Scientists step closer to developing new drug in fight against antimicrobial resistance

Scientists have for the first time determined the molecular structure of a new antibiotic which could hold the key to tackling drug resistant bacteria.

The team at the University of Lincoln, UK, previously produced two synthetic derivatives of teixobactin -- which has been hailed as a 'game-changer' in the fight against antimicrobial resistance -- and the researchers have now become the first in the world to document the molecular make-up of the antibiotic.

This development is an important next step in understanding how different derivatives of teixobactin function, and which building blocks are needed for it to successfully destroy drug resistant bacteria.

Teixobactin, which kills pathogens without any detectable resistance, was first discovered in 2015 by scientists in the USA. It was isolated from microorganisms (which do not grow under laboratory conditions) found in soil -- the natural source of nearly all antibiotics developed since the 1940s. Scientists around the world then began exploring ways of creating versions of the antibiotic via chemical synthesis, in order for it to be developed as a potential drug treatment.

At the University of Lincoln, Dr Ishwar Singh from the School of Pharmacy led a team which synthetically produced different derivatives of teixobactin. These derivatives were biologically tested by Dr Edward Taylor, from Lincoln's School of Life Sciences. The researchers have now published new findings on the relationship between the antibiotic's molecular structure and its biological activity.

The study is published in the Royal Society of Chemistry journal, Chemical Communications.

Dr Singh said: "The increasing level of antimicrobial resistance represents a major global health challenge. The discovery of the highly potent antibiotic teixobactin to cope with this growing problem has provided a much-needed impetus to antibiotic research around the world. Although teixobactin does not mitigate all problems related to antimicrobial resistance, it is a definite step in the right direction, and our research continues to work towards this vital end goal."

The University of Lincoln team discovered that the molecular structure of teixobactin directly relates to its antimicrobial activity and its effectiveness at destroying pathogens. The researchers found that being relatively unstructured is essential to the biological activity of teixobactin, with more structured variants of the antibiotic proving to be inactive. They also identified a way of maintaining this 'disorder' when synthesising different derivatives.

"We successfully defined the molecular structure of seven teixobactin analogues," Dr Singh explained. "This enabled us to understand the importance of the individual amino acids within the antibiotic, and to understand the contribution they each make to the molecular structures of teixobactin. We found that one particular amino acid (D?Gln4) is essential and another (D?Ile5) is important for maintaining the disordered structure of teixobactin, which is imperative for its biological activity."

Dr Taylor said: "By exploring the structures of different versions of teixobactin we are, for the first time, able to begin to understand how this molecule works. This knowledge will enable us to produce different forms of teixobactin more easily and on a larger scale with potentially better pharmaceutical properties."

This work represents a significant step towards the development of teixobactin as a drug, as scientists will now have a much clearer understanding of which building blocks are central to ensuring it works effectively and which are not.

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Materials provided by University of Lincoln. Note: Content may be edited for style and length.

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Journal Reference:

1. Anish Parmar, Stephen H. Prior, Abhishek Iyer, Charlotte S. Vincent, Dorien Van Lysebetten, Eefjan Breukink, Annemieke Madder, Edward J. Taylor, Ishwar Singh. Defining the molecular structure of teixobactin analogues and understanding their role in antibacterial activities. Chem. Commun., 2017; DOI: 10.1039/C6CC09490B

Preventing blood clots with a new metric for heart function

The heart is a wonder of design -- a pump that can function for 80 years, and billions of heartbeats, without breaking down. But when it does malfunction, the results can be dire.

In research reported in the International Journal of Cardiology this month, scientists from Johns Hopkins University and Ohio State presented a new method for predicting those most at risk for thrombus, or blood clots, in the heart.

The critical factor, the researchers found, is the degree to which the mitral jet -- a stream of blood shot through the mitral valve -- penetrates into the left ventricle of the heart. If the jet doesn't travel deep enough into the ventricle, it can prevent the heart from properly flushing blood from the chamber, potentially leading to clots, strokes and other dangerous consequences.

The findings were based on simulations performed using the Stampede supercomputer at the Texas Advanced Computing Center and validated using data from patients who both did and did not experience post-heart attack blood clots. The work was supported by grants from the National Science Foundation.

The metric that characterizes the jet penetration, which the researchers dub the E-wave propagation index (EPI), can be ascertained using standard diagnostic tools and clinical procedures that are currently used to assess patient risk of clot formation, but is much more accurate than current methods.

"The beauty of the index is that it doesn't require any additional measurements. It simply reformulates echocardiogram data into a new metric," said Rajat Mittal, a computational fluid dynamics expert and professor of engineering at Johns Hopkins University and one of the principal investigators on the research. "The clinician doesn't have to do any additional work."

Heart disease is the leading cause of death in the U.S. and by far the most expensive disease in terms of health care costs. Heart attacks cause some deaths; others result from blood clots, frequently the result of a heart weakened by disease or a traumatic injury.

Clots can occur whenever blood remains stagnant. Since the chambers of the heart are the largest reservoirs of blood in the body, they are the areas most at risk for generating clots.

Predicting when a patient is in danger of developing a blood clot is challenging for physicians. Patients recovering from a heart attack are frequently given anticoagulant drugs to prevent clotting, but these drugs have adverse side-effects.

Cardiologists currently use the ejection fraction -- the percentage of blood flushed from the heart with each beat -- as well as a few other factors, to predict which patients are at risk of a future clot.

For healthy individuals, 55 to 70 percent of the volume of the chamber is ejected out of the left ventricle with every heartbeat. For those with heart conditions, the ejection fraction can be reduced to as low as 15 percent and the risk of stagnation rises dramatically.

Though an important factor, the ejection fraction does not appear to be an accurate predictor of future clotting risk.

"Because we understood the fluid dynamics in the heart using our computational models, we reached the conclusion that the ejection fraction is not a very accurate measure of flow stasis in the left ventricle," Mittal said. "We showed very clearly that the ejection fraction is not able to differentiate a large fraction of these patient and stratify risk, whereas this E-wave propagation index can very accurately stratify who will get a clot and who will not," he said.

The results were the culmination of many years of investigation by Mittal and his collaborators into the fundamental relationship between the structure and function of the heart. To arrive at their hypothesis, the researchers captured detailed measurements from 13 patients and used those to construct high-fidelity, patient-specific models of the heart that take into account fluid flow, physical structures and bio-chemistry.

These models led, in turn, to new insights into the factors that correlate most closely to stagnation in the left ventricle, chief among them, mitral jet penetration.

Working in collaboration with clinicians, including lead author, Thura Harfi of Ohio State University, the team tested their hypothesis using data from 75 individual -- 25 healthy patients, 25 patients who experienced clots in their left ventricle, and 25 patients who had a compromised heart but who didn't have any clots.

Pending validation in a larger cohort of patients, the researchers found that based on the EPI measurement, one in every five patients with severe cardiomyopathy who are currently not being treated with anticoagulation, would be at risk of a left ventricular clot and would benefit from anticoagulation.

"Physicians and engineers don't interact as often as they should and that creates a knowledge gap that can be closed with this type of collaborative research," Harfi said. "Computational fluid dynamics is such an established way of studying phenomena in mechanical engineering, but has rarely been tried in humans. But now, with the development of high-resolution cardiac imaging techniques like cardiac computed tomography (CT) and the availability of supercomputing power, we can apply the power of computational fluid dynamics simulations to study blood flow in human beings. The information you get from a computer simulation you cannot get otherwise."

Mittal and his team required large computing resources to derive and test their hypothesis. Each simulation ran in parallel on 256 to 512 processors and took several 100,000 computing hours to complete.

"This work cannot be done by simulating a single case. Having a large enough sample size to base conclusions on was essential for this research," Mittal said. "We could never come close to being able to do what we needed to do it if weren't for Stampede."

Mittal foresees a time where doctors will perform patient-specific heart simulations routinely to determine the best course of treatment. However, hospitals would need systems hundreds of times faster than a current desktop computer to be able to figure out a solution locally in a reasonable timeframe.

In addition to establishing the new diagnostic tool for clinicians, Mittal's research helps advance new, efficient computational models that will be necessary to make patient-specific diagnostics feasible.

The team plans to continue to test their hypothesis, applying the EPI metric to a larger dataset. They hope in the future to run a clinical study with prospective, rather than retrospective, analysis.

With a better understanding of the mechanics of blood clots and ways to the predict them, the researchers have turned their attention to other sources of blood clots, including bio-prosthetic heart valves and atrial fibrillation (AFib) -- a quivering or irregular heartbeat that affects 2.7 million Americans.

"These research results are an important first step to move our basic scientific understanding of the physics of how blood flows in the heart to real-time predictions and treatments for the well-being of patients," said Ronald Joslin, NSF Fluid Dynamics program director.

"The potential for impact in this area is very motivating," Mittal said, "not just for me but for my collaborators, students and post-docs as well."

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Materials provided by University of Texas at Austin, Texas Advanced Computing Center. Note: Content may be edited for style and length.

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Journal Reference:

1. Thura T. Harfi, Jung-hee Seo, Hayder S. Yasir, Nathaniel Welsh, Susan A. Mayer, Theodore P. Abraham, Richard T. George, Rajat Mittal. The E-wave propagation index (EPI): A novel echocardiographic parameter for prediction of left ventricular thrombus. Derivation from computational fluid dynamic modeling and validation on human subjects. International Journal of Cardiology, 2017; 227: 662 DOI: 10.1016/j.ijcard.2016.10.079

What primary care providers should know about diabetic neuropathy

An estimated 60 to 70 percent of people with diabetes develop some form of diabetic neuropathy, or the chronic nerve damage diabetes causes, according to the National Institute of Diabetes and Digestive and Kidney Diseases.

With so many people affected, researchers at Michigan Medicine led a group of internationally recognized endocrinologists and neurologists from both sides of the Atlantic and teamed up with the American Diabetes Association to craft a new position statement on the prevention, treatment and management of the condition.

The statement provides recommendations for physicians on the overall prevention of diabetic neuropathy, noting that preventing this complication is a key component of diabetes care because treatments to reverse the underlying nerve damage are lacking. It also delves into various diabetic neuropathies and suggests guidelines to manage and treat each.

The ADA last released a statement on diabetic neuropathy in 2005. This update better reflects the current landscape of diabetic neuropathy care.

"Our goal was to update the document so that it not only had the most up-to-date evidence, but also was easy to understand and relevant for primary care physicians," says Rodica Pop-Busui, M.D., Ph.D., professor of internal medicine at Michigan Medicine Division of Metabolism, Endocrinology and Diabetes and lead author of the statement. "We wanted it to be accessible to whoever takes care of diabetes patients, not just specialists."

Another goal of the statement was to clarify the multiple forms of diabetic neuropathy that exist.

"We wanted to unify all of the various forms of diabetic neuropathy in a more objective and easy-to-follow recommendation method," Pop-Busui says. "Many physicians have used different classifications for neuropathies. We came to a consensus to classify them in a more logical pattern, or format, for clinical care."

"We asked ourselves: What are the critical steps that have to be followed to diagnose diabetic neuropathy efficiently without ordering unnecessary evaluations for the patient, which can be expensive and may involve long wait times?" Pop-Busui says. "We agreed on an algorithm that can be used in the clinical care setting so physicians have an easier understanding of when to perform a center evaluation or when they should refer the patient to a neurologist."

Prevention and treatment recommendations

The research team includes a classification system for diabetic neuropathies within the statement, which describes the three main types: diffuse neuropathy, mononeuropathy, and radiculopathy or polyradiculopathy.

Diffuse neuropathy can be broken down into two categories, peripheral, which affects the feet and hands, and autonomic, which affects the internal organs. Common examples of diffuse neuropathy are distal symmetric polyneuropathy (DSPN) and cardiovascular autonomic neuropathy (CAN).

Mononeuropathy occurs when a single nerve or an isolated nerve group is damaged. Radiculopathy occurs when the root of a nerve is pinched.

After establishing the classification system, the research team provides recommendations for overall prevention of diabetic neuropathy, including:

• In type 1 diabetes, work to effectively control glucose as soon as possible to prevent or delay the development of DSPN and CAN.
• In type 2 diabetes, work to effectively control glucose to prevent or slow the progression of DSPN.
• With type 2 diabetes, consider a multifactorial approach with targeting glycemia and other risk factors to prevent CAN.

Recommendations for screening and diagnosing, managing and treating the specific forms are also now available.

For example, with DSPN, one of the most common forms of diabetic neuropathy encountered in the clinical setting, the researchers say:

• All patients should be screened for DSPN as soon as they are diagnosed with type 2 diabetes and five years after the diagnosis of type 1 diabetes, with annual screenings afterward.
• If you have a patient with prediabetes who has symptoms of peripheral neuropathy, consider screening.
• Assessment should include a careful history check, in addition to either a temperature or pinprick sensation (if the patient has small-fiber function) or a vibration sensation using a 128-hertz tuning fork (if the patient has large-fiber function). All patients should have an annual 10-gram monofilament testing to determine if their feet are at risk for ulceration or amputation.
• Electrophysiological testing or referring the patient to a neurologist is rarely needed for screening, except if the symptoms presenting are atypical, such as motor greater than sensory neuropathy, rapid onset or asymmetrical presentation. You can also refer if the diagnosis is unclear or different etiology is suspected.

DSPN pain management

Pop-Busui mentions pain is often the reason many diabetic neuropathy patients seek help from their providers. The researchers recommend:

• As the initial approach, consider either pregabalin or duloxetine.
• Gabapentin can also be considered as an effective initial approach, but the patient's socioeconomic status, comorbidities and potential drug interactions have to be taken into consideration.
• Tricyclic antidepressants are also effective but are not approved by the U.S. Food and Drug Administration and should be used with caution because of the higher risk of serious side effects.
• Opioids are not recommended as first- or second-line agents for treating pain associated with DSPN because of the high risks of addiction and other complications.

The importance of guidelines for diabetic neuropathy pain management

Pop-Busui says the position statement update is especially timely.

"Treatment of neuropathy pain is specifically relevant because, unfortunately, there has been much overprescribing of narcotics for neuropathic pain," Pop-Busui says. "We now provide clear evidence to fellow physicians that other agents are available and are more effective in treating diabetic neuropathy. We also demonstrate that there are ways to stay away from prescribing opioids and avoiding the epidemic of addiction and serious health consequences associated with opioid use in patients with diabetes."

She adds, "We hope these guidelines bring together primary care physicians, endocrinology specialists and neurologists to expand the care provided to diabetic patients."

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Story Source:

Materials provided by Michigan Medicine - University of Michigan. Note: Content may be edited for style and length.

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Journal Reference:

1. Rodica Pop-Busui, Andrew J.M. Boulton, Eva L. Feldman, Vera Bril, Roy Freeman, Rayaz A. Malik, Jay M. Sosenko, Dan Ziegler. Diabetic Neuropathy: A Position Statement by the American Diabetes Association. Diabetes Care, 2016; 40 (1): 136 DOI: 10.2337/dc16-2042

High-altitude living decreases the risk of heart disease

Could something as simple as the geographic area in which you live contribute to your risk of developing heart disease and diabetes, or suffering a stroke? A new study, published in the open-access journal Frontiers in Physiology, has revealed that the incidence of Metabolic Syndrome could be linked to the altitude of where a person lives. Metabolic syndrome is the medical term for the combination of high blood pressure, sugar and cholesterol levels, as well as excess body fat around the waist, and contributes to serious health problems.

"We found that those people living between 457 to 2297 meters, had a lower risk of developing Metabolic Syndrome than those living at sea level (0 to 121 meters),"says Amaya López-Pascual, who conducted this research as part of her PhD thesis in the Department of Nutrition, Food Science and Physiology and the Centre for Nutrition Research of the University of Navarra, Spain.

"Unfortunately, Metabolic Syndrome is very common and increasing worldwide. For example, 34% of the US population suffers Metabolic Syndrome. Our research will help us to understand what factors contribute to its development," explains López-Pascual.

This new research is the first to assess the link between living at high altitudes and the risk to initially healthy people developing all the criteria that make up the Metabolic Syndrome.

While the reported increase in the Metabolic Syndrome is principally blamed on higher obesity rates, smoking and increasingly inactive lifestyles, less is known about the effect our environment may have on us. Previous studies have suggested that people living at higher altitudes, where the body has to work harder to get the oxygen it needs, have noticeably fewer problems linked to the Metabolic Syndrome.

"Living or training at high altitudes or under a simulated hypoxic (oxygen deficient) environment seems to help with heart and lung function, losing weight, and improves insulin sensitivity," explains Pedro González-Muniesa, associate professor at the University of Navarra and co-senior author of this study, who is also a member of the CIBERobn consortium and IDISNA (Navarra's Health Research Institute), Spain.

The researchers used data from the Spanish SUN project, where participants have been voluntarily submitting information about their health twice-yearly since 1999. Information from thousands of initially healthy participants were used to investigate the development of Metabolic Syndrome in relation to the altitude of where they lived.

The results were quite clear -- the higher the altitude, the less likely you were of developing Metabolic Syndrome. Interestingly, using information about the participants' family history, the researchers could also assess if those more prone to this health problem also saw these benefits. "We found our results were independent of the genetic background of the individuals," reveals González-Muniesa.

While the findings of the study appear simple, there were lots of factors to consider and the limitations of the study have been highlighted by the authors. For instance, the self-reporting of data can suffer problems, whereby people over-report more socially acceptable information.

"While we tried to account for influences that may have impacted our results, there are a number of factors to consider. All the participants were graduate students, implying they have a higher educational level than the general population. While they have been shown to be better at self-reporting data, they typically have a different diet and levels of physical activity. These results should only be applied to people with similar lifestyles," explains J. Alfredo Martínez, professor at the University of Navarra and the other co-senior author of this study, also a member Navarra's Health Research Institute.

"We assumed participants remained living at the same altitude and at present, we do not know the influence that humidity, temperature, climate and pollution may have at various levels of altitude. However, we do know the participants were recruited from a range of locations at all altitudes, so any effects from being in a city or countryside were spread over all the participants we studied," further explains López-Pascual.

It is hoped this research will open up new avenues for understanding the health benefits of high altitude living. "Our group considers studying the health benefits of hypoxia a very promising area of research," says González-Muniesa. "We need more studies to understand the mechanisms involved. In addition, we can start to look at the altitude at which we start to obtain benefits and where they stop and/or turn harmful."

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Story Source:

Materials provided by Frontiers. Note: Content may be edited for style and length.

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Journal Reference:

1. Amaya Lopez-Pascual, Maira Bes-Rastrollo, Carmen Sayón-Orea, Aurora Perez-Cornago, Jesús Díaz-Gutiérrez, Juan J. Pons, Miguel A. Martínez-González, Pedro González-Muniesa, J. Alfredo Martínez. Living at a Geographically Higher Elevation Is Associated with Lower Risk of Metabolic Syndrome: Prospective Analysis of the SUN Cohort. Frontiers in Physiology, 2017; 7 DOI: 10.3389/fphys.2016.00658

Misdiagnosed foot, ankle injuries may result in arthritis, chronic pain and disability

Front-line physicians are advised to err on the side of caution and opt for additional imaging and second opinions when diagnosing six common foot and ankle injuries. A new study by orthopedic surgeons finds misdiagnosis often results in poor long-term patient outcomes, including arthritis and disability.

Their clinical review, published in the February edition of the Journal of the American Osteopathic Association, outlined subtleties that complicate identification and treatment of snowboarder's fracture (lateral talar process fractures) as well as os trigonum injuries, Lisfranc injuries, turf toe, navicular stress fractures and syndesmotic injuries.

More than 3 million emergency room visits in the United States each year are related to common foot and ankle injuries. The authors encourage clinicians to be suspicious and obtain additional imaging or a second opinion from an orthopedic surgeon to confirm the initial diagnosis.

"These types of trauma are a clinically significant source of morbidity and long-term disability among patients, not just those who are elite athletes. In many cases, the clinical symptoms are vague and tough to detect with standard imaging," said lead author Jessica Reissig, DO, of the Department of Orthopedics at Plainview Hospital in New York. "As an osteopathic physician, I view treatment of foot and ankle injuries as acute and preventative care because a mismanaged injury leads to so many future problems for patients."

Dr. Reissig noted that untreated snowboarder's fractures, Lisfranc injuries and turf toe have a high correlation to future arthritis, as well as the potential for severe pain and disability years after the injury. Improper treatment of other foot and ankle traumas can result in compensation injuries and other issues including tendinitis and recurrent ankle sprains.

While in many cases, these injuries can be resolved with a combination of medication, immobilization, ice and rest, some require surgical intervention. Elite athletes may also opt for surgery in order to resume their sport sooner, said co-author Adam Bitterman, DO, of the Hofstra Northwell School of Medicine.

"Once the diagnosis is confirmed, in many cases patients can be offered a range of treatment options from conservative to surgical. Choosing the best treatment for the individual can prevent the injury from decreasing the patient's future quality of life," Dr. Bitterman explained.

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Story Source:

Materials provided by American Osteopathic Association. Note: Content may be edited for style and length.

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Journal Reference:

1. Jessica Reissig, Adam Bitterman, Simon Lee. Common Foot and Ankle Injuries: What Not to Miss and How Best to Manage. The Journal of the American Osteopathic Association, 2017; 117 (2): 98 DOI: 10.7556/jaoa.2017.020

Physically active children are less depressed

Previous studies have shown that adults and young people who are physically active have a lower risk of developing depression. But the same effect has not been studied in children -- until now.

Results from a new study are showing that children receive the same beneficial effect from being active. We're talking about moderate to vigorous physical activity that leaves kids sweaty or out of breath.

Researchers at the Norwegian University of Science and Technology (NTNU) and NTNU Social Research have followed hundreds of children over four years to see if they could find a correlation between physical activity and symptoms of depression.

Healthy to roughhouse

Researchers examined just under 800 children when they were six years old, and conducted follow-up examinations with about 700 of them when they were eight and ten years old. Physical activity was measured with accelerometers, which served as a kind of advanced pedometer, and parents were interviewed about their children's mental health.

"Being active, getting sweaty and roughhousing offer more than just physical health benefits. They also protect against depression," says Tonje Zahl, a PhD candidate at NTNU. She is first author of the article on the study findings, which was recently published in the February 2017 issue of Pediatrics.

The work was conducted as part of Tidlig Trygg i Trondheim, a multi-year study of child development and mental health.

Fewer symptoms

Physically active six- and eight-year-olds showed fewer symptoms of depression when they were examined two years later. Physical activity thus seems to protect against the development of depression.

"This is important to know, because it may suggest that physical activity can be used to prevent and treat depression already in childhood," says Silje Steinsbekk, associate professor in NTNU's Department of Psychology. Steinsbekk and Professor Lars Wichstrøm are Zahl's mentors and coauthors.

Steinsbekk stresses that these results should now be tested in randomized studies where researchers increase children's physical activity and examine whether those who participate in these measures have fewer symptoms of depression over time than those who do not participate.

"We also studied whether children who have symptoms of depression are less physically active over time, but didn't find that to be the case," she says.

Facilitate activity for children

Previous findings in adolescents and adults showed that sedentary lifestyles -- like watching television and computer gaming -- are associated with depression, but the NTNU children's study found no correlation between depression and a sedentary lifestyle.

Depressive symptoms did not lead to greater inactivity and a sedentary lifestyle did not increase the risk of depression.

So the message to parents and health professionals is: Facilitate physical activity, which means that children get a little sweaty and breathless. Try a bike ride or outdoor play. Limiting children's TV or iPad screen time is not enough. Children need actual increased physical activity.

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Story Source:

Materials provided by Norwegian University of Science and Technology. Note: Content may be edited for style and length.

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Journal Reference:

1. Tonje Zahl, Silje Steinsbekk, Lars Wichstrøm. Physical Activity, Sedentary Behavior, and Symptoms of Major Depression in Middle Childhood. Pediatrics, 2017; e20161711 DOI: 10.1542/peds.2016-1711

How Cinnamon Helps Diabetes and Cholesterol

Cinnamon, used extensively in the Indian Diet, results in healthier blood. This amazing spice significantly reduces blood sugar levels in diabetics. Several studies have revealed that a diet high in spices like cinnamon, black pepper and turmeric or curcumin, can do wonders for the heart and your overall health. Happy Healthy Eating 

Easiest Tips to Prevent Weight Gain

Here is some easiest tips to beat weight gain

Drink water:- People often mistake thirst for hunger, so next time you feel like noshing, reach for water first. Drinking also helps you to feel full.

Eat more often:- Light, frequent meals curb your appetite and boost your energy. Control your environment and stock your home and office with healthy snacks.

Use low-calorie condiments:- Condiments can stand in for mayo to deliver plenty of flavors without the fat. Mustard, vinegar, yogurt, ketchup, soy sauce, salsa, spices and rubs are very low in calories.

Go easy on the alcohol:- Remember that alcohol is a source of calories. A 12-ounce beer has 150 calories; a 3.5-ounce glass of wine, 85 calories.

Write notes to yourself;- To help you stay on track, post positive notes to yourself on the fridge and the pantry.

Be mindful:- Eating on the run or in front of the TV or computer invites mindless munching. Instead, set the table every time you eat. Make a conscious choice to sit down and savor every bite.

Consume your protein:- Protein prolongs the feeling of fullness better than carbohydrates or fats do. Stick to low-fat protein sources like low-fat yogurt, hard-boiled eggs.

Make smart substitutions:- Look for nutritious, low-calorie alternatives to sugary, high-fat treats. Try frozen grapes or a frozen banana instead of ice cream or cake. Use air-popped popcorn instead of oil-popped. Bake an apple or a pear with cinnamon and Splenda.

Be active:- Start your day with physical activity. Take a walk at lunch. Try a kick-boxing or yoga class.

Give yourself a break and relax:- No one says you have to reach your goal without making mistakes along the way. Tell yourself you can succeed in losing weight by taking things one step at a time and starting fresh whenever you slip up. If you overeat one night, just get back on track in the morning by focusing on what's worked for you in the past

Diabetes accounts for more US deaths than previously thought, study shows

Diabetes accounts for 12 percent of deaths in the United States, a significantly higher percentage than previous research revealed, making it the third-leading cause of death after heart disease and cancer, according to findings from the University of Pennsylvania and Boston University published in PLOS ONE.

"Another way of saying that is, if diabetes were eliminated as a disease process, the number of deaths would decline by 12 percent," said Samuel Preston, a sociology professor in Penn's School of Arts & Sciences and part of the Population Studies Center. "There has been only one similar, earlier research effort, and it was based on data from the 1980s and early '90s. It showed deaths attributable to diabetes amounted to roughly 4 percent of total deaths."

Andrew Stokes, a demographer at Boston University who earned a master's degree and a Ph.D. from Penn, and Preston had published a series of articles about excess mortality associated with obesity, focusing recently on diabetes, one of its main consequences. They turned to two well-known, nationally representative datasets, the National Health and Nutrition Examination Survey, or NHANES, and the National Health Interview Survey, or NHIS.

"These are the two major health surveys in the United States," Stokes said. "We can follow people into death records and compare those who have diabetes to those without diabetes."

For the researchers' study purposes, each had its distinct advantages. NHIS was large, providing a sample size of more than 282,000 people, a subset of which self-reported they had diabetes. Though generating smaller numbers, around 21,800, NHANES offered something NHIS did not: a hemoglobin A1c measure, an objective biomarker indicating whether a person met diabetes criteria without needing that person's account of having such a diagnosis. It also captured those who didn't know they had the disease.

The data showed that people with diabetes have about 90 percent higher death rates than people without diabetes. The researchers also found that diabetes as the "underlying cause of death" had been grossly underreported, giving the disease itself less weight as a major contributor to mortality patterns in the U.S.

"When we monitor trends in the health of populations," Stokes said, "and we look at the mortality statistics, some major threats to U.S. mortality and life expectancy stand out, like drug and alcohol poisonings and suicide. Diabetes didn't."

Annually, the U.S. government releases mortality estimates per disease, including diabetes. But, because someone with diabetes often has other health-care complications -- cardiovascular disease, kidney disease -- it can be challenging to pinpoint exact cause of death, leading to ambiguity on a death certificate and to inaccurate mortality statistics.

"There is only one underlying cause of death on a death certificate," Preston said. But "diabetes is not listed as frequently as it is involved in the death of individuals."

More accurate assessment of this epidemic is crucial now, given the sharp increases in its prevalence. In 1980, the Centers for Disease Control and Prevention reported 5.53 million people in the United States with diabetes; in 2014, the most recent year for which statistics exist, that number jumped to 21.95 million people, a nearly 300 percent increase.

"American life expectancy has been growing at a very slow rate for the past decade or so, even decreasing slightly in 2015," Preston said. "It hasn't yet been established statistically, but it's fairly likely that obesity and diabetes together are an important factor in this slowdown. We believe that these estimates will prove useful in helping to more precisely identify their roles."

For now, Stokes and Preston stress the necessity for large-scale solutions in general.

"What our results point to," Stokes said, "is the need for strategies at the population level to combat the epidemics of obesity and diabetes. We need something on a population scale because it's a major issue. It's not an issue that's confined to certain subsets of the population."

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Story Source:

Materials provided by University of Pennsylvania. Note: Content may be edited for style and length.

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Journal Reference:

1. Andrew Stokes, Samuel H. Preston. Deaths Attributable to Diabetes in the United States: Comparison of Data Sources and Estimation Approaches. PLOS ONE, 2017; 12 (1): e0170219 DOI: 10.1371/journal.pone.0170219

Too much sitting, too little exercise may accelerate biological aging

Researchers at University of California San Diego School of Medicine report that elderly women who sit for more than 10 hours a day with low physical activity have cells that are biologically older by eight years compared to women who are less sedentary.

Older women with low physical activity and 10 hours of daily sit time had even 'older' cells

The study, publishing online January 18 in the American Journal of Epidemiology, found elderly women with less than 40 minutes of moderate-to-vigorous physical activity per day and who remain sedentary for more than 10 hours per day have shorter telomeres -- tiny caps found on the ends of DNA strands, like the plastic tips of shoelaces, that protect chromosomes from deterioration and progressively shorten with age.

As a cell ages, its telomeres naturally shorten and fray, but health and lifestyle factors, such as obesity and smoking, may accelerate that process. Shortened telomeres are associated with cardiovascular disease, diabetes and major cancers.

"Our study found cells age faster with a sedentary lifestyle. Chronological age doesn't always match biological age," said Aladdin Shadyab, PhD, lead author of the study with the Department of Family Medicine and Public Health at UC San Diego School of Medicine.

Shadyab and his research team believe they are the first to objectively measure how the combination of sedentary time and exercise can impact the aging biomarker.

Nearly 1,500 women, ages 64 to 95, participated in the study. The women are part of the larger Women's Health Initiative (WHI), a national, longitudinal study investigating the determinants of chronic diseases in postmenopausal women. The participants completed questionnaires and wore an accelerometer on their right hip for seven consecutive days during waking and sleeping hours to track their movements.

"We found that women who sat longer did not have shorter telomere length if they exercised for at least 30 minutes a day, the national recommended guideline," said Shadyab. "Discussions about the benefits of exercise should start when we are young, and physical activity should continue to be part of our daily lives as we get older, even at 80 years old."

Shadyab said future studies will examine how exercise relates to telomere length in younger populations and in men.

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Story Source:

Materials provided by University of California - San Diego. Note: Content may be edited for style and length.

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Journal Reference:

1. Aladdin H. Shadyab et al. Associations of Accelerometer-Measured and Self-Reported Sedentary Time With Leukocyte Telomere Length in Older Women. American Journal of Epidemiology, January 2017 DOI: 10.1093/aje/kww196

New insights into brain circuit for hunger responses during starvation

The empty stomach releases the hormone called ghrelin. By receiving ghrelin, the hypothalamus in the brain senses hunger and produces "hunger signaling" through the action of neuropeptide Y (NPY). The hunger signaling activates neurons in the reticular formation of the medulla oblongata, which then inhibit sympathetic output to reduce metabolic heat production and simultaneously provide masticatory motor rhythm to facilitate feeding.

Researchers uncover mechanism by which hypothalamic neural signaling drives hunger responses to survive starvation.

The human body responds to starving conditions, such as famine, to promote the chance of survival. It reduces energy expenditure by stopping heat production and promotes feeding behavior. These "hunger responses" are activated by the feeling of hunger in the stomach and are controlled by neuropeptide Y (NPY) signals released by neurons in the hypothalamus.

However, how NPY signaling in the hypothalamus elicits the hunger responses has remained unknown.

Sympathetic motor neurons in the medulla oblongata are responsible for heat production by brown adipose tissue (BAT). Researchers centered at Nagoya University have now tested whether the heat-producing neurons respond to the same hypothalamic NPY signals that control hunger responses. They injected NPY into the hypothalamus of rats and tested the effect on heat production. Under normal conditions, blocking inhibitory GABAergic receptors or stimulating excitatory glutamatergic receptors in the sympathetic motor neurons induced heat production in BAT. After NPY injection, stimulating glutamatergic receptors did not produce heat, but inhibiting GABAergic receptors did. The study was recently reported in Cell Metabolism.

"This indicated that hypothalamic NPY signals prevent BAT thermogenesis by using inhibitory GABAergic inputs to sympathetic motor neurons," study lead author Yoshiko Nakamura says.

Retrograde and anterograde tracing with fluorescent dyes revealed which brain region provided the inhibitory GABAergic inputs to heat-producing motor neurons.

"Tracing experiments showed that sympathetic motor neurons are directly innervated by GABAergic inputs from reticular nuclei in the medulla oblongata," corresponding author Kazuhiro Nakamura explains, "selective activation of these GABAergic reticular neurons inhibits BAT thermogenesis."

The researchers' further findings showed that GABAergic inputs from medullary reticular neurons are involved in hypothalamic NPY-mediated inhibition of heat production in BAT. This hunger response circuit probably explains why anorexic individuals suffer from hypothermia.

Interestingly, stimulation of these medullary reticular neurons prompted rats to begin chewing and feeding. This effect was similar to injecting NPY into the hypothalamus, suggesting that hypothalamic NPY signaling activates reticular neurons in the medulla oblongata to promote feeding and mastication during the hunger response.

Abnormal activation of these neurons under non-starved conditions may contribute to obesity. Understanding these mechanisms could lead to development of more effective treatments for obesity.

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Story Source:

Materials provided by Nagoya University. Note: Content may be edited for style and length.

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Journal Reference:

1. Yoshiko Nakamura, Yuchio Yanagawa, Shaun F. Morrison, Kazuhiro Nakamura. Medullary Reticular Neurons Mediate Neuropeptide Y-Induced Metabolic Inhibition and Mastication. Cell Metabolism, 2017; DOI: 10.1016/j.cmet.2016.12.002

How to identify the good and bad Calories for your health

Calories are the most important factor that determines both weight gain and weight loss, and a healthy weight loss plan creates a safe calorie deficit to promote weight loss. The game of weight loss is all about calorie intake and calories burnt. In case of weight balance, all calories are same, but when it comes to overall health, all calories are not the same. The three main sources of calories are fats, carbohydrates, and proteins. Sources of unhealthy saturated fats are butter, cheese and fatty cuts of meats; whereas sources of healthy unsaturated fats are nuts, vegetable oils, olives and seafood. Just like healthy and unhealthy fats, there are healthy and unhealthy carbs as well.

Simple carbs like white rice, sugar, white flour, soda, fruit juices and baked goods are the ones that make you fat. Complex carbohydrates such as brown rice, wheat flour, beans, lentils, legumes, fruits and vegetables aid in weight loss. Proteins are necessary for increasing muscle mass, and the best low saturated fat natural sources of protein are egg whites and Protein Shakes. So, it is important to identify the good and the bad calories and include the right foods in your diet plan to make it healthy and balanced.

4 Craving Crushing Foods

Tough time avoiding the snack drawer ‘til that next meal? Crush cravings by making these four foods a big part of your daily menu.

Besides spending an ample amount of time on the gym floor, satiety is an important part of the fat-fighting equation since people who feel satisfied more often are less likely to snack needlessly between meals. That’s why we rounded up a quartet of the best foods that will take a sledgehammer to your hunger so you won’t be tempted by the vending machine and torpedo your six-pack.

Oatmeal

If you want to silence your hunger pangs all morning long, then make sure to rise and dine on ye olde oatmeal. A 2015 study published in the Annals of Nutrition and Metabolism found that subjects who consumed oatmeal for breakfast felt a greater sense of fullness and consumed 31 percent fewer calories during a follow-up meal than when they consumed the same number of calories in the form of a sugary boxed cereal. The hunger-crushing affects of oatmeal can likely be attributed to its high levels of soluble fiber, which slows down digestion.

Need to know: To bolster satiety and also keep your gut-busting sugar intake in check, be sure to forgo the sugar laden packets of flavored oatmeal in favor of plain oats and jazz them up with some chopped nuts and fresh berries. Or even better, opt for steel-cut oatmeal. Soaking steel-cut oats overnight can slash the cooking time by half.

Greek Yogurt

Here’s more proof that deliciously thick Greek-style yogurt is worthy of a resounding Opa! Scientists at the University of Missouri discovered that healthy volunteers who consumed a high-protein yogurt snack in the afternoon experienced a greater reduction in hunger and calorie consumption during a dinner meal compared to when they ate a snack consisting of chocolate or crackers. During digestion, the sky-high levels of muscle-friendly protein in Greek yogurt sends satiety signals from your gut to your brain thereby acting as a natural appetite depressant and making this great white a near perfect option when a snack attack strikes.

Need to know: To limit your intake of excessive sugar and fat calories, choose a Greek yogurt that is unflavored and with no more than 2 percent fat.

Spinach

That pipe-puffing sailor was onto something when he turned to this green giant to build his hulking pipes. A recent study in the Journal of the American College of Nutrition discovered that compounds in spinach called thylakoids can dull hunger and cravings. A nifty little trick attributed to the power of thylakoids to increase the release of satiety hormones. This can be incredibly valuable when going on a carb- or calorie-restricted diet.

Need to know: To limit your desire for second helpings of pasta Bolognese, kick off a meal with a big bowl of a hunger-fighting spinach laced salad.

Avocado

Yes, you can eat fat to lose fat. Investigators at Loma Linda University determined that participants who included half of an avocado with their lunch reduced their desire to eat by 40 percent over a three-hour period and by 28 percent over a five-hour period following the meal compared to when lunch was consumed sans avocado. The dynamic duo of fiber and healthy fats in this creamy delight can improve blood sugar control, which helps waylay hunger.

Need to know: Instead of nutritionally lackluster mayo, try mashing up a ripe avocado and use this instead for your lunch sandwich spread.