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EL PASO, Texas - Biology students and faculty members from The University of Texas at El Paso have discovered a new target for tuberculosis drug development. Their study recently was published in the Journal of Biological Chemistry, a publication of the American Society of Biochemistry and Molecular Biology (ASBMB).

Jianjun Sun, Ph.D., associate professor in UTEP's Department of Biological Sciences, led the research on Mycobacterium tuberculosis (Mtb), the bacterial pathogen that causes tuberculosis diseases, or TB.

TB is one of the leading infectious diseases in the world. Development of novel therapeutics against TB is urgently needed. Sun's lab has been investigating the mechanisms of Mtb pathogenesis for more than 10 years at UTEP with a specific focus on EsxA, which is a virulence factor essential for Mtb virulence and a preferred target for developing novel anti-TB drugs and vaccines.

During infection, Mtb is "eaten up" by human immune cells. Normally, the bacteria are killed within the immune cells, but Mtb releases virulence factors, such as EsxA, to disarm the host's immune defense. The study discovered that the Nα-acetylation of EsxA can drastically affect the course of the infection.

"This research was technically challenging, but the students were able to overcome the challenges and accomplished the goals," Sun said. "All the hard work from the students and collaborators has finally come together to contribute a beautiful story in the prestigious Journal of Biological Chemistry from ASBMB."

The study had many collaborators including Javier Aguilera, a doctoral student in Sun's lab who is supported by the Research Initiative for Scientific Enhancement (RISE) Program. Other contributors include Salvador Vazquez-Reyes, a doctoral student in Sun's lab, and Qi Zhang, Ph.D., a previous postdoctoral fellow in Sun's lab.

"Knowing this work has a great impact in the TB research feels great," Aguilera said. "Although it resulted in so many late nights of hard work and headaches for so many people, the end result was very well worth it!"

The study benefited from a collaboration with Lin Li, Ph.D., assistant professor of computational biophysics and bioinformatics in UTEP's Department of Physics. Chitra B. Karki, a doctoral student in Li's lab, provided help with molecular dynamic simulations to model the effects of Nα-acetylation on EsxA function. Igor Estevao and Brian I. Grajeda, from the Proteomics Analysis Core Facility of UTEP's Border Biomedical Research Center, helped to identify the Nα-acetylation by using state-of-the-art mass spectrometry. Hugues Ouellet, Ph.D., associate professor of biological sciences, and his doctoral student Chenoa D. Arico assisted with mycobacterial biology and protein binding measurements.

BOSTON - (June 30, 2020) - Researchers from the Joslin Diabetes Center investigated time trends in pregnancy-related outcomes among women with type 1 diabetes between 2004 and 2017, and found that the percentage of mothers with excess weight gain during pregnancy as well as the use of insulin pumps and CGMs increased significantly, while the prevalence of nephropathy fell dramatically to zero. Furthermore, the research highlights a trend toward increased pre-pregnancy obesity in this population, but the percentage of very large babies born remained the same. The research is published online on June 2, 2020 by the Journal of Perinatology.

The percentage of women with type 1 diabetes before pregnancy has climbed nearly 40% in the past two decades, according to the Centers for Disease Control and Prevention.

"Originally, our aim was to look at why women with type 1 diabetes have large birth weight babies, and to determine whether the prevalence of babies born very large has changed over the years in our population," says Florence Brown, MD, study coauthor and Co-Director of the Joslin and Beth Israel Deaconess Medical Center Diabetes in Pregnancy Program in Boston. "To understand this relationship, it is necessary to understand the influence of a broad number of variables."

For the study, researchers reviewed medical records of 700 pregnant women with type 1 diabetes who attended the Joslin Diabetes Center and Beth Israel Deaconess Medical Center Diabetes in Pregnancy Program between 2004 and 2017. Currently, this is the largest U.S. database on pregnant women with type 1 diabetes.

Researchers analyzed data on treatment, delivery and neonatal outcomes, as well as the mothers' glucose levels, gestational weight gain and other maternal factors that impact outcomes in pregnancy. To calculate trends in these areas over time, patients were divided into three groups based on their delivery date: 2004 to 2008; 2009 to 2012; and 2013 to 2017. Researchers then compared changes over these time periods. The study revealed:

A1c levels of the mothers remained steady in each trimester across the entire study period.

The prevalence of diabetic nephropathy fell dramatically, dropping from 4.8% in 2004 -2008 to 0% in 2013-2017.

The percentage of mothers with excessive gestational weight gain increased by about 10% from 2004-2008 to 2013-2017. "This underscores the need to address BMI prior to pregnancy, making sure women have regular nutrition counseling to achieve weight goals," says Brown.

Length of pregnancy increased slightly over time, and the number of vaginal deliveries rose from about 21% in the early years of the study to 29% in the later years. The prevalence of babies born very large remained high throughout the study period. These babies are at greater risk for later-life metabolic diseases, says Brown.

Insulin pump use increased by about 23% between 2004 and 2017. In addition, CGM use also rose, from no use at the start of the study to nearly 40% during the later years of the study. "Our next study will look at the differences in women who use insulin pumps and CGMs and how that use effects diabetes control and neonatal outcomes," says Brown.

These findings are important because they are a stepping stone to our next analysis, says Brown. "This is the first time we've really been able to paint a big picture, and identify the clues as to which factors may be associated with large birthweight, such as maternal BMI, maternal gestational weight gain and A1c levels."

Deep Brain Stimulation (DBS) implanted in early stage Parkinson's disease decreases the risk of disease progression and the need to prescribe multiple drugs to patients simultaneously, according to a five-year outcomes study of 30 patients released in the July 2020, issue of Neurology®, the medical journal of the American Academy of Neurology.

The journal released a Classification of Evidence statement along with the study stating that it provides "Class II evidence that DBS implanted in early stage Parkinson disease decreases the risk of disease progression and polypharmacy compared to optimal medical therapy alone."

"Parkinson's is relentless. There's nothing that slows down its progression. With this pilot study, we've shown that if DBS is implanted early it's likely to decrease the risk of progression, and if this is borne out in our larger study it would be a landmark achievement in the field of Parkinson's disease," said senior author David Charles, MD, professor and vice-chair of Neurology at Vanderbilt University Medical Center (VUMC).

The FDA has approved VUMC to lead a 130-patient, multi-site double-blinded randomized clinical trial of DBS for early stage Parkinson's; if results of the pilot trial are replicated in that larger study, DBS will become the first therapy proven to slow the progression of any element of Parkinson's.

Parkinson's is a long-term neurodegenerative disorder most obviously characterized by tremor, rigidity, slow movement (bradykinesia) and difficulty with balance and walking.

As of 2016, some 6.2 million people worldwide were living with Parkinson's. According to the Parkinson's Foundation, as many as 60,000 Americans are diagnosed each year with the disease.

Early stage Parkinson's disease is defined as within four years of disease onset.

From 2006 to 2009, the investigators enrolled 30 patients, all of whom received optimum drug therapy, with a random half additionally receiving DBS, which is often characterized as a pacemaker for the brain.

The DBS surgery uses a pair of ultra-thin electrodes surgically implanted deep into the brain to deliver electric pulses to the subthalamic nucleus, a small cluster of neurons. As with a heart pacemaker, the electric pulses are supplied by a battery implanted under the skin near the collarbone.

After five years, the patients who received optimal drug therapy only but not surgery in early-stage Parkinson's had five-fold greater odds of experiencing worsening of their rest tremor, a hallmark of this disease, as compared to patients who received early DBS in addition to drug therapy.

In other five-year outcomes from the study, the DBS patients required considerably less of the medication used to manage symptoms of Parkinson's.

"Patients who were randomized to receive early optimal drug therapy had 15-fold greater odds of needing multiple types of Parkinson's disease medications," said project leader Mallory Hacker, PhD, MSCI, assistant professor of Neurology at VUMC.

In a marked but uncertain trend falling just short of statistical significance, Parkinson's patients randomized to receive drugs alone were more than twice as likely to have worse motor symptoms than patients who received early DBS.

"What this pilot study is most clearly telling us is that the new FDA-approved Phase III study must be done to definitively determine whether DBS slows the progress of Parkinson's disease when implanted in the very earliest stages," Charles said.

"While this is an incredibly exciting finding, patients and physicians should not change clinical practice at this time," he added.

(PHILADELPHIA) - Women carrying twins are at higher risk for premature birth and miscarriage - those whose cervix dilates before 24 weeks are at highest risk - and yet one common treatment is not recommended for this population. A new multi-center randomized-controlled trial from Thomas Jefferson University shows that cerclage, an intervention that sutures a dilating cervix closed, can help prevent preterm birth and miscarriage. The findings could overturn existing guidelines.

The clinical trial was stopped early because of positive results in the intervention group. The researchers showed that perinatal mortality was significantly decreased in women receiving cerclage.

"For women with twin pregnancies and early signs of labor and cervix dilation, there was really very little we could offer," says first author, Amanda Roman, MD, Associate Professor in the Department of Obstetrics and Gynecology at Thomas Jefferson University. "This study provides powerful evidence that there is an effective treatment we can use."

The results were published online in the American Journal of Obstetrics and Gynecology (AJOG) on June 24th.

Women who showed signs of preterm labor, as confirmed by a cervical exam that indicates dilation, were enrolled in the study and randomized to either receive cerclage plus antibiotics and indomethacin (an anti-pain medication) , or standard of care. Of the 30 women enrolled, 17 women were randomized to the cerclage group and 13 to non-cerclage. The women in both groups were similar in demographics including age, race, body-mass index and other factors for preterm birth.

The trial enrolled 30 patients across 8 medical centers over the course of four years. "The small number of participants reflects how rare this condition is among all pregnancies," says Dr. Roman. "But because women were randomized to treatment and non-treatment groups, the results are strong, as confirmed by the independent Data Safety Monitoring Board."

The analysis showed that in the group that received cerclage, gestation was prolonged by an average of 5.6 weeks (with a range of 2.0 to 9.3 weeks), and reduced infant mortality by 77%.

"Cerclage is a heroic intervention in this group of women," says Dr. Roman. "The possibility of losing a pregnancy is devastating. So we're very encouraged by these results demonstrating a life-saving intervention for women with twins experiencing early asymptomatic cervical dilation."

"We've already incorporated this cerclage into our practice and have been able to offer this to pregnant mothers with twins with great success," says senior author Vincenzo Berghella, MD, Director of the Division of Maternal Fetal Medicine at Jefferson. "These results have the potential to change practice, and help many more women have healthy twin babies."

Dr. Roman and her collaborators are also exploring whether cerclage might prove effective for another subset of women carrying twins, specifically women whose cervical length has shortened, which is a precursor to cervical dilation, between 16 and 23 weeks. They have a clinical trial currently open. Women participating in the study will be randomized to receiving cerclage or no cerclage (ClinicalTrials.gov # NCT03340688).

PHILADELPHIA (June 29, 2020)- The COVID-19 pandemic has led to drastic changes in how hospitals provide end-of-life care to patients and their families. With strict no-visiting limitations in place in an effort to stem contagion, patients have been dying alone.

Extraordinary circumstances require extraordinary problem solving. The pandemic is an opportunity for clinicians to think differently and consider a decision-making framework that minimizes infection risk, honors patient/family relationships, upholds culturally important rituals of dying, and mitigates potential psychological harm precipitated by the trauma of family separation.

In an editorial in the journal Intensive Care Medicine, researchers suggest an alternative pathway to patients dying alone in a hospital. They advocate that infection control, public health concerns, and family-centered care can coexist and urge reconsideration of adult family member presence at the bedside of patients during COVID-19.

"With careful screening, education, pragmatic psychosocially oriented facilitation, and teamwork, we can accommodate the very real needs of patients to not be alone, for families to fulfill their sense of responsibility and duty, and for staff to uphold the tenets of family-centered care," writes Martha A. Q. Curley, PhD, RN, FAAN, Professor of Nursing at the University of Pennsylvania School of Nursing (Penn Nursing), one of the editorial's authors. "Dying alone, despite adhering to social distancing, should not be part of dying at all."

The editorial, "Alone, the Hardest Part," is available online. Coauthors of the editorial include Elizabeth Broden, Penn Nursing PhD Student, and Elaine Meyer from the Center for Bioethics, Harvard Medical School.

NEW YORK, NY (June 29, 2020) -- Researchers at Columbia University Irving Medical Center have developed eye drops that could prevent vision loss after retinal vein occlusion, a major cause of blindness for millions of adults worldwide.

A study, in mice, suggests that the experimental therapy -- which targets a common cause of neurodegeneration and vascular leakage in the eye -- could have broader therapeutic effects than existing drugs.

The study was published in Nature Communications.

What is Retinal Vein Occlusion?

Retinal vein occlusion occurs when a major vein that drains blood from the retina is blocked, usually due to a blood clot. As a result, blood and other fluids leak into the retina, damaging specialized light-sensing neurons called photoreceptors.

Standard treatment for the condition currently relies on drugs that reduce fluid leakage from blood vessels and abnormal blood vessel growth. But there are significant drawbacks. These therapies require repeated injections directly into the eye, and for the patients who brave this daunting prospect, the treatment ultimately fails to prevent vision loss in the majority of cases.

The new treatment targets an enzyme called caspase-9, says Carol M. Troy, MD, PhD, professor of pathology & cell biology and of neurology in the Taub Institute for Research on Alzheimer's Disease and the Aging Brain at Columbia University Vagelos College of Physicians and Surgeons, who led the studies. Under normal conditions, caspase-9 is believed to be primarily involved in programmed cell death, a tightly regulated mechanism for naturally eliminating damaged or excess cells.

However, in studies of mice, the Troy lab discovered that when blood vessels are injured by retinal vein occlusion, the caspase-9 becomes uncontrollably activated, triggering processes that can damage the retina.

Eye Drops Prevent Retinal Injury

The Troy lab found that a highly selective caspase-9 inhibitor, delivered in the form of eye drops, improved a variety of clinical measures of retinal function in a mouse model of the condition. Most importantly, the treatment reduced swelling, improved blood flow, and decreased neuronal damage in the retina.

"We believe these eye drops may offer several advantages over existing therapies," says Troy. "Patients could administer the drug themselves and wouldn't have to get a series of injections. Also, our eye drops target a different pathway of retinal injury and thus may help patients who do not respond to the current therapy."

Next Steps

The researchers are preparing to test the eye drops in people with retinal vein occlusion during a phase I clinical trial.

Moving forward, the Troy lab will also study whether caspase-9 inhibitors can be used to treat other vascular injuries caused by overactivation of the enzyme, including diabetic macular edema (another common cause of blindness) and stroke.

"Vascular dysfunction is at the heart of many chronic neurological and retinal disorders, because high energy demands in the brain and eye render these tissues exceptionally vulnerable to disruption in blood supply," says the study's first author, Maria Avrutsky, PhD, postdoctoral research scientist in pathology & cell biology at Columbia University Vagelos College of Physicians and Surgeons.

HUNTINGTON, W.Va. - New research from a team at the Marshall University Joan C. Edwards School of Medicine reveals the central role of fat cells in the systemic oxidant stress observed in renal failure-associated cardiomyopathy.

The research, published June 25 in the Journal of the American Society of Nephrology, is the first publication to demonstrate such an important role for fat cells known as adipocytes in a disease previously thought to have little involvement of such tissues.

Using a mouse model of experimental renal failure and a diet enriched in fat and fructose to simulate a western diet, the researchers found that production of the peptide NaKtide in fat cells inhibited the signaling function of the sodium pump, Na/K-ATPase. The peptide also prevented the development of renal failure-associated cardiomyopathy as well as other consequences of renal failure such as anemia. Targeting NaKtide production to skeletal muscle cells with a similar manipulation had essentially no effect on the cardiomyopathy or anemia in mice with experimental renal failure.

"This research provides an important breakthrough with translational application and demonstrates that Na/K-ATPase oxidant-amplification loop and/or adipocytes are potential targets for disease intervention," said lead author Komal Sodhi, M.D., associate professor of surgery and biomedical sciences at the Marshall University Joan C. Edwards School of Medicine.

Future research will help determine if these findings can be confirmed in humans, representing a novel and successful therapeutic target in chronic renal failure.

"According to this novel study, targeting this oxidant amplification loop in adipocytes could serve as a viable clinical strategy for the prevention and treatment of renal failure-associated cardiomyopathy," said Joseph I. Shapiro, M.D., dean of the Joan C. Edwards School of Medicine and the study's senior author.

Below please find a summary and link(s) of new coronavirus-related content published today in Annals of Internal Medicine. The summary below is not intended to substitute for the full article as a source of information. A collection of coronavirus-related content is free to the public at http://go.annals.org/coronavirus.

1. Why N95 Should Be the Standard for All COVID-19 Inpatient Care

Guidelines differ in their guidance on the use of N95 respirators versus medical masks for frontline health care workers working with patients with COVID-19, particularly when aerosolized procedures are not involved. Authors from Providence-St. Jude Medical Center and Marshall B. Ketchum University College of Pharmacy make the case that the existing data do not show facemasks as equivalent in protection to N95 and are often misinterpreted. Authors suggest a reevaluation of this evidence and make the argument that N95 should be routinely used for inpatient COVID-19 care. Read the full text: https://www.acpjournals.org/doi/10.7326/M20-2623.

Media contacts: A PDF for this article is not yet available. Please click the link to read full text. The lead author, Harry Peled, MD, can be reached directly through Dru Ann Copping at DruAnn.Copping@stjoe.org.

2. Worldwide Effect of COVID-19 on Physical Activity: A Descriptive Study

Physical activity is an important determinant of health and is likely affected by social distancing measures due to the COVID-19 pandemic. Researchers from the University of California examine worldwide changes in step count before and after the announcement of COVID-19 as a global pandemic. They found that rapid worldwide step count decreases have been seen during COVID-19, with regional variability, and that regional step count trends may reflect adherence to social distancing measures. Read the full text: https://www.acpjournals.org/doi/10.7326/M20-2665.

Media contacts: A PDF for this article is not yet available. Please click the link to read full text. The lead author, Geoffrey H. Tison, MD, MPH, can be reached through Katherine at katherine.ramsey@ucsf.edu.

New Rochelle, NY, June 29, 2020--Women are significantly more likely to receive prescriptions of opioid analgesics. Read the study, which was performed in a nationally representative sample of adults in the U.S., in Journal of Women's Health. Click here to read the article now.

Researchers from University of California Davis School of Medicine identified three main factors driving this discrepancy. These included lower, more adverse socio-economic status among women and more adverse health status-related factors. Another factor was higher rates of overall healthcare utilization.

"Our analysis found no evidence that the treatment of pain was driving women's higher rates of prescription opioids," said Alicia Agnoli, MD and coauthors.

"Future research and prevention efforts should target these factors to help combat the growing opioid epidemic," says Journal of Women's Health Editor-in-Chief Susan G. Kornstein, MD, Executive Director of the Virginia Commonwealth University Institute for Women's Health, Richmond, VA.

Yale Cancer Center (YCC) scientists have found that combining the targeted drug trastuzumab with chemotherapy significantly improves survival rates for women with a rare, aggressive form of endometrial cancer. These results may help to change the standard of care worldwide for the disease. The findings are published today in the journal Clinical Cancer Research.

"The randomized, multi-institutional phase 2 trial studied 58 women with uterine serous carcinoma (USC) whose tumors expressed high levels of the HER2 protein, which is known to drive several forms of cancer in women," said Alessandro Santin, M.D., professor of gynecology, obstetrics & reproductive sciences, Leader of the Disease Aligned Research Team of the Gynecologic Oncology Program at Smilow Cancer Hospital and YCC, and senior author of the study. After surgery, women were either given a standard chemotherapy regimen of carboplatin and paclitaxel, or the same combination chemotherapy regimen followed by trastuzumab. Trastuzumab targets HER2, a surface receptor, and has long improved outcomes for women whose breast cancers display high levels of HER2 expression.

The combination therapy with trastuzumab was particularly effective among 41 women with advanced stage 3 and stage 4 USC receiving their first treatment for the disease. Average progression-free survival (PFS) doubled from about 9 months in the control arm to 18 months in women given the treatment, "which is unprecedented for this cancer," Santin said.

"Importantly, the trial showed no difference in toxicity between the two groups," said Santin. "Trastuzumab is a humanized antibody, a natural product of our bodies, and it is extremely well tolerated."

Each year, more than 65,650 women in the United States are diagnosed with endometrial cancer, and over 12,590 die of the disease. "As this country's population ages and obesity rates climb, these numbers are likely to double in the next decade," said Santin. "USC accounts for only three to ten percent of all these cases of endometrial cancer, but it kills over 40% of the patients because it's so aggressive," he added.

Among the 17 women in the study where USC recurred, the combination treatment prolonged the disease-free interval but did not significantly improve survival when compared to the standard chemotherapy regimen. "These are patients who return with large amounts of metastatic cancer," Santin said. "Most likely their tumor burden is so high and heterogenous that the tumor becomes resistant also to trastuzumab."

In 2018, after examining preliminary data on the phase 2 trial, the National Comprehensive Cancer Network (NCCN) adopted the chemotherapy/trastuzumab combination for new treatment of women with HER2-positive USC as a guideline for treatment. NCCN is widely recognized by both clinicians and payers as the U.S. standard-setting body for oncology clinical guidelines. "With those NCCN guidelines, everybody started using it," Santin said. Now that the final results for the trial are published, he expects much broader worldwide adoption of the combination.

Researchers from the Social Cognition Center Cologne at the University of Cologne and from the University of Bremen report that participants in three experiments, each involving more than 500 adults in the United States, tended to assume the number of COVID-19 cases grew linearly with time, rather than exponentially. As a result, they underestimated actual virus growth. Interventions designed to help people avoid this bias led to an improved understanding of virus growth and increased support for social distancing measures compared with participants who did not receive such instructions.

The experiments were conducted by the social psychologist Dr Joris Lammers of the Social Cognition Center Cologne and the University of Bremen and his co-authors, the social psychologists Jan Crusius and Anne Gast, also from the University of Cologne. The article 'Correcting misperceptions of exponential coronavirus growth increases support for social distancing' has been published in the current issue of Proceedings of the National Academy of Sciences of the United States of America.

The most effective way to stem the spread of a pandemic such as COVID-19 is what has come to be known as 'social distancing'. But the introduction of such measures is hampered by the fact that a sizeable part of the population fails to see their need. Many social scientists see the root of this perception in what they call the exponential growth bias. 'In general, people have difficulty understanding exponential growth and erroneously interpret it in linear terms instead', explains first author Joris Lammers. The result is a gross underestimation of the growth of the infection rate and a misunderstanding of the potential to slow it down through social distancing. 'Our current work tests the role of exponential growth bias in shaping the public's view on social distancing to contain the coronavirus's spreading.'

Three studies were conducted during the mass spreading of the virus in the United States toward the end of March 2020. The first study focused on participants' understandings of linear growth, showing that many Americans mistakenly perceive the virus's exponential growth in linear terms. Interestingly, political orientation also played a role: conservatives were more prone to this misunderstanding than liberals. Studies 2 and 3 showed that instructing people to avoid the exponential growth bias significantly increases correct perceptions of the virus's growth and thereby support for social distancing. 'Together, these results show the importance of statistical literacy to recruit support for fighting pandemics such as the coronavirus,' said Lammers.

'Our results stand in contrast to earlier literature showing that the exponential growth bias is difficult to overcome', he explained. 'The reason for this is that the current study focuses on a threat with great personal relevance and media presence, which likely increases subjective availability and thus the estimated probability of the risk.'

Given that social distancing is the most effective way to combat the coronavirus currently available, these findings can have a significant impact: They show that bias, among other things, influences political opinions about matters of life and death, Lammers believes. Most important for team is to show the necessity of statistical literacy and to improve that skill among the general public.

Monday, 29 June: Research undertaken by RCSI University of Medicine and Health Sciences suggests that integrating pharmacists into general practice (GP) teams facilitates collaboration to optimise treatment plans for patients with long-term medical needs and alleviate pressures on GP practices.

The study, conducted by researchers in RCSI's Department of General Practice and School of Pharmacy and Biomolecular Sciences, is published today in BMJ Open.

General practitioners (GPs) frequently manage medications for patients with multiple complex health conditions, further complicated by long-standing prescriptions from previous doctors and the evolving nature of treatment. Pharmacists are well placed to assist with this, working collaboratively with GPs to decide on the most appropriate treatment options.

Although not yet introduced in Ireland, general practice pharmacists are common in other countries and have been shown to provide essential support to GP teams, with the potential to optimise treatment and lower costs. The pilot study led by RCSI is the first evaluation of pharmacists in this role in Ireland.

Researchers selected four GP practices with approximately 35,000 patients to participate in the study over a six-month period. During this time, pharmacists were integrated into and worked in these practices reviewing prescriptions to support existing GP teams. They flagged 786 patients who had 1,521 potential issues relating to medication effectiveness or concerns over possible side effects. The most common medications involved were proton pump inhibitors used to suppress stomach acid, benzodiazepines used to treat anxiety or insomnia and anti-inflammatory drugs.

Over 50% of these issues resulted in a change being made by the patient's GP, such as reducing the dose or ending a prescription where the risks outweighed the benefits or the medication was no longer necessary. Overall, the changes to prescriptions in the four GP practices amounted to potential cost savings of approximately €57,000 each year.

"Our findings clearly demonstrate the possible benefit of introducing general practice pharmacists to the Irish healthcare system. While further study is needed to establish the cost-effectiveness of such an initiative nationwide, implementing it would work towards alleviating the pressure our GPs are under and improving the quality of care for Irish patients," said senior author Dr Frank Moriarty, a pharmacist and lecturer at the School of Pharmacy and Biomolecular Sciences.

Leading the study alongside Dr Frank Moriarty are GP and Professor of Primary Care Medicine, Professor Susan Smith and research lecturer Dr Barbara Clyne, both from the RCSI Department of General Practice.

"As demands on primary care increase, integrating pharmacists into GP practices has the potential to bring a more closely integrated model of care to patients with multiple complex needs. The best patient care in general practice includes multidisciplinary collaboration across healthcare professionals and I look forward to further studies in this area to explore the feasibility of introducing this practice in Ireland," said Professor Susan Smith and Professor of Primary Care Medicine at RCSI.

A new polymeric heart valve with a life span potentially longer than current artificial valves that would also prevent the need for the millions of patients with diseased heart valves to require life-long blood thinning tablets has been developed by scientists at the universities of Bristol and Cambridge. The team's latest in-vitro results, published in Biomaterials Science, suggest that the PoliValve could last for up to 25 years.

More than 1.3 million patients with diseased heart valves need valve replacement therapy globally each year. There are two artificial valves currently available for this; both have limitations either in durability or in biocompatibility. Biological valves are made from fixed pig or cow tissue and have good biocompatibility, meaning patients do not need life-long blood thinning tablets. However, they only last ten to 15 years before failing. While mechanical valves have very good durability, they have poor biocompatibility and patients must take daily blood thinning drugs to prevent life threatening complications due to blood clots.

Professor Geoff Moggridge, Head of the Structured Materials Group at Cambridge's Department of Chemical Engineering and Biotechnology and Professor Raimondo Ascione, NHS Adult Cardiac Surgeon and Head of the Translational Biomedical Research Centre (TBRC) at the University of Bristol have spent three years conducting developmental work and extra-vivo and in-vivo testing on the new PoliValve.

The PoliValve, created by Professor Moggridge, Dr Marta Serrani and Dr Joanna Stasiak at Cambridge and Professor Ascione in Bristol, and building on earlier work with Professor Costantino's group, is made from a special co-polymer and is designed to resemble the flexibility, biocompatibility and durability of a natural heart valve.

The device combines excellent durability with biocompatibility, addressing the limitations of current biological and mechanical artificial valves. It is made through a simple moulding process; hence it also reduces markedly manufacture and quality control costs.

Professor Moggridge, said: "These impressive results show the PoliValve is a promising alternative for valve replacement surgery. While further testing is needed, we think it could make a major difference to the hundreds of thousands of patients who get valve replacement surgery every year."

Initial testing in animal has been undertaken at Bristol's TBRC facility as a first mandatory in-vivo testing step to ensure safety. Long-term in-vivo testing is already planned and funded as a necessary additional step before bringing this new treatment to patients.

Professor Sir Nilesh Samani, Medical Director at the British Heart Foundation, said: "Patients requiring an artificial heart valve are often faced with the dilemma of choosing between a metallic or tissue valve replacement.

"A metallic valve is long lasting but requires the patient to take lifelong blood thinning drugs. Although this medication prevents clots forming on the valve, it also increases the risk of serious bleeding.

"Patients who have a tissue valve replacement usually don't need to take this medication. However, the valve is less durable and means the patient may face further surgery.

"The polymer valve combines the benefits of both - it is durable and would not require the need for blood thinning drugs. While further testing is needed before this valve can be used in patients, this is a promising development, and the BHF is pleased to have supported this research."

According to the ISO standards a new artificial heart valve must withstand a minimum of 200 million repetitions of opening and closing during bench testing (equivalent to five-year of life span) to be tested in humans. The new Cambridge-Bristol polymeric valve has comfortably surpassed this.

The PoliValve has also exceeded the requirements of ISO standards for hydrodynamic testing, showing a functional performance in-vitro comparable to the best-in-class biological valve currently available on the market. The small feasibility pilot study in-vivo in three sheep at one to 24 hours after surgery has demonstrated the valve is easy to stitch in, no mechanical failure, no trans-valvular regurgitation, low trans-valvular gradients, and good biocompatibility at histopathology.

Professor Ascione added: "The transformational PoliValve results from an advanced Bristol/Cambridge-based biomedical cross-fertilisation between experts in biomaterials, computational modelling, advanced preclinical development/testing and clinical academics understanding the patient needs. The new valve could help millions of people worldwide and we aim to test in patients within the next five years."

A type of smart MRI scan used in people with heart disease could help assess whether children's cancers are especially aggressive and spot early signs that targeted treatments are working, a new study suggests.

Researchers showed that the MRI imaging technique, known as T1-mapping, could offer crucial insights into the biology of childhood cancers and give an early warning of how effective targeted treatments were likely to be.

T1 mapping scans measure how water molecules interact at a microscopic level inside cells to understand the cellular make-up of tissue, and are used in heart disease to assess damage to heart muscle tissue.

Now scientists at The Institute of Cancer Research, London, have shown that the non-invasive scanning technique has the potential to pick out children with high-risk forms of neuroblastoma, a type of childhood tumour.

The researchers believe T1 mapping scans could improve the use of precision medicine in children with neuroblastoma and potentially in cancer patients more widely, by ensuring treatments are tailored for each patient, and rapidly stopped when they are not working.

The study was published today (Monday) in the journal Cancer Research and funded by Children with Cancer UK, Cancer Research UK and The Rosetrees Trust.

Researchers studied T1 mapping in mice with an aggressive form of neuroblastoma to get a clear picture of the microscopic and physical characteristics of the tumour.

The team at The Institute of Cancer Research (ICR) used artificial intelligence to map the different cell populations in tumours and compared these maps with those created using non-invasive T1 mapping MRI scans.

The researchers found that regions with high T1 values - where water molecules can behave 'more freely' - corresponded to hotspots of more aggressive cancer cells, which spread and grow faster. Meanwhile, areas with low T1 values corresponded to more benign or dead tissue, which is less harmful.

The researchers also looked at whether the imaging technique could help assess how mice with neuroblastoma would respond to two targeted drugs, alisertib and vistusertib, which target MYCN, a key protein linked to aggressive forms of the disease.

They found that when alisertib and vistusertib successfully stopped the growth of tumours in mice, there was a decrease in T1 measures - reflecting the death of aggressive cancer cells. This suggests T1 measures could be used as a biomarker - a measurable indicator which can guide treatment by indicating whether a drug is working or not.

The researchers believe aggressive cancer cells have high T1 values because they tend to be small, but have large nuclei - the control centres within each cell containing our DNA, near which water can behave 'more freely'.

By evaluating tumours' cellular make-up with T1 MRI scans, clinicians would be able to get an accurate understanding of the stage and aggressiveness of the disease in children with neuroblastoma.

Next, researchers at the ICR - a charity and research institute - plan to assess the clinical benefit of T1 mapping as part of a clinical study involving children.

The new research is the first to assess the benefit of the MRI technique as a 'smart' cancer biopsy - and researchers believe the results could be replicated more widely in other cancer types in children and adults.

Study leader Dr Yann Jamin, Children with Cancer UK Research Fellow at The Institute of Cancer Research, London, said:

"Our findings show that an imaging technique readily available on most MRI scanners has the potential to pick out children with aggressive cancer and give us early signs of whether a treatment is working. We've shown in mice that this technique can give us detailed insights into the biology of neuroblastoma tumours and help guide use of precision medicine, and next we want to assess its effectiveness in children with cancer.

"It is easy to perform and analyse T1 MRI scans, and they could be used to provide insights into many aspects of cancer biology - and help doctors to design tailored treatments based on how aggressive a tumour appears to be."

Professor Paul Workman, Chief Executive of The Institute of Cancer Research, London, said:

"It's exciting that we've shown that a scan widely used to image the heart has the potential to greatly improve our understanding and treatment of cancer too. There is already a lot of experience in using this technique in NHS hospitals, and I hope we can rapidly move to assessing its use in clinical trials of cancer patients.

"It's vital that we find ways to improve treatments for aggressive childhood cancers like neuroblastoma - and also that we spare children unnecessary side effects by minimising exposure to drugs that do not seem to be working."

Mark Brider, Chief Executive Officer, Children with Cancer UK said:

"Neuroblastoma is one of the most common childhood tumours with around 100 children, mostly under five years old, diagnosed every year in the UK. Yet it also has one of the lowest survival rates and in its high-risk form is one of the most difficult childhood cancers to cure.

"It is crucial that we find more effective and personalised treatments for children with neuroblastoma. The findings of Dr Jamin and his team represent an important step towards the development of new and kinder treatments that reduce the burden of toxicity for young cancer patients and improve survival rates in this aggressive and hard-to-treat cancer."

TROY, N.Y. -- Chemically engineered peptides, designed and developed by a team of researchers at Rensselaer Polytechnic Institute, could prove valuable in the battle against some of the most persistent human health challenges.

The team’s findings, recently published in Nature Scientific Reports, demonstrate how researchers can engineer peptides capable of selectively and specifically binding to polysialic acid (PSA) — a unique carbohydrate that is present on critical human cells and plays a key role in various physiological and pathological processes, including neurological development and disease progression.

This foundational research lays the groundwork for further study into the ability of these peptides to provide an effective vehicle for therapeutics in the treatment of diseases such as Alzheimer's, Parkinson's, and cancer. The team's findings suggest the peptides may also prove valuable in providing a barrier between cells and viruses, such as the one that causes COVID-19 - a possibility the research team now hopes to study.

"Because these peptides bind to PSA, they also mask PSA, and could potentially be used to inhibit the binding of viruses and their entry into cells," said Pankaj Karande, an associate professor of chemical engineering, a member of the Center for Biotechnology and Interdisciplinary Studies (CBIS), and one of the lead authors on this paper. "The idea is to see if these peptides could inhibit that interaction and therefore inhibit the infectivity of those viruses."

Taking inspiration from nature, Karande said the team modeled its peptides based on the binding of proteins known as Sialic acid-binding immunoglobulin-type lectins, or Siglecs, which occur naturally and inherently bind to sialic acids.

The research laid out in the paper was also led by Divya Shastry, a former doctoral student in biological sciences at Rensselaer. It was completed in collaboration with Robert Linhardt, an endowed professor of chemistry and chemical biology, and Mattheos Koffas, an endowed professor of chemical and biological engineering, both of whom are members of CBIS as well. The Rensselaer team also worked with a team from Syracuse University that used computational modeling to provide the Rensselaer researchers with a molecular-level look at the peptides they designed.

"These significant and promising research advances are a prime example of how a collaborative approach can solve persistent human health challenges," said Deepak Vashishth, the director of CBIS.