Culture

Pregnant mice fed a diet high in omega-6 fats and low in omega-3 fats produce offspring that go on to exhibit "hedonic"--pleasurable but excessive--levels of consumption of hyper-caloric diets, according to researchers at Hiroshima University.

Omega-6 fats are found in grapeseed oil, corn oil and sesame oil, and are a staple of several salad dressings in world cuisine. Omega-3 fats are found in fish, perilla oil, and linseed oil. A diet balanced with these fats is considered essential for healthy brain growth.

The researchers also found that the offspring exhibit increased in utero growth of dopamine-producing neurons in the midbrain--the neurological reward system. They believe that exposure to this high omega-6/low omega-3 diet increases growth in these neurons in the fetus's brain during a specific period during pregnancy, driving dopamine release in the offspring's brain, and thus primes the offspring for hedonic consumption of sugar- or fat-rich diets over the course of their life.

The findings were published in the peer-reviewed journal Communications Biology, on August 28.

Meanwhile, mice whose mothers had not consumed the imbalanced omega-6/omega-3 diet did not exhibit as much overeating behavior, even when tempted by the presence of such food.

Since the 1960s, the Western diet has experienced a significant uptick in the presence of polyunsaturated omega-6 fats, and in ratios to polyunsaturated omega-3 fats that historically humans had never experienced before.

The ratio between these two types of fats is important because biochemically they compete with each other for incorporation into cell membranes, and an omega-6/omega-3 imbalance in the membranes of red blood cells is correlated with weight gain. An earlier study on mice had found that consumption of an imbalanced omega-6/omega-3 diet by the pregnant mother replicates this imbalance in the offspring's brain and even impairs brain development.

The Hiroshima researchers also found that a dopamine-inhibiting drug eliminates the hedonic consumption of the offspring, further supporting the notion that the dopamine signaling plays a critical role in driving this behavior.

"This suggests that adult mice gorging themselves on hyper-caloric diets were in effect neurologically programmed to do so by their mother's own consumption patterns," said Nobuyuki Sakayori, paper author and assistant professor from the Graduate School of Biomedical and Health Sciences at Hiroshima University.

The scientists were keen to stress that the ratio of omega-6 to omega-3 fat in the mouse diet is much higher than that experienced by most humans, and that their work lays the foundation for further, epidemiological studies on humans to see if the pattern holds for us.

But if it does, this could provide a new strategy for preventing obesity in children by managing the type of fats that pregnant mothers consume, akin to how mothers today generally avoid consumption of alcohol.

"This could work much better than existing anti-obesity campaigns or food taxes," Sakayori continued, "because instead of fighting against the brain's reward system, such a strategy focuses right from the start on the development of that system."

(LOS ANGELES) - In a newly published paper, the authors first paint the vision of what optimal patient advocacy can do to overcome the challenges described by kidney transplant patients and donors, and then describe how to make that vision a reality, especially during the COVID-19 pandemic. Dr. Amy Waterman, Deputy Director at the Terasaki Institute for Biomedical Innovation and leader of the Transplant Research and Education Center (TREC), assembled a panel of patients to learn their priorities for their care during this unprecedented time.

The authors describe the vision of optimal patient advocacy as patients feeling informed and empowered to make appropriate decisions about their care. The three key areas the patient panel identified for making that vision a reality are: "including the patient voice in all healthcare decisions and drug development, ensuring equitable access to the best evidence-based treatments and educate patients fully in their care decision process, and honoring patient priorities in all care innovations and policies." The way those key areas look in practice are described throughout the paper.

The authors explain that diverse patient voices should be included, especially those from populations at higher risk of contracting and dying from COVID-19. These patient voices should drive outcomes of interest for transplant centers and educators. Patients were once encouraged to bring family members along with them to care, but due to the COVID-19 pandemic they are no longer able to do so. Patients and their families should strive to find new ways to engage in care and provide support, while also recognizing there may be increased burden on caregivers for immunocompromised kidney recipients.

Centers should be providing equitable access to up-to-date information for their patients about how their care is impacted by answering questions like, what precautions is the center taking to prevent the spread of COVID-19? It is vital that this information be health literate, written at a 6th grade reading level, and in multiple languages, so that all patients can be informed and make empowered choices about their care. It also means that educational information should be disseminated through multiple channels like text messages, social media, and emails so that patients have easy access to the information they need to make empowered decisions.

Lastly, optimal patient advocacy at the policy level includes changes like the Comprehensive Immunosuppressive Drug Coverage for Kidney Transplant Patients Act which makes life-sustaining immunosuppressive drugs covered by Medicare beyond the former 36-month post-transplant coverage period.

Dr. Waterman concludes the paper by writing "Patient empowerment is essential through the COVID-19 pandemic given changes in the healthcare system, and transplant recipients' increased risk of contracting COVID-19 and suffering negative outcomes. Patient advocacy is not simply a moral imperative. If we are acting as true patient advocates and empowering patients in their own healthcare, this commitment will result in more patients being alive and thriving--the entire purpose of healthcare itself."

In addition to the information provided in the body of the article, the authors include a table in the publication with specific action steps to overcome barriers to optimal transplant patient advocacy.

Co-author, Senior Research Associate of the KFU Quantum Informatics Lab Kamil Khadiev, explains, "The Dyck problem is designed to check the program code and allows you to find out whether it satisfies the rules or not. The problem, on the one hand, is an important subtask of parsers and compilers, and on the other hand, it is interesting from a theoretical point of view. The classical solution to the problem has been known for a long time, but no one thought about a quantum algorithm for the problem until 2018. Particular attention to the construction of a quantum algorithm for the Dyck problem appeared after a publication by Scott Aaronson and his co-authors two years ago. Aaronson showed, in particular, that a program for an ordinary computer would solve the problem for a year, but on a quantum computer it can be solved in a few seconds."

In the paper, Khadiev and his colleagues demonstrated an algorithm that can solve the problem in 40 seconds and also proved that it cannot be solved in less than 10 second on a quantum computer.

"Scientists are developing quantum algorithms in parallel with the creation of the quantum computer itself. The emergence of another effective algorithm spurs physicists to create quantum computers as soon as possible and makes the prospect of a quantum computer more and more enticing," adds Khadiev.

Does the COVID-19 cytokine storm exist?

Inflammatory proteins, also known as cytokines, play a crucial role in the immune response. If this immune response is too strong, a phenomenon known as "cytokine storm", it can cause harm to the patient. It has been thought that a cytokine storm contributes to disease severity in patients with COVID-19. Following the measurement of several important cytokines in patients with COVID-19 and various other severe diseases, researchers at Radboud university medical center now show that COVID-19 is not characterized by a cytokine storm. This may have consequences for the treatment of these patients, the researchers write in JAMA.

The cytokine storm in COVID-19 patients is not clearly defined. In many cases, different cytokines are evaluated and no comparison has been made with other diseases. Therefore, uncertainty and doubt exists concerning the cytokine storm in these patients.

Various patient groups

Researchers from the Intensive Care (IC) department at Radboud university medical center have now measured the concentration of three essential cytokines in the blood of patients admitted to the IC with several distinct conditions. They performed these measurements in patients with COVID-19 who met the criteria for a severe acute respiratory infection (ARDS), patients with bacterial septic shock (with and without ARDS), and patients who had been admitted to the IC after a cardiac arrest or severe trauma. The cytokines were measured using the same methods for each of the groups of patients.

Cytokine storm?

In the abovedescribed five patient groups, the concentration of tumor necrosis factor alpha (TNF-?) and interleukins 6 and 8 (IL-6, IL-8) was measured. The results were remarkable. Researcher Matthijs Kox: "The level of cytokines was significantly less elevated in COVID-19 patients than in patients with septic shock and ARDS. Compared to patients with septic shock without ARDS, so without severe pulmonary disease, patients with COVID-19 also displayed markedly lower levels of IL-6 and IL-8. The cytokine concentrations in COVID-19 patients were similar to those in IC patients with trauma or cardiac arrest, conditions that are not noted for a cytokine storm."

Possible consequences

The results from this study show that COVID-19 is not characterized by a cytokine storm. Professor of Intensive Care Medicine Peter Pickkers: "The severe disease observed in critically ill COVID-19 patients is therefore not explained by strongly elevated levels of inflammatory proteins in the blood. This means that critically ill COVID-19 patients likely will not benefit from specific anti-cytokine therapies."

AURORA, Colo. (Sept. 3, 2020) - A new study led by researchers from the University of Colorado School of Medicine compares adolescent siblings to determine the impact of early and frequent use of marijuana on cognitive function.

This study, published in the journal Addiction, contrasts with previous studies by finding that moderate adolescent cannabis use may have adverse effects that cannot be explained by the genetic or environmental factors that siblings may have in common.

"We wanted to expand our understanding of whether cannabis use is related to lower cognitive functioning," said lead author Jarrod M. Ellingson, PhD, assistant professor of psychiatry at the CU School of Medicine. "There's a large body of evidence that cannabis use is linked to cognitive functioning, but we know that cannabis use is not isolated from other important risk factors. That was the primary motivation behind this study, in which we compared siblings to account for many of these risk factors."

Such possibilities include environmental risk factors, such as peer group influence, parental behavior, and socioeconomic status. In addition, by designing the study to look at siblings, researchers could consider whether genetic factors explain a shared risk for worse cognitive functioning and earlier or heavier cannabis use.

With this study, Ellingson and his colleagues were able to establish comparisons between siblings and then determine that differential levels of cannabis use were related to poorer cognitive functioning, particularly verbal memory.

The study participants were 1,192 adolescents from 596 families. They were primarily male - 64 percent - and racially and ethnically diverse, with non-Hispanic whites accounting for 45 percent. The families were from metro Denver and San Diego. Drug use was assessed through clinical interviews and cognitive abilities were analyzed through a battery of neuropsychological tests. Two waves of data were collected. The first wave was from participants with an average age of 17 from 2001-2006; the second wave was collected from 2008-2013, with an average participant age of 24.

"More work needs to be done to determine how cannabis use is related to cognitive functioning and we hope that our study can help inform future study designs," Ellingson said. "These studies are particularly important because cannabis is becoming more potent and more accessible as states legalize its recreational use."

In the article, Ellingson and his co-authors: "Due to changes in the legality of recreational and medical cannabis and widespread access in many states, valid empirical data must be available to inform policy and public health decisions, including how cannabis use may affect the developing brain."

In a retrospective study of patients tested for COVID-19, researchers at the University of Chicago Medicine found an association between vitamin D deficiency and the likelihood of becoming infected with the coronavirus.

"Vitamin D is important to the function of the immune system and vitamin D supplements have previously been shown to lower the risk of viral respiratory tract infections," said David Meltzer, MD, PhD, Chief of Hospital Medicine at UChicago Medicine and lead author of the study. "Our statistical analysis suggests this may be true for the COVID-19 infection."

The research team looked at 489 UChicago Medicine patients whose vitamin D level was measured within a year before being tested for COVID-19. Patients who had vitamin D deficiency (

The study, Association of Vitamin D Status and Other Clinical Characteristics With COVID-19 Test Results, was published Sept. 3 in JAMA Network Open. Findings were previously reported on medRxiv, a preprint server for the health sciences.

Half of Americans are deficient in Vitamin D, with much higher rates seen in African Americans, Hispanics and individuals living in areas like Chicago where it is difficult to get enough sun exposure in winter.

"Understanding whether treating Vitamin D deficiency changes COVID-19 risk could be of great importance locally, nationally and globally," Meltzer said. "Vitamin D is inexpensive, generally very safe to take, and can be widely scaled."

Meltzer and his team emphasize the importance of experimental studies to determine whether vitamin D supplementation can reduce the risk, and potentially severity, of COVID-19. They also highlight the need for studies of what strategies for vitamin D supplementation may be most appropriate in specific populations. They have initiated several clinical trials at UChicago Medicine and with partners locally.

Over the next two weeks, The Lancet will be publishing two reports calling for urgent global action on non-communicable diseases (NCDs).

The NCD Countdown to 2030 tracks global progress on non-communicable diseases against commitments to reduce deaths from NCDs by a third by 2030. The report will publish 6.30pm [New York time] Thursday 3rd September (details below).

On Tuesday 14th September 6.30pm [New York time], The Lancet will publish a new Commission urging greater action to combat one of the world's biggest and most neglected health disparities: non-communicable diseases and injuries (NCDI) that kill and disable the poorest billion people, many of them children and young adults - and many of them at dire risk amid the COVID-19 pandemic. The report will be launched at a virtual event on 15th September https://zoom.us/webinar/register/WN_N1ES-NafRQilBe8IEuo5HA

For further information, or for an advance copy of the report, please contact The Lancet press office pressoffice@lancet.com

Peer reviewed / Review and modelling

Among high-income countries, only Denmark, Luxembourg, New Zealand, Norway, Singapore, and South Korea are on track to meet the SDG target of a third reduction in non-communicable disease (NCD) mortality by 2030 for both men and women at current rates of decline.

Relationship between COVID-19 and non-communicable diseases highlights urgent need for governments to implement policies to prevent avoidable deaths from chronic diseases.

Around the world, the risk of dying prematurely from preventable and largely treatable chronic diseases such as stroke, heart disease, and stomach cancer has declined steadily over the past decade, but death rates from other chronic diseases such as diabetes, lung cancer, colon cancer, and liver cancer are declining too slowly or worsening in many countries.

Many countries are falling short or behind on their commitments to reducing premature mortality from chronic diseases, or non-communicable diseases (NCDs). Among high-income countries, only Denmark, Luxembourg, New Zealand, Norway, Singapore, and South Korea are on track to meet the SDG target for both men and women if they maintain or surpass their recent rates of progress.

These are the findings of the 2nd edition of the NCD Countdown 2030 report, published today in The Lancet, ahead of the Global Week of Action on NCDs next week. The 1st NCD Countdown Report was released in 2018 [1].

NCDs currently kill over 40 million people a year worldwide, making up seven out of ten deaths globally. 17 million of these deaths are of people younger than 70 years old and classed as premature; the great majority (15 million) of these deaths are between 30 and 70 years.

In 2015, world leaders signed up to achieve the United Nations' Sustainable Development Goal 3.4 of a one-third reduction in deaths between 30 and 70 years of age from four key NCDs - cancer, cardiovascular disease, chronic respiratory disease, and diabetes - by the year 2030. The NCD Countdown 2030 report, led by Imperial College London, World Health Organization, and the NCD Alliance, reveals that the global goal to reduce premature mortality from NCDs by one third by 2030 is still achievable but many countries are falling short.

"No country can reach that target by simply addressing a single disease - what is needed is a package of measures, a strong health system, which addresses prevention, early detection and treatment, tailored to the national situation," said Majid Ezzati, Professor of Global Environmental Health at Imperial College London, who led the study. [2]

"Young people must lead the fight against NCDs. An estimated 150 million people will lose their lives too early from a noncommunicable disease over the next decade and right now NCDs are intensifying the impact of COVID-19," said Dr Bente Mikkelsen, Director of Noncommunicable Diseases, World Health Organization. "We must ensure that all NCDs are addressed in COVID-19 recovery plans so that we can turn this deadly tide. We cannot allow NCDs to become a generational catastrophe, where human potential is wasted, and inequality is exacerbated." [2]

NCDs in the context of the COVID-19 pandemic

People living with many NCDs are being disproportionately affected by COVID-19 - they are at a considerably higher risk of suffering severe illness and dying from the disease. At the same time, the ability to reach the UN targets is being challenged by the added impact of the COVID-19 pandemic which is severely disrupting the capacity of national health services to deliver regular screening, diagnosis, treatment and prevention of NCDs.

"COVID-19 has exposed how a failure to invest in effective public health to prevent NCDs and provide health care for people living with NCDs can come back to bite us," said Katie Dain, CEO of the NCD Alliance. "The good news is that all countries can still meet the 2030 targets, with sound policies and smart investments. NCD prevention and treatment can no longer be seen a 'nice to have', it must be considered as part of pandemic preparedness." [2]

In an editorial, The Lancet highlights that: "COVID-19 and NCDs form a dangerous relationship, experienced as a syndemic that is exacerbating social and economic inequalities... COVID-19 is a pandemic that must highlight the high burden that NCDs place on health resources. It should act as a catalyst for governments to implement stricter tobacco, alcohol, and sugar controls, as well as focused investment in improving physical activity and healthy diets. COVID-19 has shown that many of the tools required for fighting a pandemic are also those required to fight NCDs: disease surveillance, a strong civil society, robust public health, clear communication, and equitable access to resilient universal health-care systems... COVID-19 must stimulate far greater political action to overcome inertia around NCDs."

Tracking country progress on SDG 3.4

The UN measure of progress towards the SDG target 3.4 is reducing by one-third the risk of death between 30 and 70 years of age from four major groups of NCDs (cancers, cardiovascular diseases (CVDs), chronic respiratory diseases, and diabetes), termed NCD4. Based on recent (2010-2016) trends, the NCD Countdown 2030 report finds that:

Among high-income countries, only Denmark, Luxembourg, New Zealand, Norway, Singapore, and South Korea are on track to meet this target for both men and women if they maintain or surpass their 2010-16 average rates of decline.

17 countries are already on track to reach the SDG target 3.4 for women: Belarus, Denmark, Iran, Kazakhstan, South Korea, Kuwait, Luxembourg, Latvia, Maldives, Norway, New Zealand, Russian Federation, Singapore, Serbia, Timor-Leste, Ukraine.

And 15 countries are on track for men: Bahrain, Belarus, Czech Republic, Denmark, Finland, Iran, Iceland, Kazakhstan, South Korea, Luxembourg, Maldives, Norway, New Zealand, Singapore, Slovakia.

The risk of dying prematurely from NCD4 is declining rapidly in central and eastern Europe.

However, large countries that showed stagnation or small increases in risk of premature death from these NCDs are Bangladesh (men), Egypt (women), Ghana (men and women), Cote d'Ivoire (men and women), Kenya (men and women), Mexico (men), Sri Lanka (women), Tanzania (men) and the USA (women).

Tracking progress on four major groups of NCDs

Worldwide, deaths from stroke, heart disease and stomach cancer are falling, although overall progress has slowed compared to the previous decade, according to WHO [3]. Deaths from diabetes, lung cancer, colon cancer and liver cancer are stagnating or rising in many countries. The NCD Countdown 2030 report shows that (see figure 2):

The risk of premature death from ischaemic and haemorrhagic stroke, heart disease, chronic lung diseases and stomach cancer declined faster than that of other causes. However, heart disease remains the leading cause of premature death in most countries for men and in about half the countries for women.

In contrast, the risk of premature death from diabetes, colorectal cancer, liver cancer, breast cancer and prostate cancer declined more slowly than other causes, as did lung cancer among women.

For lung cancer in women and colorectal, liver and prostate cancers in men, the risk of premature death increased in more than half of countries.

Policies to accelerate decline in premature mortality

The report notes that although premature death from NCDs is declining in the majority of countries, the pace of change is too slow to achieve SDG target 3.4 in most. The authors used mathematical modelling to assess how many options countries have for accelerating mortality decline.

"To move forward we must learn from those countries that are doing well and replicate their strategies to NCD prevention and healthcare," said Professor Ezzati. "Our analysis shows that every country still has options to achieve SDG target 3.4 but they need to address multiple diseases and have strong health systems." [2]

To that end the report highlights the set of interventions needed to move countries forward:

Tobacco and alcohol control and effective health system interventions, such as a ban on advertising, increasing taxes, plain packaging, public smoking/drinking bans.

Quality primary care - including equitable access to doctors' surgeries and community-based clinics.

Quality referral systems and consistent maintenance of people in care to help patients get the right treatment at the right time.

A range of medicines and techniques available for early diagnosis and treatment - such as increased equitable access to preventative cholesterol-lowering, hypertension and diabetes medicines.

Effective cancer screening and treatment - to diagnose and treat cancers earlier, reducing long-term health impacts and premature deaths.

International team of scientists discover link between genes and penicillin allergy using biobanks from Estonia, UK and USA

Penicillin, a life-saving medicine, is the most common cause of drug allergy, with clinical manifestations ranging from temporary skin reactions to life-threatening systemic syndromes. Thus far, genetic factors have only been found for rare severe allergic reactions to penicillin. However, less is known about the genetics behind milder forms of penicillin hypersensitivity reactions that occur in a larger proportion of the population.

A collaborative effort by scientists from the Estonian Genome Center, University of Tartu, Statens Serum Institut, University of Oxford, Vanderbilt University Medical Center, Harvard Medical School, Broad Institute of MIT and Harvard, and 23andMe sought to identify genetic risk factors underlying penicillin-induced hypersensitivity reactions by harnessing self-reported data and the electronic health records of more than 600,000 participants of European ancestry from the UK Biobank, Estonian Biobank and Vanderbilt University Medical Center's biobank (BioVU).

The genome-wide association study (GWAS) of self-reported penicillin allergy in the different biobanks revealed a locus located in the major histocompatibility complex (MHC) I gene HLA-B. Fine-mapping of the association narrowed the signal down to the HLA-B*55:01 allele, which was further confirmed by independent replication in 23andMe's research cohort. Overall, carriers of the allele were found to have a 33% higher relative odds of penicillin allergy. The study also detected a genome-wide significant missense variant in the PTPN22 gene. This variant has been associated with several autoimmune diseases and more recently with drug-induced liver injury.

Dr Kristi Krebs, first author of the study, said: "When examining other conditions associated with the HLA-B*55:01 allele, we found a significant association with lower white blood cell counts. Further, the top hit overlapped with regions found to have regulatory function in T-cells and correlated with the expression levels of PSORS1C3, which has previously been associated with hypersensitivity reactions to several medications. These findings together raise the possibility that the variant may predispose to a T-cell-mediated process leading to a delayed penicillin reaction."

Dr João Fadista, one of the lead authors of the paper, further shared that "a genome-wide genetic correlation analysis of the self-reported penicillin allergy results revealed overlap with the autoimmune diseases rheumatoid arthritis and psoriasis. This, together with the finding in the PTPN22 gene, indicates a possible underlying autoimmune factor in the development of penicillin allergy investigated in our study."

Prof. Lili Milani, one of the lead authors of the paper, emphasized the power of biobanks, "We have leveraged data from four large-scale cohorts, including more than 100,000 cases, to provide insights into the genetic architecture associated with self-reported penicillin allergy, and provide robust evidence implicating the HLA-B*55:01 allele and autoimmune factors in this condition. Further studies are necessary to determine the precise underlying immune processes and how these change over time, as several studies have reported that a large proportion of patients labelled as allergic to penicillin develop tolerance over time."

An infection with the coronavirus SARS-CoV-2 can affect multiple organs. With this in mind, researchers of the German Center for Neurodegenerative Diseases (DZNE) and Cornell University in the US have investigated cellular factors that could be significant for an infection. To this end, they analysed the activity of 28 specific genes in a wide range of human tissues. Their findings, which provide a map of potentially disease-relevant factors across the human body, are published in the journal Cell Reports.

"SARS-CoV-2 not just infects the respiratory system, it has the potential to affect many other organs in the body. Even if the virus infects the respiratory system first, it is essential to be able to predict where it might go next. This aids to develop therapies. Our goal was thus to learn more about what makes the different organs susceptible to infection," explained Dr. Vikas Bansal, a data scientist at the DZNE's Tuebingen site. "Therefore, we looked at different tissues to see which components of the cellular machinery might be relevant for infection and also which cell types appear to be particularly susceptible." Bansal co-authored the current paper with Manvendra Singh, a Cornell presidential fellow, and with Cedric Feschotte, professor in the Department of Molecular Biology and Genetics at the Cornell University.

Searching candidates

In cooperation with his US colleagues, Bansal started by identifying 28 human genes, respectively cellular factors, that enable the virus to enter human cells or that might otherwise be important for an infection. In addition to receptors on the cell surface, these included, for example, proteins that the pathogen presumably needs in order to multiply within a cell. Importantly, the list of studied factors also contains enzymes that block the penetration of pathogens into cells - known as "restrictors factors". In summary, the 28 analysed cellular features are dubbed "SCARFs" for "SARS-CoV-2 and coronavirus associated receptors and factors".

"The virus is known to misuse the so-called ACE2 receptor, which occurs on the surface of human cells, to dock and infiltrate them. A lot of attention is therefore paid to this receptor and other factors associated with it. They are potential starting points for therapies," said Bansal. However, related corona viruses are known to use a broad range of possibilities to infect cells. According to the researcher, evidence suggests that this also applies to SARS-CoV-2. "Therefore, we have extended our analysis to cellular factors that have been found to be relevant in other corona viruses and may therefore also be important for SARS-CoV-2."

Whether this is actually the case, future experiments will have to show, explained Bansal. For such investigations, he said, the aim was to identify promising candidates. "Our study is only a snapshot, however. Research is developing rapidly. We are constantly learning new facts about this virus."

Profiles of gene activity

Using information from scientific databases, the researchers analysed gene activity - also known as "expression patterns" - in around 400,000 human cells from various types of tissue. These included nasal mucosa, lungs, gut, kidneys, heart, brain and reproductive organs. Analysis was done on a single-cell level and using sophisticated bioinformatics methods. "This enabled us to investigate in which cells the SCARFs are expressed and also what percentage of cells within a given tissue express these factors," said Bansal. "Our results are certainly limited by the fact that expression patterns can change in the course of an infection and that such activity profiles do not directly reflect the abundance of proteins such as cell receptors. However, expression patterns are good indicators."

Battlegrounds and hotspots

In line with the known fact that SARS-CoV-2 attacks in particular the respiratory tract, the expression patterns identify the nasal mucosa as a "battleground". Accordingly, cells of the nasal mucosa contain both factors that facilitate infection like the ACE2 receptor as well as factors that inhibit viral entry, like IFITM3 and LY6E. "IFITM3 is a protein known to prevent other coronaviruses from crossing the cell membrane. Same might also apply to SARS-CoV-2. LY6E also acts as a defensive mechanism", said Bansal. "It thus seems that contact of the virus with the nasal mucosa leads to a tug-of-war. The question therefore is, who will emerge as the winner. Interestingly, our data suggest that the expression level of entry factors in the human nasal tissue shift with age. This could be a reason why the elderly are more susceptible to infection by SARS-CoV-2."

According to the current study, the intestine, kidneys, testes and placenta are potential hotspots, that is, these areas seem to be characterized by significant co-expression of ACE2 with TMPRSS2, an enzyme involved in viral entry in combination with ACE2. "We were also able to identify a number of cellular factors that, as alternatives to the ACE2 receptor, could contribute to SARS-CoV-2 entering the lungs, heart and central nervous system," said Bansal. "SARS-CoV-2 is by now known to be able to trigger neurological disorders. Although the virus has not yet been detected in neurons, the nervous system includes other cells such as astrocytes and pericytes that are for example involved in the regulation of the blood-brain barrier, which is the interface between the brain and the bloodstream. According to our study these cells might well be susceptible to infection. This could possibly involve a receptor called BSG. All in all, our study therefore provides a wealth of data and specific clues for future studies on the coronavirus."

Molecules are the building blocks of everyday life. Many materials are composed of them, a little like a LEGO model consists of a multitude of different bricks. But while individual LEGO bricks can be simply shifted or removed, this is not so easy in the nanoworld. Atoms and molecules behave in a completely different way to macroscopic objects and each brick requires its own "instruction manual". Scientists from Jülich and Berlin have now developed an artificial intelligence system that autonomously learns how to grip and move individual molecules using a scanning tunnelling microscope. The method, which has been published in Science Advances, is not only relevant for research but also for novel production technologies such as molecular 3D printing.

Rapid prototyping, the fast and cost-effective production of prototypes or models - better known as 3D printing - has long since established itself as an important tool for industry. "If this concept could be transferred to the nanoscale to allow individual molecules to be specifically put together or separated again just like LEGO bricks, the possibilities would be almost endless, given that there are around 1060 conceivable types of molecule," explains Dr. Christian Wagner, head of the ERC working group on molecular manipulation at Forschungszentrum Jülich.

There is one problem, however. Although the scanning tunnelling microscope is a useful tool for shifting individual molecules back and forth, a special custom "recipe" is always required in order to guide the tip of the microscope to arrange molecules spatially in a targeted manner. This recipe can neither be calculated, nor deduced by intuition - the mechanics on the nanoscale are simply too variable and complex. After all, the tip of the microscope is ultimately not a flexible gripper, but rather a rigid cone. The molecules merely adhere lightly to the microscope tip and can only be put in the right place through sophisticated movement patterns.

"To date, such targeted movement of molecules has only been possible by hand, through trial and error. But with the help of a self-learning, autonomous software control system, we have now succeeded for the first time in finding a solution for this diversity and variability on the nanoscale, and in automating this process," says a delighted Prof. Dr. Stefan Tautz, head of Jülich's Quantum Nanoscience institute.

The key to this development lies in so-called reinforcement learning, a special variant of machine learning. "We do not prescribe a solution pathway for the software agent, but rather reward success and penalize failure," explains Prof. Dr. Klaus-Robert Müller, head of the Machine Learning department at TU Berlin. The algorithm repeatedly tries to solve the task at hand and learns from its experiences. The general public first became aware of reinforcement learning a few years ago through AlphaGo Zero. This artificial intelligence system autonomously developed strategies for winning the highly complex game of Go without studying human players - and after just a few days, it was able to beat professional Go players.

"In our case, the agent was given the task of removing individual molecules from a layer in which they are held by a complex network of chemical bonds. To be precise, these were perylene molecules, such as those used in dyes and organic light-emitting diodes," explains Dr. Christian Wagner. The special challenge here is that the force required to move them must never exceed the strength of the bond with which the tip of the scanning tunnelling microscope attracts the molecule, since this bond would otherwise break. "The microscope tip therefore has to execute a special movement pattern, which we previously had to discover by hand, quite literally," Wagner adds. While the software agent initially performs completely random movement actions that break the bond between the tip of the microscope and the molecule, over time it develops rules as to which movement is the most promising for success in which situation and therefore gets better with each cycle.

However, the use of reinforcement learning in the nanoscopic range brings with it additional challenges. The metal atoms that make up the tip of the scanning tunnelling microscope can end up shifting slightly, which alters the bond strength to the molecule each time. "Every new attempt makes the risk of a change and thus the breakage of the bond between tip and molecule greater. The software agent is therefore forced to learn particularly quickly, since its experiences can become obsolete at any time," Prof. Dr. Stefan Tautz explains. "It's a little as if the road network, traffic laws, bodywork, and rules for operating the vehicle are constantly changing while driving autonomously." The researchers have overcome this challenge by making the software learn a simple model of the environment in which the manipulation takes place in parallel with the initial cycles. The agent then simultaneously trains both in reality and in its own model, which has the effect of significantly accelerating the learning process.

"This is the first time ever that we have succeeded in bringing together artificial intelligence and nanotechnology," emphasizes Klaus-Robert Müller. "Up until now, this has only been a 'proof of principle'," Tautz adds. "However, we are confident that our work will pave the way for the robot-assisted automated construction of functional supramolecular structures, such as molecular transistors, memory cells, or qubits - with a speed, precision, and reliability far in excess of what is currently possible."

A team led by researchers at the University of Toronto and The Hospital for Sick Children has found that mothers of preterm babies have highly individual breast milk microbiomes, and that even short courses of antibiotics have prolonged effects on the diversity and abundance of microbes in their milk.

The study is the largest to date of breast milk microbiota in mothers of preterm infants, and it is the first to show that antibiotic class, timing and duration of exposure have particular effects on the most common microbes in breast milk -- many of which have the potential to influence growth and immunity to disease in newborns.

"It came as quite a shock to us that even one day of antibiotics was associated with profound changes in the microbiota of breast milk", says Deborah O'Connor, who is a professor and chair of nutritional sciences at U of T and a senior associate scientist at SickKids. "I think the take-home is that while antibiotics are often an essential treatment for mothers of preterm infants, clinicians and patients should be judicious in their use."

Most antibiotic stewardship programs in neonatal intensive care focus on limiting use in newborns themselves. The current study adds to growing evidence that these programs should include a focus on mothers as well, says O'Connor, principal investigator on the study who is also a scientist in the Joannah & Brian Lawson Centre for Child Nutrition.

The journal Cell Host and Microbe published the study today.

The researchers looked at 490 breast milk samples from 86 mothers whose infants were born preterm, during the first eight weeks after delivery. They found that the mothers' body mass index and mode of delivery influenced the breast milk microbiota, consistent with some other studies.

But the effects of antibiotics were the most pronounced, and in some cases they lasted for weeks. Many of the antibiotic-induced changes affected key microbes known to play a role in fostering disease, or in gut health and metabolic processes that promote babies' growth and development.

"Overall we saw a decrease in metabolic pathways, and increase in more pathogenic pathways in bacteria over time," says Michelle Asbury, a doctoral student in O'Connor's lab and lead author on the paper. "Of particular concern was an association between antibiotics and a member of the Proteobacteria phylum called Pseudomonas. When elevated, Proteobacteria in a preterm infant's gut can precede necrotizing enterocolitis."

About seven per cent of babies born preterm develop necrotizing enterocolitis, a frequently fatal condition in which part of the bowel dies. A class of antibiotics called cephalosporins also had a big effect on the overall diversity of breast milk microbiota.

Asbury says it is too early to know what the findings mean for preterm infant health and outcomes. She and her colleagues will dive into those questions over the next year, as they compare their findings with stool samples from the preterm infants involved in the study. This should reveal whether changes in the mothers' milk microbiomes are actually seeding the infants' guts to promote health or increase disease risk.

Meanwhile, she says it's important that mothers with preterm infants continue to take antibiotics for some cases of mastitis, blood infections and early rupture of membranes. Roughly 60 per cent of women in the current study took antibiotics -- highlighting both the vast need for these drugs and the potential for some overuse.

Sharon Unger is a co-author on the study and a professor of paediatrics at U of T, as well as a scientist and neonatologist at Sinai Health and SickKids. She says that the benefits of breast feeding far outweigh the risk that antibiotics can disrupt the breast milk microbiome, and that mothers should without question continue to provide their own milk when possible.

"But I think we can look to narrow the spectrum of antibiotics we use and to shorten the duration when possible," Unger says. She adds that advances in technology may allow for quicker diagnoses of infection and better antibiotic stewardship in the future.

As for the rapidly moving field of microbiome research, Unger says it holds great promise for preterm infants. "Clearly the microbiome is important for their metabolism, growth and immunity. But emerging evidence on the gut-brain axis and its potential to further improve neurodevelopment for these babies over the long term warps my mind."

The evidence for hormone involvement in COVID-19 infection and treatment will be evaluated and discussed by endocrine experts in a dedicated COVID-19 session at e-ECE 2020. The European Society of Endocrinology's annual meeting is going online 5-9 September 2020 and the e-ECE 2020 programme will feature cutting-edge science and the latest in clinical practice and patient care. This includes a new, dedicated COVID-19 session, where experts in the field will present, summarise and examine evidence for the role of the endocrine system and hormones in COVID-19 infection risk, disease severity and potential treatment.

The global COVID-19 pandemic has massively affected how we all live and work and has become the major focus of medical research, as the scientific and medical communities strive to understand it better, develop effective treatments and create a vaccine. This has led to a huge volume of studies being pushed out to the public domain, including some that have not been subject the usual rigorous, scrutiny of peer review. This has resulted in conflicting messages in the media and has contributed to mistrust of experts.

Although initially thought to be a respiratory, influenza-like condition, several studies have now implicated that the severity of COVID-19 infection is increased in people with cardiovascular disease, diabetes and obesity. This raises the possibility that the consequences of viral infection are being affected by the endocrine system. Additionally, severe illness is more common in men, further suggesting that sex, possibly male and female sex hormones, are affecting coronavirus infection. More recently the glucocorticoid, dexamethasone, has shown promise as a treatment in severely ill patients with COVID-19. All of these findings indicate a key role for the endocrine system in mediating infection, disease severity and as a possible therapeutic target.

In the dedicated COVID-19 session at 16:45 CET on 8 September, three experts will review the evidence for the endocrine system's role in SARS-C0V-2 infection, and discuss how to mitigate these risks, with a view to better managing future cases and saving more lives.

* Daniel Drucker will discuss, 'Endocrine targets related to COVID infection'

* Julia Prado will discuss, 'Managing the cytokine storm'

* Matteo Rottoli will discuss, 'How strong is obesity as a risk factor for COVID-19 patients?'

These sessions aim to critically evaluate the role of the endocrine system and endocrinology in the COVID-19 pandemic, with expert debate and hopes of identifying new protective strategies and treatment options, to reduce the disease severity and risk of death in the future.

CATONSVILLE, MD, September 3, 2020 - Social media has forever changed our society and how people do business. A 2013 report by J.D. Power found nearly two-thirds of customers have used a company's social media site to connect with customer service. New research in the INFORMS journal Information Systems Research finds businesses that use Twitter as a social care channel are seeing a 19% increase in customer satisfaction.

The study, "The Voice of the Customer: Managing Customer Care on Twitter," looks at data from Twitter service accounts for the four big telecommunications firms in the United States. The two that rise to the top among online customer care are AT&T and Verizon compared to Sprint and T-Mobile.

"It's clear more customers than ever use social media to seek help from businesses. We strive to determine an optimal strategy to manage digital customer care such as Twitter," said Vijay Mookerjee of the University of Texas at Dallas.

Mookerjee alongside Reza Mousavi and Monica Johar of the University of North Carolina at Charlotte conducted the study. They found that responding to customer queries on social media has profound impacts on customer sentiment as well as the appearance of service quality.

"The top two firms, AT&T and Verizon, do better in terms of the effectiveness of care support over Sprint and T-Mobile," continued Mookerjee, a professor of information systems at UT Dallas. "Good digital care consists not merely of responding to tweets, but effort-intensive activity in which customer tweets need to be carefully examined and adequately addressed."

Customers also expect better quality of care from firms that charge more money for similar cellular plans.

"This type of quality care may require designing some sort of ticket generation system that would detect the tweets that require follow up. Then put in place a good customer service team that would be able to resolve the issues. Simply sending out automated tweets is not sufficient for achieving good quality care," said Mookerjee.

Meanwhile, an event that is perceived positive by customers would lower their expectations of care quality. But the researchers say an event that is perceived as negative by the customer, such as a price hike, would increase customers' expectations of care quality. One way around negative events is tailoring response efforts in anticipation of potentially influential events, such as marketing campaigns, a new product release or even a data security breach.

BINGHAMTON, NY -- Although researchers have known for decades that depression runs in families, new research from Binghamton University, State University of New York, suggests that children suffering from social anxiety may be at particular risk for depression in the future.

"We already know from previous research that children with social anxiety symptoms are at high risk of developing depression, as are offspring of depressed mothers," said Holly Kobezak, co-author of the new paper and lab manager at the Mood Disorders Institute at Binghamton University. "Our findings take what is already known one step further by suggesting that the combination of these risk factors may be even more insidious than the presence of either risk factor alone."

The researchers invited approximately 250 eight- to 14-year-old children whose mothers either did or did not have a history of major depressive disorder (MDD) into their lab to complete questionnaires measuring social anxiety and depression symptoms. Symptoms were reassessed at six-month intervals over a period of two years in order to capture changes in symptom levels over time as children progressed further into adolescence, which is a critical time period for the development of depression.

Their results showed that high levels of social anxiety predicted increases in depression symptoms over time, but only among children of mothers with a history of MDD.

"This provides preliminary evidence that risk for the development of depression among children with social anxiety may be particularly high among children who are already at risk for depression based on a maternal history of the disorder," Kobezak said.

According to Kobezak, these findings allow the researchers to pinpoint a subgroup of children who may be at particularly high risk for developing depression on the basis of two established risk factors that have rarely, if ever, been evaluated in combination.

"This information is useful because it can help us more precisely identify children at need of early intervention and may lay the groundwork for research that works to identify mechanisms of risk that can be targeted in clinical interventions for this group of children," she said.

The researchers hope that their findings will encourage others to explore the specific ways in which social anxiety symptoms and exposure to maternal depression may work together to increase risk of depression in children over time.

"An important point is that our findings provide insight into the circumstances that may put children at heightened risk of depression, but equally important is research that will help us understand why this may be true," said Kobezak. "With that said, we hope future research will investigate additional variables that can explain the impact of the transactional relationship between social anxiety and maternal MDD on depression. For example, future research could focus on disruptions in social functioning and interpersonal relations resulting from these experiences and whether this might be why these children are at such elevated risk. If so, this could be specifically targeted by interventions."

NASA-NOAA's Suomi NPP satellite provided a nighttime look at Hurricane Nana just after it began making landfall in Belize.

At 11 p.m. EDT on Sept. 2, Nana strengthened to a Category 1 hurricane on the Saffir-Simpson hurricane wind scale. It had maximum sustained winds near 75 mph (120 kph). At the time, it was just 60 miles (95 km) southeast of Belize City, Belize. At 2 a.m. EDT on Sept. 3, Hurricane Nana made landfall on the coast of Belize between Dangriga and Placencia with maximum sustained winds near 75 mph (120 kph). By 5 a.m. EDT, the storm had weakened to a tropical storm as it continued to move inland.

NASA's Night-Time View of Nana's Landfall

The Visible Infrared Imaging Radiometer Suite (VIIRS) instrument aboard NASA-NOAA's Suomi NPP satellite passed the Caribbean Sea overnight on Sept. 3 at 3:25 a.m. EDT (0725 UTC) and captured a nighttime image of Hurricane Nana just after making landfall in southern Belize.  Bands of thunderstorms wrapped around the storm's center and extended into the Caribbean Sea. At NASA's Goddard Space Flight Center in Greenbelt, Md., the imagery was created using the NASA Worldview application.

Warnings and Watches on Sept. 3

NOAA's National Hurricane Center (NHC) noted on Sept. 3 that a Tropical Storm Warning is in effect for the Caribbean Sea coast of Guatemala, Isla Roatan and the Bay Islands of Honduras.  A Tropical Storm Watch is in effect for the northern coast of Honduras from Punta Patuca westward to the Guatemala border.

Tropical Storm Nana's Status on Sept. 3

At 8 a.m. EDT (1200 UTC) on Sept. 3, the center of Tropical Storm Nana was located near latitude 16.6 north, longitude 89.7 west. Nana is moving toward the west-southwest near 15 mph (24 kph), and this general motion is expected to continue through today with some decrease in forward speed.  Maximum sustained winds have decreased to near 60 mph (95 kph) with higher gusts. The estimated minimum central pressure is 1000 millibars.

Nana's Fated Forecast

On the forecast track, Nana will continue to move inland over Guatemala and extreme southeastern Mexico today and tonight. Rapid weakening is forecast today and tonight, and Nana will likely become a remnant low-pressure area on Friday, Sept. 4.