Body

East Hanover, NJ. July 29, 2020. Researchers in regenerative rehabilitation conducted a pilot study of a new approach to the treatment of treatment-resistant shoulder pain in wheelchair users with spinal cord injury (SCI) and rotator cuff disease. Results were encouraging in the study of six participants who received a combination of a single injection of platelet-rich plasma (PRP) into the supraspinatus tendon and a home-based exercise program of stretching and strengthening.

The article, "Ultrasound-guided platelet-rich plasma injection for the treatment of recalcitrant rotator cuff disease in wheelchair users with spinal cord injury: A pilot study", (doi: 10.1080/10790268.2020.1754676) was epublished ahead of print on May 7, 2020 by the Journal of Spinal Cord Medicine.

The authors are scientists with expertise in regenerative rehabilitation and SCI rehabilitation: Trevor Dyson-Hudson, MD, and Nathan Hogaboom, PhD, at Kessler Foundation, Reina Nakamura, DO, of the University of Michigan, Alon Terry, MD, of Summit Medical Group, Summit, NJ, and Gerard Malanga, MD, from Kessler Institute for Rehabilitation and the New Jersey Regenerative Institute.

The study was conducted at the Derfner-Lieberman Laboratory for Regenerative Rehabilitation Research in the Center for Spinal Cord Injury Research at Kessler Foundation, both under the direction of Dr. Dyson-Hudson, MD. Dr. Hogaboom is co-director of the Derfner-Lieberman Laboratory.

The objective of the pilot study was to evaluate the safety and treatment effect of PRP injection in wheelchair users with SCI and shoulder pain unresponsive to conservative treatment. Six male participants competed the study (3 paraplegia; 3 tetraplegia). All were wheelchair users with a history of chronic SCI (26.7 year ± 11.1 years) and bilateral shoulder pain (> 6 months).

Treatment consisted of bilateral injection of PRP into the shoulder joints. After a 24-hour rest period, participants started a stretching regimen that transitioned to a strengthening protocol at one-month post injection. Followup was conducted at 4, 8, 12, and 24 weeks, consisting of ultrasound evaluation, physical examination, and assessment of pain level. All participants reported decreased pain, with three describing their pain as 'much improved' and one 'very much improved'. No adverse effects were reported.

In this population, shoulder pain is a common cause of disability that hinders functional independence, according to Dr. Dyson-Hudson, director of the Center for Spinal Cord Research. While surgery is an option for pain that fails to respond to conservative treatment, drawbacks include the costs and the functional limitations during prolonged post-operative recovery.

"Conservative treatments that provide alternatives to surgery are needed for this population," he emphasized. "Injection of PRP, which may promote healing of the injured tendon, combined with a graduated exercise program, is a potential option for these individuals. Based on our pilot study, a larger randomized controlled trial is warranted."

Hamilton, ON (July 27, 2020) - As provinces across Canada are deciding how to restart schools during the pandemic, a research review has found children are not a major source of transmission of COVID-19.

A second review has found strain on families, particularly women with children.

The rapid evidence reviews were completed by the National Collaborating Centre for Methods and Tools (NCCMT) hosted by McMaster University and funded by the Public Health Agency of Canada. The reviews are from the centre's rapid evidence service, which provides high quality summaries of research evidence to support public health professionals and policy makers in making evidence-based decisions.

The review of the role of daycare centres and schools in COVID-19 transmission had consistent findings across all research evidence available by July 20, 2020.

"The bottom line thus far is that children under 10 years of age are unlikely to drive outbreaks of COVID-19 in daycares and schools and that, to date, adults were much more likely to be the transmitter of infection than children," said Sarah Neil-Sztramko, an assistant professor with the NCCMT and McMaster's Department of Health Research Methods, Evidence, and Impact.

The review found among children who were infected, transmission was traced back to community and home settings or adults, rather than amongst children within daycares or schools even in jurisdictions where schools remained open or have since reopened.

"Within household clusters, adults were much more likely to be the index case than children. The quality of evidence is moderate, and the findings are consistent," the authors say.

The review which included consideration of 33 research publications may be found here.

The second research review by the NCCMT found that families are undergoing considerable stress during the pandemic.

"We found that families are under strain, especially female caregivers and children, with increasing gender gaps in employment and household labour and poor mental health outcomes in children," said Neil-Sztramko.

The review included 38 publications and found gender gaps in employment between women and men have grown during the pandemic, with women more than men experiencing reduced hours and job losses.

Women and higher-income earners are more likely to be in occupations that could be done from home, and among parents who can work from home, mothers reduced their work hours more than fathers, particularly mothers of primary school-aged children.

This review may be found here.

Maureen Dobbins, scientific director of the NCCMT and a professor of McMaster's School of Nursing, added: "We recognized early on that there was a significant need to summarize the overwhelming amount of research evidence emerging on COVID-19, appraise its quality, and distribute widely that evidence to support public health decision making in Canada.

"As a former public health nurse who has encouraged the use of the best available evidence research in public health decision making for decades, this is one contribution to ensure public health measures in Canada being informed by current and best evidence."

PHILADELPHIA -- Black and Hispanic pregnant women in Philadelphia are five times as likely as white and Asian women to have been exposed to the novel coronavirus, according to a new study led by Scott Hensley, PhD, an associate professor of Microbiology in the Perelman School of Medicine at the University of Pennsylvania, and Karen Marie Puopolo, MD, PhD, an associate professor of Pediatrics and neonatologist at the Children's Hospital of Philadelphia. The study was published today in Science Immunology.

"Pregnant women are fairly representative of community exposure, and these data provide more evidence, on top of what we already know with COVID-19, that health and socio-economic equity are inextricably linked," Hensley said, "Hopefully, this will help lead to policies that address these inequities."

The research team measured levels of SARS-CoV-2 antibodies to estimate rates of exposure to the novel coronavirus in pregnant women cared for at two Philadelphia hospitals. They found that, overall, 6.2 percent of these women possessed antibodies to the virus, but with significant variation across racial and ethnic groups -- 9.7 percent in Black women, 10.4 percent in Hispanic/Latina women, 2.0 percent in White/Non-Hispanic women, and 0.9 percent in Asian women.

Researchers said these data can inform clinical practice and care for pregnant women during the coronavirus pandemic, and be used to better understand the prevalence of the virus in the community, and how socio-economic factors and inequities may affect its spread.

"Identifying the disparity in virus exposure will ideally help lead to the discovery of what is causing these differences, including factors rooted in systemic racism, and inform public health measures aimed at preventing further infections," Puopolo said.

As of June 2020 - the time period encompassed in this study - there were 23,160 confirmed cases of COVID-19 in the city of Philadelphia, which has a population size of nearly 1.6 million people. This suggests an infection rate of approximately 1.4 percent, which is more than 4 times lower than the estimates based on the research team's serological data.

Researchers analyzed 1,293 women who gave birth between April and June at Pennsylvania Hospital and the Hospital of the University of Pennsylvania, which combined represent 50 percent of live births during that time in Philadelphia. The research team's serological test utilized a SARS-CoV-2 spike protein receptor binding domain antigen and a modified ELISA protocol. Researchers used samples stored at the Penn Medicine Biobank collected from 834 people prior to the pandemic and 31 people who recovered from known Covid-19 infections to test the efficacy of their antibody test. The researchers also tested samples from 140 pregnant women collected before the pandemic. Based on these data, the overall false positive rate is ~1.0 percent in the serological assay used for this study.

The researchers caution that the clinical meaning of the detected antibody remains unknown. Additionally, estimates of virus prevalence need to be interpreted carefully until studies directly comparing pregnant women and the general population are completed.

A group of researchers from Brazil, Denmark, Italy and Spain analyzed 884 samples of fungi of the genus Candida collected from 16 hospitals and found a significant number of clusters in more than one hospital. Clusters are groups of fungal isolates with identical DNA sequences. The discovery may point to the presence of more virulent and drug-resistant varieties.

The study, published
in the journal Frontiers in Cellular and Infection Microbiology, was supported by São Paulo Research Foundation - FAPESP .

Fungi, such as yeasts of the genus Candida, are part of the human gut microbiota - bacteria, archaea and other microorganisms that live in the digestive tract. They cause no problems when the host organism is healthy, but if imbalances occur due to chronic disease or therapeutic procedures involving long hospital stays, they may enter the bloodstream and cause severe, potentially lethal infections.

Candidemia is the most common fungal bloodstream infection in hospitalized patients. It mainly occurs in intensive care units (ICUs) and in patients that received organ transplants or treatment for some kinds of cancer, such as leukemia.

"We must monitor possible sources of infection even more carefully than usual at a time when so many critical COVID-19 patients are being hospitalized. Many remain in intensive care for two to three weeks and are exposed to antibiotics, immunomodulators, invasive medical procedures and/or dialysis," said Arnaldo Lopes Colombo, a professor in the Federal University of São Paulo's Medical School (EPM-UNIFESP) and the only Brazilian coauthor of the study.

Most Candida infections occur when the fungus breaks through the intestinal barrier and enters the bloodstream as a result of severe illness and a long hospital stay. Some infections, however, are due to breaches of hand hygiene protocols by health workers and careless handling of patients submitted to invasive medical procedures.

"These factors permit horizontal transmission among different patients, which explains the clusters of infections found in certain hospital wards and less frequently the clusters found in more than one institution," Colombo said.

In the 884 samples analyzed from 16 hospitals, the researchers identified 723 genotypes of three species: Candida albicans (534 samples), C. parapsilosis (282), and C. tropicalis (68). UNIFESP's hospital (Hospital São Paulo), the only representative not only of Brazil but also of Latin America in the study, displayed no significant differences from developed-country hospitals in terms of cluster formation frequency.

All the hospitals involved in the study have hospital infection control programs, which should theoretically reduce the number of cross-infections between patients. However, 78 isolates (11% of the total) were found to be clusters, with the same genetic profile infecting several patients. A majority of these clusters (45 or 57%) did not involve more than one hospital, but a small proportion of the total number of isolates (52 or 7.2%) involved different hospitals (21 in the same city and 31 in different cities).

Analysis

The analysis was led by Jesús Guinea at the Complutensian University of Madrid's Gregorio Marañon Health Research Institute (UCM-IISGM) in Spain.

Isolates were genotyped by species-specific microsatellite markers, which are repetitive DNA sequences usually several base pairs in length. The technique is not as precise as whole-genome sequencing but permits the analysis of many samples for a reasonable cost and with sufficient precision to differentiate samples.

In the future, the researchers will perform whole-genome sequencing on a group of isolates to confirm genetic similarity within clusters and refine the microsatellite marker methodology for genetic studies of Candida. In addition, they hope to determine what makes the strains that form clusters so virulent in order to develop more effective therapies.

"We've found that the strains involved in cluster episodes are better at producing biofilm, an extracellular matrix that binds to surfaces and protects them from inhospitable environments, in this case, the human immune system," Colombo said.

With communities throughout the United States combating surges in COVID-19 cases and hospitalizations, researchers at The University of Texas at Austin and Northwestern University have created a framework that helps policymakers determine which data to track and when to take action to protect their communities. The model specifies a series of trigger points to help local entities know when to tighten social distancing measures to prevent hospitals from being overrun by virus patients. The method also aims to minimize the economic impact to communities by suggesting the earliest times for safely relaxing restrictions.

The framework is described in a new paper out today in the Proceedings of the National Academy of Sciences.
The United States' continued high rate of infection means lawmakers around the country need to continue to make decisions about reinstating and relaxing social-distancing measures. Using hospital data, the new model lets local leaders know when it is time to tap the brakes on reopening versus easing restrictions.

For example, in Austin, Texas, the modelers applied this framework to help city leaders decide when to toggle between five different COVID-19 alert levels. The city is now tracking the daily number of new hospital admissions, and it recently tightened measures when the data surpassed the prescribed threshold.

"We developed this framework to ensure that COVID-19 never overwhelms local health care capacity while minimizing the economic and societal costs of strict social-distancing measures," said Lauren Ancel Meyers, a co-author of the paper and the director of The University of Texas COVID-19 Modeling Consortium.

Northwestern's Daniel Duque, the first author, said that "the approach provides clear indications of when measures should be enacted and relaxed to manage risk."

There are two key components to successfully implementing the strategy -- closely monitoring data about hospitalizations for COVID-19 and ensuring communities protect those most vulnerable to the disease.

"While many cities have implemented alert levels and new policies, our research may be the first to provide clear guidance for exactly what to track (hospital admissions data) and exactly when to act (strict thresholds)," said David Morton, chair and professor of industrial engineering and management sciences at Northwestern and a co-author of the paper. "Communities need to act long before hospital surges become dangerous. Hospital admissions data give an early indication of rapid pandemic growth, and tracking that data will ensure that hospitals maintain sufficient capacity."
In recent weeks, public health officials have expressed concerns that hospitalization data has been inconsistent, as the federal government moved the data to a new portal housed within the Department of Health and Human Services.

"COVID-19 hospitalization data is vital to tracking the changing pace of the pandemic and informing good decision-making," Meyers said.

The team also determined that preventing an unmanageable surge in hospitalizations requires adherence to strict social distancing for high-risk populations, known as cocooning. For example, the researchers estimated that failing to protect vulnerable populations more than doubles resulting deaths while also doubling the number of days in lockdown to prevent overrunning hospitals.

The framework combines two mathematical models: an underlying model that predicts how the pandemic will likely spread and an optimization model that uses admissions data from Austin hospital systems. It attempts to walk a fine line of preventing economic disaster and keeping hospital systems from becoming overwhelmed. Though the researchers used Austin data, the framework can easily be used by other communities with publicly available hospital admissions data.

"This is a general framework that can be used to design multistage triggers -- not just for lockdowns but for moving between phases -- exactly like we have done for Austin," Morton said. "Our framework has already guided policy changes in Austin."

Wealthier communities went from being the most mobile before the COVID-19 pandemic to the least mobile, while poorer areas have gone from the least mobile to the most mobile, according to a study by the University of California, Davis.

The study, published today in the Proceedings of the National Academy of Sciences, used anonymized data from mobile device location pings between January and April 2020 to find that social distancing in the United States varies strongly by income.

The study showed about a 25 percentage point jump of the wealthiest census tracts staying completely at home compared with a 10 percentage point increase in staying at home in the poorest communities.

"We found that before the pandemic, individuals in the wealthiest neighborhoods tended to be the least likely to stay completely at home on a given day," said lead author Joakim Weill, a graduate student with the UC Davis Department of Agricultural and Resource Economics. "But when the states of emergency came into play, individuals living in the wealthiest areas stayed home the most. It was a complete reversal."

The study does not determine the causes for this reversal, though the researchers highlight plausible mechanisms and note that lower-income communities tend to have more essential workers who also have less capacity to work at home compared to people in more affluent areas.

DOUBLE BURDEN

The results indicate a double burden of the pandemic for lower-income communities, which previous studies show have higher levels of pre-existing health conditions and less access to healthcare. This study shows they also exhibit less of the social distancing that could help buffer against COVID-19.

"As policymakers are thinking about emergency relief packages, this points to the need for lower-income regions to be an area of focus in order to build capacity for social distancing and other measures critical to reduce the spread of this disease," said senior author Michael Springborn, an environmental economist and associate professor with the UC Davis Department of Environmental Science and Policy. "This is just one piece of a broader set of emerging results showing that lower-income neighborhoods are particularly vulnerable as the pandemic proceeds."

The scientists compared mobility data from SafeGraph, Place IQ and Google Mobility, which was freely shared to the researchers for the study.

Ice formation and accumulation are challenging concerns for several industrial applications including heating ventilation air conditioning and refrigeration (HVAC&R) systems, aircraft, energy transmission, and transportation platforms. Frost formation on heat exchangers, for example, reduces heat transfer efficiency and results in significant economic losses. Moreover, defrosting and de-icing techniques are energy-intensive, requiring large masses of ice to be melted completely and surfaces to be cleaned of leftover water during cyclic operation, making frosting-defrosting a multi-billion-dollar problem in the U.S.

Nenad Miljkovic, along with researchers in his group, have discovered a way to significantly improve the defrosting of ice and frost on heat exchangers. Their findings, "Dynamic Defrosting on Superhydrophobic and Biphilic Surfaces," have been published in Matter.

Defrosting of heat exchangers is a highly inefficient process. Common defrosting methods not only require significant energy to melt the frost but additional energy to evaporate melted water from the wettable surface. Researchers in the past have investigated the use of non-wettable surfaces (hydrophobic or superhydrophobic) to delay frosting and reduce ice adhesion, which does indeed improve defrosting performance. However, water retention remains prevalent on such heat exchangers during frost, defrost, and re-frost cycles.

In an effort to eliminate water retention, Miljkovic and a team led by graduate student Yashraj Gurumukhi and postdoctoral scholar Dr. Soumyadip Sett studied dynamic defrosting on heterogeneous surfaces with spatially distinct domains of wettability, known as biphilic surfaces. These biphilic surfaces have alternating superhydrophobic (water-repelling) and hydrophilic (water-loving) regions. Through optical imaging, the researchers showed that during defrosting, the frost layer on a superhydrophobic region melts into a highly mobile slush, which is pulled toward the hydrophilic regions by surface forces. This mobility enables removal of slush from the superhydrophobic regions prior to it completely melting, thereby cleaning the surface. Water is then restricted to hydrophilic areas, where it evaporates quickly due to the larger contact area.

Additionally, to optimize the design of their biphilic surfaces and understand the effects of pattern heterogeneity, the team studied banana-leaf-inspired branched biphilic patterns to determine if it would reduce cleaning time. They observed that binary biphilic designs were simpler to manufacture when compared to branched designs and offered better surface cleaning performance during defrosting.

"Defrosting cycles require systems to be shut down, frost completely melted, and surfaces cleaned before restarting the system, consuming significant time and energy. Enhancing cleaning efficiency by utilizing wettability-patterned biphilic surfaces can reduce system downtime and defrost energy input, thereby increasing overall efficiency," Miljkovic said.

In effect, when combined with suitable large-scale manufacturing methods, biphilic surfaces have the potential to outperform homogenous surfaces in terms of heat transfer enhancements and energy requirements.

Their work not only provides fundamental design guidelines for fabricating biphilic surfaces, it illustrates the role of wettability gradients on defrosting dynamics. Future work from the researchers will further decrease defrost time by identifying critical bottlenecks in the process and provide design methodologies to create effective defrost-enhancing surfaces for industrial applications.

Philadelphia, July 29, 2020 - A new study in the Journal of the Academy of Nutrition and Dietetics, published by Elsevier, found that between 2002 and 2018 purchases by US households of foods and beverages containing caloric sweetener (CS, i.e., sugar) declined while purchases of products containing both caloric sugars and nonnutritive sweeteners (NNS, i.e., sugar substitutes) increased. Beverages accounted for most of the products purchased containing NNS only or combined with CS.

"With excessive sugar consumption linked to chronic cardiometabolic diseases, sugar reduction has become an important public health strategy. This has resulted in greater innovation by the food industry and increased use of NNS in our food supply," said lead investigator Barry Popkin, PhD, W.R. Kenan Jr. Distinguished Professor, Department of Nutrition, Gillings Global School of Public Health, and Carolina Population Center, The University of North Carolina at Chapel Hill, NC, USA.

NNS include aspartame, saccharin, rebaudioside A (reb-A), and sucralose, which provide sweetness to products without the calories of sugar or high fructose corn syrup.

The study looked at how the prevalence and volume of foods that contain commonly consumed NNS types in the US packaged food supply had changed between 2002 and 2018. Co-investigator and Gillings Global School of Public Health Associate Professor Shu Wen Ng, PhD, said the study found a decline in prevalence of products containing aspartame and saccharin, but an increase in those with sucralose (increased from 38.7 percent to 71.0 percent) and reb-A (increased from 0.1 percent to 25.9 percent). Beverages accounted for most of products purchased containing NNS only or combined with CS. Compared to households without children, households with children are buying more packaged beverages and foods products that contain NNS. While this aligns with the public health objectives, it also raised other concerns about exposure to NNS.

The study also showed that non-Hispanic whites purchased almost double the volume of products containing NNS compared to Hispanics and non-Hispanic blacks throughout the study period. However, non-Hispanic black households showed a 42 percent increase in the proportion of households purchasing beverage products containing both CS and NNS between 2002 and 2018, indicating that purchasing behavior may be changing for this race-ethnic group.

The analysis used a nationally representative dataset on household purchases at the barcode level (Nielsen Homescan) in 2002 and 2018 linked with Nutrition Facts Panel (NFP) data and ingredient information using commercial nutrition databases that are updated regularly to capture reformulations. Keyword searches were performed on ingredient lists to classify products containing various types of NNS. The investigators then derived each household's total volume purchased per capita per day in 2002 and 2018 that contained NNS and/or caloric sugars and the percent of households purchasing foods and beverages by sweetener type.

Dr. Elizabeth Dunford, also affiliated with UNC's Gillings Global School of Public Health, and Carolina Population Center, noted, "There is a need to be able to track our exposure to specific types of sweeteners in order to properly understand their health implications. The change to the food supply our study documents reinforces the need to develop and maintain the data systems to monitor what companies are putting in their foods. This work can help complement new and emerging clinical evidence about the different cardiometabolic and health effects of each NNS type."

"Considering further improvements to the Nutrition Facts label to include the amounts of NNS when present in products can allow monitoring of our exposure to these additives so that we can better assess their potential harms or benefits on health," said Dr. Ng.

Previous observational studies have linked NNS consumption to increased body weight, type 2 diabetes, and other adverse cardiometabolic outcomes, while others have found the opposite effect. Results from randomized controlled trials and meta-analyses have not demonstrated any relationship between NNS and increased consumption of sweet foods. It is unclear whether the inconsistency of the findings is due to studies typically categorizing all NNS together, rather than examining differences in the effect of specific types of NNS on outcomes.

Prescription medication of cannabis extract cannabidiol, or CBD, is safe for daily use in treating cannabis use disorder, and could help people to cut down on cannabis use, according to an initial randomised controlled trial published in The Lancet Psychiatry journal.

The study is the first to report that daily prescribed medical-use CBD use can cause reduction in cannabis use among people with cannabis use disorder, but the four-week study was not designed to provide robust estimates of the magnitude or duration of efficacy and further studies are needed.

Researchers found an optimal daily dose of between 400mg and 800mg of CBD, which is considerably higher than concentrations found in CBD products that are available without prescription (which typically contain around 25mg CBD). They warn that such products should not be used for medicinal purposes.

The authors say that these findings are important in light of major policy changes surrounding the production and sale of cannabis products, increases in the number of people entering treatment for cannabis use disorders worldwide, and the current absence of recommended treatments for cannabis use disorder.

Dr Tom Freeman, the study's lead author and Director of the Addiction and Mental Health Group at the University of Bath, UK, said: "Our study provides the first causal evidence to support cannabidiol, or CBD, as a treatment for cannabis use disorders. This is encouraging, as there are currently no drug treatments for cannabis addiction. CBD products are widely available in many countries but we would not advise people to self-medicate with these products. People with concerns about their cannabis use should always speak to a healthcare professional in the first instance." [1]

Cannabis addiction affects an estimated 22 million people worldwide - similar to the prevalence of opioid use disorders - and the proportion of people seeking help for cannabis use disorders has risen in all world regions apart from Africa. However, there are currently no medications recommended for the treatment of cannabis use disorders.

Cannabidiol, also known as CBD, is one of more than 80 chemicals present in cannabis. By itself, CBD has been reported to induce feelings of relaxation and calm, but it does not cause the "high" associated with cannabis use, which is caused by a different chemical called tetrahydrocannabinol, or THC. As a result, CBD is sold legally in many countries in oils, capsules, creams, tea and other products.

Previous studies have suggested that taking CBD products could help to reduce withdrawal symptoms in people who are actively trying to quit cannabis use. However, it hasn't been possible to determine whether these effects were due to CBD, because the studies either used an open-label design (where the participants knew what medications they were taking and so the results could have been biased), or CBD was given together with THC so it wasn't possible to say to which chemical the effects were attributable.

In this latest study, researchers carried out the first randomised clinical trial of cannabidiol for the treatment of cannabis addiction. All 82 people who took part in the study had been diagnosed with a cannabis use disorder of at least moderate severity, which means they experienced at least four out of 11 possible symptoms of addiction. They had all expressed a desire to quit within the next month, and had tried to quit on at least one occasion before.

Participants were randomly assigned to treatment groups and asked to take two capsules of CBD twice daily for four weeks. The placebo group were given sham capsules containing no CBD, while the others received a daily dose of either 200mg, 400mg or 800mg CBD. All of the participants received six counselling sessions designed to help them quit using cannabis, which took place before and during the study period.

Weekly urine samples were tested for levels of THC to assess how much cannabis had been consumed in the past week. Participants were also asked to report how many days they had abstained from using cannabis that week.

The trial used an adaptive design to identify which doses of CBD were effective or ineffective compared to placebo. In the first stage of the trial, 12 people per group were assigned to either placebo, 200mg, 400mg or 800mg CBD (48 total). After the first phase of the study, the 200mg dose was found to be ineffective and these participants were removed from the trial. A further 34 people were recruited to the second stage of the study and randomly assigned to receive daily doses of either the placebo (11 people), 400mg CBD (12 people) or 800mg CBD (11 people).

Daily CBD doses of 400mg and 800mg were both found to reduce participants' cannabis intake (reducing THC levels in the urine by -94.21ng/mL and -72.02ng/mL, respectively). In addition, abstinence from cannabis use increased by an average of 0.5 days per week in the group who received the 400mg daily dose of CBD and 0.3 days per week in the group who received 800mg CBD daily.

The researchers observed no difference in side effects experienced by the placebo group and those receiving any dose of CBD. 77 of 82 participants completed the treatment and those who dropped out did so because of missing study visits, being lost to follow up, not taking the study medication, or taking additional medications, and not because of the CBD treatment. There were no serious adverse events during the study, suggesting that CBD is safe and well tolerated at the doses tested.

Professor Valerie Curran, senior author and Director of the Clinical Psychopharmacology Unit at University College London, UK, said: "Our findings indicate that CBD doses ranging from 400mg to 800mg daily have the potential to reduce cannabis use in clinical settings, but higher doses are unlikely to bring any additional benefit. Larger studies are needed to determine the magnitude of the benefits of daily CBD for reducing cannabis use." [1]

The study was carried out over a four week treatment period with follow up extending to six months. The researchers say additional research is needed to investigate the extent to which their findings translate to different durations of treatment. Studies are also needed to investigate whether CBD directly reduces cannabis use or if it reduces other mental health symptoms which might indirectly affect cannabis use, such as anxiety.

New research published this week in Experimental Physiology found that in prostate cancer survivors, a moderate bout of exercise kept the cell count of certain type of immune cells at a normal level, suggesting the exercise is safe for prostate cancer survivors. After 24 hours after a moderate bout of cycling, the immune cell count of natural killer (NK) cells, part of the body's first line of defence, had returned to resting levels.

Prostate cancer treatments, including androgen deprivation therapy (ADT), have numerous adverse effects that reduce physical function and quality of life. Exercise is recommended for cancer survivors to reduce the side effects of treatment and has shown to have many benefits.

However, the effects of prostate cancer treatment and acute exercise on the immune system have only been briefly examined. Exercise oncology guidelines were initially based on the responses seen in healthy, older adults. But individuals with cancer have different physiological responses to exercise, many of which we are only just beginning to understand.

Exercise helps the immune system mobilise by causing NK cells to move into the blood and be transported them to areas of need, such as sites of infection or tumours. At the tissues, these cells move out of circulation and in cancer patients they can the infiltrate the tumour and potentially slow the tumour's rate of growth. This has been shown very elegantly in animal models but the exercise and immune response in cancer survivors is limited, with only a few studies in prostate cancer.

The researchers, based at Victoria University in Australia, had volunteers (11 cancer survivors currently receiving ADT treatment, and 14 men with prostate cancer not on ADT, and 8 healthy controls) completed a cycling task to determine their maximal aerobic fitness.

The researchers chose to use a moderate intensity exercise session that was consistent with current exercise oncology guidelines but was also a bout that would be practical for prostate cancer survivors to perform on their own.

To ensure that the exercise bout used to stimulate the immune system was the same degree of difficulty for everyone, they standardised based on their maximal effort.

To determine immune function, they obtained blood samples before exercise, immediately after and 2h after they finished cycling. The participants then came back the next day (24h) after exercise, and immune function was assessed again after one night of recovery. They also measured several key hormone levels, including adrenaline and noradrenaline, as they play a role in activating and mobilising the NK immune cells.

The researchers found that 24 hours after a moderate bout of cycling, the immune cell count of natural killer (NK) cells, part of the body's first line of defence, had returned to resting levels.

They also showed that the immune cell mobilisation with exercise does not appear to be significantly altered during prostate cancer treatment, which provides direct evidence that acute exercise that falls within current oncology guidelines also appears to be beneficial for the immune system.

A limitation of the study is the modest sample size, and also that they examined cytokines and proteins that are related to NK cell function but did not directly assess the killing capacity of the NK cells.

Erik D Hanson, first author on the study said,

"One of the most enjoyable aspects of working with these men is how willing these men are to help their fellow prostate cancer survivors. Many of them realise that these studies are not likely to benefit them directly. However, they do not hesitate to volunteer and are willing to do just about whatever is asked of them for the collective good."

Results from the first-ever randomised clinical trial of CBD for cannabis use disorder suggests that prescribed doses of the non-intoxicating constituent part of the cannabis plant could help people kick the habit.

In the MRC-funded trial, published in the Lancet Psychiatry (embargo - Tuesday 28 July 23:30 UK time; 18:30 Eastern Time), researchers administered CBD or placebo to 82 volunteers who were motivated to quit using cannabis but had previously failed to do so.

They measured the effects of the drug on levels of cannabis use both during a four-week treatment period and up to six months follow-up.

As this was the first clinical trial to assess CBD for reducing cannabis use, they tested three different doses of CBD in an adaptive design to find out which doses might be most effective:

- In the first stage of the trial, 48 volunteers received either placebo or CBD at doses of 200mg, 400mg or 800mg. The researchers found that the lowest dose of 200mg CBD was ineffective and so they dropped it from the trial.

- In the second stage of the trial, the researchers recruited an additional 34 volunteers to receive either placebo, 400mg or 800mg CBD. At the end of the trial, they found consistent evidence that CBD at 400mg or 800mg was more effective than placebo at reducing cannabis use.

Their results showed that participants treated with CBD showed lower levels of cannabis in their urine and an increased number of days abstinent compared to those treated with placebo.

CBD was well tolerated at all doses and there were no increases in side effects compared to placebo. 94% of the volunteers completed treatment. Importantly, the doses of CBD tested were significantly higher than CBD products purchased online or from the High Street (typically 25mg per day).

All participants in the trial met a clinical diagnosis of cannabis use disorder, indicating a problematic pattern of cannabis use which had created significant impairment and distress for the individual. All participants had previously failed to quit cannabis use at least once and took part in the trial as part of a cessation attempt.

Lead author Dr Tom Freeman, Director of the Addiction and Mental Health Group within the Department of Psychology at the University of Bath explains: "The results from our trial open up a novel therapeutic strategy for managing problematic cannabis use in clinical settings. As we highlight, CBD at daily oral doses of 400mg and 800mg has potential to address the substantial and currently unmet clinical need for a pharmacological treatment of cannabis use disorders.

"Whilst it may seem counterintuitive to treat problematic cannabis use with CBD - a constituent part of the cannabis plant - THC and CBD have contrasting effects on our own endogenous cannabinoid system. Unlike THC, CBD does not produce intoxicating or rewarding effects and it shows potential for a treating several other medical disorders."

Cannabis is now the primary drug cited by first-time clients presenting at addiction services across Europe, with the number of people entering treatment increasing by 76% over the past decade. The increase in treatment for cannabis problems has occurred alongside an increase in concentrations of THC, the intoxicating component of cannabis. Daily use of cannabis with high THC concentrations is associated with a five-times increased risk of psychosis.

At present there are no recommended pharmacotherapies to help people with problematic cannabis use to quit. In demonstrating how CBD could be a promising treatment strategy, this trial adds to existing research on the potential medicinal uses of CBD, including the treatment of severe childhood epilepsy syndromes and psychosis. Importantly, treatment with CBD does not include any of the intoxicating constituent of cannabis (THC) which might carry a risk of adverse effects.

Professor Valerie Curran, senior author and Director of the Clinical Psychopharmacology Unit at University College London, UK, said: "Our findings indicate that CBD doses ranging from 400mg to 800mg daily have the potential to reduce cannabis use in clinical settings, but higher doses are unlikely to bring any additional benefit. Larger studies are needed to determine the magnitude of the benefits of daily CBD for reducing cannabis use."

BIRMINGHAM, Ala. - Precision medicine in cancer treatment uses genetic changes in the cancer cells to select the best therapies for individual patients.

Now researchers led by James Bibb, Ph.D., professor of surgery at the University of Alabama at Birmingham, suggest using a broader lens of post-translational modification analysis to identify new biomarkers of cancer drivers that may allow a much more precise prediction of patient responses to treatments. In a study published in Proceedings of the National Academy of Sciences, they demonstrate this diagnostic alternative for neuroendocrine neoplasms driven by an aberrantly activated protein kinase called Cdk5.

"Our findings show that precision medicine is a realizable goal for the treatment of rare and recalcitrant cancers," said Angela Carter, Ph.D., principle author of the paper and a postdoctoral fellow in the Bibb lab at UAB.

"The same approach," Bibb said, "could be adapted to identify markers of other tumor drivers. As the number of cancer types in which Cdk5 is implicated is rising, and as drugs with the potential to selectively target Cdk5 are moved toward the clinic, the translational potential of this diagnostic-therapeutic coupled system will be broad."

UAB researchers are now in collaboration with the National Cancer Institute to adapt the biomarkers the team discovered into a clinically applicable diagnostic assay, and move new drugs targeting these pathways to clinical trials.

Cdk5 is a cyclin-dependent kinase that phosphorylates target proteins as part of signaling sequences in cells. Cdk5 activity is mostly restricted to neuronal cells, where it is important for central nervous system development and cognitive processes such as learning and memory.

In the PNAS paper, Carter, Bibb and colleagues first examined multiple samples of neuroendocrine tumor and cancer types and found that Cdk5 and its activators p35 and p25 characterized a large portion of all neuroendocrine neoplasms. Also, a Cdk5 inhibitor blocked growth of the neoplasms, showing that Cdk5 activity is a major contributor to the growth of these cancer cells.

To find biomarkers, the researchers first used a unique mouse model of medullary thyroid carcinoma, or MTC, whose growth of the tumor can be turned on or off. They then looked for global differences in phosphorylated peptide fragments between arrested and growing MTC. The 50 most highly upregulated phosphorylation sites in growing MTC were examined further, using short interfering peptides that would block phosphorylation. Fifteen interfering peptides were found to inhibit growth of neuroendocrine cancer cells but not normal fibroblasts, which identified the downstream targets of Cdk5 needed for cancer cell growth. The 15 targets of the Cdk5 signaling cascade were shown to come from proteins associated with common cancer mechanisms.

Phosphorylation state-specific antibodies were generated to detect six of those sites and two other sites previously identified as targets of Cdk5. Six of the eight sites showed dose-dependent reduction by a Cdk5 inhibitor in a human neuroendocrine cancer cell line, meaning decreased phosphorylation of the proteins the peptides came from. "Our overall data demonstrated that phosphorylation of these six proteins is critical in driving these cancers and is dependent upon Cdk5 activity. It also suggested that these phosphorylation sites could serve as biomarkers for many types of Cdk5-driven neuroendocrine tumors," Bibb said.

Three showed significant elevation in a cohort of human MTC patient tumors and a positive correlation with Cdk5 expression; another was increased in just a small portion of tumor samples but had a positive correlation with Cdk5 expression. Nearly three-fourths of patient tumors tested showed elevated Cdk5 levels; but only one-fifth had elevation of all four biomarkers of Cdk5 pathway activity, emphasizing that presence of a protein does not correlate completely with function of that protein.

The researchers then showed that Cdk5 inhibition blocked the growth of tumors in distinct MTC animal models. They then tested patient-derived xenograft models for presence of the putative Cdk5 biomarkers, and showed that growth of two biomarker-positive cancers was reduced by treatment with the Cdk5 inhibitor, while tumor growth of the two biomarker-negative cancers was not. These results strongly supported the ability of the biomarkers to predict responsiveness to anti-Cdk5 therapy.

However, tumor regression was not seen, and higher levels of the Cdk5 inhibitor were quite toxic. So the researchers tested a biomimetic nanoparticle-based drug delivery system called leukosomes, or LKs, which were generated from a combination of synthetic phospholipids and leukocyte membrane extracts. LKs have the ability to target the inflamed environment of a tumor, and their leukocyte membrane proteins camouflage them from removal by the immune system.

The LKs showed increased localization at MTC tumors in mice, where they could deliver a lower dose of the Cdk5 inhibitor that had the same effectiveness as a higher, toxic dose of free Cdk5 inhibitor.

"The current study reveals that Cdk5 is likely a contributor to at least a portion of all neuroendocrine tumor types," Bibb said. "This study also identifies a set of phosphorylation-based biomarkers, which indicate that not only are Cdk5 pathway components present, but Cdk5 is actively modulating the signaling network and regulating cancer physiology.

"To be useful clinically, antibodies to detect these biomarkers will need to be developed into an easy-to-use assay that allows reliable quantitation of biomarker levels in patient tumors, preferably in relatively small samples such as core biopsies."

BIRMINGHAM, Ala. - The University of Alabama at Birmingham and Southern Research have discovered a new drug candidate that offers a major advance in the treatment for diabetes.

Tested on isolated human and mouse pancreatic islets, mouse and rat cell cultures and animal models of both Type 1 and Type 2 diabetes, the experimental drug significantly improved four detrimental characteristics of diabetes: hyperglycemia, known as high blood sugar; hyperglucagonemia, elevation in the hormone glucagon that counteracts the effects of insulin, promotes glucose production and increases blood glucose; excessive production of glucose by the liver; and fatty liver, known as hepatic steatosis.

The drug candidate SRI-37330 is a non-toxic small molecule that effectively rescued mice from streptozotocin- and obesity-induced diabetes and improved glucose homeostasis.

A study published in the journal Cell Metabolism describes the strong anti-diabetic properties of this newly designed chemical compound. The researchers, led by Anath Shalev, M.D., director of UAB's Comprehensive Diabetes Center, said that "compared to currently available diabetes therapies, the compound may provide a distinct, effective and highly beneficial approach to treat diabetes."

"While the safety and efficacy of SRI-37330 in humans still remains to be determined," Shalev said, "it is highly effective in human islets, is orally bioavailable and is well tolerated in mice."

SRI-37330 was discovered through two decades of research by Shalev, followed by high-throughput screening of 300,000 compounds and extensive medicinal chemistry optimization at Southern Research, headquartered in Birmingham.

Diabetes is a disease affecting two hormones -- insulin and glucagon. In healthy individuals, insulin helps cells take up glucose from the blood when glucose levels are high, and glucagon helps the liver release glucose into the bloodstream when glucose levels are low. In diabetes, insulin release is diminished, cell sensitivity to insulin can decrease, and glucagon release is excessive. This can cause a vicious cycle of escalating blood glucose levels.

SRI-37330 appears to act beneficially on pancreatic islets that produce the two hormones, and also at the liver.

Diabetes affects 425 million people worldwide and more than 30 million in the United States. It is a growing epidemic, with 1.5 million Americans newly diagnosed each year. The preclinical studies led by Shalev suggest that the potential drug SRI-37330 could be beneficial in both Type 1 and Type 2 diabetes, including both lean and obese individuals. Also, diabetes appears to be a significant co-morbidity in the current COVID-19 pandemic.

The 80 million people in the United States who have prediabetes might also benefit from the potential drug. Furthermore, the effectiveness of SRI-37330 in reducing fatty liver in mice suggested it might have potential to treat non-alcoholic fatty liver disease, which affects about 100 million people in the United States and 1 billion worldwide.

The path to discovery of SRI-37330 began 18 years ago when Shalev and colleagues identified the protein TXNIP -- pronounced "tix-nip" -- as the top glucose-induced gene in human islets, which are the cell groups in the pancreas that produce insulin and glucagon. This was followed by their work showing that TXNIP negatively affected islet function and survival, suggesting that TXNIP might play an important detrimental role in diabetes.

In previous research, Shalev and colleagues also showed that TXNIP was increased in different mouse models of diabetes and in diabetic human islets, and that deletion of the TXNIP gene protected mice from diabetes and had beneficial effects on pancreatic islet biology. Altogether, these data suggested that a search for a TXNIP inhibitor could provide a novel approach to diabetes treatment.

Study details

Some of the details of the current study -- which covers 10 years of work -- involve the inhibitory effect of SRI-37330 on the TXNIP gene. SRI-37330 inhibited activity of the TXNIP promoter by 70 percent, and it showed a dose-dependent inhibition of TXNIP mRNA and protein.

RNA sequencing of isolated human pancreatic islets treated with SRI-37330 showed that TXNIP signaling was inhibited as demonstrated by a number of upregulated and downregulated genes. It further showed that SRI-37330 specifically inhibited TXNIP, but not other members of the arrestin family or general transcription.

Importantly, the Shalev lab previously showed that non-specific inhibition of TXNIP signaling by the calcium channel blocker verapamil has beneficial effects in human subjects with recent onset Type 1 diabetes, suggesting that this approach might be translatable.

Of note, SRI-37330 is effective in reducing TXNIP in the nanomolar range, has an oral bioavailability of 95 percent, shows no cytotoxicity in vitro and no toxicity in mice, even at doses about 10-fold above its therapeutic dose, and has already tested negative in Ames mutagenicity assays, CYP450 inhibition, hERG inhibition and Eurofins SafetyScreen for off-target liabilities, including no inhibition of calcium channels.

Strikingly, addition of SRI-37330 to the drinking water of obese diabetic db/db mice, a model of severe Type 2 diabetes, led within days to normalization of their blood glucose. Similarly, SRI-37330 also protected mice from streptozotocin-induced diabetes, a model of Type 1 diabetes. Of note, SRI-37330 achieved even better blood glucose control than two of the leading oral anti-diabetic drugs, metformin and empagliflozin.

"Together with the fact that SRI-37330 was also effective after the onset of overt diabetes, as well as when just dosed twice a day by oral gavage, is particularly promising and raises the possibility that SRI-37330 may ultimately lead to a much-needed oral drug that could also be used for Type 1 diabetes," Shalev said.

Surprisingly, SRI-37330 decreased blood glucose levels primarily via lowering of serum glucagon levels and inhibition of basal glucose production from the liver. This mode of action is very different from that of currently used anti-diabetic drugs.

Despite SRI-37330's reduction of glucagon release from pancreatic islets and reduction of glucose production by the liver, the inhibitor did not cause any low blood glucose events or create a hypoglycemic liability in mice, even in the context of insulin-induced hypoglycemia.

In another surprising result -- and in contrast to previous attempts to inhibit glucagon function for the treatment of diabetes -- the inhibitor dramatically improved the severe fatty liver observed in obese diabetic db/db mice. "This now raises the intriguing possibility," Shalev said, "that SRI-37330 might also be beneficial in the context of non-alcoholic fatty liver disease, a complication frequently associated with diabetes and/or obesity.

"In summary," Shalev said, "our studies have identified a novel substituted quinazoline sulfonamide, SRI-37330, that is orally bioavailable, has a favorable safety profile and inhibits TXNIP expression and signaling in mouse and human islets, inhibits glucagon secretion and function, lowers hepatic glucose production and hepatic steatosis, and exhibits strong anti-diabetic effects in mouse models of Type 1 and Type 2 diabetes."

What The Study Did: Researchers compared the accuracy of the blood biomarker tau phosphorylated at threonine 217 (P-tau217) with other biomarkers for distinguishing Alzheimer from other neurodegenerative diseases in individuals with or at risk for dementia.

Authors: Oskar Hansson, M.D., Ph.D., of Lund University in Lund, Sweden, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jama.2020.12134)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

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Media advisory: The full study is linked to this news release. The study is being released to coincide with its presentation at the Alzheimer's Association International Conference.

Embed this link to provide your readers free access to the full-text article This link will be live at the embargo time https://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2020.12134?guestAccessKey=42d098cb-7eca-4a1c-9d7b-9951b104b003&utm_source=For_The_Media&utm_medium=referral&utm_campaign=ftm_links&utm_content=tfl&utm_term=072820

What The Study Did: Weighted and unweighted population data are compared to assess inequities in COVID-19 deaths by race/ethnicity as reported by the U.S. Centers for Disease Control and Prevention in this observational study.

Authors: Tori L. Cowger, M.PH., of the Harvard T.H. Chan School of Public Health in Boston, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamanetworkopen.2020.16933)

Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

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Media advisory: The full study is linked to this news release.

Embed this link to provide your readers free access to the full-text article This link will be live at the embargo time http://jamanetwork.com/journals/jamanetworkopen/fullarticle/10.1001/jamanetworkopen.2020.16933?utm_source=For_The_Media&utm_medium=referral&utm_campaign=ftm_links&utm_term=072820

About JAMA Network Open: JAMA Network Open is the new online-only open access general medical journal from the JAMA Network. On weekdays, the journal publishes peer-reviewed clinical research and commentary in more than 40 medical and health subject areas. Every article is free online from the day of publication.