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Dr. Marie Gabrielle Laguna

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Medical doctor-internist

body's waste systemBy scanning the brains of healthy volunteers, researchers at the National Institutes of Health saw the first, long-sought evidence that our brains may drain some waste out through lymphatic vessels, the body’s waste system. The results further suggest the vessels could act as a pipeline between the brain and the immune system.
Daniel S. Reich, M.D., Ph.D., senior investigator at the NIH’s National Institute of Neurological Disorders and Stroke (NINDS) and the senior author of the study published online in eLife. “We hope that our results provide new insights to a variety of neurological disorders.”
Researchers use primarily magnetic resonance imaging (MRI) to investigate multiple sclerosis and other neurological disorders which are thought to involve the immune system. Led by post-doctoral fellows, Martina Absinta, Ph.D. and Seung-Kwon Ha, Ph.D., along with researchers from the National Cancer Institute, the team discovered lymphatic vessels in the dura, the leathery outer coating of the brain.
In 2015, two studies of mice found evidence of the brain’s lymphatic system in the dura. Coincidentally, that year, Dr. Reich saw a presentation by Jonathan Kipnis, Ph.D., a professor at the University of Virginia and an author of one of the mouse studies.
“I was completely surprised. In medical school, we were taught that the brain has no lymphatic system,” said Dr. Reich. “After Dr. Kipnis’ talk, I thought, maybe we could find it in human brains?”
To look for the vessels, Dr. Reich’s team used MRI to scan the brains of five healthy volunteers who had been injected with gadobutrol, a magnetic dye typically used to visualize brain blood vessels damaged by diseases, such as multiple sclerosis or cancer. The dye molecules are small enough to leak out of blood vessels in the dura but too big to pass through the blood-brain barrier and enter other parts of the brain.
“These results could fundamentally change the way we think about how the brain and immune system inter-relate,” said Walter J. Koroshetz, M.D., NINDS director.
Dr. Reich’s team plans to investigate whether the lymphatic system works differently in patients who have multiple sclerosis or other neuroinflammatory disorders.
“For years we knew how fluid entered the brain. Now we may finally see that, like other organs in the body, brain fluid can drain out through the lymphatic system,” said Dr. Reich.

yogurtResearchers at the Virginia-Maryland College of Veterinary Medicine at Virginia Tech have released findings that explain how a type of healthy bacteria in yogurt and other dairy products might reduce disease symptoms in certain patients with lupus.
Xin Luo, assistant professor of immunology in the Department of Biomedical Sciences and Pathobiology, and her colleagues expanded upon earlier research linking a lack of Lactobacillus, which produces lactic acid and is an important part of gut microbiota in both humans and mice, and autoimmune diseases such as lupus. The new research describes the mechanism behind this association.
“In our 2014 paper, we found that mice with lupus had decreased amounts of Lactobacillus, which led to our hypothesis that adding this bacteria could ameliorate disease symptoms,” said Luo, who added that she and her colleagues also found that the mice had a “leaky gut,” a condition that affects the intestinal lining. “Probiotics, such as Lactobacillus, work by patching up and reversing the leaky gut.”
“In addition, we found that the addition of Lactobacillus to the diet only affected female mice and not males,” said Luo, who explained that lupus is 10 times more prevalent in females than in males. “We think that testosterone is suppressing the effect of the healthy bacteria. Before our study, researchers had never looked at male hormones suppressing the probiotic effect before.”
The research team included Qinghui Mu, a Ph.D. student in the biomedical and veterinary sciences program and recent recipient of an American Association of Immunologists Careers in Immunology Fellowship, and S. Ansar Ahmed, professor of immunology and associate dean of research and graduate studies at the veterinary college. Ahmed is also one of the leading authorities on the effect of hormones on lupus and other autoimmune disorders.
Although the research was limited to mice with lupus and kidney inflammation, and more work would need to be done to determine whether Lactobacillus has the same effect in humans, Luo emphasized that yogurt and probiotic supplements are considered safe.
“If a lupus patient is female and also has kidney inflammation, there would be no harm in adding yogurt or a probiotic supplement to the diet,” she said.
Now that researchers have identified the “good” bacteria that affect the severity of lupus, they hope to turn their attention to other areas of research.

vitamin kScientists have found another reason for children to eat their green leafy vegetables- Vitamin K.
A study of 766 otherwise healthy adolescents showed that those who consumed the least vitamin K1- found in spinach, cabbage, iceberg lettuce and olive oil, were at 3.3 times greater risk for an unhealthy enlargement of the major pumping chamber of their heart, according to the study published in The Journal of Nutrition. Vitamin K1, or phylloquinone, is the predominant form of vitamin K in the U.S. diet.
“Those who consumed less had more risk,” says Dr. Norman Pollock, bone biologist at the Georgia Prevention Institute at the Medical College of Georgia at Augusta University and the study’s corresponding author.
Overall, about 10 percent of the teens had some degree of this left ventricular hypertrophy, Pollock and his colleagues report.
Left ventricular changes are more typically associated with adults whose hearts have been working too hard, too long to get blood out to the body because of sustained, elevated blood pressure. The scientists believe theirs is the first study exploring associations between vitamin K and heart structure and function in young people. While more work is needed, their findings suggest that early interventions to ensure young people are getting adequate vitamin K1 could improve cardiovascular development and reduce future disease risk, they write.
In the 14-18 year olds who consumed the least vitamin K1, the study found the overall size and wall thickness of the left ventricle were already significantly greater and the amount of blood the heart pumped out significantly lower, Pollock says.
Only 25 percent of the teens in the study met current adequate intake levels of the Food and Nutrition Board of the Institute of Medicine, Pollock notes.
Vitamin K is known to be important to blood clotting and healthy bones. There is increasing evidence of its cardiovascular impact as well. For example, one direct, negative impact of low vitamin K intake on the heart may be reduced activity of matrix Gla protein, which helps prevent calcium deposits on blood vessel walls.
Further study is needed to clarify the importance of vitamin K1 intake to cardiovascular development and to better understand how vitamin K dependent proteins, like matrix Gla protein, aid cardiovascular development and health, the scientists note.

skipping breakfastSkipping breakfast is associated with an increased risk of atherosclerosis, or the hardening and narrowing of arteries due to a build-up of plaque, according to research published in the Journal of the American College of Cardiology.
Previous studies have linked skipping breakfast to coronary heart disease risk, this is the first study to evaluate the association between breakfast and the presence of subclinical atherosclerosis.
“People who regularly skip breakfast likely have an overall unhealthy lifestyle,” said study author Valentin Fuster, MD, PhD, MACC director of Mount Sinai Heart and editor-in-chief of the Journal of the American College of Cardiology. “This study provides evidence that this is one bad habit people can proactively change to reduce their risk for heart disease.”
Researchers in Madrid examined male and female volunteers free from cardiovascular or chronic kidney disease. A computerized questionnaire was used to estimate their usual diet, and breakfast patterns were based on the percentage of total daily energy intake consumed at breakfast. Three groups were identified: those consuming less than five percent of their total energy intake in the morning (skipped breakfast and only had coffee, juice or other non-alcoholic beverages); those consuming more than 20 percent of their total energy intake in the morning (breakfast consumers); and those consuming between five and 20 percent (low-energy breakfast consumers). Of the 4,052 participants, 2.9 percent skipped breakfast, 69.4 percent were low-energy breakfast consumers and 27.7 percent were breakfast consumers.
Atherosclerosis was observed more frequency among participants who skipped breakfast and was also higher in participants who consumed low-energy breakfasts compared to breakfast consumers. Additionally, cardio-metabolic risk markers were more prevalent in those who skipped breakfast and low-energy breakfast consumers compared to breakfast consumers. Participants who skipped breakfast had the greatest waist circumference, body mass index, blood pressure, blood lipids and fasting glucose levels.
“Aside from the direct association with cardiovascular risk factors, skipping breakfast might serve as a marker for a general unhealthy diet or lifestyle which in turn is associated with the development and progression of atherosclerosis,” said Jose L. Peñalvo, PhD, assistant professor at the Friedman School of Nutrition Science and Policy at Tufts University and the senior author of the study. “Our findings are important for health professionals and might be used as a simple message for lifestyle-based interventions and public health strategies, as well as informing dietary recommendations and guidelines.”

exerciseA landmark study led by the Black Dog Institute has revealed that regular exercise of any intensity can prevent future depression — and just one hour can help.
Published in the American Journal of Psychiatry, the results show even small amounts of exercise can protect against depression, with mental health benefits seen regardless of age or gender.
This most extensive and largest study involved 33,908 Norwegian adults who had their levels of exercise and symptoms of depression and anxiety monitored over 11 years.
The international research team found that 12 percent of cases of depression could have been prevented if participants undertook just one hour of physical activity each week.
“We’ve known for some time that exercise has a role to play in treating symptoms of depression, but this is the first time we have been able to quantify the preventative potential of physical activity in terms of reducing future levels of depression,” said lead author Associate Professor Samuel Harvey from Black Dog Institute and UNSW.
“These results highlight the great potential to integrate exercise into individual mental health plans and broader public health campaigns. If we can find ways to increase the population’s level of physical activity even by a small amount, then this is likely to bring substantial physical and mental health benefits.”
A healthy cohort of participants was asked at baseline to report the frequency of exercise they participated in and at what intensity: without becoming breathless or sweating, becoming breathless and sweating, or exhausting themselves. At follow-up stage, they completed a self-report questionnaire (the Hospital Anxiety and Depression Scale) to indicate any emerging anxiety or depression.
The research team also accounted for variables which might impact the association between exercise and common mental illness. These include socio-economic and demographic factors, substance use, body mass index, new onset physical illness and perceived social support.
Results showed that people who reported doing no exercise at all at baseline had a 44% increased chance of developing depression compared to those who were exercising one to two hours a week.
However, these benefits did not carry through to protecting against anxiety, with no association identified between level and intensity of exercise and the chances of developing the disorder.

meat consumptionLower meat consumption by women during pregnancy was linked with an increased risk of substance misuse by their children during adolescence. The findings come from a study published in Alcoholism: Clinical and Experimental Research.
In the study that included 5109 women and their offspring, less frequent consumption of red meat, poultry, and meat products during pregnancy were associated with greater risks of adverse alcohol, cannabis and cigarette use.
Lower meat consumption disproportionally increased the risks of offspring substance misuse among mothers with optimally functional variants of the gene that encodes a vitamin B12 transport protein. Because vitamin B12 insufficiencies are highly likely to have a contributing role to the study’s findings, greater meat consumption need not be advised to modify this risk. For example, fortification of foods with vegetarian sources of vitamin B12 and more widespread use of supplements may be other options.
“The U.S. Dietary Guidelines for Americans includes recommendations for healthy vegetarian eating patterns,” said Dr. Joseph Hibbeln, lead author of the study. “Our study points to the need to investigate potential health impacts, and solutions, for some women who choose to restrict certain food categories during pregnancy.”

dietary potassiumBananas and avocados, foods rich in potassium, may help protect against pathogenic vascular calcification or hardening of the arteries.
University of Alabama at Birmingham researchers have shown that reduced dietary potassium promotes elevated aortic stiffness in a mouse model, compared with normal-potassium-fed mice. Such arterial stiffness in humans is predictive of heart disease and death from heart disease, and represents an important health problem for the nation as a whole.
The UAB researchers found that increased dietary potassium levels lessened vascular calcification and aortic stiffness. Furthermore, they unravelled the molecular mechanism underlying the effects of low or high dietary potassium.
Such knowledge of how vascular smooth muscle cells in the arteries regulate vascular calcification emphasizes the need to consider dietary intake of potassium in the prevention of vascular complications of atherosclerosis. It also provides new targets for potential therapies to prevent or treat atherosclerotic vascular calcification and arterial stiffness.
A UAB team led by Yabing Chen, Ph.D., UAB professor of pathology and a Research Career Scientist at the Birmingham VA Medical Center, explored this mechanism of vascular disease three ways: living mice fed diets that varied in potassium, mouse artery cross-sections studied in culture medium with varying concentrations of potassium, and mouse vascular smooth muscle cells grown in culture medium.
The animal work was carried out in the atherosclerosis-prone mouse model, the apoliprotein E-deficient mice, a standard model that are prone to cardiovascular disease when fed a high-fat diet. Using low, normal or high levels of dietary potassium (0.3 percent, 0.7 percent and 2.1 percent weight/weight). The UAB team found that the mice fed a low-potassium diet had a significant increase in vascular calcification. In contrast, the mice fed a high-potassium diet had markedly inhibited vascular calcification. Also, the low-potassium mice had increased stiffness of their aortas, and high-potassium mice had decreased stiffness, as indicated by the arterial stiffness indicator called pulse wave velocity, which is measured by echocardiography in live animals.
The different levels of dietary potassium were mirrored by different blood levels of potassium in the three groups of mice.
“The findings have important translational potential,” said Paul Sanders, M.D., professor of nephrology in the UAB Department of Medicine and a co-author, “since they demonstrate the benefit of adequate potassium supplementation on prevention of vascular calcification in atherosclerosis-prone mice, and the adverse effect of low potassium intake.”

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surgical glueA highly elastic and adhesive surgical glue that quickly seals wounds without the need for common staples or sutures could transform how surgeries are performed.
Biomedical engineers from the University of Sydney and the United States collaborated on the development of the potentially life-saving, called MeTro.
MeTro’s high elasticity makes it ideal for sealing wounds in body tissues that continually expand and relax such as lungs, hearts and arteries, which are otherwise at risk of re-opening.
The material also works on internal wounds that are often hard-to-reach areas and have typically required staples or sutures due to surrounding body fluid hampering the effectiveness of other sealants.
MeTro sets in just 60 seconds once treated with UV light, and the technology has a built-in degrading enzyme which can be modified to determine how long the sealant lasts from hours to months, to allow adequate time for the wound to heal.
The liquid or gel-like material has quickly and successfully sealed incisions in the arteries and lungs of rodents and the lungs of pigs, without the need for sutures and staples.
The results were published in Science Translational Medicine, in a paper by the University of Sydney’s Charles Perkins Centre and Faculty of Science; Boston’s Northeastern University, the Wyss Institute for Biologically Inspired Engineering at Harvard University and the Beth Israel Deaconess Medical Center (BIDMC) in Boston.
MeTro combines the natural elastic protein technologies developed in collaboration with author and University of Sydney McCaughey Chair in Biochemistry Professor Anthony Weiss, with light sensitive molecules developed in collaboration with author and Director of the Biomaterials Innovation Research Center at Harvard Medical School Professor Ali Khademhosseini.
Lead author of the study, Assistant Professor Nasim Annabi from the Department of Chemical Engineering at Northeastern University, oversaw the application of MeTro in a variety of clinical settings and conditions.
“The beauty of the MeTro formulation is that, as soon as it comes in contact with tissue surfaces, it solidifies into a gel-like phase without running away,” she said.
“We then further stabilise it by curing it on-site with a short light-mediated crosslinking treatment. This allows the sealant to be accurately placed and to tightly bond and interlock with structures on the tissue surface.”
The University of Sydney’s Professor Anthony Weiss described the process as resembling that of silicone sealants used around bathroom and kitchen tiles.

urinary tract infectionDrinking an additional three pints of water a day may keep the urinary tract infection (UTI) away — at least for women who are prone — suggests a study being presented at IDWeek 2017â„¢.
The study found women at risk of UTIs who increased their water intake by about that much water every day were nearly half as likely to get UTIs as women who did not.
“While doctors have long assumed this is the case and often recommended that women at risk for UTIs increase their fluid intake, it’s never really undergone a prospective trial before,” said Thomas M. Hooton, MD, lead author of the study and clinical director of the Division of Infectious Diseases, University of Miami School of Medicine. “It’s good to know the recommendation is valid, and that drinking water is an easy and safe way to prevent an uncomfortable and annoying infection.”
The study included 140 healthy premenopausal women who had at least three UTIs in the last year and reported low daily fluid intake. Half of the women (70) who served as the control group continued their usual daily fluid intake, while the remainder were told to drink 1.5 liters of water a day (about three 16-ounce glasses) in addition to their usual daily fluid intake. After one year, women in the control group had 3.1 UTIs on average, whereas those in the water group had 1.6 UTIs on average, a 48 percent reduction. As a result, the water group averaged fewer regimens of antibiotics (1.8) than the limited-water group (3.5), a reduction of 47 percent.
Researchers followed the women throughout the year using visits and telephone calls. They documented that over the course of the study, on average women in the water group increased their daily water intake by 1.15 liters (about 2-1/2 pints) for a total daily fluid intake (including water and other beverages) of 2.8 liters, whereas women in the control group did not increase the amount of water they drank and had a total daily fluid intake of 1.2 liters.
“If a woman has recurrent UTIs and is looking for a way to reduce her risk, the evidence suggests that if she increases the amount of water she drinks and stays with it, she’ll likely benefit,” Dr. Hooton said.

antifungalUniversity of Liverpool researchers, working with F2G Limited (Eccles, Manchester), have developed a new antifungal drug to help in the treatment of life threatening invasive fungal infections such as invasive aspergillosis.

Invasive fungal infections are common and often lethal. Despite optimal medical care mortality is 20-30% at six weeks and dramatically rises to 80-100% for drug resistant infection.
These infections occur most commonly in the context of leukemia and bone marrow transplantation and often in young patients with otherwise curable disease.
The researchers, led by Professor William Hope from the University’s Antimicrobial Pharmacodynamics and Therapeutics (APT) Group, have characterised the biochemical and physiologic effects or the pharmacodynamics of F901318, which is the lead compound of the new class of drugs termed the ‘orotomides’.
The ‘orotomides’, discovered by F2G Limited, have a novel mechanism of action which is the specific biochemical interaction through which a drug substance produces its pharmacological effect.
This is the first new class of antifungal agent to be discovered in the last three decades.
The study, which was supported by a research grant by F2G, has been published in mBio.
APT’s work provides the underpinning evidence for efficacy and dosage justification for the very first patients receiving the new drug. Such information is required by regulatory agencies such as the European Medicines Agency and the Food and Drug Administration before clinical studies can proceed.
Professor Hope, said: “Antifungal resistance represents a major global clinical challenge. This study provides the necessary information to enable F901318 to be developed for clinical use.”