Genetic risk score is effective in diagnosing type 1 diabetes in Indians – News-Medical.Net

June 19, 2020 medical

A new way of using genetics to diagnose diabetes could pave the way for better diagnosis and treatment in Indians, new research has concluded.

Misdiagnosis of diabetes could be an issue in India because of features of diabetes in Indians which might vary from the standard western textbooks. Until recently, it was widely believed that type 1 diabetes appeared in children and adolescents, and type 2 diabetes in obese and older (typically after 45 years of age). However, recent findings have shown that type 1 diabetes can occur later in life, while type 2 diabetes is on the rise among younger and thinner Indians. Distinguishing the two types of diabetes has therefore, become more complex. The two types follow different treatment regimes with type 1 diabetes needing lifelong insulin injections but type 2 diabetes often being managed with diet or tablet treatment. Misclassification of the type of diabetes may lead to sub-standard diabetes care and possible complications.

A new publication conducted between researchers at the KEM Hospital, Pune, CSIR-Centre for Cellular and Molecular Biology (CCMB), Hyderabad, and the University of Exeter in the UK shows that a genetic risk score is effective in diagnosing type 1 diabetes in Indians.

The genetic risk score, developed by the University of Exeter, takes into account detailed genetic information known to increase the chance of developing type 1 diabetes. The score may be used at the time of diabetes diagnosis to help decide if someone has type 1 diabetes.

Up to now, the bulk of research in this field has been conducted in European populations. Now, in a paper published in Scientific Reports, researchers have analysed whether the European risk score is effective in diagnosing type 1 diabetes in Indians. The team studied people with diabetes from Pune, India. The team analysed 262 people with type 1 diabetes, 352 people with type 2 diabetes, and 334 people without diabetes. All were of Indian (Indo-European) ancestry. Outcomes from the Indian populations were compared with those of Europeans from the Wellcome Trust Case Control Consortium study.

The research, supported by Diabetes UK, the KEM Hospital Research Centre, Pune and the Council of Scientific and Industrial Research (CSIR) in India, found that the test is effective in diagnosing the right type of diabetes in Indians, even in its current form, which is based on European data. Authors also found genetic differences between the populations which mean the test could be further improved to enhance outcomes for Indian populations.

Diagnosing the right diabetes type is an increasingly difficult challenge for clinicians, as we now know that type 1 diabetes can occur at any age. This task is even harder in India, as more cases of type 2 diabetes occur in people with low BMI. We now know that our genetic risk score is an effective tool for Indians, and can help get people on the treatment they need to avoid life threatening complications such as diabetic ketoacidosis and to achieve the best health outcomes."

Dr. Richard Oram, University of Exeter Medical School

Dr Chittaranjan Yajnik of the KEM Hospital & Research Centre, Pune agrees with Dr Oram. He said, that the escalating epidemic of diabetes in young Indians makes it imperative that we diagnose the type of diabetes correctly to avoid mistreatment and its long term biological, social and economic implications. The new genetic tool will be a great help in this. It will help decide when diabetes is mainly caused by autoimmune destruction of pancreatic beta cells (type 1 diabetes), and when diabetes is mainly caused by reduced action of insulin due to excess fat and smaller muscle mass in the body of Indians ('thin-fat Indians'), as is the case in type 2 diabetes. He said, "we look forward to using this test in diabetic patients from different parts of India where the physical characteristics of diabetic patients differ from the standard description".

The authors found nine genetic areas (called the SNPs) that correlate with type 1 diabetes both in Indian and European populations, and can be used to predict the onset of type 1 diabetes in Indians. Dr GR Chandak, Chief Scientist leading the study at the CSIR-Centre for Cellular and Molecular Biology (CCMB), said: "It's interesting to note that different SNPs are more abundant among Indian and European patients. This opens up the possibility that environmental factors might be interacting with these SNPs to cause the disease."

Given the genetic diversity of the population of India, the study's results need to be validated in other ethnic groups of the country too. Dr Rakesh K Mishra, Director of the CSIR-Centre for Cellular and Molecular Biology (CCMB), said: "Since more than 20 per cent of people with type 1 diabetes below the age of 15 years of age are in India, developing a genetic test kit to reliably detect type 1 from type 2 diabetes holds a lot of significance for the country."

Source:

Journal reference:

Harrison, J.W., et al. (2020) Type 1 diabetes genetic risk score is discriminative of diabetes in non-Europeans: evidence from a study in India. Scientific Reports. doi.org/10.1038/s41598-020-65317-1.

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Genetic risk score is effective in diagnosing type 1 diabetes in Indians - News-Medical.Net

Immunology

How does the body fight COVID-19? U of T researcher’s work could aid vaccine development – News@UofT

June 18, 2020 medical

JenGommerman, an immunologist at the University of Toronto, wants everyone to know one important point about the COVID-19 pandemic: The human immune system is working to fight off this novel coronavirus.

Many thousands of people have died from the virus. But many more thousands have contracted it and survived. That is because when the virus first enters your body, usually through your nose or mouth, it triggers the immune system to send antibodies in response. Antibodies are proteins in your blood that your body uses to fight infection. In diseases such as chicken pox, the antibodies usually prevent you from getting the illness again. The formal term for the generation of antibodies is a humoral immune response.

But COVID-19 the illness caused by the SARS-CoV-2 virus is puzzling scientists with some challenging questions: If a person recovers from COVID-19, will the antibodies keep that person from being infected again? Why dont some people show symptoms? What happens as soon as the virus enters the body?

Gommerman, a professor in the department of immunology in the Faculty of Medicine, has received support from the Ontario COVID-19 Rapid Research Fund to conduct research in collaboration with an interdisciplinary team of scientists to answer these and other questions.

She emphasizes that the greatest challenge in understanding anything to do with COVID-19 is the fact that it is new.

Understanding how SARS CoV-2 induces a humoral immune response is vital to scientists eventually developing a vaccine, she says. But the world has only known about this virus since December or January. It is brand new. The science community doesnt fully understand yet how the immune system responds to the virus.

So my teams work will shed some light on that, which, in turn, could help with the development of a vaccine.

The provinces rapid research fund is also supporting the work ofJean-Philippe Julien, senior scientist in molecular medicine at the Hospital for Sick Children and an assistant professor in biochemistry and immunology at U of T. His projectwill usemolecular technology to develop a potent and broad antiviral treatment.

As forGommerman, she will be developing an assay (the scientific term for a test or experiment) to identify antibodies in saliva in the hopes of better understanding the early immune response when the virus enters the oropharyngeal tract (a part of the throat behind the mouth and nasal cavity).

Like so much of the COVID-19 research being conducted now, the work being spearheaded byGommermanis a collaboration with a number of other scientists at U of T and the universitys partner hospitals.

Gommermansresearch into saliva, for example, will be compared with assays being done byAnne-Claude Gingras, a senior investigator at Sinai Healths Tanenbaum Lunenfeld Research Institute and a professor of molecular genetics at U of T.

Gingras has led the development of a blood test that can detect antibodies in the immune system of infected patients. The test has the potential to enable hospitals and other institutions to screen up to 10,000 samples at once. This type of analysis is called serosurveillance the study of blood serum, especially as it relates to the work of the immune system response to pathogens entering the body.

Serosurveillanceis an important weapon in our fight against COVID-19,Gommermansays. It has the power to tell us what is the true scope of the pandemic. This is what the blood experiments at Mount Sinai get us.

For the saliva experiments, we will learn more about what is happening early in the immune response in asymptomatic patients in the oropharyngeal tract where the virus is first introduced. This has the potential to reveal what aspects of the immune response might confer protection to those people who never show symptoms or only show mild symptoms.

Key to understanding the early immune response is a collaboration withDarrell Tan, an infectious diseases physician and clinician-scientist at St. Michaels Hospital. Tan, who is also an assistant professor in U of Ts Faculty of Medicine and at the Institute of Health Policy, Management and Evaluation at the Dalla Lana School of Public Health, is enrolling 1,000 subjects, via contact tracing, who have been linked to patients infected with COVID-19. Tan and his team will test the saliva of these people regularly over a number of weeks.

The contacts are called a ring of associates.

Because the people in that ring have a higher chance of contracting COVID-19 than the general public, we will presumably have people who are just getting infected, saysGommerman. This will allow us to learn why some people dont show symptoms but still have the illness and how the early immune response actually works.

BothGommermanand Gingras are using proteins produced by U of TsJames Rini, professor in the departments of molecular genetics and biochemistry. The proteins are highly purified pieces of the SARS-CoV-2 virus that are used as bait to catch antibodies in the saliva or in the blood so that the researchers can measure them.

Without Jims work on these proteins, we wouldnt be able to go further in our research, saysGommerman. Hes been studying coronavirus proteins since SARS first hit North America in 2003. The science community doesnt know nearly as much about coronaviruses as we do, for example, influenza.

We owe a lot to researchers like Jim who have been building up a knowledge base about coronaviruses. Were relying on them now.

Further to the collaborative nature of the research,Gommermansteam is using saliva samples from patients who have had the virus, andwho have recovered. The samples were collected by:Mario Ostrowski, a professor in the departments of medicine, immunology and laboratory medicine and pathobiology at U of T;AllisonMcGeer, director of the Infectious Diseases Research Unit at Mount Sinai Hospital and a U of T professor in the departments of medicine and laboratory medicine and pathobiology (LMP), as well as at the Dalla Lana School of Public Health; andSamiraMubarekaan assistant professor in the department of laboratory medicine and pathobiology who is at Sunnybrook Health Sciences Centre.

The multidisciplinary nature of the research is what enabledGommermanto pivot from her usual work on autoimmune diseases, especially multiple sclerosis, and gut immunology. The ability to draw on the skills and experiences of members of her team was also key.

Our research associate, Dr.Olga Rojas, had worked on saliva antibodies to a disease called rotavirus when she was studying in Columbia, South America.

Also key to the pivot were three first-year doctoral students BaweletaIsho,Annie PuandMichelle Zuo.

I didnt want to pull more senior students from their doctoral work, so I asked these first-year students to help with the work,Gommermansays. Theyve been amazing, as well as our project manager, Dr.Gary Chao,who organized all the samples and made sure we were compliant from a biosafety and ethics perspective. This was urgent work and they all rose to the occasion under a lot of pressure.

with files from Amanda Ferguson

Immunology

Asthma Not Associated With Increased Risk of Hospitalization Among COVID-19 Patients – PR Web

June 18, 2020 medical

More studies must be done to look at the underlying immune modulation caused by asthma or asthma treatment to see what impact it may have on COVID-19 outcomes. - Anju T. Peters, MD, MSCI, FAAAAI

MILWAUKEE (PRWEB) June 18, 2020

According to research from The Journal of Allergy and Clinical Immunology (JACI), patients with asthma were not more likely to be hospitalized due to COVID-19 than those without asthma. This finding comes despite asthmatics being more prevalent in the studys cohort than would be expected given the estimates of asthma prevalence nationwide.

This study set out to examine the prevalence of asthma and comorbidities in asthmatics with COVID-19. In addition, researchers determined the risk of hospitalization due to COVID-19 in asthmatics and looked at inhaled corticosteroid use and risk of hospitalization due to COVID-19.

The retrospective study was conducted across 10 hospitals affiliated with NorthwesternMedicine via automated chart review using Northwestern Medicines Enterprise Data Warehouse, an electronic repository of health records. In total, 1,526 patients with COVID-19 were identified and used in the study. Of those, 220 (14.4%) had asthma, which is significantly higher than the national asthma prevalence rate of eight to nine percent. These numbers were in line with published U.S. data from the Centers for Disease Control and Preventions Morbidity and Mortality Weekly Report during the study period.

Two models were used to examine if asthma was a risk for hospitalization due to COVID-19. The first model adjusted for demographic data including age, gender, and ethnicity, while the second model also adjusted for multiple risk factors, including smoking and obesity. In both models, there was no significant difference in the risk of hospitalization between asthmatics and non-asthmatics.

The prevalence of many comorbidities including obesity, hypertension, sleep apnea, COPD, and gastroesophageal reflux disease was higher in patients with asthma and COVID-19 than in non-asthmatics with COVID-19. However, these comorbidities did not translate to a higher rate of hospitalization in asthmatics compared to non-asthmatics with COVID-19. Patients with asthma also had a higher prevalence of allergic rhinitis, rhinosinusitis, and immunodeficiencies. Interestingly, rhinosinusitis was associated with a lower risk of hospitalization.

Dramatic racial disparities have been reported during the COVID-19 pandemic and this was true in this study. Non-Hispanic African Americans and Hispanics or Latinos comprised a significant proportion of the asthma cohort with COVID-19 and had higher likelihood of COVID-19 related hospitalizations in general.

Chart review was completed to document which asthmatic patients with COVID-19 had a prescription of an inhaled corticosteroid (ICS), combination inhaled corticosteroid plus long-acting beta-agonist (ICS/LABA), and/or systemic corticosteroids. Only one patient was on a biologic. Just under half (48.2%) of the patients were prescribed the aforementioned medications, and in general the risk of hospitalization for these patients was not significantly greater than for those not on them.

There was also no observable difference in mortality rates between patients with COVID-19 who had asthma and those who did not. Laboratory assessment actually saw lower levels of biomarkers used to identify COVID-19 severity in patients with asthma, though additional studies must be performed to understand why this is and if asthmatics may have any protection against the virus.

We would usually expect for asthmatic patients to have worse outcomes, as viral illness often can set off asthma exacerbations, said Anju T. Peters, MD, MSCI, FAAAAI, corresponding author of the study. More studies must be done to look at the underlying immune modulation caused by asthma or asthma treatment to see what impact it may have on COVID-19 outcomes.

Another limitation of the study, according to Dr. Peters, was that they were not able to assess the contribution of asthma severity or asthma endotypes to COVID-19 disease severity and cautioned that healthcare workers need to be vigilant of older patients, those with certain comorbidities, African Americans, and Hispanics as they are at increased risk of hospitalization in general due to COVID-19.

You can learn more about asthma and COVID-19 on the American Academy of Allergy, Asthma & Immunology website, aaaai.org.

The American Academy of Allergy, Asthma & Immunology (AAAAI) represents allergists, asthma specialists, clinical immunologists, allied health professionals and others with a special interest in the research and treatment of allergic and immunologic diseases. Established in 1943, the AAAAI has more than 7,100 members in the United States, Canada and 72 other countries. The AAAAIs Find an Allergist/Immunologist service is a trusted resource to help you find a specialist close to home.

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Asthma Not Associated With Increased Risk of Hospitalization Among COVID-19 Patients - PR Web

Immunology

Want to Avoid Another Shutdown? Wear a Mask, Experts Advise – Duke Today

June 18, 2020 medical

DURHAM, N.C. -- If youre in public and see someone wearing a mask, that person is doing it for your benefit.

So return the favor.

That was one of several themes to emerge Thursday from a media briefing featuring two Duke medical scholars with vast expertise in vaccines, immunology and the spread of infectious diseases like COVID-19.

Drs. Sallie Permar and Cameron Wolfe took questions for an hour on myriad issues. Here are excerpts:

Dr. Cameron Wolfe, infectious disease specialist

The scientific consensus is actually quite clear. The consensus exists on both the types of masks and their protective efficacy of the individual wearing it, and also the collective benefit for the community.

That second part has really not been emphasized sufficiently. People have sort of viewed a mask as something designed to protect them. While that may be true in a hospital ward in the community the drive is very clearly to protect everyone else.

We understand now very clearly this virus has a pre-symptomatic phase of shedding. Even though I may not be symptomatic today, even though I may have no idea of the fact I may become sick in a day or two I can pass it to other people unwittingly. So my wearing a mask fundamentally protects you when I dont know Im sick or infectious. That part of the science is actually pretty clear.

The wearing of any mask, including cloth masks that folks will now see for sale widely, is very satisfactory at me preventing you getting sick. Thats the public health part of this. When I walk down the street wearing a mask, Im doing that for other folk around me, not fundamentally for me.

Dr. Sallie Permar, pediatric infectious disease specialist

The data has really shown that wearing a mask and preventing those respiratory droplets from spreading on other people is really effective.

The masks are super useful in protecting those that you are around. You wear a mask to prevent infecting others. It does play some role in protecting yourself as well. When we think about requiring masks I think its something that the benefit versus the inconvenience weighs towards the benefit.

Permar

Its hard to remember to wear a mask, and its uncomfortable, so the more you see other people doing it, the more youll be reminded to do it.

I went out and bought some designer masks. I think everyone can show their personality in what masks they choose. The more we require masks, the more it will become normal in our everyday lives.

Wolfe

A lot of it is about good leadership and good example-setting. That is something I wish we could do better on as a community. We have almost politicized mask-wearing. That is some sort of dystopian reality where the wearing of a mask has become something that can be judged.

It comes from political leaders buying into this, it also comes from state and federal politics, with leaders visibly taking this to heart. That has not yet happened, and that needs to change if we want people to buy into this.

Wolfe

Being prepared to put a pause on things should be the first step. Im heartened that our state health departments are finally talking about the implications of what a pause to phase 3 for us would look like. If we consider ourselves to be data-driven and we see the data heading in the wrong way, its nonsense to think we can continue doing the same thing and expect that trajectory to change.

Re-crunching down can still be avoided if you put your efforts into the right mitigation strategies.

If you want to keep opening and if we want to allow businesses to function, an individual choice on behalf of our collective, for me to wear a mask, seems like a smaller move than closing down again.

Permar

School reopening is a really difficult decision that were facing. We will dig into the data that shows that children have a very different course of the infection. They are mostly asymptomatic. Whats really important to understand is how much do they transmit the virus? How much do they transmit virus to their peers? How much do they transmit virus to the staff and teachers? What about when we wear masks? Can we reduce that risk?

What I hope will transpire over the next couple months is the development of child-specific metrics. How many children who are presenting with routine health care test positive? How many children are testing positive in our community? Another example might be absenteeism for influenza-like illness.

What I hope is that the education leaders and the public health leaders can think about schools differently than how we treat bars and restaurants. The appropriate metrics for opening up the community in many places where adults are going to congregate -- the number that are hospitalized, the percent testing positive every day -- I dont know (if) we should apply those same metrics to children and schools.

We know that as much as teachers try and as much as parents try, the virtual learning will not be the same, especially (for) the youngest children who really need the face-to-face interaction.

Wolfe

Many of us, frankly, are starting to see some fatigue in the community. I think that fatigue expands to many things. It extends to mask-wearing, it extends to social-distancing fatigue. Those things have played into disease transmission. Unfortunately, the phased reopening has, I suspect, encouraged a little bit of a letdown of folks guard. You really are seeing that steady march of increasing cases, increasing hospitalizations. Weve got to figure out a way to turn that around.

Permar

I often think about what are going to be the impacts on children now and for the future. They are the ones who will be living with the impacts of this virus the longest.

Its a respiratory virus where children are not often severely affected during the acute infection. However, one thing that has been very new and still developing is seeing this post-infectious syndrome that happens almost exclusively in children. Theres an inflammatory syndrome that can be very severe.

It can land children in the hospital. Were still really understanding what that post-infectious syndrome is. But it has reminded us that children are not completely unaffected by this pandemic.

We know that despite them being a minority of the hospitalizations, they have been impacted majorly when it comes to their development, their education and even their routine health care that has fallen behind in this time.

As we look towards a vaccine, the vaccine is being developed at a most amazing speed. As a vaccinologist, I never thought Id see a vaccine developed within a year. Thats being solely focused on adults, and I think we need to consider adding children to that vaccine development as well. We know children are the targets of most vaccines.

They, of course, are often routes to adults becoming infected as well. Adding children into vaccine development is very important for us to think about now rather than waiting until all adults are vaccinated.

Wolfe

Id be nave not to be concerned. I think it is going to be really incumbent upon public health leaders and federal government leaders to demonstrate a clarity of message here that needs to be uniquely available and visible to the public. Yes, I am worried about skepticism. We have to continue to reiterate active demonstrations of safety.

Permar

If we roll out a vaccine to a large percent of the population and then have a safety concern, that will diminish the faith in vaccines. While were going at this with the most rapid speed because the pandemic is not ending until we have a vaccine, we are also facing the challenge of making sure its the safest vaccine we can put out in a rapid fashion.

Faculty Participants

Dr. Sallie PermarDr. Sallie Permarisa professor of pediatric infectious disease, immunology and molecular genetics atthe Duke School of Medicine. Permar can address how COVID-19 affects mothers and children, how viruses transmit between people and general questions on vaccine development. Read her USA Today op-ed.sallie.permar@duke.edu

Dr. Cameron WolfeDr. Cameron Wolfeis an associate professor of medicine and who can discuss transplant-related infectious diseases, general infectious diseases, biological and emergency preparedness for hospital systems, and influenza and respiratory viral pathogens.cw74@duke.edu

Duke experts on a variety of other topics related the coronavirus pandemic can be found here.

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Want to Avoid Another Shutdown? Wear a Mask, Experts Advise - Duke Today

Immunology

Peter Svennilson Elected to RAPT Therapeutics Board of Directors – GlobeNewswire

June 18, 2020 medical

SOUTH SAN FRANCISCO, Calif., June 18, 2020 (GLOBE NEWSWIRE) -- RAPT Therapeutics, Inc. (Nasdaq: RAPT), a clinical-stage immunology-based biopharmaceutical companyfocused on discovering, developing and commercializing oral small molecule therapies for patients with significant unmet needs in oncology and inflammatory diseases, today announced the election of Peter Svennilson, Managing Partner of The Column Group, to its Board of Directors. Mr. Svennilson will replace David Goeddel, Ph.D., who did not stand for reelection to RAPTs Board of Directors due to other responsibilities, but will remain a member of RAPTs Scientific Advisory Board (SAB).

Peter has been integrally involved with RAPT over the course of the last several years, helping to steer our strategic direction and expanding our network within the industry, and we welcome his consistent counsel as an active Board member moving forward, said Brian Wong, M.D., Ph.D., President and CEO of RAPT Therapeutics. On behalf of the Board and the entire Company, Id like to thank David for his guidance and strategic direction, as well as his mentorship over the course of the last five years. We very much appreciate his contributions and are thrilled he will continue his involvement with RAPT through our SAB.

Mr. Svennilson was elected to the Board of Directors at RAPTs Annual Stockholder Meeting on Thursday, June 18, 2020. He is currently Managing Partner and Founder of The Column Group, a San Francisco-based biotechnology venture capital firm. Prior to founding The Column Group, Mr. Svennilson founded Three Crowns Capital, where he served as Managing Partner, and before that was Associate Managing Director in charge of European Investment Banking Origination at Nomura Securities in London. In addition to serving on RAPTs Board of Directors, Mr. Svennilson serves on the Boards of Directors of ORIC Pharmaceuticals, Inc., Ribon Therapeutics, Circle Pharma and Revolution Medicines, Inc. Previously, he served as Chairman of the Board of Directors of Seragon Pharmaceuticals, Inc. and Aragon Pharmaceuticals, Inc. Mr. Svennilson also served as a member of the Boards of Directors of Gritstone Oncology, Inc., Constellation Pharmaceuticals, Inc., NGM Biopharmaceuticals, Inc., PTC Therapeutics, Inc., Immune Design, Rosetta Inpharmatics LLC, ChemoCentryx, Inc. and Somalogic, Inc. and as Board Observer of Arcus Biosciences. Mr. Svennilson is currently a Trustee for The Institute for Advanced Study in Princeton, New Jersey. He received his M.B.A. from the Stockholm School of Economics and Finance.

Im delighted to join the Board of Directors at this exciting time in RAPTs history, commented Mr. Svennilson. With proof-of-concept data expected for both FLX475 and RPT193 this year and a robust early-stage portfolio of small molecules advancing through development, the Company is poised for growth. I look forward to working with the experienced management team to support the Companys evolution and advancement across a number of segments and therapeutic areas within our industry.

AboutRAPT Therapeutics, Inc.RAPT Therapeutics is a clinical stage immunology-based biopharmaceutical company focused on discovering, developing and commercializing oral small molecule therapies for patients with significant unmet needs in oncology and inflammatory diseases. Utilizing its proprietary discovery and development engine, the Company is developing highly selective small molecules designed to modulate the critical immune drivers underlying these diseases. RAPT has discovered and advanced two unique drug candidates, FLX475 and RPT193, each targeting C-C motif chemokine receptor 4 (CCR4), for the treatment of cancer and inflammation, respectively. The Company is also pursuing a range of targets, including hematopoietic progenitor kinase 1 (HPK1) and general control nonderepressible 2 (GCN2), that are in the discovery stage of development.

Forward-Looking Statements

This press release contains forward-looking statements. These statements relate to future events and involve known and unknown risks, uncertainties and other factors that may cause our actual results, performance or achievements to be materially different from any future performances or achievements expressed or implied by the forward-looking statements. Each of these statements is based only on current information, assumptions and expectations that are inherently subject to change and involve a number of risks and uncertainties. Forward-looking statements include, but are not limited to, statements about clinical development progress and the timing of results from clinical trials of FLX475 and RPT193. Detailed information regarding risk factors that may cause actual results to differ materially from the results expressed or implied by statements in this press release may be found in RAPTs Form 10-Q filed with the Securities and Exchange Commission on May 14, 2020 and subsequent filings made by RAPT with the Securities and Exchange Commission. These forward-looking statements speak only as of the date hereof. RAPT disclaims any obligation to update these forward-looking statements.

Media Contact:Angela Bittingmedia@rapt.com(925) 202-6211

Investor Contact:Sylvia Wheelerswheeler@wheelhouselsa.com

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Peter Svennilson Elected to RAPT Therapeutics Board of Directors - GlobeNewswire

Immunology

Tonix Pharmaceuticals and Southern Research Announce Expansion of COVID-19 Vaccine Collaboration – BioSpace

June 18, 2020 medical

NEW YORK, June 18, 2020 (GLOBE NEWSWIRE) -- Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a clinical-stage biopharmaceutical company, announced today an expansion of its strategic collaboration with Southern Research to include a study of T cell immune responses to SARS-CoV-2 in volunteers who have recovered or remain asymptomatic after exposure to COVID-19. The research is part of an ongoing and broader collaboration between Tonix and Southern Research to develop and conduct animal testing of Tonixs TNX-1800, which is a live replicating virus vaccine designed to protect against COVID-19. The data will support the interpretation of animal trial results with TNX-1800, which are expected in the fourth quarter of 2020 and subsequent human trials.

More than 200 years of vaccine experience, beginning with Dr. Edward Jenners landmark discoveries with horsepox and cowpox vaccines, have shown that T cell eliciting vaccines are particularly effective against viruses, said Seth Lederman, M.D., President and CEO of Tonix. We believe that protective vaccines against the SARS-CoV-2 virus will be similar in that regard. The data we plan to collect from recovered and asymptomatic COVID-19 volunteers will inform vaccine development on how to safely provide to vaccine recipients the same immune responses that others got from recovering from actual CoV-2 infection. If approved by the U.S. Food and Drug Administration (FDA) for use in healthy, non-pregnant adults without moderate or severe eczema, TNX-1800 would feature single-dose immunity without the use of adjuvants, ease of manufacturing on readily available systems, and glass-sparing distribution since we believe 100 doses of TNX-1800 could be packaged in a single vial. Our goal with TNX-1800 is to develop a vaccine that is well tolerated, produces strong, long-lasting immunity, and can be rapidly and broadly deployed.

Dr. Lederman, a former tenured professor at Columbia Medical School, who has made original contributions to immunology and virology, continued, Tonixs TNX-1800 is based on a virus that we believe is closely related to Dr. Jenners first vaccine. Vaccines that descended from Dr. Jenners vaccine were used to eradicate smallpox globally, the only virus ever successfully eradicated. Smallpox was spread through the respiratory route, but it was eradicated with a vaccine administered in the arm. Tonixs lead COVID-19 vaccine candidate, TNX-1800, is designed to elicit a predominant T cell response, with some antibody response, while three other early candidates in the Companys vaccine portfolio are designed to elicit almost pure T cell responses. Dr. Lederman added, The features of a protective immune response to SARS-CoV-2 remain unknown. But since SARS-CoV-2 is a virus, we believe that T cell responses, in particular T Helper Type 1, or TH1 responses, will play an important if not dominant role in protecting against serious illness from COVID-19. These studies will provide us with a blueprint for interpreting the results of planned animal and human studies with TNX-1800.

Raj Kalkeri, Ph.D., from Southern Research and technical lead for this study, said, This is groundbreaking research with regards to COVID-19. As scientists, we know that the most successful vaccines mimic and potentiate how the immune system responds to an invader. This additional work we are doing with Tonix will add focus to that objective. We are looking forward to a timely completion of this study, utilizing readouts from a variety of assays that can provide information about TH1 or other types of immunity.

An expert team of scientists from Southern Research, including Raj Kalkeri, Ph.D., Elizabeth Wonderlich, Ph.D., John Farmer, Ph.D. and Fusataka Koide, Director of Virology, is working on this collaboration.

About TNX-1800, TNX-1810, TNX-1820, TNX-1830 and TNX-801*

TNX-1800 is a live modified horsepox virus vaccine for percutaneous administration that is designed to express the Spike protein of the SARS-CoV-2 virus that causes COVID-19 and to elicit a predominant T cell response. TNX-1810, TNX-1820 and TNX-1830 are modified horsepox viruses that are designed to express different SARS-CoV-2 proteins than Spike and to elicit almost pure T cell responses. TNX-801 is a live horsepox virus vaccine 1. Horsepox and vaccinia are closely related orthopoxviruses that are believed to share a common ancestor. Live replicating orthopoxviruses, like vaccinia or horsepox, can be engineered to express foreign genes and have been explored as platforms for vaccine development because they possess; (1) large packaging capacity for exogenous DNA inserts, (2) precise virus-specific control of exogenous gene insert expression, (3) lack of persistence or genomic integration in the host, (4) strong immunogenicity as a vaccine, (5) ability to rapidly generate vector/insert constructs, (6) readily manufacturable at scale, and (7) ability to provide direct antigen presentation. Relative to vaccinia, horsepox has substantially decreased virulence in mice1. TNX-801 vaccinated macaques showed no overt clinical signs after monkeypox challenge2. Horsepox-based vaccines are designed to be single dose, vial-sparing vaccines, which can be manufactured on conventional cell culturing systems, with the potential for mass scale production.

1Noyce RS, et al. (2018) PLoS One. 13(1):e01884532Noyce, RS, et al. Synthetic Chimeric Horsepox Virus (scHPXV) Vaccination Protects Macaques from Monkeypox* Presented as a poster at the American Society of Microbiology BioThreats Conference - January 29, 2020, Arlington, VA. (https://content.equisolve.net/tonixpharma/media/10929ac27f4fb5f5204f5cf41d59a121.pdf )

*TNX-801 and TNX-1800 are in the pre-IND stage and have not been approved for any indication

About Southern Research

Founded in 1941, Southern Research (SR) is an independent, 501(c)(3) nonprofit, scientific research organization with more than 400 scientists and engineers working across four divisions: Drug Discovery, Drug Development, Engineering, and Energy & Environment. SR supports the pharmaceutical, biotechnology, defense, aerospace, environmental, and energy industries. SR works on behalf of the National Cancer Institute, National Institutes of Health, the U.S. Department of Defense, the U.S. Department of Energy, NASA, major aerospace firms, utility companies, and other private and government organizations. SR pursues entrepreneurial and collaborative initiatives to develop and maintain a pipeline of intellectual property and innovative technologies that positively impact real-world problems. SR is developing 18 drugs to combat various forms of cancer, ALS, Alzheimers, diabetes, kidney disease, Parkinsons and tuberculosis, among others. SR has developed 20 other drugs, including seven FDA-approved cancer drugsa number rivaling any other U.S. research institute. SR is headquartered in Birmingham, Alabama with additional laboratories and offices in Wilsonville, Alabama; Frederick, Maryland; Cartersville, Georgia; and Houston, Texas.

Further information about SR can be found at https://southernresearch.org

About Tonix Pharmaceuticals Holding Corp.

Tonix is a clinical-stage biopharmaceutical company focused on discovering, licensing, acquiring and developing small molecules and biologics to treat and prevent human disease and alleviate suffering. Tonixs portfolio is primarily composed of central nervous system (CNS) and immunology product candidates. The immunology portfolio includes vaccines to prevent infectious diseases and biologics to address immunosuppression, cancer and autoimmune diseases. The CNS portfolio includes both small molecules and biologics to treat pain, neurologic, psychiatric and addiction conditions. Tonixs lead vaccine candidate, TNX-1800*, is based on the horsepox viral vector platform to protect against COVID-19, primarily by eliciting a T cell response. Tonix expects data from animal studies of TNX-1800 in the fourth quarter of this year. TNX-801*, live horsepox virus vaccine for percutaneous administration, is in development to protect against smallpox and monkeypox and serves as the vector platform on which TNX-1800 is based. Tonixs lead CNS candidate, TNX-102 SL**, is in Phase 3 development for the management of fibromyalgia. The Company expects results from an unblinded interim analysis in September 2020 and topline data in the first quarter of 2021. TNX-102 SL is also in development for agitation in Alzheimers disease and alcohol use disorder (AUD). The agitation in Alzheimers disease program is Phase 2 ready with FDA Fast Track designation, and the development program for AUD is in the pre-Investigational New Drug (IND) application stage. Tonixs programs for treating addiction conditions also include TNX-1300* (T172R/G173Q double-mutant cocaine esterase 200 mg, i.v. solution), which is in Phase 2 development for the treatment of cocaine intoxication and has FDA Breakthrough Therapy designation. TNX-601 CR (tianeptine oxalate controlled-release tablets) is another CNS program, currently in Phase 1 development as a daytime treatment for depression while TNX-1900, intranasal oxytocin, is in development as a non-addictive treatment for migraine and cranio-facial pain. Tonixs preclinical pipeline includes TNX-1600 (triple reuptake inhibitor) , a new molecular entity being developed as a treatment for PTSD, TNX-1500 (anti-CD154), a monoclonal antibody being developed to prevent and treat organ transplant rejection and autoimmune conditions, and TNX-1700 (rTFF2), a biologic being developed to treat gastric and pancreatic cancers.

*TNX-1800, TNX-801 and TNX-1300 are investigational new biologics and have not been approved for any indication.

**TNX-102 SL (cyclobenzaprine HCl sublingual tablets) is an investigational new drug and has not been approved for any indication.

This press release and further information about Tonix can be found at http://www.tonixpharma.com.

Forward Looking Statements

Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of forward-looking words such as anticipate, believe, forecast, estimate, expect, and intend, among others. These forward-looking statements are based on Tonix's current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, risks related to failure to obtain FDA clearances or approvals and noncompliance with FDA regulations; delays and uncertainties caused by the global COVID-19 pandemic; risks related to the timing and progress of clinical development of our product candidates; our need for additional financing; uncertainties of patent protection and litigation; uncertainties of government or third party payor reimbursement; limited research and development efforts and dependence upon third parties; and substantial competition. As with any pharmaceutical under development, there are significant risks in the development, regulatory approval and commercialization of new products. Tonix does not undertake an obligation to update or revise any forward-looking statement. Investors should read the risk factors set forth in the Annual Report on Form 10-K for the year ended December 31, 2019, as filed with the Securities and Exchange Commission (the SEC) on March 24, 2020, and periodic reports filed with the SEC on or after the date thereof. All of Tonix's forward-looking statements are expressly qualified by all such risk factors and other cautionary statements. The information set forth herein speaks only as of the date thereof.

Jessica Morris (corporate)Tonix Pharmaceuticalsinvestor.relations@tonixpharma.com(212) 688-9421

Travis Kruse (media)Russo Partnerstravis.kruse@russopartnersllc.com(212) 845-4272

Peter Vozzo (investors)Westwickepeter.vozzo@westwicke.com(443) 213-0505

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Tonix Pharmaceuticals and Southern Research Announce Expansion of COVID-19 Vaccine Collaboration - BioSpace

Immunology

Biomarker combo forecasts improved survival with antiPD-1/L1 agents in bladder cancer – Urology Times

June 18, 2020 medical

The dual biomarker of ARID1A mutations and CXCL13 expression at baseline predicted improved overall survival (OS) in patients with advanced bladder cancer, according to a retrospective analysis published in Science Translational Medicine.1,2

Researchers have struggled to develop predictive biomarkers for outcomes with immune checkpoint agents in patients with metastatic urothelial carcinoma. Single-biomarker research with PD-L1 level and tumor mutation burden (TMB) status have shown potential, but each has its pitfalls.

Most biomarker studies have been limited to a single biomarker, such as tumor mutational burden or PD-L1 expression, leadstudy author Sangeeta Goswami, MD, PhD, assistant professor ofGenitourinary Medical Oncology at The University of Texas MD Anderson Cancer Center, stated in a press release. Our study indicates that combinatorial biomarkers that reflect both the tumor mutational status and immune response will improve predictive capability of the biomarker and may enable better patient selection for treatment with immune checkpoint therapy.

For the discovery component of their research, the investigators used tumor samples from 2 clinical trials (NCT02387996 and NCT01928394) obtained at MD Anderson Cancer Center. Using these samples in multiplatform analyses with mouse models, the researchers found strong clinical activity with checkpoint inhibitors in patients whose tumors cells had ARID1Amutations and enriched expression of CXCL13 in surrounding immune cells

The researchers followed this discovery by retrospectively assessing data from the IMvigor210 and CheckMate-275 trials to independently confirm the predictive value of the biomarkers. The single-arm phase 2 IMvigor210 study (NCT02108652) examined atezolizumab (Tecentriq) in patients with locally advanced or metastatic urothelial cancer. The IMvigor210 study supported the FDA accelerated approval of atezolizumab for the treatment of patients with locally advanced or metastatic urothelial carcinoma who are cisplatin ineligible.

The phase 2 single-arm CheckMate-275 trial (NCT02387996) explored nivolumab (Opdivo) in patients with metastatic or unresectable bladder cancer who progressed or recurred after treatment with a platinum agent. The CheckMate-275 trial supported the FDA accelerated approval of nivolumab for use in this setting.

Analysis of the IMvigor210 data showed that the median OS was 7.2 months higher in patients with ARID1A mutations versus those without, at 15.4 versus 8.2 months, respectively. The median OS in patients with high versus low CXCL13 expression was 17.1 versus 8 months, respectively. The median OS was 17.8 months in patients who had both biomarkers. Among those without either ARID1A mutations or CXCL13 expression, the median OS was only 7.1 months.

Similar outcomes were observed in the CheckMate-275 trial data. The median OS was 11.4 versus 6 months in patients with and without ARID1A mutations, respectively. The median OS was improved by 7.8 months in patients with high versus low CXCL13 expression, at 13.5 versus 5.7 months, respectively. The median OS increased to 19.1 months in patients with both biomarkers. Patients without either biomarker had a median OS of just 5.3 months.

We hope that our study will highlight the importance of developing combinatorial biomarkers that consider both tumor cells and immune cells, corresponding author Padmanee Sharma, MD, PhD, professor of Genitourinary Medical Oncology and Immunology at MD Anderson, stated in the press release. This approach may identify better biomarkers that can reliably predict response to immune checkpoint therapy across various tumor types.

Regarding next steps the investigators plan to launch a prospective study to assess the dual biomarker in patients receiving immune checkpoint therapy.

References

1. Combination biomarker predicts response to immune checkpoint therapy in patients with advanced bladder cancer. Published June 18, 2020. https://bit.ly/2AGKzt8. Accessed June 18, 2020.

2. Goswami S, Chen Y, Anandhan S, et al. ARID1Amutation plus CXCL13 expression act as combinatorial biomarkers to predict responses to immune checkpoint therapy in mUCC. Sci Transl Med. 2020;12(548):eabc4220. doi: 10.1126/scitranslmed.abc4220

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Biomarker combo forecasts improved survival with antiPD-1/L1 agents in bladder cancer - Urology Times

Physiology

Navy Clear on Causes of Physiological Events in Pilots; Final Recommendations Released for PE Mitigation – USNI News

June 18, 2020 medical

Lt. Joshua Chester, a Navy pilot from Corton, West Virginia, poses in front of an F/A-18E Super Hornet, assigned to the Sunliners of Strike Fighter Squadron (VFA) 81 on the flight deck of the Nimitz-class aircraft carrier USS Harry S. Truman (CVN-75) in the Atlantic Ocean. US Navy Photo

The Navy now understands what has been causing physiological events in aviators which spiked so sharply in 2017 that flight instructors refused to get into their jets to train new student pilots with a recently completed root cause analysis pointing to a complex relationship between aircrew, their flight gear and their aircraft.

Rear Adm. Fredrick Luchtman, the commander of the Naval Safety Center and the lead of the Physiological Episodes Action Team (PEAT), told reporters today that two root cause corrective action (RCCA) teams one looking at the T-45 Goshawk trainer jet and one looking at the F-18 family of fighters had completed their work in December and briefed naval aviation leaders in February on their findings. The teams spent three years and $50 million on this work, drafting more than 8,000 pages of technical documentation and proposing combined 567 recommendations for how to keep pilots and weapons officers safer in the cockpit in the future.

Ultimately, the teams found that there was no simple fix. Despite early theories, the PEs werent caused by contaminated air, a lack of oxygen or systems not designed well enough to keep humans safe in harsh environments.

The bad news is that theres no single causal factor that leads to physiological events, Luchtman told reporters today, though he noted that a string of pilot programs and early mitigation efforts to tackle contributing factors have already resulted in a 96-percent decrease in the PE rate in the T-45 fleet, and a 74-percent reduction in the PE rate in the F-18 fleet since 2017.

Physiological events fall in two main categories: those related to oxygen in the air, and those related to air pressure. Luchtman said its not as simple as the systems that control these two factors not working; rather, breathing concentrated oxygen in a small cockpit with restrictive flight gear is hard on the body, and something as simple as a mask not fitting quite right could lead to PE symptoms.

Though physiological episodes have long existed, Luchtman said with symptoms ranging from headaches to tingly fingers to dizziness to loss of consciousness around 2010 the naval aviation community started to see a rise in PEs believed to be related to aircraft malfunctions. That combination of a physiological episode related to an aircraft malfunction was dubbed a physiological event Luchtman noted and apologized for the confusion between the names of physiological episodes and the subcategory of physiological events. In 2017, physiological events skyrocketed with T-45s reaching their highest PE rates in March and F-18s in November.

After a comprehensive review was released in June 2017 and the RCCA teams were created shortly after, early theories emerged. One was that pilots were breathing in contaminated air from the Onboard Oxygen Generating System (OBOGS).

It was an early theory, its a valid theory and we needed to address it. And contamination could be a logical theory in both those aircraft, so we addressed it with both root cause corrective action teams. The bottom line is that the teams took over 21,000 samples of air from naval aircraft over the course of 20 months, and there were compounds identified, as you can imagine, but they were in such small amounts that a team of medical doctors and toxicologists concluded that the presence of those compounds in those amounts would not result in physiological symptoms, Luchtman said.

Sailors assigned to Aviation Survival Training Command, Norfolk operate a normobaric hypoxia trainer (NHT). An NHT allows for safer hypoxia training for pilots and aircrewman while providing a more realistic experience on Jan. 27, 2020. US Navy Photo

To be sure, the Navy asked a team from Johns Hopkins University to review the data, and they agreed: the air provided by Navy onboard oxygen generating systems, which we abbreviate OBOGS, is and was extremely clean, Luchtman said.

Another early theory was that aircrews werent getting enough oxygen, leading to hypoxia.

We took a hard, hard look at that, and after extensive testing this theory has been disproven, the rear admiral said.

A final theory questioned the basic design of OBOGS and the Environmental Control System (ECS) that controls air pressure in the F-18 cabin, suggesting that the systems were not suitable to protect human health while the jets flew challenging flight profiles. Luchtman said the testing proved the two systems were robust.

So what was causing the hundreds of PEs naval aviators reported?

On the F-18s the legacy F/A-18A-D Hornets, the newer F/A-18E/F Super Hornets and the electronic warfare EA-18G Growlers Luchtman said both oxygen- and pressure-related PEs had been occurring.

On the oxygen side, the air produced by OBOGS was found to be clean, and though aviators showed symptoms of hypoxia, it turned out they didnt actually have hypoxia where the bodys tissues are deprived of sufficient oxygen.

Instead, even under benign conditions, the act of breathing highly concentrated air from a closed-loop system while encumbered by bulky flight gear in a cramped cockpit is not easy. And in the dynamic environment of a fighter cockpit, we also add to the equation temperature variance, exposure to continual changes in Gs and pressure, all while managing an overwhelming amount of sensory input. All this amounts to increased what we call work of breathing. Over time, increased levels of work of breathing can lead to fatigue and changes in breathing patterns, leading to inefficient gas exchange, and many of those symptoms look a lot like hypoxia, he said.

Aviation Structural Mechanic 3rd Class Jeffery Hendricks removes a screw from an Onboard Oxygen Generating System (OBOGS) while performing special maintenance in the airframes shop aboard the Nimitz-Class nuclear powered aircraft carrier USS Harry S. Truman (CVN 75) on Jan. 5, 2008. US Navy photo.

Further, the F-18 RCCA team found that work of breathing could also be affected by improperly fit or worn flight gear, malfunctions in the oxygen mask, and malfunctions of the OBOGS unit itself, Luchtman added. Though OBOGS has an alert system to warn pilots if it malfunctions, there is no such alert for flight gear and masks that dont fit, arent being worn properly or have experienced some kind of malfunction. Luchtman said efforts to create some kind of gear alert system are immature at this point, but that the Navy is trying to explore this avenue to protect pilots against failures in the gear meant to protect their bodies.

In the meantime, based on everything weve learned about human physiology through research and testing, many of our training syllabi are under modification to address some of those shortfalls in training related to the flight gear and masks including a course that would teach maintainers how to properly pack parachutes and other gear with PE-avoidance in mind.

On the air pressure side, which Luchtman said tends to cause more severe PEs, the OBOGS design was fine, but components of it had been failing and causing pressure anomalies that might not affect some aircrew but did cause PE symptoms in others.

On the legacy Hornets, the Navy set strict limits on how long OBOGS components can be used in an aircraft before being replaced and mandated periodic inspections. Luchtman said this was the single most important thing the Navy did for legacy Hornets, leading to an 88-percent reduction in pressure-related PEs. Similar component replacement requirements have been put in place for the Super Hornets and Growlers, and the admiral said that redesign efforts are ongoing for many of the components the two most important being the primary and secondary bleed air valves to create new parts that are more reliable and can go longer between replacement.

He praised Naval Air Systems Command for sending aircrew up with a small slam stick to record air pressure, which after flights was downloaded and paired with aircraft maintenance data. Through data analytics, he said, NAVAIR has created a Hornet Health Assessment Readiness Tool (HhART) that can now identify components that are sub-performing and flag them for replacement before a failure and possible a PE ever occur.

Think of the significance of that: that is a tremendous paradigm shift in the way we do maintenance, we can actually identify parts that are sub-performing, replace those parts and prevent the PE from ever happening, he said.

Since the HhART pilot program kicked off in January 2019, pressure-related PEs in F-18s overall are down 80 percent.

Finally, he said, the F-18 RCCA team looked at aeromedical factors such as dehydration, fatigue, diet, hypoglycemia, stress, physical conditioning and more.

A T-45C Goshawk training aircraft assigned to Training Air Wing (TW) 2 lands on the flight deck of the aircraft carrier USS John C. Stennis (CVN-74) in the Atlantic Ocean on Dec. 9, 2019. US Navy Photo

We shouldnt be surprised that if you go flying dehydrated and youre breathing dry air from our OBOGS concentrator, that youre not going to feel well after awhile, Luchtman said.

On the T-45 side, Luchtman said the RCCA team came closer to a single root cause: with the PEs primarily being oxygen-related rather than pressure-related, the team narrowed in on the airflow from the engine to the OBOGS and then into the cockpit. While the air coming out of OBOGS was clean, in some flight profiles the engine wasnt putting out much air, meaning the OBOGS wasnt taking in much air to purify, and therefore the aircrewtemporarilywerent getting as much air out of OBOGS.

In two relatively simple changes, the RCCA team recommended straightening out what had been an angled pipe to bring air from the engine to the OBOGS, increasing overall air flow, as well as altering the engine to increase the rotations per minute so it would spin faster and provide more air to OBOGS.

Those two things, along with implementation of an ECS hygiene inspection regimen, has resulted in a 96-percent reduction in the PE rate across the T-45 fleet since its peak rate in March of 2017. So I think thats actually a pretty good news story, he said.

Despite the significant decreases in PEs since 2017, they havent ceased altogether. Luchtman told USNI News that between October 2019 and the end of May the first eight months of Fiscal Year 2020 the Navy had seen 27 PEs across all Navy aircraft types. Just one of those was in the T-45, with 20 coming from F-18s and six coming from other kinds of non-fighter aircraft.

This compares to 35 PEs in T-45s in FY 2016, 31 in 2017, six in 2018 and one in the first half of 2019, USNI News previously reported. In the F-18s, there had been 87 PEs in FY 2016, 73 in 2017, 65 in 2018, and 41 in the first half of FY 2019.

To continue working to eliminate PEs, Luchtman said several initiatives are ongoing. The PE Action Team, which he led for two years previously out of Arlington, Va., was recently pulled under the Naval Safety Center in Norfolk, Va. The relocated office has continued funding for several initiatives, he said.

Cmdr. Leslie Mintz, executive officer of the Blacklions of Strike Fighter Squadron (VFA) 213, inspects an F/A-18F Super Hornet prior to her flight on board Naval Air Station Oceana, Va., on Feb 28, 2019. US Navy Photo

Soon the Navy will install a Cockpit Pressure and OBOGS Monitoring System (CPOMS) into all F-18s more than 1,000 jets, USNI News has previously reported which will record oxygen concentration levels and pressurization data from cockpit and alert air crew if either level is off.

Luchtman told USNI News in an interview last year that CPOMS involves some pretty significant engineering modification to the aircraft. That will be done by professionals from Boeing, and its going to take 10 to 14 days per aircraft, times over 1,000 aircraft. Weve never done anything of that scale before.

Additionally, a Life Support Systems Integration for the F-18s will include a new OBOGS concentrator, as well as the ability to electronically schedule oxygen delivery to the aircrew based on their altitude a capability the Navy wanted before but hadnt been able to achieve. LSSI, which will also bring additional data recording capabilities, is still several years from being operational.

On the T-45s, the OBOGS will get a new concentrator, though Luchtman said that was more of a routine modernization project rather than an attempt to address a specific PE concern. To address PEs, though, an automatic backup system will be installed where, if oxygen levels dip below a certain threshold, a liquid oxygen bottle will spray a bit of 100-percent oxygen into the cockpit for the aircrew.

Luchtman said Navy leadership has been very supportive of this effort and has fully funded all these modifications.

He added that at least 30 more studies are in the hopper for the Navy to continue to better understand aeromedical factors, and that hopefully monitoring systems could be developed to help aircrew identify when they may be on the cusp of a PE and prevent it from happening in the first place.

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Navy Clear on Causes of Physiological Events in Pilots; Final Recommendations Released for PE Mitigation - USNI News

Physiology

How to help your chickens beat the heat in summer – The Poultry Site

June 18, 2020 medical

Last year we experienced record-breaking temperatures across the UK, peaking in Faversham, Kent at 35.3oC. With the expected rise in global temperatures those sweltering summer months could be beyond our current means of coping with the heat. Every summer we experience days when just spending a few minutes in a poultry house feels unbearable, and for many broilers reaching the end of the cycle it is with mortality soaring. Thankfully the poultry industry has made a great deal of progress in the area of ventilation and cooling. As chickens are reared in hot countries such as Saudi Arabia, the technology to deal with temperatures in excess of 40oC has already been well tested.

Chickens, in general, can cope with high temperatures. The domestic fowl has a healthy body temperature of between 40C and 41.7oC, chicks under three weeks of age being at the lower end. With the birds metabolism being quite high, its ability to lose heat is imperative and it does this by radiation, conduction and the evaporation of water. Chicks, being small, have a high surface area in comparison to their body mass, which means heat is lost from the body relatively easily; as the bird increases in size this ratio changes, though, and for the hefty 3kg broiler radiation of heat via the skin is not going to be enough to keep its temperature down.

When radiation is insufficient you will see other behaviours presented: the bird will increase its surface area by lifting its wings, exposing the less feathered parts of its body; the flock will also try to move to a cooler area, away from the heat source, perhaps into the shade; or the birds will clear soil and litter away to make a cool depression.

Heat loss via conduction can only occur if the chicken is in direct contact with a substance that is cooler than itself. This could be the ground, as seen in the hollow-digging behaviour. In the main, though, conduction will occur in a well-ventilated area where the skin can contact cooler air.

Evaporation is the final key to cooling off. Like other animals that lack sweat glands, chickens main evaporative apparatus is the respiratory system and they will typically pant once temperatures become uncomfortable. Panting uses a lot of energy; this will be reflected in an increase in food consumption once the temperature starts moving toward 30oC.

Knowing how the physiology of the bird handles excess heat enables us to design environments and conditions that will support chickens in keeping cool. Space is an essential element when birds need to radiate heat, and therefore stocking densities should be reduced in the summer months. On a still day in naturally ventilated housing, you only have convection to pull the air across your birds and that is a fine balance steep roofs and tall chimneys will help increase air speed and throughput. You must maintain a minimum of ventilation rate at all times, and this can be calculated using feed consumption as a baseline, plus other factors including physiology of the birds and humidity.

Heat management in extensive systems is less of an issue, but a simple provision of shade and access to water will help tremendously. If local planning will allow, use light-coloured roofing materials. Its tricky but if you can check air speed in the house you will find that there is an optimum amount of inlet area to outlet. Too much inlet area can slow air movement in the house, so aim for a 1:1 ratio for inlet to outlet area as a guide. In a naturally ventilated building, consider placing the whole building in the shade of trees or orienting it so the sun is not blazing down on the broadside at noon. Where a source of power is available, place circulating fans around the house to get the air moving. Its important to stress that still air is a killer even in slightly elevated temperatures.

Another key element of hot-weather management is keeping the birds calm, so stick to your normal routine and avoid entering the house at the hottest part of the day. Activities such as weighing birds, routine maintenance and depletion should be postponed or relegated to early mornings.

Once you move into the realm of intensive production and complete environmental control, get it right and its plain sailing. Tweak a few buttons and gauges and the environment within the building can be optimised regardless of conditions outside. Get it wrong, though, and you could literally lose your entire flock through heat exhaustion and suffocation.

Modern intensive poultry farmers have a whole range of technologies and management tools they can use to mitigate the harshest of climatic conditions. Its important to start with the physiology and behaviour of the chicken. We can assist the chicken in optimising its body temperature by either supplying air at the right temperature or by enabling the chicken to effectively control its body temperature a combination of both will move us toward the most efficient system.

Air cooling is not widely used in the UK as it is very expensive. Air can be cooled by introducing cold water via a fine spray into the air inlet. This in principle sounds ideal; in reality there is a very fine balance between cooling the air sufficiently and not increasing the humidity to a point whereby the chickens are unable to effectively respire water away from themselves and consequently are unable to cool down. Increased humidity can also lead to an increase in moulds throughout the housing and a deterioration in the fabric of the building. Increasing the airs humidity also increases its mass, meaning that it will tend to hang around the birds rather than being lifted away from them. A better system is one in which air passes through a cooler, which is the same as a radiator only cold water is passed through the vanes cooling the air as it passes through.

Increasing air throughput to the house is the preferred method in our climate. This has been used to great effect in housing with tunnel ventilation, whereby the long broiler house becomes a tunnel with huge fans at one end and inlets covering the wall of the other end. There is, however, a limit to this system: if air speed through the flock exceeds 1.5m per second, it will create a significant wind chill, having a detrimental effect on the birds.

As summer temperatures rise and production is further challenged, other methods of keeping birds cool will no doubt come to the fore but ultimately it is the chickens physiology that will set the limits.

Physiology

Nanotoxicology of Dendrimers in the Mammalian Heart: ex vivo and in vi | IJN – Dove Medical Press

June 18, 2020 medical

Fawzi Babiker,1 Ibrahim F Benter,2 Saghir Akhtar3

1Department of Physiology, Faculty of Medicine, Health Science Center, Kuwait University, Kuwait City, Kuwait; 2Faculty of Medicine, Eastern Mediterranean University, Famagusta, North Cyprus, Republic of Cyprus; 3College of Medicine, QU Health, Qatar University, Doha, Qatar

Correspondence: Fawzi BabikerDepartment of Physiology, Faculty of Medicine, Health Science Center, Kuwait University, PO Box 24923, Safat 13110, Kuwait, Tel +965 24636360Fax +965 25338937Email Fawzi.b@hsc.edu.kwSaghir AkhtarCollege of Medicine, QU Health, Qatar University, PO Box 2713, Doha, QatarTel +974-4403 7865Email s.akhtar@qu.edu.qa

Aim: The effects of polyamidoamine (PAMAM) dendrimers on the mammalian heart are not completely understood. In this study, we have investigated the effects of a sixth-generation cationic dendrimer (G6 PAMAM) on cardiac function in control and diabetic rat hearts following ischemia-reperfusion (I/R) injury.Methods: Isolated hearts from healthy non-diabetic (Ctr) male Wistar rats were subjected to ischemia and reperfusion (I/R). LV contractility and hemodynamics data were computed digitally whereas cardiac damage following I/R injury was assessed by measuring cardiac enzymes. For ex vivo acute exposure experiments, G6 PAMAM was administered during the first 10 mins of reperfusion in Ctr animals. In chronic in vivo studies, nondiabetic rats (Ctr) received either vehicle or daily i.p. injections of G6 PAMAM (40 mg/kg) for 4 weeks. Diabetic (D) animals received either vehicle or daily i.p. injections of G6 PAMAM (10, 20 or 40 mg/kg) for 4 weeks. The impact of G6 PAMAM on pacing-postconditioning (PPC) was also studied in Ctr and D rats.Results: In ex vivo studies, acute administration of G6 PAMAM to isolated Ctr hearts during reperfusion dose-dependently impaired recovery of cardiac hemodynamics and vascular dynamics parameters following I/R injury. Chronic daily i.p. injections of G6 PAMAM significantly (P< 0.01) impaired recovery of cardiac function following I/R injury in nondiabetic animals but this was not generally observed in diabetic animals except for CF which was impaired by about 50%. G6 PAMAM treatment completely blocked the protective effects of PPC in the Ctr animals.Conclusion: Acute ex vivo or chronic in vivo treatment with naked G6 PAMAM dendrimer can significantly compromise recovery of non-diabetic hearts from I/R injury and can further negate the beneficial effects of PPC. Our findings are therefore extremely important in the nanotoxicological evaluation of G6 PAMAM dendrimers for potential clinical applications in physiological and pathological settings.

Keywords: PAMAM, postconditioning, diabetes, ischemia, reperfusion

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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Nanotoxicology of Dendrimers in the Mammalian Heart: ex vivo and in vi | IJN - Dove Medical Press