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Nobel laureate in physics Richard Feynman once described turbulence as "the most important unsolved problem of classical physics."

Understanding turbulence in classical fluids like water and air is difficult partly because of the challenge in identifying the vortices swirling within those fluids. Locating vortex tubes and tracking their motion could greatly simplify the modeling of turbulence.

But that challenge is easier in quantum fluids, which exist at low enough temperatures that quantum mechanics -- which deals with physics on the scale of atoms or subatomic particles -- govern their behavior.

In a new study published in Proceedings of the National Academy of Sciences, Florida State University researchers managed to visualize the vortex tubes in a quantum fluid, findings that could help researchers better understand turbulence in quantum fluids and beyond.

From left, Wei Guo, an associate professor of mechanical engineering at the FAMU-FSU College of Engineering, and Yuan Tang, a postdoctoral researcher at the National High Magnetic Field Laboratory, in front of the experimental setup. (Courtesy of Wei Guo)

"Our study is important not only because it broadens our understanding of turbulence in general, but also because it could benefit the studies of various physical systems that also involve vortex tubes, such as superconductors and even neutron stars," said Wei Guo, an associate professor of mechanical engineering at the FAMU-FSU College of Engineering and the study's principal investigator.

The research team studied superfluid helium-4, a quantum fluid that exists at extremely low temperatures and can flow forever down a narrow space without apparent friction.

Guo's team examined tracer particles trapped in the vortices and observed for the first time that as vortex tubes appeared, they moved in a random pattern and, on average, rapidly moved away from their starting point. The displacement of these trapped tracers appeared to increase with time much faster than that in regular molecular diffusion -- a process known as superdiffusion.

Analyzing what happened led them to uncover how the vortex velocities changed over time, which is important information for statistical modeling of quantum-fluid turbulence.

"Superdiffusion has been observed in many systems such as the cellular transport in biological systems and the search patterns of human hunter-gatherers," Guo said. "An established explanation of superdiffusion for things moving randomly is that they occasionally have exceptionally long displacements, which are known as Lévy flights."

But after analyzing their data, Guo's team concluded that the superdiffusion of the tracers in their experiment was not actually caused by Lévy flights. Something else was happening.

"We finally figured out that the superdiffusion we observed was caused by the relationship between the vortex velocities at different times," said Yuan Tang, a postdoctoral researcher at the National High Magnetic Field Laboratory and a paper author. "The motion of every vortex segment initially appeared to be random, but actually, the velocity of a segment at one time was positively correlated to its velocity at the next time instance. This observation has allowed us to uncover some hidden generic statistical properties of a chaotic random vortex tangle, which could be useful in multiple branches of physics."

Unlike in classical fluids, vortex tubes in superfluid helium-4 are stable and well-defined objects.

"They are essentially tiny tornadoes swirling in a chaotic storm but with extremely thin hollow cores," Tang said. "You can't see them with the naked eye, not even with the strongest microscope."

"To solve this, we conducted our experiments in the cryogenics lab, where we added tracer particles in helium to visualize them," added Shiran Bao, a postdoctoral researcher at the National High Magnetic Field Laboratory and a paper author.

The researchers injected a mixture of deuterium gas and helium gas into the cold superfluid helium. Upon injection, the deuterium gas solidified and formed tiny ice particles, which the researchers used as the tracers in the fluid.

"Just like tornadoes in air can suck in nearby leaves, our tracers can also get trapped on the vortex tubes in helium when they are close to the tubes," Guo said.

This visualization technique is not new and has been used by scientists in research labs worldwide, but the breakthrough these researchers made was to develop a new algorithm that allowed them to distinguish the tracers trapped on vortices from those that were not trapped.

Cambridge, Mass. - When the first COVID-19 vaccines were approved for emergency use in December 2020, healthcare systems across the Unites States needed to rapidly design and implement their own approaches to distribute COVID-19 vaccines equitably and efficiently. This new role has required Beth Israel Lahey Health (BILH) to develop new strategies and build large operational teams to organize and successfully vaccinate more than 14,000 patients a week across Eastern Massachusetts. In an Insight article published in JAMA Health Forum, Leonor Fernandez, MD, Assistant Professor of Medicine in the Department of Medicine at Beth Israel Deaconess Medical Center (BIDMC) and Peter Shorett, MPP, Chief Integration Officer at BILH, identify five key lessons about health equity that have emerged from BILH's vaccination campaign for the health system's approximately 1.6 million patients.

"This is an unprecedented public health campaign for a health system," said Fernandez, a primary care physician and Director of Patient Engagement at Health Care Associates, BIDMC's primary care practice. "Organizing our approach to COVID 19 vaccination is teaching us a lot about what we do well and how we can further advance the delivery of equitable health care. To ensure that all patients, including Black, Latinx, and other marginalized communities can access these life-saving vaccines, we have to be able to reach out, create trust, and speak their language."

Fernandez and Shorett describe five actions that help promote vaccine equity: obtain reliable patient demographic data; address structural inequalities intentionally in order to achieve equitable results; communicate with patients in understandable terms and in their preferred languages; involve diverse stakeholders in decisions; and embrace equity, diversity and inclusion as fundamental organizational values.

Obtain reliable patient demographic data
The authors note that accurate and complete demographic data are essential to identifying and deploying strategies to reach and engage patients, but data are not consistently elicited or accurate. Information about patients' race, ethnicity, preferred language and geography is helping drive greater understanding and accountability in the health system's efforts to address historic racial and ethnic health disparities.

Intentionally addressing structural inequalities and speaking patients' languages
"BILH's strategy has been to invite patients in three waves for each eligible phase, focusing first on our patients associated with our healthcare centers in Dorchester and Chelsea," said Shorett, who led the patient vaccination efforts for the health system. "We then move to patients in towns and neighborhoods in our region that have been disproportionately impacted by COVID-19, and shortly after that to randomized cohorts of eligible patients."

BILH teams developed a broader communications approach, deploying a mix of SMS texting, outgoing phone messages in many languages, and live phone outreach to patients in highly affected communities. Community health centers and primary care practices in highly affected communities have been and will continue to be critically important in the vaccination invitation, outreach and communication process as trusted messengers for their patients.

"Relying exclusively on digital invitations can mean that patients and those who lack familiarity and access to digital technology or speak a language other than English will have less access to vaccination," said Fernandez, who is also a member of the health system's vaccination leadership team.

Involving diverse stakeholders for better decision making and embracing equity as a fundamental value to create greater change

Following the widespread civil unrest in response to several high-profile incidents of police brutality, BILH's Diversity, Equity and Inclusion Taskforce developed recommendations for action incorporated in part from listening sessions including thousands of employees. This backdrop, along with extreme health disparities observed during the pandemic, made the issue of health equity both more familiar and more urgent within the health system.
"The integration of diverse institutional and community stakeholders into decisions enables better recognition of structural inequities, provides needed knowledge and skill sets, and supports more effective strategies to help the health system address health disparities," noted Shorett.

Vaccinating the U.S. population against COVID-19 will require an unprecedented ongoing public health campaign. "Sustaining this positive momentum will rely on the shared understanding that when it comes to health, we are all in this together," said Fernandez.

April 8, 2021 - Women undergoing surgery to treat stress urinary incontinence (SUI) are not at increased risk of developing pelvic cancers, according to a large-scale, population-based study in The Journal of Urology®, Official Journal of the American Urological Association (AUA). The journal is published in the Lippincott portfolio by Wolters Kluwer.

"In a very large population with extended follow-up, we found no increase in the risk of any pelvic malignancy in women who underwent stress urinary incontinence surgery," comments lead author Humberto R. Vigil, MD, MSc, of University of Ottawa, Ont., Canada. "The vast majority of stress urinary incontinence procedures performed included transvaginal mesh."

No increase in cancers after SUI surgery - with or without transvaginal mesh
Using Ontario health data, the researchers identified nearly 75,000 women who underwent SUI surgery between 2002 and 2015. Follow-up data (median 8.5 years) were used to assess for the development of pelvic cancers, such as bladder, cervical and ovarian cancer. A time to event analysis was used to determine the risk of pelvic cancer in SUI surgery patients compared to more than 5.5 million women who did not undergo SUI surgery.

On analysis of more than 40,000 pelvic cancers, there was no significant difference between groups. The event rate for pelvic malignancies was 0.90 per 1,000 person-years of follow-up in women undergoing SUI surgery, compared to 0.85 per 1,000 person-years in controls who did not have surgery.

After adjustment for multiple factors, there was a lower risk of pelvic cancers in women who underwent SUI surgery. While that may seem like a paradoxical finding, Dr. Vigil and colleagues suggest a couple of possible explanations: women opting for an elective procedure such as SUI surgery may be relatively healthier (selection bias), or cancers might be detected during assessment before SUI surgery. The study confirmed some known risk factors for pelvic cancers, including obesity and no history of childbirth.

Importantly, there was no evidence of increased cancer risk in women undergoing SUI surgery with implanted transvaginal mesh. A midurethral sling procedure using polypropylene mesh is the most commonly performed surgery for SUI.

Over the past decade, there have been public health concerns regarding complications and safety issues related to surgical mesh - particularly related to a condition called pelvic organ prolapse (POP), but also for SUI. These issues have led to some individuals being hesitant to move forward with mesh-based procedures. In the study data, more than 85 percent of women undergoing SUI surgery had a mesh-based procedure.

The new analysis may help to alleviate some patient concerns. "Our population-based study finds no evidence of increased risk of pelvic cancers following SUI surgery, with or without the use of transvaginal mesh," Dr. Vigil comments. "Providers can confidently reassure women regarding the lack of association."

INDIANAPOLIS--Worldwide, 1 in 4 people will suffer from a depressive episode in their lifetime.

While current diagnosis and treatment approaches are largely trial and error, a breakthrough study by Indiana University School of Medicine researchers sheds new light on the biological basis of mood disorders, and offers a promising blood test aimed at a precision medicine approach to treatment.

Led by Alexander B. Niculescu, MD, PhD, Professor of Psychiatry at IU School of Medicine, the study was published today in the high impact journal Molecular Psychiatry . The work builds on previous research conducted by Niculescu and his colleagues into blood biomarkers that track suicidality as well as pain, post-traumatic stress disorder and Alzheimer's disease.

"We have pioneered the area of precision medicine in psychiatry over the last two decades, particularly over the last 10 years. This study represents a current state-of-the-art outcome of our efforts," said Niculescu. "This is part of our effort to bring psychiatry from the 19th century into the 21st century. To help it become like other contemporary fields such as oncology. Ultimately, the mission is to save and improve lives."

The team's work describes the development of a blood test, composed of RNA biomarkers, that can distinguish how severe a patient's depression is, the risk of them developing severe depression in the future, and the risk of future bipolar disorder (manic-depressive illness). The test also informs tailored medication choices for patients.

This comprehensive study took place over four years, with over 300 participants recruited primarily from the patient population at the Richard L. Roudebush VA Medical Center in Indianapolis. The team used a careful four-step approach of discovery, prioritization, validation and testing.

First, the participants were followed over time, with researchers observing them in both high and low mood states--each time recording what changed in terms of the biological markers (biomarkers) in their blood between the two states.

Next, Niculescu's team utilized large databases developed from all previous studies in the field, to cross-validate and prioritize their findings. From here, researchers validated the top 26 candidate biomarkers in independent cohorts of clinically severe people with depression or mania. Last, the biomarkers were tested in additional independent cohorts to determine how strong they were at predicting who is ill, and who will become ill in the future.

From this approach, researchers were then able to demonstrate how to match patients with medications--even finding a new potential medication to treat depression.

"Through this work, we wanted to develop blood tests for depression and for bipolar disorder, to distinguish between the two, and to match people to the right treatments," said Niculescu. "Blood biomarkers are emerging as important tools in disorders where subjective self-report by an individual, or a clinical impression of a health care professional, are not always reliable. These blood tests can open the door to precise, personalized matching with medications, and objective monitoring of response to treatment."

In addition to the diagnostic and therapeutic advances discovered in their latest study, Niculescu's team found that mood disorders are underlined by circadian clock genes--the genes that regulate seasonal, day-night and sleep-wake cycles.

"That explains why some patients get worse with seasonal changes, and the sleep alterations that occur in mood disorders," said Niculescu.

According to Niculescu, the work done by his team has opened the door for their findings to be translated into clinical practice, as well as help with new drug development. Focusing on collaboration with pharmaceutical companies and other doctors in a push to start applying some of their tools and discoveries in real-world scenarios, Niculescu said he believes the work being done by his team is vital in improving the quality of life for countless patients.

"Blood biomarkers offer real-world clinical practice advantages. The brain cannot be easily biopsied in live individuals, so we've worked hard over the years to identify blood biomarkers for neuropsychiatric disorders," said Niculescu. "Given the fact that 1 in 4 people will have a clinical mood disorder episode in their lifetime, the need for and importance of efforts such as ours cannot be overstated."

Worldwide 39 percent of the adults were overweight in 2016, according to statistics of the World Health Organization. In the US the prevalence of obesity was 42.4 percent in 2017/2018, according to a survey of the National Center for Health Statistics (NCHS).

Concurrently millions of people want to lose weight. Physical exercise is an important option to achieve this. After all, more calories are consumed through sport than when sitting, standing or lying down.

But what influence does sport have on (direct) eating habits? Scientists at the Technical University of Munich (TUM) and the University of Nebraska (USA) have now investigated this question for the first time.

Randomized study

"In the sports context, we have the phenomenon of people overeating after physical activity," said Prof. Köhler, Professor of Exercise, Nutrition and Health at the Technical University of Munich. "People want to reward themselves and their bodies for being active. So we use a hypothetical experiment to find out why people eat more after exercise compared to when they don't exercise."

The aim of a randomized crossover study was to investigate the influence of exercise on hypothetical decisions regarding the amount and timing of food intake. For this purpose, 41 healthy participants (23 women, 18 men) aged between 19 and 29 years with an average BMI of 23.7 were randomly assigned to either a 45-minute exercise session or a rest period of equal duration at the first visit and completed the other study condition at the second visit.

Subjective assessment of hunger and satiety

In each case, the training group answered an electronic questionnaire before the physical activity about their subjective assessment of hunger and satiety, preferred amount of food to eat, and choice between foods that differed in timing of consumption. Subjects indicated their food quantity preferences by listing their desired portion size of each food. Preferences were obtained for both immediate and later consumption of the food after four hours.

After answering the first questionnaire, participants performed 45 minutes of aerobic exercise on a bicycle ergometer. Immediately afterwards, they completed the electronic questionnaire a second time and then a third time after a 30-minute break. The procedure for the group without training was identical; instead of 45 minutes of physical activity, these participants had a rest break.

Compared to the rest break, exercise provided a greater increase in the amount of food chosen, both immediately after exercise and 30 minutes afterwards. Physical activity also resulted in a greater increase in preference for immediate food consumption both immediately after exercise and 30 minutes afterwards.

Weight loss through exercise

"Based on this study, we were able to show for the first time that certain characteristics, such as the amount and 'urgency' with which a person wants to eat, change over the course of physical exertion," said Prof. Köhler, classifying the results. "These findings help us develop new interventions to optimize weight loss through exercise."

"The actual results suggest that physical exertion can entice those who do sport to eat larger amounts of food more quickly after the training session," says Prof. Köhler. "Since weight loss is a main motivation for exercising for many, and failure to achieve the desired weight loss makes it likely to quit exercising, it could be a good strategy to think about what you want to eat afterwards before you start to exercise."

How effective these and other possible strategies work, how they can improve long-term compliance with training programs and contribute to favorable health results through weight loss and whether the effect may eventually wear off, is the subject of the current research of the scientists.

WHO Eric Goralnick, MD, MS, Medical Director of Emergency Preparedness, Department of Emergency Medicine and the Center for Surgery and Public Health, Brigham and Women's Hospital; co-author of a new editorial published in American Journal of Public Health

Cheryl R. Clark, MD, ScD, Director, Health Equity Research & Intervention, Center for Community Health and Health Equity, Hospitalist, Division of General Medicine & Primary Care, Brigham and Women's Hospital; co-author of a new editorial published in American Journal of Public Health

WHAT During recent large-scale disasters, including the COVID-19 pandemic and major hurricanes, many hospitals and health care systems have activated their Hospital Incident Command System (HICS) to clarify roles and responsibilities and offer a clear organizational structure during a crisis. While forms of these systems have existed since the 1980s, one key element has been missing from HICS national guidelines: a focus on equity.

In a new editorial published in AJPH, Clark and Goralnick, both from the Brigham, and their co-author Richard Serino, NREMT-P, from the Harvard T.H. Chan School of Public Health, make the case for why a structural change is needed in the national HICS guidelines to ensure inclusion of an Equity Officer and subject matter experts in health care equity.

"The absence of equity as an emergency management principle in responses to COVID-19 has resulted in a slow and incomplete hospital response to the disproportionate mortality and morbidity in several historically marginalized populations," the authors write. "Defining an Equity Officer as a mandatory, core member of the command and general staff is a first step in mitigating inequities."

The authors describe the experience at the Brigham, where a diversity, equity and community health response team was established during the COVID-19 pandemic. Results from an after-action review helped identify strengths and weaknesses of the Brigham's HICS response.

"Many of those involved in the process acknowledged that we are at the beginning and have much work to do to ensure that equity is a core function of our response during the COVID pandemic and in future disasters," the authors write. "On the basis of our observations, we recommend a structural change to the national HICS guidelines: including an Equity Officer and embedded health equity specialists within each section."

Cardiovascular diseases are usually complex and affect multiple organs simultaneously. Treatments for vascular diseases in the brain may therefore have implications for the treatment of cardiac diseases. It is therefore important to understand the respective causes and effects. This study explores the causes of intracerebral haemorrhages and links them to the risk of stroke associated with atrial fibrillation. It suggests a fundamental new assessment of the effects of blood thinning on intracerebral haemorrhages.

About 1,000 patients with intracerebral haemorrhage are treated at stroke units each year in Switzerland. Intracerebral haemorrhages are more often fatal than other forms of strokes, and their incidence has not decreased in the past 30 years. The use of blood thinners was previously considered not only to be a risk factor but potential cause for a intracerebral haemorrhage.

Anticoagulation should not be regarded as primary cause

This publication includes the results of two studies conducted by the team of Prof. Werring. It contrasts the role of blood thinning with that of cerebral small vessel disease (SVD) in intracerebral haemorrhages. A moderate to severe cerebral SVD is shown to be closely associated with the occurrence of cerebral haemorrhages. Dr David Seiffge summarized the results as follows: "Our results show that SVD is a precondition for intracerebral haemorrhages under anticoagulation. The degree of SVD in the brain may be used to predict intracerebral haemorrhages. Without SVD the occurrence of intracerebral haemorrhage is close to zero. Consequently, anticoagulation should no longer be considered a cause of intracerebral haemorrhages."

Why is this important? Protection against stroke for patients with atrial fibrillation

Blood thinning offers important protection against ischemic stroke in patients with atrial fibrillation. Anticoagulation reduces the risk of ischemic stroke in these cases by two-thirds. In the past, anticoagulation has been discontinued immediately in the event of an intracerebral haemorrhage and patients were left unprotected against the risk of a stroke. The new study results now point to a new path: according to the findings, intracerebral haemorrhages can be prevented etiologically by treating cerebral SVD and protection against stroke can be maintained through an adapted continuation of blood thinning. The exact timing and gradation of the two therapies are the subject of further studies.

A challenging methodological approach: combining two multicentre studies

The publication comprises data originating from two independent studies supervised by Prof. David Werring, UCL.The publication is based on two independent, multicentre observational studies. First, a cross-sectional study was carried out with 1,030 patients with intracerebral haemorrhages. CT and MRI were used to look for markers of SVD in the brain. 1,447 patients with atrial fibrillation and cerebral circulatory disorders were enrolled in a second, prospective study. In this group, the incidence of cerebral haemorrhages and ischaemic stroke was considered in relation to blood thinning.

Using this approach, it was possible to show that SVD is a prerequisite for intracerebral haemorrhage. Patients without such a condition did not have a single brain haemorrhage within the first 2 years in the study, despite being treated with a blood thinner. In contrast, at 1.56% per year, the risk was significantly increased for moderate to severe SVD.

A new way of looking at the situation is needed

The study results suggest that blood thinning alone can no longer be considered a cause of intracerebral haemorrhages. Prof. Marcel Arnold points out: &laquoAs a new approach, microangiopathies should be systematically searched for and treated in a targeted manner in order to prevent intracerebral haemorrhages. Suitable specialist outpatient clinics are now available. This would reduce the risk of intracerebral haemorrhages.»

A large, international randomised trial (ENRICH-AF), coordinated in Switzerland by David Seiffge, is currently underway with the aim of aligning anticoagulation and microangiopathy therapies with each other.

Mobility tracking using cell phone data showing greater movement of people is a strong predictor of increased rates of COVID-19, according to new data in CMAJ (Canadian Medical Association Journal).

"This study shows that mobility strongly predicts [severe acute respiratory syndrome coronavirus 2] SARS-CoV-2 growth rate up to 3 weeks in the future, and that stringent measures will continue to be necessary through spring 2021 in Canada," writes Dr. Kevin Brown, Public Health Ontario, with coauthors.

Until Canadians are widely vaccinated against SARS-CoV-2, nonpharmaceutical public health interventions such as physical distancing and limiting social contact will be the main population-based means of controlling the spread of the virus.

"Mobility measures capturing human activity through anonymized tracking of smartphones are believed to be reasonable proxies of contact rates outside of one's own home; these measures can provide more timely and reliable sources of information on contact rates compared with time-use surveys or contact tracing," write the authors.

Researchers looked at anonymized smartphone mobility data from March 15, 2020, to March 6, 2021, both nationally and provincially, controlling for date and temperature. They found that a 10% increase in the mobility of Canadians outside their homes correlated with a 25% increase in subsequent SARS-CoV-2 weekly growth rates. They looked at the mobility threshold (the level needed to control the virus) and the mobility gap (the difference between the threshold and actual movement).

"The mobility threshold and mobility gap can be used by public health officials and governments to estimate the level of restrictions needed to control the spread of SARS-CoV-2 and guide, in real-time, the implementation and intensity of nonpharmaceutical public health interventions to control the COVID-19 pandemic," the authors write.

Cancer therapy in recent times relies on the use of several drugs derived from biological sources including different bacteria and viruses, among others. However, these bio-based drugs get easily degraded and therefore inactivated on administration into the body. Thus, effective delivery to and release of these drugs at target tumor sites are of paramount importance from the perspective of cancer therapy.

Recently, scientists have discovered unique three-dimensional, water-containing polymers, called hydrogels, as effective drug delivery systems (DDSs). Drugs loaded into these hydrogels remain relatively stable owing to the network-like structure and organic tissue-like consistency of these DDSs. Besides, drug release from hydrogels can be controlled by designing them to swell and shrink in response to certain stimuli, or minute changes in conditions, like temperature or pH (which determines the acidity of an environment). For instance, when conditions are just the right level of acidic in the tumor microenvironment, these DDSs either shrink or swell and release the drug.

However, there has been no method for the one-pot synthesis of hydrogels that respond to more than one such stimulus and degrade to release drugs at target tumor sites. Until now.

Now, a team of scientists, led by Professor Akihiko Kikuchi from Tokyo University of Science, reports the production of unique degradable hydrogels that respond to changes under multiple conditions in "reducing" environments mimicking the microenvironment of tumors. As Prof. Kikuchi observes, "In order to prepare degradable hydrogels that can release drugs in response to changes in the tumor microenvironment, we prepared hydrogels that respond to temperature, pH, and reducing environment, and analyzed their properties."

In their study published in the Journal of Controlled Release, Prof. Kikuchi--along with his colleagues from Tokyo University of Science, Dr. Syuuhei Komatsu, Ms. Moeno Tago, and Ms. Yu Ando, and his collaborator on the study, Prof. Taka-Aki Asoh from Osaka University--details the steps of designing these novel hydrogels from the synthetic polymer poly(ethylene glycol) diglycidyl ether and the sulfur-containing organic compound cystamine. In response to low temperatures, these hydrogels swell up while they shrink at the physiological temperature. Additionally, the hydrogels respond to pH changes by virtue of possessing tertiary amino groups. It must be noted here that the pH of the tumor microenvironment fluctuates between 5.5 and 6.5 owing to glycolysis in the tumor cells. Under the reducing conditions of this environment, the hydrogels degrade because of the breakage of disulfide bonds and change into low molecular-weight water-soluble oligomers that are easily excreted from the body.

To further test their drug release properties, the scientists loaded these hydrogels with specific proteins by exploiting their temperature-dependent swelling-deswelling behavior and tested the controlled release of drugs under acidic or reducing conditions. It was found that the amount of drug loaded onto these hydrogels could be controlled by changing the mesh size of the hydrogel polymer network by changing temperature, suggesting the possibility of customizing these DDSs for specific drug delivery. Besides, the hydrogel network structure and electrostatic interactions in the network ensured that the proteins were preserved intact until delivery, unaffected by the swelling and shrinking of the hydrogels with pH changes in the surrounding environment. The scientists found that the loaded protein drugs were completely released only under reducing conditions.

Using these hydrogels and the tractability that they provide, doctors may soon be able to design "customized" hydrogels that are specific to patients, giving personalized medicine a big boost. In addition to that, this new DDS provides a way to kill cancer cells that are left behind after surgery. As Prof. Kikuchi states, "The implantation of this material in the affected area after cancer resection may eliminate residual cancer cells, making it a more powerful therapeutic tool".

As cancer tightens its vise grip around the world, treatment options need to be varied and upgraded for customized and effective therapy. This unique and simple design technique to produce multi-stimuli-responsive hydrogels for effective drug delivery to target tumor sites may just be one among several such promising techniques to mount an answer to the challenge cancer poses to humanity.

New medicines for people who have diabetes seem to pop up all the time. Drugs that help the body break down carbohydrates, drugs that increase excretion of glucose in the urine, drugs that help muscles respond to insulin and drugs that stimulate the pancreas to produce it -- the list of pharmaceutical options to treat diabetes gets longer and longer.

The downside of this wealth of treatment options is that it can be difficult for health care providers to stay on top of the latest research and standards of care. Which medication is best for which patients? And what are the best medicines to prescribe that both lower blood glucose and reduce risk for cardiovascular disease?

Johns Hopkins Medicine endocrinologist and associate professor Rita Rastogi Kalyani, M.D., authored a clinical practice review article in the April 1 edition of The New England Journal of Medicine (NEJM) that distills the newest trial results and guidelines into a systematic approach for treating patients with diabetes and a risk of cardiovascular disease. Kalyani's article is the first clinical practice review that the journal has published on diabetes management in almost a decade.

Different from research studies, clinical practice reviews present a common clinical problem and the evidence supporting various treatment strategies, followed by a review of the guidelines and the author's clinical recommendations to optimize patient care.

People who have type 2 diabetes are more than twice as likely to develop atherosclerotic cardiovascular disease and heart failure than people who don't have the disease. The NEJM article presents an up-to-date approach for health care providers when choosing among glucose-lowering therapies for their patients with diabetes, particularly to reduce the risk of cardiovascular disease.

"We've seen a major shift in diabetes care over the past few years," says Kalyani. "We now have tools to better understand how to reduce both microvascular and macrovascular complications in people with type 2 diabetes."

The article examines the cardiovascular benefits and risks of the most commonly used drugs for diabetes that are currently available on the U.S. market.

Kalyani lists specific agents in two newer drug classes as beneficial for patients with diabetes who already show signs of heart or blood vessel disease.

The glucagon-like peptide 1 (GLP-1) receptor agonists liraglutide, injectable semaglutide and dulaglutide increase insulin production from the body, particularly after meals.

Sodium glucose cotransporter 2 (SGLT2) inhibitors empagliflozin and canagliflozin reduce the amount of glucose the body re-absorbs through urine.

All are effective at helping patients reduce the chance of having a major cardiovascular event, such as heart attack or stroke. The SGLT2 inhibitor, dapagliflozin, is effective at helping reduce the chance of hospitalization for heart failure.

"After metformin, which is widely considered the initial drug treatment for type 2 diabetes, specific drugs in the GLP-1 receptor agonist and SGLT2 inhibitor classes with demonstrated cardiovascular benefit should be considered as additional medications for patients who already have cardiovascular disease. This should be done irrespective of whether their A1C level is at target to reduce the risk of future cardiovascular events," says Kalyani, referring to the hemaglobin A1C test, which measures a patient's average blood glucose level over three months.

Sugar attaches to a protein in red blood cells that carries oxygen to organs and tissue and that transports carbon dioxide to the lungs. The A1C test measures the average percentage of glucose in a person's hemoglobin over the span of several months. Healthy A1C levels are below 5.7%. Generally, A1C levels higher than 6.5% indicate diabetes.

Kalyani notes that the newer drugs tend to be more expensive, and long-term effects are unknown. Before 2008, the U.S. Food and Drug Administration the agency that regulates the pharmaceutical industry -- did not require large outcome trials for drugs after their introduction to the market. As a result, says Kalyani, the cardiovascular effects of older drugs remain less certain.

The NEJM article details specific drugs that offer additional benefits for patients with diabetes who have conditions such as multiple cardiovascular disease risk factors, heart failure and chronic kidney disease.

"Some agents such as dulaglutide and dapagliflozin also have demonstrated cardiovascular benefit in patients with multiple cardiovascular risk factors," Kalyani says.

Further, specific SGLT2 inhibitors can be beneficial for patients who have heart failure with reduced ejection fraction -- a condition in which the heart muscle doesn't pump blood efficiently -- as well for patients with chronic kidney disease.

The article includes comprehensive drug tables that include the factors to consider in clinical practice when choosing a glucose-lowering drug for patients with type 2 diabetes, including A1C-lowering efficacy, route and frequency of administration, cost, effects on weight, risk of hypoglycemia, side effects and clinical benefits.

"Health care providers in primary care, endocrinology, cardiology and nephrology are now prescribing these newer glucose-lowering drugs for their patients," Kalyani says. "Diabetes care will need to be increasingly collaborative in the future and, at its core, remain patient-centered."

HERSHEY, Pa.-- Social distancing and lockdowns may have reduced the spread of COVID-19, but researchers from Penn State College of Medicine also report those actions may have affected clinical researchers' ability to finish trials. Study completion rates dropped worldwide between 13% and 23%, depending on the type of research sponsor and geographic location, between April and October 2020.

Researchers previously reported that more than 80% of clinical trials suspended between March 1 and April 26, 2020, noted the pandemic as their chief reason for halting activity. Patient enrollment in studies was lower in April 2020, compared to April 2019. Arthur Berg, associate professor of public health sciences, and Nour Hawila, a biostatistics doctoral candidate, investigated how these trends may have affected the completion of clinical trials.

The researchers examined more than 117,000 trials in the United States, Europe, Asia and other regions to study whether the pandemic affected clinical research. Their goal was to assess how the pandemic's mitigation efforts and financial setbacks may have contributed to decreased clinical trial enrollment and completion.

"The pandemic has made it more difficult for researchers to recruit and follow up on patients in clinical trials," said Hawila, a research assistant from the Department of Public Health Sciences. "This analysis revealed that the impact was substantial -- particularly for trials funded by government, academic or medical entities."

Hawila and Berg analyzed data from ClinicalTrials.gov, a website that contains information on the status of thousands of clinical trials in the U.S. Pre-COVID-19 enrollment and completion data was pulled from March 2017 to February 2020. The post-COVID-19 period was defined as April through October 2020.

According to researchers, the pandemic reduced the number of new interventional clinical trial submissions to ClinicalTrials.gov by about 10%. Completed trials were down 13% to 23%, depending on the sector and location of the trial source. Clinical trials sponsored by pharmaceutical, biotechnology and therapeutic companies were more likely to complete enrollment.

However, some regions fared better than others during the pandemic. Egypt experienced an increase in both submitted (69%) and completed (73%) clinical trials. Berg explained that the rise is likely in response to the country's recent parliamentary bill governing medical research.

Berg and Hawila also noted that the pandemic caused a shift in research priorities -- 472 (11%) of trials submitted during the post-COVID period were pandemic-related. The results were published in the journal Clinical and Translational Science.

"Clinical research response to the pandemic has been robust," said Berg, a Penn State Cancer Institute researcher and biostatistics doctoral program director. "But the impact of the pandemic on other types of clinical trials will be felt for decades to come. However, as demonstrated in Egypt, timely governmental action may be able to make a difference in reversing the pandemic's impact on research."

New research published in the British Journal of Pharmacology indicates that two currently available medications--an antifungal drug and an antidepressant--can effectively inhibit the virus that causes COVID-19 in laboratory cells.

Investigators found that the antifungal itraconazole and the antidepressant fluoxetine each blocked the production of infectious SARS-CoV-2 virus in cell culture lab tests. When either drug was used in combination with the antiviral drug remdesiver, the combination showed synergistic effects and inhibited the production of SARS-CoV-2 by more than 90%.

"Preventive vaccination and therapeutic medicines against COVID-19 are both required to effectively combat pandemics caused by emerging zoonotic viruses such as SARS-CoV-2," said senior author Ursula Rescher, PhD, of the University of Muenster, in Germany.

Smoking increases symptoms and health risks for patients with rheumatic diseases, but interventions to help patients quit are rarely available at rheumatology clinics. A study published in Arthritis Care & Research has found that Quit Connect--a protocol involving electronic health record prompts for nurses and medical assistants in rheumatology clinics--can increase electronic referrals to free, state-run tobacco quite lines.

Implementing Quit Connect led to electronic referrals for 71% of patients who were identified as ready to quit, with referrals taking less than 90 seconds for medical staff to complete.

"There's a huge opportunity to address smoking as a modifiable risk factor in rheumatology patients, and Quit Connect was 26-times more effective than usual care for delivering evidence-based quitline support," said lead author Christie M. Bartels, MD, MS, of the University of Wisconsin School of Medicine and Public Health. "Moreover, Quit Connect leverages free resources available in every state and was cost-effective for quit attempts and cessation."

On the first day of the UK campaign for COVID-19 vaccination, there were reports of two cases of anaphylaxis—a severe, potentially life-threatening allergic reaction—within minutes of administration of the Pfizer/BioNTech mRNA vaccine. Subsequently further cases of suspected anaphylaxis to the Pfizer vaccine were reported. A new report published in Clinical & Experimental Allergy reveals that an allergy to the ingredient polyethylene glycol (PEG) is a cause of anaphylaxis to the vaccine. However, this is in the context of millions of doses safely administered.

The authors note that very few people are allergic to PEG, and they provide a guide to identifying those who are at risk. “This preliminary report confirms PEG as a cause of anaphylaxis to the Pfizer/BioNTech vaccine, for the first time,” they wrote. “COVID-19 vaccine anaphylaxis and PEG allergy are both rare, so proof of PEG as the cause in one case of vaccine anaphylaxis is important. However, it is important to emphasise that PEG allergy is rare and that COVID-19 vaccines remain safe.”

URL Upon Publication: https://onlinelibrary.wiley.com/doi/10.1111/cea.13874

April 6, 2021, Alexandria, VA - The American Academy of Otolaryngology?Head and Neck Surgery Foundation published the Clinical Practice Guideline: Opioid Prescribing for Analgesia After Common Otolaryngology Operations today in Otolaryngology-Head and Neck Surgery. This specialty-specific guideline provides evidence-based recommendations on postoperative management for pain in common otolaryngologic procedures, with a focus on opioids.

"As otolaryngologist-head and neck surgeons, we can help reduce the risk of opioid use disorder among our patients and their families," said Samantha Anne, MD, MS, Chair of the Guideline Development Group (GDG). "This clinical practice guideline focuses on multimodal analgesia and judicious use of opioids for common otolaryngology procedures."

Opioid use disorder (OUD), which includes misuse, abuse, and overdose of opioids, is an epidemic in the United States. According to data from the National Survey on Drug Use and Health, more than six million people ages 12 or older misuse prescription pain relievers in a given year in the United States. Additionally, studies have shown that there is a significant risk of chronic opioid use even when used as short-term treatment for pain.

The guideline addresses assessment of patients for OUD risk factors, counseling on pain expectations, and identifying factors that can affect pain duration and/or severity. It also discusses the use of multimodal analgesia as first-line treatment and responsible use of opioids. In addition, the guideline highlights quality improvement opportunities in postoperative pain management of common otolaryngologic surgeries. Employing the key action statements from this clinical practice guideline (CPG) can help to reduce the variation in care across the specialty of otolaryngology and improve postoperative pain control while reducing the risk of OUD.

"Many times, opioids are prescribed in excessive quantities for procedures that are associated with mild-to-moderate pain, such as parathyroidectomy, thyroidectomy, and otologic surgeries. The number of opioids prescribed for these procedures can be reduced, especially if appropriate multimodal analgesia is used," says Dr. Anne. "The guideline also emphasizes the importance of counseling patients and identifying patient- and procedure-related factors that can inform shared decision-making."