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Cambridge researchers have shown how rapid genome sequencing of virus samples and enhanced testing of hospital staff can help to identify clusters of healthcare-associated COVID-19 infections.

Since the start of the UK pandemic, when the virus was spreading between people, a team of scientists and clinicians at the University of Cambridge and Cambridge University Hospitals NHS Foundation Trust (CUH) have been reading the genetic code of the virus to see if cases within the hospital are connected. This has enabled the hospital to fully investigate these outbreaks and to improve infection control measures to reduce the risk of further infections.

In addition, the introduction of a screening programme that involved repeat testing of staff, has helped the hospital to investigate clusters of COVID-19 infections, informing infection control measures and breaking chains of transmission. This has helped reduce the number of hospital-acquired infections, ensuring maximum safety for patients and staff as the NHS aims to re-start other services.

Researchers have published details of these investigations in two peer-reviewed journals, Lancet Infectious Diseases and eLife.

Genomic surveillance

Researchers in Cambridge have previously pioneered the use of genome sequencing as a way of managing hospital infections such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin resistant enterococci (VRE) and Clostridium difficile. They have also used real-time sequencing to rapidly identify transmission chains in epidemics such as the Ebola epidemic in Sierra Leone.

The researchers have now turned their attention to COVID-19.

SARS-CoV-2, the coronavirus that causes COVID-19, is an RNA virus and as such its genetic code is prone to errors each time it replicates. It is currently estimated that the virus mutates at a rate of 2.5 nucleotides (the A, C, G and T of genetic code) per month. Reading - or 'sequencing' - the genetic code of the virus can provide valuable information on its biology and transmission.

As part of the COVID-19 Genomics UK (COG-UK) Consortium, researchers have been sequencing all available positive samples from patients admitted to the hospital with COVID-19 infection as well as a selection of samples collected from patients in regional hospitals across the East of England.

In a five week period from mid-March to late April, the team sequenced over 1,000 viral genomes. They used phylogenetic trees - akin to a 'family tree' - to look at how clusters of virus samples might be related, allowing them to help pinpoint particular wards or locations where the disease was spreading.

Dr Estée Török from the Department of Medicine at the University of Cambridge said: "Genome sequencing gives us a rapid and reliable way of identifying cases of COVID-19 infection that are closely related within the hospital. This approach can provide vital information to help us to investigate the possible routes of transmission and to improve infection control measures to limit the spread of infection."

The researchers analysed 299 COVID-19 patients and found 35 clusters of genetically identical viruses involving 159 patients. By examining the patients' medical records and ward location data researchers identified strong links between 58% of cases and plausible links between 20% of cases. The epidemiological and genomic data were fed back to the hospital infection control and management teams resulting in implementation of a range of measures to prevent further transmission, including isolation of infected patients, revised procedures for ward cleaning, enhanced use of personal protective equipment (PPE) and changes in staff social distancing behaviour.

As an example, six dialysis patients were admitted to different locations in the hospital with COVID-19 infection over a three-week period. Sequencing revealed that their viral genomes were identical. Epidemiological investigation showed that the patients dialysed at the same outpatient dialysis unit on the same days of the week and identified shared patient transportation and neighbouring dialysis chairs as risk factors for transmission. This enabled the infection control team to enhance infection control measures and prevented additional cases.

Professor Ian Goodfellow, from the Department of Pathology at the University of Cambridge, said: "We're able to combine genomic data with patients' medical records to provide real time information to help the hospital review its infection control on a weekly basis. It's also highlighted possible transmission networks less well documented, such as care homes, outpatient units and ambulance services."

The COVID-19 Genomics UK Consortium is supported by funding from the Medical Research Council, part of UK Research & Innovation (UKRI), the National Institute of Health Research and the Wellcome Sanger Institute.

Screening asymptomatic and symptomatic healthcare workers

In addition to genomic surveillance, CUH has implemented a screening programme in which all staff - both symptomatic and asymptomatic - are screened.

In May, Cambridge researchers reported that of the more than 1,000 staff members reporting fit for duty during April, 3% tested positive for the coronavirus.

Now, in a follow-up study published in eLife, they have found that, alongside a decline in patient admissions with COVID-19, the proportion of both asymptomatic and symptomatic healthcare workers testing positive declined rapidly throughout the following month.

The team performed 3,388 tests at CUH between 25 April and 24 May. These included 2,611 tests on asymptomatic healthcare workers. The samples were analysed using a technique called PCR to detect genetic information from the virus on the swab.

The researchers found that just 21 (0.8%) of the 2,611 tests carried out on asymptomatic healthcare workers returned positive, a large drop compared to the previous month.

Of the 771 tests carried out on symptomatic healthcare workers or those living with someone with possible infection, just 13 (1.7%) were positive - compared to 13% the previous month.

Dr Mike Weekes, from the Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), said: "Screening all staff at the hospital regardless of whether they are showing symptoms has helped us see a dramatic fall in the number of hospital-acquired infections. It means we're able to spot new outbreaks faster, limiting their opportunity to spread.

"It's important not to be complacent, though. There will inevitably be new outbreaks that occur - that is, unfortunately, the nature of a pandemic. But we hope our approach will help reassure both staff and patients that the hospital remains a safe place to give and receive care."

In their report, the team give an example of where four symptomatic staff from the same general medical ward tested positive. In response, the team was able to carry out targeted screening of staff on the ward, allowing them to identify a cluster of infections and prevent further onward transmission.

"The existence of clusters of infection in specific areas of the hospital shows the potential for staff and patients to become infected within the hospital environment," said Professor Steve Baker from CITIID. "If left unchecked, these clusters could lead to self-sustaining outbreaks. Frequent testing at CUH allowed us to spot these clusters quickly and stop any further transmission."

A lower total dose of radiotherapy delivered in fewer but larger doses is as safe in the long term as breast cancer radiotherapy courses giving multiple small doses, according to the final results of a 10-year study.

The findings show that five larger radiotherapy doses after surgery - once-a-week sessions for five weeks instead of daily radiotherapy over the same time, totalling 25 doses - cause similarly low rates of side-effects in women with early-stage breast cancer in the long run.

Fewer treatment sessions particularly benefit patients at low risk of relapse who cannot tolerate daily radiation over long periods of time because of frailty or other chronic conditions. The 10-year study offers reassurance to these women over the long-term safety of the approach.

The 10-year results of the FAST trial, led by The Institute of Cancer Research, London, and funded by Cancer Research UK, are published in the Journal of Clinical Oncology.

The FAST trial, launched in 2004, compared radiotherapy schedules consisting of fewer but larger fractions overall, while decreasing the total dose of radiation, in order to see which course was best at reducing side-effects.

The three-year results of the FAST trial were published in 2011 and showed that reducing the number of radiotherapy fractions to five was feasible and safe in the short term.

Since then, FAST has informed the design of the FAST-Forward trial, also led by The Institute of Cancer Research (ICR), which looks at delivering the five fractions of radiotherapy in a single week. This has also been found to be safe and effective.

The 10-year results from the FAST trial now confirm that a treatment strategy involving fewer doses and fewer visits to hospital is as safe in the long term, since side-effects remain low a decade later.

Radiotherapy uses X-rays to destroy cancer cells that may be left behind after breast cancer surgery. As a consequence, having radiotherapy after surgery lowers the risk of the cancer coming back - but the radiation can affect healthy tissue around the site of the surgery and on rare occasions can result in serious side effects.

Some 915 women from 19 centres across the UK who had early-stage breast cancer participated in the FAST trial. Researchers assigned women to one of three different courses of radiotherapy following breast cancer surgery - a regimen of daily doses and two courses delivering five larger doses once weekly, all over the same time period of five weeks.

After completing the radiotherapy regimens, women were assessed annually for up to 10 years by researchers for side effects to healthy breast tissue - including hardening of the breast, swelling, skin reactions and changes in breast size.

The standard radiotherapy regimen consisted of the now outdated international standard of 50 Gray (Gy) of radiation, divided into 25 daily doses of 2 Gy, delivered every day over five weeks. The trial treatments consisted of 30 or 28.5 Gy delivered once a week for five weeks in fractions of 6 or 5.7 Gy.

Moderate or severe long-term effects were low across the three treatment groups and the most common effect was breast shrinkage. The researchers observed no changes or minor changes in healthy breast tissue in 86 per cent of all women in the trial at the 10-year time point.

Moderate or marked effects were two thirds more likely in women on the 30 Gy regimen than with 50 Gy - but the women on the 28.5 Gy and 50 Gy regimens had a similar risk of moderate or marked effects. Delivering 28.5 Gy in five fractions as a once-weekly schedule is therefore safe in the long-term for certain patients, especially those who are frailer.

Study co-leader Professor Judith Bliss, Professor of Clinical Trials at The Institute of Cancer Research, London, and Director of its Cancer Research UK-funded Clinical Trials and Statistics Unit, said:

"After undergoing surgery to remove breast cancer, patients usually undergo weeks of radiotherapy. The aim of the FAST trial was to figure out if using fewer fractions overall, with careful consideration of the total dose, would reduce the side effects observed.

"Our initial results showed that when the total dose is adjusted appropriately it is safe to deliver radiotherapy in fewer doses and now we can confirm that this is still the case 10 years down the line.

"These findings have supported a change in clinical practice that is already helping relieve pressures on the NHS - and it is great to see that after so many years, side effects from fewer but larger doses of radiation are still low."

Professor John Yarnold, Professor of Clinical Oncology at The Institute of Cancer Research, London, and Honorary Consultant at The Royal Marsden NHS Foundation Trust is chief investigator of the FAST trial. He said:

"Our findings support treatment options that are more convenient for patients who cannot tolerate long courses of daily radiation, without increasing the risk of long-term side effects.

"The FAST trial confirms the safety of a radiotherapy course consisting of a lower total dose of radiotherapy delivered in five fractions of radiation. FAST has also laid the groundwork for the FAST-Forward trial, testing an even shorter treatment course of five fractions of breast radiotherapy delivered in a single week, which is likely to become a UK standard for patients with early breast cancer.

"People are increasingly living longer with their cancer thanks to smarter, kinder treatments - so establishing long-lasting safety of treatments is of utmost importance in order to help them live well with the condition."

Professor Murray Brunt, Professor of Clinical Oncology at the University Hospitals of North Midlands and University of Keele, who is joint first author of the study, said:

"The FAST trial identifies a five-fraction once-a-week regimen that is equivalent to daily treatment over the same time period. The follow-up to 10 years is important in establishing the principle of a five-treatment option.

"For patients unable to attend daily this offers an alternative much more convenient once-a-week treatment option that is attractive to both patients and their carers."

Joyce Charlton volunteered to be part of the FAST trial while being treated for breast cancer at the University Hospitals of North Midlands in Stoke-on-Trent. She commented:

"I was diagnosed with breast cancer in 2005, when I was approaching my 66th birthday. My oncologist, Professor Murray Brunt, encouraged me to join the FAST trial. I was scared and nervous at the time but, looking back, I can confidently say joining the trial was the best decision I could have made.

"After undergoing surgery, I received one of the shorter radiotherapy courses and went into hospital once a week for five weeks. I felt tired, but didn't experience any notable discomfort immediately after treatment. A few months later, my scans came back clear and I have remained cancer-free ever since."

Professor Arnie Purushotham, Cancer Research UK's senior clinical adviser, said:

"Sparing women unnecessary treatment is always good news. And this study in women with early stage breast cancer, shows that a lower dose given weekly should be just as effective for some patients as a higher weekly dose.

"Daily visits to hospital can be difficult for some patients who may be frail, have other illnesses, or live far from hospital. Ultimately, it's important that we keep doing research which can give patients a better quality of life."

WHAT:

An investigational vaccine, mRNA-1273, designed to protect against SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), was generally well tolerated and prompted neutralizing antibody activity in healthy adults, according to interim results published online today in The New England Journal of Medicine. The ongoing Phase 1 trial is supported by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. The experimental vaccine is being co-developed by researchers at NIAID and at Moderna, Inc. of Cambridge, Massachusetts. Manufactured by Moderna, mRNA-1273 is designed to induce neutralizing antibodies directed at a portion of the coronavirus "spike" protein, which the virus uses to bind to and enter human cells.

The trial was led by Lisa A. Jackson, M.D., MPH, of Kaiser Permanente Washington Health Research Institute in Seattle, where the first participant received the candidate vaccine on March 16. This interim report details the initial findings from the first 45 participants ages 18 to 55 years enrolled at the study sites in Seattle and at Emory University in Atlanta. Three groups of 15 participants received two intramuscular injections, 28 days apart, of either 25, 100 or 250 micrograms (mcg) of the investigational vaccine. All the participants received one injection; 42 received both scheduled injections.

In April, the trial was expanded to enroll adults older than age 55 years; it now has 120 participants. However, the newly published results cover the 18 to 55-year age group only.

Regarding safety, no serious adverse events were reported. More than half of the participants reported fatigue, headache, chills, myalgia or pain at the injection site. Systemic adverse events were more common following the second vaccination and in those who received the highest vaccine dose. Data on side effects and immune responses at various vaccine dosages informed the doses used or planned for use in the Phase 2 and 3 clinical trials of the investigational vaccine.

The interim analysis includes results of tests measuring levels of vaccine-induced neutralizing activity through day 43 after the second injection. Two doses of vaccine prompted high levels of neutralizing antibody activity that were above the average values seen in convalescent sera obtained from persons with confirmed COVID-19 disease.

A Phase 2 clinical trial of mRNA-1273, sponsored by Moderna, began enrollment in late May. Plans are underway to launch a Phase 3 efficacy trial in July 2020.

The cover for issue 28 of Oncotarget features Figure 5, "TMEM165 expression levels alters N-linked glycosylation," by Murali, et al., and reported that the TMEM165 protein was not detected in non-malignant matched breast tissues and was detected in invasive ductal breast carcinoma tissues by mass spectrometry.

The hypothesis is that the TMEM165 protein confers a growth advantage to breast cancer.

The authors created a CRISPR/Cas9 knockout of TMEM165 in the human invasive breast cancer cell line MDAMB231.

Furthermore, they find that TMEM165 expression alters the glycosylation of breast cancer cells and these changes promote the invasion and growth of breast cancer by altering the expression levels of key glycoproteins involved in the regulation of the epithelial to mesenchymal transition such as E-cadherin.

These studies illustrate new potential functions for this Golgi membrane protein in the control of breast cancer growth and invasion.

"These studies illustrate new potential functions for this Golgi membrane protein in the control of breast cancer growth and invasion."

Dr. Karen L. Abbott from The University of Oklahoma Health Sciences Center, Department of Biochemistry and Molecular Biology said "Breast cancer is the most commonly diagnosed cancer in women."

The TMEM165 protein was identified by mass spectrometry in invasive breast carcinoma tissue with no detection in patient-matched adjacent normal breast tissues.

The authors analyzed TCGA breast cancer cases to examine TMEM165 expression levels in all molecular types of human breast cancer using UALCAN.

They found that TMEM165 is amplified across all types of breast cancer compared to normal breast tissue with IDC cases having the highest levels of TMEM165 expression.

In the present study, the authors report that TMEM165 is upregulated in human breast cancer cell lines and patient tumor tissues and increased expression of TMEM165 correlates with poor prognosis in breast cancer patients.

Collectively, the data demonstrate that overexpression of TMEM165 promotes EMT in breast cancer suggesting a novel role for TMEM165 as a driver of tumor invasion making it a prognostic marker and potential therapeutic target for breast cancer.

The Abbott Research Team concluded in their Oncotarget Research Paper, "we have expanded on our initial 2012 glycoproteomic study that was the first to identify TMEM165 protein as a potential biomarker for breast carcinoma. In this study, we have provided initial mechanistic studies that indicate that TMEM165 expression drives the growth and invasion of breast cancer. TMEM165 expression levels could be a potential prognostic marker for predicting DCIS cases that may progress to invasive disease. Larger prospective cohorts will need to be analyzed to determine the link between TMEM165 levels and the progression to IDC. We find that IDC patients with higher TMEM165 expression levels have reduced overall survival making this protein a target for the development of new therapeutic strategies to limit the progression of breast cancer."

A new molecular imaging approach utilizing 18F-FDG positron emission tomography (PET) and magnetic resonance imaging (MRI) can precisely identify the location of pain generators in chronic pain sufferers, often precipitating a new management plan for patients. This research was presented at the Society of Nuclear Medicine and Molecular Imaging 2020 Annual Meeting.

Pain is the most common reason to seek medical attention, and those who suffer from it outnumber those who suffer from cancer, heart disease and diabetes combined. According to the National Center for Complementary and Integrative Health, chronic pain affects nearly 50 million adults in the United States and costs the nation's healthcare system as much as $635 billion in total expenses, including imaging and treatment costs.

"In the past few decades, we have confirmed that anatomic-based imaging approaches, such as conventional MRI, are unhelpful in identifying chronic pain generators," said Sandip Biswal, MD, musculoskeletal radiologist and associate professor of radiology at Stanford University School of Medicine in Stanford, California. "We know that 18F-FDG PET has the ability to accurately evaluate increased glucose metabolism that arises from to acute or chronic pain generators. As such, in our study we examined PET/MRI as a potential solution to determine the exact molecular underpinnings of one's pain."

In the study, 65 chronic pain patients underwent 18F-FDG PET/MRI from head to foot. Maximum standardized uptake values and target-to-background ratios were measured using image analysis software. PET/MR images were evaluated by two radiologists to determine if increased 18F-FDG uptake occurred in the site of symptoms or in other areas of the body. Imaging results were then discussed with the referring physician, who determined whether a change in the pain management plan would follow.

Increased uptake of 18F-FDG in affected nerves and muscle was identified at the site of pain and other areas of the body in 58 out of 65 patients. This resulted in a mild modification of management plan (e.g., additional diagnostic test) for 16 patients and a significant modification for 36 patients (e.g., new invasive procedure suggested or ordered). In total, new management plans were implemented for 40 out of 65 patients, which had not been anticipated by the referring physician.

"The results of this study show that better outcomes are possible for those suffering from chronic pain," said Biswal. "This clinical molecular imaging approach is addressing a tremendous unmet clinical need, and I am hopeful that this work will lay the groundwork for the birth of a new subspecialty in nuclear medicine and radiology. Using this approach will require knowledge and expertise not only in nuclear medicine but also in musculoskeletal imaging, neuroradiology and potentially other fields, such as body imaging and pediatric radiology, where pain syndromes are important clinical problems."

Results from the first study using uEXPLORER to conduct total-body dynamic positron emission tomography (PET) scans in cancer patients show that it can be used to generate high-quality images of metastatic cancer. The research was presented at the Society of Nuclear Medicine and Molecular Imaging 2020 Virtual Annual Meeting on July 11-14.

While static PET provides a simple snapshot of radiopharmaceutical concentration, dynamic PET with tracer kinetic modeling can provide parametric images that show how tissue is actually behaving. Parametric images have the potential to better detect lesions and assess cancer response to therapy. This potential, however, has not been fully studied in the clinic because conventional PET scanners have a limited axial field-of-view and are not capable of simultaneous dynamic imaging of lesions that are widely separated in the body.

"The focus of our study was to test the capability of uEXPLORER for kinetic modeling and parametric imaging of cancer," explained Guobao Wang, PhD, associate professor and Paul Calabresi Clinical Oncology K12 Scholar in the department of radiology at the University of California (UC), Davis, in Sacramento, California. "Different kinetic parameters can be used in combination to understand the behavior of both tumor metastases and organs of interest such as the spleen and bone marrow. Thus, both tumor response and therapy side-effects can be assessed using the same scan."

A patient with metastatic renal cell carcinoma was injected with the radiotracer 18F-FDG and scanned on the uEXPLORER total-body PET/CT scanner. The static PET standardized uptake value (SUV) was calculated and kinetic modeling was performed for regional quantification in 16 regions of interest, including major organs and multiple metastases. The glucose influx rate was calculated and additional kinetic modeling was implemented to generate parametric images of the kinetic parameters. The kinetic data were then used to explore tumor detection and tumor characterization.

Multiple metastases were identified on the dynamic PET/CT scan, confirming that it is feasible to perform total-body kinetic modeling and parametric imaging of metastatic cancer. Parametric images of glucose influx rate showed improved tumor contrast over SUV in general, and specifically led to improved visibility of cancer lesions detection in the liver. Total-body kinetic quantification also provided multi-parametric characterization of tumor metastases and organs of interest.

"Total-body dynamic imaging and kinetic modeling enabled by total-body PET have the potential to change nuclear medicine into a multi-parametric imaging method, where many different aspects of tissue behavior can be assessed in the same clinical setting--much like the information gained from different sequences in an MRI scan," said Ramsey D. Badawi, professor in the department of radiology and co-director of the EXPLORER molecular imaging center, UC Davis. "The total-body parametric imaging technique is not limited to 18F-FDG; it is applicable to all radiotracers. It is also not limited to cancer but can be broadly applied to evaluate disease severity and organ interactions in many other systemic diseases. We expect a profound impact in the field of nuclear medicine and molecular imaging."

Type 1 diabetes mellitus and type 2 diabetes mellitus (T2DM) are the two main types of diabetes, while T2DM accounts for 90%-95% of those with diabetes. T2DM is a vital risk factor for cerebral infarction, cardiovascular disease, blindness and kidney failure. The human gut microbiota plays a fundamental role in the diseases such as obesity and diabetes. Prebiotics are defined as non-digestible food ingredients which could promote selective increase in the growth, numbers, and activity of the microbial genera or species in the gut microbiota. Traditional Chinese herb medicine had a long history in Asian countries dating from several thousand years ago. One of the most intriguing medicinal plants is Cyclocarya paliurus, which has been used as the drug formulation in traditional Chinese medicine as well as the ingredient in healthy foods and dietary supplements in China. A recent study conducted an animal trial and examined the structural alterations of the gut microbiota and related metabolites profiles for understanding the specific mechanism of the Cyclocarya paliurus polysaccharide on T2DM.

"To our knowledge, this study is the first direct evidence in vivo by rat model that CP can modulate both the gut microbiota and the metabolites by multi-path to alleviate diabetes (Figure 1)." said Prof. Shaoping Nie, the corresponding author for this work. Cyclocarya paliurus polysaccharide treatment increased the beneficial bacteria genus Ruminococcaceae UCG-005 which was reported to be a key genus for protecting against diabetes. "Although previous studies showed that Cyclocarya paliurus polysaccharide lowered serum glucose and produced beneficial effects on T2DM in murine models, the effects of this polysaccharide on diabetic related gut microbiota, metabolites, inflammation, pancreatic injuries and serum hormones had not been wholly investigated", said Dr. Jielun Hu, the co-first author for this work. Then the amplicon library for the gut microbiota was paired-end sequenced (2 × 250 bp) on an Illumina MiSeq platform, and the UPLC-Triple-TOF/MS analysis of urine samples was carried out according to our established methods. "In our study, the higher abundance of beneficial bacteria (Ruminococcus) due to CP treatment was involved in the amelioration of type 2 diabetes. The change of the beneficial bacteria genus Ruminococcaceae UCG-005 was related to expression of Bax and Bcl-2 in pancreas related to inflammation. Cyclocarya paliurus polysaccharide also could improve 7 metabolism pathways closely with the nutrition metabolisms (amino acids and purine), and energy metabolism (TCA cycle).", said Prof. Shaoping Nie, the corresponding author for this work.

The mechanistic outcome of this study indicated the specific mechanism for using dietary polysaccharides to alleviate type 2 diabetes through multi-path of gut microbiota and host metabolism, and provides important information for the potential use of the Cyclocarya paliurus polysaccharide for prevention or intervention of type 2 diabetes.

LOS ANGELES - A novel preclinical study by Keck Medicine of USC researchers, published in Arthritis & Rheumatology, reveals that a potential new opioid medication may have the ability to slow the progression of osteoarthritis while being less addictive than commonly prescribed opioid drugs.

The medication activates the kappa opioid receptor (KOR), which binds to opioid-like compounds in the central and peripheral nervous systems to alleviate pain, resulting in targeted pain relief with a reduced risk of addiction.

Previous research shows that some opioids that selectively activate only KORs relieve pain locally at the site of injury without crossing the blood brain barrier and inducing substance dependency, whereas commonly prescribed opioids that target other receptors in the brain are more addictive.

In this study, lead author Alexander Weber, MD, sports medicine physician and orthopaedic surgeon with Keck Medicine, and corresponding author Denis Evseenko, MD, PhD, vice chair for research and associate professor of orthopaedic surgery at the Keck School of Medicine of USC, locally administered a kappa opioid into arthritic mice knees and measured the progression of the disease in their joints.

The researchers confirmed that the medication effectively alleviated pain, however findings also suggest that the medication prevented the loss of cartilage, the connective tissue between the joins that pads bones, and slowed the progression of osteoarthritis.

"Arthritis affects nearly a quarter of adults in the United States, many of whom take addictive opioids to manage their pain. The implications of this study may someday alter how we provide orthopaedic care to significantly reduce the number of patients experiencing long-term pain and addiction," says Weber.

More research is needed to advance toward human clinical trials, which are paramount as treatment and pain management options for osteoarthritis are limited.

"We hope that the findings of our study will lay the foundations for clinical research to further current understandings of the relationship between kappa opioids and osteoarthritis in humans to improve clinical care and quality of life," says Evseenko.

Blood transfusion, if performed promptly, is a potentially life-saving intervention for someone losing a lot of blood. However, blood comes in several types, some of which are incompatible with others. Transfusing an incompatible blood type can severely harm a patient. It is, therefore, critical for medical staff to know a patient's blood type before they perform a transfusion.

There are four major blood types--O, A, B, and AB. These types differ based on the presence or absence of structures called A antigens and B antigens on the surfaces of red blood cells. Blood can be further divided into positive and negative types based on the presence or absence of D antigens on red blood cells. Medical professionals usually tell a patient's blood type with tests involving antibodies against the A and B antigens. When antibodies recognize the corresponding antigens, they bind to them, causing the blood cells to clump together and the blood to coagulate. Thus, specific antigen-antibody combinations tell us what the blood type of a blood sample is.

Yet, while the concept sounds straightforward, the equipment and techniques required are often very specialized. Tests, therefore, are non-portable, have high personnel cost, and can take over half an hour to yield results. This can prove problematic in several types of emergency situations.

Aiming to solve these problems, a team of scientists at Japan's Tokyo University of Science, led by Dr Ken Yamamoto and Dr Masahiro Motosuke, has developed a fully automated chip that can quickly and reliably determine a patient's blood type. In the words of Dr Motosuke, he and his colleagues "have developed a compact and rapid blood-typing chip which also dilutes whole blood automatically."

The chip contains a micro-sized "laboratory" with various compartments through which the blood sample travels in sequence and is processed until results are obtained. To start the process, a user simply inserts a small amount of blood, presses a button, and waits for the result. Inside the chip, the blood is first diluted with a saline solution and air bubbles are introduced to promote mixing. The diluted blood is transported to a homogenizer where further mixing, driven by more intensely moving bubbles, yields a uniform solution. Portions of the homogenized blood solution are introduced into four different detector chambers. Two chambers each contain reagents that can detect either A antigens or B antigens. A third chamber contains reagents that detect D antigens and a fourth chamber contains only saline solution, with no reagent, and serves as a negative control chamber in which the user should not observe any results. Antigen-antibody reaction will cause blood to coagulate, and by looking at which chambers have coagulated blood, the user can tell the blood type and whether the blood is positive or negative.

Further, the user does not require specialized optical equipment to read the results. The design of the detector chambers allows the easy identification of coagulated blood with the naked eye. The device is also highly sensitive and can even detect weak coagulation.

During testing, the research team screened blood samples from 10 donors and obtained accurate results for all 10 samples. The time needed to determine a single sample's blood type was only five minutes.

Reflecting on the potential benefits of his team's invention, Dr Motosuke remarks, "The advancement of simple and quick blood test chip technologies will lead to the simplification of medical care in emergency situations and will greatly reduce costs and the necessary labor on parts of medical staff." Given the highly portable nature of the chip, Professor Motosuke also speculates that it could be used during aerial medical transport and in disaster response settings. This is a chip that has the potential to change the way emergency medical support is given.

People who have or had COVID-19 symptoms are more likely to develop general psychiatric disorders and are lonelier, with women and young people more at risk, says a just-published study co-authored at Cambridge Judge Business School.

Having a job and living with a partner are significant protective factors against general psychiatric disorders and loneliness, says the study in the journal Psychiatry Research, based on 15,530 UK respondents, which is described as the first such large-scale, nationally representative survey in a developed country.

Although there has been previous research on specific coronavirus-related disorders such as anxiety, depression and insomnia, prior to this research we knew "little about the broader psychological impact of the pandemic on a wider population", says the study in the journal's September 2020 issue.

"Only focusing on specific disorders underestimates the psychiatric burdens of the pandemic in more subtle forms and overlooks the needs for psychiatric care of the people who have not been clinically diagnosed," the study says.

"Although the minor psychiatric disorders are often less urgent concerns of the public health policies, they are not negligible given the large proportion of the population that have been affected," says the study co-authored by Lambert Zixin Li of Stanford University, who holds an MPhil in Innovation, Strategy & Organisation from Cambridge Judge Business School (MPhil 2018), and Senhu Wang, a Research Fellow at the Centre for Business Research at Cambridge Judge Business School, who holds a PhD in Sociology from the University of Cambridge.

The study measures general psychiatric disorders based on the 12 items in the widely accepted General Health Questionnaire, which looks at factors ranging from depressive anxiety symptoms to confidence to overall happiness, while loneliness was assessed by a question adapted from the English Longitudinal Study on Aging about how often respondents felt lonely in the previous four weeks.

"Loneliness is linked to long-term health outcomes including all-cause mortality, so public health policies need to be aware of the (mental) health consequences of the disease control measures," the study says.

The research found that 29.2 per cent of all respondents (representing the general British population) scored '4' (the "caseness" or clinical referral threshold) or more on a five-point scale for general psychiatric disorders, while 35.86 per cent of respondents sometimes or often feel lonely; further analysis of the results showed that those who have or had coronavirus symptoms were more likely to have such disorders or feel lonely.

"People with current or past COVID-19 symptoms were perhaps more likely to develop general psychiatric disorders because they are more anxious about infection, and their greater loneliness may reflect the fact that they were isolated from family and friends," says co-author Senhu Wang of the Centre for Business Research at Cambridge Judge.

Women and young people (aged 18-30) who responded were significantly more at risk from general psychiatric disorders and loneliness, which the study says may reflect the fact that, compared to older people, these younger people's social and economic lives are more disrupted by the public health crisis.

Having a job and living with a partner are both "significant protective factors", said the study, which suggested further research into how social support from work and family buffer the psychological impacts of a pandemic.

The survey was conducted toward the end of April, at a time when there were around 23,000 coronavirus-related deaths in the UK. The study found no significant differences across different UK regions on either general psychiatric disorder or loneliness.

"Future research and public health policies need to move beyond specific psychiatric disorders to attend to the general psychiatric disorders and loneliness of a larger proportion of the population," the study concludes. "They need to pay special attention to vulnerable populations including women, the younger, the unemployed, those not living with a partner, and those who have or had COVID-19 symptoms.

"A pandemic like COVID-19 could exaggerate social disparities in mental health in subtle ways, calling for research on effective interventions such as mindfulness, mediation-based stress reduction and timely provision of psychiatric services."

-- But there is still an opportunity to substantially reduce the death toll by prioritising the most critical services, specifically antiretroviral therapy for HIV, timely TB diagnosis and treatment, and provision of long-lasting insecticide-treated nets for malaria, researchers say.

Some low- and middle-income countries (LMICs) could see HIV, tuberculosis (TB), and malaria deaths increase by as much as 10%, 20%, and 36% respectively over the next 5 years due to the disruption of health services caused by the COVID-19 pandemic and its response, according new modelling research published in The Lancet Global Health journal.

Modelling the public health impact of COVID-19 on HIV, TB, and malaria in LMICs over the next 5 years, researchers estimate that in areas heavily affected by these major infectious diseases, the impact of COVID-19 disruption on years of life lost (the number of years a person would have been expected to live had they not died of a particular cause) could, in the worst case, be of a similar scale to the direct impact of the pandemic itself.

The COVID-19 pandemic has the potential to cause substantial disruptions by overwhelming already fragile health systems, or through response measures limiting routine programme activities and care-seeking, and interrupting medical supply chains. But maintaining core services for HIV, TB, and malaria--specifically access to antiretroviral therapy (ART), timely TB diagnosis and treatment, and early resumption of the distribution of long-lasting insecticide-treated nets (LLINs) and antimalarial treatment--could largely mitigate the broader health impact of the COVID-19 pandemic, researchers say.

However, the authors caution that predicting the true impact of the ongoing COVID-19 pandemic and its response on other diseases is fraught with difficulty, especially when so much remains unknown about the virus and the extent to which other disease programmes may be disrupted, and how this might impact population health. They flag that their study aims to quantify the potential scale of the impact of COVID-19, and to guide how it could be minimised, rather than provide precise estimates.

Malaria deaths worldwide have reduced by half since 2000, but progress has stalled as mosquitoes and parasites gain resistance to treatment. Around 94% of deaths occur in sub-Saharan Africa where malaria claimed an estimated 380,000 lives in 2018. Similarly, global HIV/AIDS deaths have halved in a decade driven by the availability of ART. In 2019, around 690,000 people died from the disease worldwide, the vast majority in LMICs. An estimated 49 million lives were saved through TB diagnosis and treatment between 2000 and 2015, but the disease still claimed the lives of 1.8 million people in 2018--with over 95% of these deaths occurring in LMICs [2].

"The COVID-19 pandemic and actions taken in response to it could undo the some of the advances made against major diseases such as HIV, TB, and malaria over the past two decades, compounding the burden caused by the pandemic directly", says Professor Timothy Hallett from Imperial College London, UK, who co-led the research. "In countries with a high malaria burden and large HIV and TB epidemics, even short-term disruptions could have devastating consequences for the millions of people who depend on programmes to control and treat these diseases. However, the knock-on impact of the pandemic could be largely avoided by maintaining core services and continuing preventative measures." [1]

He continues, "Our findings underscore the extraordinarily difficult decisions facing policy makers. Well managed, long-term suppression measures could avert the most COVID-19 deaths. But if these interventions are not well managed, they could cause people to stay away from hospitals and clinics and force public health programmes to be cancelled, leading to a large spike in deaths from other major infectious diseases that had been coming under control." [1]

Discussing the implications of the findings in a linked Comment, Peter Sands, Executive Director of The Global Fund to Fight AIDS, Tuberculosis and Malaria, Geneva, Switzerland (who was not involved in the study) says, "The knock-on impact on HIV, tuberculosis, and malaria could potentially be even worse than this study suggests, and in some countries, it could be even worse than the direct impact of COVID-19. The Global Fund conducts a biweekly qualitative survey across the more than 100 countries in which it invests; the latest published results suggest that 85% of HIV, 78% of tuberculosis, and 73% of malaria programmes are being disrupted. 18% of HIV programmes, 17% of tuberculosis programmes, and 19% of malaria programmes are experiencing high or very high disruption."

He adds, "In countries heavily affected by HIV, tuberculosis, and malaria, COVID-19 could result in many years of hard-won gains being reversed. We cannot let this happen. We need more resources and decisive action, and we must measure success not just in terms of minimising the direct impact of COVID-19, but in terms of minimising its total impact, including the knock-on impact on HIV, tuberculosis, and malaria."

In this study, the researchers assumed a basic reproductive number (R0; the average number of people each individual with the virus is likely to infect) of 3 to develop four different policy response scenarios to the COVID-19 pandemic--no action, mitigation (which represents a 45% reduction in R0 for 6 months using interventions such as physical distancing), suppression-lift (a 75% reduction in R0 for 2 months), or suppression a 75% reduction in R0 for 1 year; see table 1). Then they used transmission models of HIV, TB, and malaria to estimate the additional impact on health that could be caused in different settings, either by COVID-19 interventions limiting routine programme activities, or due to COVID-19 cases overburdening the health system (table 2, figure 2).

Overall, the findings suggest that the impact of the pandemic varies according to the extent to which interventions against COVID-19 cause long disruptions to activities, and how successfully those measures reduce transmission of SARS-CoV-2, and avoid the health system being overwhelmed.

The greatest impact on HIV is projected to be from interruption to the supply and administering of ART, which may occur during times of high health system demand. In the worst case scenario, assuming no action or suppression-lift, countries with high rates of HIV typical in parts of southern Africa (20% prevalence among 15-49 year olds in 2018), could see up to 10% more deaths due to HIV over the next 5 years than would occur without COVID disruptions--equivalent to 612 additional HIV deaths per million population in 2020-2024. The researchers suggest that offering individuals receiving ART multi-month prescriptions or home delivery could ensure they can access treatment even in periods of highest health system demand.

For TB, the greatest impact is predicted to be from reductions in timely diagnosis and treatment of new cases, which could result from long periods of COVID-19 containment measures limiting access to services. In the worst case scenario, assuming suppression in countries with a very high burden typical in southern Africa (520 new cases per 100,000 population in 2018), TB deaths could rise by as much as 20% over the next 5 years (equivalent to 987 additional TB deaths per million population in 2020-2024) compared with when services are functioning normally.

The model predicts that the greatest impact on malaria burden could result from interruption of planned net campaigns, which usually take place every 3 years. In the worst case, with COVID-19 disruptions coinciding with the malaria transmission season and planned LLIN distribution, malaria deaths could increase by 36% over the next 5 years--equivalent to 474 additional malaria deaths per million population in 2020-2024.

"Many of the gains made in malaria control over the past decade have been due to distribution of long-lasting insecticide-treated nets in sub-Saharan Africa where the vast majority of malaria deaths occur. However, the COVID-19 pandemic will likely disrupt these distributions in 2020, resulting in more malaria deaths", says co-lead author Dr Alexandra Hogan from Imperial College London, UK. "Routine preventative measures must be prioritised, ensuring mosquito net distribution campaigns and prophylactic treatments, such as mass drug distribution and seasonal malaria chemoprevention, are maintained." [1]

A single dose of the flu drug baloxavir marboxil can reduce the spread of the illness within households, new research concludes.

A study examining 752 household contacts of 545 patients with the flu found that flu infections were much less common in household members who received the drug than among those who received a placebo. Only 1.9% of uninfected household contacts who took a single dose of baloxavir marboxil came down with the flu, compared with 13.6% of those who received the placebo.

"This trial established that baloxavir, if taken within a day or so after exposure, is highly effective for preventing influenza illness in households, a high-risk setting for virus transmission," said researcher Frederick G. Hayden, MD, of the University of Virginia School of Medicine. "The findings indicate that baloxavir prophylaxis should prove effective for prevention in other circumstances, such as outbreaks in nursing homes and healthcare facilities, although formal studies will need to be undertaken."

Reducing Influenza Spread

The double-blind study found that baloxavir marboxil, sold under the brand name Xofluza, was effective in adults, children and those at high-risk, regardless of whether they had received the flu vaccine. The frequency of adverse events, such as headaches and nausea, was similar among those who received the drug (22.2%) and those who received placebos (20.5%). There were no deaths in either group.

Hayden, a professor emeritus in UVA's Division of Infectious Diseases and International Health, was also part of a research team that published a month ago in Lancet Infectious Diseases that baloxavir treatment shortened the duration of influenza and reduced complications in adults and adolescents at high risk of complications. A single dose of the drug was as effective as a five-day course of oseltamivir (Tamiflu), the researchers concluded.

The federal Food and Drug Administration has approved baloxavir marboxil to treat flu within 2 days of symptom onset in people 12 years and older and those at high risk of developing complications. Its approval in 2018 marked the first novel flu drug in 20 years. The FDA is reviewing baloxavir applications for both treatment in children aged 1-11 years and for prophylaxis.

Findings Published

The researchers have published their findings in the prestigious New England Journal of Medicine. The study's authors were Hideyuki Ikematsu, Hayden, Keiko Kawaguchi, Masahiro Kinoshita, Menno D. de Jong, Nelson Lee, Satoru Takashima, Takeshi Noshi, Kenji Tsuchiya and Takeki Uehara. Hayden disclosed that he has received fees for serving on a data safety and monitoring board, paid to the UVA School of Medicine, from Celltrion Healthcare, GlaxoSmithKline and Vaccitech. He has served as a consultant and received travel support from F. Hoffmann-La Roche and Shionogi, and he has served as a consultant for Cidara Therapeutics, Fujifilm Corp., Genentech, Gilead Sciences, Janssen Pharmaceuticals, MediVector, Regeneron Pharmaceuticals, resTORbio, SAB Biotherapeutics, Versatope, Vir and Visterra. A full list of disclosures is included in the paper.

Meditation was linked to lower cardiovascular risk in a data analysis by Veterans Affairs researchers and colleagues.

The results appeared online June 30 in the American Journal of Cardiology.

Previous studies have suggested that meditation may have beneficial effects on a number of conditions. A 2017 American Heart Association scientific statement suggests that meditation may be of benefit for cardiovascular risk reduction. Data show that it may help with blood pressure, cholesterol level, quitting smoking, and overall cardiovascular health. However, this connection is far from definitive. By using a large national database with many participants, the authors of the new study sought further evidence on how meditation impacts cardiovascular risk.

Lead researcher Dr. Chayakrit Krittanawong--of the Michael E. DeBakey VA Medical Center, Baylor College of Medicine, and the Icahn School of Medicine at Mount Sinai--and his colleagues studied data from the National Health Interview Survey, conducted annually by the National Center for Health Statistics. It collects information on a wide range of health topics from a nationally representative sample.

The researchers looked at data on more than 61,000 survey participants. Of those, almost 6,000 (nearly 10%) said they participated in some form of meditation.

The researchers found that people who meditated had lower rates of high cholesterol, high blood pressure, diabetes, stroke, and coronary artery disease, compared with those who did not meditate.

The greatest difference was in coronary artery disease. Those who meditated were 51% as likely as those who didn't to have the disease. The prevalence of other cardiovascular risks in the meditation group compared with the non-meditation group was 65% for high cholesterol, 70% for diabetes, 76% for stroke, and 86% for high blood pressure.

The researchers controlled for other factors connected to cardiovascular risk, such as age, sex, cigarette smoking, and body mass index. After adjusting for these factors, the effect of meditation was still significant.

Many types of meditation exist. Most focus on attention and awareness. Meditation has been shown to increase physical and mental relaxation. "I believe in meditation, as it can give us a sense of calm, peace, and stress reduction, leading to improvement of our emotional well-being," explained Krittanawong.

Practicing meditation has been linked to decreased stress, greater mindfulness, and improved psychological health. It may even lead to long-term functional and anatomical changes in the brain. Meditation is also simple, cost-effective, and low-risk.

Krittanawong and colleagues did note several limitations to the study. First, the survey did not capture what type of meditation people were using. Some types of meditation may offer more cardiovascular benefit than others, say the researchers. The survey also did not ask about the duration or intensity of that meditation. It is possible that those who practice longer and more frequently will get more benefit, but the study cannot measure these effects.

Also, the researchers cannot definitively say that meditation directly decreases cardiovascular risk. It could be that people who are in better cardiovascular health to begin with are more likely to practice meditation, rather than the other way around.

Other life activities might also obscure the link between meditation and cardiovascular health. The researchers found factoring in alcohol consumption and physical activity lowered the significance of the relationship between meditation and cardiovascular risk.

Considering all these factors, the researchers concluded that meditation is "probably" associated with lower prevalence of cardiovascular risk. Krittanawong notes that, while the results suggest that meditation can improve cardiovascular health, "we would need a powerful study such as a clinical trial to determine whether meditation could benefit cardiovascular health in veterans."

Meanwhile, the study adds to a growing body of research on the potential benefits of meditation, they say.

Researchers from Sechenov University in collaboration with colleagues from Germany, Greece and Russia reviewed scientific articles on the role of zinc in the prevention and treatment of viral infections and pneumonia, with projections on those caused by SARS-CoV-2. The results were published in the International Journal of Molecular Medicine.

Zinc is necessary for normal metabolism and functioning of the reproductive, cardiovascular and nervous systems, but it is also important for the immune system, in particular for the proliferation and maturation of white blood cells (some of them are able to capture and digest microorganisms, and others - to produce antibodies). In addition, zinc is involved in the regulation of inflammation. Thus, normal levels of zinc support human resistance to inflammatory and infectious diseases.

'According to the current estimates, the risk of zinc deficiency is observed in more than 1.5 billion people in the world. In Russia, deficiency of this element occurs in 20-40% of the population; in some regions it reaches 60%. Given the crucial role of zinc in regulation of immunity, one can propose that its insufficiency may be considered as a risk factor for infectious diseases,' said the research leader, head of the Laboratory of Molecular Dietetics at Sechenov University, Professor Anatoly Skalny.

The scientists reviewed the results of studies on the use of zinc-containing drugs for increasing immunity and preventing viral infections, including SARS-CoV-2 that caused COVID-19 outbreak this year. Previous studies showed that zinc and its binding substances can slow down the work of RNA polymerase (an enzyme that synthesises viral RNA molecules) of coronaviruses and suppress their spread in the body. One of the substances that stimulate the cellular zinc uptake, chloroquine, has already been tested on patients with SARS-CoV-2, but its strong side effects make it necessary to look for other compounds with a similar effect or use zinc separately. However, both options have not been sufficiently studied or tested yet.

Observations of the development of other viruses, such as rhinoviruses (this family includes pathogens of acute respiratory diseases), show that an increase in the level of zinc in cells suppresses replication (reproduction) of the virus and stimulates production of interferon alpha, which has an antiviral activity.

In addition, zinc deficiency is considered as one of the risk factors for the development of pneumonia: it increases the susceptibility to infectious agents and the disease duration. Several studies show the effectiveness of zinc-containing drugs in decreasing severity and duration of symptoms and reducing the prevalence of pneumonia. However, in general, data on the use of zinc as a therapy, rather than prevention, are contradictory.

Another possible application of zinc is modulation of inflammation. Existing data show that zinc ions have an anti-inflammatory effect, reducing damage to lung tissue in pneumonia. Zinc also helps the body resist bacteria, and bacterial pneumonia frequently occurs in patients with secondary viral infections.

'A recent study conducted by scientists from the USA confirmed our assumptions, demonstrating the effect of zinc intake on the risk of a severe course and the need for artificial ventilation in patients with COVID-19,' said Alexey Tinkov, coauthor of the article, a leading researcher at the Laboratory of Molecular Dietetics at Sechenov University.

Therefore, according to current research, adequate zinc status can bring down the likelihood of infectious respiratory diseases, pneumonia and its complications. There are also indirect indications that zinc intake may be effective in the fight against coronavirus disease (COVID-19), but there is still insufficient data for recommendations.

Nursing homes are facing extreme challenges in the midst of the COVID-19 pandemic. Two Regenstrief Institute and Indiana University -- including IUPUI -- faculty members lay out their case that meaningful partnerships between acute care hospitals and nursing facilities can support better quality of care for people who live in the facilities.

Regenstrief research scientist and Indiana University School of Medicine Associate Professor of Medicine, Kathleen T. Unroe, M.D., MHA, and Regenstrief research scientist and Professor at IU Richard M. Fairbanks School of Public Health at IUPUI, Joshua Vest, PhD, MPH, wrote an editorial published in the Journal of the American Geriatrics Society. In it, they stated the benefits of collaboration between health systems and nursing facilities.

The authors highlighted how health systems can support nursing home staffing, which is critical to delivering quality care and a constant challenge, even in normal situations. COVID-19 has exacerbated the challenges of maintaining staffing and, in some instances, created an additional need.

They also discussed how collaboration can facilitate the necessary virus testing within nursing homes and highlighted policy and economic drivers for better cooperation.

"Closer relationships can help reduce hospital readmissions and improve safety of transitions of care, which can have a detrimental impact on people living in long-term care facilities," said Dr. Unroe. "Health systems who have invested resources in developing relationships with nursing facilities are better able to ramp up and provide critical support during a crisis." Dr. Unroe led a Centers for Medicare and Medicaid demonstration project that successfully lowered the rate of avoidable hospitalizations in Indiana nursing homes.

"The pandemic is an opportunity to build on existing relationships between health systems and nursing facilities, as well as forge new ones," said Dr. Vest. "Access to testing, data sharing and leveraging of resources are all important to improve care during the COVID-19 crisis, and closer partnerships will provide facilitation and ultimately improve care for a population that is especially vulnerable during this time." Dr. Vest leads the Fairbanks School of Public Health's Center for Health policy, which conducts research and evaluates health system performance. His research focuses on technologies that enable the sharing of data between organizations.