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Philadelphia (August 18, 2020: 7:00 AM EST) - According to a new study published today in BMJ Quality & Safety, many hospitals in New York and Illinois were understaffed right before the first surge of critically ill Covid-19 patients. The study, "Chronic Hospital Nurse Understaffing Meets Covid-19," documented staffing ratios that varied from 3 to 10 patients for each nurse on general adult medical and surgical units. ICU nurse staffing was better but also varied significantly across hospitals.

New York City, an international gateway to the US with three major international airports and the early epicenter of the Covid-19 surge in the US, had the poorest average hospital nurse staffing on the eve of the Covid-19 medical emergency.

Researchers at the University of Pennsylvania found that the workload had adverse consequences on nurses and on patient care. One third of patients in New York state and Illinois hospitals did not give their hospitals excellent ratings and would not definitely recommend their hospital to family and friends needing care.

"Half of nurses right before the Covid-19 emergency scored in the high burnout range due to high workloads, and one in five nurses said they planned to leave their jobs within a year," said lead author Karen Lasater, PhD, RN, an assistant professor and researcher at the Center for Health Outcomes and Policy Research (CHOPR) at the University of Pennsylvania School of Nursing (Penn Nursing). "It is an immense credit to nurses that in such an exhausted and depleted state before the pandemic they were able to reach deep within themselves to stay at the hospital bedside very long hours and save lives during the emergency," continued Lasater.

"It is very important for the public to take note that in this large study of nurses practicing in New York and Illinois hospitals, half of nurses gave their hospitals unfavorable grades on patient safety and two-thirds would not definitely recommend their hospital to family and friends," said CHOPR Director Linda Aiken, PhD, RN, a senior researcher and professor at the University of Pennsylvania. She noted that nurses have been rated in the Gallup poll as the profession most trusted by the American public for past 18 consecutive years.

The researchers surveyed all registered nurses (RNs) holding active licenses to practice in New York state and Illinois during the period December 16, 2019 to February 24, 2020, immediately prior to the Covid-19 medical emergency. Hospital nurses reported on the number of patients assigned to them to care for at one time. These nurse reports were linked to Medicare patient-reported outcomes for the same hospitals. They studied 254 hospitals throughout New York state and Illinois, including 47 hospitals in the metropolitan New York area (the five NYC boroughs plus Nassau and Westchester counties).

Policy debate on safe nurse staffing standards

Both New York state and Illinois have pending legislation requiring hospitals to meet minimum safe nurse staffing standards--no more than four patients per nurse on adult general medical and surgical units. The study found that most hospitals in both states currently do not meet these proposed standards, nor do they even meet the safe nurse staffing standard of five patients per nurse set by legislation in California 20 years ago.

"This study provides an important public service by documenting in real time and in states debating current nurse staffing legislation actual hospital nurse staffing levels--information not now easily accessible to the public--and the adverse consequences of such great variation in an essential component of hospital care--nursing," said Maryann Alexander, PhD, RN, coauthor and Chief Officer, Nursing Regulation at the National Council of State Boards of Nursing.

The study's authors conclude:

there is no standardization in nurse staffing in NY and IL hospitals;

the majority of hospital nurses in these states were burned out and working in understaffed conditions immediately prior to the surge in critically ill Covid-19 patients;

understaffed hospitals pose a public health risk;

pending legislation in NY and IL may result in hospital staffing more aligned with the public's interest;

the Nurse Licensure Compact also offers a solution and may ease the strain on hospitals.

More study findings...

Mean staffing in adult medical and surgical units in NY and IL hospitals varied from 3.36 patients-per-nurse to 9.7 patients per nurse and in ICUs from 1.5 to 4 patients per nurse.

Each additional patient per nurse significantly increased the proportion of both patients and nurses giving unfavorable hospital quality and safety ratings, after differences in hospital characteristics such as teaching status, size, and technology availability were taken into account.

Half of nurses were burned out, 31 percent were dissatisfied with their jobs, and 22 percent intended to leave their jobs within a year.

Half of nurses gave their hospitals an unfavorable grade on patient safety, a third gave unfavorable ratings on prevention of infections, and 70 percent would not definitely recommend the hospital where they worked to a family member or friend.

65 percent of nurses reported delays in care were common because of insufficient staff and 40 percent reported frequent delays in care due to missing supplies including medications and missing or broken equipment.

The study was carried out by the Center for Health Outcomes and Policy Research, University of Pennsylvania School of Nursing in partnership with the National Council of State Boards of Nursing. Funding for the study was from the National Council of State Boards of Nursing, the National Institute of Nursing Research/NIH, and the Leonard Davis Institute of Health Economics at the University of Pennsylvania.

Healthy people - especially women - with elevated levels of the heart failure marker NT-proBNP have a lower risk of developing type 2 diabetes. However, if these people develop diabetes nonetheless, they are more likely to suffer from macro- and microvascular complications such as heart attack, stroke, or severe damage to eyes, kidneys, or nerves. These are the findings of a recent study by DZD researchers that has now been published in Diabetes Care.

The NT-proBNP molecule is a biomarker used to predict or diagnose heart failure. On the other hand, it has a positive effect on insulin and glucose metabolism. NT-proBNP stimulates the breakdown of fat in fat cells. In the animal model, higher levels of this peptide also showed a protective effect against overweight and glucose intolerance. Furthermore, studies suggest that people with elevated baseline levels of NT-proBNP have a lower risk of developing type 2 diabetes. But what is the effect of elevated levels of NT-proBNP in people who do develop diabetes? Do they suffer more frequently from diabetes complications? Researchers from the DZD partner German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE) investigated these questions together with colleagues from Tübingen University Hospital, University College Dublin and the Federal Institute for Risk Assessment in Berlin.

First, the researchers analyzed samples from a case cohort consisting of all the incident cases of diabetes and a random sample of EPIC Potsdam to determine whether the concentration of NT-proBNP in healthy people has an influence on diabetes risk. "We found an inverse association between NT-proBNP concentration and future risk of type 2 diabetes. With every doubling of NT-proBNP levels, the risk of diabetes decreased by about 9 percent," said first author Anna Birukov of DIfE. The influence of the NT-proBNP concentration is even more evident in women. There, the risk of diabetes decreased by 20 percent when the concentration of NT-proBNP was doubled.

In samples from 545 people who later developed diabetes, the researchers then investigated whether there was a correlation between elevated baseline NT-proBNP concentrations in a still healthy state and the risk of vascular complications. In this group, 133 people later developed microvascular and 50 people macrovascular complications **. "This showed that the NT-proBNP values are linearly associated with these diabetes complications," said Prof. Dr. Matthias Schulze, head of the study, summarizing the results. With each doubling of the baseline NT-proBNP concentration, the risk of severe damage to the eyes, kidneys or nerves increased by 20 percent and the risk of a heart attack or stroke by 37 percent.

"In the future, the measurement of NT-proBNP in plasma could be informative for monitoring the risk of diabetes-associated complications," Schulze said. The extent to which the peptide is suitable as a marker for the development of diabetes-related diseases should, however, be investigated in further prospective studies. The gender-specific associations between NT-proBNP and diabetes risk should also be validated in further prospective studies.

Announcing a new article publication for BIO Integration journal. In this commentary article the authors Chi Wei Mok, Yert Li Melissa Seet and Su-Ming Tan from Changi General Hospital, Singapore and Singhealth Duke-NUS Breast Centre, Singapore consider experiences and strategies used by a Singapore breast surgical unit for multidisciplinary breast cancer management during the COVID-19 pandemic.

The COVID-19 pandemic has forced healthcare institutions around the world to direct resources to manage the pandemic. This has resulted in a sudden acute limitation of resources to care for non- COVID patients with critical conditions. In Singapore, the escalating situation has necessitated swift reaction in the Division of Breast Surgery in Changi General Hospital to develop strategies to support the battle against COVID-19 and yet deliver care to our breast cancer patients. Prompt patient stratifications, quick adaptation to restricted resources whilst balancing the risks of exposure to patients and healthcare personnel are all crucial in providing optimal patient care. The importance of multidisciplinary team effort is pivotal in ensuring optimal delivery of care to breast cancer patients.

The authors describe the challenges faced and measures adopted by the division during this pandemic in the multidisciplinary management of non-COVID breast cancer patients providing insights to serve as a guide for physicians in similar settings who are managing breast cancer patients amidst the pandemic.

Article reference: Chi Wei Mok, Yert Li Melissa Seet and Su-Ming Tan, Breast Cancer Multidisciplinary Management during COVID-19 Pandemic: Experiences and Strategies Used by a Singapore Breast Surgical Unit. BIO Integration, 2020, https://doi.org/10.15212/bioi-2020-0012

BIO Integration is fully open access journal which will allow for the rapid dissemination of multidisciplinary views driving the progress of modern medicine.

As part of its mandate to help bring interesting work and knowledge from around the world to a wider audience, BIOI will actively support authors through open access publishing and through waiving author fees in its first years. Also, publication support for authors whose first language is not English will be offered in areas such as manuscript development, English language editing and artwork assistance.

BIOI is now open for submissions; articles can be submitted online at:

https://bio-integration.org/bioiojs/index.php/bioi/login?source=%2Fbioiojs%2Findex.php%2Fbioi%2Fabout%2Fsubmissions

Opioid use among women trying to conceive may be associated with a lower chance of pregnancy, suggests a National Institutes of Health study. Moreover, opioid use in early pregnancy may be associated with a greater chance of pregnancy loss. The study appears in Epidemiology.

"Our findings indicate that women who are pregnant or planning a pregnancy should, along with their physicians, consider the potential effects opioids may have on their ability to conceive or sustain a pregnancy," said Kerry Flannagan, Ph.D., the primary author of the study and a postdoctoral researcher in the Division of Intramural Population Health Research at NIH's Eunice Kennedy Shriver National Institute of Child Health and Human Development.

According to the authors, much of the research on prescription opioid use has focused on the effects of drug dependency. Little information exists on non-habitual, periodic opioid use around the time of conception and early in pregnancy.

The researchers analyzed data from the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial, which investigated low-dose aspirin as a treatment to prevent pregnancy loss. Participants were women from 18 to 40 years old with a history of one or two pregnancy losses. Women were followed for six monthly cycles if they did not get pregnant and throughout pregnancy if they did. The women provided urine samples, which were analyzed for various prescription opioids.

Of the 1,228 women in the study, 226 (18%) had used opioids while trying to conceive and 33 (5%) of 685 women who became pregnant had used opioids in early pregnancy. None tested positive for methadone or buprenorphine, typically used to treat opioid dependence.

Opioid use before conception was associated with a 29% lower chance of achieving pregnancy during a given monthly cycle, compared to women who had not used opioids. Among the women who became pregnant, those who used opioids around the time of conception were 1.5 times as likely to have a miscarriage as women who had not. Women who used opioids in the first four weeks of pregnancy were more than twice as likely to have a miscarriage. Women who used opioids in weeks four through eight of pregnancy were 2.5 times as likely to have a miscarriage.

The authors called for additional research on how opioid use affects fertility and early pregnancy. They added that until more is known, patients and physicians should evaluate the potential risks and benefits of opioids for pain management among women who are pregnant or may become pregnant, including those undergoing assisted reproduction procedures that may involve opioid treatment to manage pain.

COLUMBUS, Ohio - Small municipalities in Ohio that rely on retail sales taxes from apparel, vehicle sales, restaurants and tourism could see as much as a 50 percent decline in tax revenue because of the COVID-19 pandemic, a new study has found.

The study, published Monday in the journal Local Development and Society, also found that municipalities that rely on grocery stores for sales tax income could see a small increase in funding.

Smaller cities and towns were likely to see big swings in lost or gained tax revenue, while larger cities will only be moderately affected, findings suggested.

And retail sales in every part of the state, no matter the geographical location or size, would be affected by the pandemic. In some areas, a village that could lose as much as 50 percent of its revenue is located adjacent to a village that could gain as much as 25 percent.

"Every metropolitan and nonmetropolitan area has winners and losers," said Yas Motoyama, the study's author and an assistant professor of city and regional planning in The Ohio State University Knowlton School of Architecture.

"I was originally worried that economically distressed parts of the state may have had more losses, but it turns out that that is not the case."

Overall, Motoyama said places with grocery stores and big-box supercenters were likely to gain tax revenue; places that relied on outlet malls, small clothing shops, restaurants, tourism or car sales were likely to lose revenue.

Ohio has a population of 11.7 million with more than 1,300 municipalities. Of those, Motoyama found that 74 had no retail or food-service establishments and another 429 had no business establishments at all. For this study, Motoyama analyzed the remaining 858 municipalities, which included the largest cities in Ohio (Columbus, Cincinnati and Cleveland), and everything smaller.

His projections showed that more than 80 percent of those municipalities would experience some revenue loss because of the COVID-19 pandemic. And about 18 percent could see an increase. The municipalities likely to see an increase in revenue were those that had only food and beverage stores and no other retail establishments.

Larger cities were likely to lose revenue, Motoyama found, but those losses were relatively lower - on the order of 9.7 to 12.5 percent - compared with smaller cities that could lose as much as 50 percent.

"Larger cities typically have larger, more diversified tax bases," he said. "Smaller municipalities -- those with fewer than 3,500 people -- typically have just a few industries. There isn't as much diversity for those municipalities to draw from."

Motoyama used data from the U.S. Department of Commerce for changes in retail sales from February to March 2020, and found that, during that time period, the retail sector in the United States declined by 8.7 percent.

But different types of stores saw different changes. For example, clothing and accessory stores saw a 50.5 percent decrease, furniture sales declined 26.8 percent and motor vehicle sales dropped 25.6 percent. But sales of food and beverages increased 25.6 percent. (That category covers grocery stores and other shops; restaurant sales declined 26.5 percent during that time.) Hotel stays declined 31 percent.

Then, he used data from InfoGroup Business, a private company that gathers data on businesses, to estimate the employment or sales at the business establishment level and to calculate aggregate sales at the municipal level.

He then built mathematical models to show how the number of employees and annual sales revenue might decline in 2020, based on the February and March decline shown in the U.S. Commerce Department data. And he assessed the level of reliance each municipality in Ohio has on each type of retail business.

For example, the village of Bratenahl, a suburb of Cleveland, has a population of fewer than 1,200 people and a handful of retail spaces, many of which closed during Ohio's COVID-19 lockdown. This city may face up to a 50 percent decline in revenue.

"For these municipalities to continue providing the services they provide - police or road maintenance or trash pickup - they are going to have to find a way to get more money," Motoyama said. "My hope is that these projections can help them prepare for that kind of situation."

The results of an online questionnaire of 609 breast cancer survivors in the U.S. suggest that nearly half of patients experienced delays in care during the early weeks of the COVID-19 pandemic. The study, by researchers at the University of Illinois Chicago, is published in the journal Breast Cancer Research and Treatment.

"The motivation for the study came from widespread reports of cancer care being delayed or procedures being canceled in the beginning of the pandemic, and we wanted to get a better handle on what was happening," said Elizabeth Papautsky, assistant professor of biomedical and health information sciences at the UIC College of Applied Health Sciences.

Papautsky and co-author Tamara Hamlish, a research scientist in the cancer survivorship program at the University of Illinois Cancer Center, developed a questionnaire that asked about care delays. They distributed the questionnaire to U.S. breast cancer survivor groups on social media and via email. They used the National Cancer Institute's definition of a cancer survivor, which includes anyone who has received a diagnosis of cancer.

Between April 2 and April 27, the researchers received 609 responses.

The questionnaire sought to identify what kinds of care was delayed: chemotherapy, radiation, cancer surgery, hormonal treatment or routine follow-up appointments. There also were demographic questions on race and age, as well as stage of cancer.

Sixty-three percent of respondents were currently receiving cancer care, and the average age was 47 years old. The respondents were diverse: 78% identified as white, 17% as Black and 3% as Asian.

The researchers found that 44% of the respondents reported a delay in care. The most commonly reported delay was for routine follow-up visits. Respondents reported the highest rate of delays in routine follow-up appointments (79%), breast reconstruction surgery (66%), diagnostic imaging (60%) and lab testing (50%). Approximately 30% of respondents reported delays in hospital- or clinic-based cancer therapies, including radiation (30%), infusion therapies (32%) and surgical tumor removal (26%).

"We expected the usual racial difference we see in health care, with Black patients being disproportionately affected, but our results showed that patients were universally affected by COVID in terms of delays in breast cancer care, likely because in those early weeks, hospitals and health care facilities were postponing visits and procedures across the board as they took on the growing burden of dealing with COVID-19," Hamlish said.

"We were surprised to see that younger women were more likely to experience delays, and we think that has to do with cancellations of hormone therapy for ovarian suppression that is given to women with certain types of breast cancer, and those women tend to be younger in general," Papautsky said. In the study, the authors found that age was the only demographic variable that had an impact on the likelihood of a delay in care.

The questionnaire also had a section for general comments. Many respondents said that their treatment may have been modified instead of totally canceled, the researchers said. One example they noted was that hormone therapies may have been spaced out more to reduce the number of clinic visits.

"Overall, we see that there is a serious gap in disaster preparedness when it comes to providing critical, and often time-sensitive care for breast cancer patients," Hamlish said.

Researchers have uncovered how the immune system is altered in a rare COVID-19 related illness in children referred to as paediatric inflammatory multisystem syndrome (PIMS-TS).

PIMS-TS is a rare syndrome which has emerged in a small number of children during the COVID-19 pandemic. The condition causes severe inflammation in blood vessels and can lead to heart damage.

The team from Evelina London Children's Hospital and King's College London analysed blood samples from 25 children who had PIMS-TS and compared these to healthy children. The study, supported by the NIHR Guy's and St Thomas' BRC and published in Nature Medicine, showed that in the acute stage of PIMS-TS, children have raised levels of molecules called cytokines, and reduced levels of white blood cells called lymphocytes. They saw that by the time the children had recovered, the immune system changes had gradually returned to normal.

Although the number of children in the study was small, this is the first evidence about the role of the immune system in the disease. It provides vital evidence for future research and will indicate what treatments may help patients with the condition.

The first cases of PIMS-TS were treated at Evelina London in mid-April 2020. Initial reports suggested the condition may be similar to existing conditions such as Kawasaki disease. However, the new research confirms that PIMS-TS affects the body in a different way to other known conditions and has been identified as a new syndrome.

The research, led by Dr Shankar-Hari within the King's College London School of Immunology and Microbial Sciences, worked to understand the immune system changes underlying this new condition.

Blood samples were analysed from 25 children who had tested positive for the Sars-COV2 virus, had symptoms of COVID-19, had been in close contact with someone who had tested positive, or whose parent was a healthcare worker.

Blood samples were tested from children these children at different stages of the disease, from the acute phase when they first came onto hospital, through to their outpatient appointments. The researchers compared these results to those of seven healthy age-matched children.

Dr Manu Shankar-Hari is a consultant in intensive care medicine at Guy's and St Thomas' and NIHR Clinician Scientist and Reader and Consultant in Intensive Care Medicine at King's College London. He said: "PIMS-TS is a new syndrome. Our research has allowed us to provide the first description of the profound immune system changes in severely ill children with this new illness.

"These immune changes are complex. The innate, otherwise known as the rapidly responding, immune cells are activated. The lymphocytes, a particular type of white cell involved in specific protective immunity, are depleted, but appear to be actively fighting infection.

"Clinically, these children respond to treatments that calm the immune system such as corticosteroid and immunoglobulins. Although there are similarities to existing conditions such as Kawasaki Disease, these clinical and immunological changes that we observe imply that PIMS-TS is a distinct illness associated with SARS-Co-V-2 infections."

Dr Shane Tibby, paediatric ICU consultant at Evelina London said: "When we first saw the immunophenotyping results in this paper, it confirmed our clinical impression: that this was neither Toxic Shock nor Kawasaki Disease, but rather a new entity that likely requires both organ support and careful, targeted immunotherapy."

Dr Michael Carter is a Paediatric NIHR Academic Clinical Lecturer and sub-speciality registrar in paediatric intensive care at Evelina London. He said: "The support of children and young people with PIMS-TS was crucial in this study. Their help enabled us to monitor changes in the immune system during their illness and recovery and may contribute towards developing targeted immune therapy for children with PIMS-TS in the future."

Despite decades of study, exactly how herpesviruses invade our cells remains something of a mystery. Now researchers studying one herpesvirus, the varicella zoster virus (VZV) that causes chicken pox, may have found an important clue: A key protein the virus uses to initiate infection does not operate as previously thought, researchers at Stanford University and the Department of Energy's SLAC National Accelerator Laboratory report August 18 in Nature Communications.

The results were made possible by high-resolution cryo-electron microscopy (cryo-EM), which showed that the immune system can prevent infection by attacking a spot on the protein in an unexpected place, said Stefan Oliver, a senior research scientist in pediatrics at Stanford and the new study's first author.

Herpesviruses including VZV - along with HIV, coronaviruses, and a number of other virus families - are enclosed in a protective membrane, and the first step in the process of invading a cell is for the viral envelope to fuse with the cell's membrane. In VZV's case, a protein called gB that sits on the outside of the viral envelope uses a set of molecular fingers to grab onto and fuse with cells.

But it turns out that's only part of the story. To investigate what was happening in more detail, Oliver and colleagues used an antibody from a patient that prevented VZV fusion with cells in cryo-EM experiments to discover where the antibody attacks gB.

To Oliver and colleagues' surprise, the antibody bound to a spot on gB far from the fusion fingers, indicating that it may not need to target the fingers to prevent fusion with a cell. This result suggests that there may be more involved in the process of fusion, which causes infection, than was realized.

Figuring out exactly how the fusion process works will take further studies that could inform the design of treatments and vaccines for other herpesviruses, Oliver said, since they also rely on gB to infect cells. "Vaccines are currently not available for herpesviruses, with the exception of the one that prevents VZV, so the development of vaccines that target this newly identified region of gB has the potential to solve an important medical need."

Oliver added, "It was only possible to uncover this mechanism by generating one of the highest resolution structures of a viral protein-antibody pair using cryo-EM. Without the cryo-EM capabilities at SLAC these fascinating insights into the molecular mechanisms of fusion function would not have been achievable".

A model for successfully managing food safety incidents has been developed by a diverse team of academics and researchers from Flinders University's College of Medicine and Public Health, and the College of Nursing and Health Sciences - and they believe the same applications can apply to pandemic management.

"It's crucial that the public does not lose trust in governments and the officials communicating information during a crisis," says Dr Annabelle Wilson from the College of Medicine and Public Health at Flinders University.

"The key is to be transparent in messaging. Our model was developed to address food incidents and it highlights strategies to use to communicate effectively with the public. The same ideas make sense in a COVID-19 situation."

The Flinders researchers' model identifies10 strategies, including transparency; development of protocols and procedures; credibility; proactivity; putting the public first; collaborating with stakeholders; consistency; education of stakeholders and the public; building your reputation; and keeping your promises.

The model has been has presented to key government bodies including SA Health and Food Standards Australia New Zealand, and the original work was then replicated in Ireland.

"We have found that in times of crisis through a major food incident - when the public may doubt who they trust - it is imperative that the messages of the food regulators and government authorities are trusted so that the public can act accordingly in line with recommendations.

"Therefore, the model we created focuses on how authorities can best communicate key messages to the public - which in a pandemic involves key behaviours like social distancing."

While pandemic management differs from a food incident - as the responsibility to act is with the public rather than identifiable regulatory bodies, and governments must weigh competing risks in creating policy - the Flinders researchers conclude that many of the strategies identified in their food trust model could be successfully applied to the maintenance of trust in public health officials prior to, during, and after pandemics.

"The ultimate goal is to maximise trust between the public and governments in Australia, to support public adherence of public health recommendations in response to COVID-19, such as social distancing and isolation," says Dr Wilson.

"Ideally, we would like to test the application of this model in the COVID-19 pandemic context, and then roll it out for use by state and federal governments across Australia. We currently have a grant application under review to ideally help us to do this."

Wareham, Mass., August 18, 2020 - A new clinical trial found consuming cranberry juice containing 44 mg of proanthocyanidins (or "PACs") per 240-mL serving twice daily for eight weeks resulted in a 20% reduction in the H. pylori infection rate in Chinese adult participants, when compared to those consuming lower amounts of juice and a placebo1. While more research is needed, these findings published in the Journal of Gastroenterology and Hepatology, a top international gastroenterology journal, show that twice daily consumption of 44 mg PAC cranberry juice has the potential to be a natural, complementary management strategy for adults in this population infected with H. pylori.

The new study, "Suppression of Helicobacter pylori Infection by Daily Cranberry Intake: A Double-Blind, Randomized, Placebo-Controlled Trial" was conducted by key scientists at the Department of Cancer Epidemiology, Peking University Cancer Hospital and Institute in Beijing, China, a leading cancer research center. The study included 522 H. pylori-positive Chinese adults between the ages of 18-60 that have never previously received antibiotic therapy for H. pylori infection. Participants assigned to specific groups consumed different amounts of cranberry juice, juice-based powder or their placebos daily for eight weeks with testing performed at 2 and 8 weeks to determine H. pylori suppression rates. Investigational products were standardized to contain different levels of PACs to evaluate their effects on H. pylori suppression.

"The study findings reveal that cranberry juice may be a useful aid in H. pylori management in adults in a high-risk region of China with an endemic infection rate of over 50%, and has potential to be a key area for future research," says lead researcher Professor Kai-Feng Pan MD, PhD, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, of Peking University Cancer Hospital & Institute. "While not alternatives to antibiotics, effective complementary strategies, like cranberry, that can contribute to managing H. pylori infections without negative side effects are highly desirable."

H. pylori bacterial infection is of worldwide concern due to its high global prevalence rate of over 80% in some developing countries and potential to cause stomach ulcers, which when untreated, increase the risk of developing stomach cancer2. The overall H. pylori prevalence rate in the current study in Linqu County, China was 51.62%, while the weighted average prevalence of H. pylori among U.S. adults is 35.6% according to a 2016 systematic review of data between 1990-2006 from 10 studies8. While H. pylori infection is the primary identified cause of gastric cancer, other major risk factors include chronic gastritis, high-salt diets and chemical carcinogens3,4. Classified as a class I carcinogen by the World Health Organization5, H. pylori infection in China is traditionally treated with costly triple or quadruple antibiotic therapies that can have significant side effects and treatment failure rates of 10-30%6,7.

Previous in vitro studies in Israel demonstrated that a cranberry extract containing PACs inhibited adhesion of H. pylori strains to human gastric mucus and stomach cells9. Results from in vitro studies provide indicators that are used as background to formulate hypotheses for other human studies.

Cranberry juice (240 mL) containing 44 mg PAC reduced H. pylori when taken twice daily for eight weeks compared to other juice treatments or placebo, showing a statistically significant positive trend over time, but was not effective if taken only once a day or if juice with the lower PAC content of 23 mg was consumed. Participants that tested negative at eight weeks were retested 45 days later after ending treatment and 75% in the juice group remained H. pylori-negative. Some subjects in the placebo group also remained negative at this time point, possibly due to ingestion of unaccounted dietary components with H. pylori inhibitory activity. Statistical analyses were not performed on these data due to limited sample sizes. Additional research is needed to further explore any bacterial eradication effects of cranberry on H. pylori. Participants who remained H. pylori-positive following the trial were provided standard triple therapy antibiotic treatments.

Cranberry juice-based encapsulated powder containing either 36 or 72 mg of PACs per day was not effective at suppressing H. pylori. Given the consumer interest in cranberry supplements, researchers suggest that future trials could test effects of twice-daily dosing of powder with higher PAC content and potentially dissolve the powder in liquid prior to consumption to improve dispersion in the stomach.

The results of this research provide details on effective amounts of cranberry juice, PAC content and frequency of consumption over an 8-week intervention period. The statistically significant 20% suppression of H. pylori infection rates in this trial following intake of the high-PAC cranberry juice by Chinese adults exceeds suppression rates found in previous trials in China10 and Chile11 that tested only one serving size of cranberry juice with unknown PAC levels. Results of the current study suggest that regular consumption of cranberry juice, when administered at certain amounts, has the potential to assist in the management of H. pylori, especially in China where endemic infection and gastric cancer rates are high.6 More research is needed to determine broader effects of cranberry juice and H. pylori infection and additional details on the mechanisms of action.

The study was supported by a grant from the Cranberry Marketing Committee (CMC). The sponsor of the study had no role in the study design, data collection, data analysis, data interpretation, or writing of the report.

Researchers at UC San Francisco have developed a "digital biomarker" that would use a smartphone's built-in camera to detect Type 2 diabetes - one of the world's top causes of disease and death - potentially providing a low-cost, in-home alternative to blood draws and clinic-based screening tools.

Type 2 diabetes affects more than 32 million Americans and more than 450 million people worldwide, and can raise the risk of diseases affecting nearly every organ system, including coronary heart disease, kidney failure, blindness and stroke. In the current pandemic, it also has been found to increase the risk of severe symptoms of COVID-19.

Yet, half of the people with diabetes are unaware of their diagnosis and risks to their health.

"The ability to detect a condition like diabetes that has so many severe health consequences using a painless, smartphone-based test raises so many possibilities," said co-senior author Geoffrey H. Tison, MD, MPH, assistant professor in cardiology, of the Aug. 17, 2020, study in Nature Medicine. "The vision would be for a tool like this to assist in identifying people at higher risk of having diabetes, ultimately helping to decrease the prevalence of undiagnosed diabetes."

Screening tools that can be deployed easily, using technology already contained in smartphones, could rapidly increase the ability to detect diabetes, the researchers said, including populations out of reach of traditional medical care.

While diabetes mellitus is the seventh highest global cause of death on its own, according to the World Health Organization, it also significantly raises the risk of heart disease, which is the leading cause of death in the United States and worldwide. The U.S. Centers for Disease Control and Prevention estimate that people with Type 2 diabetes are twice as likely to die of heart disease as those who do not have diabetes.

"Diabetes can be asymptomatic for a long period of time, making it much harder to diagnose," said lead author Robert Avram, MD, MSc, clinical instructor in cardiology. "To date, noninvasive and widely-scalable tools to detect diabetes have been lacking, motivating us to develop this algorithm."

In developing the biomarker, the researchers hypothesized that a smartphone camera could be used to detect vascular damage due to diabetes by measuring signals called photoplethysmography (PPG), which most mobile devices, including smartwatches and fitness trackers, are capable of acquiring. The researchers used the phone flashlight and camera to measure PPGs by capturing color changes in the fingertip corresponding with each heartbeat.

In the Nature Medicine study, UCSF researchers obtained nearly 3 million PPG recordings from 53,870 patients in the Health eHeart Study who used the Azumio Instant Heart Rate app on the iPhone and reported having been diagnosed with diabetes by a health care provider. This data was used to both develop and validate a deep-learning algorithm to detect the presence of diabetes using smartphone-measured PPG signals.

Overall, the algorithm correctly identified the presence of diabetes in up to 81 percent of patients in two separate datasets. When the algorithm was tested in an additional dataset of patients enrolled from in-person clinics, it correctly identified 82 percent of patients with diabetes.

Among the patients that the algorithm predicted did not have diabetes, 92 to 97 percent indeed did not have the disease across the validation datasets. When this PPG-derived prediction was combined with other easily obtainable patient information, such as age, gender, body mass index and race/ethnicity, predictive performance improved further.

At this level of predictive performance, the authors said the algorithm could serve a similar role to other widespread disease screening tools to reach a much broader group of people, followed by a physician's confirmation of the diabetes diagnosis and a treatment plan.

"We demonstrated that the algorithm's performance is comparable to other commonly used tests, such as mammography for breast cancer or cervical cytology for cervical cancer, and its painlessness makes it attractive for repeated testing," said study author Jeffrey Olgin, MD, a UCSF Health cardiologist and professor and chief of the UCSF Division of Cardiology. "A widely accessible smartphone-based tool like this could be used to identify and encourage individuals at higher risk of having prevalent diabetes to seek medical care and obtain a low-cost confirmatory test."

The authors recommend further study to determine the effectiveness of this approach for specific clinical applications, such as screening or therapeutic monitoring.

Antibiotics use, particularly antibiotics with greater spectrum of microbial coverage, may be associated with an increased risk of new-onset inflammatory bowel disease (IBD) and its subtypes ulcerative colitis and Crohn's disease. That is according to a study by researchers at Karolinska Institutet in Sweden and Harvard Medical School in the United States, published in The Lancet Gastroenterology & Hepatology. The association between antimicrobial treatment and IBD remained when patients were compared with their siblings.

IBD is becoming more common, particularly in Europe, the U.S. and other parts of the world undergoing rapid economic development, increased sanitation, and more frequent use of antibiotics. With growing appreciation for the gut microbiome's role in maintaining human health, concern has risen that antibiotics may perturb and permanently alter these fragile microbial communities. This could potential impact the risk of gastrointestinal disease.

In what is the largest study thus far linking antibiotic therapy and risk of IBD, researchers in Sweden and the U.S. were able to more definitively demonstrate that more frequent use of antibiotics was associated with the development of IBD and its subtypes, ulcerative colitis and Crohn's disease.

"I think this affirms what many of us have suspected--that antibiotics, which adversely affect gut microbial communities, are a risk factor for IBD," said lead author, Dr. Long Nguyen at Massachusetts General Hospital and Harvard Medical School, Boston, U.S. "However, despite this compelling rationale and seemingly intuitive presumption, there have been no population-scale investigations to support this hypothesis until now."

Through the Epidemiology Strengthened by histoPathology Reports in Sweden (ESPRESSO) study, the researchers identified almost 24,000 new IBD cases (16,000 had ulcerative colitis and 8,000 Crohn's disease) and compared them with 28,000 siblings, and 117,000 controls from the general population. Prior use of antibiotics (never vs. ever) was associated with a nearly two-times increased risk of IBD after adjusting for several risk factors. Increased risk was noted for both ulcerative colitis and Crohn's disease with the highest estimates corresponding to broad-spectrum antibiotics.

According to the researchers, earlier studies in the field have been small, and few have had a follow-up beyond a few years. In contrast, the researchers in this study were able to enroll all consecutive, eligible patients with new-onset IBD from a population-based register over a ten-year study period, limiting selection bias.

"In Sweden, there is universal medication coverage with virtually complete information on all drug dispensations, including antibiotics, minimizing ascertainment bias," says senior author, Professor Jonas F Ludvigsson, pediatrician at Örebro University Hospital, and professor at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet. "This makes Swedish registers ideal for the study of risk factors for IBD."

IBD affects nearly 1 percent of the Swedish population and can have a substantial effect on patients' life. It has been linked to an increased risk of both death and cancer.

"To identify risk factors for IBD is important, and ultimately our aim is to prevent the disease," adds Ludvigsson. "Our study provides another piece of the puzzle and even more reason to avoid using antibiotics needlessly."

The tuberculosis bacterium has been around as long as mankind has.

To fight the bacterium, we need to know how it attacks the body's immune system.

Researchers at the Norwegian University of Science and Technology (NTNU) have taken the next step toward that goal by filming the process.

It's thought that every fourth person harbors tuberculosis bacteria in their body, although only five to ten percent of the infected population actually get sick.

People who contract the illness need to take antibiotics for up to two years.

Antibiotic resistance in some patients means they never recover. Those who have had the disease and survive do not become immune.

One person who lives close to the tuberculosis bacterium is Professor Trude Helen Flo at NTNU's Centre of Molecular Inflammation Research (CEMIR).

Now she and nanotechnologists Kai and Marianne Sandvold Beckwith at NTNU and EMBL Heidelberg have managed to film in detail how the death process unfolds inside a cell.

This is rare fare, even among researchers, which is why the world premiere was recently published in the journal Nature Communications.

"We observed the tuberculosis bacterium and some of the proteins we study with fluorescent colours like blue, red and green in the cells. We used advanced fluorescence microscopy to film them before studying them with a 3D electron microscope that has nanometre resolution," says Flo.

The most harmful bacteria are the best at fooling the body's immune system.

The TB bacterium hides in the very cells that are supposed to kill it.

"The tuberculosis bacterium lives in macrophages that are the guards, waste removers and caretakers of the immune system," says Flo.

The main role of macrophages in the immune system is to eat and destroy microbes, while alerting the rest of the immune system. TB bacteria have found ways to hide inside the macrophage and avoid being killed.

"The tuberculosis bacterium lives in the world's best hiding place," says Flo.

The research team filmed the infection in multiple 24-hour time-lapse sequences.

When the tuberculosis bacterium makes a person sick, it is because cells full of bacteria rupture and spread the contents to other cells in the lungs, creating an inflammation that damages the lung tissue. The person begins to cough, and the bacteria spreads.

For the first time, NTNU researchers have managed to show exactly how this happens inside the cell and in what order.

The only way for the tuberculosis bacterium to spread is to first get out of the cell it lives in. The bacteria begin to reproduce and at some point kill the cell they live in in order to spread further.

"The TB bacterium does this by punching holes in the membrane that encloses the macrophages. This triggers an explosive immune response in which the cell they live in dies, allowing the bacteria to spread to other cells. The bacteria operate in two modes: one where they divide and multiply while hidden inside the cell they live in, and one where they break out and infect healthy tissue," says Flo.

Filming allowed the researchers to study this process much more precisely.

The researchers can apply this understanding in their work to treat the disease.

"Antibiotics work against the bacteria, but we envision developing a treatment that could control the cell death and tissue damage caused by the tuberculosis bacterium. Combined with antibiotics, this might provide more effective treatment, but we aren't there yet," says Flo.

Finland declared a lockdown in response to the coronavirus pandemic in March 2020, and the ensuing social distancing measures decreased the number of paediatric emergency room visits to nearly one-third of what they used to be, according to a recent register-based study conducted in collaboration between the University of Eastern Finland, Kuopio University Hospital and the National Institute for Health and Welfare.

The researchers looked at the number of paediatric emergency room visits in two Finnish hospitals (Kuopio University Hospital, Mikkeli Central Hospital) four weeks before and four weeks after the country went into lockdown. In addition, nationwide weekly numbers of influenza (A + B) and respiratory syncytial virus (RSV) in children were collected from the national infectious disease register for the influenza season 2019-2020, and compared against numbers from 2015.

Besides a decrease in paediatric emergency room visits, the number of hospital referrals was also decreased by half since the start of the lockdown. A similar decrease was observed in both hospitals and in children of all ages.

Most paediatric emergency room visits are caused by viral respiratory tract infections, and especially cases of upper respiratory tract infections and middle ear infections decreased significantly. The change was most visible in cases of lower respiratory tract infections, i.e. bronchitis and pneumonia, whose incidence decreased to around one-fifth. A similar decrease was not seen in the numbers from spring 2019.

The influenza season and RS virus epidemic ended soon after the lockdown was declared. In comparison to earlier years, the influenza season lasted only for roughly half of its normal duration (8 weeks vs. 13-20 weeks in earlier years). No paediatric cases of COVID-19 were found in participating hospitals during the study period.

"We are used to the idea that children have respiratory tract infections almost all the time; most commonly they suffer from bronchitis and middle ear infections. Children under the age of one are also frequently hospitalised due to RSV or influenza. However, our findings now show that social distancing plays a major role in reducing paediatric infections, emergency room visits and hospitalisation," Professor of Paediatrics Marjo Renko from the University of Eastern Finland says.

The study was published in Pediatric Infectious Diseases Journal in late July.

The multiplication of genes located in extrachromosomal DNA that have the potential to cause cancer drives poor patient outcomes across many cancer types, according to a Nature Genetics study published Aug. 17, 2020 by a team of researchers including Professors Vineet Bafna and Dr.Paul Mischel of the University of California San Diego and Professor Roel Verhaak of Jackson Laboratories.

This is the first time that a study has shown that the multiplication of these extrachromosomalDNA (ecDNA) genes--a phenomenon called ecDNA oncogene amplification-- is present in a broad range of cancer tumor types. The researchers found that ecDNA is a common event in human cancer, occuring at minimum in 14% of human tumors, with far, far higher frequencies in the most malignant forms of cancer, including glioblastoma, sarcoma, esophageal, ovarian, lung, bladder, head and neck, gastric, and many others. The findings demonstrate that ecDNA plays a critical role in cancer.

"We also find that patients whose cancers have ecDNA have significantly shorter survival than all other cancer patients, whose tumors are driven by other molecular lesions, even when grouped by tumor type," said Dr. Mischel, one of the study's authors and a distinguished professor at the UC San Diego School of Medicine and a member of the Ludwig Institute for Cancer Research.

The shorter overall survival raises the possibility that cancer patients whose tumors are driven by ecDNA may not be as responsive to current therapies and may be in need of new forms of treatment. The researchers' hope is that these findings will be applied to the development of powerful anti-cancer therapies for individuals with ecDNA-driven cancers.

"This study provides a new window into the molecular epidemiology of ecDNA in cancer, providing a unique opportunity to study patients longitudinally to better understand how and why they respond poorly to treatment," Dr. Mischel said.

The researchers observed that ecDNA amplification occurs in many types of cancers, but not in normal tissue or in whole blood, and that the most common recurrent oncogene amplifications frequently arise on ecDNA. Notably, ecDNA-based circular markers of amplification were found in 25 of 29 cancer types analyzed, and at high frequency in many cancers that are considered to be among the most aggressive histological types, such as glioblastoma, sarcoma, and esophageal carcinoma.

"It seems that cancers have pulled an ancient evolutionary trick. Oncogenes and surrounding regulatory regions untether themselves from their chromosomal constraints, driving high oncogene copy number, accelerating tumor evolution, contributing to therapeutic resistance, and endowing tumors with the ability to rapidly change their genomes in response to rapidly changing environments, thereby accelerating tumor evolution and contributing to therapeutic resistance," Dr. Mischel said.

To get to this finding, the research team used intensive computational analysis of whole-genome sequencing data from more than 3,200 tumor samples in The Cancer Genome Atlas (TCGA) and the Pan-Cancer Analysis of Whole Genomes (PCAWG), totaling over 400 terabytes of raw sequencing data, to observe the impact of ecDNA amplification on patient outcomes.

"We developed a powerful computational approach called Amplicon Architect, which identifies ecDNA based on three key features- circularity, high copy number, and "reuse of breakpoints," said paper coauthor Bafna,a professor in the UC San Diego Department of Computer Science and Engineering.

Dr. Mischel and Bafna are cofounders of Boundless Bio, a company developing innovative new therapies directed to extrachromosomal DNA (ecDNA) in aggressive cancers.

"These results point to the urgent need for therapies that can target ecDNA and interfere with their ability to drive aggressive cancer growth, resistance, and recurrence," said Jason Christiansen, chief technology officer of Boundless Bio.

What is ecDNA?

Extrachromosomal DNA, or ecDNA, are distinct circular units of DNA containing functional genes that are located outside cells' chromosomes and can make many copies of themselves. ecDNA rapidly replicate within cancer cells, causing high numbers of oncogene copies, a trait that can be passed to daughter cells in asymmetric ways during cell division. Cancer cells have the ability to upregulate or downregulate oncogenes located on ecDNA to ensure survival under selective pressures, including chemotherapy, targeted therapy, immunotherapy, or radiation, making ecDNA one of cancer cells' primary mechanisms of recurrence and treatment resistance. ecDNA are rarely seen in healthy cells but are found in many solid tumor cancers. They are a key driver of the most aggressive and difficult-to-treat cancers, specifically those characterized by high copy number amplification of oncogenes.