Body

PHILADELPHIA--People who have recovered from COVID-19 had a robust antibody response after the first mRNA vaccine dose, but little immune benefit after the second dose, according to new research from the Penn Institute of Immunology. The findings, published today in Science Immunology, suggest only a single vaccine dose may be needed to produce a sufficient antibody response. The team found that those who did not have COVID-19--called COVID naïve--did not have a full immune response until after receiving their second vaccine dose, reinforcing the importance of completing the two recommended doses for achieving strong levels of immunity.

The study provides more insight on the underlying immunobiology of mRNA vaccines, which could help shape future vaccine strategies.

"These results are encouraging for both short- and long-term vaccine efficacy, and this adds to our understanding of the mRNA vaccine immune response through the analysis of memory B cells," said senior author E. John Wherry, PhD, chair of the department of Systems Pharmacology and Translational Therapeutics and director of the Penn Institute of Immunology in the Perelman School of Medicine at the University of Pennsylvania.

The human immune response to vaccines and infections result in two major outcomes--the production of antibodies that provide rapid immunity and the creation of memory B cells, which assist in long-term immunity. This study represents one of the first to uncover how memory B cell responses differ after vaccination in people who previously experienced infection, compared to those who have not have COVID-19.

"Previous COVID-19 mRNA vaccine studies on vaccinated individuals have focused on antibodies more than memory B cells. Memory B cells are a strong predictor of future antibody responses, which is why it's vital to measure B cell responses to these vaccines," Wherry said. "This effort to examine memory B cells is important for understanding long-term protection and the ability to respond to variants."

The researchers recruited 44 healthy individuals who received either the BioNTech/Pfizer or Moderna mRNA COVID-19 vaccine at the University of Pennsylvania Health System. Of this cohort, 11 had a prior COVID-19 infection. Blood samples were collected for deep immune analyses four times prior to and after vaccine doses.

The data shows key differences in vaccine immune responses in COVID naïve versus COVID-19 recovered individuals. The findings suggest that only a single vaccine dose in individuals recovered from COVID-19 may be enough to induce a maximal immune response, based on both strong antibody and memory B cell responses. This is likely due to a primary immune response because of their natural infection.

In contrast, it took two vaccine doses to demonstrate considerable antibody and memory B cell responses for those who did not have COVID-19, underlying the importance of the two-dose mRNA vaccine schedule to achieve optimal levels of immunity.

These findings were also reflected in an analysis of antibodies against the D614G mutation and the B.1.351 South African variant of COVID-19. For those who did not have COVID-19, it took a second dose to get a robust enough immunity level against the mutation and variant, whereas those recovered from COVID-19 had a strong enough antibody response after one dose.

"This is important for us to keep in mind as we consider vaccination strategies in the future and potential viral variants," Wherry said. "We need to make sure people have the strongest memory B cell responses available. If circulating antibodies wane over time, our data suggests that durable memory B cells could provide a rapid source of protection against re-exposure to COVID-19, including variants."

The researchers also examined vaccine-induced side effects in relation to immune responses. While seen in a smaller cohort of 32 COVID naïve people, they found that those who experienced systemic side effects after receiving a vaccine dose--such as fever, chills, headache, and fatigue--had stronger post-vaccination serum antibodies, but not memory B cells. Although more data is needed and all subjects developed robust immunity, it is possible that inflammation and side effects early after vaccination could signal stronger immune reactions.

"Everyone has good responses to the vaccines. They work to protect people against COVID-19. But for those who may be worried about side effects, they are not necessarily a bad thing--they may actually be an indicator of an even better immune response," Wherry said.

The researchers are continuing larger-scale studies, which are necessary to fully examine the question of a one- or two-dose regimen in COVID-19-recovered individuals and to see how long the vaccine antibodies last. Wherry and his team are continuing to study the vaccine's effect on virus-specific T cell responses, another element of the body's immune response.

PASADENA, Calif. -- The numbers of recommended vaccine doses, including measles vaccine, administered to children decreased dramatically after the declaration of a national state of emergency on March 13, 2020, due to the COVID-19 pandemic, according to a Kaiser Permanente study published in Pediatrics. While the decrease was lower and recovered in children under 2 years of age, it was more severe and persistent in older children.

"When vaccination rates decline, we worry about an increase in vaccine-preventable diseases that can be harmful to children," said the study's lead author, Bradley Ackerson, MD, a Kaiser Permanente South Bay Medical Center pediatric infectious disease specialist and an investigator with the Kaiser Permanente Southern California Department of Research & Evaluation's vaccine team. "Also, we know there has been a reduction in childhood vaccinations worldwide, and as COVID-19 restrictions are relaxed, there will be an increased risk of outbreaks due to vaccine-preventable diseases among children returning from outside the United States, unless children here are vaccinated."

To determine the trends in vaccination, researchers assessed the uptake and coverage for recommended vaccines including measles among nearly 1 million children from birth to18 years at Kaiser Permanente in Southern California. Vaccination coverage is a measure of the proportion of children vaccinated at specific ages, while vaccine uptake is the number of children getting vaccinated. The study showed that vaccination coverage continued to decline even after vaccine uptake recovered because vaccinations did not return to pre-pandemic levels in most age groups, causing the number of unvaccinated children continued to grow. Researchers also looked at measles vaccination rates separately because measles is particularly contagious and causes severe disease in all age groups.

The researchers compared January through August 2020 with the same period in 2019. The patient group was 49% female, 24% non-Hispanic white, and nearly 50% Hispanic.

While overall vaccinations declined in all children during the pandemic period in 2020 compared with 2019, they recovered completely in children under 2 by May. They partially recovered in older children.

After an initial decline in measles vaccinations of up to 93% among children aged 2 to 18 years during the pandemic, measles vaccinations partially recovered, but remained lower in 2020 than in 2019.

While measles vaccination coverage was unchanged in the 7-year-old patients, there was a significant decrease in measles vaccination coverage among 16-month-old patients that worsened over time.

"While the severe decrease in measles vaccine uptake among children improved, measles vaccine uptake remained substantially reduced, so the population of unvaccinated children is continuing to grow," Dr. Ackerson said. "The decrease in measles vaccine uptake is very concerning as even a 2% to 5% reduction in measles vaccination coverage is projected to result in exponential increases in measles outbreaks."

At Kaiser Permanente in Southern California, clinicians are addressing childhood vaccination concerns by contacting members whose children are due for vaccination and providing reassurance about safety measures being taken for vaccination visits. Besides implementing masking, distancing, and hygiene measures, sick visits are separated from well visits by location and time. Drive-through vaccinations were also provided at certain facilities

Study co-author Robert Riewerts, MD, a pediatrician with the Southern California Permanente Medical Group, said he understands that parents may feel uneasy about taking their children to medical offices for vaccinations. However, "This is a case where the benefit of vaccination far outweighs the risk of visiting a medical office. Our medical offices are taking every precaution to keep kids and their families safe."

An imaging agent allows scientists to better visualize Enterobacterales infections in patients, helping to address pathogens that can be life-threatening and frequently resist antibiotics. The agent was safe in 26 patients and differentiated infections from either sterile inflammation or COVID-19-linked pneumonia in hamsters. Enterobacterales is the largest group of disease-causing bacteria in humans, and includes common pathogens such as Escherichia coli, Salmonella, and Klebsiella pneumoniae. These species have become increasingly resistant to common antibiotics, which has led the Centers for Disease Control to label some drug-resistant strains as urgent threats to human health. However, scientists still lack tools that can rapidly and noninvasively detect Enterobacterales infections and determine where they are in the body, which is key for proper treatment and for research into new therapies. Building on previous work in mice, Alvaro Ordonez and colleagues tested an imaging agent they developed named 18F-FDS, which can detect Enterobacterales infections when combined with standard PET imaging. The agent safely and rapidly identified sites such as the lungs and liver that were infected by either drug-susceptible or drug-resistant Enterobacterales, and could differentiate infections from inflammation or cancerous lesions. The agent also revealed how 13 of the patients responded to antibiotics and helped identify patients who weren't responding to treatment. 18F-FDS also distinguished K. pneumoniae-caused pneumonia from pneumonitis caused by SARS-CoV-2 in a hamster model, suggesting it could help clinicians pinpoint secondary bacterial infections. The researchers also developed a cartridge system that can rapidly synthesize 18F-FDS from a commercially available precursor, which they say is a major advantage of their system.

ROCHESTER, Minn. - Though researchers have long known that several physiological and anatomical changes occur during pregnancy that can contribute to kidney stone formation, evidence of the link has been lacking. But now Mayo Clinic researchers believe they have that evidence.

An observational study that reviewed the medical records for nearly 3,000 female patients from 1984 to 2012 finds that pregnancy increases the risk of a first-time symptomatic kidney stone. The risk peaks close to delivery and then improves by one year after delivery, though a modest risk of developing kidney stones continues beyond one year after delivery.

The study, published in the American Journal of Kidney Diseases, included 945 women who experienced a first-time symptomatic kidney stone and 1,890 age-matched female control subjects. The study's objective was to determine whether the risk of a first-time symptomatic kidney stone increased with pregnancy and if the risk varied across different time periods before, during and after pregnancy.

"We suspected the risk of a kidney stone event would be high during pregnancy, but we were surprised that the risk remained high for up to a year after delivery," says Andrew Rule, M.D., a Mayo Clinic nephrologist and the study's senior author. "There also remains a slightly increased risk of a kidney stone event beyond a year after delivery. This finding implies that while most kidney stones that form during pregnancy are detected early by painful passage, some may remain stable in the kidney undetected for a longer period before dislodging and resulting in a painful passage."

A symptomatic kidney stone event is the most common nonobstetric hospital admission diagnosis for pregnant women. A symptomatic kidney stone event occurs in 1 of every 250-1,500 pregnancies, research shows, most often occurring during the second and third trimesters. Kidney stones, though uncommon, can cause significant complications, ranging from preeclampsia and urinary tract infection to preterm labor and delivery, and pregnancy loss.

Diagnosis of kidney stones during pregnancy can be challenging, given limited diagnostic imaging options due to concern about radiation exposure, says Dr. Rule. Treatment can be complicated by obstetric concerns, as well.

Several physiological reasons may contribute to why pregnancy contributes to kidney stone formation, says Charat Thongprayoon, M.D., a Mayo Clinic nephrologist and the study's corresponding author. During pregnancy, ureteral compression, and ureteral relaxation due to elevated progesterone hormone can cause urinary stasis in the body. In addition, increased urine calcium excretion and elevated urine pH during pregnancy can lead to calcium phosphate stone formation.

Awareness of a higher risk of kidney stones during pregnancy and the postpartum period can help health care providers offer diagnostic and preventive strategies for women.

"Urinary obstruction due to kidney stones can cause pain that some patients describe as the worst pain they have ever experienced," says Dr. Thongprayoon. "During pregnancy, a kidney stone may contribute to serious complication, and the results of this study indicate that prenatal counseling regarding kidney stones may be warranted, especially for women with other risk factors for kidney stones, such as obesity."

General dietary recommendations for preventing kidney stone disease include high fluid intake and a low-salt diet. Mayo Clinic experts also recommend appropriate calcium intake during pregnancy of at least 1,000 milligrams per day, preferably from dietary sources such as dairy products rather than calcium supplements.

The research examined data from the Rochester Epidemiology Project, a collaboration of clinics, hospitals and other health care facilities in Minnesota and Wisconsin, and community members who have agreed to share their health records for research. This project enables vital research that can find causes, treatments, and cures for disease. It is supported by the National Institutes of Health, U.S. Public Health Service, and National Center for Advancing Translational Sciences.

Sophia Antipolis - 15 April 2021: An observational study in nearly 20,000 individuals has found that greater intake of red and processed meat is associated with worse heart function. The research is presented at ESC Preventive Cardiology 2021, an online scientific congress of the European Society of Cardiology (ESC).1

"Previous studies have shown links between greater red meat consumption and increased risk of heart attacks or dying from heart disease," said study author Dr. Zahra Raisi-Estabragh of Queen Mary University of London, UK.2,3 "For the first time, we examined the relationships between meat consumption and imaging measures of heart health. This may help us to understand the mechanisms underlying the previously observed connections with cardiovascular disease."

The study included 19,408 participants of the UK Biobank.4 The researchers examined associations of self-reported intake of red and processed meat with heart anatomy and function.

Three types of heart measures were analysed. First, cardiovascular magnetic resonance (CMR) assessments of heart function used in clinical practice such as volume of the ventricles and measures of the pumping function of the ventricles. Second, novel CMR radiomics used in research to extract detailed information from heart images such as shape and texture (which indicates health of the heart muscle). Third, elasticity of the blood vessels (stretchy arteries are healthier).

The analysis was adjusted for other factors that might influence the relationship including age, sex, deprivation, education, smoking, alcohol, exercise, high blood pressure, high cholesterol, diabetes, and body mass index (BMI) as a measure of obesity.

The researchers found that greater intake of red and processed meat was associated with worse imaging measures of heart health, across all measures studied. Specifically, individuals with higher meat intake had smaller ventricles, poorer heart function, and stiffer arteries - all markers of worse cardiovascular health.

As a comparison, the researchers also tested the relationships between heart imaging measures and intake of oily fish, which has previously been linked with better heart health. They found that as the amount of oily fish consumption rose, heart function improved, and arteries were stretchier.

Dr. Raisi-Estabragh said: "The findings support prior observations linking red and processed meat consumption with heart disease and provide unique insights into links with heart and vascular structure and function."

The associations between imaging measures of heart health and meat intake were only partially explained by high blood pressure, high cholesterol, diabetes, and obesity.

"It has been suggested that these factors could be the reason for the observed relationship between meat and heart disease," said Dr. Raisi-Estabragh. "For example, it is possible that greater red meat intake leads to raised blood cholesterol and this in turn causes heart disease. Our study suggests that these four factors do play a role in the links between meat intake and heart health, but they are not the full story."

She noted that the study did not look into alternative mechanisms. But she said: "There is some evidence that red meat alters the gut microbiome, leading to higher levels of certain metabolites in the blood, which have in turn been linked to greater risk of heart disease."

Dr. Raisi-Estabragh said: "This was an observational study and causation cannot be assumed. But in general, it seems sensible to limit intake of red and processed meat for heart health reasons."

A technique called percutaneous peripheral nerve stimulation yields "impressive" reductions in pain scores and opioid use during the first week after common orthopedic surgery procedures, concludes a randomized clinical trial published Online First in Anesthesiology, the official peer-reviewed journal of the American Society of Anesthesiologists (ASA), today.

The benefits of postoperative nerve stimulation were "much greater than what we had anticipated, concurrently reducing pain scores by more than 50 percent and opioid consumption by 80 percent," according to the randomized trial report by Brian M. Ilfeld, M.D., MS, and colleagues. With further study, they believe that peripheral nerve stimulation could be a safe, effective, opioid reducing, non-drug adjunct for pain management after surgery.

In percutaneous peripheral nerve stimulation, a tiny electrical lead (insulated wire) is placed alongside a nerve and connected to a battery-powered pulse generator. The generator delivers mild electrical stimulation to the nerve, interrupting pain transmission. Although this "neuromodulation" technique has been widely used for patients with chronic pain, the new study is the first randomized, controlled trial to evaluate its use for acute pain after surgery.

The study enrolled 65 patients undergoing common outpatient joint surgery, such as bunion surgery in the foot or rotator cuff repair in the shoulder. All patients underwent lead placement near the nerve(s) serving the surgical joint. Half of the patients were randomly assigned to active electrical stimulation, adjusted to achieve the desired sensory change - sometimes described as feeling like a "pleasant massage." The remaining patients received an inactive "sham" treatment, with a pulse generator that appeared to function normally, but did not deliver any electrical current. After one week, pain scores and opioid use were compared between groups. Evaluations were performed in "double-masked" fashion: neither the researchers nor the patients knew which treatment the patient was receiving.

The results showed significantly lower pain ratings in the active nerve stimulation group. Mean pain score (on a 0 to 10 scale) was 1.1 in patients receiving active treatment, compared to 3.1 in the sham group.

Active nerve stimulation was also associated with a much lower use of opioids to control postoperative pain. Median opioid dose (oral morphine equivalents) for the entire first week after surgery was 5 milligrams in the active treatment group, compared to 48 milligrams in the sham group. That's an important benefit due to the possible adverse effects of postoperative opioids, such as nausea, constipation, sedation, and respiratory depression.

Although the trial was designed as a pilot study, the results "stand on their own and indicate that percutaneous peripheral nerve stimulation is highly effective for acute pain," Dr. Ilfeld and coauthors wrote. They outlined plans for a subsequent study that is currently enrolling a far larger number of patients and will include a more complete assessment of the treatment effect across patient subgroups.

OAK BROOK, Ill. - A deep learning algorithm accurately predicts the risk of death from cardiovascular disease using information from low-dose CT exams performed for lung cancer screening, according to a study published in Radiology: Cardiothoracic Imaging.

Cardiovascular disease is the leading cause of mortality worldwide. It even outpaces lung cancer as the leading cause of death in heavy smokers.

Low-dose CT lung scans are used to screen for lung cancer in high-risk people such as heavy smokers. These CT scans also provide an opportunity to screen for cardiovascular disease by extracting information about calcification in the heart and aorta. The presence of calcium in these areas is linked with the buildup of plaque and is a strong predictor for cardiovascular disease mortality, heart attacks and strokes.

Previous studies have used information extracted from CT images as well as other risk factors, such as cholesterol levels and blood pressure, and self-reported clinical data, such as history of illness.

For the new study, researchers tested a faster, automated method that can predict five-year cardiovascular disease mortality with only minimal extra workload. The method draws upon the power of deep learning, an advanced type of artificial intelligence in which the computer algorithm essentially learns from the images the important features for mortality prediction.

Using data from 4,451 participants, median age 61 years, who underwent low-dose CT over a two-year period in the National Lung Screening Trial, the researchers trained the method to quantify six types of vascular calcification. They then tested the method on data from 1,113 participants.

The prediction model using calcium scores outperformed the baseline model that used only self-reported participant characteristics, such as age, history of smoking, and history of illness.

The method works in two stages, according to study lead author Bob D. de Vos, Ph.D., from Amsterdam University Medical Center in Amsterdam and the Image Sciences Institute, University Medical Center Utrecht, in Utrecht, the Netherlands. The first stage determines the amount and location of arterial calcification in the coronary arteries and the aorta using deep learning. The second stage uses a more conventional statistical approach for mortality prediction. The second stage also indicates which features are most predictive for five-year mortality.

"The analysis shows we found predictors that are typically not described in a literature, possibly because we performed analysis in lung cancer screening participants who are already at high risk of cardiovascular disease from a history of heavy smoking and the presence of extensive arterial calcification," Dr. de Vos said.

The method could easily be integrated into lung cancer screening, Dr. de Vos said. It does not require any special equipment and would not add time to the exam.

"The method uses only image information, it is fully automatic, and it is fast," Dr. de Vos said. "The method obtains calcium scores in a complete chest CT in less than half a second. This means that the method should be easy to implement in routine patient work ups and screening."

Most importantly, the method could help identify people in a population of heavy smokers who might be at increased risk of death from cardiovascular disease-related causes.

"Lung screening studies show that heavy smokers die from cardiovascular disease as much as from lung cancer," Dr. de Vos said. "But we also see that some people with very high calcium scores survive, while others with low scores do suffer from major cardiac events. The work offers a direction for future research to precisely pinpoint which calcifications are dangerous."

The researchers have developed a number of methods for automatic calcium scoring that can be applied to a wide variety of data. They are now working toward a calcium scoring method that accurately detects arterial calcification in low-quality data, like data affected by cardiac motion, low image resolution or high noise levels.

"We developed a method, for example, that can detect coronary calcifications even when the lesions are below the clinically used threshold," Dr. de Vos said. "This way, we hope to increase the reproducibility of calcium scoring and enable more accurate prediction."

The United States Preventive Services Task Force (USPSTF) recently expanded its recommendation for low-dose CT lung cancer screening to include high-risk individuals, 50 to 80 years of age, who have a 20-pack-year or more history of smoking and are either current smokers or former smokers who have quit within the last 15 years, facilitating screening access for a larger and more diverse population. Read more in RSNA News.

The COVID-19 disease due to infection by the SARS-CoV2 virus has changed the behavior patterns of humanity by becoming a pandemic of international scope. To date, more than 136 million people have suffered from the disease and more than 2.9 million of them have lost their lives. It is important to remember that the symptoms of the infection vary widely in the population, from individuals who do not present any symptoms to those who need admission to intensive care units with emergency assisted ventilation. It is largely unknown what factors are responsible for this range of very different clinical pictures.

Today, an article published in the journal EBioMedicine,The Lancet's sister journal for laboratory findings, by the group of Dr. Manel Esteller, Director of the Josep Carreras Leukaemia Research Institute, ICREA Research Professor and Chairman of Genetics at the University of Barcelona and Dr. Aurora Pujol, also ICREA Professor, geneticist of the Center for Biomedical Network Research on Rare Diseases (CIBERER) and head of the Neurometabolic Diseases Group of the Bellvitge Biomedical Research Institute (IDIBELL), shows that the epigenetic endowment of each person influences the severity of the COVID-19 disease.

"Given the high number of people infected by the virus that have saturated all health systems in the world, it would be nice to have ways to predict in advance whether the virus infection in a given individual will require hospitalization or can simply be controlled on an outpatient basis. It is known that advanced age and the co-existence of other pathologies (cardiovascular, obesity, diabetes, immune defects) are associated with a greater severity of the infection, but what happens to the rest of the population that also reaches the ICU without these factors?" -Dr. Esteller wondered in the article in the EBiomedicine journal and adds - "We decided to study more than 400 people who had tested positive for COVID-19 who did not belong to any of these risk groups and study their genetic material depending on whether they had not had symptoms, or they were very mild, or instead they had been admitted to the hospital requiring respiratory assistance. We found that there were epigenetic variations, the chemical switches that regulate DNA activity, in the individuals positive for the virus who developed a severe COVID-19. These modifications occurred mainly in genes associated with an excessive inflammatory response and in genes that reflect an overall worse state of health. Interestingly, 13% of the world population presents this epigenetic signature (EPICOVID), thus, this is the group at maximum risk that we must take special care of. " - concludes the researcher.

"These results complement and confirm the implication of the interferon-directed antiviral response and its importance in the evolution of the disease, as we explained in a complete genome sequencing study published in the journal Science last September," says Dr. Pujol and continues: "With these advanced tools of personalized medicine, both in the field of genomics and epigenomics, it is possible to design predictive models that allow detecting patients at risk of a worse prognosis and therefore improve their treatment and avoid the collapse of the health system."

The project is part of the "More unstoppable than ever" campaign that the Josep Carreras Foundation launched in April 2020 with the aim of raising funds for lines of research on COVID-19 and immunosuppression. The article published today shows the results of the research carried out during these months of prognostic stratification in COVID-19, with the intention of contributing to improve the clinical management of patients infected with SARS-CoV-2. The results of these investigations will have a favorable impact on the health of the general population, particularly in people affected by leukemias and malignant hematological diseases, especially vulnerable to this disease.

Detecting hidden genetic defects by applying an existing method to an existing datasets. Researchers at Radboud university medical center have succeeded: they showed that the 'Expansion Hunter' method can detect errors in the DNA that lead to repeat expansion diseases, such as the movement disorder ataxia. This result provides guidance to fellow researchers worldwide on how to use this method to diagnose patients with genetic disorders.

With current diagnostic technology for genetic disorders, it is possible to map all 20,000 genes in our DNA at once. Doctors are increasingly opting for this so-called exome technique: it is widely applicable and increasingly provides molecular diagnoses. The exome technique is particularly suitable for finding simple changes in DNA.

In a publication in Genetics in Medicine, researchers from the Radboudumc have now shown that the technique can also be used to find a much more difficult type of change in the DNA: so-called repeat expansions. This is a type of mutation in which the same number of, usually three, building blocks of DNA (nucleotides) in the genome are repeated many times. Examples of disorders that arise from repeat expansions are fragile X syndrome and Huntington's disease. Erik-Jan Kamsteeg, laboratory specialist at the Clinical Genetics Department: "Sometimes we knew there had to be an abnormality in the DNA, but it did not show up in the exome test. Then the dataset was ignored, discarded as it were. But we knew there were gaps; that we weren't seeing everything."

At this, the researchers investigated the possibility of applying repeat expansion analysis to already available data from 2,700 patients with movement disorders. Reading out their genes had previously revealed no cause, even though there was a very strong suspicion of a hereditary defect in this group of patients. With this new analysis the cause of the defect was found in seven patients, without having to carry out additional laboratory experiments.

Associate Professor of Genome Bioinformatics Christian Gilissen: "These numbers may seem small, but the impact on diagnostics is of great value. If every genetic center starts doing this, and we have now shown that this can be done easily without additional experiments, you can obtain a diagnosis for a lot of patients for whom the cause of their condition has remained unknown. We know that a diagnosis in itself is very important for the patient, because it provides certainty and an explanation, can give a prognosis of the course of the disease, but also the possibility of contact with patients with the same diagnosis." In addition, finding the right molecular diagnosis also helps to determine the risk for the disorder in children and other relatives of patients.

Ataxia

In this case, the researchers looked in particular at the movement disorder ataxia, because repeat expansions are a known cause of these disorders. Ataxia is primarily caused by disease or damage to the cerebellum. The main function of the cerebellum is to ensure perfect adjustment in the cooperation between muscles, so that a smooth movement occurs. When the cerebellum is affected, people develop problems with their motor skills: walking, articulating and swallowing become more difficult, and they may experience trembling hands or double vision. The seven new molecular diagnoses now found for ataxia consist of six relatively known causes, which despite years of searching had not been detected before. The researchers also found one exotic dominant ataxia (type 12) that to date has only been described three times worldwide.

High intensity interval training has become increasingly popular as it's a quick and effective way to improve health. This is all the more important as countries around the world emerge from lockdowns due to coronavirus and are looking for quick and easy way to exercise again.

Recently, researchers have been studying whether shorter variations of HIIT, involving as little as 4-min of high intensity exercise per session (excluding a warm up and cool down), also improve health.

A new review paper published in the Journal of Physiology collates a decade's worth of research on the topic of this so-called low-volume high HIIT for health.

The current World Health Organisation (WHO) physical activity guidelines (150-300 min of moderate activity/week or 75-100min of vigorous activity/week) may be unattainable for a large portion of the population who are time poor due to family or work commitments.

This hypothesis is supported by the increasing rates of physical inactivity amongst adults in high income countries.

The findings of this study show that low-volume HIIT (typically involving less than ~20 mins total exercise time - inclusive of warm up and cool down) yields comparable improvements to interventions meeting the current guidelines despite requiring significantly less time.

So, what is low-volume HIIT? As HIIT involves active periods of work interspersed with recovery periods, the researchers defined low-volume HIIT as interventions which included less than 15 minutes of high intensity exercise per session (not including recovery periods).

This review builds on the authors' recent study published in Diabetes Care which showed that as little as 4-min of HIIT 3 times per week for 12 weeks significantly improved blood sugar levels, fat in the liver, and cardiorespiratory fitness in adults with type 2 diabetes. They also showed that these improvements were comparable to an intervention involving 45-min of moderate intensity aerobic exercise (2).

Beyond its effect on metabolic health, the new review reported that low-volume HIIT can also improve heart function and arterial health.

While the overwhelming majority of available evidence shows that low-volume HIIT is a safe way to exercise, including in populations with metabolic and heart problems, individuals should always determine their individual suitability for such programs with their health care professional.

This research was performed by collating and critically appraising over a decade's worth of research on the topic.

Further research should explore whether low-volume HIIT is sustainable in the longer-term and whether combining low-volume HIIT with other training interventions, such as resistance training, can maximise health outcomes.

Many of the participants in the study published in Diabetes Care reported being in disbelief over how short the training was yet how great they felt after training.

Dr. Angelo Sabag, corresponding author of the study said:

"While the WHO guidelines may serve their purpose at a populational level, individualised and tailored low-volume HIIT interventions delivered by appropriately trained exercise professionals may be more effective at an individual level, especially for time-poor individuals.

This research is especially important now as people are looking for new and exciting ways to engage in regular exercise, after a year of lower physical activity due to the pandemic."

The results of the first clinical trial of a new vaccine for a neglected tropical disease have demonstrated that it is safe and induces immune responses in patients with the infection.

There are currently no vaccines to prevent leishmaniasis which is spread by the bite of sand flies and existing drugs have many side effects and are difficult to administer.

The potential new vaccine was developed by researchers at the Hull York Medical School, which is the joint medical school of the Universities of Hull and York.

Professor Paul Kaye from the Hull York Medical School was the principal investigator on the Wellcome Trust Translation Award that funded the development of the vaccine.

Professor Kaye said: "We have always thought that vaccines should be our greatest weapon against the different forms of leishmaniasis, but it has been a long journey to develop vaccines for testing in the clinic.

"These results are very encouraging, showing that the vaccine we have developed is safe and immunogenic in patients. It is now important to test this vaccine as a therapy in different forms of leishmaniasis where drugs are poorly effective, and to see if it can prevent the spread of the disease."

The new vaccine, called ChAd63-KH, uses a non-replicating virus to introduce genes that code for Leishmania proteins into the human body. The design of the vaccine is very similar to the Oxford / Astra Zeneca vaccine being used to prevent COVID-19.

In the current clinical trials, ChAd63-KH is being tested to see if it can be used to treat rather than prevent disease.

The vaccine was given to patients with a chronic skin form of leishmaniasis and was shown to be safe and to stimulate immune responses associated with a cure.

A second trial of the vaccine is currently underway that will determine whether vaccination helps patients to recover from their disease without the need for drugs. The research team is also planning to test the vaccine in healthy volunteers to determine whether it can protect them from getting the disease after exposure to infected sand flies.

Leishmaniasis results in up to one million new cases each year across 98 countries. Infection can lead to different forms of disease, ranging from persistent and disfiguring skin ulcers to death.

Philadelphia, April 15, 2021 - Early and accurate diagnosis leads to optimal recovery from concussion. Over the past year across a series of studies, the Minds Matter Concussion Program research team at Children's Hospital of Philadelphia (CHOP) has systematically evaluated the use of the visio-vestibular examination (VVE) and its ability to enhance concussion diagnosis and management. The latest of these studies published online today in the Clinical Journal of Sports Medicine.

The VVE involves a series of brief eye movement and balance tests intended to identify deficits in brain function involving the visual and vestibular systems. Researchers found that the VVE presents several advantages over current clinical measures, moving beyond subjective symptoms with a rapid, repeatable and quantifiable clinical exam. The team also found that the VVE is easy to administer across various clinical settings where children are initially seen following head injury when a concussion is suspected. In doing so, researchers believe there is the opportunity to ensure the diagnosis is made accurately and soon after injury to improve outcomes for all youth who suffer a concussion.

"There is growing evidence that visual, vestibular, and balance impairments are common after concussion, and these impairments have been linked to worse outcomes, including a delayed return to school and sports," says lead investigator Christina L. Master, MD, a sports medicine pediatrician and co-director of the Minds Matter Concussion Program at CHOP. "Recently, we have focused our efforts on developing objective measures of impaired eye movement and pupil response as physiological biomarkers of concussion. In this line of research, we also wanted to see if this simple and rapid clinical exam could provide diagnostic utility for a variety of providers outside the specialist setting."

Across four different studies published over the past year, the CHOP research team make a strong case for the implementation of the VVE across a variety of practice settings:

In this most recent study, the researchers focused on the assessment of saccadic eye function, which involves assessing the level of symptom provocation with rapid eye movements between two fixed objects, and gaze stability, where symptoms are assessed with head movement while the eyes are fixed on a stationary object. Previously, these assessments were performed up to 10 repetitions in a traditional screening, but this study showed that raising the number of repetitions to 20 increased the sensitivity of the test. This more demanding task provides a more rigorous 'stress test' for the brain and can help to identify subtle deficits that may go unnoticed in regular clinical assessments and avoids the ceiling effect of a test that is too easy.

A second study compared clinical and device-based metrics to measure gait and balance in the diagnosis of concussion. The study found that the complex tandem gait used in the VVE performed as well as, if not slightly better than, a biomechanical force plate device for assessing deficits in concussion. The most challenging component of the complex tandem gait from the VVE - having the subject walk backward with his or her eyes closed - had the highest sensitivity for diagnosing a concussion of any of the clinical balance tests.

Another study established the reliability of VVE among providers in a pediatric emergency department in patients presenting after a head injury. The individual elements of the VVE showed fair to moderate agreement between providers and moderate to substantial agreement within the same provider, especially when used with adolescents. When comparing abnormalities on exam between patients with and without a final diagnosis of a concussion, the researchers found each additional abnormal examination element more than doubled the odds of a concussion diagnosis.

A final study showed that patients who were immediately diagnosed with a concussion in the emergency department were significantly more likely to have received a VVE during that visit compared with patients who were evaluated in the ED for a head injury, but not diagnosed with a concussion until later at a subsequent medical visit. The patients who received these early and appropriate diagnoses were nearly three times less likely to experience prolonged symptoms, suggesting that a VVE can improve both diagnostic accuracy as well as patient outcomes.

"With its ease-of-administration, the visio-vestibular examination can be conducted in multiple care settings where children are initially seen with head injury to effectively diagnose concussion," says co-author Daniel J. Corwin, MD, MSCE, an emergency medicine physician, associate director of research in the Division of Emergency Medicine at CHOP, and Minds Matter Concussion Program researcher. "This is particularly important since many concussed youth are diagnosed outside of the specialty setting where these tests were initially developed. Our previous research also underscores how early and accurate diagnosis can improve outcomes in children."

With training and clinical support tools, pediatricians, emergency medicine clinicians, and advanced practice practitioners are able to conduct the VVE assessments for saccades, gaze stability, and tandem gait in a repeatable manner in the workflow of a high-volume acute care setting.

"Health care professionals have new important considerations for evaluating and managing sports-related concussion," Master said. "The visio-vestibular examination is an inexpensive, feasible, and readily available means by which concussions can be more accurately diagnosed, thereby improving outcomes for these vulnerable patients. In doing so, we have the opportunity to shorten the time to diagnosis and treatment to improve outcomes for all youth who suffer a concussion."

Young adults must step up their exercise routines to reduce their chances of developing high blood pressure or hypertension - a condition that may lead to heart attack and stroke, as well as dementia in later life.

Current guidelines indicate that adults should have a minimum of two-and-a-half hours of moderate intensity exercise each week, but a new study led by UCSF Benioff Children's Hospitals reveals that boosting exercise to as much as five hours a week may protect against hypertension in midlife - particularly if it is sustained in one's thirties, forties and fifties.

In the study publishing in American Journal of Preventive Medicine on April 15, researchers followed approximately 5,000 adults ages 18 to 30 for 30 years. The participants were asked about their exercise habits, medical history, smoking status and alcohol use. Blood pressure and weight were monitored, together with cholesterol and triglycerides.

Hypertension was noted if blood pressure was 130 over 80 mmHg, the threshold established in 2017 by the American College of Cardiology/American Heart Association.

The 5,115 participants had been enrolled by the Coronary Artery Risk Development in Young Adults (CARDIA) study and came from urban sites in Birmingham, Ala., Chicago, Minneapolis and Oakland, Calif. Approximately half the participants were Black (51.6 percent) and the remainder were White. Just under half (45.5 percent) were men.

Fitness Levels Fall Fast for Black Men Leading to More Hypertension

Among the four groups, who were categorized by race and gender, Black men were found to be the most active in early adulthood, exercising slightly more than White men and significantly more than Black women and White women. But by the time Black men reached age 60, exercise intake had slumped from a peak of approximately 560 exercise units to around 300 units, the equivalent to the minimum of two-and-a-half hours a week of moderate intensity exercise recommended by the U.S. Department of Health and Human Services. This was substantially less exercise than White men (approximately 430 units) and slightly more than White women (approximately 320 units). Of the four groups, Black women had the least exercise throughout the study period and saw declines over time to approximately 200 units.

"Although Black male youth may have high engagement in sports, socio-economic factors, neighborhood environments, and work or family responsibilities may prevent continued engagement in physical activity through adulthood," said first author Jason Nagata, MD, of the UCSF Division of Adolescent and Young Adult Medicine. Additionally, Black men reported the highest rates of smoking, which may preclude physical activity over time, he noted.

Physical activity for White men declined in their twenties and thirties and stabilized at around age 40. For White women, physical activity hovered around 380 exercise units, dipping in their thirties and remaining constant to age 60.

Rates of hypertension mirrored this declining physical activity. Approximately 80-to-90 percent of Black men and women had hypertension by age 60, compared with just below 70 percent for White men and 50 percent for White women.

"Results from randomized controlled trials and observational studies have shown that exercise lowers blood pressure, suggesting that it may be important to focus on exercise as a way to lower blood pressure in all adults as they approach middle age," said senior author Kirsten Bibbins-Domingo, MD, PhD, of the UCSF Department of Epidemiology and Biostatistics.

"Teenagers and those in their early twenties may be physically active but these patterns change with age. Our study suggests that maintaining physical activity during young adulthood - at higher levels than previously recommended - may be particularly important."

More Exercise from Youth to Midlife Offers Best Protection Against Hypertension

When researchers looked at the 17.9 percent of participants who had moderate exercise for at least five hours a week during early adulthood - double the recommended minimum - they found that the likelihood of developing hypertension was 18 percent lower than for those who exercised less than five hours a week. The likelihood was even lower for the 11.7 percent of participants who maintained their exercise habits until age 60.

Patients should be asked about physical activity in the same way as they are routinely checked for blood pressure, glucose and lipid profiles, obesity and smoking, Nagata said, and intervention programs should be held at schools, colleges, churches, workplaces and community organizations. Black women have high rates of obesity and smoking, and low rates of physical activity, he said, and should be an important group for targeted intervention.

"Nearly half of our participants in young adulthood had suboptimal levels of physical activity, which was significantly associated with the onset of hypertension, indicating that we need to raise the minimum standard for physical activity," Nagata said. "This might be especially the case after high school when opportunities for physical activity diminish as young adults transition to college, the workforce and parenthood, and leisure time is eroded."

Despite surgery and subsequent treatment with chemotherapy and radiation, the majority of patients experience recurrence of malignant brain tumours. Researchers at Linköping University, Sweden, and the Medical University of Graz, Austria, have shown in cells in culture that an ion pump can deliver drugs more accurately, which gives less severe adverse effects in chemotherapy. The results have been published in Advanced Materials Technologies.

"This is the first time an ion pump has been tested as a possible method to treat malignant brain tumours. We used cancer cells in the lab, and the results are extremely promising. However, it will probably take five to ten years before we see this new technology used in treatments for brain tumours", says Daniel Simon, associate professor at the Laboratory of Organic Electronics at the Department of Science and Technology at Linköping University .

The scientists have used cells from glioblastoma, which is the most common and most aggressive type of cancer that can arise in the brain. When a brain tumour is surgically removed, small parts of the tumour are often left behind, embedded between the brain cells. Even high-precision surgery cannot remove these cells without damaging the surrounding healthy brain tissue. This means that radiation treatment and chemotherapy are used to stop the recurrence of the tumour.

In Sweden, around 30 cytostatics are available to treat different types of cancer. These chemotherapy agents are most often given either intravenously or as a tablet. But in order to reach the brain, they must first spread through the circulatory system and then pass through the blood-brain barrier. The walls of the small blood vessels in the brain are much less permeable than blood vessels in the rest of the body, and can prevent many substances in the blood entering the brain. Thus, only a few drugs that work against cancer can pass through.

Scientists at Linköping University and at the Medical University of Graz have now developed a method in which an implanted ion pump can be used to get around the blood-brain barrier and supply gemcitabine - an extremely effective chemotherapy agent that cannot normally pass the blood-brain barrier - directly into the brain with high precision. Gemcitabine is currently used to treat cancers in the pancreas, bladder and breast, where it acts by disrupting the cell division process in rapidly growing tumours. This means that gemcitabine does not affect brain cells, since these do not, in general, undergo cell division.

"The traditional glioblastoma treatment currently used in the clinics harms both cancer and neuronal cells to the same extent. However, with the gemcitabine ion pump, we tackle only the cancerous cells, while neurons stay healthy. In addition, our experiments on cultured glioblastoma cells show that more cancer cells are killed when we use the ion pump than when we use manual treatment", says Linda Waldherr, postdoctoral fellow at the Medical University of Graz. She has conducted the study together with researchers at Linköping University.

When the ion pump is to transport gemcitabine from an electrolyte reservoir into cells or a tumour, a low current is used to "pump" the positively charged drug through an ion transport channel. The method is known as electrophoresis. The ion pump needs only a low current to pump the gemcitabine, which is an advantage since it avoids the risk that brain cells are activated and transmit unintended nerve signals. The low current and voltage also mean that eventual therapeutic technology will not require large power supplies or batteries to operate.

Rainer Schindl, associate professor at the Medical University of Graz, describes other advantages.

"The pressure inside the brain is extremely sensitive, and using an ion pump to transport the drug instead of a fluid-driven device means that the pressure is not affected. Also, the dosage is controlled by electrical charging, which makes the supply of the chemotherapy agent extremely precise. The next step will be to use the ion pump to evaluate different chemotherapy agents that have previously given adverse effects that are too serious or that are unable to pass the blood-brain barrier", he says.

Oakland, CA-In the first study to report on the health effects of exposure to a toxic environmental chemical over three human generations, a new study has found that granddaughters whose grandmothers were exposed to the pesticide DDT have higher rates of obesity and earlier first menstrual periods. This may increase the granddaughters' risk for breast cancer as well as high blood pressure, diabetes and other cardiometabolic diseases.

The research by the Public Health Institute's Child Health and Development Studies (CHDS) and the University of California at Davis was published today in Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research. It suggests that effects from the pesticide DDT -- despite being banned in the U.S. nearly 50 years ago -- may contribute to the falling age of first periods and increases in obesity rates among young women today.

The study found that the risk of obesity in young adult granddaughters was 2 to 3 times greater when their grandmothers (who were not overweight) had higher levels of o,p'-DDT (a contaminant of commercial DDT) in their blood during or just after pregnancy. Granddaughters were twice as likely to have earlier first menstrual periods when their grandmothers had higher o,p'-DDT blood levels. DDT and its related chemicals, including o,p'-DDT, are known to be endocrine disrupting chemicals, compounds that can alter and interfere with natural hormones that are essential for development.

"We already know that it's nearly impossible to avoid exposures to many common environmental chemicals that are endocrine disruptors. Now our study shows for the first time in people that environmental chemicals like DDT may also pose health threats to our grandchildren," said Barbara Cohn, director of CHDS and senior author of the study. "In combination with our on-going studies of DDT effects in the grandmother's and mother's generations, our work suggests we should take precautionary action on the use of other endocrine disrupting chemicals, given their potential to affect generations to come in ways we cannot anticipate today."

The Child Health and Development Studies is a unique project that has followed 20,000 pregnant women and their families for more than 60 years. CHDS enrolled and began following pregnant women in the Bay Area between 1959 and 1967, a time of high pesticide use before DDT was banned in 1972. These "founding grandmothers" in the study gave blood samples at each trimester during pregnancy and one sample shortly after birth. The blood samples were tested for levels of DDT and its related chemicals, including active ingredients, contaminants and their metabolites. The study today focused on o,p'-DDT as it has previously been linked to breast cancer, obesity and other harmful health effects in daughters, and is believed to be the most sensitive biomarker for exposures before and immediately after birth. Since granddaughters' exposure would occur via their mothers' in utero egg cell development, o,p'-DDT levels are a potential predictor of granddaughters' exposure outcomes.

"These data suggest that the disruption of endocrine systems by DDT initiates in immature human eggs, decades before the eggs are fertilized," said Michele La Merrill, associate professor at UCD who was co-lead author of the study.

The CHDS study included interviews, home visits and questionnaires from the daughters and granddaughters of the original enrollees. During home visits, blood pressure and height and weight measurements were taken. The study today is based on 365 adult granddaughters who completed questionnaires, participated in a home visit, had available DDT measures from grandmothers' serum, and (for 285 of them) had available information on body mass index (BMI) in all three generations. Information on the age of first period for all three generations was available from 235 granddaughters.

Previous CHDS studies have shown that mothers' DDT exposure during pregnancy or immediately after birth correlates with increased daughters' risk of breast cancer and the prevalence of breast cancer risk factors, including obesity, among adult daughters. Other prior studies have linked DDT exposure to birth defects, reduced fertility and an increased risk of diabetes.

A commentary in the journal Reproductive Toxicology last year called CHDS "a national treasure that keeps on giving" and noted that "There are no other U.S. studies as well defined, sampled, and followed as the CHDS....The CHDS provides unique and essential value in understanding health effects of environmental exposures as they relate to life-stage sensitivity."