Newswise — It’s time for your primary care check-up, and the doctor asks you to list any known drug allergies. “Penicillin,” you say immediately, although you can’t remember actually taking the drug or having a reaction to it—it was your parents who said so. According to a Texas A&M Health Science Center allergist, many people who believe they’re allergic to this antibiotic may not actually be allergic at all. “Hypersensitivity reactions are the major problem in the use of penicillin,” said Thomas Leath, M.D., an allergist with the Texas A&M College of Medicine. “Many people who report a penicillin allergy don’t even know why. It could be because they had a reaction when they were very young, or, because a family member had an allergic reaction and told their children not to take penicillin.” Penicillin, which has been around since 1928, is used to treat a variety of conditions, from strep throat to ear infections. It’s also the base of many front-line drugs. When you are allergic to penicillin, you’re often forced to take more expensive alternatives, which can have more side effects. Penicillin allergies are widely listed in patient histories, but, a Mayo Clinic study found 80 to 90 percent of patients who listed a penicillin allergy had no real evidence of a true reaction and avoided the drug unnecessarily. Moreover, anaphylaxis (a severe, potentially life-threatening allergic reaction) to penicillin is still quite rare. Inappropriate prescribing of antibiotics for conditions they cannot treat (cold, flu etc.,) has led to a rise in deadly ‘superbugs’—bacteria that can’t be killed with standard antibiotics—and could be another reason why people suspect they have a penicillin allergy. “Penicillin will not treat viruses like the common cold,” Leath said. “When someone is prescribed an antibiotic for a virus they may break out in a rash, or experience other side effects, falsely attributed to penicillin.” An actual allergic reaction to penicillin can cause symptoms along a wide spectrum. A person with a mild reaction to the drug may break out in hives, but more severe signs can occur, including swelling of the lips, tongue and throat, as well as asthma-like symptoms. Vomiting, nausea and diarrhea also indicate a true allergic reaction. “Penicillin allergies can even drop your blood pressure, cause dizziness or loss of consciousness,” Leath said. “If you experience almost all these symptoms listed, and at the same time, you’re having an anaphylactic (life-threatening) reaction and need to see a health care provider immediately.” According to Leath, it’s important to recognize the difference between an allergic reaction to penicillin and the drug’s reported side effects. “True allergic reactions happen quickly after exposure—usually within 10 to 15 minutes or within an hour or two of taking the drug,” he said. “If you have a reaction, like an upset stomach, three days after beginning a penicillin regimen, you probably aren’t allergic.” That sort of reaction would be considered a side effect, not an allergy. Worth noting: Penicillin is the only antibiotic with a skin test protocol—there’s really no standard way to test and confirm allergies to other antibiotics. However, experts can often discover what’s wrong. “As an allergist, I can frequently tease out the real reason for the problem just by talking with the patient about how and when certain symptoms occurred,” Leath said. “We can then discern if they are truly allergic or not.” This skin test protocol helps determine if a patient’s penicillin allergy actually exists if they have outgrown the allergy. If a penicillin reaction was reported when a patient was very young, the immune system may ‘forget’ the allergy if the antibiotic is never taken again. Leath said 10 years later, up to 90 percent of people will have outgrown a penicillin allergy. “This is because the immune system doesn’t receive the stimulus that prompts an allergic reaction,” he said. “Even if a patient did have a true allergy, the chances of it still being present in the next 10 years is very low.” Nonetheless, this doesn’t always mean it’s safe to take penicillin after reporting an allergic reaction to it. “If patients have an allergic reaction to penicillin—even a mild one—it ups the potential for having another more severe reaction,” Leath said. “This is always a conversation to have with your health care provider to discuss the best options for your health and treatment.”
Newswise — Researchers report in the journal Cancer Cell an experimental therapy that in laboratory tests on human cells and mouse models stops aggressive, treatment-resistant and deadly brain cancers called glioblastoma and high-grade gliomas. A multi-institutional team led by researchers at Cincinnati Children’s Hospital Medical Center publishes their results on May 9. Testing a multi-step therapeutic strategy, the scientists found a way to use a gene therapy to shut down a gene long-implicated in the formation of high-grade gliomas called Olig2. The protein encoded by Olig2 is expressed in the majority of gliomas. Removing the Olig2 gene halts tumor growth, while elimination of Olig2-producing cells blocks tumor formation. “We find that elimination of dividing Olig2-expressing cells blocks initiation and progression of glioma in animal models and further show that Olig2 is the molecular arbiter of genetic adaptability that makes high-grade gliomas aggressive and treatment resistant,” said Qing Richard Lu, PhD, lead investigator and scientific director of the Brain Tumor Center at Cincinnati Children’s. “By finding a way to inhibit Olig2 in tumor forming cells, we were able to change the tumor cells’ makeup and sensitize them to targeted molecular treatment. This suggests a proof of principle for stratified therapy in distinct subtypes of malignant gliomas.” The current study may apply to high-grade brain gliomas and a fatal brainstem tumor called DIPG (Diffused Intrinsic Pontine Glioma), which expresses Olig2 and is inoperable because of its location in a brain region controlling vital functions. Even if these cancers do initially respond to a specific targeted treatment, they adapt by finding genetic/molecular workarounds, evade treatment and continue growing. Researchers caution the experimental therapeutic approach they describe requires extensive additional research and remains years away from possible clinical testing. Still, Dr. Lu said the data are a significant research breakthrough. The current study finds a potential chink in the molecular armor of these stubborn cancers that – even after an initial round of successful treatment – almost always relapse and kill the patients who get them. The cancers form from precursors of supporting brain cells called oligodendrocytes, which help generate insulation for neural connections. Olig2 appears at the early stages of brain cell development. Through extensive analysis of human brain cancer cells and mouse models, the researchers observed Olig2 expression in early-stage dividing and replicating cells in tumors. Olig2 contributes to the transformation of normal precursor cells into abnormal malignant cells that divide uncontrollably. In the context of cancer cell formation, the researchers saw Olig2 drive molecular processes that allow forming glioma cells to be highly adaptable and susceptible to the tumor-promoting effects of additional genetic changes. Researchers then decided to eliminate Olig2-positive dividing cells during tumor formation. To use an approach more rapidly translatable from the laboratory bench to clinical bedside, they successfully tested a gene therapy that uses an engineered herpes simplex virus (viral vector) to deliver a suicide gene into replicating Olig2-positive cancer cells. They next administered an anti-herpes drug already in clinical use, ganciclovir (GCV). The Olig2-deleted tumors were not able to grow. Researchers also found that after Olig2 was inhibited, the forming brain cancer cells switched directions and molecular composition– going from the cells resembling oligodendrocyte precursors to assume astrocyte-like brain cell characteristics. They continued to form tumors, however these newly formed astrocyte-like brain cancer cells produce the epidermal growth factor receptor (EGFR) gene at high levels. EGFR is a common and effective target for chemotherapy drugs used clinically to treat tumors such as breast cancers. In repeated tests in mouse models, Olig2 inhibition prompted the glioma-forming cells to transform into EGFR-expressing astrocyte-like cells. Then, in subsequent and repeated testing on the transformed human and mouse model astrocyte-like cancer cells, the researchers treated the cells with an EGFR-targeted chemotherapy drug called gefitinib. The treatment stopped the growth of new tumor cells and tumor expansion. Dr. Lu said that with additional testing, verification and refinement the experimental therapy could be especially helpful in preventing a recurrence of brain cancer in patients who have undergone an initial round of successful treatment. He added the new treatment approach would likely be used in combination with other existing therapies like radiation, surgery, other chemotherapies and targeted molecular treatments. The scientists continue their research with additional testing in human cell lines and “humanized” mouse models of high-grade glioma. The mouse models are engineered to grow brain tumors derived from the tumor cells of specific patients whose families have donated biopsy samples for research. This allows researchers to test different targeted drugs in their therapeutic protocol that may best match the genetic makeup of tumors from specific individuals. Funding support for the study came in part from the National Institutes of Health (R01NS078092, R01NS075243).About Cincinnati Children’sCincinnati Children’s Hospital Medical Center ranks third in the nation among all Honor Roll hospitals in U.S. News and World Report’s 2015 Best Children’s Hospitals. It is also ranked in the top 10 for all 10 pediatric specialties, including a #1 ranking in pulmonology and #2 in both cancer and nephrology. Cincinnati Children’s, a non-profit organization, is one of the top three recipients of pediatric research grants from the National Institutes of Health, and a research and teaching affiliate of the University of Cincinnati’s College of Medicine. The medical center is internationally recognized for improving child health and transforming delivery of care through fully integrated, globally-recognized research, education and innovation. Additional information can be found at www.cincinnatichildrens.org. Connect on the Cincinnati Children’s blog, viaFacebook and on Twitter.
Newswise — A new registry that launches this month gives women who have uterine fibroids the opportunity to help determine which strategies are most effective in treating the common condition. The registry, called Comparing Options for Management: Patient-Centered Results for Uterine Fibroids (COMPARE-UF), will enroll more than 10,000 women at clinics affiliated with nine medical centers across the country. Participating women will be asked at annual intervals specific questions about the treatments they’ve elected to receive, and how well the treatments seem to be working for them. Approximately three years after initial treatment, researchers at the Duke Clinical Research Institute (DCRI) will analyze the patients’ feedback to determine which procedures provide the greatest benefit to women – insights that have been lacking for both women and their physicians. Specifically, studies will focus on symptom relief, reproductive effects, and effectiveness among different patient subgroups, including African-American women, who are disproportionately affected by uterine fibroids. “This is a common condition – it affects up to 75 percent of women to varying degrees and is the leading cause of hysterectomies in the country – yet we don’t know which treatment works best for a given patient,” said the study’s principal investigator, Evan Myers, M.D., professor in the Department of Obstetrics and Gynecology at Duke University School of Medicine. “Patients have clearly stated that they wanted these questions answered, but preferred a registry to randomized trials, particularly because hysterectomy is one of the current options,” Myers said. The registry was funded in 2013 with a $20 million funding award from the Patient-Centered Outcomes Research Institute (PCORI), in partnership with the Agency for Healthcare Research and Quality (AHRQ), which provides scientific oversight and administration. The DCRI serves as the research and data coordinating center for the five-year project. Enrollments sites include Mayo Clinic Collaborative Network, University of California Fibroid Network, Henry Ford Health System, University of Mississippi Medical Center, University of North Carolina, Brigham and Women/Harvard Clinical Center, Inova Health Systems and the Department of Defense Clinical Consortium. The University of Michigan will become an enrollment site later this year. Potential participants must have a documented diagnosis of uterine fibroids and be older than 18 and young enough to still have menstrual periods. Current treatments to be evaluated are hysterectomy (removal of the uterus), myomectomy (removal of the fibroids within the uterus), endometrial ablation (laser or heat treatments to destroy the uterine lining), radiofrequency ablation (using radio waves to destroy the fibroid), uterine artery embolization (blocking blood supply to the uterus), and magnetic resonance guided focused ultrasound (using ultrasound to destroy the fibroids). The study will add other treatments, including medications. “Uterine fibroids have a big impact on women’s quality of life, affecting their ability to work and to participate in the things that they enjoy,” Myers said. “There are also high costs, both in treatments and in managing the pain and heavy bleeding that many women experience. “One of the things that makes fibroids difficult to study is that they cause lots of different kinds of symptoms, and the symptoms can be complex, ranging from fairly minor discomfort to infertility,” Myers said. “This registry for the first time will help us collect strong, relevant information from the patients themselves that can then be analyzed to determine what treatments work best for which women.” Patient advocacy groups, which had been integral in helping design the study, said the registry launch this month is a much-anticipated milestone. "There are far too many women suffering with complications from uterine fibroids. This research effort initiated by AHRQ and PCORI is groundbreaking and crucial,” said Sateria Venable, founder & executive director of the Fibroid Foundation. “My hope is that COMPARE-UF will lead the way to more consistently and adequately funded fibroid research. If we focus our efforts, we will reap the rewards - health, fertility and quality of life."
Newswise — It is well known that men and women differ in terms of cancer susceptibility, survival and mortality, but exactly why this occurs at a molecular level has been poorly understood. A study at The University of Texas MD Anderson Cancer Center reviewed 13 cancer types and provided a molecular understanding of sex effects in diverse cancers. The research revealed two cancer-type groups associated with cancer incidence and mortality, suggesting a “pressing need” to develop sex-specific therapeutic strategies for some cancers. The research findings are published in the May 9 online issue of Cancer Cell. Using data from The Cancer Genome Atlas, a team led by Han Liang, Ph.D., associate professor of Bioinformatics and Computational Biology, found more than half of the genes studied that were related to clinical practice of cancer treatment showed sex-biased signatures in certain cancer types. “Our study helps elucidate the molecular basis for sex disparities in cancer and lays a critical foundation for the future development of precision cancer medicine that is sex-specific,” said Liang. “This is a crucial finding as currently, male and female patients with many cancer types often are treated in a similar way without explicitly considering their gender.” Liang’s group performed a comprehensive analysis of molecular differences between male and female patients, revealing two sex-effect groups associated with distinct incidence and mortality profiles and accounting for 53 percent of clinically actionable genes. Those genes are informative for clinical decisions and are either therapeutic targets or biomarkers that can help predict patient survival or tumor response. In the study, Liang found one group contained a small number of sex-affected genes (weak group), while the other showed a much greater number of sex-biased molecular signatures (strong group). Liang said the current equal treatment of both genders may be appropriate for those in the “weak” group, but observations in the “strong” group are clinically significant. “Special consideration should be given to those in the strong sex-effect group in terms of both drug development and practice,” said Liang. “For a therapeutic target with a strong sex-biased signature, sex-specific clinical trials may be more likely to succeed. This new information is vital as the fundamental issue of sex differences for cancer prevention and therapy has not been investigated systematically.” Liang’s team analyzed data in patient cohorts of 30 or greater samples for each sex for various cancers of the bladder, colon, kidney, brain, rectum, thyroid, liver and lung as well as acute myeloid leukemia. They looked for specific molecular data including somatic mutations, copy alterations, protein and gene expression and DNA methylation. The study included controls for other factors such as race, age, disease stage, smoking status and tumor purity. “Interestingly, our analysis also suggested that sex bias might be amplified during the tumor formation process,” said Liang. “However this observation should be interpreted with caution at this early stage as further efforts are needed to determine the relative contributions of other factors, including tumorigenesis, sex chromosomes and hormones.” MD Anderson members of the study team included Yuan Yuan, Ph.D., and Jun Li, Ph.D., of Bioinformatics and Computational Biology; Huzhang Ma, Ph.D., and Liang Li, Ph.D., Biostatistics; and Gordon Mills, M.D., Ph.D., Systems Biology. Other participating institutions included Baylor College of Medicine, Houston; Johns Hopkins University, Baltimore; The University of Texas Health Science Center at Houston; and Nanjin Medical University, Nanjing, China. The study was funded by the National Institutes of Health (CA175486 and CA016672), the Cancer Prevention and Research Institute of Texas (RP140462), the Jeanne F. Shelby Scholarship Fund, the Lorraine Dell Program in Bioinformatics for Personalization of Cancer Medicine, the National Natural Science Foundation of China (81472782), the Natural Science Foundation of Jiangsu Province (BK20141491), Six Talent Peaks Foundation of Jiangsu Province (2012-WS-026) and the “333” Talents Project of Jiangsu Province.
Newswise — Consuming a high-fructose diet during pregnancy may cause defects in the placenta and restrict fetal growth, potentially increasing a baby’s risk for metabolic health problems later in life, according to research in mice and people by a team at Washington University School of Medicine in St. Louis. However, giving the mice allopurinol, a generic drug frequently prescribed to treat gout and kidney stones, appears to mitigate the negative maternal and fetal effects. The findings suggest it may be possible to devise a prenatal screening test and treatment plan for pregnant women with high fructose levels. The study is available online in Scientific Reports, a journal affiliated with Nature Publishing Group. Fructose, a sugar occurring naturally in fruits and honey, has been popular for decades among food manufacturers who process it into high-fructose corn syrup used to sweeten food and beverages. In fact, researchers have reported that the refined sugar accounts for more than half of all sweeteners used in the U.S. food-supply chain. And in recent years, there’s growing concern that fructose in processed foods and sugary drinks may be linked to diabetes and obesity. “Since the early 1970s, we’ve been eating more fructose than we should,” said Kelle H. Moley, MD, the School of Medicine’s James P. Crane Professor of Obstetrics and Gynecology and the study’s senior author. “It is becoming increasingly critical to understand how fructose consumption is impacting human health. This study shows potentially negative effects of a high-fructose diet during pregnancy.” Fructose is processed differently than other sugars such as glucose, which the body converts into energy. Instead, fructose is broken down by liver cells that turn the sugar into a form of fat known as triglycerides while also driving high levels of uric acid, a normal waste product found in urine and stool. Too much uric acid can create metabolic mayhem resulting in obesity, type 2 diabetes and other health conditions. Studying mice, the researchers found elevated uric acid and triglycerides in otherwise healthy mice who were fed a high-fructose diet during pregnancy. Additionally, the mice developed smaller fetuses and larger placentas than those fed standard rodent chow. Genetically, Moley said, a small fetus may become wired to grow more after birth than a normal-sized fetus. “The body tries to compensate for the small growth in utero,” Moley said. “These babies can become kids and then adults struggling with obesity and other health problems.” Maternal health also may suffer. Metabolic problems caused by high levels of uric acid and fat increase a woman’s risk of developing pregnancy complications such as preeclampsia — a potentially serious condition in pregnancy often marked by high blood pressure, swelling and high protein levels in the urine — and gestational diabetes, Moley said. To assess the relevance of the mouse data in pregnant women, the researchers examined the association between fructose and placental uric acid levels in a small controlled group of 18 women who underwent scheduled cesarean sections. The women had no disorders that would have caused elevated uric acid. “We found a correlation suggesting similar maternal and fetal effects occur in humans,” Moley said. In the mouse model, researchers found that giving mice with high-fructose levels the common drug allopurinol – a prescription medication that reduces uric acid — reversed the refined sugar’s negative maternal and fetal effects by reducing the levels of uric acid in the placenta. “The negative effect of excess fructose in humans is likely to lead to an exacerbation of the problems seen in the mice,” said Moley, who believes additional research may lead to a prenatal screening test for measuring fructose levels. This can be determined by simple blood work. Besides advising pregnant women to limit fructose in their diets, treatment for those with high-fructose levels may include administering allopurinol, which crosses the placenta and generally is considered safe to take late in the second trimester or third trimester during pregnancy, Moley said. “One of the best ways to ensure healthy maternal and fetal outcomes is by eating natural foods,” she said. Future studies will test the effectiveness of giving allopurinol to pregnant women when there is concern about fetal growth, Moley added. The study’s lead author was Zeenat Asghar, a graduate student in molecular cell biology in the university’s Division of Biology and Biomedical Sciences.
Newswise — Pterostilbene (PS), a component of blueberries, have been found to protect against dry eye disease according to a new study. The research is being presented at the 2016 Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO) this week in Seattle, Wash. When introduced to human corneal epithelial cells, PS significantly reduced the levels of oxidative damage, which in turn reduced inflammation. Inflammation can contribute to dry eye disease, a condition that becomes increasing common with age. PS is a molecule chemically related to resveratrol. Abstract Title: Blueberry Component Pterostilbene Protects Corneal Epithelial Cells from Inflammatory and oxidative stress The Association for Research in Vision and Ophthalmology (ARVO) is the largest eye and vision research organization in the world. Members include nearly 12,000 eye and vision researchers from over 75 countries. ARVO advances research worldwide into understanding the visual system and preventing, treating and curing its disorders.All abstracts accepted for presentation at the ARVO Annual Meeting represent previously unpublished data and conclusions. This research may be proprietary or may have been submitted for journal publication. Embargo policy: Journalists must seek approval from the presenter(s) before reporting data from paper or poster presentations. Press releases or stories on information presented at the ARVO Annual Meeting may not be released or published until the conclusion of the presentation.
Newswise — In a study prompted in part by suggestions from people with mental illness, Johns Hopkins researchers found that a history of Candida yeast infections was more common in a group of men with schizophrenia or bipolar disorder than in those without these disorders, and that women with schizophrenia or bipolar disorder who tested positive for Candida performed worse on a standard memory test than women with schizophrenia or bipolar disorder who had no evidence of past infection. The researchers caution that their findings, described online on May 4 in npj Schizophrenia — a new publication from Nature Publishing Group — do not establish a cause-and-effect relationship between mental illness and yeast infections but may support a more detailed examination into the role of lifestyle, immune system weaknesses and gut-brain connections as contributing factors to the risk of psychiatric disorders and memory impairment. “It’s far too early to single out Candida infection as a cause of mental illness or vice versa,” says Emily Severance, Ph.D., assistant professor of pediatrics and member of the Stanley Division of Developmental Neurovirology at the Johns Hopkins University School of Medicine. “However, most Candida infections can be treated in their early stages, and clinicians should make it a point to look out for these infections in their patients with mental illness.” She adds that Candida infections can also be prevented by decreased sugar intake and other dietary modifications, avoidance of unnecessary antibiotics, and improvement of hygiene. Candida albicans is a yeastlike fungus naturally found in small amounts in human digestive tracts, but its overgrowth in warm, moist environments causes burning, itching symptoms, thrush (rashes in the throat or mouth) in infants and those with weakened immune systems, and sexually transmittable genital yeast infections in men and women. In its more serious forms, it can enter the bloodstream. In most people, the body’s own healthy bacteria and functioning immune system prevent its overgrowth. Severance says she and her team focused on a possible association between Candida susceptibility and mental illness in the wake of new evidence suggesting that schizophrenia may be related to problems with the immune system, and because some people with weakened immune systems are more susceptible to fungal infections. Also, she says, patients and parents of patients had shared personal stories and testimonials with the researchers about their experience with yeast infections, and these discussions prompted the investigation into possible links between mental illness and the microbiome — the body’s natural collection of bacteria. The researchers, she adds, chose to focus on Candida because it is one of the most common types of yeast in the body. For the study, colleagues from the Sheppard Pratt Health System took blood samples from a group of 808 people between the ages of 18 and 65. This group was composed of 277 controls without a history of mental disorder, 261 individuals with schizophrenia and 270 people with bipolar disorder. The researchers used the blood samples to quantify the amount of IgG class antibodies to Candida, which indicates a past infection with the yeast. After accounting for factors like age, race, medications and socioeconomic status, which could skew the results, they looked for patterns that suggested links between mental illness and infection rates. Significantly, the team says, it found no connection between the presence of Candida antibodies and mental illness overall in the total group. But when the investigators looked only at men, they found 26 percent of those with schizophrenia had Candida antibodies, compared to 14 percent of the control males. There wasn’t any difference found in infection rate between women with schizophrenia (31.3 percent) and controls (29.4 percent). The higher infection rate percentages in women over men likely reflects an increased susceptibility for this type of infection in all women. Men with bipolar disorder had clear increases in Candida as well, with a 26.4 percent infection rate, compared to only 14 percent in male controls. But, after accounting for additional variables related to lifestyle, the researchers found that the association between men with bipolar disorder and Candida infection could likely be attributed to homelessness. However, the link between men with schizophrenia and Candida infection persisted and could not be explained by homelessness or other environmental factors. Many people who are homeless are subjected to unpredictable changes in stress, sanitation and diet, which can lead to infections like those caused by Candida. Severance says the data add support to the idea that environmental exposures related to lifestyle and immune system factors may be linked to schizophrenia and bipolar disorder, and that those factors may be different for each illness. Similarly, specific mental illnesses and related symptoms may be very different in men versus women. This Johns Hopkins research group, led by Robert Yolken, M.D., director of the Stanley Division of Developmental Neurovirology, had previously shown that toxoplasmosis infection could trigger schizophrenia, and this could lead to neurocognitive problems. The organism that causes toxoplasmosis is a parasite that uses cats as its primary host, but it can also infect humans and other mammals. To determine whether infection with Candida affected any neurological responses, all participants in the new study took a 30-minute assessment of cognitive tasks to measure immediate memory, delayed memory, attention skills, use of language and visual-spatial skills. Each of the five skills tests are scored based on an adjusted 100-point system. Results showed that control men and women with and without prior Candida infection had no measureable differences in scores in the five neurological responses. However, the researchers noticed that women with schizophrenia and bipolar disorder who had a history of Candida infection had lower scores on the memory portions of this test compared to those women with no prior infection. For example, women with schizophrenia and the highest Candida antibody levels scored about an average of 11 points lower on the test for immediate memory than the controls, from a score of 68.5 without infection to 57.4 with infection. And the women with schizophrenia and the highest Candida antibody levels scored almost 15 points lower on the test for delayed memory, from a score of 71.4 without infection to 56.2 with infection. The effect of Candida infection in women with bipolar disorder on memory test scores was smaller than that seen in women with schizophrenia but was still measureable. “Although we cannot demonstrate a direct link between Candida infection and physiological brain processes, our data show that some factor associated with Candida infection, and possibly the organism itself, plays a role in affecting the memory of women with schizophrenia and bipolar disorder, and this is an avenue that needs to be further explored,” says Severance. “Because Candida is a natural component of the human body microbiome, yeast overgrowth or infection in the digestive tract, for example, may disrupt the gut-brain axis. This disruption in conjunction with an abnormally functioning immune system could collectively disturb those brain processes that are important for memory.” Severance says they plan to take their studies of the gut-brain connection into mouse models to test for a cause-and effect-relationship with Candida and memory deficits. The researchers emphasized that the current study design had limitations. For example, they were unable to tell where in the body the infection was located and whether or not participants had a current or past infection of Candida. The researchers were also not able to account for every possible lifestyle variable that might contribute to these results. The researchers in the Stanley Division of Developmental Neurovirology are investigating whether pathogens, such as bacteria or viruses, may contribute or trigger certain mental disorders. According to the National Institute of Mental Health, about 1 percent of people in the U.S. have schizophrenia and about 2 percent have bipolar disorder. Although these diseases have a genetic component, there is evidence that they may also be triggered by environmental factors and stress. Additional authors on the study include Kristin Gressitt of Johns Hopkins Medicine; Catherine Stallings, Emily Katsafanas, Lucy Schweinfurth, Christina Savage, Maria Adamos, Kevin Sweeney, Andrea Origoni, Sunil Khushalani and Faith Dickerson of Sheppard Pratt Health System; and F. Markus Leweke of Heidelberg University.The study was supported by a research grant from the National Institute of Mental Health (MH-94268) and a grant from the Stanley Medical Research Institute. The authors also thank the individuals with psychiatric disorders and their families who originally suggested this line of research.
Newswise — The discovery of long non-coding RNA (lncRNA) has dramatically changed the understanding of the biology of diseases such as cancer. The human genome contains about 20,000 protein-coding genes – less than 2 percent of the total – but 70 percent of the genome is made into non-gene-encoding RNA. Take triple-negative breast cancer (TNBC), an aggressive subtype with poor clinical outcome, for example. Genomic studies of TNBC to crack its tough-to-treat status have mainly focused on protein-coding genes and the function of non-coding genes is still largely unknown. Using a clinically guided genetic screening approach, researchers from the Perelman School of Medicine at the University of Pennsylvania identified LINP1, a lncRNA. This lncRNA is overexpressed in triple-negative breast cancer cells and regulated by the tumor suppressor p53 and the activated cell surface protein, EGFR. LINP1 enhances the repair of DNA breaks by serving as a scaffold that links two other proteins in the repair machinery. A BRCA1 mutation is associated with a higher risk for TNBC, which represents about 10 to 20 percent of all breast cancer cases. TNBC test negative for both the estrogen and progesterone receptors and the cell surface receptor Her2, hence its name. Since hormones are not supporting growth, the cancer is unlikely to respond to hormonal therapies and medications that target HER2. Because of these limited therapeutic targets, many cancers, including TNBCs, are typically treated with surgery and a combination of radiation and chemotherapy that induce various types of DNA damage. However, many TNBC patients are resistant to these combination therapies. With support from the Basser Center for BRCA at Penn, the team was led by senior authors Lin Zhang, MD, the Harry Fields Associate Professor of Obstetrics and Gynecology, Chi V. Dang, MD, PhD, director of the Abramson Cancer Center, and first author Youyou Zhang, MD, PhD, a postdoctoral fellow in the department of Obstetric and Gynecology. They published their findings this week in Nature Structural & Molecular Biology. Recent studies, including publications from the Penn group, have identified lncRNAs with tumor suppressive and oncogenic activities in cancers. Building BridgesThe two repair scaffold proteins, Ku80 and DNA-PKcs, that LINP1 links coordinate the non-homologous end-joining (NHEJ) repair molecules that fix double-strand breaks in DNA. Importantly, the team found that blocking LINP1 significantly increases sensitivity by the tumor cells to radiation therapy. The NHEJ pathway, which repairs double-strand breaks in DNA, is one of the major pathways in tumor cells that respond to radiation treatment and chemotherapeutic agents. Inhibition of the NHEJ pathway has been proposed by oncology researchers to synergize DNA-damaging therapies for better treatment outcomes for TNBCs. “Given the important role of LINP1 in the NHEJ pathway, our study indicates that this new class of cancer-driver gene -- the lncRNAs -- may serve as unique therapeutic targets and novel biomarkers in cancer,” Zhang said. “Collectively, our study provides new insight into the DNA damage repair pathway, long non-coding RNAs, and triple-negative breast cancer.” Qun He, Zhongyi Hu, Yi Feng, Lingling Fan, Zhaoqing Tang, Jiao Yuan, Weiwei Shan, Chunsheng Li, Xiaowen Hu, Janos L Tanyi, Yi Fan, Qihong Huang, and Kathleen Montone, all from Penn, are coauthors. The research was also supported by the National Institutes of Health (R01CA142776, R01CA190415; P50CA083638, P50CA174523, R01CA148759, R01NS094533), the Breast Cancer Alliance, the Ovarian Cancer Research Fund, the Foundation for Women’s Cancer, and the Marsha Rivkin Center for Ovarian Cancer Research. Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $5.3 billion enterprise. The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 18 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $373 million awarded in the 2015 fiscal year. The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center -- which are recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report -- Chester County Hospital; Lancaster General Health; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Chestnut Hill Hospital and Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine. Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2015, Penn Medicine provided $253.3 million to benefit our community.
Newswise — Researchers have known for more than a decade that the risk of heart disease and stroke increases when people take pain relievers like ibuprofen and other non-steroidal anti-inflammatory drugs, or NSAIDs. Now, scientists from the University of California, Davis, have uncovered some of the reasons why these drugs can harm heart tissue. The study was recently published online in the Journal of Molecular and Cellular Cardiology. Working with heart cells from rats and mice, the team found that NSAIDs: ∙ Attack mitochondria, reducing the cardiac cell’s ability to produce energy;∙ Cause the production of reactive oxygen species, which stresses heart cells and is associated with many diseases, including heart disease;∙ Impair the cardiac cell’s proteasome, the mechanism for degrading harmful proteins. This leads to toxic buildup and eventually to the death of cardiac cells. “We knew these non-steroidal anti-inflammatories had negative side effects for heart disease and stroke risk, “ said corresponding author Aldrin Gomes, a UC Davis associate professor of Neurobiology, Physiology and Behavior. “But now we have an idea of some of the mechanisms behind it.” Drugs affect cardiac cells The scientists compared naproxen, considered the safest available NSAID and available over the counter, with another, more potent anti-inflammatory, the prescription drug meclofenamate sodium. They found that: ∙ The prescription drug was more likely to negatively impact heart health than naproxen.∙ Naproxen did not affect proteasome function or cause heart cells to die. It did, however, impair mitochondrial function and increase reactive oxygen species produced in cardiac cells. It also is associated with an increase in the chance of stroke.∙ Meclofenamate sodium increased reactive oxygen species, impaired mitochondrial function, decreased proteasome function, and increased cardiac cell death.∙ “We were surprised to see that many of the NSAIDs we tested were causing the cardiac cell to die when used for prolonged periods,” said Gomes. “Some people are taking these drugs too often, and this is a problem. These drugs are abused.”Vitamin C may help decrease risk The study results suggest that ingesting an antioxidant, like vitamin C, before taking a NSAID may prevent cardiac cell death without interfering with the drug’s ability to provide pain relief. Gomes said that, for moderate pains, rubbing the anti-inflammatory topically onto the pained area can be effective without exposing the entire body to increased cardiovascular risk. Yet he advised caution when using NSAIDs either topically or orally. The study was funded by the University of California and a Hellman Fellowship.
Newswise — As we better understand the role food plays in our overall health and wellbeing, the closer the connection becomes between nutrition and medicine. Malnutrition is a critical public health problem, affecting many people across the United States and around the world. Unfortunately, the modern day manifestations of hunger are increasingly complex. In an effort to explore this evolving landscape, the May issue of the Journal of the Academy of Nutrition and Dietetics offers insights from leading registered dietitian nutritionists and other health professionals, providing a comprehensive look at malnutrition. While traditionally thought of as starvation or famine, malnutrition in the modern world is much more complicated and often affects the most vulnerable populations: children, the elderly, and the sick. With this new issue, the Academy of Nutrition and Dietetics hopes to inform its professional community and the public about the changing face of malnutrition. “In the community in the United States it’s clear that there are plenty of food deserts where availability of quality food and nutrition is a concern,” comments Gordon Jenson, PhD, MD, Department Head and Professor of Nutritional Sciences at Penn State University in an interview conducted by Journal of the Academy of Nutrition and Dietetics Editor-in-Chief Linda G. Snetselaar, PhD, RDN, LD. We’re dealing with a challenging continuum of malnutrition within the community setting today that is far more than classic undernutrition and starvation. It really is a continuum of individuals afflicted with disease, with injuries, in social isolation, or with limited resources. Ultimately this is all about how we get the appropriate resources and interventions to the individuals who need them. An integrated approach is critical with support from social services, mental health professionals, and medical care whenever appropriate.” The issue includes original research reports and accompanying editorials focusing on different facets of modern malnutrition including establishing evidence-based nutrition practices, malnutrition in hospitals, malnutrition in a rapidly increasing elderly population, inflammation and its relationship to malnutrition, and developing workflows for the identification of malnutrition in a clinical setting. An interview with past Academy president Susan Finn, PhD, RD, FAND, who served on the National Hunger Commission, provides a behind-the-scenes look at the National Commission on Hunger Report to Congress from the perspective of a registered dietitian nutritionist on the Commission. Dr. Finn and her colleagues delivered their final report to Congress in January 2016 and their findings will help guide policy makers on how to improve government programs. In the interview, Dr. Finn offered several findings from the report that can help Academy members in the fight against malnutrition: • Focus special attention on nutrition outreach for people with disabilities, seniors, military family, and families with small children.• Support nutrition pilot programs that can yield innovative solutions.• Engage with members of Congress by responding to Action Alerts.• Become active in advocacy efforts to reduce food insecurity at the community level.• Share information on nutrition programs available in your area and encourage partnerships to improve food security. Nutrition is now an integral part of medical treatment of disease. For example, within the last decade enteral feeding has become more routine than parenteral feeding for nutrition support among hospital patients and there is growing evidence for the effective modulation of inflammatory response with nutrients. Addressing malnutrition in hospitals, the issue offers several resources for ameliorating the problem. The article “Building a Connection between Senior Hunger and Health Outcomes” highlights the challenges presented by the hospitalization of malnourished elderly patients. Lead investigator Stefanie Winston Rinehard, JD, MPH, Director, Department of Health and Human Services Legislation and Policy, explains, “Malnutrition affects an estimated 30% to 50% of adult hospitalized patients in the United States, but only 3.2% of these patients are discharged with a diagnosis of malnutrition. Malnourished patients have worse health outcomes when compared with well-nourished patients, including increased physician visits, longer hospital stays and readmissions, decreased function and quality of life, and increased health care costs.” Other articles focus on the task of diagnosing malnutrition in hospital patients. “Diagnosing Malnutrition: Where Are We and Where Do We Need to Go?” discusses how accurate nutritional assessments are not always successfully integrated into clinical workflows. “Malnutrition is the skeleton in the hospital closet that continues to haunt us,” notes author Charlene Compher, PhD, RD, LDN, FADA, FASPEN. “Following decades of reports describing the prevalence and influence of malnutrition on hospital outcomes, we have seen a renewed interest in defining and classifying malnutrition.” As the relationship between nutrition and medicine continues to develop, the Academy hopes that this collection of articles can renew the conversation about malnutrition and help practitioners better understand ways to combat hunger in their professional lives. “In past years, the ethical debate involving nutrition was primarily related to terminal or irreversible illness and the withdrawal of artificial nutrition,” emphasizes Louise Merriman, MS, RD, CDN, Director, Clinical Nutrition, New York Presbyterian Hospital, co-author of “Implementing the Care Plan for Patients Diagnosed with Malnutrition—Why Do We Wait.” “Now, with malnutrition finally recognized to be prevalent and problematic in hospitalized patient populations, the ethical debate is shifting as we ask ourselves and our team members: Why do we wait?”