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The tuberculosis (TB) vaccine Bacillus Calmette-Guerin (BCG) could protect newborns against a variety of common infections, such as upper respiratory tract infections, chest infections and diarrhoea, according to a new study in The Lancet Infectious Diseases.

The research is the first of its kind to rigorously investigate the full range of illnesses BCG could protect infants against. It suggests that vaccinating all babies on the day of birth with BCG could reduce neonatal infections and death in areas with high infectious disease rates, potentially saving thousands of lives a year. The results also increase the possibility that the vaccine might be used to protect children and adults against COVID-19 and other new infectious diseases.

Led by the London School of Hygiene & Tropical Medicine (LSHTM) through the MRC/UVRI & LSHTM Uganda Research Unit, and funded by the Wellcome Trust, the study involved a randomized control trial of 560 newborns in Uganda, who were monitored for a range of illnesses.

After six weeks, infection rates from any disease were 25% lower in the group who received the vaccine at birth, compared to the group that had not yet received the vaccination. Particularly vulnerable groups such as low birth weight babies, and boys, seemed to be protected the most. Importantly, BCG appeared to protect against mild, moderate and severe types of infections.

Sarah Prentice, lead author from LSHTM, said: "Nearly a million babies die every year of common infections so we urgently need better ways to protect them. Our research suggests that ensuring that BCG is given at birth could make a big difference in low income countries, potentially saving many lives."

In the study, healthy Ugandan infants were randomly assigned to receive BCG at birth or at six weeks of age. The infants were followed-up by doctors, blinded to the intervention, for 10 weeks to look for episodes of any type of illness or infection.

The research team then compared how often infants in the two groups presented to doctors with infections of any kind, except TB, to see whether having BCG made a difference. They also took blood samples from both groups, to look at differences in their innate immune system, the body's first line of defence against infections.

Infants who had been vaccinated with BCG at birth presented to doctors with any kind of infection 25% less often than infants who had not. Protection from BCG didn't seem to be against one specific type of infection, but for all types, such as common colds, chest infections, and skin infections.

After the group receiving BCG at six weeks had been vaccinated, there was no difference in the rates of infection between the two groups - the delayed group's immunity 'caught-up' once they'd received BCG.

Hazel Dockrell, Professor of Immunology at LSHTM and one of the co-authors of the study, adds: "It's very exciting to think that BCG vaccination might help keep newborns safe against other dangerous infections, in addition to providing protection against TB. Although BCG is recommended at birth in many countries, it is often delayed due to logistical difficulties. Ensuring that the vaccine is given on day one, in areas with high rates of infectious disease, could have a major impact on infections and deaths in the newborn period."

The team can't definitively say why BCG offered this additional non-specific protection, but the research showed evidence of changes in the innate immune system of vaccinated infants, which may suggest that BCG boosts the immune system to work better against any infection.

This has led the researchers to suggest that it could provide protection in the early stages of novel outbreaks, such as COVID-19 or Ebola, before specific vaccines have been developed.

Further studies are already underway to explore whether BCG could play a role in the response to COVID-19, with large trials involving health care workers and the elderly. The Director General of WHO Dr Tedros Ghebreyesus has co-authored an article expressing interest in the possible use of BCG for protection against COVID-19.

Dr Prentice said "Since the findings show that BCG seems to offer wider protection against a range of infections, our study also raises hopes it might be useful in protecting the general population against COVID-19 and future pandemics - though we will need to see the results of other, more specific studies to know for sure."

The researchers also believe it is worth investigating whether reintroduction of BCG in countries where it is no longer in routine use, such as the UK, is beneficial, not for its effects against TB, but to protect vulnerable infants in neonatal units against other infections.

The authors acknowledge limitations of their study. As it was relatively small, it was not possible to show an effect of BCG on numbers of deaths from infections in the study participants. Also, because the study was only conducted in Uganda, it cannot be certain that these extra, beneficial effects of BCG would be seen in other settings. However, previous studies conducted in West Africa have shown a reduction in neonatal deaths following BCG at birth, to a similar extent as the reduction in infection rates seen in this study.

A neural network system that analyzes photographs can rank and distinguish suspicious, potentially precancerous skin lesions, which can turn into the deadly skin malignancy melanoma if not caught and removed early. The system accurately scoped out suspicious lesions from 68 patients in a manner that mostly matched tried-and-true evaluations from dermatologists. The results suggest the platform could help clinicians spot suspicious lesions during clinical visits faster and on a larger scale, potentially allowing for earlier diagnosis and treatment. Melanoma is the deadliest form of skin cancer, but outcomes can be very good for patients who have their melanomas removed during the disease's earliest stages, when the lesion is still thin and has not spread deep into the skin. To screen for melanomas, clinicians typically evaluate large skin surfaces with the ABCDE set of criteria, searching for "ugly duckling" lesions that show signs of being pre-cancerous. Authorities have also started to roll out large skin cancer screening programs to reduce the burden of melanoma, but clinics lack scalable tools that can assess lesions in large numbers of patients. Here, Luis Soenksen and colleagues designed a neural network platform that takes photographs of skin lesions - even those taken with a cell phone camera - and rapidly identifies suspicious markings that may need follow-up testing. The team trained their technology with 38,283 photographs, including skin photos from 133 patients, and observed the method distinguished suspicious lesions from nonsuspicious ones with a sensitivity and specificity of 90.3% and 89.9%, respectively. In a separate experiment, the strategy also ranked "ugly duckling" lesions on the skin of 68 patients, yielding rankings that mostly matched assessments from 3 dermatologists. The authors add that future improvements may help address some current limitations with the system, such as by making it work with a wider range of cameras, light settings, and photographers.

The trial found that using sensor-based asthma inhalers may improve control of the condition and improve the quality of life for caregivers.

Greatest gains were among non-Hispanic Black participants, who experience more frequent and severe asthma than other groups.

Based on the study results, this asthma intervention should be considered for use by primary care, allergy and pulmonary care providers, to help engage diverse populations of pediatric asthma patients and their caregivers.

CHICAGO (February 17, 2021) -- Sensor-based inhalers integrated into health care providers' clinical workflows may help improve medication adherence and support children with asthma - and their families - to more effectively manage this condition, according to a new Northwestern and Lurie Children's study published in Pediatrics. The study, developed in collaboration with UnitedHealth Group, showed the use of sensor-based inhaler monitoring may help improve asthma symptom control and caregiver quality of life.

Connected inhalers, which use Bluetooth sensors that attach to participants' asthma inhalers to detect medication use and share the data with physicians, may promote adherence to recommended controller medication use and proactively detect worsening of asthma symptoms, according to the study. As a result, this may enable health care providers to intervene more rapidly--before patients become critically ill--and improve communication between patients, caregivers and asthma care providers.

"Emerging connected technologies can help improve patient health, with this randomized-controlled clinical trial showing that pediatric asthma patients with access to inhaler sensors report better asthma control and quality of life than patients who only received a standardized asthma education curriculum," said study lead Dr. Ruchi Gupta, professor of pediatrics at Northwestern University Feinberg School of Medicine, physician at Ann & Robert H. Lurie Children's Hospital of Chicago and the Director of the Center for Food Allergy & Asthma Research (CFAAR).

Children participating in the study were evaluated based on an Asthma Control Test questionnaire, which measured their asthma symptom control on a scale from 0 (poor control) to 27 (well-controlled). Average scores among the intervention increased by 10.1% over the course of the study, with the greatest improvements among non-Hispanic Black participants.

Caregivers who participated in the study were assessed based on a Pediatric Asthma Caregiver's Quality of Life questionnaire, measuring how the sensor-based monitoring adherence affected their day-to-day involvement. Caregivers reported improvement to their quality of life after the first month of the study, which was sustained through the year-long trial, due to greater ease of asthma management.

"This study is another clear example that digital health is here to stay, as it allows for us to stay connected to patients living with chronic disease, provide a level of automated watchfulness, and intercept disease in a timely manner," said Deneen Vojta, MD, Chief Physician Executive for Optum Labs, part of UnitedHealth Group. "This is a terrific example of moving from the best care out there today to the best care possible."

More than 25 million Americans currently have asthma, most of whom are prescribed inhalers designed to prevent and treat asthma attacks. With appropriate management, most asthma patients can control their disease and live symptom-free. However, for patients with moderate-to severe disease, this generally requires daily use of "controller" medications -- typically an inhaled corticosteroid -- as well as occasional use of "rescue" medications (i.e. albuterol).

While previous studies have also explored the feasibility and effectiveness of using these sensor-based mobile interventions to improve asthma management, this study was the first to systematically evaluate its effectiveness in a large, racially/ethnically and socioeconomically diverse sample of children.

All 252 children enrolled in this study had moderate/persistent asthma and were recruited from five clinics (three primary care, one allergy and one pulmonary). Participants were 24% non-Hispanic White, 23% non-Hispanic Black and 40% Hispanic, while 60% were on public insurance. The study lasted 12 months and included assessment at enrollment, three months, six months, nine months, and one year.

Durham, NC- Can stem cells alleviate lymphedema, a chronic debilitating condition affecting up to one in three women treated for breast cancer? Results of a phase I clinical trial released today in STEM CELLS Translational Medicine (SCTM) show there is a strong possibility that the answer is yes.

Lymphedema is swelling due to a build-up of fluid in lymph nodes - vessels that help rid the body of toxins, waste, and other unwanted materials- usually occurring in an arm or leg. While it can be the result of an inherited condition, its most common cause in the Western world is the removal of or damage to the lymph nodes during the course of cancer treatment. The results can be both physical (the swollen area can be stiff and/or sore and there is an increased chance of infection) and cosmetic (the skin can become leathery and scarred, and the affected limb can be grossly swollen and deformed).

Mads Gustaf Jørgensen, M.D., of the Department of Plastic Surgery, Odense University Hospital in Denmark, is corresponding author of the study whose results are detailed in SCTM. "Patients with breast cancer-related lymphedema (BCRL) have reduced quality of life and arm function. Current treatments are palliative only. The focus is on controlling the condition through exercise, compression garments and pumps, manual drainage, meticulous skin care, therapy and a healthy lifestyle.

"However, while treatments to improve lymphedema are lacking, preclinical studies suggest that adipose-derived regenerative cells (ADRCs) can alleviate lymphedema," he said. "We, therefore, aimed to assess whether ADRCs can alleviate lymphedema in clinical reality with long-term follow-up."

The study's primary endpoint was change in arm volume, with secondary endpoints of safety, change in lymphedema symptoms, quality of life, lymphedema-associated cellulitis and conservative treatment use.

To conduct their study, the team treated 10 BCRL patients with ADRCs - which are harvested from adult fat - and a scar-releasing lipotransfer to the axillary region. When they followed up with each patient at intervals of 1, 3, 6, 12 and 48 months post-treatment, they saw no significant decrease in BCRL volume.

"However," Dr. Jørgensen said, "self-reported upper extremity disability and arm heaviness and tension improved. Six patients reduced their use of conservative BCRL treatment. Five felt that their BCRL had improved substantially, and four of these would redo the treatment. We did not observe any cases of locoregional breast cancer recurrence."

"This has led us to conclude that axillary-delivered ADRCs and lipotransfer are safe, feasible and improved BCRL symptoms and upper extremity function. Their effectiveness was observed shortly after treatment and sustained for up to four years. Randomized controlled trials are needed to confirm the results of this study," he added.

"These results are certainly promising because the therapy appears to be safe, feasible and minimally invasive," said Anthony Atala, M.D., Editor-in-Chief of STEM CELLS Translational Medicine and Director of the Wake Forest Institute for Regenerative Medicine. "This study highlights the ability of these fat-derived stem cells to potentially alleviate lymphedema and cellulitis in patients. We look forward to the continuation of this research to further document clinical efficacy."

After more than 1,000 orthopaedic procedures at a city health system, roughly 61 percent of the opioids prescribed to patients went unused, according to new research. This was discovered within a study at the Perelman School of Medicine of the University of Pennsylvania that showed most patients responded to text messages designed to gauge patients' usage of their prescriptions. Knowing that so many patients are comfortable texting this information to their care teams is extremely useful as medical professionals look to right-size painkiller prescriptions and reduce the amount of opioids that might be misused when they're left over. This study was published in NEJM Catalyst.

"This approach is a step toward building a dynamic learning health system that evolves to treat patients," said the study's lead author, Anish Agarwal, MD, an assistant professor of Emergency Medicine. "We know that the opioid epidemic has struck the nation in many ways. One of the key areas to address is reducing the amount of 'leftover' opioid pills in the community which pose a risk to individuals, families, and children."

Clinicians know that a balance needs to be struck between pain management and opioid pain medications, but there is little by way of patient data to guide them. Opioid prescription quantities have largely been best estimates based on how clinicians were trained or a rough estimate using a patient's medical history. Agarwal, senior author M. Kit Delgado, MD, co-chair of the Penn Medicine Opioid Task Force and an assistant professor of Emergency Medicine, and their colleagues sought to fine-tune those estimates and adjust guidance on a procedure-by-procedure case. To do that, they sought a way to deliver real-time numbers on how much pain medication patients actually use. The system they developed centered on automated conversational text messaging.

Patients were recommended to join the automated system by their clinical team, then would receive text messages introducing them to the program on the fourth day following their procedure. If the patient responded that they'd like to take part, the automated system triggered a simple text conversation. It asked questions about things like patients' levels of pain, their ability to manage the pain, and their use of their prescription opioids. These messages were set to go out on the fourth, seventh, fourteenth, and twenty-first days after their procedures. If patients indicated at any point that they weren't taking the opioid pain medication anymore, the messages stopped.

The research team reached out to roughly 2,400 patients of orthopaedic procedures between September 2018 and January 2020. Roughly half consented to taking part in the program, which, in itself, was a significant finding for the researchers because it showed a widespread willingness to use this type of system. On top of that, the researchers saw an extremely high rate of responses among these patients with 88 percent responding on the fourth post-operative day. The lowest rate of responses was seen on the patients' seventh day (at 69 percent). For those patients using medications at day 21, 95 percent responded.

Overall, patients reported a decrease in their pain levels across all procedures. But this appeared to be accomplished without the majority of the opioids that were prescribed. More than 1,100 patients took part in the texting system, and from that population, the researchers discovered that more than 10,000 opioid tablets were left unused, roughly 61 percent of those that had been prescribed. While research is slim on the subject, that is within the range, though on the higher end, of what is thought to be the average amount of leftover opioids from medical procedures.

Agarwal believes that through establishing a system like this - which patients took up at high rates - gives clinicians a patient-centered, real-time feedback system that could be used to adjust opioid prescription levels and reduce the chance of their being leftover pills that could be misused.

"Our system works as a quality improvement mechanism and a way for providers to see trends in patient-reported pain and opioid use following their surgeries," Agarwal said. "We can collect the data, analyze it, and inform future prescribing to predict and meet the needs of our patients going forward."

One of the goals of the team researching this texting system is to potentially pinpoint what levels of opioids would be needed for each type of procedure. For instance, current prescribing practices may be overshooting the pain management needs of a shoulder surgery patient, but roughly right for someone getting a hip replacement.

"As orthopaedic surgeons, we are always concerned that we will not provide enough medicine to care for our patients' post-operative pain. In the past, it was truly a calculated guess erring on the side of not underprescribing," explained study co-author Brian Sennett, MD, the chief of Sports Medicine and an associate professor of Orthopaedic Surgery at Penn Medicine. "Our goal is to treat our patients well while not overprescribing. In the future, I am excited about sharing this data with our patients and having them involved in their post-operative pain management, which I believe will result in the next great reduction in opioid prescribing."

Although this study used orthopaedic surgeries to test the system, Agarwal said it opens the door for pain management observations across many departments.

"This is the beginning of a lot of exciting work supported by many Departments, the University, and the FDA," Agarwal said.

BOSTON -- Numerous studies have demonstrated the role of physical activity in improving heart health for patients with type 2 diabetes. But whether exercising at a certain time of the day promises an added health bonus for this population is still largely unknown. Now, research published in Diabetes Care by Brigham and Women's Hospital and Joslin Diabetes Center investigators, along with collaborators, reports a correlation between the timing of moderate-to-vigorous physical activity and cardiovascular fitness and health risks for individuals who have type 2 diabetes and obesity or overweight.

The research team found that, in its study of 2,035 people, men who performed physical activity in the morning had the highest risks of developing coronary heart disease (CHD), independent of the amount and intensity of weekly physical activity. Men most active midday had lower cardiorespiratory fitness levels. In women, the investigators did not find an association between specific activity timing and CHD risk or cardiorespiratory fitness.

"The general message for our patient population remains that you should exercise whenever you can as regular exercise provides significant benefits for health," said corresponding author Jingyi Qian, PhD, of the Division of Sleep and Circadian Disorders at the Brigham. "But researchers studying the effects of physical activity should take into account timing as an additional consideration so that we can give better recommendations to the general public about how time of day may affect the relationship between exercise and cardiovascular health."

The researchers analyzed baseline data from the Look AHEAD (Action for Health in Diabetes) study, a multi-site, randomized clinical investigation that began in 2001 and monitored the health of more than 5,000 individuals with type 2 diabetes and overweight or obesity. Among them, over 2,000 individuals had objectively measured physical activity at baseline.

"The study population was very well characterized at baseline, with detailed metabolic and physical activity measurements, which was an advantage of using this dataset for our work," said corresponding author Roeland Middelbeek, MD, of the Joslin Diabetes Center, who is a co-investigator of the Look AHEAD study.

For the Diabetes Care article, the researchers reviewed data from hip-mounted accelerometers that participants wore for one week at the beginning of the Look AHEAD study. The researchers tracked the "clock-time" of daily moderate-to-vigorous activity, including labor-intensive work that extends beyond more traditionally defined forms of exercise. To assess the participants' risk level of experiencing CHD over the next four years, the researchers used the well-known, sex-specific Framingham risk score algorithm.

Sex-specific physiological differences may help explain the more prominent correlations seen in males, who tend to be at risk of CHD earlier in life. However, the researchers note that other factors could also be at play. It remains unclear why time-specific activity may be associated with different levels of health and fitness.

The researchers also could not account for participants' varying circadian rhythms: whereas a jog at 6 p.m. for one participant may be "evening exercise," another participant prone to waking later in the day may, biologically, consider it to be "afternoon," regardless of how the clock-time of the activity was recorded in the study.

"Interest in the interaction between physical activity and the circadian system is still just emerging," Qian said. "We formed a methodology for quantifying and characterizing participants based on the clock-time of their physical activity, which allows researchers to carry out other studies on other cohorts."

Beyond further integrating circadian biology with exercise physiology, the researchers are also excited to use longitudinal data to investigate how exercise timing relates to cardiovascular health outcomes, particularly among diabetes patients more vulnerable to cardiovascular events.

WASHINGTON --- Recent data reveals that gay men living with HIV report having supportive relationships with family, friends, or in informal relationships rather than with primary romantic partners, while gay men who are HIV negative report having relationships mainly with primary partners. Additionally, gay men living with HIV were more likely to report no primary or secondary supportive partnerships compared to men who are HIV negative. The analysis was led by researchers at Georgetown University Medical Center.

Along with successful HIV treatments, it is known that the presence of social support impacts long-term survival among men living with HIV. However, little has been known about the types of supportive relationship among gay men in general, and none for those men living with HIV. Identifying the types of relationships could inform how they impact healthy aging among this community of men.

To fill this knowledge gap, Georgetown researchers conducted a study to identify the types of supportive relationships among middle-aged and older gay men living with and without HIV.

The finding appears February 17, 2021, in PLOS ONE.

Lead author Matthew Statz, a 3rd year medical student at Georgetown University School of Medicine, and his colleagues, collected supportive relationship data from 1,054 men participating in the Multicenter AIDS Cohort Study (Baltimore-Washington, DC, Chicago, Pittsburgh, and Los Angeles) from 2016-2019.

The average age of the men was 62, with similar numbers of HIV positive and negative men. The study participants were asked about any primary or secondary supportive relationships in their life. A primary relationship was defined as a long-term relationship that included marriage, other forms of legal commitment, or a strong romantic commitment between partners. Secondary relationships included close friends, biological family members, chosen family sexual partners, or former romantic partners.

"We recognized that little was known about the types of supportive relationships these men had -- whether they were in committed romantic relationships, or if they relied on other non-romantic partnerships, such as family and friends," said Statz.

"The large number of older gay men, regardless of their HIV status, who reported having neither a primary nor secondary supportive relationship was unexpected and concerning," said Statz. "The importance of social support has been clearly established in the management of chronic illness, including HIV."

Statz says the study paves the way for further research into how these men’s partnerships impact all aspects of their mental and physical health, including implications for HIV viral suppression, frailty and loneliness.

Tsukuba, Japan -- As March comes around, many people experience hay fever. As excessive immune responses go, most would admit that hay fever really isn't that bad. At the other end of the spectrum are severely debilitating autoimmune diseases like rheumatoid arthritis and multiple sclerosis. A common thread in all these conditions are cytokines, molecules that cause inflammation. Recent research by the University of Tsukuba sheds light on the effect of excessive cytokines on neuronal and glial cells in the brain.

Researchers led by Professor Yosuke Takei and Assistant Professor Tetsuya Sasaki at the University of Tsukuba in Japan have been studying an important cytokine called interleukin (IL)-17A. Their recent study shows that chronic increases in the levels of IL-17A circulating in mouse blood can reduce the microglia activity in one part of the brain's hippocampus. This might explain why it's related to several neurological diseases.

The researchers focused on IL-17A because it is known to be involved in neurological autoimmune disorders as well as disorders of the mind. "In addition to being linked to multiple sclerosis," explains Sasaki, "recent reports show that IL-17A is also a factor in Alzheimer's disease, schizophrenia, and autism spectrum disorder." To study how chronically high levels of IL-17A can affect the brain, the team used their knowledge of how IL-17A is made naturally in the body.

The researchers focused on immune cells called helper T-cells. Helper T-cells come in many varieties, each one making its own cytokine, and each one created from a generic helper T-cell. "Our strategy," says Sasaki, "was to induce more generic helper T-cells to become the kind that produce IL-17A." With more of these helper T-cells, called Th17, the mutant mice did indeed produce more IL-17A in the gut, which spread throughout the body in the blood.

IL-17A is known to interact with two kinds of glial cells in the nervous system, astrocytes and microglia. The researchers found that chronically high IL-17A led to reduced activity and density of microglia in one region of the hippocampus, a part of the brain that is needed for learning and forming memories. In contrast, astrocytes in the brain did not differ between the mutant and control mice. Thus, there was reason to believe that chronic IL-17A inflammation would affect cognition, specifically memory. Surprisingly, spatial memory seemed to be just as good in the mutant mice as in the control mice.

"These mutant mice can be used in future studies as a model for chronic IL-17A-related inflammation," says Takei. "Further neuronal and behavioral testing will help us begin to understand IL-17A's role in a range of debilitating neurological disorders."

Women who received physical therapy after undergoing a cesarean section had significantly improved outcomes compared to those who did not according to a new study from University of Missouri Health Care.

"C-section is one of the most commonly performed inpatient procedures, and women who require C-section instead of a spontaneous vaginal delivery are at least twice as likely to suffer low back and pelvic pain," said study author Jennifer Stone, DPT, of MU Health Care's Mizzou Therapy Services. "Our goal was to evaluate the impact of comprehensive physical therapy on recovery following a cesarean birth."

Stone's study recruited 72 women who delivered by cesarean section between 37 and 42 weeks gestation. A control group of 39 patients received the standard of care for the hospital, which included a physical therapy consultation, written information about scar management and a suggested abdominal exercise. The remaining 33 patients received six weeks of physical therapy, which included scar therapy and mobilization for the lower back, hip joint and soft tissue. They also received stretching, core stabilization exercises and exercises to do at home. Researchers used a visual pain rating scale, a disability index scale, a patient satisfaction questionnaire and a self-rated exercise confidence scale to measure outcomes at eight and 14 weeks, and then at six,12 and 18 months.

"We found that participants who received physical therapy once or twice per week achieved substantially lower pain levels more quickly than participants in the standard-of-care group," Stone said. "Those in the physical therapy group also had higher patient satisfaction scores at both 14 weeks and six months."

Stone also learned that there was significantly improved self-reported ability to perform exercise in the physical therapy group at 14 weeks and one year as compared to the control group. However, study results do not support statistically significant differences between groups in pain after six months or patient satisfaction after one year or 18 months. Stone said more studies will be needed with a larger sample size to provide more insightful outcomes.

Scientists from the Stanley Manne Children's Research Institute at Ann & Robert H. Lurie Children's Hospital of Chicago demonstrated that a nanotherapy reduces intestinal inflammation and shrinks lesions in a rodent model of severe Crohn's disease. This approach could become an alternative to biologic antibody therapies that carry many side effects, including increased risk of certain cancers. It might also prevent the need for surgery in the future. Findings were published in the journal Advanced Therapeutics.

Crohn's disease is an inflammatory bowel disease characterized by chronic inflammation of the digestive tract, most often in the small intestine. It can lead to intestinal obstruction and perforation, bleeding, abdominal pain, severe diarrhea, fatigue, weight loss and malnutrition leading to growth abnormalities in children. One of the key features of Crohn's disease is lesions along discontinuous segments of the intestine. Current treatments include biologic antibody therapies, and in severe cases surgery, which is not curative. It is estimated that 70 percent of patients with Crohn's disease will require surgery during their lifetime and many will require additional surgery.

"We injected into the intestinal lesion nanomolecules that carry an anti-inflammatory peptide, which is a tiny portion of a protein," says senior author Arun Sharma, PhD, Director of Surgical Research at the Manne Research Institute at Lurie Children's and Research Associate Professor of Urology and Biomedical Engineering at Northwestern University Feinberg School of Medicine and McCormick School of Engineering. "The results were phenomenal. We saw reduction in inflammation based upon reductions in pro-inflammatory immune cells and proteins. The lesion size shrunk dramatically, which gives us hope that with this therapy we can salvage inflammatory tissue and avoid needing to surgically remove segments of the intestine in severe cases of Crohn's disease."

Based upon their design, these nanomolecules allow for a very concentrated dose to be introduced into a lesion. Dr. Sharma and colleagues observed that it creates an anti-inflammatory environment that not only keeps the lesion from growing but also reduces its size.

"Our study provides proof of principle findings that this nanotherapy can be effective for Crohn's disease and may be applicable to other inflammatory bowel diseases, such as ulcerative colitis," says Dr. Sharma. "Before we can translate this work to clinical application, we need to develop a less invasive mode of delivery, such as oral or via endoscopy."

INFORMS Journal on Applied Analytics Key Takeaways:

Although waiting times in walk-up clinics are shorter, people preferred the convenience of drive-through clinics.

People believe drive-through clinics are safer, more convenient and less contagious.

You can vaccinate a large number of people without a lot of waiting and confusion using a drive-through clinic.

CATONSVILLE, MD, February 17, 2021 - Policymakers at all levels of government are racing to vaccinate hundreds of millions of people to save lives and blunt the deadly COVID-19 pandemic. New research published in the INFORMS Journal on Applied Analytics provides a simulated model for drive-through clinics that can be used for mass COVID-19 vaccinations based on the successful use of such a clinic to address H1N1.

The paper, "Lessons from Modeling and Running the World?s Largest Drive-Through, Mass Vaccination Clinic," looks at data from The Louisville Metro Public Health and Wellness department during the H1N1 vaccinations. The authors, Sunderesh Heragu of Oklahoma State University and Thomas van de Kracht of Vanderlande Industries, note that a total of 19,318 residents were vaccinated via a drive-through and a walk-up clinic over 1.5 days - nearly two-thirds of whom specifically used the drive-through clinic. The authors found that people preferred the convenience of drive-through clinics because they perceived it was safer, more convenient and less contagious.

"As policymakers address how to bolster mass vaccinations for COVID-19, drive-through vaccination sites offer a means to inoculate people faster and with less waiting and confusion as compared to other mass vaccination approaches," said Heragu, a Regents professor and head of the School of Industrial Engineering and Management at OSU. "This could readily be done in literally every single community, transforming the trajectory of the COVID-19 pandemic once and for all."

Adequate spacing between births can help to alleviate the likelihood of stunting in children, according to a new study from the Tata-Cornell Institute for Agriculture and Nutrition (TCI).

In an article published in the Proceedings of the National Academy of Sciences of the United States of America, TCI postdoctoral associate Sunaina Dhingra and Director Prabhu Pingali find that differences in height between firstborn and later-born children may be due to inadequate time between births. When children are born at least three years after their older siblings, the height gap between them disappears.

India's family planning policies have focused on lowering population growth and postponing pregnancy to improve maternal health outcomes. But while the overall fertility rate has fallen as low as 2.1, there has been little progress increasing the period between births. In 2015, approximately 60% of women surveyed waited less than the recommended period of three years between children.

The TCI study shows that placing a greater focus on sufficient birth spacing in maternal and child nutritional policies and public health programs could help to prevent stunting.

"Our research suggests that adequately spacing out births can significantly lower stunting and the myriad bad effects it causes," Dhingra said. "Policymakers should ensure that family planning programs emphasize the importance of allowing sufficient time between pregnancies, in addition to reducing the number of births and delaying first pregnancies."

A marker of chronic undernutrition, stunting is widespread in low- and middle-income countries, with significant, long-lasting implications for children's wellbeing. Beyond low height, stunting leaves children vulnerable to disease and at risk of lower cognitive ability.

Among the known causes of stunting are poverty, inadequate nutrition, poor diet, poor maternal health during pregnancy and breastfeeding, teen pregnancy, poor disease environment, and frequent illness. Considerable evidence also shows that birth order influences stunting, with children born after the first child at higher risk.

Using data from the fourth round of the Indian Demographic and Health Survey conducted in 2014-15, Dhingra and Pingali confirm that birth order affects height when births occur less than three years apart, with height gap increasing between later-born children. However, when the time between births is three years or more, they find that the height advantage of earlier-born children is insignificant.

The amount of time between pregnancies affects maternal and child health in several ways. A mothers' body needs time after birth to replenish key micronutrients, so getting pregnant again too quickly may reduce the nutrients available to the fetus and limit milk production. Having children too close together also makes it more difficult for parents to devote adequate time and resources to each child.

Because of the ubiquity of stunting in developing countries and the serious nature of its social and economic costs, dedicated efforts have been made to curb stunting around the world. As a result, stunting has decreased by 35% since 1990.

Yet, as recently as 2020, 141 million children under the age of five were reported as stunted, and global reductions mask regional disparities. Over 69 million stunted children live in South Asia, with most in India. Understanding the regional and local drivers of stunting can help reduce its incidence in such burdened countries.

Modern medical technology is helping scholars tell a more nuanced story about the fate of an ancient king whose violent death indirectly led to the reunification of Egypt in the 16th century BC. The research was published in Frontiers in Medicine.

Pharaoh Seqenenre-Taa-II, the Brave, briefly ruled over Southern Egypt during the country's occupation by the Hyksos, a foriegn dynasty that held power across the kingdom for about a century (c. 1650-1550 BCE). In his attempt to oust the Hyskos, Seqenenre-Taa-II was killed. Scholars have debated the exact nature of the pharaoh's death since his mummy was first discovered and studied in the 1880s.

These and subsequent examinations -- including an X-ray study in the 1960s -- noted the dead king had suffered several severe head injuries but no other wounds to his body. The prevailing theory, based on the evidence, was that the king had been captured in battle and then executed afterward, possibly by the Hyksos king himself. Others have suggested he was murdered in his sleep by a palace conspiracy.

In addition, the poor condition of the mummy suggested the embalming had been done hastily, away from the royal mummification workshop.

But computed tomography (CT) scans of the mummified remains of Seqenenre revealed new details about his head injuries, including previously undetected lesions that embalmers had skillfully concealed.

The authors of the new paper offer a novel interpretation of the events before and after the king's death based on the computer-processed X-ray images: Seqenenre had indeed been captured on the battlefield, but his hands had been tied behind his back, preventing him from defending against the attack.

"This suggests that Seqenenre was really on the front line with his soldiers risking his life to liberate Egypt," said lead author Dr. Sahar Saleem, a professor of radiology at Cairo University who specialises in paleoradiology. This investigative technique employs medical imaging technologies to non-invasively study a cross section of archaeological remains, including bodies. It can help determine age at death, sex and even how the person died.

For example, the CT scans, combined with other evidence, suggest the execution had been carried out by multiple attackers, which the scientists confirmed by studying five different Hyksos weapons that matched the king's wounds.

"In a normal execution on a bound prisoner, it could be assumed that only one assailant strikes, possibly from different angles but not with different weapons," Saleem explained. "Seqenenre's death was rather a ceremonial execution."

The CT study also determined that Seqenenre was about 40 when he died, based on the detailed morphology revealed in the images, providing the most precise estimate to date.

Saleem and co-author Zahi Hawass, an archaeologist and former Egyptian minister of antiquities, have pioneered the use of CT scans to study the New Kingdom pharaohs and warriors, including well-known names such as Hatshepsut, Tutankhamun, Ramesses III, Thutmose III and Rameses II. Yet Seqenenre, based on the available evidence, appears to be the only one among this illustrious group to have been on the frontline of the battlefield.

In addition, the CT study revealed important details about the mummification of Seqenenre's body. For instance, the embalmers used a sophisticated method to hide the king's head wounds under a layer of embalming material that functioned similarly to the fillers used in modern plastic surgery. This would imply that mummification took place in a real mummification laboratory rather than in a poorly equipped place, as previously interpreted.

Saleem said the CT scan study provides important new details about a pivotal point in Egypt's long history. "Seqenenre's death motivated his successors to continue the fight to unify Egypt and start the New Kingdom," she said.

Using advanced RNA sequencing, scientists have identified two unique subtypes of a prominent mutation present in many patients with Acute Myeloid Leukemia (AML) - called NPM1 - that could help predict survival and improve treatment response for patients whose leukemic cells bear the mutation.

In research published Feb. 16, in Nature Communications, a team led by Princess Margaret Cancer Centre Senior Scientists, Drs. Benjamin Haibe-Kains, Aaron Schimmer and Mark Minden, have discovered that within the NPM1 mutation of AML there exists two unique subtypes, one of which can be effectively treated with drugs already in use.

It is the first study to classify within the common NPM1 mutant form of AML two subtypes, one being "primitive" and the other "committed." Furthermore, the research shows that each subtype has a different response to treatment and long-term survival, cracking open opportunities to personalize treatment plans and introduce new targeted therapies in the future.

"Patients with NPM1 mutated AML face a relapse rate of around 40 per cent," says Dr. Schimmer, Research Director and acute leukemia physician at the Princess Margaret, which is part of University Health Network. "While we're getting better at incorporating new monitoring techniques, we're still not at a point where we can adequately predict what side of the curve a patient might fall.

By going deeper with our sequencing, we can better predict outcomes and adjust treatment accordingly for each patient."

NPM1 mutated AML makes up around 30 per cent of all AML cases, but therapeutic discoveries for these patients have been limited.

"While the NPM1 mutation is relatively common, AML is a rare disease to begin with," says Dr. Haibe-Kains, who is also an Associate Professor of Medical Biophysics at the University of Toronto. "Generating enough data to be able to sequence and understand the biology of this mutation is very challenging."

This was made possible in large part thanks to a team led by Dr. Minden, Senior Scientist and medical oncologist, and Andrea Arruda, staff scientist at the Princess Margaret Cancer, who have been collecting samples to enable deeper learning since the mid-1980s thanks to the willingness, generosity and foresight of patients.

"Recognizing those 'needles in a haystack' - the small groups of patients that don't benefit from certain treatments is critically important for improving personalized medicine," says Dr. Minden. "Now we can start to improve outcomes for this more discreet patient population."

An advanced computational model was custom-built to analyze RNA from patient leukemic cells obtained from the Leukemia Live Cell Tissue Bank, along with other data published from NPM1 mutant leukemia studies.

"We developed a unique machine-learning model that was able to clearly discriminate two subtypes of NPM1 mutant AML in datasets collected from patients," says Dr. Haibe-Kains.

These two subtypes both contain mutant AML but they express different genes that can now separate them into two clear subtypes based on their RNA.

The study also suggests that certain drugs already used to treat other types of cancer could be effective in the primitive subtype.

"Once we were able to identify the pattern of each subtype, we analyzed existing pharmacogenomics data to narrow a list of drugs that might be able to target one subtype or the other," explained Dr. Haibe-Kains. "We found two drugs that seemed to effectively target the primitive subtype in the lab, with potential to move to clinical trials in the future."

"This finding could change the way we treat patients," says Dr. Schimmer. "It opens up the opportunity to better refine and time treatments - whether it's the decision for a stem cell transplant early on, or choosing more effective and less toxic therapies throughout the course of treatment.

Our goal with all of our patients is to get better and better outcomes. This is one step towards doing better."

This research was supported by funds from the Canadian Institutes for Health Research, the Orsino Chair in Leukemia Research and the Princess Margaret Cancer Foundation.

ADS has received research funding from Takeda Pharmaceuticals and Medivir AB, and consulting fees/honorarium from Takeda, Novartis, Jazz, and Otsuka Pharmaceuticals. ADS holds stock in Abbvie. ADS, is an inventor on patent applications claiming the use of DNTs for the treatment of AML.

DARIEN, IL – A new study found that treating obstructive sleep apnea with CPAP therapy increased self-reported physical activity in adults with a history of heart disease.

During a mean follow-up period of 3.7 years, the group treated with CPAP therapy reported approximately 20% higher levels of moderate physical activity compared with the control group. The study also found the CPAP group was more likely to report activity levels consistent with expert recommendations.

“We were pleased to find that our CPAP users reported that they were better able to maintain their levels of activity over the four years of the study, and that they reported fewer limitations in moderate and vigorous activities including those that are important for independent aging, like walking up the stairs,” said study co-author Kelly Loffler, who has a doctorate in biochemistry and molecular biology and is a research fellow at the Adelaide Institute for Sleep Health at Flinders University in Adelaide, South Australia.

The study is published in the February issue of the Journal of Clinical Sleep Medicine.

Nearly 30 million adults in the U.S. have obstructive sleep apnea, a chronic disease that involves the repeated collapse of the upper airway during sleep. Common warning signs include snoring and excessive daytime sleepiness. A common treatment is CPAP therapy, which uses mild levels of air pressure, provided through a mask, to keep the throat open during sleep.

The Sleep Apnea cardioVascular Endpoints (SAVE) study was an international, randomized controlled trial of patients with a history of cardiovascular disease and sleep apnea who were recruited from diverse socioeconomic and health care settings. This analysis examined activity data among 2,601 participants between the ages of 45 and 75 years. More than 80% of participants were men, about 63% were Asian, and 25% were white.

Participants were randomly assigned to one of two groups: One group was treated with CPAP and usual cardiovascular care, while a second group received only usual care. While there was no specific exercise intervention, participants reported physical activity using the Leisure-Time Exercise Questionnaire at the start of the study and over six, 24 and 48 months.

According to the authors, the increased level of physical activity found in this study would likely convey substantial health benefits over longer periods of time, such as lowering the recurrence of cardiovascular events.

“CPAP represents a useful tool to assist health care providers caring for populations with comorbidities and combined with lifestyle interventions like diet and targeted exercise will likely provide many users with a symptomatic benefit that goes beyond their reported sleep,” said Loffler.