeves, remaining physically distanced in the kitchen when possible, adding floor markings to manage traffic flow, installing barriers between cashiers and customers or for curbside pick-up.

Most restaurants are obligated to follow health and safety guidelines regarding preparation and storage of food and most of what they do to prevent other food issues is going to be useful to limit the spread of COVID-19, says Navarre. Restaurant workers should be more careful about always wearing masks in the kitchen and only using clean hands when preparing food. Better yet, utensils and tongs to touch food when possible. All restaurants should be tripling their efforts.

Now that the weather is warmer, he says, its beneficial to keep restaurant back doors open while a fan blows air out, as viral particles in the air build up over time when there is poor ventilation. Gloves need to be regularly cleaned or changed. While disposables may not be the best environmental choice, they can be safer, more efficient and better for your skin.

These should be the new rules, says Navarre. Lets hope, when COVID-19 is old news, some kitchens might consider keeping some of the new rules.

@_sadafahsan

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How to safely handle delivery and takeout food - NOW Magazine

Kyle Caires takes a selfie with prized wagyu cattle. Photos courtesy of Kyle Caires

Animal scientist Kyle Caires and a research team have found a way to nearly double pregnancy rates in wagyu, a Japanese breed of cattle that typically has low rates of reproduction but is prized for its meat.

By using technologies, such as artificial insemination, and pairing them with nutrition, management techniques and healthy and controlled environments, ranchers can improve their cattles reproductivity for less costs.

And meat lovers and chefs can have more access to high-quality beef.

Outcomes are much better when you work with Mother Nature, instead of against her, and the same is true when raising livestock, said Caires, the Maui extension agent for the University of Hawaii-Manoa College of Tropical Agriculture and Human Resources. Therefore, choosing genetics with production levels calving ease, growth rate, milk production to fit a ranchs forage resources, rainfall level and availability of labor, is a great approach for all ranchers in Hawaii.

Caires, who works in the Department of Human Nutrition, Food and Animal Sciences, recently published his research on how to improve the reproductive rates of the Japanese Black. He also spent the last six weeks setting up programs for ranchers and beef producers across Maui County.

Kyle Caires, Maui extension agent for the University of Hawaii-Manoa College of Tropical Agriculture and Human Resources, analyzes cattle embryo samples.

CTAHR programs include educational programs and outreach assistance to ranchers that want to consider estrus synchronization, artificial insemination, semen testing and pregnancy checking. He said that embryo transfers will be offered in the near future.

Excellent pregnancy rates are achieved with integrated approaches that combine genetic improvement strategies with good management practices on a case-by-case basis, not a one-size-fits-all approach, he said.

These safe procedures are no different than what would happen naturally in cattle reproduction, he said. For example, for ranchers breeding first-calf heifers, artificial insemination could help improve productivity because semen from bulls are proven to produce low-weight births, which makes the birthing process easier for first-time mothers, which in turn is better for the cows longevity and health.

Likewise, the semen used in artificial insemination protocols also must pass biosecurity measures to eliminate disease transmission, an added bonus, he said.

In collaboration with researchers from Washington state and Brazil, the article titled, The outcome and economic viability of production using IVF and SOV techniques in the Wagyu breed of cattle, was published May 1 in Veterinary Sciences.

The methods showed a 70 percent decrease in cost compared to typical genetic improvement strategies, Caires said.

Seven ranches on Maui, as well as several on Molokai, Oahu, Kauai and Hawaii island, are utilizing wagyu genetics already. However, due to their lower productivity, Caires said that most ranches maintain wagyu cross-breeds, not pure-breds.

Successful conception rates are between 75 and 80 percent following a single round of artificial insemination, he said, which is much greater than the national average of 60 percent for cows.

Other tips to improve beef reproduction include good nutrition, lowering stress, routine vaccinations, pasture and grazing management, as well as scoping out cows with genetic potential.

All the little things add up to a strong foundation that pays big dividends to set ranchers up for success when using technologies, like artificial insemination, where they can also utilize elite genetics from across the country at a fraction of the cost, he said. In order for AI to be consistently successful at the ranch, reproductive management protocols are used to help ranchers better time the delivery of semen in to match the ovulation event in the cows.

Moving forward, Caires plans to continue his applied research in order to improve genetics, reproductive efficiency and overall productivity for local farmers.

The main goal of our research is to help Hawaiis ranchers remain competitive in a dynamic, ever-changing global beef industry, he said.

To review the results of the study, visit mdpi.com/2306-7381/7/2/58/htm. For information about CTAHR programs on Maui, visit ctahr.hawaii.edu/Maui/pages/Programs.aspx.

* Dakota Grossman can be reached at dgrossman@mauinews.com.

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Where's the wagyu? | News, Sports, Jobs - Maui News

Abstract

Increasing occurrence of moderate to severe intrauterine adhesion (IUA) is seriously affecting the quality of human life. The aim of the study was to establish IUA models in nonhuman primates and to explore the dual repair effects of human umbilical cordderived mesenchymal stem cells (huMSCs) loaded on autocrosslinked hyaluronic acid gel (HA-GEL) on endometrial damage and adhesion. Here, we recorded the menstrual cycle data in detail with uterine cavities observed and endometrial tissues detected after intervention, and the thicker endometria, decreased amount of fibrotic formation, increased number of endometrium glands, etc., suggested that both HA-GEL and huMSC/HA-GEL complexes could partially repair IUA caused by mechanical injury, but huMSC/HA-GEL complex transplantation had notable dual repair effects: a reliable antiadhesion property and the promotion of endometrial regeneration.

Intrauterine adhesion (IUA), known as Asherman syndrome, is described as the partial or complete binding of the uterine cavity due to the buildup of scar tissue formation in the upper functional layer, resulting from endometrial damage to the lower basal layer (1). Repeated intrauterine operations, such as dilatation and curettage (D&C) and hysteroscopy, are the main cause of the common prevalence of IUA, with approximately 45% of moderate-to-severe cases occurring in these circumstances (2). Severe endometrium dysfunction will cause women within reproductive age to have this reproductive disadvantage, which was once considered a terminal disease that caused infertility (3, 4).

Therefore, the vital aim for IUA treatment is to re-establish the uterine cavity and restore endometrial function. The current and standard operation method for IUA is hysteroscopic transcervical resection of adhesion (TCRA), while the preferred alternative involves the combined application of various adjuvant therapies, including physical barriers (contraceptive device, intrauterine balloon device, Foley balloon, etc.) for postoperative adhesion and estrogen therapy and amnion graft for endometrial regeneration (58). Although there is a certain therapeutic efficacy of these antiadhesion strategies, there are some disadvantages and shortcomings to the strategies that cannot be ignored, such as resistance to secondary surgery, limited area of isolation, induction of intrauterine inflammatory response, and difficulty in endometrial regeneration (9). Further, the high recurrence rate of postoperative adhesion and the low clinical pregnancy rate are still a focus and are universally recognized as a problem for patients with severe IUAs (4, 10).

Autocrosslinked hyaluronic acid gel (HA-GEL), another promising physical barrier with natural mix of extracellular matrix and synovial fluid, has been approved by China Food & Drug Administration (CFDA) as a medical device for clinical practice after hysteroscopic adhesiolysis to achieve improvement in histocompatibility and viscosity, and the American Association of Gynecologic Laparoscopists has reported the effectiveness of HA-GEL in the prevention of IUAs in 2017 (11). The application of HA-GEL in uterine cavity treatment has its own advantages of few degradations by product retention following the outflow of menstrual blood (11, 12). Compared to the previously used biomaterials, HA-GEL has a prolonged absorption time (as long as 7 to 14 days), the expansion characteristics of which can continuously isolate the postoperative uterine cavity to resist adhesion recurrence, and its other material properties can regulate the inflammatory response and repair endometrial injuries. Related experimental and clinical studies have suggested that HA-GEL is effective in the prevention of postoperative adhesion, and when combined application with a TCRA operation, it showed increases (~58.5%) in the effective rate of postoperative antiadhesion and decreases (~66.1%) in the postoperative recurrence rate (13). However, for severe IUA with a seriously injured basal layer and a loss of functional endometrium, endometrial regeneration remains an enormous challenge owing to the limited efficacy of current interventions.

Recently, stem cellbased therapy has emerged as a promising and exciting method of tissue regeneration (1416). Human umbilical cordderived mesenchymal stem cells (huMSCs) originate from the embryonic mesoderm and have the potential for multipotent differentiation; they have been regarded as a promising and extensive source for cell-based therapies due to their easy collection from discarded umbilical cords and their low immunogenicity. Some studies have shown the potential of huMSCs to repair damaged tissue (1720), and the feasibility of stem cells in restoring the endometrial structure and function has also been verified by additional clinical and experimental studies (2124). In this study, we used rhesus monkeys to construct a previously unidentified animal model of IUA and aimed to develop a complex of huMSCs loaded on HA-GEL to increase the local perseverance and activity of the stem cells and to improve the poor prognosis with the following dual functions: preventing postoperative adhesion with biomaterials and repairing the full layer of uterine wall. We also aimed to analyze the related repair or endometrial injuries, to study the motivation behind endometrial regeneration, and to explore the underlying mechanisms.

huMSCs [passage 3 (P3) to P9] had an appearance that was similar to typical spindle-shaped fibroblast-like cells, and they were arranged closely with vortex-like growth (fig. S1A1). The positive cells that were expanded in the enriching culture were successfully induced to become osteoblasts with bone matrix formation and adipocytes with lipid droplet formation (fig. S1A2 and A3). In addition, fluorescence-activated cell sorting (FACS) showed that the targeted cells expressed CD44 (99.40%), CD73 (99.56%), CD90 (99.92%), and CD105 (99.80%), but not CD34, CD45, and HLA-DR (<1%; fig. S1B).

To further evaluate the safety of huMSCs on HA-GEL, FACS results preliminarily verified that there was a low parentage of apoptotic cells in the coculture group (huMSCs/HA-GEL), and there was no notable difference between the coculture group and the culture-separated group (huMSCs) (fig. S2, A to C). In addition, the live-dead cell staining result we obtained before was added, and the result showed a small number of dead cells in both the huMSCs/HA-GEL and huMSCs groups, without significant difference compared with that in the culture-separated group (huMSCs) (fig. S2, D and E).

Two months after endometrial intervention by uterine D&C, all six monkeys stopped menstruating; smaller uterine cavities and pale and uneven endometrial surfaces were observed, which had an adhesive zone full of endometrial cavity fluid. Thinner endometrial tissue was detected and observed under Doppler ultrasound scanning with discontinuous endometria and strong echo (Fig. 1A), and the endometrial thickness (1.9833 0.4298 mm) after mechanical injury showed significant differences when compared with the thickness (4.0333 0.5185 mm) before intervention (P < 0.01, n = 6; Fig. 1B and table S1). Changes in the structure of the endometrial tissues were assessed by hematoxylin and eosin (H&E) staining. Two months after mechanical injury, the endometrium was disorganized and had few or no glands (Fig. 1C). Endometrial gland numbers decreased markedly compared with those of the premechanical injury (0.6839 0.8608 versus 6.8576 2.6901 per unit area, respectively) (P < 0.001, n = 6; Fig. 1D and table S1). Similarly, to further evaluate the degree of fibrosis, Masson staining was performed at 2 months after mechanical injury (Fig. 1E). Increased fibrotic area ratios were detected and were analyzed quantitatively; more collagen deposition was observed at 2 months after mechanical injury compared with that of the premechanical injury (0.6557 0.6359% versus 0.0716 0.0942%) (P < 0.05, n = 6; Fig. 1F and table S1).

(A) Detection of Doppler ultrasound. A1: Representative image of endometrial thickness for pre-D&C; A2: Representative image of endometrial thickness at 2 months post-D&C (red arrow, the endometrium echo; blue area, the largest cross section of endometrium). (B) Comparisons of endometrial thickness for pre- or post-D&C. (C) H&E staining of endometria for pre-D&C (C1, C3, and C5) and post-D&C (C2, C4, and C6); 10401, 10403, and 10406, respectively; see table S3 for details. Inserted overview pictures are of lower magnification; black squares are highly magnified regions. (D) Masson staining of endometria for pre-D&C (D1, D3, and D5) and post-D&C (D2, D4, and D6); 10401, 10403, and 10406, respectively; see table S3 for details. Inserted overview pictures are of lower magnification; black squares are highly magnified regions. (E) Comparisons of endometrial gland numbers per unit area for pre- or post-D&C. (F) Comparisons of fibrotic area ratios for pre- or post-D&C. *P < 0.05, **P < 0.01, and ***P < 0.001 versus the pre-D&C group, and the results shown are the mean SEM of three technical replicates from each animal.

Two months after the huMSCs/HA-GEL complex was transplanted into the uterine cavity, menstruation resumed cycling in all monkeys, and there were significantly more endometrial gland numbers (4.9662 1.4935, per unit area) than there were (3.6320 1.0060, per unit area) after HA-GEL transplantation alone (P < 0.01; Fig. 2, A and B, and table S2). Moreover, the huMSCs/HA-GEL transplantation group showed marked decreases in fibrotic areas (5.5955 3.6572%) compared with that of the HA-GEL transplantation group (14.2131 13.7193%) (P < 0.01; Fig. 2, C and D, and table S2).

(A) Endometrial H&E staining at 2 months after HA-GEL transplantation (A1, A3, and A4 correspond to 10401, 10403, and 10404, respectively) and huMSCs/HA-GEL transplantation (A2, A5, and A6 correspond to 10402, 10405, and 10406, respectively); 10401 to 10406, see table S3 for details. (B) Endometrial Masson staining at 2 months after HA-GEL transplantation (B1, B3, and B4 correspond to 10401, 10403, and 10404, respectively) and huMSCs/HA-GEL transplantation (B2, B5, and B6 correspond to 10402, 10405, and 10406, respectively); 10401 to 10406, see table S3 for details. (C) Comparisons of endometrial gland numbers per unit area between the HA-GEL transplantation group and the huMSC/HA-GEL transplantation group. (D) Comparisons of fibrotic area ratios between the HA-GEL transplantation group and the huMSCs/HA-GEL transplantation group. ##P < 0.01 versus HA-GEL transplantation group, and the results shown are the mean SEM of three technical replicates from each animal.

Abdominal surgeries were carried out, and three normal uterine cavities were exposed and revealed a thicker endometrium without an adhesive zone and endometrial cavity fluid in the huMSCs/HA-GEL transplantation group, whereas three uterine cavities in the HA-GEL transplantation group were still found to be abnormal with a mild to moderate amount of adhesion and a thinner rough endometrium (Fig. 3A). In addition, the smooth and thicker endometrial tissue with a third-line echo was also revealed and verified by ultrasound examination in the huMSCs/HA-GEL transplantation group (Fig. 3B), and the endometrial thickness (4.2667 0.5558 mm) was significantly different compared with that (1.0667 0.6650 mm) in the HA-GEL transplantation group (P < 0.01; Fig. 3C and table S2). Furthermore, the ultrastructure of the endometrium in the huMSCs/HA-GEL transplantation group showed short and sparse microvilli on the surface of epithelial cells, mucinous secretions in the glandular cavity with orderly arranged cells, tight intercellular junctions, and obvious edema of stroma, but the endometrial ends were uneven and the cellular edges had a frayed morphology. Further, loose connections between cells were observed in the HA-GEL transplantation group (Fig. 3D).

(A) Representative images of uterine cavities in the HA-GEL transplantation and huMSCs/HA-GEL transplantation groups (the dotted area and the red arrow mark the endometrial area). (B) Representative images of endometrial thickness for ultrasound detection in the HA-GEL transplantation and huMSCs/HA-GEL transplantation groups (the red arrow marks the endometrial echo; the blue area marks the largest cross section of the endometrium). (C) Comparisons of endometrial thickness between the HA-GEL transplantation group and the huMSCs/HA-GEL transplantation group. (D) Representative images of ultrastructural changes in the HA-GEL transplantation and huMSCs/HA-GEL transplantation groups (the left panel shows the surface of epithelial cells; the right panel shows the intercellular changes). ##P < 0.01 versus 2 months postHA-GEL, and the results shown are the mean SEM of three technical replicates from each animal. Photos provided by Lingjuan Wang and Chengliang Xiong (Institute of Reproductive Health, Center of Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology).

By systematic and comprehensive comparison of endometrial tissues before surgery, increased gland numbers were found both in the HA-GEL transplantation group (3.63 1.01 versus 0.68 0.86, respectively, per unit area; P < 0.001) and in the huMSCs/HA-GEL transplantation group (4.97 1.49 versus 0.68 0.86, respectively, per unit area; P < 0.001). The gland numbers were approaching normal levels (6.86 2.69, per unit area; pre-D&C) 2 months after huMSCs/HA-GEL transplantation (Fig. 4A and table S3). Conversely, the Masson staining showed an increasing degree of fibrotic aggravation 2 months after HA-GEL transplantation (14.21 13.72% versus 0.66 0.64%; P < 0.05), but there was only a slight increase in fibrosis and some relief of aggravation after transplantation of the huMSCs/HA-GEL complex (5.60 3.66 versus 0.66 0.64; P < 0.01) (Fig. 4B and table S3). There was no significant difference in endometrial thickness or after mechanical injury (1.07 0.67 versus 1.98 0.41 mm) 2 months after HA-GEL transplantation compared with that of the HA-GEL transplantation, while the endometrial thickness was notably increased after transplantation of the huMSCs/HA-GEL complex (4.27 0.56 versus 1.98 0.41 mm; P < 0.01) that was similar to the normal levels observed before mechanical injury of the endometria (4.03 0.52 mm; pre-D&C) (Fig. 4C and table S3).

(A) Comparisons of endometrial gland numbers per unit area. (B) Comparisons of ratios of fibrotic area (%). (C) Comparisons of endometrial thickness (mm). *P < 0.05, **P < 0.01, and ***P < 0.001, all versus pre-D&C; ###P < 0.001 versus pre-D&C; #P < 0.05, ##P < 0.01, and ###P < 0.001, all versus 2 months post-D&C; ##P < 0.01 versus 2 months postHA-GEL, and the results shown are the mean SEM of three technical replicates from each animal.

The probe Vysis SRY Probe LSI SRY Spectrum Orange/Vysis CEP X Spectrum Green was used to mark huMSCs by a fluorescence in situ hybridization (FISH) technique. However, it was unclear if there was homology of probe sequences for the Yp11.3 region [sex-determining region Y (SRY), associated probe sequence] and DXZ1 (Xp11.1-Xq11.1) (CEP X, associated probe sequence) between human and rhesus monkeys. By directly extracting DNA from huMSCs (containing XY chromosome) and the spleens of rhesus monkeys, it was verified that the two probe sequences did not share homology between human and rhesus monkey (fig. S3). Then, human endometrial tissue was obtained as a positive control group (Fig. 5A), and one of the three endometria in the HA-GEL transplantation group was randomly selected as a negative control (Fig. 5B). FISH detection showed the absence of a positive signal (green/orange double signal or green signal) in the endometria 2 months after huMSCs/HA-GEL transplantation (Fig. 5, C to E), suggesting that huMSCs failed to locate to the endometrium after transplantation into the uterine cavity.

(A) Positive control, human endometrium (containing XX chromosomes); the red arrow indicates the green signal for Vysis CEP X (DXZ1). (B) Endometrial localization of huMSCs in the HA-GEL transplantation group (negative control). (C to E) Distribution of huMSCs in endometria 2 months after huMSCs/HA-GEL co-transplantation. Double/single-labeled staining (orange/green signal or just green signal) cells were defined as huMSCs. For details on 10402, 10405, and 10406, see table S3. Inserted overview pictures show a lower magnification.

Furthermore, potential cytokines secreted by huMSCs were further detected in the endometria by immunofluorescence staining, and as expected, increased positive expression was found in the endometria of the huMSCs/HA-GEL transplantation group; there were significant differences in insulin-like growth factor (IGF-1), epidermal growth factor (EGF), and brain-derived neurotrophic factor (BDNF) between the two transplanted groups (P < 0.05), but there were no significant differences in vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) (Fig. 6, A and B). In addition, when compared with the HA-GEL transplantation group, the expression levels of proinflammatory cytokines [interferon- (IFN-)] were significantly decreased in the huMSCs/HA-GEL transplantation group (P < 0.01, Fig. 6C1), and significantly up-regulated expression was found for the anti-inflammatory cytokine [interleukin 4 (IL-4)] (P < 0.01, Fig. 6C2), as well as related cytokines that promote cell proliferation and tissue repair (IGF-1 and EGF) (P < 0.001, P < 0.05, respectively; Fig. 6, C3 and C4).

(A) The expression and localization of the potential cytokines secreted by huMSCs in the HA-GEL transplantation group and the huMSCs/HA-GEL transplantation group; inserted overview pictures show a lower magnification. (B) The optical density (OD) value of IGF-1, EGF, BDNF, VEGF, and HGF 2 months after HA-GEL transplantation or huMSCs/HA-GEL co-transplantation. (C1) Comparison of IFN- mRNA expression between the HA-GEL transplantation group and the huMSC/HA-GEL transplantation group. (C2) Comparison of IL-4 mRNA expression between the HA-GEL transplantation group and the huMSC/HA-GEL transplantation group. (C3) Comparison of IGF-1 mRNA expression between the HA-GEL transplantation group and the huMSC/HA-GEL transplantation group. (C4) Comparison of EGF mRNA expression between the HA-GEL transplantation group and the huMSC/HA-GEL transplantation group. *P < 0.05, **P < 0.01, and ***P < 0.001 versus 2 months postHA-GEL; the results shown are the mean SEM of three technical replicates from each animal.

At present, according to relevant reports, approximately 2.8 to 45.5% of women with impaired fertility suffer from IUA, and more than 90% of cases occur after pregnancy-related D&C (25). In this study, an IUA model was successfully established with an invasive surgery in nonhuman primates (rhesus monkeys), which have a genetic background, endocrine system, menstrual cycle, and anatomical structure that are similar to humans (26). This model allowed us to further explore new approaches for the intervention and treatment of adhesion, especially the thin endometrium caused by endometrial injury.

In the primate experiments, 6- to 7-year-old rhesus monkeys (reproductive age) were identified as the ideal subjects for establishing IUA models; they had regular menstrual cycles of approximately 21 to 30 days, which was observed and recorded in succession for the 2 months before mechanical injury. We developed the first model of endometrial injury in rhesus monkeys by open abdominal surgery; we verified the successful establishment by visualizing the hard and narrow cervix and confirmed that D&C could ultimately lead to severe IUA, which was characterized by severe endometrial fibrosis, loss of normal endometrial glands, paper-thin and discontinuous endometria, full of adhesive zone and endometrial cavity fluid, as well as amenorrhea, as noted by the American Fertility Society scoring method (27).

This study explored the effect of transplantation huMSCs combined with HA-GEL on intrauterine reconstruction and endometrial regeneration in an IUA model. In our study, when compared with the control group (transplantation of only HA-GEL), the effects of the group with huMSCs were confirmed by Doppler ultrasonic scanning, histological inspection, and ultrastructure detection 2 months after transplantation. In the experimental group, the injured endometrial tissue presented with a thicker endometrium, an increased number of endometrial glands, a decreased fibrotic area, and typical changes in the secretory phase, showing how the positive huMSCs acted upon endometrial repair and regeneration through secreting cytokines and growth factors (16); further, the HA-GEL acted as a physical barrier to severe adhesion and provided an ideal physical support for the attachment of huMSCs to prevent their rapid outflow from uterine cavity.

Specifically, in the control group (HA-GEL transplanted alone), subjects did not recover menstruation and normal uterine cavity. However, recovery of menstruation, the appearance of a normal uterine cavity, and normal cycling were observed in the other three rhesus monkeys 2 months after huMSCs/HA-GEL co-transplantation, suggesting the great effect of the huMSCs/HA-GEL complex on the reconstruction of the uterine cavity and on the blocking of adhesion. Meanwhile, we also found that HA-GEL transplantation could increase the number of endometrial glands, but it played no effective role in endometrial thickness, which was important because it was less effective than the huMSCs/HA-GEL complex. This amelioration of the damage to the endometria resulted in nearly normal levels and suggested the re-emergence of endometrial repair and regeneration after huMSCs/HA-GEL co-transplantation. In addition, the degree of fibrosis in the damaged endometria was found to be increasingly worse 2 months after transplantation despite HA-GEL or huMSCs/HA-GEL intervention, and it remained unclear whether HA-GEL had an effect on resisting fibrogenesis because of the small sample size of rhesus monkeys. Obviously, huMSCs/HA-GEL intervention relieved the worse aspects of fibrogenesis, suggesting a better outcome and potential effect on the reconstruction of abnormal tissue.

Then, it was unclear what the underlying mechanism of endometrial reconstruction was. Transplanted huMSCs were tracked in endometria, and the result showed no obvious labeled signal in endometrial tissue at 2 months after huMSCs/HA-GEL complex transplantation, which was contrary to a previous report (28, 29). To explain these conflicting results, three possibilities were proposed: (i) missed target area due to random sampling, (ii) completely eliminated following the outflow of menstrual blood, and (iii) huMSC apoptosis and depletion. However, the last two assumptions were preferred for the reason of multipoint sampling and continuous paraffin section, and if the endometrial tissues were obtained at 1 week or 2 weeks after huMSCs/HA transplantation, we might get different results owing to the similar menstrual cycles to human and different physiological function from animal models such as mice and rabbits. Alternatively, some cytokines and growth factors related to huMSCs were detected, and the results showed that huMSCs/HA-GEL complex transplantation could obviously increase the expression of IGF-1, EGF, BDNF, and so on compared to that of the control group (HA-GEL transplanted alone). Growth factors and their related peptides were deemed to mediate and regulate hormones working on target tissues through autocrine or paracrine function, and some growth factors, the endocrine basis of endometrium recycling including transforming growth factor, EGF, IGF, fibroblast growth factor, etc., were reported to regulate the differentiation and proliferation of endometrial cells (30). EGF, present in stromal and epithelial cells of the endometrium, could regulate endometrial proliferation, gland secretion, and decidual transformation (31). IGF played important roles in endometrial physiology and could regulate the cell cycle and promoted the proliferation of endometrial epithelial cells after the activation of estrogen (32, 33). Moreover, some reports showed the key role of BDNF in the regulation of endometrial cell proliferation by the downstream signal transducer and activator of transcription 3 signaling pathway and participating in the damage repair of endometrium (34, 35). Furthermore, considering the effect of huMSCs on uncontrolled fibrogenesis resulting from inflammatory activity and endometrial cell proliferation, anti-inflammatory cytokines (IL-4) were observed to be up-regulated, and proinflammatory cytokines (IFN-) were down-regulated; further, related cytokines that promote cell proliferation and tissue repair were up-regulated, such as IGF-1 and EGF, suggesting that excessive fiber formation could be inhibited by anti-inflammatory effects due to the advantageous microenvironment constructed by abundant huMSCs in the uterine cavity. VEGF, as the most important vascular growth factor, could be stimulated by ischemia and hypoxia in the endometrial layer after endometrial injury and played an important role in the early stage of endometrial repair and proliferation; during the time, angiogenesis could be promoted rapidly, but no effects were shown once the neovascularization was over (3639). We speculated that no difference found in VEGF expression might be related to the samples extracted from the endometrium during the secretory phase, a plateau stage of vascular repair and VEGF secretion in the endometrial basal layer. Overall, all of these results further verified the important role of huMSCs in damage repair by secreting a series of paracrine factors, such as anti-inflammatory factors, growth factors, and cytokines, related to constructing the microenvironment with properties such as anti-inflammatory, promoting repair, maintaining cell function, angiogenesis, etc., which was consistent with the previous report (40).

In conclusion, this study showed that both HA-GEL and huMSC/HA-GEL complexes could partially repair severe IUA caused by mechanical injury, but huMSC/HA-GEL complex transplantation indicated significant advantages in the dual repair effects of antiadhesive property and promotion of endometrial regeneration. By constructing a complex of huMSCs/HA-GEL with a biomaterial to prevent adhesion and allow stem cells to act at the appropriate site of repair of the endometrium, we have provided a method for solving a problem for patients with moderate to severe IUA and thin endometria caused by IUA. We hope that this novel strategy using the huMSCs/HA-GEL complex will be offered as a basic clinical research strategy in the future, and it might be a potential valuable treatment for gel loaded with cytokines to repair moderate to severe IUA.

The basic information for the six rhesus monkeys used in this study is shown in table S4. They were bred and supplied by Fujian Experiment Center of Nonhuman Primate for Family Planning, where they were maintained the clean-class animal feeding standards. We used these rhesus monkeys in the study following the outlined steps of the flowchart (fig. S4) from 17 September 2018 to 16 March 2019 with regular menstrual cycle observed (26). All experiments were conducted in accordance with the National Research Councils Guideline for the Care and Use of Laboratory Animals and approved by the Ethics Committee of the Center of Reproductive Medicine of Tongji Medical College of Huazhong University of Science and Technology in China.

The six rhesus monkeys were chosen for IUA models following mechanical injury, and intraperitoneal surgery was the proper choice for curettage in view of the special structure of the vagina and the cervix, which are characterized by hardness, toughness, a small aperture, and a long cervix. All monkeys were provided general anesthesia with an appropriate dose of ketamine by intramuscular injection, and then a mid-abdominal longitudinal incision was made to expose the uterus. A vertical incision (~0.5 cm) was made in the lower uterine segment. A small curettage spoon was used to deeply scrape the uterine walls until they became rough and pale, and the collected endometrial tissues were stored at 80C. Subsequently, the uterine and abdominal incisions were closed by continuous stitching with 6-0 Vicryl sutures and 3-0 silk absorbable sutures, respectively. After the operation, antibiotics were used to prevent infection, and observation on the first day after the operation showed that these rhesus monkeys were in good condition.

huMSCs were kindly provided by the Stem Cell Laboratory of the Center of Reproductive Medicine (Tongji Medical College, Huazhong University of Science and Technology, China). Frozen huMSCs between P3 and P9 were freshly seeded in 10-cm culture dishes (1 106 cells per dish) in Iscoves modified Dulbeccos medium (IMDM, Genom, China) supplemented with 10% (v/v) fetal bovine serum (FBS, Gibco, USA), penicillin (100 U/ml), and streptomycin (100 mg/ml; Gibco, USA). Briefly, the phenotypes of huMSCs were specifically identified by FACS, and the osteogenic and adipogenic capacities of the mesenchymal stem cells were assessed with a MesenCult Osteogenic Stimulatory Kit (STEMCELL Technologies Inc., Canada) and a MesenCult Adipogenic Differentiation Kit (STEMCELL Technologies Inc., Canada). P3 to P9 were used for the experiments.

To further evaluate the safety of huMSCs on HA-GEL, we mixed huMSCs (1 105 to 2 105 per well) and 300 l of HA-GEL [Con., 5 mg/ml; Bioregen, Co., Ltd., China, approved by CFDA as a medical device (no. 20153641542)] evenly with sterile syringes in 24-well plates and then added IMDM (Genom, China), including 10% (v/v) FBS (Gibco, USA), penicillin (100 U/ml), and streptomycin (100 mg/ml) (Gibco, USA). After co-culture for 48 hours, 0.8% collagenase type I supplemented with appropriate hyaluronidase was used to digest HA-GEL and release huMSCs, and FACS was chosen for the detection of cell apoptosis index in the coculture group (huMSCs/HA-GEL) and the culture-separated group (huMSCs), as well as live-dead cell detection with Live-Dead Cytotoxicity Assay Kit (MesGen Biotechnology, Shanghai).

Briefly, 50 l of huMSCs (1 107 to 2 107 cells) were injected into 200 l of HA-GEL (Bioregen, Co., Ltd. China), and then they were immediately transplanted into the uterine cavity through the open abdominal cavity. At the same time, the uterine cavity in the negative control group was injected into 200 l of HA-GEL following the same procedure that was used for the huMSC/HA-GEL transplantation group. All operations were performed under sterile conditions.

The endometrial thickness (before mechanical injury or after surgery for 2 months) was measured by an abdominal two-dimensional ultrasound system (Medison SA-600 Ultrasound System, Korea) with 3.5-MHz pulse repetition frequency to evaluate the damage to the endometrium and the endometrial regeneration.

The scraped pieces of endometrium were fixed in 4% paraformaldehyde for 24 hours and then embedded in paraffin. Serial paraffin-embedded sections (4 m) were obtained, sequentially dewaxed in xylene I and xylene II for 20 min each, and rehydrated in a series of ethanol solutions with a decreasing concentration (100% for 10 min, 100% for 10 min, 95% for 5 min, 90% for 5 min, 80% for 5 min, and 70% for 5 min). Then, the sections were rinsed in distilled water (three times, 5 min each). The sections were stained with an H&E solution (Servicebio, China) according to the manufacturers instructions. After staining, endometrial morphologic features were observed, and the number of uterine glands per unit area was counted according to five randomly selected high-power fields of each slide.

The 4-m paraffin sections of endometrium were dewaxed and rehydrated as described above and then were immersed in Masson A solution (Servicebio, China) overnight, which was followed by a brief wash under running water. Then, the sections were stained in a mixed solution of Masson A and Masson B (1:1, Servicebio, China) for 1 min, washed under running water, and placed in 1% hydrochloric acid alcohol for 10 s before they were washed again. Subsequently, sections were immersed in Masson D solution (Servicebio, China) for 6 min and then were stained in Masson E solution (Servicebio, China) for 1 min. The solution was then slightly drained, and the sections were placed directly in Masson F solution (Servicebio, China) for 2 to 30 s, and then they were rinsed in 1% glacial acetic acid for differentiation of the signals. Last, the sections were dehydrated in absolute ethyl alcohol, clarified in xylene for 5 min, and sealed in Permount Mounting Medium (Sinopharm Chemical Reagent Co., Ltd., China). Endometrial fibrosis was assessed according to five random fields on each slide, and the fibrotic area ratios were calculated using Image-Pro Plus software (version 6.0).

The total DNA samples were extracted from spleen tissue of rhesus monkeys and huMSCs carrying XY or XX chromosomes with a TIANamp Genomic DNA Kit (Tiangen Biotech Co., Ltd., Beijing). mRNA samples were extracted from endometrial tissue, and cDNA was synthesized with a RevertAid First Strand cDNA Synthesis Kit (Thermo, USA). Subsequently, quantitative real-time polymerase chain reaction (qRT-PCR) was performed to verify the specific expression of the DXZ1 gene on the X chromosome, SRY on the Y chromosome, and IFN-, IL-4, IGF-1, and EGF using StepOne and StepOnePlus Real-Time PCR Systems Version 2.3. The final reaction volume of 20 l contained 10 l of Bestar qPCR MasterMix (SYBR Green) (DBI Bioscience), 4 l of DNA samples, 0.4 l of forward/reverse primer (10 M), and 5.2 l of DNA/RNase-free double-distilled water (ddH2O). Last, agarose gel electrophoresis was performed to verify the expression of DXZ1 and SRY in the spleen and huMSC tissues. In addition, primer sequences used for DXZ1 (Xp11.1-Xq11.1), SRY (Yp11.3 Region), IFN-, IL-4, IGF-1, and EGF are summarized in table S5.

FISH analysis was performed to trace huMSCs for 2 months after the huMSCs/HA-GEL complexes were transplanted into the uterine cavity. Endometrial tissue was collected and immediately fixed in 10% paraformaldehyde before paraffin embedding. A Vysis SRY Probe LSI SRY Spectrum Orange/Vysis CEP X Spectrum Green Kit (Abbott Laboratories, USA) was used to mark huMSCs in the endometrium. All paraffin sections were dewaxed, rehydrated, hybridized with the probe, and so on according to the probes instructions; a final counterstaining of 4,6-diamidino-2-phenylindole (DAPI) was added, and visualization took place with fluorescence microscopy (Nikon Eclipse Ci, Nikon DS-U3). The orange (SRY/Y chromosome) and/or green (DXZ1/X chromosome) signals were used to verify the presence or absence of huMSCs in the endometrium.

The following factors were analyzed after transplantation of the huMSCs/HA-GEL complex: trophic factors (cytokines) that are secreted by huMSCs [according to relevant reports (17)], proinflammatory cytokines, anti-inflammatory cytokines, and related cytokines that promote cell proliferation and tissue repair. After fixation with 4% paraformaldehyde, paraffin embedding, and cutting 4-m paraffin sections, the slides were immersed in xylene and rehydrated through incubation in a series of alcohol gradients. The following specific antibodies were applied to sections at 4C overnight in humidified chambers: recombinant anti-BDNF antibody (EPR1292) (ab108319, Abcam), anti-VEGF antibody (C-1: sc-7269, Santa Cruz), antiIGF-1 antibody (W18: sc-74116, Santa Cruz), anti-HGFa antibody (H-10: sc-374422, Santa Cruz), and anti-EGF antibody (F-9: sc-166779, Santa Cruz). Then, these sections were incubated with a Cy3-tagged secondary antibody for 1 hour at room temperature and were then rinsed in ddH2O three times. Counterstaining was performed with DAPI for 5 min, and the fluorescence signal was detected under a fluorescence microscope (Nikon Eclipse Ci, Nikon DS-U3).

We collected three technical replicates from each animal and repeated the experiments at least three times. The data presented as the mean SEM were analyzed with Statistical Package for the Social Sciences Statistics 17.0. The normally distributed numerical variance was assessed by a t test with homogeneity of variance, and 2 tests were used to analyze the differences between two or more rates. The percentage of positive area after H&E staining and Masson staining was measured using ImageJ 1.43u (Wayne Rasband, National Institutes of Health, USA). Statistical significance was assumed for P < 0.05.

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.

Acknowledgments: We acknowledge the breeding and technical assistance of Fujian Experiment Center of Nonhuman Primate for Family Planning. We thank C. Yu for the operation of uterine D&C and open abdominal surgery. We thank C. Xiong and P. Su for their invaluable contributions in critically revising the manuscript and providing guidance for important intellectual content. We thank M. Zhang, T. Chang, and S. Song for analyzing the data and collecting the samples. Funding: This work was supported by the National Natural Science Foundation of China (NSFC 81571434) and the National Key Research and Development Program of China (2017YFC1002002). The funders played no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Author contributions: W.X. designed the study and published this manuscript; L.W. and C.Y. performed the experiments and wrote the manuscript; M.Z., T.C., and S.S. analyzed the data and collected the samples; C.X. and P.S. provided their invaluable contributions in critically revising the manuscript and providing guidance for important intellectual content. Competing interests: The authors declare that they have no competing interests. Data and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Additional data related to this paper may be requested from the authors.

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In situ repair abilities of human umbilical cordderived mesenchymal stem cells and autocrosslinked hyaluronic acid gel complex in rhesus monkeys with...

Liposuction Equipment Marketreport focused on the comprehensive analysis of current and future prospects of the Liposuction Equipment industry. This report is a consolidation of primary and secondary research, which provides market size, share, dynamics, and forecast for various segments and sub-segments considering the macro and micro environmental factors.

This report provides an in-depth analysis of past trends, future trends, demographics, technological advancements, and regulatory requirements for the Liposuction Equipment market has been done in order to calculate the growth rates for each segment and sub-segments. The report also provides the market impact and new opportunities created due to the COVID19 pandemic.

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Top Key Vendors of this Market are:

Alma Lasers, Ambicare Clinics, Bruker Corporation, Cutera, Cynosure Inc., Erchonia, Genesis Biosystems, AMD Global Telemedicine, Invasix Aesthetic Solutions, Ambicare Clinics, Sciton Inc., Solta Medical, Valeant Pharmaceuticals, Wells Johnson Co, Zeltiq aesthetics Inc, Carl Zeiss Meditec, Inc.

Various factors are responsible for the markets growth trajectory, which are studied at length in the report. In addition, the report lists down the restraints that are posing threat to the global Liposuction Equipment market. It also gauges the bargaining power of suppliers and buyers, threat from new entrants and product substitute, and the degree of competition prevailing in the market. The influence of the latest government guidelines is also analyzed in detail in the report. It studies the Liposuction Equipment markets trajectory between forecast periods.

The report provides insights on the following pointers:

Market Penetration:Comprehensive information on the product portfolios of the top players in the Liposuction Equipment market.

Product Development/Innovation:Detailed insights on the upcoming technologies, R&D activities, and product launches in the market.

Competitive Assessment: In-depth assessment of the market strategies, geographic and business segments of the leading players in the market.

Market Development:Comprehensive information about emerging markets. This report analyzes the market for various segments across geographies.

Market Diversification:Exhaustive information about new products, untapped geographies, recent developments, and investments in the Liposuction Equipment market.

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The report summarized the high revenue that has been generated across locations like, North America, Japan, Europe, Asia, and India along with the facts and figures of Liposuction Equipment market. It focuses on the major points, which are necessary to make positive impacts on the market policies, international transactions, speculation, and supply demand in the global market.

Global Liposuction Equipment Market Segmentation:

Market Segmentation by Type:

Negative-pressure Liposuction EquipmentUltrasonic Liposuction EquipmentPower Assisted Liposuction Equipment

Market Segmentation by Application:

HospitalsAmbulatory Surgical CentersCosmetic Surgical Centers

Table of Contents

Global Liposuction Equipment Market Research Report 2020 2026

Chapter 1 Liposuction Equipment Market Overview

Chapter 2 Global Economic Impact on Industry

Chapter 3 Global Market Competition by Manufacturers

Chapter 4 Global Production, Revenue (Value) by Region

Chapter 5 Global Supply (Production), Consumption, Export, Import by Regions

Chapter 6 Global Production, Revenue (Value), Price Trend by Type

Chapter 7 Global Market Analysis by Application

Chapter 8 Manufacturing Cost Analysis

Chapter 9 Industrial Chain, Sourcing Strategy and Downstream Buyers

Chapter 10 Marketing Strategy Analysis, Distributors/Traders

Chapter 11 Market Effect Factors Analysis

Chapter 12 Global Liposuction Equipment Market Forecast

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Liposuction Equipment Market will touch a new level in upcoming year with Top Key players like Alma Lasers, Ambicare Clinics, Bruker Corporation,...

We look to centenarians as our guides for living life to the fullest. The Blue Zones refers to the regions where people often live up to triple digits relatively free of diseases. Thats why we pay attention to the food they eat, the wine they drink, and a certain activity that keeps them, uh, lively. Yes, there seems to be a link between sex and longevity of life.

In the Blue Zones region of Ikaria, Greece, for example, more than 80 percent of people between ages 65 and 100 are still having sex. Eighty percent! Now thats something to look forward to if I ever make it that far. Whats more illuminating is that good health seems to inform a longer sex life which in turn informs a longer life in general; its a very uplifting loop. For example, one of the secrets of these long-lasting folk is that they maintain a diet thats 95 to 100 percent plant-based, which is obviously a solid lifestyle switch, but its thought that it could make sex better, too. Theres even research pointing out that men who eat less red meat and lots of fruits, vegetables, and whole grains have less erectile dysfunction. Neat.

Likewise, research has previously revealed the benefits of sex when it comes to the health of middle-agers. A 2016 study on partnered sex and cardiovascular risk revealed a connection between lowered mortality rate and frequency of orgasm in women. And take this with the tiniest grain of salt, but a small study of college students noted that those who had sex two times a week had an overall higher immunity than those who were socializing far less.

Although a lot of research leans towards heterosexual sexual intercourse, your climax in general can be a boon for your longevity. After all, the benefits of orgasmsinclude lowered stress due to feel-good oxytocin release, aquicker and deeper nights sleep, and yes, good heart health. Seeking your pleasure by any means is probably a boon to your sexuality and lifespan.

Its nice to consider this life hack (is that what this is?) if youre looking to spend your golden years with a special someone. Remember, sex can be a bonding agent that helps strengthen your relationship (see: oxytocin release), and while long passages of time with a person might diminish arousal, there are plenty of ways to diversify your sexual experience. If youre extremely pro-orgasms, you want a beautifully long life, and you want to get there with your significant other, keep sex as a regular part of your wellness routine.

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More than 80% of the worlds longest-living people are having sex between age 65 and 100heres their secret - Well+Good

Humans are living longer than ever before, but with the increases in lifespan there are also increases in the occurrence of ageing related diseases such as dementia, frailty, and cancer. Gaining a better understanding of the biology of aging and knowing the genes and proteins involved in these processes will help to increase our healthspan to go along with longevity to live as healthy as we can for as long as we can.

In a recent study, the novel anti-aging protein Gaf1 was identified, it was found to control protein metabolism which has been implicated in aging and disease; cells without Gaf1 were found to have a shorter lifespan.

The complex process of aging depends on genetic and environmental factors such as diet. Calorie restricted diets have been shown to promote prolonged lifespans, and this holds true for a variety of organisms with short term studies suggesting that it also helps to improve human health.

Emerging evidence now suggests that it may actually be the quantity of specific nutrients such as amino acids that are linked to the increased longevity rather than the amount of calories consumed. Cells can sense the amount of nutrients in their environment through specific molecules within the cells such as TOR which senses the amount of amino acids that are present in the body and available to the cells.

Amino acids are the building blocks of proteins, when our body has an ample supply the TOR enzyme will trigger our metabolism to instruct the cells to grow by making a lot of proteins, this process is called protein translation. However, if amino acids are low TOR will instruct the body to be on alert which is referred to as a mild stress response that is thought to be beneficial for the cells and the organism overall while increased protein translation and turnover is detrimental.

Longevity is related to an organisms ability to find a way to effectively manage both internal and external stressors. Cells that are on alert have been shown to cope better, as when a cell invests in protein translation and growth it lowers its defenses and is not able to cope with stress as effectively.

A recent study analyzing the turnover of proteins within cells of different animals with lifespans ranging from 4-200 years found that the longer lived animals had lower protein turnover and energy demand within their cells as compared to the shorter lived animals.

DNA carries genetic information, genes are pieces of DNA and many are responsible for making proteins. For a protein to be made the cell needs to produce a mRNA copy of the corresponding gene through a transcription process; mRNA guides the cell ribosomes on the order that amino acids should be linked together to make proteins.

Cells also require ATP energy, amino acids, and small tRNA molecules for protein translation which takes a lot of energy; each cell may need tens of thousands of ribosomes to translate its proteins. The more food a cell has the more active TOR will be instructing the cell to grow and divide. When TOR is inactive as in dietary restriction it will stop translation by preventing existing ribosomes from functioning, as well as stopping the production of new ribosomes.

Scientists recently discovered new function of the Gaf1 protein which is a transcription factor that is able to bind on cell DNA and activate/repress specific genes. When TOR is active Gaf1 can be found in the cytoplasm of the cell and it does not bind on the DNA, but when TOR is inactivated Gaf1 can travel to the nucleus and bind to DNA. When it binds to DNA it stops all the genes that are responsible for making tRNAs as well as other genes needed for translation. This is done by controlling a network of genes that are responsible for providing all of the building blocks for making proteins to stop the cell from putting energy into translation by preventing it from making the components needed for the process; but this is only temporary as when amino acids are available this halt is reversed.

Cells lacking in Gaf1 have been found to be short-lived; TOR signals cells to grow which contributes to aging, but when TOR is inhibited the growth is halted and extends lifespan. When Gaf1 is not present growth is not halted and the observed extension in lifespan is not taking place fully, meaning a molecule was found by the scientists that mediates some of the beneficial effects of dietary restriction.

This study was examining yeasts, but proteins similar to Gaf1 exist in many animals which includes humans, and they have been shown to control development as well as stem cells which are important in whether we develop diseases. It may be possible that these proteins have the same functions in humans that were observed with Gaf1 in yeast.

TOR function, cell growth and protein production are important to physiology and healthspan but they can also contribute to the development of certain diseases. This study has demonstrated how dietary restriction is controlled down to the cells genes, and the findings may allow for the examination of how specific drugs or diets can work to enhance the function of these factors for beneficial effects that may even increase human healthspan.

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Anti-Aging Protein Shown To Slow Cell Growth Important To Longevity - Anti Aging News

Betty White has joked that vodka helps keep her young.

Betty White. Source: Bang Showbiz

The 98-year-old actress is quarantining at home amid the Covid-19 pandemic and sometimes treats herself to a "vodka martini with hot dogs and french fries", although she is not a big drinker.

A source told Closerweekly.com: "Betty loves to joke that vodka keeps her young.

"She loves the image of her sitting at home in a rocking chair, drinking a martini and watching game shows, but she's not really a big drinker. That's not her. She'll only take a few sips of a cocktail if the occasion calls for it."

And Betty believes the global health crisis is a chance for people to stop and reevaluate their lives.

The insider explained: "Betty's message to the world is to slow down and enjoy what you have: family, friends, your pets. She says that the pandemic is serious, but we have come through worse. It's Mother Nature's way of telling us all to slow down."

Betty has been passing the time in isolation by reading the newspaper and doing crossword puzzles.

Her friend Tom Sullivan said: "She reads the L.A. Times cover to cover. She owns literally thousands of crossword puzzle books and is constantly doing them to keep her mind jumping. This is really serious with her."

However, Betty's beloved Scrabble nights with her friends have had to be put on hold.

One source said: "She's tried Zooming her Scrabble game with her friends, but it's not quite the same."

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Veteran actress Betty White jokingly reveals secret of her longevity - 1News

News

Modified 26 May 2020, 14:47 IST

Roger Federer, Rafael Nadal and Novak Djokovic's stunning longevity has evoked respect and admiration from all corners of the world. And now, Nadal himself has shared his views on what makes the mythical Big 3 of men's tennis so special.

Speaking to ESPN Argentina, the 19-time Grand Slam champion singled out the unbridled passion for the sport within each of the Big 3 as the single biggest reason for their dominance.

The legendary trio have revolutionized the game with their ability to win the biggest titles even in their mid-30s, changing the very notion of a career in tennis. Gone are the days when turning 30 would mean bidding adieu to the sport for good.

Federer, Nadal and Djokovic have shown that age is just a number if you are fully aware of what your body needs. Their iron grip on the sport has earned them a staggering 56 out of the last 67 Slams, which has practically shut the door on the next generation.

According to Rafael Nadal, while passion is important, it is not the only thing needed for such a long reign at the top. The Spaniard stressed on a player's ability to adapt to different surfaces, conditions and the growing demands of the sport as yet another requisite for a long and successful career.

Having a team that can help in the clarity of your thought process and eliminate all your doubts is essential too, as per the southpaw. Surrounding yourself with the right people who can show you the right direction and can motivate you everyday to reach your desired goal is absolutely crucial.

Re-iterating what he had said yesterday about never resting on your past laurels, the 12-time French Open winner once again harped on the importance of constant self-improvement as the key to prosperity and longevity.The fact that each of the Big 3 has made continuous efforts to build on their game is what has made them versatile and, in turn, helped them master all surfaces for such a long time.

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Rafael Nadal reveals the reasons behind Big 3's success and longevity - Sportskeeda

We continue our look at the greatest players for each position that have played for the Miami Heat. The center position is filled with some great players, and its a little bit of choice where you want to put them.

Wed love for you to read through and tell us what you think.

**These rankings are based on both longevity and impact. A player is not ineligible if they played for a short amount of time, but their impact must be high.**

Lets take a look at the best centers to play for the Miami Heat.

#5 Rony SeikalyFor six seasons in Miami, Seikaly was the starting center in Miami as the franchise began. He was a good center, averaging 15.4 PPG and 10.4 RPG. He also won the NBAs Most Improved Player Award in 1989-90.

Seikaly never did anything to wow you, but he was a consistent presence on a young team and for that, he make the list.

#4 Hassan WhitesideTheres a lot of mixed feelings about Whitesides time in Miami. It started out with such intrigue and promise as a D-League call-up who started getting triple doubles with blocks. Whiteside was a double-double machine in his 5 seasons with the Heat. He led the league in rebounding with 14.1 in 2016-17. And he led the league in blocks with 3.7 in 2015-16.

Whiteside signed a massive 4-year, $98 million deal in 2016 and he had his best season in that first year averaging 17 PPG and 14 RPG. But after than, his minutes started to decline, as well as his numbers...and some suggested his effort. He was disgruntled and the Heat traded him away.

Regardless, he was a powering presence that played 5 seasons in Miami.

#3 Bam AdebayoAt 22 years-old, Edrice Adebayo became only the third center for Miami to become an All-Star. Adebayo has only been in Miami for three seasons, and this is his first time as a full-time starter, but he hasnt disappointed. He is well rounded, averaging 5 APG, which is by far the best for any center in Heat history.

His sky is the limit. Yes, Seikaly and Whiteside probably have room to grumble being behind him, but the fact that he so quickly became an All-Star and is on his way to a stellar career, I went ahead and penciled him in above him. In October of 2018, Alonzo Mourning predicted that Adebayo would be the best player in the organization...

#2 Shaquille ONealShaq is probably the greatest center to ever play the game, so dominant. But we are judging his time in Miami. And when he arrived at age 32, he was good, but not unstoppable. Shaq had a near MVP season in 2004-05, claiming second to Steve Nash. And then you know he led the Heat, alongside Dwyane Wade to the 2006 title.

In Miami, Shaq averaged 19.6 PPG and 9.1 RPG. His first two years in Miami, he led the NBA in FG%. He was the Diesel, but only spent 3 and a half seasons here as things went south immediately after the title. Still, hes the second best center to lace them up here.

#1 Alonzo MourningThere is a reason he is still around and involved as a part of the Miami Heat organization today.

Alonzo Mourning is one of the best players to ever play for Miami. And his longevity and skill lead him to the top for this category. Its interesting because for much of his career, Zo was overshadowed by Shaq...maybe all of his career. He averaged 21 and 10 as a rookie, but Shaq was the story.

Mourning spent 11 different seasons with the Heat, including the 2006 title team. Mourning was a 5-time All-Star with the Heat (7 overall). He won NBA Defensive Player of the Year in back to back years in 1999 and 2000. He was second in MVP voting in 1999. He led the league in blocks twice. Hes got All-NBAs and all kinds of things.

He was the center of the 90s teams that made a real push and he came back after his kidney disease and played for the Heat again after a stint in New Jersey. Mourning is the best and will always be a legend in Miami.

COMMENT BELOWLet me know what you think of the list! What would you change? Brian Grant was someone I considered but he didnt make the list.

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The Top 5 Miami Heat Centers of All-Time. - Hot Hot Hoops

In times of economic distress, (re)insurance is typically considered by investors to be a defensive sector. This view is well merited: it has less exposure to economic cycles than other industries and has a strong track record in navigating macroeconomic and capital crises.

This is not to say the sector will be unaffected by the COVID-19 crisis. Access to capital has reduced while carriers assets have clearly been hit by lower interest rates, wider credit spreads and an equity crash. A fall back into recession will also hinder growth opportunities, given the long-standing correlation between economic output and premium growth.

It is nevertheless important to point out that most carriers investment portfolios are invested conservatively, with a predominance of (high-grade) fixed income securities and low equity gearings. Whilst investment returns are likely to drop to new lows, such conservative allocations are likely to insulate property and casualty insurance carriers from significant investment portfolio risks. The sector also remains well capitalized. Ultimately, the fundamentals of the (re)insurance market remain strong.

COVID-19 Risks Outlook: A Preliminary Mapping and Its Implications, published by the World Economic Forum with support from Marsh & McLennan, examines familiar risks that may be amplified by the pandemic and new ones that may emerge.

The report draws on survey results of nearly 350 senior risk professionals who were asked to identify their biggest concerns over the next 18 months for both the world and their business.

The likely depth and longevity of the economic fallout unsurprisingly dominates companies risks perceptions. These include a prolonged recession, the weakening fiscal position of major economies, tighter restrictions on the cross-border movement of goods and people, the protracted disruption of global supply chains, and an increase in cyberattacks and data fraud.

Guy Carpenter has convened a COVID-19 task force to help support clients through these extraordinary times. By leveraging the deep expertise within our firm and aggregating information from daily colleague and market interactions, we are able to provide our clients with unique perspectives across all lines of business and geographies.

As reinsurers escalate efforts to introduce COVID-19-related exclusions or wording changes to contracts on upcoming renewals, the task force is coordinating responses in a thoughtful manner focused on the best outcome for our clients. The task force is also monitoring regulatory activity for all regions and classes of business and disseminating timely and insightful thought leadership on matters such as these to help clients make the most informed decisions.

Read the COVID-19 Risks Outlook report >>

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COVID-19 Risks Outlook: A Preliminary Mapping and Its Implications - GC Capital Ideas

Rajasekharreddy Pala,1,2 VT Anju,3 Madhu Dyavaiah,3 Siddhardha Busi,4 Surya M Nauli1,2

1Department of Biomedical and Pharmaceutical Sciences, Harry and Diane Rinker Health Science Campus, Chapman University, Irvine, CA 92618, USA; 2Department of Medicine, University of California Irvine, Irvine, CA 92868, USA; 3Department of Biochemistry and Molecular Biology, School of Life Sciences, Pondicherry University, Puducherry, India; 4Department of Microbiology, School of Life Sciences, Pondicherry University, Puducherry, India

Correspondence: Rajasekharreddy Pala; Surya M Nauli Tel +714-516-5462; +714-516-5480Fax +714-516-5481Email rrpala@chapman.edu; nauli@chapman.edu

Abstract: Cardiovascular diseases (CVDs) are one of the foremost causes of high morbidity and mortality globally. Preventive, diagnostic, and treatment measures available for CVDs are not very useful, which demands promising alternative methods. Nanoscience and nanotechnology open a new window in the area of CVDs with an opportunity to achieve effective treatment, better prognosis, and less adverse effects on non-target tissues. The application of nanoparticles and nanocarriers in the area of cardiology has gathered much attention due to the properties such as passive and active targeting to the cardiac tissues, improved target specificity, and sensitivity. It has reported that more than 50% of CVDs can be treated effectively through the use of nanotechnology. The main goal of this review is to explore the recent advancements in nanoparticle-based cardiovascular drug carriers. This review also summarizes the difficulties associated with the conventional treatment modalities in comparison to the nanomedicine for CVDs.

Keywords: cardiovascular diseases, nanoscience, nanoparticles, nanomedicine, nanocarriers, treatment

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

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Nanoparticle-Mediated Drug Delivery for the Treatment of Cardiovascula | IJN - Dove Medical Press

Nanomedicine Market was valued US$ XX Bn in 2018 and is expected to reach US$ XX Bn by 2026, at CAGR of XX% during forecast period of 2019 to 2026.

Nanomedicine Market Drivers and Restrains:Nanomedicine is an application of nanotechnology, which are used in diagnosis, treatment, monitoring, and control of biological systems. Nanomedicine usages nanoscale manipulation of materials to improve medicine delivery. Therefore, nanomedicine has facilitated the treatment against various diseases. The nanomedicine market includes products that are nanoformulations of the existing drugs and new drugs or are nanobiomaterials. The research and development of new devices as well as the diagnostics will become, more effective, enabling faster response and the ability to treat new diseases are likely to boost the market growth.

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The nanomedicine markets are driven by factors such as developing new technologies for drug delivery, increase acceptance of nanomedicine across varied applications, rise in government support and funding, the growing need for therapies that have fewer side effects and cost-effective. However, long approval process and risks associated with nanomedicine (environmental impacts) are hampering the market growth at the global level. An increase in the out-licensing of nanodrugs and growth of healthcare facilities in emerging economies are likely to create lucrative opportunities in the nanomedicine market.

The report study has analyzed revenue impact of covid-19 pandemic on the sales revenue of market leaders, market followers and disrupters in the report and same is reflected in our analysis.

Nanomedicine Market Segmentation Analysis:Based on the application, the nanomedicine market has been segmented into cardiovascular, neurology, anti-infective, anti-inflammatory, and oncology. The oncology segment held the dominant market share in 2018 and is projected to maintain its leading position throughout the forecast period owing to the rising availability of patient information and technological advancements. However, the cardiovascular and neurology segment is projected to grow at the highest CAGR of XX% during the forecast period due to presence of opportunities such as demand for specific therapeutic nanovectors, nanostructured stents, and implants for tissue regeneration.

Nanomedicine Market Regional Analysis:Geographically, the Nanomedicine market has been segmented into North America, the Europe, Asia Pacific, Latin America, and Middle East & Africa. North America held the largest share of the Nanomedicine market in 2018 due to the rising presence of patented nanomedicine products, the availability of advanced healthcare infrastructure and the rapid acceptance of nanomedicine. The market in Asia Pacific is expected to expand at a high CAGR of XX% during the forecast period thanks to rise in number of research grants and increase in demand for prophylaxis of life-threatening diseases. Moreover, the rising investments in research and development activities for the introduction of advanced therapies and drugs are predicted to accelerate the growth of this region in the near future.

Nanomedicine Market Competitive landscapeMajor Key players operating in this market are Abbott Laboratories, CombiMatrix Corporation, General Electric Company, Sigma-Tau Pharmaceuticals, Inc, and Johnson & Johnson. Manufacturers in the nanomedicine are focusing on competitive pricing as the strategy to capture significant market share. Moreover, strategic mergers and acquisitions and technological innovations are also the key focus areas of the manufacturers.

The objective of the report is to present a comprehensive analysis of Nanomedicine Market including all the stakeholders of the industry. The past and current status of the industry with forecasted market size and trends are presented in the report with the analysis of complicated data in simple language. The report covers all aspects of the industry with a dedicated study of key players that includes market leaders, followers and new entrants by region. PORTER, SVOR, PESTEL analysis with the potential impact of micro-economic factors by region on the market are presented in the report. External as well as internal factors that are supposed to affect the business positively or negatively have been analyzed, which will give a clear futuristic view of the industry to the decision-makers. The report also helps in understanding Nanomedicine Market dynamics, structure by analyzing the market segments and project the Nanomedicine Market size. Clear representation of competitive analysis of key players By Type, Price, Financial position, Product portfolio, Growth strategies, and regional presence in the Nanomedicine Market make the report investors guide.

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Scope of the Nanomedicine Market:

Nanomedicine Market by Modality:

Diagnostics TreatmentsNanomedicine Market by Diseases:

Oncological Diseases Infectious Diseases Cardiovascular Diseases Orthopedic Disorders Neurological Diseases Urological Diseases Ophthalmological Diseases Immunological DiseasesNanomedicine Market by Application:

Neurology Cardiovascular Anti-Inflammatory Anti-Infectives OncologyNanomedicine Market by Region:

Asia Pacific North America Europe Latin America Middle East AfricaNanomedicine Market Major Players:

Abbott Laboratories CombiMatrix Corporation General Electric Company Sigma-Tau Pharmaceuticals, Inc Johnson & Johnson Mallinckrodt plc. Merck & Company, Inc. Nanosphere, Inc. Pfizer, Inc. Teva Pharmaceutical Industries Ltd. Celgene Corporation UCB (Union Chimique Belge) S.A. AMAG Pharmaceuticals Nanospectra Biosciences, Inc. Arrowhead Pharmaceuticals, Inc. Leadiant Biosciences, Inc. Epeius Biotechnologies Corporation Cytimmune Sciences, Inc.

MAJOR TOC OF THE REPORT

Chapter One: Nanomedicine Market Overview

Chapter Two: Manufacturers Profiles

Chapter Three: Global Nanomedicine Market Competition, by Players

Chapter Four: Global Nanomedicine Market Size by Regions

Chapter Five: North America Nanomedicine Revenue by Countries

Chapter Six: Europe Nanomedicine Revenue by Countries

Chapter Seven: Asia-Pacific Nanomedicine Revenue by Countries

Chapter Eight: South America Nanomedicine Revenue by Countries

Chapter Nine: Middle East and Africa Revenue Nanomedicine by Countries

Chapter Ten: Global Nanomedicine Market Segment by Type

Chapter Eleven: Global Nanomedicine Market Segment by Application

Chapter Twelve: Global Nanomedicine Market Size Forecast (2019-2026)

Browse Full Report with Facts and Figures of Nanomedicine Market Report at: https://www.maximizemarketresearch.com/market-report/nanomedicine-market/39223/

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Nanomedicine Market: Industry Analysis and forecast 2026: By Modality, Diseases, Application and... - Azizsalon News

New York, May 27, 2020 (GLOBE NEWSWIRE) -- Reportlinker.com announces the release of the report "Global Nanotechnology in Drug Delivery Industry" - https://www.reportlinker.com/p05621749/?utm_source=GNW 1 Billion by the end of the analysis period. An unusual period in history, the coronavirus pandemic has unleashed a series of unprecedented events affecting every industry. The Nanocrystals market will be reset to a new normal which going forwards in a post COVID-19 era will be continuously redefined and redesigned. Staying on top of trends and accurate analysis is paramount now more than ever to manage uncertainty, change and continuously adapt to new and evolving market conditions.

As part of the new emerging geographic scenario, the United States is forecast to readjust to a 17% CAGR. Within Europe, the region worst hit by the pandemic, Germany will add over US$4.1 Billion to the regions size over the next 7 to 8 years. In addition, over US$3.7 Billion worth of projected demand in the region will come from Rest of European markets. In Japan, the Nanocrystals segment will reach a market size of US$3 Billion by the close of the analysis period. Blamed for the pandemic, significant political and economic challenges confront China. Amid the growing push for decoupling and economic distancing, the changing relationship between China and the rest of the world will influence competition and opportunities in the Nanotechnology in Drug Delivery market. Against this backdrop and the changing geopolitical, business and consumer sentiments, the worlds second largest economy will grow at 25.2% over the next couple of years and add approximately US$20.2 Billion in terms of addressable market opportunity. Continuous monitoring for emerging signs of a possible new world order post-COVID-19 crisis is a must for aspiring businesses and their astute leaders seeking to find success in the now changing Nanotechnology in Drug Delivery market landscape. All research viewpoints presented are based on validated engagements from influencers in the market, whose opinions supersede all other research methodologies.

Competitors identified in this market include, among others, AbbVie Inc.; Aquanova AG; BlueWillow Biologics; Camurus AB; Celgene, Inc.; Ceramisphere Health Pty Limited; Cristal Therapeutics; CYTIMMUNE SCIENCES, Inc.; EnColl Corporation; EyePoint Pharmaceuticals; Lena Nanoceutics Ltd.; Nanobiotix; NanoCarrier Co., Ltd.; NanOlogy LLC; Nanospectra Biosciences, Inc.; Parvus Therapeutics Inc.; Selecta Biosciences; Starpharma Holdings Limited; Taiwan Liposome Co., ; Tarveda Therapeutics

Read the full report: https://www.reportlinker.com/p05621749/?utm_source=GNW

NANOTECHNOLOGY IN DRUG DELIVERY MCP-7MARKET ANALYSIS, TRENDS, AND FORECASTS, JUNE 2CONTENTS

I. INTRODUCTION, METHODOLOGY & REPORT SCOPE

II. EXECUTIVE SUMMARY

1. MARKET OVERVIEW Nanotechnology, A Critical Part of Healthcare Reform Recent Market Activity Nanomedicine, Revolutionizing the Basics of Medicine A Peek Into the Evolving Role of Nanoparticles in Nanomedicine Nanocrystals Continue to Gain Momentum as Alternatives to Traditional Nanocarriers Nanocarriers Enable Targeted Drug Delivery Systems to Improve Therapeutic Outcomes Advanced Liposomes Enable Low Soluble Drugs to Achieve Targeted Delivery Multifunctional Dendrimers Present an Ideal Structure for Targeted Drug Delivery High Drug Loading Capacity of PAMAM Dendrimers Bodes Well for Targeted Drug Delivery Systems Nanotechnology-Based Strategies for siRNA Grows in Popularity NEM Devices as Drug Delivery Vehicles Nanotechnology - In Pursuit of Co-Delivery of Drugs Nanoemulsions Begin to Make a Mark Nanotechnology Finds Increasing Role in Fighting Infectious Diseases List of Select Nanotechnology-based Antimicrobial Drugs in Clinical Use Nanotechnology Opening New Avenues in Antiretroviral Therapy Demonstrated Activity of Select Nanotechnology- Delivered Antiretroviral Therapies Nanotechnology in Delivery of CNS Therapeutics Market Outlook Global Competitor Market Shares Nanotechnology in Drug Delivery Competitor Market Share Scenario Worldwide (in %): 2020 & 2029 Impact of Covid-19 and a Looming Global Recession 2. FOCUS ON SELECT PLAYERS AbbVie Inc. (USA) Aquanova AG (Germany) BlueWillow Biologics (USA) Camurus AB (Sweden) Celgene, Inc. (Canada) Ceramisphere Health Pty Limited (Australia) Cristal Therapeutics (The Netherlands) CYTIMMUNE SCIENCES, INC. (Italy) EnColl Corporation (USA) EyePoint Pharmaceuticals (USA) Lena Nanoceutics Ltd. (UK) NanOlogy LLC (USA) NanoCarrier Co., Ltd. (Japan) Nanobiotix (France) Nanospectra Biosciences, Inc (USA) Parvus Therapeutics Inc. (USA) Selecta Biosciences (USA) Starpharma Holdings Limited (Australia) Taiwan Liposome Co. (Taiwan) Tarveda Therapeutics (USA) 3. MARKET TRENDS & DRIVERS Growing Need for Alternative Approaches to Conventional Chemotherapy Creates Opportunities for Nanoparticles Stimuli Responsive Polymeric Micelles Promise Enhanced Therapeutic Effect for Hydrophobic Anticancer Drugs Inorganic Nanocarriers Facilitate High Payload Capacity and Co -Delivery Platforms for MDR Cancer Therapy Solid Lipid Nanoparticles Provide Increased Physical Stability in Targeted Drug Delivery Pulmonary Delivery of Nanoparticle-Based Drugs Receives Increased Interest Inhalable Liposome Formulations Attract Research Interest in Pulmonary Delivery SLNs in Pulmonary Delivery of Drugs Market Challenges Increasing Environmental and Health Concerns Limited Success and Scaling Up Issues Pose a Major Hurdle to Further Advancement Higher Concentration of Research in Academia limits Commercialization Collaborations Assume Importance Nanomedicine Regulation 4. GLOBAL MARKET PERSPECTIVE Table 1: Nanotechnology in Drug Delivery Global Market Estimates and Forecasts in US$ Million by Region/Country: 2020-2027 Table 2: Nanotechnology in Drug Delivery Market Share Shift across Key Geographies Worldwide: 2020 VS 2027 Table 3: Nanocrystals (Technology) World Market by Region/Country in US$ Million: 2020 to 2027 Table 4: Nanocrystals (Technology) Market Share Breakdown of Worldwide Sales by Region/Country: 2020 VS 2027 Table 5: Nanocarriers (Technology) Potential Growth Markets Worldwide in US$ Million: 2020 to 2027 Table 6: Nanocarriers (Technology) Market Sales Breakdown by Region/Country in Percentage: 2020 VS 2027 III. MARKET ANALYSIS GEOGRAPHIC MARKET ANALYSIS UNITED STATES Market Facts & Figures US Nanotechnology in Drug Delivery Market Share (in %) by Company: 2020 & 2025 Market Analytics Table 7: Nanotechnology in Drug Delivery Market in US$ Million in the United States by Technology: 2020-2027 Table 8: United States Nanotechnology in Drug Delivery Market Share Breakdown by Technology: 2020 VS 2027 CANADA Table 9: Nanotechnology in Drug Delivery Market Analysis in Canada in US$ Million by Technology: 2020-2027 Table 10: Canadian Nanotechnology in Drug Delivery Market Share Breakdown by Technology: 2020 VS 2027 JAPAN Table 11: Japanese Medium & Long-Term Outlook for Nanotechnology in Drug Delivery Market in US$ Million by Technology: 2020-2027 Table 12: Japanese Nanotechnology in Drug Delivery Market Percentage Share Distribution by Technology: 2020 VS 2027 CHINA Table 13: Nanotechnology in Drug Delivery Market Estimates and Forecasts in China in US$ Million by Technology: 2020-2027 Table 14: Nanotechnology in Drug Delivery Market in China: Percentage Share Analysis by Technology for 2020 and 2027 EUROPE Market Facts & Figures European Nanotechnology in Drug Delivery Market: Competitor Market Share Scenario (in %) for 2020 & 2025 Market Analytics Table 15: European Nanotechnology in Drug Delivery Market Demand Scenario in US$ Million by Region/Country: 2018-2025 Table 16: European Nanotechnology in Drug Delivery Market Share Shift by Region/Country: 2020 VS 2027 Table 17: European Nanotechnology in Drug Delivery Market Assessment in US$ Million by Technology: 2020-2027 Table 18: Nanotechnology in Drug Delivery Market in Europe: Percentage Breakdown of Sales by Technology for 2020 and 2027 FRANCE Table 19: French Nanotechnology in Drug Delivery Market Estimates and Projections in US$ Million by Technology: 2020-2027 Table 20: French Nanotechnology in Drug Delivery Market Share Breakdown by Technology: 2020 VS 2027 GERMANY Table 21: German Nanotechnology in Drug Delivery Latent Demand Forecasts in US$ Million by Technology: 2020-2027 Table 22: German Nanotechnology in Drug Delivery Market Share Breakdown by Technology: 2020 VS 2027 ITALY Table 23: Nanotechnology in Drug Delivery Market Estimates and Forecasts in Italy in US$ Million by Technology: 2020-2027 Table 24: Nanotechnology in Drug Delivery Market in Italy: Percentage Share Analysis by Technology for 2020 and 2027 UNITED KINGDOM Table 25: United Kingdom Medium & Long-Term Outlook for Nanotechnology in Drug Delivery Market in US$ Million by Technology: 2020-2027 Table 26: United Kingdom Nanotechnology in Drug Delivery Market Percentage Share Distribution by Technology: 2020 VS 2027 SPAIN Table 27: Nanotechnology in Drug Delivery Market Analysis in Spain in US$ Million by Technology: 2020-2027 Table 28: Spanish Nanotechnology in Drug Delivery Market Share Breakdown by Technology: 2020 VS 2027 RUSSIA Table 29: Nanotechnology in Drug Delivery Market in US$ Million in Russia by Technology: 2020-2027 Table 30: Russian Nanotechnology in Drug Delivery Market Share Breakdown by Technology: 2020 VS 2027 REST OF EUROPE Table 31: Rest of Europe Nanotechnology in Drug Delivery Market Assessment in US$ Million by Technology: 2020-2027 Table 32: Nanotechnology in Drug Delivery Market in Rest of Europe: Percentage Breakdown of Sales by Technology for 2and 2027 ASIA-PACIFIC Table 33: Asia-Pacific Nanotechnology in Drug Delivery Market Estimates and Forecasts in US$ Million by Region/Country: 2020-2027 Table 34: Asia-Pacific Nanotechnology in Drug Delivery Market Share Analysis by Region/Country: 2020 VS 2027 Table 35: Asia-Pacific Nanotechnology in Drug Delivery Market Estimates and Projections in US$ Million by Technology: 2020-2027 Table 36: Asia-Pacific Nanotechnology in Drug Delivery Historic Market Analysis in US$ Million by Technology: 2020 VS 2027 AUSTRALIA Table 37: Australian Nanotechnology in Drug Delivery Latent Demand Forecasts in US$ Million by Technology: 2020-2027 Table 38: Australian Nanotechnology in Drug Delivery Market Share Breakdown by Technology: 2020 VS 2027 INDIA Table 39: Nanotechnology in Drug Delivery Market Analysis in India in US$ Million by Technology: 2020-2027 Table 40: Indian Nanotechnology in Drug Delivery Market Share Breakdown by Technology: 2020 VS 2027 SOUTH KOREA Table 41: Nanotechnology in Drug Delivery Market in South Korea: Recent Past, Current and Future Analysis in US$ Million by Technology for the Period 2020-2027 Table 42: Nanotechnology in Drug Delivery Market Share Distribution in South Korea by Technology: 2020 VS 2027 REST OF ASIA-PACIFIC Table 43: Rest of Asia-Pacific Medium & Long-Term Outlook for Nanotechnology in Drug Delivery Market in US$ Million by Technology: 2020-2027 Table 44: Rest of Asia-Pacific Nanotechnology in Drug Delivery Market Percentage Share Distribution by Technology: 2020 VS 2027 LATIN AMERICA Table 45: Latin American Nanotechnology in Drug Delivery Market Trends by Region/Country in US$ Million: 2020-2027 Table 46: Latin American Nanotechnology in Drug Delivery Market Percentage Breakdown of Sales by Region/Country: 2020 and 2027 Table 47: Nanotechnology in Drug Delivery Market Estimates and Forecasts in Latin America in US$ Million by Technology: 2020-2027 Table 48: Nanotechnology in Drug Delivery Market in Latin America : Percentage Analysis by Technology for 2020 and 2027 ARGENTINA Table 49: Argentinean Nanotechnology in Drug Delivery Market Assessment in US$ Million by Technology: 2020-2027 Table 50: Nanotechnology in Drug Delivery Market in Argentina: Percentage Breakdown of Sales by Technology for 2020 and 2027 BRAZIL Table 51: Brazilian Nanotechnology in Drug Delivery Market Estimates and Projections in US$ Million by Technology: 2020-2027 Table 52: Brazilian Nanotechnology in Drug Delivery Market Share Breakdown by Technology: 2020 VS 2027 MEXICO Table 53: Mexican Nanotechnology in Drug Delivery Latent Demand Forecasts in US$ Million by Technology: 2020-2027 Table 54: Mexican Nanotechnology in Drug Delivery Market Share Breakdown by Technology: 2020 VS 2027 REST OF LATIN AMERICA Table 55: Nanotechnology in Drug Delivery Market in US$ Million in Rest of Latin America by Technology: 2020-2027 Table 56: Rest of Latin America Nanotechnology in Drug Delivery Market Share Breakdown by Technology: 2020 VS 2027 MIDDLE EAST Table 57: The Middle East Nanotechnology in Drug Delivery Market Estimates and Forecasts in US$ Million by Region/Country: 2018-2025 Table 58: The Middle East Nanotechnology in Drug Delivery Market Share Breakdown by Region/Country: 2020 and 2027 Table 59: The Middle East Nanotechnology in Drug Delivery Market Analysis in US$ Million by Technology: 2020-2027 Table 60: The Middle East Nanotechnology in Drug Delivery Market Share Breakdown by Technology: 2020 VS 2027 IRAN Table 61: Iranian Medium & Long-Term Outlook for Nanotechnology in Drug Delivery Market in US$ Million by Technology: 2020-2027 Table 62: Iranian Nanotechnology in Drug Delivery Market Percentage Share Distribution by Technology: 2020 VS 2027 ISRAEL Table 63: Israeli Nanotechnology in Drug Delivery Market Assessment in US$ Million by Technology: 2020-2027 Table 64: Nanotechnology in Drug Delivery Market in Israel: Percentage Breakdown of Sales by Technology for 2020 and 2027 SAUDI ARABIA Table 65: Nanotechnology in Drug Delivery Market Estimates and Forecasts in Saudi Arabia in US$ Million by Technology: 2020-2027 Table 66: Nanotechnology in Drug Delivery Market in Saudi Arabia: Percentage Share Analysis by Technology for 2020 and 2027 UNITED ARAB EMIRATES Table 67: Nanotechnology in Drug Delivery Market in the United Arab Emirates: Recent Past, Current and Future Analysis in US$ Million by Technology for the Period 2020-2027 Table 68: Nanotechnology in Drug Delivery Market Share Distribution in United Arab Emirates by Technology: 2020 VS 2027 REST OF MIDDLE EAST Table 69: Rest of Middle East Nanotechnology in Drug Delivery Latent Demand Forecasts in US$ Million by Technology: 2020-2027 Table 70: Rest of Middle East Nanotechnology in Drug Delivery Market Share Breakdown by Technology: 2020 VS 2027 AFRICA Table 71: Nanotechnology in Drug Delivery Market in US$ Million in Africa by Technology: 2020-2027 Table 72: African Nanotechnology in Drug Delivery Market Share Breakdown by Technology: 2020 VS 2027 IV. COMPETITION

Total Companies Profiled: 43 Read the full report: https://www.reportlinker.com/p05621749/?utm_source=GNW

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Amid the COVID-19 crisis and the looming economic recession, the Nanotechnology in Drug Delivery market worldwide will grow by a projected US$124.7...

President Donald Trump pondered if he should take insulin while announcing a plan to reduce the price of the drug typically prescribed to diabetics. USA TODAY

WASHINGTON President Donald Trump pondered on Tuesday whether he should be taking insulin,a hormone typically prescribed to diabetics, during an announcement foraplan which would aim to drastically reduce the price of insulin for people on Medicare.

"I don't use insulin," Trump said. "Should I be? Huh? I never thought about it. But I know a lot of people are very badly affected, right? Unbelievable."

In people with Type 1 diabetes, the pancreas cant make insulin. Those with the condition require several doses of insulin a day.

'Contain potentially misleading information': Twitter fact-checks Trump's tweets

All people with Type 1 and some with Type 2, whose body doesnt use insulin the way it should, need the drug.

Trump has no known history of diabetes.

More than 30.3 million people in the U.S. have diabetes, and 90% to 95% of them have Type 2 diabetes, according to the 2017 National Diabetes Statistics Report. Unlike people with Type 1 diabetes, those with Type 2 can in many caseslessen their dependence on insulin through healthier diet and exercise.

Clyburn: I 'cringed' at Biden 'you ain't black' comment but compare him 'to the alternative, not the Almighty'

Asked later by a reporter why he would take insulin, Trump asked surgeon general Jerome Adams to answer, in which he explained to the president that, "Your body, Mr. President, actually makes insulin endogenously."

He continued that "people such as you and I, we make our own insulin. So yes we do utilize insulin, but we make it ourselves.

Trump saysmost senior Medicare recipients willget prescription plans that would cap copay costs, giving them access to several types of insulinat no more thana $35 copayfor a month's supply, underneath the planannounced Tuesday.

Struggling to stay alive: Rising insulin prices cause diabetics to go to extremes

The price of modern versions of a drug that more than 7 million Americans need to livenearly tripled from 2002 to 2013, according to onestudy.Type 1 diabetics paid an average of $5,705 for insulin in 2016 nearly double what they paid in 2012, according to the Health Care Cost Institute.

Costs for insulin have continuedto rise, so much so that almost half of people with diabeteshave temporarily skipped taking their insulin, according to a 2018 survey by UpWell Health, a Salt Lake City company that provides home delivery of medications and supplies for chronic conditions.

Contributing:Ken Alltucker, USA TODAY;Megan Henry, The Columbus Dispatch.

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Trump asks whether he should take insulin despite not being diabetic - USA TODAY

DUBLIN--(BUSINESS WIRE)--he "United States Diabetic Food Market By Product Type (Baked Products For Diabetics, Beverages For Diabetics, Confectionery For Diabetics, Ice Cream For Diabetics, Others), By Distribution Channel, By End Users, By Region, Forecast & Opportunities, 2025" report has been added to ResearchAndMarkets.com's offering.

The United States Diabetic Food Market is expected to grow at a formidable rate of during the forecast period. The United States Diabetic Food Market is driven by the growing awareness regarding various health issues associated with diabetes, increasing prevalence of obesity and diabetes owing to a lack of physical activity among children and adolescents, rising awareness among consumers regarding the preventive measures that can be taken against diabetes, among others. Additionally, growing research and development (R&D) to produce diabetic food products and flaunting a diversified product portfolio that caters to the requirements of a wide consumer base is further expected to propel the market during forecast years.

The United States Diabetic Food Market is segmented based on product type, distribution channel, end-user, company and region. Based on product type, the market can be fragmented into baked products for diabetics, beverages for diabetics, confectionery for diabetics, ice cream for diabetics, dairy products for diabetics and breakfast cereals for diabetics. The beverages for diabetics segment is expected to dominate the market during the next five years. This can be ascribed to the varied products available under dietary beverages and relatively large consumption of these beverages.

Companies Mentioned

Objective of the Study:

Key Topics Covered:

1. Product Overview

2. Research Methodology

3. Executive Summary

4. Voice of Customer

5. United States Diabetic Food Market Outlook

5.1. Market Size & Forecast

5.1.1. By Value

5.2. Market Share & Forecast

5.2.1. By Product Type (Baked Products For Diabetics, Beverages For Diabetics, Confectionery For Diabetics, Ice Cream For Diabetics, Dairy Products For Diabetics and Breakfast Cereals For Diabetics)

5.2.2. By Distribution Channel (Grocery Stores, Supermarkets/Hypermarkets, Online, Drug Stores/Pharmacies and Others)

5.2.3. By End Users (Adults v/s Children)

5.2.4. By Region

5.2.5. By Company (2018)

5.3. Product Market Map

6. United States Baked Products For Diabetics Market Outlook

6.1. Market Size & Forecast

6.1.1. By Value

6.2. Market Share & Forecast

6.2.1. By Distribution Channel

6.2.2. By End Users

7. United States Beverages For Diabetics Market Outlook

7.1. Market Size & Forecast

7.1.1. By Value

7.2. Market Share & Forecast

7.2.1. By Distribution Channel

7.2.2. By End Users

8. United States Confectionery For Diabetics Market Outlook

8.1. Market Size & Forecast

8.1.1. By Value

8.2. Market Share & Forecast

8.2.1. By Distribution Channel

8.2.2. By End Users

9. United States Ice Cream For Diabetics Market Outlook

9.1. Market Size & Forecast

9.1.1. By Value

9.2. Market Share & Forecast

9.2.1. By Distribution Channel

9.2.2. By End Users

10. United States Dairy Products For Diabetics Market Outlook

10.1. Market Size & Forecast

10.1.1. By Value

10.2. Market Share & Forecast

10.2.1. By Distribution Channel

10.2.2. By End Users

11. United States Breakfast Cereals For Diabetics Market Outlook

11.1. Market Size & Forecast

11.1.1. By Value

11.2. Market Share & Forecast

11.2.1. By Distribution Channel

11.2.2. By End Users

12. Market Dynamics

12.1. Drivers

12.2. Challenges

13. Market Trends & Developments

14. Supply Chain Analysis

15. Policy & Regulatory Landscape

16. United States Economic Profile

17. Competitive Landscape

17.1. Competition Outlook

17.2. Company Profiles

18. Strategic Recommendations

19. About Us & Disclaimer

For more information about this report visit https://www.researchandmarkets.com/r/wgptnq

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Insights on the US Diabetic Food Industry to 2025 - Featuring Unilever, Kellogg Company & Fifty 50 Foods Among Others - ResearchAndMarkets.com -...