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Today, OncoTartis, Inc. and Children's Cancer Institute jointly announced the publication of two research manuscripts in a leading onco-hematological journal Leukemia, both devoted to the OncoTartis' clinical drug candidate OT-82.

A significant proportion of blood cancers in both adults and children remain resistant to current treatments and are often fatal. The results of studies conducted collaboratively by teams in Buffalo and Sydney open a new treatment opportunity for patients with currently incurable blood cancers by introducing a new drug candidate shown to be highly effective in preclinical models.

The first paper describes the discovery, mechanism of action, toxicological profile and preclinical efficacy of OT-82 that was developed by OncoTartis for treatment of refractory leukemias and lymphomas. It takes advantage of the discovery of an extremely high dependence of malignancies originating from the hematopoietic system on elevated levels of nicotinamide dinucleotide (NAD), an essential component of multiple metabolic and stress response mechanisms of the cell. OT-82 inhibits one of the major enzymes, nicotinamide phosphoribosyl transferase (NAMPT) responsible for NAD production. Its further clinical development is specifically focused on blood-derived cancers as the main disease target. OT-82 is currently undergoing a multicenter Phase I trial in the US.

The second paper on OT-82 describes a study conducted at Children's Cancer Institute (Sydney). The Institute has been a world leader in establishing a large collection of refractory children's leukemias grown in laboratory mice for new drug testing. These are widely accepted to be the most clinically-relevant models of childhood leukemia anywhere in the world.

This collection was utilized to compare the efficacy of OT-82 with current treatments for childhood leukemia. OT82 demonstrated remarkable efficacy when used alone and was even more effective when used in combination with conventional treatments, thereby indicating promise for children with high risk blood cancers.

Currently, OT-82 is being tested in a clinical trial of adults with relapsed or refractory lymphoma. Following the successful completion of this trial, it is anticipated that the drug will proceed to clinical trial in children with high-risk acute lymphoblastic leukemia.

Professor Andrei Gudkov from Roswell Park Comprehensive Cancer Center in Buffalo NY, a Chief Scientific Officer of OncoTartis, said: "The main principle of the research strategy that led us to OT-82 was identification of a pharmacological agent specifically toxic for malignant cells of blood origin. We were surprised when the compound that came out of an unbiased search appeared to be a NAMPT inhibitor, an enzyme that has been considered as a target for cancer treatment but whose association with malignancies of blood origin was unknown. We are especially excited about the potential use of OT-82 for treatment of refractory childhood malignancies, an opportunity revealed in the joint studies with our Australian partners."

Professor Michelle Haber AM, Executive Director of Children's Cancer Institute in Sydney, indicated this was a promising development for children with high-risk leukemia.

"For children with particularly aggressive leukemia, the options for effective yet safe treatments are extremely limited and therefore novel therapeutic options are urgently needed. If OT-82 is found to be safe and effective in adults, we are very hopeful that it may provide an exciting new treatment approach for the worst cases of paediatric leukemia, with the added potential benefit of allowing reductions in doses of chemotherapy and hence diminished adverse treatment side-effects for these children."

Dr Michelle Henderson, Senior Scientist, who together with Dr Klaartje Somers led the research at Children's Cancer Institute, added: "In our hands, OT-82 has proven to be one of the more broadly active compounds tested so far in this panel of high-risk pediatric acute lymphoblastic leukemia." Dr Somers concluded: "OT-82 thus appears to be a promising anti-cancer drug for the treatment of a broad range of high-risk and aggressive pediatric acute lymphoblastic leukemia subtypes for which novel therapeutic options are urgently needed."

LOS ANGELES (EMBARGOED UNTIL Jan. 15, 2020, at 11AM EST) -- New research from the Smidt Heart Institute at Cedars-Sinai showed for the first time that women's blood vessels - including both large and small arteries - age at a faster rate than men's. The findings, published Wednesday in the journal JAMA Cardiology, could help to explain why women tend to develop different types of cardiovascular disease and with different timing than men.

"Many of us in medicine have long believed that women simply 'catch up' to men in terms of their cardiovascular risk," said Susan Cheng, MD, MPH, MMSc, senior author of the study and director of Public Health Research at the Smidt Heart Institute. "Our research not only confirms that women have different biology and physiology than their male counterparts, but also illustrates why it is that women may be more susceptible to developing certain types of cardiovascular disease and at different points in life."

Using community-based data amassed from multiple sites across the country, Cheng and her research team conducted sex-specific analyses of measured blood pressure - a critical indicator of cardiovascular risk. The data represented nearly 145,000 blood pressure measurements, collected serially over a 43-year period, from 32,833 study participants ranging in age from 5 to 98 years old.

Because a person's risk for developing a heart attack, heart failure, or a stroke typically begins with having high blood pressure, Cedars-Sinai researchers combed through their massive data looking for clues and patterns regarding how blood pressure starts to rise. Then, instead of comparing the data from men and women to each other, investigators compared women to women and men to men.

This approach allowed investigators to identify that the progression and evolution of women's vascular function is very different than for men. In fact, women showed signs of blood pressure elevation much earlier in life than men.

"Our data showed that rates of accelerating blood pressure elevation were significantly higher in women than men, starting earlier in life," said Cheng, the Erika J. Glazer Chair in Women's Cardiovascular Health, who also serves as director of Cardiovascular Population Sciences at the Barbra Streisand Women's Heart Center. "This means that if we define the hypertension threshold the exact same way, a 30-year old woman with high blood pressure is probably at higher risk for cardiovascular disease than a man with high blood pressure at the same age."

Christine Albert, MD, MPH, founding chair of the newly established Department of Cardiology at the Smidt Heart Institute, says this new research should help guide clinicians and researchers to think differently when it comes to treating and studying women and their cardiovascular health.

"Our women's heart health experts have a long history of advocating for adequate inclusion of women in research and the need to both recognize and study sex differences in cardiovascular physiology and disease," said Albert. "This study is yet another reminder to physicians that many aspects of our cardiovascular evaluation and therapy need to be tailored specifically for women. Results from studies performed in men may not be directly extrapolated to women."

A pilot study of 25 donor-recipient pairs reveals that healthy young donors of stem cells harbor previously undetected and potentially disease-causing mutations in their blood stem cells, which were transferred to unrelated recipients of the transplants. Although more comprehensive studies are needed, the findings imply that these mutations - which have been linked to post-transplant complications - are more prevalent in young donors than previously thought. Stem cell transplants can treat or even cure blood-related diseases such as enzyme deficiencies and some blood cancers. Studies have shown that stem cell donors over the age of 50 have accumulated at least some mutations in blood stem cells, a process referred to as clonal hematopoiesis. These mutations don't lead to immediate signs of disease, but recent research has connected them to serious conditions such as coronary artery disease and graft-versus-host disease in patients who receive the transplants. Wing Hing Wong and colleagues used advanced sequencing methods to study clonal hematopoiesis in adolescents and young adults, who make up 86% of eligible, unrelated stem cell donors. Among 25 matched donors and recipients, 11 of the donors (median age of 26) had clonal mutations that couldn't be detected with standard sequencing techniques, and 84% of these mutations were predicted to be pathogenic. Importantly, all of the mutations engrafted in the transplant recipients, and the clones expanded in the patients in the first 100 days after transplantation. The clinical implications of the findings remain to be further studied, said Wong. "Once we have a more comprehensive study, we might need to carefully screen donors for mutations that are otherwise undetectable, but are associated with clinical complications in recipients," he added.

New Haven, Conn. -- In the largest examination to date of the health consequences of ageism, or age-based bias, researchers at the Yale School of Public Health have found evidence that it harms the health of older people in 45 countries and across 5 continents. The study included over 7 million participants.

Yale Professor Becca Levy was asked by the World Health Organization to lead the analysis as part of its newly launched Global Campaign to Combat Ageism, which is supported by 194 countries. Levy is a professor at the Yale School of Public Health and in the Yale Psychology Department.

The analysis was based on a systematic review of 422 studies around the world. There was evidence of the adverse effects of ageism on older persons in 96% of the studies.

"The injurious reach of ageism that our team documented demonstrates the need for initiatives to overcome ageism," said Levy, the study's senior author. The study appears in the current PLOS ONE journal.

The Yale School of Public Health study is the first systematic review of ageism that simultaneously considered structural-level ageism, such as denied access to health care, and individual-level ageism, such as the power of stress-inducing negative age stereotypes assimilated from culture to affect the health of older persons.

The Yale team found evidence that ageism led to worse outcomes in a number of mental health conditions, including depression, and a number of physical health conditions, including shorter life expectancy. Ten studies showed that when older persons assimilate negative age stereotypes from the culture, they have a shorter life expectancy. This survival finding, which was originally identified by Levy in previous research, was later found by the studies of others in multiple countries, including Australia, Germany, and China.

In the current study, Levy and her team found that ageism adversely affected whether or not older patients received medical treatment and, if they received the treatment, the duration, frequency, and appropriateness of the treatment provided. Evidence of denied access to health care treatments was found in 85% of all relevant studies. In 92% of the international studies of health care students and professionals, there were indications of ageism in medical decisions, and this trend has increased over time, said the researchers.

This systematic review also found ageism affected older persons regardless of their age, sex, and racial/ethnic membership.

"Our research highlights the importance of recognizing the influence of ageism on health," said first author E-Shien Chang, a Ph.D. candidate in the Department of Social and Behavioral Sciences at the Yale School of Public Health. "Policies to improve older persons' health must take ageism into account."

Boston, MA -- A new analysis provides evidence that may change the current thinking around categorizing patients with heart failure prior to implanting a left-ventricular assist device (LVAD). Currently, clinicians and regulatory agencies divide patients who receive LVADs into two distinct categories: those receiving a device as a bridge to transplant (BTT) and those for whom the device is considered a destination therapy (DT). For BTT patients, the device is intended to extend survival until they can receive a heart transplant. For DT patients, the device is intended for long-term use. Not all patients fit neatly into these categories -- many are stuck in a gray zone known as bridge to transplant candidacy (BTC). But regardless of category and the intended goal of therapy, patients who received an LVAD known as the HeartMate 3 had a similarly low rate of disabling stroke of reoperations and their outcomes were significantly better compared to patients who received an older generation LVAD. These findings, led by investigators at Brigham and Women's Hospital, call into question the current practice of dividing patients into categories, suggesting that a single treatment goal may suffice: to extend survival and improve quality of life for patients with heart failure who haven't responded to therapy. The team's findings are published in JAMA Cardiology.

"This is an important analysis that could lead to a major change in thinking around adjudication of LVADs into discrete categories," said corresponding author Mandeep Mehra, MD, Executive Director of the Brigham's Center for Advanced Heart Disease. "We often fear that the focus on categorizing patients based on the goal of therapy, especially for patients who fall into the gray zone, may cause significant delays in decision making. Our data indicate that with the new generation LVAD, important clinical outcomes are relatively similar between these groups, suggesting that our attention should be on the patient's journey, not the destination. We should be focused on the patient's characteristics and identifying those who are transitioning into advanced heart failure for whom an LVAD may improve quality of life."

The current study leverages data from the Multicenter Study of MagLev Technology in Patients
Undergoing Mechanical Circulatory Support Therapy with HeartMate 3 (MOMENTUM 3), a randomized clinical trial sponsored by Abbott Laboratories, the manufacturer of HeartMate 3. MOMENTUM 3 enrolled patients irrespective of their intended goal of therapy. Patients were randomized to receive either the HeartMate II -- an older generation axial flow pump -- or the HeartMate 3 -- a magnetically-levitated, continuous centrifugal-flow circulatory pump. The trial evaluated how many participants, two years after receiving their device, had not suffered a disabling stroke or had an operation to replace or remove a malfunctioning device.

A total of 1,020 patients received an LVAD. Of these patients, 396 (39 percent) were initially categorized by their clinicians as BTT or BTC and 624 (61 percent) were DT. Patients who received the HeartMate3 had a significantly lower rate of disabling stroke or reoperation than those who received the HeartMate II than those who received the HeartMate II in both the BTT/BTC group (77 percent versus 67 percent) and DT group (73 percent versus 59 percent). There were no differences in rates of pump thrombosis or stroke.

"The use of these designations based on current or uncertain future transplant eligibility is not necessary," said Mehra. "Patients with medically refractory heart failure can be successfully treated under a single preimplant strategy with the goal of extending survival and improving quality of life."

NOx gases is the generic term to refer to the group of gases made up of nitric oxide and nitrogen dioxide, gases that result from burning fossil fuel, and also from forest fires, volcanic eruptions and natural processes of transforming nitrogen in soil. Even so, the greatest concentration is usually found in urban areas, where they are toxic for our health and contribute to global warming and acid rain.

The research community has been working on creating decontaminating materials, which when used in buildings and urban structures, are able to trap these pollutants when exposed to light. However, until now, no one had proven the mitigating potential of something in the natural world that supports life on our planet: soil.

In this regard, Agronomy Department Professor Vidal Barrón, along with a team made up of researchers from the departments of Agronomy, Inorganic Chemistry and Chemical Engineering and Botany, Ecology and Plant Physiology at the University of Cordoba as well as from other international research centers, discovered that there is an exchange of gases in soil enhanced by solar radiation (mostly ultraviolet) that allows for the sequestration of NOx gases and their transformation into nitrate. In this way, the photocatalytic properties of some minerals would generate "soil photosynthesis" in which soil would capture NOx gases from the atmosphere and change them into nitrate, which is the natural way that plants get nitrogen, an essential for their survival.

This discovery has turned into the missing puzzle piece in the nitrogen cycle, since, though we have known about it for over a hundred years, it did not include the effect of the Sun playing a role in said cycle. Now, solar radiation has become an active agent.

Catalytic activity varies depending on the soil. In sandy soils with a lot of quartz, it is not very significant, whereas clay soils with great amounts of smectite have high rates of NOx sequestration and nitrate fixation. The countryside around Cordoba is a good example of an area with high capacity to eliminate air pollution.

This influential article paves the way for those who work in the field of decontamination and could inspire new techniques to manage fertilizers in order to avoid nitrate loss and mitigate NOx pollution. Moreover, it will help to better understand the characteristics and mechanisms within soil.

SINGAPORE, 15 January 2020 - A key mechanism underlying neuronal dysfunction in Angelman syndrome (AS), a syndromic form of autism spectrum disorder, has - for the first time - been revealed through innovative research led by Duke-NUS Medical School and the National Neuroscience Institute (NNI) under the National Neuroscience Research Institute Singapore (NNRIS) - a joint venture combining neuroscience research expertise from both organisations. The finding may bring researchers closer to developing treatment options for this rare genetic condition which occurs in about 1 in 15,000 live births in Singapore.

Using human induced neurons, the team discovered that one specific ion channel which allows potassium to pass through cells was misregulated in neurons from AS patients' cells. This change, which was caused by a missing gene, seems to be responsible for frequent seizures in AS patients. Hence, suppressing the specific ion channel activity could ultimately resolve seizures experienced by AS patients. As the missing gene is common to other forms of autism, the same mechanism may be responsible for the broader range of symptoms seen in autism and finding a treatment for it could potentially benefit people with autism in general.

In Singapore, one in 150 children has autism, a developmental disorder that affects communication and behaviour - higher than the global average of one in 160 children. Unfortunately, there is currently no one standard treatment for autism, partly because its underlying cause and mechanism has so far remained unknown.

AS patients require life-long care as they live with developmental delay, lack of speech and frequent seizures. AS and autism share a common genetic basis, specifically, a disruption in the number of copies of the Ubiquitin Protein Ligase E3A (UBE3A) gene. Because of this, many researchers believe that identifying the mechanism underlying AS can lead to therapeutic options for disorders with similar symptoms, such as seizures and learning disability. However, existing studies using mouse models - currently the go-to experimental models for biomedical research on AS - have not fully addressed the underlying mechanism of network hyperactivity leading to epileptic seizures observed in AS. Furthermore, it is unclear whether similar pathological mechanisms operate in human AS cases.

"Findings from mouse models of AS have been hard to translate into human trials because of key differences between human and mouse neurons, resulting in an inability to identify a clear mechanism that can lead to effective therapeutics," explained Associate Professor Hyunsoo Shawn Je, from Duke-NUS' Neuroscience and Behavioural Disorders Programme, senior author of the study.

To date, the few studies that have used human neurons derived from AS patient-induced pluripotent stem cells (iPSCs) were unable to sufficiently explain the epileptic network activity observed in AS patients. A key concern regarding these studies is that the limited functional maturation of human neurons grown in long-term cultures may affect the modelling of true disease phenotypes in human patients.

The research team from Duke-NUS and NNI, together with collaborators from the Genome Institute of Singapore (GIS), the Singapore Bioimaging Consortium (SBIC), the Agency for Science, Technology and Research (A*STAR), the National University of Singapore (NUS), and Duke University therefore focused on studying the functional changes of human neurons induced from AS patient-derived iPSCs at both the individual cell and the network ensemble levels with the use of functionally mature two-dimensional (2D) human neuronal cultures as well as three-dimensional (3D) human cortical organoids, or mini brains.

"Our study used 2D human neuronal cultures that enabled the accelerated discovery of functional differences at the individual cell level in the brains of normal individuals versus those with AS," Assoc Prof Je clarified. "The use of 3D human mini brains then allowed us to monitor spontaneous network activities, connecting the findings of abnormal firing by single neurons and seizure-like activities just like the ones observed in AS patient brains."

"We found that dysfunction of a specific molecule, known as the large conductance calcium-activated potassium (BK) channel, was misregulated in neurons derived from AS patients' cells, and this change seems to be responsible for frequent seizures in AS patients," Dr Alfred Sun, Junior Principal Investigator at NNI and co-first author of the study, elaborated.

"The integrative data analysis obtained from functionally mature 2D neurons and 3D organoids using a combination of genetic, biochemical, electrophysiological, and imaging assays represents an advanced platform for investigating neuronal phenotypes in vitro. This approach may be applicable to disease modelling studies performed in other tissues or organs," Dr Qiang Yuan, co-first author from Duke-NUS, highlighted.

"Novel approaches such as those used in this study have the potential to unlock new avenues of discovery where conventional methods have fallen short," commented Professor Patrick Casey, Senior Vice Dean for Research at Duke-NUS. "This fascinating study not only identified a plausible drug target to treat epilepsy in AS patients, but also suggests a paradigm change in designing experimental methodology to tackle human brain disorders."

"AS patients have to live and cope with the frequent bouts of seizures - every day is an uphill battle for not only the patients but their families as well. This research exemplifies the active collaborations and leverages on the different expertise within the NNRIS. The team has broken new ground with these discoveries and it is important that we continue to pursue science for better treatment options so that our patients can lead happier and healthier lives," said Professor Tan Eng King, Director, Research and Senior Consultant, Department of Neurology at NNI.

Following on from this study, the researchers are next developing a high-throughput drug-screening platform using human induced neurons to screen US Food and Drug Administration approved drugs that can potentially be repurposed for treatment of epilepsy in AS patients.

A new computer algorithm can predict in the early stages of pregnancy, or even before pregnancy has occurred, which women are at a high risk of gestational diabetes - according to a study by researchers at the Weizmann Institute of Science reported today in Nature Medicine. The study analyzed data on nearly 600,000 pregnancies available from Israel's largest health organization, Clalit Health Services. Based on these predictions, it may be possible to prevent gestational diabetes using nutritional and lifestyle changes.

"Our ultimate goal has been to help the health system take measures so as to prevent diabetes from occurring in pregnancy," says senior author Prof. Eran Segal of the Computer Science and Applied Mathematics and the Molecular Cell Biology Departments.

Gestational diabetes is characterized by high blood sugar levels that develop during pregnancy in women who did not previously have diabetes. It occurs in 3 to 9 percent of all pregnancies and is fraught with risks for both mother and baby. Typically, gestational diabetes is diagnosed between the 24th and 28th weeks of pregnancy, with the help of a glucose tolerance test in which the woman drinks a glucose solution and then undergoes a blood test to see how quickly the glucose is cleared from her blood.

In the new study, Segal and colleagues started out by applying a machine learning method to Clalit's health records on some 450,000 pregnancies in women who gave birth between 2010 and 2017. Gestational diabetes had been diagnosed by glucose tolerance testing in about 4 percent of these pregnancies. After processing big data - an enormous dataset made up of more than 2,000 parameters for each pregnancy, including the woman's blood test results and her and her family's medical histories - the scientists' algorithm revealed that nine of the parameters were sufficient to accurately identify the women who were at a high risk of developing gestational diabetes. The nine parameters included the woman's age, body mass index, family history of diabetes and results of her glucose tests during previous pregnancies (if any).

Next, to make sure that the nine parameters could indeed accurately predict the risk of gestational diabetes, the researchers applied them to Clalit's health records on about 140,000 additional pregnancies that had not been part of the initial analysis. The results validated the study's findings: The nine parameters helped to accurately identify the women who ultimately developed gestational diabetes.

These findings suggest that by having a woman answer just nine questions, it should be possible to tell in advance whether she is at a high risk of developing gestational diabetes. And if this information is available early on - in the early stages of pregnancy or even before the woman has gotten pregnant - it might be possible to reduce her risk of diabetes through lifestyle measures such as exercise and diet. On the other hand, women identified by the questionnaire as being at a low risk of gestational diabetes may be spared the cost and inconvenience of the glucose testing.

Research team leader Marina Gomzikova, employee of the Gene and Cell Technologies Lab, started working on extracellular microvesicles (ECMVs) in 2013, when she was enrolled in her PhD course. Since then, very promising properties were found in ECMVs derived from human mesenchymal stem cells (MSCs).

ECMVs are microstructures surrounded by a cytoplasm membrane; they have proven to be a prospective therapeutic tool due to their biocompatibility, miniature size, safety, and regenerative properties. Microvesicles can be applied to circumvent the existing limitations in cell therapy without losing in effectiveness. At Kazan Federal University, cytochalasin B-induced membrane vesicles (CIMVs) are currently studied. They are derived from mesenchymal stem cells, which are very similar to natural ECMVs.

In this paper, the authors produced, studied and characterized the biological activity of MSC-derived CIMVs. A number of biologically active molecules were found in CIMVs, such as growth factors, cytokines, and chemokines; their immunophenotype was also described. Most importantly, CIMVs were found to stimulate angiogenesis, the growth of blood vessels, in the same way as stem cells.

Therefore, the team believes that human CIMVs-MSCs can be used for cell free therapy of degenerative diseases. CIMVs-MSCs are able to induce therapeutic angiogenesis, which is necessary for the treatment of ischemic tissue damage (for example, ischemic heart disease, hind limb ischemia, diabetic angiopathies, and trophic ulcers) and stimulate regeneration processes in cases of skin damage (wounds and burns), neurodegeneration (multiple sclerosis and Alzheimer's disease), or traumatic injuries (damage of peripheral nerves and spinal cord injury).

Gomzikova's group continues to research the therapeutic potential artificial microvesicles for autoimmune diseases. Vector properties, i. e. the capacity for delivery, of vesicles for tumor therapy is also of interest.

CIMVs can become a new therapeutic tool in regenerative medicine and a new class of effective and safe medications.

Amsterdam, NL, January 15, 2020 -In this collection of articles in the Journal of Pediatric Rehabilitation Medicine (JPRM) experts highlight the emerging trends in spina bifida care in response to challenges faced by spina bifida patients and their physicians due to demographic shifts in age and ethnicity and other societal factors.

Focusing on health disparities, transitional care, and other care needs, this special issue is guest-edited by Timothy J. Brei, MD, Department of Pediatrics, Division of Developmental Medicine, Seattle Children's Hospital, and University of Washington School of Medicine, Seattle, WA, and Jonathan Porter Castillo, MD, MPH, Director of the Spina Bifida Program within the Meyer Center for Developmental Pediatrics at Texas Children's Hospital, Baylor College of Medicine, Houston, TX.

Spina bifida is a birth defect that occurs when the spine and spinal cord fail to form properly. Depending on the type of defect, its size, location, and complications, it can range from mild to severe and can also differ between individuals. Investigators have begun to recognize existing disparities within growing minority populations affected by spina bifida. Neural tube defects like anencephaly and spina bifida have a birth prevalence of nearly six per 10,000 live births in the US. Prevalence rates of spina bifida are also influenced by the mother's race/ethnicity; Hispanics/Latinos consistently have a higher birth prevalence of spina bifida compared with the other racial and ethnic groups in the US.

The number of immigrants, refugees and internally displaced persons around the globe is escalating. At the same time these individuals are also living longer, so these demographic shifts in age and ethnicity are giving rise to a new era in care for patients with spina bifida. "While immigration is often a result of social determinants, including political discrimination, poverty, education, and work-related prospects, immigration itself can also be conceptualized as a social determinant of health," explained Dr. Castillo.

Dr. Brei noted, "A call has gone out for multicenter learning collaboratives to face these newfound challenges. An example of such emergent learning collaboratives is the American Academy of Pediatrics (AAP) Spina Bifida Transition Project sponsored by the Centers for Disease Control and Prevention (CDC), an approach in accordance with the recently published Guidelines for the Care of People with Spina Bifida."

In the US, 25% of children live in immigrant families, and of the estimated 55 million Latinos, nearly three of every four speak Spanish at home. Even so, there is a lack of research on quality of life (QOL) and social determinants of health among patients living with spina bifida. At the same time, in spite of Congress's NIH Revitalization Act of 1993, calling for efforts to ensure that minority groups are included in representative numbers in research studies; few health-related QOL studies have documented inclusion of Spanish-speaking Latinos.

A study conducted at Baylor College of Medicine undertook a systematic review of the scientific literature on language and Latino immigrants in the US living with spina bifida. Eighteen studies met the inclusion criteria (children and adolescents 5-21 years of age with spina bifida and/or myelomeningocele; quantitative studies; health-related QOL outcome measured by validated instrument determinants; and US-based studies). Researchers concluded that QOL in individuals with spina bifida is mediated by a wide range of interrelated factors. They recommend that, in order to better serve this vulnerable population as they transition across the lifespan, multilingual condition-specific QOL measures need to be developed further and implemented among Latino individuals with spina bifida, especially those who are recent immigrants.

"The Spina Bifida Association has updated the spina bifida healthcare guidelines. Therefore, nationally and internationally, we now have guidance and the opportunity to care for all individuals as whole persons as they transition across the continuum of care, holistically approaching them in their language and cultural context," stated Dr. Castillo. "Globally, there has been a 49% increase in immigration since 2000, thus linguistically-congruous study of QOL has increasing relevance not only locally, but also abroad."

"In the face of the documented demographic shifts and demonstrable health disparities, the need for timely and culturally competent studies among Hispanics/Latinos, who have the highest spina bifida prevalence, is self-evident," commented Dr Brei and Dr Castillo.

A study conducted at the University of Pittsburgh School of Nursing evaluated the feasibility of implementing a brief educational training program based on an evidence-based intimate partner violence (IPV) intervention in a pediatric spina bifida clinic. Frequency of IPV discussion was assessed through patient feedback evaluation and provider surveys.

"The educational intervention increased provider comfort with addressing IPV within a specialty clinical setting," commented lead investigator Brenda Cassidy, DNP, University of Pittsburgh School of Nursing, University of Pittsburgh, Pittsburgh, PA. "The frequency of IPV communication by spina bifida patients significantly increased, both immediately and at two months, compared to baseline. Patients reported the discussions were beneficial, and providers reported greater comfort discussing IPV and referring patients to resources."

The issue covers also the following topics: differences in continence rates based on ethnicity; environmental buttocks burns in children and adolescents; emergency department utilization among pediatric spina bifida patients; needs assessment survey for children and adults; an assessment of the degree to which of adolescents and emerging adults with spina bifida understand their individual education programs; two studies on use of a Transition Readiness Assessment Questionnaire (TRAQ-SB); and guidelines for the transition of young spina bifida patients to adult healthcare.

"The commentaries and original research published in JPRM will continue to serve as a catalyst for culturally-competent research, as well as thoughtful investigation and comparative analysis of management practices in order to improve the care among the diverse and aging community of individuals affected with spina bifida around the world," concluded Dr Brei and Dr Castillo.

"Improving the health of children and adolescents with complex medical needs by disseminating peer-reviewed research worldwide is a core mission of JPRM. I am grateful for the dedication of Dr. Brei and Dr. Castillo and all the researchers and contributors to the journal. This special spina bifida issue brings together a wonderful collaboration of international experts," added Elaine Pico, MD, Editor-in-Chief, JPRM, Pediatric Rehabilitation, UCSF Benioff Children's Hospital Oakland, CA.

LA CROSSE, Wis. -- Fewer physicians are pursuing careers in obstetrics, in part because of the intense, round-the-clock demands of the job and a high burnout rate. An unusually large number of practicing obstetricians are expected to retire within the next decade, which will add to an already acute physician shortage.

One solution to this staffing challenge is a collaborative care model used at Mayo Clinic Health System ? Franciscan Healthcare in La Crosse, where certified nurse-midwives lead the care team. Certified nurse-midwives provide care for obstetric patients who are at low to moderate risk as part of a team model described in Mayo Clinic Proceedings: Innovations, Quality & Outcomes.

Patients choose whether to use the care model, which ensures that a certified nurse-midwife is in the hospital around the clock, with generalist obstetricians on call, when needed. The nurse-midwife cares for obstetric patients only, and admits labor induction, pre-labor and active labor patients. The report says the model could be used by similar hospitals that do not employ obstetricians dedicated to labor and delivery.

"Across the country, hospital delivery units are facing a shortage of obstetricians due to a change in the workforce and increasing demands," says Gokhan Anil, M.D., an OB-GYN at Mayo Clinic Health System in Mankato, Minnesota, and first author of the report. "Innovative approaches to staffing are needed to serve the needs of the patient, increase collaboration and improve patient safety."

The collaborative care model has had several positive outcomes since it was implemented in July 2014. The primary cesarean section birth rate has declined, as have vaginal operative deliveries. And the rate of vaginal births after C-section has increased. Admissions to the neonatal ICU decreased from 14.9% in 2012 ? before the care model was offered ? to 10.9% in 2017.

"This approach also has resulted in a shorter length of stay in the hospital for our patients, which always is a good thing for patients, especially a new mother and child," says Dr. Anil, who previously was on staff at Franciscan Healthcare.

The model has won high marks from patients and helped address staffing challenges.

"Based on previous research and our experience, women who receive midwife-led continuity of care are less likely to need an intervention and are more likely to be satisfied with their care," says Costa Sousou, M.D., chair of the Department of Obstetrics and Gynecology at Franciscan Healthcare. "This team approach allows us to continue to provide high-quality care with a more sustainable and cost-effective staffing model. We think it's a model that other institutions may find worth exploring."

NEW YORK, NY (Jan. 15, 2020)--The source of essential tremor--a movement disorder that causes involuntary trembling of the hands, arms, and head--has been enigmatic, impeding the development of effective treatments for a condition that affects 4% of people over 40.

Now a new study from Columbia University Irving Medical Center and NewYork-Presbyterian suggests the tremors are caused by overactive brain waves at the base of the brain, raising the possibility of treating the disorder with neuromodulation to calm the oscillations.

"Past studies have identified changes in brain structure in people with essential tremor, but we didn't know how those changes caused tremors," says Sheng-Han Kuo, MD, the study's senior author and assistant professor of neurology at Columbia University Vagelos College of Physicians and Surgeons.

"This study pins down how those structural changes affect brain activity to drive tremor."

The study was published online today in Science Translational Medicine.

About Essential Tremor

Essential tremor is the most common movement disorder in the United States, affecting about 10 million Americans (approximately eight times as many people as Parkinson's disease). The condition causes involuntary, rhythmic trembling, usually in the hands, and is exacerbated during such activities as buttoning a shirt or using utensils. Although essential tremor is not life-threatening, it can severely impact quality of life.

Some beta blockers and anti-epileptic drugs can reduce symptoms, but they carry side effects, such as fatigue and shortness of breath. They also don't work very well in essential tremor patients, which Kuo says isn't surprising since the cause of the condition hasn't been well understood.

Tremor Patients Have Excessive Brain Activity in the Cerebellum

The researchers have previously identified structural changes in the cerebellum of essential tremor patients and used a new cerebellar encephalogram (EEG) technique to search for unusual brain waves in this part of the brain.

Among 20 essential tremor patients examined with cerebellar EEG, most had strong oscillations (between 4 and 12 Hz) in the cerebellum that were not found in any of the 20 control subjects. Patients with more severe tremors had stronger oscillations.

Oscillations First Found in Mice

The researchers first discovered the cerebellar oscillations in mice that had developed tremors closely resembling those seen in essential tremor patients.

The tremors could be turned on and off by stimulating certain neurons in the mouse brain, alternately suppressing and unleashing the oscillations. "These results established a causal relationship between the brain oscillations and tremor, which cannot be directly tested in patients," says Kuo, who is also an assistant attending neurologist at NewYork-Presbyterian/Columbia University Irving Medical Center.

Excessive Oscillations Stem from Extra Synapses

In previous studies of postmortem brain tissue from essential tremor patients, the Columbia team discovered that patients with essential tremor had an abnormally high number of synapses, or connections, between two types of nerve cells in the brain's cerebellum--climbing fibers and Purkinje cells.

In the current study, again using postmortem brain tissue, the researchers found that the formation of these synapses appears to be influenced by a protein called glutamate receptor delta 2 (GluR?2). "When this protein is underexpressed, any excess synapses that form between climbing fibers and Purkinje cells are not eliminated, resulting in too many neuronal connections," says Kuo.

When the team reduced expression of GluR?2 in mice, the animals developed tremors similar to those seen in humans. Restoring GluR?2 function suppressed the tremors, proving that the protein plays a key role in essential tremor.

Potential for New Treatments

The study opens several new possibilities for treatment of essential tremor, Kuo says.

"Using cerebellar EEG as a guide, we may be able to use neuromodulation techniques such as tDCS or TMS (transcranial direct-current stimulation or transcranial magnetic stimulation) to reduce tremor, or even drugs to reduce transmission between the climbing fibers and Purkinje cells."

Kuo is also working to develop medications that increase GluR?2 expression in the brain, which may reduce tremor.

DALLAS - Jan. 15, 2020 - A UT Southwestern study is challenging concerns that a federal health policy enacted in 2012 to reduce hospital readmissions leaves patients more vulnerable.

The researchers, whose findings published today in BMJ, poured over nine years' worth of Medicare claims data to report on outcomes of patients who received care in observation units and emergency departments in the 30-day period following hospitalization.

The investigation by UT Southwestern cardiology experts was motivated by a rise in post-hospitalization deaths among heart failure and pneumonia patients targeted in the Hospital Readmissions Reduction Program (HRRP). The program reduces payments to hospitals with excess readmissions.

"Our research results were reassuring. We found that although the use of observation units and the emergency department as avenues of care in the post-hospitalization period has increased in recent years, there was no increase in mortality risk in these settings," says Rohan Khera, M.D., a cardiology fellow at UT Southwestern and lead author for the study.

Khera and his team analyzed inpatient and outpatient Medicare claims from 2008-16. This time frame spanned the announcement and implementation of the HRRP.

During that period, there were 3.7 million hospital admissions for heart failure, 1.6 million hospitalizations for myocardial infarction, and more than 3.2 million for pneumonia among Medicare beneficiaries 65 years of age and older.

The overall post-discharge 30-day mortality rate was 8.7 percent for heart failure, 7.3 percent for acute myocardial infarction, and 8.4 percent for pneumonia.

Patients with heart failure, but not those with acute myocardial infarction or pneumonia, experienced an increase in post-discharge 30-day mortality; however, researchers say this increase preceded the announcement of the program and was concentrated among patients who sought no post-discharge acute care, nearly half of whom had been sent to hospice.

"While observation units and the emergency department were increasingly used as avenues of care in the post-discharge period, there has been no increase in the mortality risk in either setting," explains Khera. "Our findings suggest that some of the increase in mortality may be due to transition of end-of-life care from being in the hospital to the period following hospitalization."

Khera says he's putting that hypothesis to the test in his next study.

His health policy research occurs in collaboration with Harlan Krumholz, M.D., S.M., and other investigators at Yale University and is funded by the National Center for Advancing Translational Sciences of the National Institutes of Health.

One in five young people have fatty liver disease (steatosis), with one in 40 having already developed liver scarring (fibrosis), research published today [15 January] has found. The study, published in The Lancet Gastroenterology & Hepatology, is the first to attempt to determine the prevalence of fatty liver disease and fibrosis in young healthy adults in the UK.

Fatty liver disease is a condition in which fats build up in the cells of the liver. It is broadly split into non-alcoholic fatty liver disease (NAFLD), which is usually seen in people who are overweight or obese, and alcohol related fatty liver disease, which is associated with harmful levels of drinking. If left untreated both can lead to fibrosis (scarring of the liver) and in severe cases eventually cirrhosis of the liver, which is irreversible. Worldwide NAFLD affects approximately a quarter of adults in developed countries.

The research, conducted by Dr Kushala Abeysekera and researchers from the University of Bristol, looked at data collected from 4,021 participants of the Children of the 90s study also known as Avon Longitudinal Study of Parents and Children (ALSPAC). Based in Bristol, participants from the health study - who had previously been assessed for NAFLD as teenagers using ultrasound - were invited for assessment using transient elastography with FibroScan as part of the Focus @24 clinic.

Researchers first looked at those participants who did not report harmful alcohol consumption and found that one in five had non-alcoholic fatty liver disease. On widening the data to include all participants, they again found that over 20 per cent displayed evidence of fatty liver and one in 40 had already developed fibrosis, with those participants who had both fatty liver and harmful alcohol use at greatest risk of liver scarring. As a comparison, at 17 years of age, 2.5 per cent of participants had moderate to severe levels of fatty liver, whilst at the age of 24 this number had increased to 13 per cent.

Dr Abeysekera, Honorary Lecturer in the Bristol Medical School: Population Health Sciences, explained: "Children of the 90s data has highlighted the potential importance of liver health amongst young adults. This age group remains a blind spot for clinicians, as they are typically considered a "healthy" age group that are rarely studied. If the obesity epidemic and culture of alcohol abuse aren't tackled nationally, we may see increasing numbers of patients presenting with end-stage liver disease, and at earlier ages.

"It is important to note that whilst we identified that 20 per cent of the cohort had fatty liver - only a small percentage of the individuals will go on to develop cirrhosis (irreversible liver scarring), and the vast majority of participants should be fine if they manage their diet and exercise appropriately."

The next steps will be to take a closer look at how environmental and genetic factors may lead to individuals developing non-alcoholic fatty liver disease earlier in life.

New Rochelle, NY, January 15, 2020--As more states legalize medicinal and recreational cannabis use and increasingly decriminalize cannabis, the risk to the growth and development of breastfeeding infants whose mothers use cannabis becomes a growing public health concern. The critical role that certified lactation consultants (CLCs) could play in postpartum management of cannabis use and a Call to Action to expand the role of CLCs is published in Breastfeeding Medicine, the official journal of the Academy of Breastfeeding Medicine published by Mary Ann Liebert, Inc., publishers. Click here to read the protocol free on the Breastfeeding Medicine website through February 15, 2020.

The article entitled "Management of Cannabis Use in Breastfeeding Women: The Untapped Potential of Certified Lactation Consultants" was coauthored by Kara Skelton, PhD and Sara Benjamin-Neelon, PhD, MD, MPH RD, Johns Hopkins Bloomberg School of Public Health (Baltimore, MD) and Kelly Young-Wolff, PhD, MPH, Kaiser Permanente Northern California (Oakland, CA) and University of California, San Francisco.

CLCs are specialized healthcare professionals who provide evidence-based support for the clinical management of breastfeeding. The authors encourage obstetricians and pediatricians to partner with CLCs to help identify women who are using cannabis while breastfeeding and to provide education and counseling to encourage them to suspend or at least minimize cannabis use while nursing. Data have shown that the active ingredient in cannabis is transferred to the infant via breastmilk and remains in the infant's system for about 6 days, raising concern what adverse effect it may have on the infant's long-term growth and neurodevelopment.

Arthur I. Eidelman, MD, Editor-in-Chief of Breastfeeding Medicine, states: "CLCs are a potential asset to the healthcare team caring for the maternal/infant dyad, and because of their intimate personal involvement with mothers they can serve as the critical professional in guiding nursing mothers on the proper use of cannabis products."

Research reported in this publication was supported by the National Institutes of Health under Award Number K01 DA043604. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.