Body

A new study from Lund University and Region Skåne in Sweden indicates that potency-enhancing PDE5 inhibitor drugs have an anti-cancer potential with the ability to improve the prognosis in patients with colorectal cancer. PDE5 inhibitors include a few approved drugs in which sildenafil (Viagra) is the most well-known. The article is published in Nature Communications.

"Available preclinical evidence suggests that PDE5 inhibitors could slow down the tumor growth and progression in mice, but it is still unknown whether PDE5 inhibitors can hinder the proliferation of cancer in humans. We tried to explore this using real-world medical data in Sweden", says Wuqing Huang, a PhD student at Lund University and one of the researchers behind the study.

By linking several nationwide registers, Wuqing Huang identified all Swedish male patients with colorectal cancer who had used PDE5 inhibitors after their cancer diagnosis (1 136 patients). During the follow-up period, around 10.2% of patients had died from colorectal cancer among those who used PDE5 inhibitors after diagnosis, whereas the probability was 17.5% in patients who did not use PDE5 inhibitors (11 329). After consideration of a range of clinical confounding factors, the relative risk of death caused by colorectal cancer was 18% lower among patients who used the drugs. The risk of metastases, especially distant metastases which is the main cause of death due to cancer, was also lower among patients who used PDE5 inhibitors.

"In addition, the protective effect was even stronger in men who used these drugs after receiving open surgery. This finding provides the first-ever human-based evidence in terms of the anti-tumor effect of PDE5 inhibitors on colorectal cancer, which complements the preclinical evidence.", says Wuqing Huang.

One of the mechanisms that has been suggested to be a critical process that leads to adverse outcomes among patients with cancer post-surgery, is surgery-induced immune suppression.

"The results of our study suggest that the anti-cancer ability of PDE5 inhibitors might be related to regulating immunosuppressive effects. However, randomized clinical trials are needed to confirm our research findings before PDE5 inhibitors can be used as an adjuvant drug for men with colorectal cancer, as well as experiments that explore the underlying biological mechanisms", says Wuqing Huang.

"The observed findings should be interpreted with caution as this is an observational study and the biological mechanisms need to be explored further. We have already collaborated with other scientists to explore the underlying mechanisms by utilizing animal experiments and cancer organoid", comments Jianguang Ji, a researcher at Lund University involved in the study.

Osteoarthritis treatment conducted digitally via an app costs around 25% of what conventional care costs, according to a study from Lund University in Sweden published in the research journal PLOS ONE. The researchers have previously shown that osteoarthritis patients were able to halve their pain in just 6 months, using an app to track simple, daily exercises.

"The osteoarthritis treatment in the study is the same and complies with the National Board of Health and Welfare's guidelines. The only thing that is new is that it is delivered digitally instead, which makes it easier to continuously monitor the patients, something that is important in a chronic disease. If the app-based treatment can also be delivered more cheaply and with a greater effect, which the results of this study suggest, this is obviously even better", says Håkan Nero, physiotherapist and one of the researchers behind the study.

The study, which compared digital osteoarthritis treatment with conventional treatment of osteoarthritis at a clinic, compiled costs for patient visits, administration, training and education of physiotherapists, as well as costs for the patient in the form of travel and absence from work. A cost-effectiveness analysis was also carried out in which the pain level results for each treatment alternative were taken into account.

"It shows that the digital treatment programme for osteoarthritis costs approximately 25 per cent of the conventional treatment programme. The digital method is also more cost-effective in terms of the effect on the patient's pain level, which means that a higher positive effect on pain is obtained for the same amount spent. The study also shows that if half of the patients who received the standard treatment would have instead been in the digital programme, it would be possible to save approximately SEK 87 million per year in Sweden."

The study is a follow up of a previous study about the digital treatment of osteoarthritis that the researchers published in the spring of 2020. Over an extensive period, the 500 patients with osteoarthritis of the knee or hip involved in the study received new exercises and lessons daily via an app in their mobile phones. The patients digitally reported their results every week.

After six months the patients, using simple exercises that they received to strengthen the musculature around the area affected by osteoarthritis, had on average almost halved their pain level. In addition, physical mobility for the entire group had improved on average by 43 per cent. The patients who continued the programme for up to one year also showed equally good results - something that surprised the researchers.

"We expected that the patients would improve, but not that it would be this effective. It shows that it is possible to treat chronic diseases such as osteoarthritis using digital technology", said Håkan Nero in connection with the publication of the study. Håkan Nero thinks that digital treatment of osteoarthritis will become more common in the future.

"Due to the prevailing pandemic, the development and testing of digital alternatives has accelerated. In addition, there is a constant stream of new research that shows the advantages of well-designed digital treatment programmes", he concludes.

New insight into a gene that controls energy production in cancer stem cells could help in the search for a more effective treatment for glioblastoma. A McGill-led study published in Nature Communication reveals that suppressing the OSMR gene can improve the effectiveness of radiation therapy.

This approach, led by the laboratory of Arezu Jahani-Asl, Assistant Professor of Medicine at McGill University, was successful in preclinical mouse models where the deletion of the OSMR gene resulted in a significant improvement of tumour response to therapy and expanded lifespan.

Glioblastoma is the most common and aggressive cancerous brain tumour in adults due to its resistance to therapy. Treatment usually involves surgery, followed by chemotherapy and radiation therapy. Despite these intensive efforts, in most cases tumour cells regrow after treatment and the cancer recurs.

Starving cancer stem cells

Glioblastoma tumours contain rare cancer stem cells responsible for therapeutic resistance and tumour regrowth. In the study, researchers uncover the unique role OSMR plays in fortifying cancer stem cells' resistance to therapy by strengthening mitochondria, the powerhouse of cell energy production. It makes the long journey to the mitochondria and interacts with energy-producing machineries to force them to generate more energy for cancer cells.

"To improve patient response to glioblastoma treatment, we must find new vulnerabilities in cancer stem cells and overcome their resistance to therapy. By suppressing OSMR, we were able to halt energy production in cancer stem cells, essentially starving them to death," says Jahani-Asl.

The study provides evidence that targeting OSMR gene, in combination with radiation therapy, can pave the way for future clinical trials that better treat glioblastoma tumours. The next step is to leverage these tools into a clinical trial, the researchers say.

Patients who need surgery to fix major bone fractures use fewer opioid pills after their procedure if they're reminded of their values - and those reminders don't necessarily need to come from a doctor, according to a new study published in the Journal of Medical Internet Research.

"We showed that opioid medication utilization could be decreased by more than a third in an at-risk patient population by delivering psychotherapy via a chatbot," said the study's lead author, Christopher Anthony, MD, the associate director of Hip Preservation at Penn Medicine and an assistant professor of Orthopaedic Surgery. "While it must be tested with future investigations, we believe our findings are likely transferrable to other patient populations."

Although opioids can be appropriate to treat the pain that results from an injury like a broken leg or arm, there is a concern that a large prescription of opioids might be an on-ramp to dependence for many. The researchers - who included Edward Octavio Rojas, MD, a resident in Orthopaedic Surgery at the University of Iowa Hospitals & Clinics - believe a low-effort, patient-centered approach to reducing the number of opioids taken can be a valuable method for cutting into the opioid epidemic.

To test this approach, 76 patients who went to a Level 1 Trauma Center at the University of Iowa Hospitals & Clinics for fractures that required a surgery to fix were randomly divided into two groups. Although each group received the same prescription of an opioid medication for pain, just one group was enrolled in a daily text-messaging program. That group received two daily text messages to their phones for two weeks after their procedure from an automated "chatbot" - a computer that uses artificial intelligence to send messages - starting the day after their surgery. The goal of each message was to help focus patients and hone their coping skills for the inevitable pain after such a procedure.

While they don't expressly discourage using opioid pills, the messages, designed by a pain psychologist who specialized in acceptance and commitment therapy (ACT), are designed to direct thoughts away from taking a painkiller.

Each message fell under one of six "core principles": Values, Acceptance, Present Moment Awareness, Self-As-Context, Committed Action, and Diffusion.

So, for example, a message a patient could receive under the Acceptance principle could be: "Feelings of pain and feelings about your experience of pain are normal after surgery. Acknowledge and accept these feelings as part of the recovery process. Remember how you feel now is temporary and your healing process will continue. Call to mind pleasant feelings or thoughts that you experienced today." Or a Committed Action message might urge a patient to work toward a life goal, even if some pain might be present.

Overall, the patients who didn't receive the messages took 41 opioid tablets after their surgeries, on average. The group who were regularly contacted by the chatbot averaged just 26, a 37 percent difference. Moreover, they reported less pain, overall, just two weeks after their procedure.

Importantly, the messages each patient received were not curated for their individual personality. This type of effectiveness was seen without the messages needing to be overly personalized. Combined with the using a chatbot instead of a human-intensive effort, this could be a low-cost, low-effort for orthopaedic and other procedures that provides significant protection from opioid dependence.

"A realistic goal for this type of work is to decrease opioid utilization to as few tablets as possible, with the ultimate goal being to eliminate the need for opioid medication in the setting of fracture care," Anthony said.

A Rutgers-led team may have found the key to treating inflammatory diseases like asthma, allergies, chronic fibrosis and chronic obstructive pulmonary disease (COPD).

In a study published in the journal Nature Immunology, researchers discovered that neuromedin B (NMB), a protein produced by the nervous system, was responsible for preventing overactive immune responses and damaging inflammation. An immune response refers to the body's ability to recognize and defend itself against harmful substances. Although beneficial to help clear infections, an immune response can also promote damaging inflammation if not properly restricted. The researchers found that the NMB protein can stop the type of inflammation that that occurs in diseases like asthma, allergies, chronic fibrosis and COPD.

"For many years, the mechanism through which the body shuts down an inflammatory response to heal itself after worm infections remained poorly understood," said Mark C. Siracusa, lead author and an assistant professor at the Rutgers New Jersey Medical School. "Our study provided that understanding and a hope for possible treatments using NMB, which has great potential to treat inflammatory diseases like asthma, allergies and COPD."

COPD is the third most common cause of death among inflammatory diseases and allergies the sixth in the United States.

"Scientists previously thought the immune system was capable of regulating itself in order to resolve inflammation to prevent tissue damage. However, emerging work is beginning to reveal that complex interactions between the immune system and the nervous system serve to restrict inflammation and promote health," said Siracusa.

A patent cooperation treaty (PCT) patent application was filed by Rutgers Office of Research Commercialization. The next steps for researchers include developing drugs using the protein to treat diseases like asthma, COPD, and allergies.

Women are having a difficult time getting into treatment for opioid addictions, according to a Vanderbilt University Medical Center study published today in JAMA Network Open.

The "secret shopper" study used trained actors attempting to get into treatment with an addiction provider in 10 U.S. states. The results, with more than 10,000 unique patients, revealed numerous challenges in scheduling a first-time appointment to receive medications for opioid use disorder, including finding a provider who takes insurance rather than cash.

The situation only gets worse for women who are pregnant and addicted to opioids. Overall, pregnant women were about 20% less likely to be accepted for treatment than nonpregnant women.

"It wasn't just that pregnant women had a hard time getting into treatment; everyone did. It was pretty extraordinary," said Stephen Patrick, MD, director of the Center for Child Health Policy at Vanderbilt University School of Medicine.

"We have been in the middle of an epidemic of opioid overdose for years now. There are just too many barriers into getting treatment. We are still setting records levels of overdose deaths in the U.S., likely made worse by the COVID-19 pandemic. We know these medicines save lives; it shouldn't be this hard to get them," he said.

Providers in the study were randomly selected from government lists of persons providing either buprenorphine or methadone treatment for opioid addiction.

Medications for opioid use disorder such as buprenorphine, most commonly received from providers in an outpatient clinic, and methadone, received in an opioid treatment program, have been proven to reduce overdose risk and improve pregnancy outcomes for patients, Patrick said, including a reduction in the risk of preterm births.

A total of 10,871 unique patient profiles of pregnant vs. nonpregnant women and private vs. public insurance were randomly assigned to 6,324 clinicians or clinics.

About a quarter of the time, callers tried at least five times to reach a provider without success; another 20% of the time they reached a provider who didn't provide addiction treatment.

"For women trying to get into treatment, just getting someone on the phone proved to be a challenge," Patrick said. "Only about half of the time - if they actually reached a provider - were they able to make an appointment for treatment the first time. "

A large portion of the clinicians from 10 states did not accept insurance and required cash payment for an appointment.

"Only about half of women were given an appointment for treatment with their insurance, the rest were either told no or had to pay cash. In some states, only about 1-in-5 women were given appointments with their insurance," Patrick said. "That's really staggering. You are telling folks in the middle of an epidemic, folks who are disproportionately impoverished, that you need to get into treatment. But then most providers either say no or don't take any insurance."

Insurance was not accepted by 26% of buprenorphine prescribers and one-third of the opioid treatment programs in total. Median out-of-pocket costs for initial appointments were $250 for buprenorphine prescribers and $34 for methadone prescribers.

Overall, about two-thirds of callers were able to make an appointment (67.6%) with outpatient buprenorphine providers, but pregnant women received an appointment only 61.4% compared to non-pregnant women at 73.9%.

For opioid treatment programs about 9-in-10 callers were able to get an appointment and there was no difference between pregnant and non-pregnant women.

"We found that opioid treatment programs took pregnant women at the same rate that they took nonpregnant women. That is not true for buprenorphine providers," Patrick said. "It is also important to note that opioid treatment programs are far rarer than buprenorphine providers."

Patrick said the study results should serve as an immediate call for policymakers to intervene.

"Reducing barriers to medications for opioid use disorder has been identified as key public health goal by the U.S. Surgeon General, the President's Commission on Opioids, but our research suggests substantial barriers remain," said Patrick.

"We need to begin to put systems in place where people can get the treatment they need when they want it. For pregnant women, not only does it save their lives if they get this medicine, but it also makes it more likely that their infant is going to be delivered at term."

A new Boston University School of Public Health (BUSPH) study finds that changes in weight between young adulthood and midlife may have important consequences for a person's risk of early death.

Published in JAMA Network Open, the study found that participants whose BMIs went from the "obese" range in early adulthood down to the "overweight" range in midlife halved their risk of dying during the study period, compared with individuals whose BMIs stayed in the "obese" range. On the other hand, weight loss after midlife did not significantly reduce participants' risk of death.

The researchers estimate that 12.4% of early deaths in the US may be attributable to having a higher body mass index (BMI) at any point between early- and mid-adulthood.

"The results indicate an important opportunity to improve population health through primary and secondary prevention of obesity, particularly at younger ages," says study corresponding author Dr. Andrew Stokes, assistant professor of global health at BUSPH.

"The present study provides important new evidence on the benefit of maintaining a healthy weight across the life course," says lead author Dr. Wubin Xie, a postdoctoral associate in global health at BUSPH.

The researchers used data from 1998 through 2015 for 24,205 participants from the National Health and Nutrition Examination Survey. The participant were 40-74 years old when they entered the study, and the data included participants' BMI at age 25, 10 years before they entered the study, and when they entered the study. The researchers then analyzed the relationship between BMI change and the likelihood that a participant died over the course of the observed period, controlling for other factors such as participants' sex, past and current smoking, and education level.

They found that study participants whose BMIs went from the "obese" range at age 25 down to the "overweight" range in midlife were 54% less likely to have died than participants whose BMIs stayed in the "obese" range. Instead, these participants with an "obese" to "overweight" trajectory had a risk of death closer to that of participants whose BMIs had been in the "overweight" range all along.

The researchers estimated that 3.2% of deaths in the study would have been avoided if everyone with a BMI in the "obese" range at age 25 had been able to bring their BMIs down to the "overweight" range by midlife. However, they noted that weight loss was rare overall, and only 0.8% of participants had BMIs that went from the "obese" to the "overweight" range.

The researchers did not find a similar reduction in risk of death for participants who lost weight later in their lives. They wrote that this may be because weight loss later in life is more likely to be tied to an aging person's worsening health.

"Although this study focused on preventing premature deaths, maintaining a healthy weight will also reduce the burden of many chronic diseases such as hypertension, diabetes, heart disease, and even cancer," says study co-author Dr. JoAnn Manson, chief of preventive medicine at Brigham and Women's Hospital, and professor of medicine and Michael and Lee Bell Professor of Women's Health at Harvard Medical School.

Doctors can predict patients' risk for ischemic stroke based on the severity of their metabolic syndrome, a conglomeration of conditions that includes high blood pressure, abnormal cholesterol levels and excess body fat around the abdomen and waist, a new study finds.

The study found that stroke risk increased consistently with metabolic syndrome severity even in patients without diabetes. Doctors can use this information - and a scoring tool developed by a UVA Children's pediatrician and his collaborator at the University of Florida - to identify patients at risk and help them reduce that risk.

"We had previously shown that the severity of metabolic syndrome was linked to future coronary heart disease and type 2 diabetes," said UVA's Mark DeBoer, MD. "This study showed further links to future ischemic strokes."

Ischemic Stroke Risk

DeBoer developed the scoring tool, an online calculator to assess the severity of metabolic syndrome, with Matthew J. Gurka, PhD, of the Department of Health Outcomes and Biomedical Informatics at the University of Florida, Gainesville. The tool is available for free at https://metscalc.org/.

To evaluate the association between ischemic stroke and metabolic syndrome, DeBoer and Gurka reviewed more than 13,000 participants in prior studies and their stroke outcomes. Among that group, there were 709 ischemic strokes over a mean period of 18.6 years assessed in the studies. (Ischemic strokes are caused when blood flow to the brain is obstructed by blood clots or clogged arteries. Hemorrhagic strokes, on the other hand, are caused when blood vessels rupture.)

The researchers used their tool to calculate "Z scores" measuring the severity of metabolic syndrome among the study participants. They could then analyze the association between metabolic syndrome and ischemic stroke risk.

The subgroup with the highest association between metabolic syndrome and risk for ischemic stroke was white women, the researchers found. In this group, the research team was able to identify relationships between the individual contributors to metabolic syndrome, such as high blood pressure, and stroke risk.

The researchers note that race and sex did not seem to make a major difference in stroke risk overall, and they caution that the increased risk seen in white women could be the results of chance alone. "Nevertheless," they write in a new scientific article outlining their findings, "these results are notable enough that they may warrant further study into race and sex differences."

The overall relationship between metabolic syndrome severity and stroke risk was clear, however. And this suggests people with metabolic syndrome can make lifestyle changes to reduce that risk. Losing weight, exercising more, choosing healthy foods - all can help address metabolic syndrome and its harmful effects.

DeBoer hopes that the tool he and Gurka developed will help doctors guide patients as they seek to reduce their stroke risk and improve their health and well-being.

"In case there are still individuals out there debating whether to start exercising or eating a healthier diet," DeBoer said, "this study provides another wake-up call to motivate us all toward lifestyle changes."

WHAT:
New research supported by the National Institutes of Health delineates how two relatively common variations in a gene called KIF3A are responsible for an impaired skin barrier that allows increased water loss from the skin, promoting the development of atopic dermatitis, commonly known as eczema. This finding could lead to genetic tests that empower parents and physicians to take steps to potentially protect vulnerable infants from developing atopic dermatitis and additional allergic diseases.

Atopic dermatitis is an inflammatory skin condition that affects up to 20% of children in developed countries. This chronic disease is characterized by dry, thickened and intensely itchy skin, particularly in skin folds. People with eczema are more susceptible to bacterial, viral and fungal skin infections and frequently develop additional allergic diseases such as asthma.

KIF3A is a gene that codes for a protein involved in generating signals from the outside to the inside of a cell, part of a complex sensory apparatus. Previously, scientists had identified an association between two genetic variations in KIF3A and asthma in children who also had eczema. In the new study, the researchers found that these variations, or single nucleotide polymorphisms (SNPs), changed parts of the KIF3A gene to a form that can regulate, through a process called methylation, the rate at which a gene is transcribed into the blueprint for protein production. The investigators confirmed that skin and nasal-lining cells from people with the KIF3A SNP variants had more methylation and contained fewer blueprints for the KIF3A protein than cells in which KIF3A lacked the SNPs. In addition, the researchers demonstrated that people with the SNP-created regulating sites had higher levels of water loss from the skin.

To determine whether lower levels of KIF3A caused atopic dermatitis, the scientists studied mice lacking the mouse version of KIF3A in skin cells. They found that these mice also had increased water loss from the skin due to a dysfunctional skin barrier and were more likely to develop features of atopic dermatitis. The investigators concluded that the presence of either or both of the two SNPs in human KIF3A leads to lower production of the KIF3A protein, promoting dysfunction of the barrier that normally keeps skin well hydrated, thereby increasing the likelihood that a person will develop atopic dermatitis.

Now that investigators have established that these KIF3A SNPs increase the risk for atopic dermatitis, infants could potentially be screened for them. Therapies directed specifically at water loss from the skin, such as intensive topical moisturization regimens, could be evaluated for their ability to prevent atopic dermatitis in children with the SNPs. Preventing atopic dermatitis in early childhood could in turn prevent a cascade of additional allergic diseases later in life, such as asthma, food allergy and allergic rhinitis--a cascade known as the atopic march.

This research was co-funded by the National Institute of Allergy and Infectious Diseases and the National Center for Advancing Translational Sciences, both part of NIH. The study was led by Gurjit K. Khurana Hershey, M.D., Ph.D., professor of pediatrics and director of the Division of Asthma Research at Cincinnati Children's Hospital Medical Center, which is part of the NIAID-supported Asthma and Allergic Diseases Cooperative Research Centers.

Two common variants in the KIF3A gene increase the risk of young children having a dysfunctional skin barrier and developing the skin condition atopic dermatitis. This, in turn, can allow environmental exposures to more easily cross the skin barrier and contribute to the development of food allergies and asthma as they grow up.

These findings, led by scientists at Cincinnati Children's, were published online Aug. 14, 2020, in Nature Communications. The first author was Mariana Stevens, PhD, and the senior corresponding author was Gurjit Khurana Hershey, MD, PhD, Director, Division of Asthma Research.

The study sheds new light on the genetic and molecular mechanisms at work in atopic dermatitis, a common condition (also known as eczema) that affects as many as 20 percent of all children. Although eczema usually resolves as children age, many children with disrupted skin barriers go on to develop more severe conditions including asthma and food allergies.

The study findings could make it easier to identify which children with eczema are most likely to progress to other allergic conditions. This would allow lifestyle interventions and other preventive therapies to be targeted toward high-risk children. The study also suggests a new target for potential treatment.

"Food allergies are rising and the causes are not entirely clear," Hershey says. "This study adds evidence to a rising theory that skin health is more closely connected to lung and gut health than many have suspected."

Two tiny SNPs play big roles in skin health

A single nucleotide polymorphism (SNP) is a common genetic variation in a DNA sequence. In this study, researchers found two SNPs in the KIF3A gene that were confirmed through a series of experiments in children, as well as preclinical studies in mice, to play direct roles in developing eczema.

These SNPs (rs11740584 and rs2299007) are linked to increased water loss through the skin, dry skin and the characteristic damage seen in atopic dermatitis. Measuring the rate of this type of water loss is one method for determining how severe a child's eczema may be.

Proper function of the KIF3A gene is important because it helps cells form their primary cilia, a structure on cell surfaces that acts as an antenna to receive important signal information from other cells. Previous studies led by experts at Cincinnati Children's and others have already shown that malfunctioning KIF3A in lung tissue can lead to asthma. Likewise, malfunctions of the same gene in gut tissues can increase risk of food allergies.

Now, this study helps connect both of these allergy risks to a damaged skin barrier, which allows more allergy-triggering substances to get inside our bodies to prompt immune system over-reactions.

"We are working to better understand how skin, gut and lung health are connected. In fact, we have a grant from the National Institutes of Health to further study this connection," Hershey says.

Development underway for screening test

The research team at Cincinnati Children's has begun searching for drug compounds that might someday be useful in restoring the disrupted functions of the KIF3A gene. But the first next step based on this study will be to continue an ongoing hunt for a rapid screening test.

The new study in Nature Communications builds on findings from two other studies published earlier this year from Cincinnati Children's scientists.

In February, a study in the Journal of Allergy and Clinical Immunology reported that the allergy risk posed by atopic dermatitis was higher than having a parent with allergic disease.

Then in April, a study in the same journal demonstrated the value of using pain-free tape stripping as a less-invasive tool than skin biopsies for gathering data about skin health.

The goal, Hershey says, would be to use skin tape strip samples to quantify KIF3A expression as a possible tool for predicting disease risk. The team is studying this approach in a group of 600 children from the Cincinnati region who were identified with atopic dermatitis early in life. This group, the first cohort of its kind in the US, will be followed for five years to directly evaluate the ability of KIF3A genetic variations and skin expression to predict disease risk.

UNIVERSITY PARK, Pa. -- While many programs and initiatives have been implemented to address the prevalence of substance abuse among homeless youth in the United States, they don't always include data-driven insights about environmental and psychological factors that could contribute to an individual's likelihood of developing a substance use disorder.

Now, an artificial intelligence (AI) algorithm developed by researchers at the College of Information Sciences and Technology at Penn State could help predict susceptibility to substance use disorder among young homeless individuals, and suggest personalized rehabilitation programs for highly susceptible homeless youth.

"Proactive prevention of substance use disorder among homeless youth is much more desirable than reactive mitigation strategies such as medical treatments for the disorder and other related interventions," said Amulya Yadav, assistant professor of information sciences and technology and principal investigator on the project. "Unfortunately, most previous attempts at proactive prevention have been ad-hoc in their implementation."

"To assist policymakers in devising effective programs and policies in a principled manner, it would be beneficial to develop AI and machine learning solutions which can automatically uncover a comprehensive set of factors associated with substance use disorder among homeless youth," added Maryam Tabar, a doctoral student in informatics and lead author on the project paper that will be presented at the Knowledge Discovery in Databases (KDD) conference in late August.

In that project, the research team built the model using a dataset collected from approximately 1,400 homeless youth, ages 18 to 26, in six U.S. states. The dataset was collected by the Research, Education and Advocacy Co-Lab for Youth Stability and Thriving (REALYST), which includes Anamika Barman-Adhikari, assistant professor of social work at the University of Denver and co-author of the paper.

The researchers then identified environmental, psychological and behavioral factors associated with substance use disorder among them -- such as criminal history, victimization experiences and mental health characteristics. They found that adverse childhood experiences and physical street victimization were more strongly associated with substance use disorder than other types of victimization (such as sexual victimization) among homeless youth. Additionally, PTSD and depression were found to be more strongly associated with substance use disorder than other mental health disorders among this population, according to the researchers.

Next, the researchers divided their dataset into six smaller datasets to analyze geographical differences. The team trained a separate model to predict substance abuse disorder among homeless youth in each of the six states -- which have varying environmental conditions, drug legalization policies and gang associations. The team observed several location-specific variations in the association level of some factors, according to Tabar.

"By looking at what the model has learned, we can effectively find out factors which may play a correlational role with people suffering from substance abuse disorder," said Yadav. "And once we know these factors, we are much more accurately able to predict whether somebody suffers from substance use."

He added, "So if a policy planner or interventionist were to develop programs that aim to reduce the prevalence of substance abuse disorder, this could provide useful guidelines."

Other authors on the KDD paper include Dongwon Lee, associate professor, and Stephanie Winkler, doctoral student, both in the Penn State College of Information Sciences and Technology; and Heesoo Park of Sungkyunkwan University.

Yadav and Barman-Adhikari are collaborating on a similar project through which they have developed a software agent that designs personalized rehabilitation programs for homeless youth suffering from opioid addiction. Their simulation results show that the software agent -- called CORTA (Comprehensive Opioid Response Tool Driven by Artificial Intelligence) -- outperforms baselines by approximately 110% in minimizing the number of homeless youth suffering from opioid addiction.

"We wanted to understand what the causative issues are behind people developing opiate addiction," said Yadav. "And then we wanted to assign these homeless youth to the appropriate rehabilitation program."

Yadav explained that data collected by more than 1,400 homeless youth in the U.S. was used to build AI models to predict the likelihood of opioid addiction among this population. After examining issues that could be the underlying cause of opioid addiction -- such as foster care history or exposure to street violence -- CORTA solves novel optimization formulations to assign personalized rehabilitation programs.

"For example, if a person developed an opioid addiction because they were isolated or didn't have a social circle, then perhaps as part of their rehabilitation program they should talk to a counselor," explained Yadav. "On the other hand, if someone developed an addiction because they were depressed because they couldn't find a job or pay their bills, then a career counselor should be a part of the rehabilitation plan."

Yadav added, "If you just treat the condition medically, once they go back into the real world, since the causative issue still remains, they're likely to relapse."

HERSHEY, Pa. -- Pregnant women from sub-Saharan Africa with malaria and human immunodeficiency virus (HIV) have a higher prevalence of anemia than pregnant women without infections, according to Penn State College of Medicine researchers. The findings may have implications for reducing the risk of death in pregnant women and preventing low birth weights and neurocognitive impairment in their children as a result of anemia.

Coinfections of HIV and malaria are common among expectant mothers in sub-Saharan Africa. Dr. Paddy Ssentongo, a doctoral student in epidemiology, led a study, published in BMC Pregnancy and Childbirth, that assessed the association of malaria with anemia and the effects of malaria and HIV on anemia in pregnant women.

The researchers analyzed demographic and health surveys from 2012 and 2017 across seven countries in sub-Saharan Africa and examined blood samples from 947 pregnant women, ages 15 to 49 years old. Their results show that malaria was associated with an increased prevalence of anemia during pregnancy. The prevalence of anemia was higher in pregnant women with malaria and HIV coinfections (60%) than in pregnant women without infections (45%).

"Pregnant women in sub-Saharan Africa suffer a double burden of malaria and HIV infections, and these infections interact with each other to cause anemia," Ssentongo said. "Multipronged strategies to prevent and treat malaria and HIV in pregnant women are critical to ensure the survival of mothers and their unborn babies."

Anemia is a condition where the body lacks enough healthy red blood cells to carry adequate oxygen to body tissue, resulting in fatigue. Diseases like HIV and malaria can destroy red blood cells and cause a person to become anemic.

The interaction between malaria and HIV leading to anemia in dually-infected patients is synergistic and bidirectional. Malaria leads to an increase in HIV viral load, a decline in the level of immune cells and an increase in inflammation. In addition, malaria increases the rate of disease progression from HIV to AIDS. HIV contributes to more frequent and more severe cases of malaria and increases the density of malaria parasites, which leads to either the destruction of the red blood cells, reduced iron absorption or reduced rate of formation of new red blood cells in the bone marrow.

According to the researchers, preventative strategies for anemia in pregnancy due to malaria and HIV include the use of trimethoprim-sulfamethoxazole (co-trimoxazole), a malaria prophylactic treatment, in addition to antiretroviral therapy, which both lower the odds of coinfection. In addition, vector control using insecticide-treated bed nets and residual spraying is effective. Although intermittent preventive treatment with sulfadoxine/pyrimethamine has been shown to be effective in parts of Africa, intermittent preventive treatment should be avoided in pregnant women, who are on antiretroviral therapy and co-trimoxazole prophylaxis, because of the risk of adverse drug reactions.

BOSTON - Researchers from Massachusetts General Hospital (MGH) have identified a set of modifiable factors from a field of over 100 that could represent valuable targets for preventing depression in adults. In a study published in The American Journal of Psychiatry, the team named social connection as the strongest protective factor for depression, and suggested that reducing sedentary activities such as TV watching and daytime napping could also help lower the risk of depression.

"Depression is the leading cause of disability worldwide, but until now researchers have focused on only a handful of risk and protective factors, often in just one or two domains," says Karmel Choi, PhD, investigator in the Department of Psychiatry and the Harvard T.H. Chan School of Public Health, and lead author of the paper. "Our study provides the most comprehensive picture to date of modifiable factors that could impact depression risk."

To that end, researchers took a two-stage approach. The first stage drew on a database of over 100,000 participants in the UK Biobank -- a world-renowned cohort study of adults - to systematically scan a wide range of modifiable factors that might be associated with the risk of developing depression, including social interaction, media use, sleep patterns, diet, physical activity, and environmental exposures. This method, known as an exposure-wide association scan (ExWAS), is analogous to genome-wide association studies (GWAS) that have been widely used to identify genetic risk factors for disease. The second stage took the strongest modifiable candidates from ExWAS and applied a technique called Mendelian randomization (MR) to investigate which factors may have a causal relationship to depression risk. MR is a statistical method that treats genetic variation between people as a kind of natural experiment to determine whether an association is likely to reflect causation rather than just correlation.

This two-stage approach allowed the MGH researchers to narrow the field to a smaller set of promising and potentially causal targets for depression. "Far and away the most prominent of these factors was frequency of confiding in others, but also visits with family and friends, all of which highlighted the important protective effect of social connection and social cohesion," points out Jordan Smoller, MD, ScD associate chief for research in the MGH Department of Psychiatry, and senior author of the study. "These factors are more relevant now than ever at a time of social distancing and separation from friends and family." The protective effects of social connection were present even for individuals who were at higher risk for depression as a result of genetic vulnerability or early life trauma.

On the other hand, factors associated with depression risk included time spent watching TV, though the authors note that additional research is needed to determine if that risk was due to media exposure per se or whether time in front of the TV was a proxy for being sedentary. Perhaps more surprising, the tendency for daytime napping and regular use of multivitamins appeared to be associated with depression risk, though more research is needed to determine how these might contribute.

The MGH study demonstrates an important new approach for evaluating a wide range of modifiable factors, and using this evidence to prioritize targets for preventive interventions for depression. "Depression takes an enormous toll on individuals, families, and society, yet we still know very little about how to prevent it," says Smoller. "We've shown that it's now possible to address these questions of broad public health significance through a large-scale, data-based approach that wasn't available even a few years ago. We hope this work will motivate further efforts to develop actionable strategies for preventing depression." The study's two-stage approach could also be used to inform the prevention of other health conditions.

The dynamics of the current COVID-19 pandemic could offer valuable insights for the efforts to mitigate climate change. Highlighting the parallels between the global health and the climate emergency, a team of researchers from the Potsdam Institute for Climate Impact Research (PIK) has analyzed what policy makers and citizens can learn from the corona outbreak and how to apply it to the global effort of reducing CO2 emissions. Their proposal: A Climate Corona Contract that unites the younger and the older generations.

"The corona crisis is a test case for global emergency prevention and management in general," says lead author Kira Vinke. "The pandemic has shown that when reaction time is kept to a minimum, a larger public health crisis can be averted. In fact, we should take this very lesson to heart and apply it to managing the climate emergency."

Assessing risks and predicting outcomes

Vinke and the team of authors have looked at four dimensions of risk management: diagnosis, prognosis, therapy, and rehabilitation. They deduced which lessons of the COVID-19 pandemic could be used to stabilize global mean temperature. "The risks and causes of both the coronavirus and the climate crisis have to be scientifically assessed and quantified," explains PIK director and co-author Johan Rockström. But just as important as diagnostics are prognostic approaches: "Countries like New Zealand and Germany were able to predict the outbreak's possible effects and moreover had the ability of immediate action. In the same vein, the global community must integrate climate risks assessments into decision making and act accordingly."

The authors argue that insights from the Corona crisis can help to identify pathways for treating the causes and symptoms of climate change. "Both the Corona and the climate crisis are the result of increasing human pressure on the planet," says co-author Sabine Gabrysch, "But the good news is that the pandemic has demonstrated that with a combination of government action and individual lifestyle changes, it is possible to prevent damages. If there is a will, there is a way."

Compassion and solidarity as guiding principles

The researchers conclude by proposing an intergenerational Climate Corona Contract informed by reason and the principle of social justice. Former PIK director and co-author Hans Joachim Schellnhuber explains: "Younger generations would agree to protect the elderly from COVID-19 by adhering to social distancing measures, while the older generations would push for measures to keep global warming in line with the Paris Agreement." Thus, the researchers' outlook is cautiously optimistic: The outpouring of generosity and new forms of social interactions in the wake of the pandemic show great potentials for cooperation towards the much needed stabilization of the global climate.

PULLMAN, Wash. - Scientists have found clear indicators for how the interaction of poor hygiene and antibiotic use contribute to the colonization of antimicrobial-resistant (AMR) bacteria in humans, a problem that contributes to hundreds of thousands of deaths annually.

The findings by researchers at Washington State University's Paul G. Allen School for Global Animal Health (Allen School) and Universidad del Vale de Guatemala (UVG) were published Thursday in the journal Scientific Reports.

"Coupled with antibiotic stewardship, these new findings support the critical need to improve sanitation and hygiene as an intervention to slow the spread of antimicrobial-resistant bacteria," said co-author Dr. Mark Caudell, AMR coordinator, Food and Agriculture Organization of the United Nations. "Poor sanitation has a primary effect on antimicrobial resistance so investing in better infrastructure will help reduce the incidence of AMR infections."

This  collaborative effort lead by WSU and UVG in Guatemala,  is part of a larger research program to understand how prevailing patterns of antibiotic use and regulations, access to human and animal healthcare services, and sanitation impact AMR patterns in high- and low-income countries.

Surveying households in rural and urban Guatemalan communities, they examined how the distribution of antimicrobial-resistant Escherichia coli was related to population density, access to antibiotic therapies, sanitation and hygiene indicators such as access to clean water and prevalence of open defecation, and food preparation and milk consumption practices.

Results confirmed that AMR was associated with increasing frequency of antibiotic use, poor household hygiene levels, milk consumption, and diarrhea episodes.

"Improved antibiotic stewardship, including control of unregulated access to antibiotics is critical to reducing the prevalence of antimicrobial-resistant bacteria, but stewardship alone will not successfully impact the prevalence of resistance when hygiene is compromised," stated Dr. Brooke Ramay, co-lead researcher and professor with Allen School and UVG.