192 Clinical News Report 26 OCT 2014

192CNO23OCT2014

cnosmCNO Report 192

Release Date 26 OCT 2014

Draft Report Compiled by

Ralph Turchiano

http://www.clinicalnews.org

 

In this Issue:

1.      Chemical derived from broccoli sprouts shows promise in treating autism

2.      Disputed theory on Parkinson’s origin strengthened

3.      More Physical Activity Improved School Performance

4.      I have to walk how many miles to burn off this soda?

5.      Resveratrol boosts spinal bone density in men with metabolic syndrome

6.      Sugared soda consumption, cell aging associated in new study

7.      Adenosine can melt ‘love handles’

8.      Vitamin D deficiency increases poor brain function after cardiac arrest by sevenfold

9.      Panic attacks associated with fear of bright daylight

10.   Vaccines and the Risk of Multiple Sclerosis and Other Central Nervous System Demyelinating Diseases

11.   Fresh milk keeps infections at bay

12.   Study suggests altering gut bacteria might mitigate lupus

13.   Resetting the circadian clock: Shift workers might want to skip high-iron foods

14.   Olive oil more stable and healthful than seed oils for frying food

15.   Beetroot beneficial for athletes and heart failure patients, research finds

 

Chemical derived from broccoli sprouts shows promise in treating autism

Improvements were seen within 4 weeks and generally persisted during treatment duration

Results of a small clinical trial suggest that a chemical derived from broccoli sprouts — and best known for claims that it can help prevent certain cancers — may ease classic behavioral symptoms in those with autism spectrum disorders (ASDs).

The study, a joint effort by scientists at MassGeneral Hospital for Children and the Johns Hopkins University School of Medicine, involved 40 teenage boys and young men, ages 13 to 27, with moderate to severe autism.

In a report published online in the journal Proceedings of the National Academy of Sciences during the week of Oct. 13, the researchers say that many of those who received a daily dose of the chemical sulforaphane experienced substantial improvements in their social interaction and verbal communication, along with decreases in repetitive, ritualistic behaviors, compared to those who received a placebo.

“We believe that this may be preliminary evidence for the first treatment for autism that improves symptoms by apparently correcting some of the underlying cellular problems,” says Paul Talalay, M.D., professor of pharmacology and molecular sciences, who has researched these vegetable compounds for the past 25 years.

“We are far from being able to declare a victory over autism, but this gives us important insights into what might help,” says co-investigator Andrew Zimmerman, M.D., now a professor of pediatric neurology at UMass Memorial Medical Center.

ASD experts estimate that the group of disorders affects 1 to 2 percent of the world’s population, with a much higher incidence in boys than girls. Its behavioral symptoms, such as poor social interaction and verbal communication, are well known and were first described 70 years ago by Leo Kanner, M.D., the founder of pediatric psychiatry at The Johns Hopkins University.

Unfortunately, its root causes remain elusive, though progress has been made, Talalay says, in describing some of the biochemical and molecular abnormalities that tend to accompany ASD.

Many of these are related to the efficiency of energy generation in cells. He says that studies show that the cells of those with ASD often have high levels of oxidative stress, the buildup of harmful, unintended byproducts from the cell’s use of oxygen that can cause inflammation, damage DNA, and lead to cancer and other chronic diseases.

In 1992, Talalay’s research group discovered that sulforaphane has some ability to bolster the body’s natural defenses against oxidative stress, inflammation and DNA damage. In addition, the chemical later turned out to improve the body’s heat-shock response — a cascade of events used to protect cells from the stress caused by high temperatures, including those experienced when people have fever.

Intriguingly, he says, about one-half of parents report that their children’s autistic behavior improves noticeably when they have a fever, then reverts back when the fever is gone. In 2007, Zimmerman, a principal collaborator in the current study, tested this anecdotal trend clinically and found it to be true, though a mechanism for the fever effect was not identified.

Because fevers, like sulforaphane, initiate the body’s heat-shock response, Zimmerman and Talalay wondered if sulforaphane could cause the same temporary improvement in autism that fevers do. The current study was designed to find out.

Before the start of the trial, the patients’ caregivers and physicians filled out three standard behavioral assessments: the Aberrant Behavior Checklist (ABC), the Social Responsiveness Scale (SRS) and the Clinical Global Impressions-Improvement scale (CGI-I). The assessments measure sensory sensitivities, ability to relate to others, verbal communication skills, social interactions and other behaviors related to autism.

Twenty-six of the subjects were randomly selected to receive, based on their weight, 9 to 27 milligrams of sulforaphane daily, and 14 received placebos. Behavioral assessments were again completed at four, 10 and 18 weeks while treatment continued. A final assessment was completed for most of the participants four weeks after the treatment had stopped.

Most of those who responded to sulforaphane showed significant improvements by the first measurement at four weeks and continued to improve during the rest of the treatment. After 18 weeks of treatment, the average ABC and SRS scores of those who received sulforaphane had decreased 34 and 17 percent, respectively, with improvements in bouts of irritability, lethargy, repetitive movements, hyperactivity, awareness, communication, motivation and mannerisms.

After 18 weeks of treatment, according to the CGI-I scale, 46, 54 and 42 percent of sulforaphane recipients experienced noticeable improvements in social interaction, aberrant behaviors and verbal communication, respectively.

Talalay notes that the scores of those who took sulforaphane trended back toward their original values after they stopped taking the chemical, just like what happens to those who experience improvements during a fever. “It seems like sulforaphane is temporarily helping cells to cope with their handicaps,” he says.

Zimmerman adds that before they learned which subjects got the sulforaphane or placebo, the impressions of the clinical team — including parents — were that 13 of the participants noticeably improved. For example, some treated subjects looked them in the eye and shook their hands, which they had not done before. They found out later that all 13 had been taking sulforaphane, which is half of the treatment group.

Talalay cautions that the levels of sulforaphane precursors present in different varieties of broccoli are highly variable. Furthermore, the capacity of individuals to convert these precursors to active sulforaphane also varies greatly. It would be very difficult to achieve the levels of sulforaphane used in this study by eating large amounts of broccoli or other cruciferous vegetables.

Disputed theory on Parkinson’s origin strengthened

Parkinson’s disease is strongly linked to the degeneration of the brain’s movement center. In the last decade, the question of where the disease begins has led researchers to a different part of the human anatomy. In 2003, the German neuropathologist Heiko Braak presented a theory suggesting that the disease begins in the gut and spreads to the brain. The idea has since, despite vocal critics, gained a lot of ground. Researchers at Lund University in Sweden now present the first direct evidence that the disease can actually migrate from the gut to the brain.

The so-called Braak’s hypothesis proposes that the disease process begins in the digestive tract and in the brain’s center of smell. The theory is supported by the fact that symptoms associated with digestion and smell occur very early on in the disease.

Researchers at Lund University have previously mapped the spread of Parkinson’s in the brain. The disease progression is believed to be driven by a misfolded protein that clumps together and “infects” neighboring cells. Professor Jia-Yi Li’s research team has now been able to track this process further, from the gut to the brain in rat models. The experiment shows how the toxic protein, alpha-synuclein, is transported from one cell to another before ultimately reaching the brain’s movement center, giving rise to the characteristic movement disorders in Parkinson’s disease.

“We have now been able to prove that the disease process actually can travel from the peripheral nervous system to the central nervous system, in this case from the wall of the gut to the brain. In the longer term, this may give us new therapeutic targets to try to slow or stop the disease at an earlier stage”, says Professor Jia-Yi Li, research group leader for Neural Plasticity and Repair at Lund University.

The research team will now carry out further studies in which the mechanisms behind the transport of the harmful protein will be examined in detail. The current study suggests that the protein is transferred during nerve cell communication. It is at this point of interaction that the researchers want to intervene in order to put a stop to the further spread of the disease.

More Physical Activity Improved School Performance

News: Oct 06, 2014

Just two hours of extra physical activity each week can improve school performance. This has been shown by a study of approximately 2,000 twelve-year-olds carried out by scientists at the Sahlgrenska Academy.

The scientists Lina Bunketorp Käll, Michael Nilsson and Thomas Linden, at the Centre for Brain Repair and Rehabilitation at the Sahlgrenska Academy, University of Gothenburg, have tested the hypothesis that increased physical activity stimulates learning and improves school performance.

In the study, published in the scientific periodical “Journal of School Health”, 408 twelve-year-olds in the Gothenburg region were given two hours of extra play and motion activities per week, in collaboration with a local sports club. This was approximately twice the normal amount of curricular physical activity.

Comparing the achievment

The effect of the intervention was evaluated by comparing the achievement of national learning goals by the children four years before and five years after its implementation. The results were compared to control groups in three schools that did not receive extra physical activity.

The results are clear, according to the scientists: A larger proportion on students in the intervention school did achieve the national learning goals in all subjects examined – Swedish, English and mathematics compared to the control groups.

“You can express it that two hours of extra physical education each week doubled the odds that a pupil achieves the national learning goals. We did not see a corresponding improvement in the control schools, where the pupils did not receive extra physical activity – rather the contrary, a deterioration,” says scientist and neurologist Thomas Linden at the Sahlgrenska Academy.

Carefully chosen schools

The participating schools had been carefully chosen, and the scientists point out that they are fully comparable with respect to the number of boys and girls, the fraction of pupils with foreign background, and the average level of income, unemployment and education of the parents.

“It’s difficult in a study like this to have control of all factors that can influence school performance. But the results are so consistent and point clearly in one direction that we believe that we have a scientific base for our conclusion: extra physical activity seems to help children succeed in school.”

“The results from the current study are in line with other studies in both animals and humans demonstrating links between physical activity and cognition. We have previously found a strong correlation between cardiovascular fitness, IQ and brain resilience in young adults. Interestingly, we now demonstrate a link between physical activity and school performance in young children adding to this exciting line of research, Professor Michael Nilsson says.”

Better understanding

“We have obtained a significantly better understanding of the mechanisms of learning in recent years. And it’s very gratifying to be able to conclude that it is possible to improve the school performance of young pupils with relatively simple means,” says Thomas Linden.

Important to policy-makers

“Our hope is that planners and policy-makers will take our results into consideration”, says Lina Bunketorp Käll the researcher and project leader of the study.

“In an in-depth study we further investigate gender differences, psychological health and mechanisms behind the observed effects”, Dr Bunketorp Käll further explains.

“It’s being discussed whether more physical education in school would take time from academic subjects, and in this way weaken school performance. Our study shows that exactly the opposite may be the case.” says Thomas Lindén.

The study was financed by the Sten A Olsson Foundation for Research and Culture, the Swedish Brain Foundation, the Swedish National Centre for Research in Sports, and the Kempe-Carlgrenska Foundation.

The article The Impact of a Physical Activity Intervention Program on Academic Achievement in a Swedish Elementary School Setting was published in the Journal of School Health in August.

Link to the article: onlinelibrary.wiley.com/doi/10.1111/josh.12179/abstract

 

Corruption of the Health Care Delivery System

Higher Integrity Health Care for Evidence-Based Decision Making

LEBANON, NH – The foundation of evidence-based research has eroded and the trend must be reversed so patients and clinicians can make wise shared decisions about their health, say Dartmouth researchers in the journal Circulation: Cardiovascular Quality and Outcomes.

 

Drs. Glyn Elwyn and Elliott Fisher of The Dartmouth Institute for Health Policy & Clinical Practice are authors of the report in which they highlight five major problems set against a backdrop of “obvious corruption.” There is a dearth of transparent research and a low quality of evidence synthesis. The difficulty of obtaining research funding for comparative effectiveness studies is directly related to the prominence of industry-supported trials: “finance dictates the activity.”

 

The pharmaceutical industry has influenced medical research in its favor by selective reporting, targeted educational efforts, and incentivizing prescriber behavior that influences how medicine is practiced, the researchers say.  The pharmaceutical industry has also spent billions of dollars in direct-to-consumer advertising and has created new disease labels, so-called disease-mongering, and by promoting the use of drugs to address spurious  predictions.

 

Another problem with such studies is publication bias, where results of trials that fail to demonstrate an effect remain unpublished, but trials where the results are demonstrated are quickly published and promoted.

“We do not know when healthcare decisions are guided by sound interpretations of the evidence and whether patients are engaged in the process,” say Elwyn and Fisher. “Rather we observe that in the United States, one of the most highly developed healthcare systems, consumer demand for healthcare is manufactured and manipulated, driving up cost, waste and harm.”

And even if the synthesis is competent, they say, more evidence remains inaccessible and presented in a way that is difficult to translate into effective communication about harms and benefits.

 

“The problems of greatest concern to patients are often left uninvestigated, with emphasis given to research that expands market share,” say Elwyn and Fisher.

The authors offer possible solutions:

 

Problem: Weak Research Foundation
Solution: Regulators should require that trials be compared against the best current therapy rather than placebos; measure outcomes that matter to patients; and have a registry that requires publication of all trial protocols, making it possible to track studies that have not reported results. Also, research outputs should have prominent warnings when the trial design, management and analysis were not done independently of a company who stood to profit by the outcomes.

 

Problem: Low-Quality Evidence Synthesis
Solution: Conflicts of interests must be made transparent and minimized where possible.

 

Problem: Evidence Remains Inaccessible to Those Who Need It
Solution: Redesign the tools of synthesis so the guidelines are shorter and understood by patients and clinicians so they may engage in a meaningful dialogue about the harms and benefits in order to make a shared decision about the course of treatment.

 

Problem: Ineffective Performance Measurement and Accountability
Solution: Measuring volumes while not paying attention to quality leaves patients vulnerable. Two broad initiatives have emerged. One is focused on payment reforms, such as bundled payments and accountable care organizations; the other on advancing performance measurements, such as patient reported outcomes that include improved function, quality of life and meaningful engagement in decision making.

 

Problem: Manufacturing Consumer Demand
Solution: These issues defy an easy solution. The public and the media need to be more skeptical of industry claims and be wary of hype that over promises.

“Solutions to these problems are visible but will be difficult to introduce unless there is a much wider recognition that healthcare has become less about well-founded, trusted relationships between healthcare professionals and patients,” Elwyn and Fisher say. “Rather it looks more like a profit-driven service industry, where commercial interests have influence the value chain.”

 

I have to walk how many miles to burn off this soda?

Easy-to-understand signs linking exercise to sugar-sweetened beverage consumption helps teens make healthier choices, researchers say

Adolescents who saw printed signs explaining the number of miles they would need to walk to burn off the calories in a sugary drink were more likely to leave the store with a lower calorie beverage, a healthier beverage or a smaller size beverage, according to new Johns Hopkins University Bloomberg School of Public Health research.

And those healthier choices persisted weeks after the signs came down.

A report on the findings, published online Oct. 16 in the American Journal of Public Health, adds to the growing evidence suggesting that simply showing calorie counts on products and menus isn’t enough to break Americans from their bad eating habits. With calorie counts expected on menus in chain restaurants with more than 20 outlets by early next year the Affordable Care Act, the researchers say policymakers may need to rethink how that information is communicated.

“People don’t really understand what it means to say a typical soda has 250 calories,” says study leader Sara N. Bleich, PhD, an associate professor in the Department of Health Policy and Management at the Bloomberg School. “If you’re going to give people calorie information, there’s probably a better way to do it. What our research found is that when you explain calories in an easily understandable way such as how many miles of walking needed to burn them off, you can encourage behavior change.”

For six-week stretches between August 2012 and June 2013, Bleich and her colleagues installed signs in six corner stores in low-income, predominantly black Baltimore neighborhoods. The signs, four in all, presented a key fact about the number of calories in a 20 oz. bottle of soda, sports drink or fruit juice: that each bottle contained 250 calories, had 16 teaspoons of sugar, would take 50 minutes of running to work off those calories or would take five miles to walk the calories off. Researchers observed 3,098 drink purchases in the stores by black adolescents between the ages of 12 and 18 and interviewed 25 percent of them after leaving the store about whether they saw and understood the signs. Of the 35 percent of kids who said they saw the signs, 59 percent said they believed them and 40 percent said they changed their behavior as a result.

The researchers posted the brightly colored, 8.5-by-11-inch signs with the calorie information, displaying one sign at a time, on beverage cases in full view of customers. Before the signs were put up, researchers found that 98 percent of drink purchases in the stores were sugary beverages. After, regardless of the type of sign the adolescent saw, the number dropped to 89 percent. When compared with purchasing behaviors during times when there was no signage, the most effective sign, Bleich says, was the one which told shoppers they would have to walk five miles to burn off the drink calories.

Overall, the number of sugary drink calories purchased went from 203 calories before the miles of walking sign to 179 after. The size of the purchases also fell from 54 percent buying more than 16 oz. to 37 percent. Regardless of which sign was posted, the percentage of adolescents who chose to buy no beverage at all increased from 27 percent to 33 percent over the study period. Water purchases, meanwhile, increased from 1 percent to 4 percent.

“This is a very low-cost way to get children old enough to make their own purchases to drink fewer sugar-sweetened beverages and they appear to be effective even after they are removed,” Bleich says. “Black adolescents are one of the groups at highest risk for obesity and one of the largest consumers of sugary beverages. And there is a strong scientific link between consumption of sugary beverages and obesity. Using these easy-to-understand and easy-to-install signs may help promote obesity prevention or weight loss.”

Resveratrol boosts spinal bone density in men with metabolic syndrome

Study suggests compound found in red wine has potential as osteoporosis treatment

Washington, DC—Resveratrol, a natural compound found in red wine and grapes, increased spinal bone density in men with metabolic syndrome and could hold promise as a treatment for osteoporosis, according to a new study published in the Endocrine Society’s Journal of Clinical Endocrinology & Metabolism.

Resveratrol is one of a group of plant compounds known as polyphenols. In addition to red wine and grapes, resveratrol is found in nuts. The compound has anti-inflammatory properties and has been found to protect against bone loss in mice and rats.

Danish researchers set out to investigate whether resveratrol could help men with metabolic syndrome, which has been linked to low-grade inflammation that can cause bone loss. Metabolic syndrome is a cluster of risk factors that raise the risk of developing heart disease, stroke and diabetes. Risk factors can include abdominal obesity, high levels of fats in the blood called triglycerides, elevated blood pressure, high fasting blood sugar and reduced high-density lipoprotein (HDL), or good, cholesterol levels.

“Our study is the first to reveal resveratrol’s potential as an anti-osteoporosis drug in humans,” said one of the study’s authors, Marie Juul Ørnstrup, MD, of Aarhus University Hospital in Aarhus, Denmark. “Our findings suggest the compound stimulates bone-forming cells within the body.”

The randomized, double-blinded, placebo-controlled trial assessed bone mineral density and signs of bone formation and resorption in 66 middle-aged men with metabolic syndrome. For a 16-week period, the men took either a 500-miligram dose of resveratrol, a 75-miligram dose of the compound or a placebo twice a day.

Men who took the higher dose of resveratrol had a 2.6 percent increase in lumbar spine volumetric bone mineral density compared to men who had taken the placebo. The high resveratrol group also had a 16 percent increase in levels of the bone formation marker bone alkaline phosphatase (BAP) compared to the control group.

“In just four months on high-dose resveratrol, we saw significant improvements in bone mineral density at the spine and elevated levels of the bone formation marker BAP,” Ørnstrup said. “These are encouraging results. Additional research is needed to assess whether these bone protective effects occur in populations at risk of osteoporosis during the course of long-term treatment.”

Sugared soda consumption, cell aging associated in new study

UCSF scientists find shorter telomeres in immune cells of soda drinkers

Sugar-sweetened soda consumption might promote disease independently from its role in obesity, according to UC San Francisco researchers who found in a new study that drinking sugary drinks was associated with cell aging.

The study revealed that telomeres — the protective units of DNA that cap the ends of chromosomes in cells — were shorter in the white blood cells of survey participants who reported drinking more soda. The findings were reported online October 16, 2014 in the American Journal of Public Health.

The length of telomeres within white blood cells — where it can most easily be measured — has previously been associated with human lifespan. Short telomeres also have been associated with the development of chronic diseases of aging, including heart disease, diabetes, and some types of cancer.

“Regular consumption of sugar-sweetened sodas might influence disease development, not only by straining the body’s metabolic control of sugars, but also through accelerated cellular aging of tissues,” said Elissa Epel, PhD, professor of psychiatry at UCSF and senior author of the study.

“This is the first demonstration that soda is associated with telomere shortness,” Epel said. “This finding held regardless of age, race, income and education level. Telomere shortening starts long before disease onset. Further, although we only studied adults here, it is possible that soda consumption is associated with telomere shortening in children, as well.”

The authors cautioned that they only compared telomere length and sugar-sweetened soda consumption for each participant at a single time point, and that an association does not demonstrate causation. Epel is co-leading a new study in which participants will be tracked for weeks in real time to look for effects of sugar-sweetened soda consumption on aspects of cellular aging. Telomere shortening has previously been associated with oxidative damage to tissue, to inflammation, and to insulin resistance.

Based on the way telomere length shortens on average with chronological age, the UCSF researchers calculated that daily consumption of a 20-ounce soda was associated with 4.6 years of additional biological aging. This effect on telomere length is comparable to the effect of smoking, or to the effect of regular exercise in the opposite, anti-aging direction, according to UCSF postdoctoral fellow Cindy Leung, ScD, from the UCSF Center for Health and Community and the lead author of the newly published study.

The average sugar-sweetened soda consumption for all survey participants was 12 ounces. About 21 percent in this nationally representative sample reported drinking at least 20 ounces of sugar-sweetened soda a day.

“It is critical to understand both dietary factors that may shorten telomeres, as well as dietary factors that may lengthen telomeres,” Leung said. “Here it appeared that the only beverage consumption that had a measurable negative association with telomere length was consumption of sugared soda.”

The finding adds a new consideration to the list of links that has tied sugary beverages to obesity, metabolic syndrome, type 2 diabetes, and cardiovascular disease, and that has driven legislators and activists in several U.S. jurisdictions to champion ballet initiatives that would tax sugar-sweetened beverage purchases with the goal of discouraging consumption and improving public health.

The UCSF researchers measured telomeres after obtaining stored DNA from 5,309 participants, ages 20 to 65, with no history of diabetes or cardiovascular disease, who had participated in the nation’s largest ongoing health survey, called the National Health and Nutrition Examination Survey, during the years 1999 through 2002. They found that the amount of sugar-sweetened soda a person consumed was associated with telomere length, as measured in the laboratory of Elizabeth Blackburn, PhD, professor of biochemistry at UCSF and a winner of the 2009 Nobel Prize in Physiology or Medicine for her telomere-related discoveries.

Adenosine can melt ‘love handles’

Researchers at the University of Bonn discover a new signaling pathway to combat excess body weight

The number of overweight persons is greatly increasing worldwide – and as a result is the risk of suffering a heart attack, stroke, diabetes or Alzheimer’s disease. For this reason, many people dream of an efficient method for losing weight. An international team of researchers led by Professor Alexander Pfeifer from the University Hospital Bonn, have now come one step closer to this goal. The scientists discovered a new way to stimulate brown fat and thus burn energy from food: The body’s own adenosine activates brown fat and “browns” white fat. The results are now being published in the renowned journal “Nature”.

“Not all fat is equal,” says Professor Alexander Pfeifer from the Institute of Pharmacology and Toxicology of the University Hospital Bonn. Humans have two different types of fat: undesirable white fat cells which form bothersome “love handles”, for example, as well as brown fat cells, which act like a desirable heater to convert excess energy into heat. “If we are able to activate brown fat cells or to convert white fat cells into brown ones, it might be possible to simply melt excess fat away” reports the pharmacologist.

The group of Prof. Pfeifer together with an international team from Sweden, Denmark, Finland, as well as from the Helmholtz-Center Dresden-Rossendorf and the University of Düsseldorf now discovered a new signalling molecule capable of activating brown fat cells: adenosine. Adenosine is typically released during stress. Crucial for transmitting the adenosine signal is the adenosine receptor A2A.

Adenosine activates brown adipose tissue

“If adenosine binds to this receptor in brown fat cells, fat burning is significantly stimulated,” reports Dr. Thorsten Gnad from Prof. Pfeifer’s team. It was previously thought not possible for adenosine to activate brown fat. Several studies with rats and hamsters demonstrated that adenosine blocks brown fat.

However, the researchers from the University of Bonn were not mislead by these previous findings. In contrast, using brown fat cells removed from humans during surgery, the scientists investigated the signaling pathway for fat activation using adenosine. The results showed that rats and hamsters react differently than humans in this regard. “The brown fat in mice on the other hand behaves just as in humans,” summarizes Prof. Pfeifer.

“Browning” of white fat by adenosine

In addition, the research team investigated the possibility that adenosine transforms white fat cells into brown fat cells – a process termed “browning”. White fat cells normally cannot be induced to burn excess fat by adenosine, as they simply lack the A2A receptor. For this reason, the team of scientists transferred the A2A receptor gene from brown fat cells to white fat cells in mice. Consequently, the white fat cells also have A2A receptors and start browning and burning energy.

Clinical application is still far off

As a result, it was possible for the researchers from the University of Bonn to comprehend the significance of adenosine for brown cells in mice and humans for the first time. “Through the administration of adenosine-like substances, the mice actually lost weight,” reports Prof. Pfeifer. However, many questions in this regard still need to be investigated. For this reason, clinical application is still far off.

Vitamin D deficiency increases poor brain function after cardiac arrest by sevenfold

Lack of vitamin D also increases mortality

Geneva, Switzerland – 18 October 2014: Vitamin D deficiency increases the risk of poor brain function after sudden cardiac arrest by seven-fold, according to research presented at Acute Cardiovascular Care 2014 by Dr Jin Wi from Korea. Vitamin D deficiency also led to a higher chance of dying after sudden cardiac arrest.

Acute Cardiovascular Care is the annual meeting of the Acute Cardiovascular Care Association (ACCA) of the European Society of Cardiology (ESC) and takes place 18-20 October in Geneva, Switzerland.

Dr Wi said: “In patients resuscitated after sudden cardiac arrest, recovery of neurological function is very important, as well as survival. Vitamin D deficiency has been reported to be related to the risk of having various cardiovascular diseases, including sudden cardiac arrest. We investigated the association of vitamin D deficiency with neurologic outcome after sudden cardiac arrest, a topic on which there is no information so far.”

The researchers prospectively analysed clinical data from all unconscious patients resuscitated from sudden cardiac arrest of presumed cardiac cause at Severance Cardiovascular Hospital in Seoul, Korea. Neurologic outcome was assessed by the Cerebral Performance Category (CPC) score at 6 months after discharge.1 Good neurologic outcome was defined as a CPC score of 1 or 2, whereas poor neurological outcome was defined as a CPC score of 3 to 5. Vitamin D deficiency was defined as 25-hydroxyvitamin D less than 10 ng/mL.

The study included 53 patients. Bystander cardiopulmonary resuscitation (CPR) was performed in 41 patients (77%). The first monitored heart rhythm was shockable in 36 patients (68%) and non-shockable in 17 patients (32%). The average vitamin D level was 10.3 ng/mL and 31 patients (59%) were deficient.

Patients with a poor neurological outcome had a significantly lower vitamin D level (7.9 ng/mL) compared to those with a good neurological outcome (12.4 ng/mL) (p=0.002). The researchers found that 65% of patients with vitamin D deficiency had a poor neurological outcome at 6 months after discharge compared to 23% of patients with healthy vitamin D levels. They also found that 29% of patients with vitamin D deficiency had died at 6 months compared to none of the patients with good vitamin D levels (p=0.007).

Dr Wi said: “Patients with vitamin D deficiency were more likely to have a poor neurological outcome or die after sudden cardiac arrest than those who were not deficient. Nearly one-third of the patients who were deficient in vitamin D had died 6 months after their cardiac arrest, whereas all patients with sufficient vitamin D levels were still alive.”

The researchers conducted a multivariate logistic analysis to assess the impact of a number of factors on neurological outcome after sudden cardiac arrest. They found that vitamin D deficiency independently predicted poor neurological outcome with an odds ratio of 7.13.

Dr Wi said: “Vitamin D deficiency increased the risk of poor neurological outcome after sudden cardiac arrest by 7-fold. The only factors that had a greater impact on poor neurological outcome were the absence of bystander CPR or having a first monitored heart rhythm that was non-shockable.”

He added: “Our findings suggest that vitamin D deficiency should be avoided, especially in people with a high risk of sudden cardiac arrest. People are at higher risk if they have a personal or family history of heart disease including heart rhythm disorders, congenital heart defects and cardiac arrest. Other risk factors for cardiac arrest include smoking, obesity, diabetes, a sedentary lifestyle, high blood pressure and high cholesterol, and drinking too much alcohol.”

Dr Wi continued: “Vitamin D is found in oily fish, such as salmon, sardines, and mackerel, eggs, fortified fat spreads, fortified breakfast cereals and powdered milk. Most of our vitamin D stores are made by the body when our skin reacts to sunlight.”

He concluded: “A large randomised clinical trial is needed to find out whether supplements of vitamin D can protect high risk groups from having a sudden cardiac arrest.”

Panic attacks associated with fear of bright daylight

Berlin, 20 October 2014 Fear of bright daylight is associated with panic disorder, according to new presented at the ECNP congress in Berlin.

Panic disorder is where a person has recurring and regular panic attacks. In the UK, it affects about two in 100 people, and it’s about twice as common in women as it is in men1. Previous studies have shown that there is a strong seasonal component in panic disorder, but this is the first study to look specifically at panic disorder patients’ reactions to light.

A group of researchers from the University of Siena (Italy) compared 24 patients with panic disorder (PD) against 33 healthy controls. Using a standard Photosensitivity Assessment Questionnaire (PAQ), they found that healthy controls showed a slight (not statistically significant) tendency to be photophilic – to be attracted to bright light. In contrast, the patients with panic disorder showed medium to high levels of aversion to bright light.

The Photosensitivity Assessment Questionnaire asks subjects to agree or disagree with a series of questions about their attitude towards light, for example “My ideal house has large windows” or “Sunlight is so annoying to me, that I have to wear sunglasses when I go out”. The mean values in the Photosensitivity Assessment Questionnaire were as follows: patients with photophobia scored 0.34 (± 0.32 SD), healthy subjects scored 0,11 (± 0,13 SD).

According to lead researcher, Dr Giulia Campinoti:

“There have been several hints that photophobia is associated with panic disorder; for example in some people, fluorescent light can induce panic attacks. It had also been noted that people with panic disorder often protect themselves from light, for example by wearing sunglasses.

We believe that photophobia is one of the elements which may increase the risk of people suffering from panic attacks, but this is a small study, so it needs to be confirmed by a longer-term follow-up trial. For example, we need to understand if the photosensitivity and panic attacks continue to be related over time. If we can confirm this, then we may be able to take steps to avoid some of the triggers to panic attacks. It is important to note that our work shows an association, not necessarily a cause and effect. We don’t yet know exactly what the relationship might be, but there is probably some underlying biochemical basis”.

Commenting for the ECNP, Professor Siegfried Kasper (Vienna) said: “This is a very interesting study that confirms our previous finding that anxiety components within depression cannot be treated with light therapy”.

 
Vaccines and the Risk of Multiple Sclerosis and Other Central Nervous System Demyelinating Diseases

 

Importance  Because vaccinations are common, even a small increased risk of multiple sclerosis (MS) or other acquired central nervous system demyelinating syndromes (CNS ADS) could have a significant effect on public health.

 

Objective  To determine whether vaccines, particularly those for hepatitis B (HepB) and human papillomavirus (HPV), increase the risk of MS or other CNS ADS.

 

Design, Setting, and Participants  A nested case-control study was conducted using data obtained from the complete electronic health records of Kaiser Permanente Southern California (KPSC) members. Cases were identified through the KPSC CNS ADS cohort between 2008 and 2011, which included extensive review of medical records by an MS specialist. Five controls per case were matched on age, sex, and zip code.

 

Exposures  Vaccination of any type (particularly HepB and HPV) identified through the electronic vaccination records system.

 

Main Outcomes and Measures  All forms of CNS ADS were analyzed using conditional logistic regression adjusted for race/ethnicity, health care utilization, comorbid diseases, and infectious illnesses before symptom onset.

 

Results  We identified 780 incident cases of CNS ADS and 3885 controls; 92 cases and 459 controls were females aged 9 to 26 years, which is the indicated age range for HPV vaccination. There were no associations between HepB vaccination (odds ratio [OR], 1.12; 95% CI, 0.72-1.73), HPV vaccination (OR, 1.05; 95% CI, 0.62-1.78), or any vaccination (OR, 1.03; 95% CI, 0.86-1.22) and the risk of CNS ADS up to 3 years later. Vaccination of any type was associated with an increased risk of CNS ADS onset within the first 30 days after vaccination only in younger (<50 years) individuals (OR, 2.32; 95% CI, 1.18-4.57).

 

Conclusions and Relevance  We found no longer-term association of vaccines with MS or any other CNS ADS, which argues against a causal association. The short-term increase in risk suggests that vaccines may accelerate the transition from subclinical to overt autoimmunity in patients with existing disease. Our findings support clinical anecdotes of CNS ADS symptom onset shortly after vaccination but do not suggest a need for a change in vaccine policy.

 

 

Fresh milk keeps infections at bay

München, 10/20/2014

A study by LMU researchers shows that infants fed on fresh rather than UHT cow’s milk are less prone to infection. The authors recommend the use of alternative processing methods to preserve the protectants found in the natural product.

 

Foto: Marco2811 / Foltolia.com

A pan-European study, led by Professor Erika von Mutius, Professor of Pediatric Allergology at LMU and Head of the Asthma and Allergy Department at Dr. von Hauner’s Children’s Hospital, reports that fresh cow’s milk protects young children from respiratory infections, febrile illness and inflammation of the middle ear. Their results appear in the “Journal of Allergy and Clinical Immunology”. As untreated cow’s milk may itself contain pathogenic microorganisms and could pose a health risk, the researchers argue for the use of processing methods that preserve the protective agents present in raw milk.

The findings are the latest to emerge from the long-term PASTURE study, which is exploring the role of dietary and environmental factors in the development of allergic illness. The study initially recruited 1000 pregnant women who were asked to document their children’s diet and state of health at weekly intervals during the first year of life. “Among children who were fed on fresh, unprocessed cow’s milk the incidence of head colds and other respiratory infections, febrile and middle-ear inflammation was found to be significantly lower than in the group whose milk ration consisted of the commercially processed ultra-pasteurized product,” says Dr. Georg Loss of Dr. von Hauner’s Hospital, first author of the new paper. Ingestion of farm milk reduced the risk of developing these conditions by up to 30%, and the effect was diminished if the milk was heated at home before consumption. Conventionally pasteurized milk retained the ability to reduce the risk of febrile illness, while exposure to the higher temperatures used in UHT processing eliminated the effect altogether. Importantly, the positive impact of raw milk could be clearly separated from the confounding effects of other elements of the children’s nutrition.

Impact on inflammation
“The effects of diverse milk treatments are presumably attributable to differentially heat-resistant components present in fresh milk. Compounds that are sensitive to heating seem to play a particularly important role in protection against respiratory-tract and ear infections,” says Loss.

At the end of the first year of life, blood samples were obtained from the children enrolled in the study, and tested for biochemical indicators of immunological function. Infants fed on unprocessed milk were found to have lower levels of the C-reactive protein, which is a measure of inflammation status. “Other studies have shown that higher levels of inflammation are related to the subsequent emergence of chronic conditions such as asthma and obesity. Consumption of unprocessed milk may therefore reduce the risk of developing asthma,” Loss explains.

Industrial processing of milk involves short-term heating of the raw product. Conventionally pasteurized milk has been exposed to temperatures of 72-75°C for 15 seconds, while ultra-pasteurized milk undergoes heating at around 135°C for a few seconds. The latter is also homogenized to disperse the milk fats, which prevents the formation of cream. “Consumption of unprocessed milk itself is not entirely without risk,” says Loss. Indeed, untreated milk may contain pathogenic bacteria that cause serious illnesses. Examples include the enterohemorrhagic Escherichia coli (EHEC) strains that are associated with severe diarrhea and kidney failure, and the microorganisms that cause listeriosis and tuberculosis. The researchers therefore suggest that alternative processing methods are needed for the industrial treatment of raw milk. “With novel, milder treatments one could produce milk that is free of pathogenic microorganisms but retains the protective agents found in fresh milk,” says Loss.

The perks of country life
In addition to fats and carbohydrates, cow’s milk contains proteins that can modulate the function of the immune system. “In many respects, the composition of cow’s milk is similar to that of human milk,” says Loss. It has long been known that breast-feeding protects infants from infection, although how milk actually affects the early immune function remains unclear. It is possible that some of the factors involved interact directly with viruses or that they promote the development of a healthy immune system by altering the composition of the gut microflora.

Feeding young children with cow’s milk is also contentious because it can provoke allergic reactions. Among the children who participated in the PASTURE study only 2% had developed an allergy to milk or other food items prior to their first birthday.

That living in the country has positive effects on the immune system has been demonstrated in several previous studies. Together these investigations show, as Erika von Mutius notes, that “children who grow up on traditional dairy farms are least likely to develop allergies.”

The 1000 pregnant women involved in the PASTURE study were recruited in rural areas of Bavaria, Finland, France, Switzerland and Austria, and approximately half of them live on farms. As well as monitoring maternal nutrition during pregnancy, the study will regularly assess their children’s health and developmental status during the first 10 years of life, in order to elucidate the role of environmental factors in the etiology of allergic disease. The study is being carried out by teams at LMU and the German Center for Lung Research, universities in Ulm, Marburg, Basel, Helsinki, Kuopio (Finland) and Besançon (France) and children’s hospitals in St. Gallen (Switzerland) and Schwarzach (Austria).
(Journal of Allergy and Clinical Immunology)

Study suggests altering gut bacteria might mitigate lupus

WASHINGTON, DC – October 20, 2014 — Lactobacillus species, commonly seen in yogurt cultures, correlate, in the guts of mouse models, with mitigation of lupus symptoms, while Lachnospiraceae, a type of Clostridia, correlate with worsening, according to research published ahead of print in Applied and Environmental Microbiology. “Our results suggest that the same investigation shold be performed in human subjects with lupus,” says principal investigator Xin Luo of Virginia Tech, Blacksburg, VA.

In the study, the investigators first showed that mouse models of lupus had higher levels of Lachnospiraceae (a type of Clostridia), and lower Lactobacillus than control mice. They also compared male and female mice, and found that the differences were present only in females. These results suggest that the gut bacteria may contribute to lupus, a disease which is nine times as prevalent in women as in men, says first author Husen Zhang.

They also monitored the gut microbiota over time in both lupus and control mice, and found that in the former, Clostridia increased in both early and late stages of the disease.

In further experiments, the investigators treated the symptoms in the lupus mice with either retinoic acid alone or vitamin A plus retinoic acid. The latter worsened the symptoms—surprisingly, Luo says, because it had been expected to reduce them—and in those mice, Clostridia increased, while Lactobacillus declined. Retinoic acid alone improved the symptoms, with opposite population changes in the gut bacteria.

The research suggests, but does not prove that altering the gut microbiota could mitigate lupus. Nonetheless, Luo suggests that people with lupus should eat Lactobacillus-containing probiotics, such as live culture yogurts, to reduce lupus flares. More generally, “The use of probiotics, prebiotics, and antibiotics has the potential to alter microbiota dysbiosis, which in turn could improve lupus symptoms,” says co-principal investigator Husen Zhang. Ultimately, says Luo, fecal transplant might prove valuable as a treatment for lupus.

“We were inspired in part to perform this research by a study on type 1 diabetes, which found that that disease is dependent on gut microbiota,” says Zhang. “Like type 1 diabetes, lupus is an autoimmune disease that is even more prevalent [than type 1 diabetes] in women.”

Resetting the circadian clock: Shift workers might want to skip high-iron foods

Researchers identify role of iron in liver’s regulation of blood glucose levels

(SALT LAKE CITY)—Workers punching in for the graveyard shift may be better off not eating high-iron foods at night so they don’t disrupt the circadian clock in their livers.

Disrupted circadian clocks, researchers believe, are the reason that shift workers experience higher incidences of type 2 diabetes, obesity and cancer. The body’s primary circadian clock, which regulates sleep and eating, is in the brain. But other body tissues also have circadian clocks, including the liver, which regulates blood glucose levels.

In a new study in Diabetes online, University of Utah researchers show that dietary iron plays an important role in the circadian clock of the liver. Judith A. Simcox, Ph.D., a University of Utah postdoctoral fellow in biochemistry, is the study’s lead author.

“Iron is like the dial that sets the timing of the clock,” Simcox says. “Discovering a factor, such as iron, that sets the circadian rhythm of the liver may have broad implications for people who do shift work.”

Each of the body’s circadian clocks operates on its own schedule to perform its necessary functions. The circadian clock in the brain, for example, is set by light, telling people to wake up in the morning and sleep when it’s dark. Ideally all the body’s clocks would work on their correct schedules. But, as anyone who has ever been on a graveyard or swing shift knows, working off-hours can cause one’s circadian clocks to get out of synch and disrupt sleeping and eating patterns.

Numerous studies have found that shift workers experience higher incidences of obesity, diabetes and other metabolic disorders. The risk for cardiovascular disease, stroke and cancer also is higher among those workers. In 2007, a World Health Organization subcommittee declared that shift work is probably carcinogenic.

External Signals

The liver’s circadian clock is set by food intake. As people sleep this clock helps maintain a constant blood glucose level, but then causes it to spike just before they wake up. When the clock in the liver gets out of synch with the one in the brain, it may contribute to metabolic diseases, according to Donald A. McClain, M.D., Ph.D., University of Utah professor of medicine (endocrinology) and biochemistry and senior author on the study.

McClain and Simcox wanted to identify external signals that set the circadian clock in the liver. They fed iron to mice as part of their natural eating cycle and observed that dietary iron increases the cellular concentration of heme, an oxygen-carrying iron compound found in hemoglobin. They found that when heme binds to a circadian protein–a substance whose function Simcox likens to that of a cog in a mechanical clock–the protein’s activity increases and causes the liver to optimally control blood glucose levels.

Increased activity of a circadian protein is healthy when it occurs in the liver’s natural clock cycle. But if this happens at a time that is out of synch with the circadian clock, such as during a graveyard shift, it could result in abnormal blood glucose levels.

“When a shift worker eats foods high in iron at night it could exacerbate the lack of synchronization between the clock in the liver and the main one in the brain,” says McClain, who’s also the University Health Sciences’ associate vice president for clinical research and director of the Center for Clinical and Translational Science. “By tending to flatten the circadian variation of metabolism, high iron in tissues may also interfere with the normal day to night fluctuations associated with a healthy metabolic system.”

More research is needed to see how the results of their study could affect dietary recommendations for everyone, and shift workers in particular. The investigators are quick to point out that too little iron is also unhealthy. Ultimately, they hope their studies define an optimal range of iron that is much narrower than the current “normal” range.

Olive oil more stable and healthful than seed oils for frying food

Frying is one of the world’s most popular ways to prepare food — think fried chicken and french fries. Even candy bars and whole turkeys have joined the list. But before dunking your favorite food in a vat of just any old oil, consider using olive. Scientists report in ACS’ Journal of Agricultural and Food Chemistry that olive oil withstands the heat of the fryer or pan better than several seed oils to yield more healthful food.

Mohamed Bouaziz and colleagues note that different oils have a range of physical, chemical and nutritional properties that can degrade oil quality when heated. Some of these changes can lead to the formation of new compounds that are potentially toxic. By-products of heating oil can also lower the nutritional value of the food being fried. Bouaziz’s team wanted to find out which cooking oil can maintain its quality under high heat and repeated use.

The researchers deep- and pan-fried raw potato pieces in four different refined oils — olive, corn, soybean and sunflower — and reused the oil 10 times. They found that olive oil was the most stable oil for deep-frying at 320 and 374 degrees Fahrenheit, while sunflower oil degraded the fastest when pan-fried at 356 degrees. They conclude that for frying foods, olive oil maintains quality and nutrition better than seed oils.

Beetroot beneficial for athletes and heart failure patients, research finds

MANHATTAN, Kansas — Football teams are claiming it improves their athletic performance, and according to new research from Kansas State University, it also benefits heart failure patients. The special ingredient: beetroot.

Recently, the Auburn University football team revealed its pregame ritual of taking beetroot concentrate, or beet juice, before each game. The juice may have contributed to the team’s recent winning season — and one exercise physiologist who has been studying the supplement for several years says that may be the case.

“Our research, published in the journal Physiology in 2013, has shown that the nitrate found in beetroot concentrate increases blood flow to skeletal muscles during exercise,” said David Poole, professor of exercise kinesiology and anatomy and physiology at Kansas State University. The journal Physiology is widely regarded as the world’s premiere physiology journal.

The researchers’ latest study, “Microvascular oxygen pressures in muscles comprised of different fiber types: Impact of dietary nitrate supplementation,” was published in the Journal of Nitric Oxide, Biology and Chemistry. This work provides the basis for how beetroot juice may benefit football players by preferentially increasing blood flow to fast-twitch muscle fibers — the ones used for explosive running. This work was performed by Poole; Scott Ferguson, doctoral student in anatomy and physiology; and Timothy Musch, professor of exercise kinesiology and anatomy and physiology, all at Kansas State University.

In addition to improving athletic performance, the research also found that beetroot juice can improve the quality of life for heart failure patients.

“Remember, for every one football player in the United States, there are many thousands of heart failure patients that would benefit from this therapy,” Poole said. “It’s a big deal because even if you can only increase oxygen delivery by 10 percent, that can be the difference between a patient being wheelchair-bound versus getting up and walking around and interacting with his or her family.”

The benefits of beetroot come from the nitrate found within it. The amount of nitrate in one 70-milliliter bottle of beetroot juice is about the same amount found in 100 grams of spinach.

“When consumed, nitrate is reduced in the mouth by bacteria into nitrite,” Ferguson said. “The nitrite is swallowed again and then reduced to nitric oxide, which is a potent vasodilator. The nitric oxide dilates the blood vessels, similar to turning on a water faucet, and allows blood to go where it needs to go.”

The beetroot juice consumption resulted in a 38 percent higher blood flow to the skeletal muscles during exercise and was preferential to the less-oxygenated, fast-twitch muscles.

“Heart failure is a disease where oxygen delivery to particular tissues, especially working skeletal muscles, is impaired, decreasing the capacity to move the arms or legs and be physically active,” Poole said. “The best therapy for these patients is getting up and moving around. However, that is often difficult. Increasing the oxygen delivery to these muscles through beetroot can provide a therapeutic avenue to improve the quality of life for these patients.”

Clinical trials are currently underway.

 

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