Body

Bottom Line: The U.S. Preventive Services Task Force (USPSTF) recommends against screening for bacterial vaginosis in someone without symptoms and who is pregnant but not at increased risk for preterm delivery. Bacterial vaginosis is a common condition caused by an overgrowth of bacteria in the vagina and it has been associated with adverse pregnancy outcomes including preterm delivery. The USPSTF found insufficient evidence to make a recommendation on screening those who are pregnant and at increased risk for preterm delivery.  The USPSTF routinely makes recommendations about the effectiveness of preventive care services and this statement reaffirms its 2008 recommendations.

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

(doi:10.1001/jama.2020.2684)

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

People with celiac disease have increased risk of dying prematurely, despite increased awareness of the disease in recent years and better access to gluten-free food. This is according to a new study from Karolinska Institutet in Sweden and Columbia University in the U.S. published in the prestigious journal JAMA. Celiac disease was linked to increased risk of death from cardiovascular disease, cancer and respiratory disease.

Previous studies have demonstrated a modest but persistent increased risk of premature death in patients with celiac disease. However, in recent years, more people with milder disease have been diagnosed and gluten-free food is widely available. It has therefore been hypothesised that celiac disease may no longer be associated with an increased risk of death.

Using nationwide data from Sweden's pathology departments, linked to national healthcare registers, researchers at Karolinska Institutet and Columbia University examined almost 50,000 patients with celiac disease and their risk of death.

Compared with controls, overall mortality was increased by 21 percent in those with celiac disease. The relative increase in mortality risk was present in all age groups and greatest in those diagnosed in the age range of 18 to 39 years old.

"We have known that celiac disease can cause a number of long-term complications that can impact life expectancy, but this study examines an entire population in the most recent era, at a time when awareness of celiac disease and access to gluten-free food is widespread," says Benjamin Lebwohl, Director of Clinical Research at the Celiac Disease Center at Columbia University and first author of the study. "Despite this, we found that celiac disease is associated with long-term consequences."

Individuals with celiac disease were at increased risk of death from cardiovascular disease, cancer and respiratory disease. Compared with controls, the overall mortality risk was greatest in the first year after diagnosis but the risk increase persisted beyond 10 years after diagnosis. The increased risk was present also in patients diagnosed during recent years (2010-2017).

"Celiac disease is characterised by inflammation, which is generally bad for your health," says corresponding and last author, Jonas F Ludvigsson, senior paediatrician at Örebro University Hospital and professor of clinical epidemiology at the Department of Medical Epidemiology and Biostatistics at Karolinska Institutet. "I am therefore not surprised that we found an increased mortality for a number of causes of death in individuals with celiac disease."

The fact that the relative risks were highest in the first year of follow-up can have several explanations, says Jonas F Ludvigsson.

"The intestinal inflammation is often most intense around diagnosis, and before a gluten-free diet has had an effect on mucosal healing. Another possible explanation is that the celiac diagnosis may have been made in patients who were very ill from other causes."

In separate analyses, the authors adjusted for socioeconomic status and comorbidity but the increased mortality risk for people with celiac disease remained.

The research was funded by the Swedish Research Council, the Celiac Disease Foundation and the Louis and Gloria Flanzer Philanthropic Trust. Jonas F Ludvigsson has previously coordinated another study that received funding from the pharmaceutical company Janssen. No other potential conflicts of interest are reported in the paper.

What The Study Did: Researchers used urinary measures of biomarkers of phthalates (a group of chemicals used in plastics) and phthalate substitutes from couples undergoing fertility care and examined if higher concentrations prior to conception were associated with an increased risk of preterm birth.

Authors: Carmen Messerlian, Ph.D., of the Harvard T.H. Chan School of Public Health in Boston, is the corresponding author.

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

(doi:10.1001/jamanetworkopen.2020.2159)

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

What The Study Did: This survey study assessed public concerns about symptoms of coronavirus disease 2019 and individual actions in response to the pandemic.

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

(doi:10.1001/jamainternmed.2020.1369)

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

What The Viewpoint Says: Exploring the challenges in the Italian health care system during the coronavirus disease 2019 pandemic and how other countries can plan for optimal actions.

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

(doi:10.1001/jamainternmed.2020.1447)

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

The research team, based at the NIHR Applied Research Collaboration (ARC) West in collaboration with the West of England Academic Health Science Network (AHSN), studied the impact of NEWS scores collected for more than 13,000 urgent GP referrals to hospital. They found that higher scores are associated with patients being taken to hospital by ambulance more quickly. Average transfer time was 94 minutes for patients with the highest scores, compared with 132 minutes for those with the lowest. Patients with high scores were also reviewed more quickly after arriving at hospital.

Patients with higher scores were sicker, with longer hospital stays and more of them being admitted to intensive care. Patients with the highest scores were nearly five times more likely to have sepsis than those with the lowest scores and eight times more likely to die within two days of hospital admission.

Early warning scores (EWS) are designed to help healthcare staff identify patients whose condition is deteriorating, to allow them to get the treatment they need quickly. Higher scores indicate poorer health.

The National Early Warning Score (NEWS) is a simple scoring system of six clinical measurements which are added together to give an overall score, with various thresholds triggering different clinical responses.

National Early Warning Scores are already used in hospitals across England and by ambulance call handlers and paramedics for triage. However, they aren't consistently used outside hospital and ambulance services, for example in GP surgeries and community settings.

The researchers also suggest that patients and carers could benefit from education about NEWS to enable the sickest patients to be transferred to hospital quickly.

These findings come at a time when the Royal College of General Practitioners (RCGP) is endorsing the use of NEWS in GP surgeries as part of a system-wide response to the COVID-19 pandemic, with new guidance for GPs issued last week in their COVID-19 resource hub.

Lauren Scott, Senior Research Associate at NIHR ARC West, said: "Ambulance call handlers, paramedics and hospital staff are already using NEWS to triage patients. We believe calculating NEWS at an earlier point in the patient pathway, in GP surgeries for example, could help the sickest patients receive timely care and therefore save lives. Our findings are particularly relevant in the context of the coronavirus pandemic, as some COVID-19 patients develop sepsis as a result of the infection.

"We found that higher NEWS values recorded at referral into hospital were associated with poorer clinical outcomes, which is to be expected as these patients will usually be the most ill. But we also found that higher NEWS scores meant patients conveyed by ambulance were taken to hospital more quickly, and were assessed more quickly when they got there."

Dr Alison Tavare acute; GP and Primary Care Clinical Lead at the West of England AHSN, said: "As a GP I use NEWS alongside clinical judgement when arranging admissions to help secondary care colleagues decide where patients should be seen, by whom, and with what urgency. I feel strongly that NEWS also protects me as a clinician; if a patient unexpectedly has a high NEWS it makes me think 'have I missed something?"

Dr Tavare's acute;'s personal experience of being a patient with sepsis is also published in BJGP this week.

April 7, 2020 - People living with HIV/AIDS are at increased risk of depressive disorders. But all too often, these conditions go unrecognized or untreated, suggests a literature review in the May/June issue of Harvard Review of Psychiatry. The journal is published in the Lippincott portfolio by Wolters Kluwer.

Proper diagnosis and management are essential to reduce negative health effects of depression in patients with HIV/AIDS, according to the report by Gustavo C. Medeiros, MD, of University of Texas Southwestern Medical Center, Dallas, and colleagues. Based on an analysis of 125 research publications, "We provide evidence-based recommendations to improve assessment and management of depressive disorders in seropositive persons," the researchers write.

Diagnosis and Treatment of Depression in Patients with HIV/AIDS

People with HIV/AIDS are at higher risk of depression than the general population - including a two- to four-fold increase in the risk of major depressive disorder (MDD). Depressive disorders are linked to negative health outcomes including poorer compliance with antiretroviral therapy, lower immune function (CD4 cell count), and a higher mortality rate. Dr. Medeiros and colleagues seek to provide an "updated, practical, and global overview" of depression in HIV/AIDS, focusing on:

Assessment and diagnosis. "Depressive disorders are vastly underdiagnosed in HIV/AIDS," according to the authors. Patient assessment is complex due to the overlap between depression and HIV/AIDS symptoms, including fatigue, insomnia, and reduced appetite. Making the correct diagnosis is essential for providing the appropriate treatment.

In addition to MDD, depressive symptoms in patients with HIV/AIDS may be due to other medical conditions, medications or addictive substances, adjustment disorder, or other psychiatric disorders. Other contributing factors may include direct brain damage caused by HIV, as well as psychosocial factors such as chronic stress, HIV-related stigma, and social isolation.

Treatment. Many if not most patients with HIV/AIDS do not receive recommended treatment for depression. One study reported that only seven percent of HIV-positive patients with MDD had access to adequate treatment. Selective serotonin reuptake inhibitors (SSRIs) are the first-choice medications; other antidepressants may be used but require close monitoring for side effects and drug interactions. Other helpful treatments include individual or group psychotherapy. It's also essential to ensure proper management of HIV/AIDS and related medical conditions.

Special challenges. Studies have found that persons with HIV/AIDS have low adherence to recommended treatment for depression - possibly related to HIV-related stigma and feelings of shame. The combination of depression and HIV/AIDS is strongly linked to suicide, with rates eight to ten times higher than in the general population. Depression also poses special challenges in adolescents and older adults with HIV/AIDS.

The article includes detailed information on the differential diagnosis of MDD and other forms of depression, key points related to the use of antidepressant medications, and 'clinical pearls' in managing depressive disorders in patients with HIV/AIDS. Dr. Medeiros and colleagues conclude: "Evidence-based recommendations are available for improving the assessment and management of depression in seropositive persons, and they should be implemented in real-life practice to improve outcomes."

Cataract is among the most widespread eye diseases. According to WHO, up to a third of all visual impairments have to do with cataract. The treatment methods are well-known but can sometimes be traumatizing. Scientists from ITMO and the S.N. Fyodorov Eye Microsurgery Complex spent over 20 years working on reducing the side effects of cataract surgery. As a result, they came up with a technology where a laser is used both to destroy the clouded eye lens and to stimulate the regeneration of adjacent tissue. The researchers gave a detailed description of their method in an article that has been recently published in Optical and Quantum Electronics.

The eye is a very important organ. A healthy eye lets us see in the light and in the dark, read fine print and trace fast objects. But if something goes wrong, the eyesight can rapidly degrade or even disappear completely. One of the common problems is the clouding of the lens, or cataract. The methods for treating cataract are being constantly improved; for one, scientists from ITMO University work on this topic in collaboration with specialists from the S.N. Fyodorov Eye Microsurgery Complex.

"The treatment method is surgical and has to do with removing the clouded eye lens and replacing it with an artificial one made of plastic or sapphire, comments Andrey Belikov, a professor at ITMO University. "The eye lens is destroyed either with ultrasound or a laser. When using a laser, a special tip is inserted into the anterior chamber of the eye close to the lens, and the laser breaks the lens into tiny fragments that are then removed from the eye. An artificial lens is then put in their place. The problem is that this process damages the adjacent tissue, and the regeneration doesn't always go well."

In the recent decades, many researchers placed their focus on reducing the traumatizing effect of cataract surgery. In 1997, scientists from ITMO University and S.N. Fyodorov Eye Microsurgery Complex, as well as several other research institutions, started to experiment with the use of laser radiation for destroying the cataract. With time, surgeons noticed that the less powerful laser can not only illuminate the surgical field but also stimulate the regeneration of the damaged tissue. So they started conducting experiments aimed at finding the optimal interaction method between the destroying and the illuminating lasers. It turned out that using both lasers simultaneously is the most efficient method. This idea called for elaborate work of optical engineers: as entering the eye with two instruments at the same time is highly undesirable, for the radiation of both lasers it was necessary to use a common optical fiber.

"The simultaneous use of two lasers is good because we get cells that are damaged but not destroyed," comments Prof. Belikov. "And it's very important to stimulate their regeneration at once. This way, the regeneration process takes place in the most favourable conditions."

As of now, the method has already been introduced at the clinic of the S.N. Fyodorov Eye Microsurgery Complex, and almost all of their cataract surgeries make use of two lasers. It has been clinically proved that in the long-term, the use of this method allows to reduce the loss of corneal endothelial cells by 1.8 times in comparison with ultrasonic phacoemulsification, and there have yet been no reports of macular edema or endothelial-epithelial corneal dystrophy.

WEST LAFAYETTE, Ind. - In 2018, approximately 324,000 men died from cancer in the United States. The combination of lung cancer, prostate cancer and colorectal cancer equated to half of those deaths.

Large percentages of each of these cancers can be prevented or treated if caught early. Now, Purdue University scientists have created a new therapy option that may help halt tumor growth in certain cancers such as prostate, which is among the most common types of cancer in men.

"We have designed a therapy that can help recruit immune cells to kill cancer and also help repair bone and tissues damaged by tumors," said Marxa Figueiredo, associate professor of basic medical sciences in Purdue's College of Veterinary Medicine, who helped lead the research team and is working with the Purdue Research Foundation Office of Technology Commercialization to patent the innovation. "One of the best features of this technology is that it shows great promise in enabling treatment for many other cancers and diseases that could benefit from halting tumor growth and promoting bone repair."

The therapy technology is presented in the journal Molecular Therapy: Methods & Clinical Development.

The Purdue team used a protein called interleukin-27, or IL-27, which has shown promise in reducing tumor growth and helping stop cancer from spreading in the body. IL-27 is a cytokine, a kind of protein secreted by cells of the immune system that act as chemical messengers and can help the immune system target cancer and other diseases.

"Immune cells are naturally attracted to areas of the body with lots of signals that come from proteins such as IL-27," Figueiredo said. "So, with our novel approach of targeting the IL-27 to the tumor or bone cells, we can use these proteins to produce signals that bring healthy cells to areas of the body with cancer or other disease and kill the tumors and begin the process of repairing bone and other musculoskeletal tissues."

Figueiredo said the new Purdue therapy technology has applications for people and animals with many different types of cancer, including breast and lung, and other diseases where protein targeting could improve the immune system's response.

Texas A&M University scientists found that a surprising number of fungi naturally associated with cultivated cotton were capable of curtailing the negative effects of a plant parasite known as the Southern root knot nematode, an economically damaging pest of cotton with the ability to significantly reduce yields. These fungi live in the soil or even inside of the cotton plants themselves but their effects on plant health have been mostly overlooked.

Gregory Sword and colleagues at Texas A&M University inoculated cotton seeds with a diverse array of fungal isolates and tested the resulting seedlings in greenhouse trials for susceptibility to gall formation by root knot nematodes. A majority (77 percent) of the fungal treatments reduced galling and these reductions were highly repeatable across independent trials.

"Our findings indicate that many fungi associated with cotton may have previously unappreciated positive effects on plant health and tolerance to stressors," said Sword. "Our research provides a rich pool of candidate fungi for further testing as potential biological tools for root knot nematode management in cotton and other plants."

Taxonomy was not a reliable predictor of the fungal effects, according to Sword. Isolates of the same fungal species had contrasting efforts, as some isolates increased galling while others decreased it.

While this study primarily draws on microbiology, nematology, and plant pathology, Gregory Sword, who started the research, is an insect ecologist with no formal training in those fields.

"The study is an example of multidisciplinary collaboration coming together to conduct a project that otherwise would not have been possible," Sword said. "It's also an example of not being afraid to think outside the box. Lots of people were skeptical at first when I started this research, including some of the co-authors who went on to become very important collaborators!"

Sword first worked with fungal endophytes at the University of Sydney. He accepted a position at Texas A&M University to work on cotton and immediately began compiling a fungal endophyte collection from cotton grown around the state. He used this data to see if he could find fungi that might have a negative effect on insects when inoculated back to the plant.

"The most surprising outcome has been the large number of isolates that we've found so far that have positive effects on plants when they are challenged with a range of biotic and abiotic stressors, including nematodes as we show in the current study," said Sword. "The work even captured the interest of an industry partner that licensed my entire endophyte library for commercial product development."

BOSTON - (April 6, 2020) - Fatty liver disease not associated with alcohol consumption, which is called Nonalcoholic Fatty Liver Disease or NAFLD, affects more than one billion people worldwide. Even in children the numbers are overwhelming, with up to 80 percent of pediatric patients who are considered obese affected worldwide. People with NAFLD can progress to a severe form known as nonalcoholic steatohepatitis (NASH), which puts patients at higher risk for cirrhosis or liver cancer.

With no definitive treatment options or early detection methods yet discovered, researchers have been hard at work to identify early biomarkers of this disease. "This becomes also especially important in the context of diabetes because individuals with Type 2 diabetes are much more susceptible to this disease," says Rohit N. Kulkarni, MD, PhD, Section Head, Senior Investigator, Islet Cell and Regenerative Biology, Joslin Diabetes Center, and Professor of Medicine, Harvard Medical School.

But recent research from Dr. Kulkarni's lab at Joslin has uncovered a biomarker in humans tied to the development of NAFLD that might help doctors detect early stages of the disease. The researchers also determined that this biomarker, a protein known as "neuronal regeneration related protein" (or NREP), plays a significant role in the regulation of a pathway that is currently being reviewed in clinical trials as a treatment option for the disease. The study was published today in Journal of "Clinical Investigation."

"We identified NREP as a new biomarker for NAFLD that is involved in the regulation of liver fat metabolism and in a process called fibrosis that occurs during the progression of the fatty liver disease that may lead to cirrhosis and liver cancer" says Dario F. De Jesus, MSc, PhD, a postdoctoral research fellow in the Kulkarni Lab at Joslin and lead author on the study.

Previous studies had indicated genetics played a large role in who got NAFLD. But other evidence suggests that environmental factors such as the parental health status are also at play. "One of the causative factors that has been suggested is the parental influence in the offspring, in the sense that if either the mother or the father [or particularly both] has metabolic syndrome (a medical condition associated with obesity, high blood glucose, high cholesterol, and elevated insulin levels) then the chances of the offspring developing this disease is greater," says Dr. Kulkarni.

Dr. Kulkarni's research team and collaborators tested this hypothesis first in animal models in their recently published study. They used two groups of mice; one group had a genetic modification to have the markers of metabolic syndrome. Another group was not genetically modified. They studied the offspring from these groups in three different categories: either one of the parents had metabolic syndrome, both parents did, or neither did. Then they selected genetically normal offspring from each of these parents and fed them either a normal diet or a high caloric diet rich in fat to mimic obesity, and monitored their development.

"When the offspring were fed a normal diet, they did not experience much change in body fat percentage. But when the offspring [of parent groups affected by metabolic syndrome] were fed a slightly high fat diet, their body fat content went up dramatically in comparison with the offspring of the healthy parents," says Dr. Kulkarni.

When they looked in more depth at where the body fat accumulated, they saw a striking increase of fat in the liver. These offspring also had increased cholesterol and triglycerides in the liver.

They took a deep dive into the genetic pathways that were active in the healthy offspring versus the offspring that developed NAFLD. They noticed the protein NREP was reduced in the unhealthy offspring. This was the first time NREP was linked to liver metabolism. They then either increased (e.g. overexpressed) or decreased (e.g. knocked down) NREP in culture dishes to study this newly discovered function.

"When we decreased NREP levels in human liver cells, the cholesterol pathway and markers associated with the development of fibrosis went up resembling what happens during the progression of NAFLD" says Dr. Kulkarni.

They wanted to see if this association of lower levels of NREP with NAFLD was also true in humans. They collaborated with researchers in Finland who had a large database of information from patients in various stages of the liver disease to better understand the correlation with NREP levels.

"We detected this protein really clearly and we could show a pattern that tracks the progression of the disease. So, this is really exciting," says Dr. Kulkarni. In other words--as soon as NAFLD started, NREP circulating levels got lower, suggesting NREP is an early biomarker of NAFLD.

In this study, they also showed that NREP modulates a protein called ATP citrate lyase (or ACLY). ACLY is actively being investigated in clinical trials as a possible treatment for NAFLD. This means that the discovery of NREP's role in NAFLD not only yields a useful biomarker for tracking disease course, it can also help further the development of a treatment.

As a follow-up, they plan to specifically track the pathways by which parental metabolic syndrome modifies how NREP is expressed in offspring. But for now, they have a valuable biomarker to track NAFLD in the general population.

"We can really begin to consider, in the clinic, using this protein as a biomarker to identify those individuals in that risk window. We can also track those who already have low NREP but don't have the disease, with the assumption that when it is low, then they're much more susceptible and should be followed up very carefully," says Dr. Kulkarni. "That gives an important perspective for extra, personalized care."

Boston, Mass. - While the majority of people with COVID-19 won't require hospitalization, those who do are likely to seek medical help as a result of acute respiratory distress syndrome, or ARDS, a severe lung injury common in patients with critical illnesses. At present, there is no effective treatment for ARDS other than supportive care with mechanical ventilation.

A team of physician-scientists at Beth Israel Deaconess Medical Center (BIDMC) -- part of Beth Israel Lahey Health -- are now enrolling patients in a clinical trial to evaluate a common anti-clotting drug for the treatment of COVID-19-positive patients with ARDS. The newly launched trial follows a special report the team published in the Journal of Trauma and Acute Care Surgery that suggested the use of a drug called tPA could reduce deaths among patients with ARDS as a complication of COVID-19.

Epidemiological models predict that thousands of Americans will require mechanical ventilation in the coming months as a result of the COVID-19 pandemic, far exceeding the estimated 200,000 ventilators currently available in the United States.

"As the global pandemic of COVID-19 begins to oversaturate the world's medical capacity to accommodate a surge of patients with ARDS, it's critical we consider how existing therapies that are widely available may be of use in this unprecedented public health emergency," said the special report's lead author and clinical trial investigator, Christopher D. Barrett, MD, a senior surgical resident at BIDMC and a research fellow at MIT.

"If effective and safe for the treatment of ARDS in patients with COVID-19, tPA could save lives by reducing recovery time and freeing up more ventilators for other patients in need."

An anticoagulant naturally produced by the body, tPA was approved by the U.S. Food and Drug Administration in 1996 for use in patients experiencing heart attack, stroke and pulmonary embolism. Researchers have considered the use of anti-coagulant drugs to reduce ARDS-induced death for two decades. Though the approach has never been widely adopted or formally FDA-approved, a clinical observation made about a subset of patients with COVID-19 induced ARDS made the idea seem newly relevant.

"We're hearing anecdotally that a subset of patients with COVID-19 induced ARDS are clotting abnormally around their catheters and IV lines," said senior author, Michael B. Yaffe, MD, PhD, an attending surgeon in the departments of Acute Care Surgery, Trauma, and Surgical Critical Care, and in Surgical Oncology at BIDMC. "We suspect these patients with aggressive clotting are will show the most benefit from tPA treatment, and this new clinical trial will reveal whether that's the case."

Led by Yaffe, Barrett, and colleagues from BIDMC's Department of Anesthesia, Critical Care and Pain Medicine, including Shahzad Shaefi, MD, and Department Chair Daniel S. Talmor, MD, MPH, the tPA clinical trial is now open and enrolling patients with COVID-19 induced ARDS admitted to BIDMC. Next steps will include identifying biomarkers -- measurable characteristics such as blood levels of clotting factors -- to help more accurately determine which patients are most likely to respond to tPA as a treatment for ARDS, said Yaffe, who is also a Professor of Biology and Biological Engineering at the Massachusetts Institute of Technology.

The collaborative research was facilitated by Beth Israel Lahey Health COVID-19 Innovation Hub -- an effort led by Gyongyi Szabo, MD, PhD, Chief Academic Officer at Beth Israel Lahey Health -- to address the emerging challenges related to the pandemic.

Since the publication of the special report on March 23, Barrett and Yaffe have already heard from physicians across the country eager to try tPA for the treatment of COVID-19 induced ARDS. Because the medication is an FDA-approved drug already in widespread use for patients who have had heart attacks or strokes, doctors are permitted to prescribe it for off-label usage.

Globally, human society is aging. A side-effect of this is that age-related disorders, such as frailty, are becoming increasingly common. Frailty includes, not only physical disabilities, but also a decline in cognitive function and an increase in various social problems. The prevalence of this disorder among those aged 65 and over is estimated at 120 million people worldwide.

But, due to their small range of activities, people who suffer from frailty are often hidden. They tend to stay at home and out of the public eye. They can struggle to walk, suffer from memory loss, and find essential tasks, like putting out the rubbish or cleaning the house, very difficult. As such, frail people require more help than their healthy peers. And although there has been some indication that frailty may be reversible, no such interventions have yet been established.

The first step to curing frailty is to find an efficient way to diagnose the disorder. Researchers from the G0 Cell Unit at the Okinawa Institute of Science and Technology Graduate University (OIST), alongside collaborators at the Geriatric Unit at Kyoto University have taken a close look at the blood metabolites of both frail and non-frail elderly patients using a technique called metabolomics. They've found 15 metabolites whose levels in the blood correlate with frailty. Their findings, published in PNAS, have shed light on what causes the disorder and how we might reverse it.

Measuring frailty

For this study, the researchers looked at 19 elderly patients, all above the age of 75, and measured whether they suffered from frailty through three clinical analysis tests - the Edmonton frail scale (EFS), the Montreal cognition assessment (MoCA-J), and the Timed Up and Go Test (TUG).

"Both the EFS and the MoCA-J gave us an indication of the individuals cognitive function, whereas the TUG allowed us to assess their motor ability," said Professor Mitsuhiro Yanagida, who runs the Unit at OIST. "Between them, they also showed health status, mood, short-term memory and other indications, so they gave us a clear idea of who suffered from the disorder."

By using these three tests, the researchers found that nine out of the 19 individuals fit into the category of being frail whereas the other ten did not, however some still did suffer from cognitive impairment or hypomobility, a syndrome which hinders movement.

Identifying markers in the blood

Next, the researchers took blood samples from the 19 patients and had a close look at the metabolites - small molecules of amino acids, sugars, nucleotides and more that make up our blood. They tested 131 metabolites and found that 22 of them correlated with frailty, cognitive impairment and hypomobility. Patients who suffered from these disorders tended to have lower levels of most of these metabolites.

"Blood metabolites are useful as biomarkers for finding, diagnosing and observing symptoms of frailty," said Dr. Takayuki Teruya, Research Unit Technician in the G0 Cell Unit. "By using a simple blood test, we could start to diagnose frailty early on and lengthen healthy life expectancies by early intervention."

The 22 metabolites identified included antioxidant metabolites, amino acids and muscle or nitrogen related metabolites. Fifteen of them correlated with frailty, six indicated cognitive impairment and twelve indicated hypomobility. The metabolites that correlated with frailty overlapped with five of those that indicated cognitive impairment and six that indicated hypomobility.

These metabolites include some of the aging markers in healthy people reported by the same group in 2016. This suggests that the severity of biological aging, which varies between individuals, could be monitored from an early stage of old age by measuring blood biomarkers.

"Notably, we found that levels of the antioxidant, ergothioneine, decreased in the frail patients," said Professor Yanagida, "This metabolite is neuroprotective, meaning that people who suffer from frailty are more vulnerable to oxidative stress."

The research indicates that frailty has a distinct metabolomic profile when compared to other age-related disorders. By demonstrating a link between these metabolites and the symptoms of the disorder, these findings could lead to a different approach to diagnosing and treating frailty.

The researchers in the G0 Cell Unit at OIST collaborated with Dr. Masahiro Kameda and Professor Hiroshi Kondoh in the Geriatric Unit, Graduate School of Medicine at Kyoto University. Kyoto University and OIST have jointly applied for a patent for these findings.

In São José do Rio Preto, state of São Paulo (Brazil), almost a third of the population aged 10-40 are estimated to have no antibodies against measles, according to a new study that tested 981 people in various age groups. São José do Rio Preto is the largest city in the state's northwestern region, with approximately half a million inhabitants.

According to the survey, 32.9% of those tested in the under-40 age group were not immune to measles, compared with the 99% immunity observed in the over-50 age group.

The study was supported by São Paulo Research Foundation - FAPESP. The principal investigator was Maurício Lacerda Nogueira, a professor in the São José do Rio Preto Medical School and former chair of the Brazilian Society for Virology. The findings are published in Scientific Reports, an online journal owned by Springer Nature.

"Considering the total number with documented evidence of vaccination, 39.3% did not have immunity against measles, and 20.2% lacked antibodies against rubella. These percentages are sufficient to protect the population against rubella but not against measles. The combined vaccine against measles, mumps, and rubella [MMR] is part of the national vaccination calendar in Brazil," Nogueira told.

The study, he added, suggests that there is a correlation linking the production of antibodies, vaccination, and exposure to the virus. The percentage of immune individuals among those aged more than 50 years who had been exposed to the virus throughout their lives was far higher than that among the younger age groups, even when they had been vaccinated.

"This relatively high seronegativity rate [lack of antibodies] needs to be investigated, but vaccination is the main weapon we have and absolutely mustn't be discarded," Nogueira said.

Measles were considered to be eradicated for years but re-emerged in several countries, including Brazil, after a decline in vaccination coverage. In the prevaccination period, it was a common disease in patients under 10 years of age, and despite a low mean mortality rate, it is estimated to have caused 5 million to 8 million deaths worldwide.

Measles is highly contagious, with a basic reproduction number (R0) of 12-18, meaning that each person with measles could transmit the virus to between 12 and 18 people in a totally susceptible population. For the sake of comparison, the novel coronavirus (SARS-CoV-2) has an R0 of 2-3, according to the World Health Organization (WHO).

"Measles can be controlled by vaccination programs that reach 95% coverage with two doses of the vaccine," Nogueira said. "In addition, cases have to be properly identified, and measures must be taken to prevent transmission."

According to a recently published study, the prevalence of measles in Brazil started to fall in 1998 as a result of vaccination. The last locally acquired case was reported in 2000.

An outbreak in 2013-15 produced 1,310 reported cases. The Pan American Health Organization (PAHO-WHO) implemented an action plan that was successful, and endemic transmission was considered eradicated in the Americas in 2016.

In 2017, however, cases were reported in the United States, Canada, Venezuela and Argentina. The disease recently began circulating in Brazil again, with 11,371 confirmed cases and 12 deaths in 2018-19.

"The spread of vaccine refusal has become a risk factor for measles outbreaks, and the WHO has identified vaccine hesitancy as one of the top ten global health threats in 2019," the researchers stress in the Scientific Reports article.

CLEMSON, South Carolina -- Although mostly preventable, tooth decay is one of the most common chronic diseases in children worldwide, particularly in developing countries. If left untreated, cavities can be painful and may negatively affect a young child's overall health, development and quality of life.

Clemson University College of Science researchers recently conducted a study that may someday lead to better cavity prevention measures and treatments. Specifically, biological sciences assistant professor Vincent Richards' group examined the oral mycobiome, including all the fungi that might live there.

"This work provides valuable insight into the oral mycobiome and the role fungi play in the mouth as it relates to caries," said Richards. "If we understand that better then researchers can develop better cavity prevention measures. For example, perhaps they can put beneficial fungal species into a pro-biotic treatment."

For years, the dental community has known that tooth decay occurs when the good and bad bacteria in our mouth become imbalanced and forms a biofilm (aka plaque). The biofilm absorbs the sugars we eat and the bacteria catabolize those sugars, turning them into acid, which decalcifies the teeth and causes cavities.

Thanks to advances in genome sequencing technology, scientists recently discovered that there is also a high diversity of fungi in the mouth, albeit in far fewer numbers than bacteria. However, little was known about the fungi's role in cavity formation and caries disease progression.

"The microbiome is a community-based thing and it's very complex," said biological sciences graduate student Lauren O'Connell, the lead author of the study.  "Because fungi are present in the tooth biofilm, they're capable of utilizing these same sugars [as bacteria] and can produce acid, but we don't fully understand their role."

In the study, O'Connell sequenced the DNA from plaque samples of 33 children with varying stages of tooth health, including healthy teeth with no cavities; teeth with enamel lesions, which are indicative of an early-stage cavity; and teeth with dentin lesions, which indicate an advanced-stage cavity requiring either a filling or extraction.

She also examined the condition of the patients' mouths, including a mouth with no cavities or lesions; a mouth with some teeth that have enamel lesions; and a mouth that has some teeth with enamel and dentin lesions.

"By looking at two variables--tooth and mouth health--we are taking a site-specific approach, which enables us to categorize each plaque sample six ways, or along a continuum," said Richards. "This is important because we have found that the bacterial microbiome from a healthy tooth in a diseased mouth is more similar to the microbiome of a diseased tooth. That microbiome has shifted its profile to more of a diseased state."

"We wanted to see how the microbiome community changed as the disease progressed," explained O'Connell. "There's only been one other study that looked at the fungi in relation to cavities, but they examined only healthy teeth and severely diseased teeth."

The research team identified 139 species of fungus that live in human dental plaque, and of those, nine were strongly associated with dental health--in other words they could be contributing to keeping teeth healthy.

The fungi associated with healthy teeth may be producing a compound called xylitol, which has been shown to inhibit the growth of the Streptococcus mutans bacteria that is known to cause cavities. Xylitol is an ingredient in sugarless gum.

"It's possible that the nine fungi are promoting health by creating xylitol and other advanced microbial compounds," said O'Connell. "But we have to do further functional testing to figure out if that is actually what is happening."

The team also discovered interesting things about fungi associated with disease. For example, they learned that Candida dubliniensis was strongly associated with late-stage cavities and was found in abundance as tooth decay progressed, which could make it a potential indicator species of early childhood caries.

According to O'Connell, a second finding related to possible disease-causing fungi was that Candida albicans, the fungus that causes yeast infections, was found in both healthy and diseased plaque samples, which makes its role in dental caries unclear.