Review: Most clinical studies on vitamins flawed by poor methodology

 CORVALLIS, Ore. – Most large, clinical trials of vitamin supplements, including some that have concluded they are of no value or even harmful, have a flawed methodology that renders them largely useless in determining the real value of these micronutrients, a new analysis suggests.

Many projects have tried to study nutrients that are naturally available in the human diet the same way they would a powerful prescription drug. This leads to conclusions that have little scientific meaning, even less accuracy and often defy a wealth of other evidence, said Balz Frei, professor and director of the Linus Pauling Institute at Oregon State University, in a new review published in the journal Nutrients.

These flawed findings will persist until the approach to studying micronutrients is changed, Frei said. Such changes are needed to provide better, more scientifically valid information to consumers around the world who often have poor diets, do not meet intake recommendations for many vitamins and minerals, and might greatly benefit from something as simple as a daily multivitamin/mineral supplement.

Needed are new methodologies that accurately measure baseline nutrient levels, provide supplements or dietary changes only to subjects who clearly are inadequate or deficient, and then study the resulting changes in their health. Tests must be done with blood plasma or other measurements to verify that the intervention improved the subjects’ micronutrient status along with biomarkers of health. And other approaches are also needed that better reflect the different ways in which nutrients behave in cell cultures, lab animals and the human body.

The new analysis specifically looked at problems with the historic study of vitamin C, but scientists say many of the observations are more broadly relevant to a wide range of vitamins, micro nutrients and studies.

“One of the obvious problems is that most large, clinical studies of vitamins have been done with groups such as doctors and nurses who are educated, informed, able to afford healthy food and routinely have better dietary standards than the public as a whole,” said Frei, an international expert on vitamin C and antioxidants.

Vitamin or mineral supplements, or an improved diet, will primarily benefit people who are inadequate or deficient to begin with, OSU researchers said. But most modern clinical studies do not do baseline analysis to identify nutritional inadequacies and do not assess whether supplements have remedied those inadequacies. As a result, any clinical conclusion made with such methodology is pretty much useless, they said.

“More than 90 percent of U.S. adults don’t get the required amounts of vitamins D and E for basic health,” Frei said. “More than 40 percent don’t get enough vitamin C, and half aren’t getting enough vitamin A, calcium and magnesium. Smokers, the elderly, people who are obese, ill or injured often have elevated needs for vitamins and minerals.

“It’s fine to tell people to eat better, but it’s foolish to suggest that a multivitamin which costs a nickel a day is a bad idea.”

Beyond that, many scientists studying these topics are unaware of ways in which nutrients may behave differently in something like a cell culture or lab animal, compared to the human body. This raises special challenges with vitamin C research in particular.

“In cell culture experiments that are commonly done in a high oxygen environment, vitamin C is unstable and can actually appear harmful,” said Alexander Michels, an LPI research associate and lead author on this report. “And almost every animal in the world, unlike humans, is able to synthesize its own vitamin C and doesn’t need to obtain it in the diet. That makes it difficult to do any lab animal tests with this vitamin that are relevant to humans.”

Even though such studies often significantly understate the value of vitamin supplements, the largest and longest clinical trial of multivitamin/mineral supplements found a total reduction of cancer and cataract incidence in male physicians over the age of 50. It suggested that if every adult in the U.S. took such supplements it could prevent up to 130,000 cases of cancer each year, Frei said.

“The cancer reduction would be in addition to providing good basic health by supporting normal function of the body, metabolism and growth,” he said. “If there’s any drug out there that can do all this, it would be considered unethical to withhold it from the general public. But that’s basically the same as recommending against multivitamin/mineral supplements

Source:Oregon State University,.”

Finnish research team reveals how emotions are mapped in the body

Researchers Aalto University have revealed how emotions are experienced in the body.

Emotions adjust our mental and also bodily states to cope with the challenges detected in the environment. These sensations arising from the bodily changes are an important feature of our emotional experiences. For example, anxiety may be experienced as pain in the chest, whereas falling in love may trigger warm, pleasurable sensations all over the body. New research from Aalto University reveals, how emotions are literally experienced through the body.

The researchers found that the most common emotions trigger strong bodily sensations, and the bodily maps of these sensations were topographically different for different emotions. The sensation patterns were, however, consistent across different West European and East Asian cultures, highlighting that emotions and their corresponding bodily sensation patterns have a biological basis.

- Emotions adjust not only our mental, but also our bodily states. This way the prepare us to react swiftly to the dangers, but also to the opportunities such as pleasurable social interactions present in the environment. Awareness of the corresponding bodily changes may subsequently trigger the conscious emotional sensations, such as the feeling of happiness, tells assistant professor Lauri Nummenmaa from Aalto University.

- The findings have major implications for our understanding of the functions of emotions and their bodily basis. On the other hand, the results help us to understand different emotional disorders and provide novel tools for their diagnosis.

The research was carried out on line, and over 700 individuals from Finland, Sweden and Taiwan took part in the study. The researchers induced different emotional states in their Finnish and Taiwanese participants. Subsequently the participants were shown with pictures of human bodies on a computer, and asked to colour the bodily regions whose activity they felt increasing or decreasing.

The research was funded by European Research Council (ERC), The Academy of Finland and the Aalto University (aivoAALTO project)

The results were published on 31 December (U.S. Eastern time) in the scientific journal Proceedings of The National Academy of Sciences of The United States of America (PNAS).

 

Pharma units will soon be asked to set up exclusive patient safety monitoring cells

Every pharmaceutical manufacturing unit in the country will have to set up patient monitoring cell, in the line of quality cells, with a view to share the onus of patients’ safety by the manufacturers.

The Central Drugs Standard Control Organisation (CDSCO) will issue direction in this regard any time in January to direct the pharma companies to set up the cells. “We are going to observe 2014 as the year of patient and animal safety and creation of monitoring cells will be part of this,” Drugs Controller General of India (DCGI) Dr G N Singh told Pharmabiz.

“We have to fix the onus of patient safety also on the manufacturers. These cells will have dedicated people and they will report to the chief executive officer of the company. We will also make several initiatives as part of the patients’ safety year,” he said.

The move will also aim at creating additional job opportunities in the pharmaceutical sector, especially for the trained pharmacists. The cells would continuously monitor the quality of the products, apart from tracking the adverse reactions of medicines once in the market.

Already on the animal safety front, the government has planned a number of steps including banning of animal testing for cosmetics. The Health Ministry has decided to amend the rules after the issues were raised some Members of the Parliament and activists,  and as per the efforts to harmonise the standards in line with the European Union directive in March this year, making the testing of cosmetics on animals completely illegal.

However, the new move to create patient monitoring cells may invite wrath from the industry as it would put additional burden on the companies by way of infrastructure and budget.
Source:Pharmabiz

Ayurveda doctors want Kerala govt to include ayurveda in state E-health programme

Even as the government of Kerala is busy preparing an E-Health Programme to bring all health related information of hospitals and patients into a centralized information system to ensure continuity in healthcare, the ayurvedic fraternity including the government doctors is intensifying their efforts to get their system included in the programme.

According to Kerala Government Ayurveda Medical Officers Association (KGAMOA), presently E-Health programme of the government includes only projects on allopathic treatments. So, to explore avenues for getting a position for ayurveda in the IT oriented health projects, KGAMOA has urged the state government to revise all projects and include the traditional system of Kerala into the e-health program of the government.

After submitting memorandum to the health minister in this regard, the general secretary of KGAMOA, Dr M Sharmad Khan said the e-health programme is an integrated health project covering the entire health sector of Kerala including all the public healthcare institutions. But in all the projects of the programme, Ayurveda has been ignored and no project for traditional medicines is envisaged.

He said, while implementing the projects, more ayurvedic and naturopathy dispensaries can be opened in the IT centres like Techno Park, Infosys and the like. The programme should not be an initiative of allopathy alone.

While speaking to Pharmabiz, Dr Sharmad alleged that the ayurvedic health sector in the state was full of problems and despite several clamors, the government was not interested to address the problems, especially the pathetic  condition of the hospitals.

“Even after 65 years of independence, more than 150 Punchayaths in the state have no government dispensaries for ayurveda which is the own traditional healing system of Kerala. Out of these 150 Punchayaths, certain villages have the central government sponsored NRHM units, whereas in 37 Punchayaths neither NRHM unit nor state dispensary is functioning,” he said.
Regarding speciality treatment facilities in government hospitals, he said not all the district hospitals or the general hospitals have such units and doctors were not appointed. He said there is no shortage of specialized PG holders looking for jobs in the government sector and they should be appointed in the vacancies of the hospitals.
Government should also envisage projects to start Taluk Hospitals for Ayurveda, unani, siddha, naturopathy and homoeopathy. Dr Sharmad said presently there are only two hospitals in the Taluk level in Kerala, one in Mavelikkara and other one in Kasargodu. All the hospitals are facing shortage of all varieties of medicines also.
“The most pathetic condition prevailing in certain government hospitals is lack of therapists for holding Panchakarma chikitsa for IP patients. Now the treatment is done in many hospitals by nurses, and they too are inexperienced in therapy. There are eight specialty treatments in Ayurveda such as Kaaya chikitsa (general medicine), Baala chikitsa (paediatrics), Graha chikitsa (psychiatry), Oordhwanga chikitsa (ENT, ophthalmology and dentistry), Salya chikitsa (ortho anorectal diseases), Damshtra chikitsa (toxicology), Jara chikitsa (geriatrics) and Vrisha chikitsa (afrodisiac). No hospital in Kerala has the facility for all these eights treatments. Only Kaaya chikitsa is available in most of the district hospitals,” the secretary of KGAMOA told Pharmabiz.
The association also demanded to the government to start more Ayurveda hospitals in the tourist centres and special packages of tourism should include ayurveda and naturopathy dispensaries.
Source:Pharmabiz

New method to detect genetic defects in egg cells could double the success rate of IVF

Infertility affects up to 15 percent of couples around the world, and in vitro fertilization (IVF) is one way to treat this common condition. A study published by Cell Press December 19th in the journal Cell reveals a safe, accurate, and low-cost method to select genetically normal embryos for the IVF procedure and thereby increase a couple's chance of producing a healthy child.
Through whole-genome sequencing of individual egg cells, the new method detects chromosomal abnormalities and DNA sequence variations associated with genetic disorders. "In this way, we kill two birds with one stone: one set of deep sequencing analysis to avoid two types of genetic problems," says study author Jie Qiao of Third Hospital, Peking University. "Theoretically, if this works perfectly, we will be able to double the success rate of test tube baby technology from 30 percent to 60 percent or even more."
The IVF procedure involves joining a woman's egg and a man's sperm in a laboratory dish and then transferring embryos into the woman's womb. Various procedures are currently available to detect genetic defects in embryos prior to implantation, but these approaches are often invasive, requiring the removal of cells from the growing embryo, and do not simultaneously detect both chromosomal abnormalities and DNA sequence variations associated with genetic disorders.
Researchers have recently developed whole-genome sequencing methods to simultaneously detect both types of defects in single human sperm cells, but until now, an analogous approach had not been applied to egg cells, even though chromosomal abnormalities are much more common in egg cells than in sperm cells.
In the new study, Sunney Xie of Peking University and Harvard University teamed up with Qiao and Fuchou Tang of Peking University to develop a method for sequencing the entire genomes of polar bodies—cells that arise as a byproduct of egg cell division and often die later on. Because polar bodies are dispensable for human embryonic development, they can be safely removed without harming the embryo. "We are now starting a clinical trial based on this approach," Xie says. "If the clinical trial works, this technique could enormously increase the success rate of IVF, especially for older women or women who have had recurrent miscarriages."
Source:Peking University and Harvard University

Nutrition influences metabolism through circadian rhythms, UCI study finds

A high-fat diet affects the molecular mechanism controlling the internal body clock that regulates metabolic functions in the liver, UC Irvine scientists have found. Disruption of these circadian rhythms may contribute to metabolic distress ailments, such as diabetes, obesity and high blood pressure.
There’s good news, though. The researchers also discovered that returning to a balanced, low-fat diet normalized the rhythms. This study reveals that the circadian clock is able to reprogram itself depending on a diet’s nutritional content – which could lead to the identification of novel pharmacological targets for controlled diets.
UC Irvine’s Paolo Sassone-Corsi, the Donald Bren Professor of Biological Chemistry and one of the world’s leading researchers on the genetics of circadian rhythms, led the study, which appears in Cell.
Circadian rhythms of 24 hours govern fundamental physiological functions in virtually all organisms. The circadian clocks are intrinsic time-tracking systems in our bodies that anticipate environmental changes and adapt themselves to the appropriate time of day. Changes to these rhythms can profoundly influence human health. Up to 15 percent of people’s genes are regulated by the day-night pattern of circadian rhythms, including those involved with metabolic pathways in the liver.
A high-fat diet reprograms the liver clock through two main mechanisms. One blocks normal cycles by impeding the clock regulator genes called CLOCK:BMAL1. The other initiates a new program of oscillations by activating genes that normally do not oscillate, principally through a factor called PPAR-gamma. Previously implicated in inflammatory responses and the formation of fatty tissue, this factor oscillates with a high-fat diet.
It’s noteworthy, Sassone-Corsi said, that this reprogramming takes place independent of the state of obesity; rather, it’s solely dependent upon caloric intake – showing the remarkable adaptability of the circadian clock.
The authors will extend their research to the effects of a high-fat diet on other body components, including muscle, fat, the brain and blood plasma.
Pierre Baldi, Kristin Eckel-Mahan, Vishal Patel, Sara de Mateo Lopez, Ricardo Orozco Solis, Nicholas Ceglia, Saurabh Sahar and Sherry Dilag-Penilla of UC Irvine; and Kenneth Dyar of the Venetian Institute of Molecular Medicine in Padova, Italy, contributed to the study, which received support from the National Institutes of Health (grants F32 DK083881, GM081634, AG033888, LM010235 and T15 LM07443), the National Science Foundation, the Merieux Research Institute and Sirtris/GSK.
Source:University of California, Irvine: Located in coastal Orange County, near a thriving employment hub in one of the nation’s safest cities, UC Irvine was founded in 1965. One of only 62 members of the Association of American Universities, it’s ranked first among U.S. universities under 50 years old by the London-based Times Higher Education. The campus has produced three Nobel laureates and is known for its academic achievement, premier research, innovation and anteater mascot. Led by Chancellor Michael Drake since 2005, UC Irvine has more than 28,000 students and offers 192 degree programs. It’s Orange County’s second-largest employer, contributing $4.3 billion annually to the local economy.

Parasitic DNA proliferates in aging tissues

The genomes of organisms from humans to corn are replete with "parasitic" strands of DNA that, when not suppressed, copy themselves and spread throughout the genome, potentially affecting health. Earlier this year Brown University researchers found that these "retrotransposable elements" were increasingly able to break free of the genome's control in cultures of human cells. Now in a new paper in the journal Aging, they show that RTEs are increasingly able to break free and copy themselves in the tissues of mice as the animals aged. In further experiments the biologists showed that this activity was readily apparent in cancerous tumors, but that it also could be reduced by restricting calories.
"As mice age we are seeing deregulation of these elements and they begin to be expressed and increase in copy number in the genome," said Jill Kreiling, a research assistant professor at Brown, and leader of the study published in advance online Dec. 7. "This may be a very important mechanism in leading to genome instability. A lot of the chronic diseases associated with aging, such as cancer, have been associated with genome instability."
Whether the proliferation of RTEs is exclusively a bad thing remains a hot question among scientists, but what they do know is that the genome tries to control RTEs by wrapping them up in a tightly wound configuration called heterochromatin. In their experiments, Kreiling and co-corresponding author Professor John Sedivy found that overall, the genomes of several mouse tissues become more heterochromatic with age. But they also found, paradoxically, that some regions where RTEs are concentrated became - loosened up instead , particularly after mice reached the 2-year mark (equivalent to about the 70-year mark for a person).
An important advance in this paper compared to the prior work in cell cultures, Sedivy said, is that the researchers were able to show the loosening of control over RTEs was associated with the chronological aging of the whole organism and specific tissues. Before in cell culture the aging they tracked was based on the number of times individual cells were able to divide. That kind of cellular aging is called "replicative senescence" and is believed to be rare in many normal tissues.
"This brings home the magnitude of the problem," Sedivy said. "We looked in some pretty major tissues. This appears to be a much more widespread phenomenon. The observation that RTEs become activated with chronological aging of mouse tissues also brings this research in close alignment with very similar discoveries using the fruit fly Drosophila in the labs of Brown Professors Stephen Helfand and Robert Reenan,. The remarkable evolutionary conservation of these fundamental molecular processes indicates that they are likely important aspects of aging. "
In the new research, the team including lead author Marco DeCecco looked at cells from the liver and skeletal muscle of mice at ages 5, 24 and 36 months. Comparing gene expression and DNA sequences from the cells, they found elevated expression in both tissues of many RTEs after 24 months. Not only were the RTEs expressed more, but also they succeeded in copying themselves and showing up elsewhere in the genome. For example, an RTE named "MusD" became more than twice as abundant in liver tissue between the ages 24 and 36 months.
The RTEs were considerably less successful in proliferating, however, in mice who were still adequately nourished, but fed 40 percent fewer calories than mice fed a standard diet. Calorie restriction has been widely shown to mitigate many consequences of aging in different animal models.
On the other hand, the researchers found that several RTEs were much more abundant in mouse tissues affected by naturally occurring cancers, such as lymphoma and hepatocellular carcinoma.
The research does not yet provide evidence that RTEs have a causal role in cancer, Sedivy said. For the time being it's only an association. But he said that researchers have a path forward to study the health consequences of the RTE proliferation that apparently occurs in aging. Certain drugs can inhibit RTE proliferation so researchers should be able to see if doing so extends the amount of time an animal is healthy and free of chronic disease in future mouse experiments.
Source:Brown University

Eradicate Quackery, Save Lives

Prevalence of quackery in our society is as old as the society itself. In olden days, folks used to blindly believe the good-at-words, weirdly dressed man sitting at the corner of the road, claiming to have remedies for all the ailments that ever saw the light of the day.

Times have changed. So has the educational levels and scientific awareness. But sadly, quackery still prevails in many forms.

The interesting part is, now the “up-market” quacks are making full use of the modern technology in selling and promoting their stuff through media like Internet and Television and other hi-tech areas.

 

Health Authorities in Haryana Crack Down on Quacks

Haryana Health authorities have cracked down on quacks who have been selling so-called herbal medicines to pregnant women by saying that these will ensure they give birth to a male child.     
National Health Mission's mission director-cum-commissioner (Food and Drug Administration) Rakesh Gupta Sunday said 15 criminal cases have been registered against unregistered medical practitioners (quacks) Saturday and six quacks have been arrested.

"The FDA has launched a special drive to combat the menace of quackery. So far, more than 100 FIRs have been against the quacks in the state," Gupta said.

The highest number of cases have been registered in Faridabad (23), Jhajjar (21) and Mewat (21).

Gupta said that recent studies by the Post-Graduate Institute of Medical Sciences, Rohtak had revealed that couples having two or more girls were taking "Su badalne ki dawai" from the quacks in the first trimester for having a male child but this only resulted in still births and congenital malformation in infants.

The quacks were giving "shivalinga" and "majuphal" during 8-10 weeks of pregnancy, which resulted in still births and congenital birth defects.

"It has been found during the research that the pregnant women taking shivalinga and majuphal given by quacks have three times more chances of still birth and congenital malformation," Gupta said.

The health authorities have directed all civil surgeons to identify such quacks and register cases against them. Gupta said the actions of the quacks were resulting in increase in infant mortality rate in the state.
 Source:Reporter from Haryana
 

New study: High mortality in US Central Southern states most likely due to smoking

 

NEW YORK (26 December 2013) — Between 1965 and 2004, the distribution of states with the highest mortality changed dramatically. In 1965, the states with the highest mortality (Rhode Island, Alaska, Delaware, Pennsylvania, and New Hampshire) were spread across geographic regions. By 2004, however, the states with the highest mortality were geographically contiguous, and located in the south. The Central South (Alabama, Kentucky, Mississippi, and Tennessee) had the highest mortality rates in the United States. A new study by Andrew Fenelon of Brown University explores the possibility that smoking behaviors account for this situation.
Fenelon used US mortality data from vital statistics on cause of death for the period 1965-2004 and, for the purposes of this study, considered lung cancer deaths to be indicative of cigarette smoking. In the US, more than 90 percent of lung cancer deaths among men and more than 80 percent among women result from smoking. Although the prevalence of smoking declined in all states in that time period, southern states, particularly Kentucky, have maintained overall high levels of smoking.
Fenelon found that in the Central South, mortality attributable to smoking peaked later than in other regions and at a significantly higher death rate, indicating a greater and more persistent burden of smoking. By 2004, the gap in mortality attributable to smoking between the Central Southern states and states in other regions was exceptionally large: among men, smoking explained as much as 75 percent of the difference between the Central South and other US regions.
Laws and policies in the Central South do not strongly discourage smoking. There are currently 10 states with no statewide ban on smoking (for example, in workplaces or restaurants); nearly all of these states are in the South. State taxes on tobacco products also remain low in the Central Southern states compared to other states with lower mortality from smoking. Studies have shown that smoking bans and tobacco taxes reduce the prevalence of smoking.
This study highlights geographic inequalities in health and mortality within the US and underscores the importance of narrowing these gaps as a public policy goal.
Source:Population Council

EU Considering a Ban on Danish Cinnamon Rolls

The European Union is considering a ban on Danish cinnamon rolls, or kanelsnegler, after finding that they contain very high levels of cinnamon, which could prove to be harmful for the liver.The 2008 EU regulations limited the amount of cinnamon to 5 and 50 milligrams per kilogram of food. The EU revealed that excess consumption of coumarin, a naturally occurring toxic chemical found in cassia cinnamon, could lead to liver damage. 
A recent study conducted by Danish Food Administration has found that the amount of cinnamon in kanelsnegler exceeds the maximum limit. While Denmark can ignore the EU regulation, with EU countries allowed the freedom to retain certain food privileges for the sake of tradition, the government has gone ahead with plans to restrict cinnamon levels to 15 mg per kilogram of baked products. The move has unsurprisingly drawn criticism from Danish bakers who say that it will be the end of cinnamon rolls as they know it. "Cinnamon rolls are of course a traditional Danish baked product. There is no point in limiting cinnamon. We have used it in Danish baking for as long as I can remember. It's the end of the cinnamon roll as we know it", Hardy Christensen, head of the Danish Baker's Association, said.
 Source:Danish Baker's Association

Survey Says Widows Better Off on Wellbeing Index

 

In a latest survey by National Australia Bank Wellbeing Index, widowed people have higher levels of well-being than married couples.

Women aged 18 to 29 are the unhappiest age group, added the survey.

When it comes to marital status, widows and widowers had the highest levels of well-being, the survey, that included 2,100 Australians, showed.

"In particular, mental well-being, feeling part of the community and physical health are significantly stronger contributors to the well-being of widows when compared to married couples," NAB economists were quoted as saying in Herald Sun.

Those with no children reported higher levels of well-being than those with children, while the highest earners were happier than those on lower incomes.

Those in regional cities reported the highest levels of well-being, compared with people in capital cities and rural areas, the survey added.

When it comes to age, women aged 18 to 29 reported the lowest levels of wellbeing while women aged 50-plus reported the highest levels.

 Source:Herald Sun.

 

Chitosan Molecule Improves Nerve Cell Adherence

Nerve cell adherence and growth along the surface of a material can now be promoted by the chitosan molecule. It can enhance the adherence and influx of Schwann cells, thus encouraging the growth of axons.
However, physical nerve guidance by a nerve conduit may not be sufficient to foster optimal recovery. Dr. Huawei Liu and colleagues from Institute of Stomatology, Chinese PLA General Hospital in China prepared microspheres containing nerve growth factor for sustained release by a compound method, and implanted them into chitosan conduits to repair 10-mm defects on the right buccal branches of the facial nerve in rabbits.

Researchers found that the sustained in vitro release of active nerve growth factor lasted for at least 90 days. The muscular atrophy induced by facial nerve defects was attenuated, and the nerve conduction velocity and amplitude were significantly increased. Moreover, microspheres for sustained release of nerve growth factor in combination with chitosan conduits improved axon and myelin sheath regeneration of injured facial nerve.

These findings, published in the Neural Regeneration Research (Vol. 8, No. 33, 2013), indicate that the combination of nerve growth factor-releasing microspheres and chitosan conduits exhibits superior effects in repairing facial nerve injury compared with nerve growth factor alone.

 Source:Neural Regeneration Research
 

Study Shows How Plants Evolved to Survive Cold Winters

Researchers have studied how flowering plants evolve specific strategies, like the seasonal shedding of leaves, to move into areas with cold winters, say researchers.
Early flowering plants are thought to have been woody-which maintain a prominent stem above ground across years and changing weather conditions, such as maple trees-and restricted to warm, wet tropical environments.

Lead author Amy Zanne, assistant professor of biology in the George Washington University's Columbian College of Arts and Sciences, said freezing is like a plant's equivalent to frostbite, asserting that their water-conducting pipes can be blocked by air bubbles as water freezes and thaws, and over time, if plants moved into colder climates, they've had to figure out how to get around these problems.

Dr. Zanne and a team of researchers identified three repeated evolutionary shifts they believe flowering plants made to fight the cold. Plants either:

dropped their leaves seasonally, shutting down the pathways that would normally carry water between roots and leaves;

made skinnier water-conducting pathways, allowing them to keep their leaves while reducing the risk of air bubbles developing during freezing and thawing, which would shut down those pathways (the fatter the pathways, the higher the risk); or

avoided the cold seasons altogether as herbs, losing aboveground stems and leaves and retreating as seeds or storage organs underground, such as tulips or tomatoes.

Source:The results have been published in journal Nature.

 

Cancer-promoting protein is vital to safe division of tumor cells

PKM2 controls mitosis, saving cancer cells from death and promoting brain tumor growth

HOUSTON – Researchers have caught a protein they previously implicated in a variety of cancer-promoting roles performing a vital function in cell division, survival and development of brain tumors.
In a paper published in Molecular Cell, Zhimin Lu, Ph.D., professor of Neuro-Oncology at The University of Texas MD Anderson Cancer Center and colleagues report how a tumor-specific protein flips a crucial switch in an irregular mechanism for mitosis that allows cancer cells to safely divide.
"Our research shows that tumor cells rely heavily on a distinct mechanism for orderly cell division that's driven by oncogene-induced pyruvate kinase M2," Lu said.
After a cell begins division by replicating all of its chromosomes, mitosis separates them into two identical sets of chromosomes for both cells. After mitosis, cytokinesis completes cell divison.
"Without PKM2 regulating a checkpoint in mitosis, the tumor cell would not successfully divide," Lu said. "Depleting PKM2 led to an uneven distribution of DNA to the two new cells, triggering programmed cell death, or apoptosis, of those cells after division."
"This new, additional role for PKM2 in cancer development and survival may provide a molecular basis for diagnosing and treating tumors with upregulated PKM2," Lu said. He and his colleagues have now identified four specific mechanisms by which PKM2 promotes cancer development.
PKM2 regulation of mitosis worsens tumors in mice; affects human glioblastoma


The key relationship between PKM2 activity and mitosis uncovered by the researchers led to rapid brain tumor growth when activated in mice, while blocking it reduced tumor volume by 83 percent and more than doubled survival from about 20 days to beyond 40 days.
Analysis of 50 human glioblastoma multiforme tumors and 50 lung cancer tumors confirmed the relationship in human cancer and indicated an effect on survival for patients with glioblastoma, the most common and lethal form of brain tumor.
PKM2 can act as a protein kinase, which gives orders to other proteins by attaching phosphate groups to them. While it plays a normal role in sugar metabolism, PKM2 also actively promotes cell growth during infancy when such growth is desired.
Usually, Lu said, it eventually turns off, but tumor cells reactivate PKM2, and it is famously overexpressed in solid tumors. This tumor-specific PKM2 is activated by the epidermal growth factor receptor (EGFR), which is overactive in a variety of cancers.
Deplete PKM2 in mitosis, tumor cells abnormally divide in multiple cancer types
A series of experiments in glioblastoma cell lines revealed that PKM2 phosphorylates a protein called Bub3, activating it to interact with others in a protein complex that assures orderly and equal chromosome separation.
Depleting PKM2 blocked Bub3 activation, leading to an increase in cells with abnormal numbers of chromosomes and programmed cell death.
The team confirmed its findings in human breast, prostate, lung, pancreatic and colon cancer cell lines.
PKM2-induced Bub3 activation was essential for development of brain tumors in mice. Experiments in the 50 glioblastoma and lung cancer tumors confirmed that phosphorylation of Bub3 correlates with phosphorylation of H3-S10, a marker of cell mitosis in tumor cells.
With low Bub3 phosphorylation, glioblastoma patients live longer Among the 50 glioblastoma patients, the 15 with low levels of Bub3 phosphorylation had a median survival of 69.8 weeks, compared to 40.5 weeks for the 35 patients with high levels of Bub3 activation.
Previous research by Lu and colleagues showed PKM2, usually active outside the cell nucleus, slips into the nucleus where it promotes cancer formation, growth and survival by:

• Activating an important transcription co-factor that, in turn, activates other cancer-promoting genes.
  
• Phosphorylating the histone protein H3, loosening the packaging of DNA and leading to the activation of cell division genes.
  
• Inducing expression of glycolytic genes (including PKM2 itself) and triggering a glucose metabolism mechanism called the Warburg effect that nourishes tumor cells.
  

Potential avenues for thwarting these effects identified in their experiments include two classes of drug that inhibit SRC and MEK activity.
"Our research further highlights the importance of PKM2 in human cancers and of developing ways to target its activity and use it as a biomarker to guide treatment," Lu said.
Source:University of Texas M. D. Anderson Cancer Center

Proportion of opioid treatment programs offering on-site testing for HIV and STIs declines

A survey of opioid treatment programs finds that the proportion offering on-site testing for human immunodeficiency virus (HIV) and sexually transmitted infections (STIs) declined substantially between 2000 and 2011, despite guidelines recommending routine opt-out HIV testing in all health care settings, according to a study appearing in the December 25 issue of JAMA.
"Opioid dependence is a risk factor for HIV, STIs, and hepatitis C virus (HCV) infection. Opioid treatment programs, which provide treatment to more than 300,000 opioid-dependent individuals in the United States, are well-positioned to offer testing for these infectious diseases to a high-risk population. They were among the first venues to offer HIV testing and are more likely to offer HIV, STI, and HCV testing than other drug treatment programs. Private for-profit opioid treatment programs are increasingly widespread and such programs offer on-site HIV testing less often than nonprofit and public programs. However, with the 2006 national recommendations for routine opt-out HIV testing, we hypothesized that the percentage of programs offering on-site testing for HIV, STIs, and HCV would increase," the authors write.
Marcus A. Bachhuber, M.D., and Chinazo O. Cunningham, M.D., M.S., of the Albert Einstein College of Medicine, New York, analyzed data from a survey sent to directors of drug treatment facilities and tabulated the percentage of opioid treatment programs offering on-site HIV, STI, and HCV testing from 2000 to 2011.
The number of U.S. opioid treatment programs increased from 849 in 2000 to 1,175 in 2011. The percentage of programs operating as for-profit businesses increased from 43 percent to 54 percent, nonprofits decreased from 43 percent to 36 percent, and public programs decreased from 14 percent to 10 percent. From 2000 to 2011, the absolute number of programs offering testing for HIV, STIs, and HCV increased but the percentage offering on-site testing for HIV declined by 18 percent and for STIs by 13 percent. There was no change for HCV testing. More than 75 percent of public programs offered on-site testing for each infection, with no change over time.
"Declines were most pronounced in for-profit programs, suggesting that persons enrolled in these programs may be at increased risk for delayed diagnosis and continued transmission of HIV, STIs, and HCV," the authors write.
"Opioid treatment programs are important venues for offering testing to high-risk individuals. As the number of for-profit opioid treatment programs increases, and the opioid, HIV, and HCV epidemics continue to intersect, further work is needed to understand and reverse declines in offering on-site testing."
Source:JAMA

NIH study shows enzyme that produces melatonin originated 500 million years ago

An international team of scientists led by National Institutes of Health researchers has traced the likely origin of the enzyme needed to manufacture the hormone melatonin to roughly 500 million years ago.
Their work indicates that this crucial enzyme, which plays an essential role in regulating the body’s internal clock, likely began its role in timekeeping when vertebrates (animals with spinal columns) diverged from their nonvertebrate ancestors.
An understanding of the enzyme’s function before and after the divergence may contribute to an understanding of such melatonin-related conditions as seasonal affective disorder, jet lag, and to the understanding of disorders involving vision.
The findings provide strong support for the theory that the time-keeping enzyme originated to remove toxic compounds from the eye and then gradually morphed into the master switch for controlling the body’s 24-hour cyclic changes in function.
The researchers isolated a second, nonvertebrate form of the enzyme from sharks and other contemporary animals thought to resemble the prototypical early vertebrates that lived 500 million years ago.
The study, published online in PNAS, was conducted by senior author David C. Klein, Ph.D., Chief of the Section on Neuroendocrinology in the NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and colleagues at NIH, and at institutions in France, Norway, and Japan.
Melatonin is a key hormone that regulates the body’s day and night cycle. Dr. Klein explained that it is manufactured in the brain’s pineal gland and is found in small amounts in the retina of the eye. Melatonin is produced from the hormone serotonin, the end result of a multistep sequence of chemical reactions. The next-to-last step in the assembly process consists of attaching a small molecule — the acetyl group — to the nearly finished melatonin molecule. This step is performed by an enzyme called arylalkylamine N-acetyltransferase, or AANAT.
Because of its key role in producing the body clock-regulating melatonin, AANAT is often referred to as the timezyme, Dr. Klein added.
The form of AANAT found in vertebrates occurs in the brain’s pineal gland and, in small amounts, in the retina. Another form of the enzyme, termed nonvertebrate AANAT, has been found only in other forms of life, such as bacteria, plants and insects.
“Nonvertebrate AANAT appears to detoxify a broad range of potentially toxic chemicals,” Dr. Klein said. “In contrast, vertebrate AANAT is highly specialized for adding an acetyl group to melatonin. The two are as different from each another as a Ferrari is from a Model-T Ford, considering the speed of the reaction and how fast it can be turned on and off.”
In 2004, Dr. Klein and his coworkers published a theory that melatonin was at first a kind of cellular waste, a by-product created in cells of the eye when normally toxic substances were rendered harmless. Because melatonin accumulated at night, the ancestors of today's vertebrates became dependent on melatonin as a signal of darkness. As the need for greater quantities of melatonin grew, the pineal gland developed as a structure separate from the eyes, to keep serotonin and other toxic substances needed to make melatonin away from sensitive eye tissue.
“The pineal glands of birds and reptiles can detect light,” Dr. Klein said. “And the retinas of human beings and other species also make melatonin. So it would appear that both tissues evolved from a common, ancestral, light-detecting tissue.”
Before the current study, the researchers lacked proof of their theory, particularly in regard to the question of how the vertebrate form of the enzyme originated because it did not appear to exist in non-vertebrates and had been found only in bony fishes, reptiles, birds, and mammals — all of which lacked the non-vertebrate form.
The first evidence of how the vertebrate form of the enzyme originated came when study co-author Steven L. Coon, also of NICHD, discovered genes for the nonvertebrate and vertebrate forms of AANAT in genomic sequences from the elephant shark, considered to be a living representative of early vertebrates.
This finding indicated that the vertebrate form of AANAT may have resulted after a phenomenon known as gene duplication, Dr. Klein said. Gene duplication, he added, typically results from any of a number of genetic mishaps during cell division. Instead of one copy of a gene resulting from the process, an additional copy results, so that there are two versions of a gene where only one existed previously. The phenomenon is thought to be a major factor influencing evolutionary change.
The researchers theorized that following duplication, one form of AANAT remained unchanged and the other gradually evolved into the vertebrate form. Dr. Klein said that at some point after vertebrate AANAT developed, vertebrates appear to have stopped making the nonvertebrate form, perhaps because it was no longer needed or because its function was replaced by a similar enzyme.
Before the researchers could continue, they needed to confirm their finding, to rule out that the nonvertebrate AANAT they found didn’t result from accidental contamination with bacteria or some other organism. The NICHD researchers sought assistance from other research teams around the world. DNA from Mediterranean sharks and sea lampreys was obtained via fishermen’s catches by Jack Falcon of the Arago Laboratory, a marine biology facility that is part of the CNRS and the Pierre and Marie Curie University in France. Samples from a close relative of the elephant shark — the ratfish — were provided by Even-Jorgensen at the Arctic University of Norway. Finally, Susumo Hyodo of the University of Tokyo contributed samples from elephant sharks he collected off the coast of Australia.
Next, the Hyodo and Falcon groups isolated RNA from the retinas and pineal glands of the animals. RNA is used to direct the assembly of amino acids into proteins. From these RNA sequences, it was possible to assemble working versions of AANAT molecules — both the vertebrate and nonvertebrate forms.
The sequences of the proteins encoded by the AANAT genes were analyzed by Eugene Koonin and Yuri Wolf of the National Library of Medicine using computer techniques designed to study evolution. Peter Steinbach, of NIH’s Center for Information Technology, examined the three-dimensional structures of nonvertebrate and vertebrate AANAT in the study animals and determined that the two forms of the enzyme likely had a common ancestor.
Taken together, their results provide evidence for the hypothesis that nonvertebrate AANAT resulted from duplication of the non-vertebrate AANAT gene about 500 million years ago and that following this event one copy of the duplicated gene eventually changed into the gene for vertebrate AANAT.
In addition to providing information on the origin of melatonin and the evolution of AANAT, the findings also have implications for research on disorders affecting vision. Vertebrate AANAT and melatonin are found in small amounts in the eyes of humans and other vertebrates. Although they may play a role in detoxifying compounds, it is also reasonable to consider that this detoxifying function is shared with other enzymes.
“It’s possible that a malfunction in these other enzymes might lead to an accumulation of chemicals known as arylalkamines — in the same family as serotonin — and this might contribute to eye disease,” Dr. Klein said. “Consequently, research into how these enzymes function might lead to therapies to protect vision.”
The NICHD sponsors research on development, before and after birth; maternal, child, and family health; reproductive biology and population issues; and medical rehabilitation.
NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the US Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases.
Source:Pharmabiz

Excitement may be Better Than Relaxation When It Comes to Anxiety-Inducing Situations

People who try to get excited may be better able to face anxiety-inducing situations like public speaking, as opposed to individuals who try to relax, a new study found.
"Anxiety is incredibly pervasive. People have a very strong intuition that trying to calm down is the best way to cope with their anxiety, but that can be very difficult and ineffective," study author Alison Wood Brooks, PhD, of Harvard Business School, said.

"When people feel anxious and try to calm down, they are thinking about all the things that could go badly. When they are excited, they are thinking about how things could go well."

Several experiments conducted at Harvard University with college students and members of the local community showed that simple statements about excitement could improve performance during activities that triggered anxiety.

Since both anxiety and excitement are emotional states characterized by high arousal, it may be easier to view anxiety as excitement rather than trying to calm down to combat performance anxiety, Brooks said.

"When you feel anxious, you're ruminating too much and focusing on potential threats," she said. "In those circumstances, people should try to focus on the potential opportunities. It really does pay to be positive, and people should say they are excited. Even if they don't believe it at first, saying 'I'm excited' out loud increases authentic feelings of excitement."

Source:The study was published online in APA's Journal of Experimental Psychology: General.


 

Researchers Discover How Rho-associated Protein Kinase Modulates Neurite Extension

An essential regulator of cytoskeletal dynamics during the process of neurite extension is rho-associated protein kinase. However, whether Rho kinase regulates microtubule remodeling or the distribution of adhesive proteins to mediate neurite outgrowth remains unclear. 
By using the ROCK inhibitor, Y-27632, and the agonist, lysophosphatidic acid, Kenen Chen and colleagues from First Affiliated Hospital of Jinan University in China observed that neurite outgrowth, microtubule remodeling and vinculin redistribution were tightly regulated by ROCK. They found that lysophosphatidic acid inhibited neurite outgrowth, which could be reversed by Y-27632.

Meanwhile, reorganization of microtubules was noticed during these processes, as indicated by their significant changes in the soma and growth cone. These findings, published in the Neural Regeneration Research (Vol. 8, No. 32, 2013), suggest that Rho kinase regulates rat hippocampal neurite growth and microtubule formation via a mechanism associated with the redistribution of vinculin. 
Source:Neural Regeneration Research

 

Study shows Where Alzheimer's starts and how it spreads

Using high-resolution functional MRI (fMRI) imaging in patients with Alzheimer's disease and in mouse models of the disease, Columbia University Medical Center (CUMC) researchers have clarified three fundamental issues about Alzheimer's: where it starts, why it starts there, and how it spreads. In addition to advancing understanding of Alzheimer's, the findings could improve early detection of the disease, when drugs may be most effective. The study was published today in the online edition of the journal Nature Neuroscience.
"It has been known for years that Alzheimer's starts in a brain region known as the entorhinal cortex," said co-senior author Scott A. Small, MD, Boris and Rose Katz Professor of Neurology, professor of radiology, and director of the Alzheimer's Disease Research Center. "But this study is the first to show in living patients that it begins specifically in the lateral entorhinal cortex, or LEC. The LEC is considered to be a gateway to the hippocampus, which plays a key role in the consolidation of long-term memory, among other functions. If the LEC is affected, other aspects of the hippocampus will also be affected."
The study also shows that, over time, Alzheimer's spreads from the LEC directly to other areas of the cerebral cortex, in particular, the parietal cortex, a brain region involved in various functions, including spatial orientation and navigation. The researchers suspect that Alzheimer's spreads "functionally," that is, by compromising the function of neurons in the LEC, which then compromises the integrity of neurons in adjoining areas.
A third major finding of the study is that LEC dysfunction occurs when changes in tau and amyloid precursor protein (APP) co-exist. "The LEC is especially vulnerable to Alzheimer's because it normally accumulates tau, which sensitizes the LEC to the accumulation of APP. Together, these two proteins damage neurons in the LEC, setting the stage for Alzheimer's," said co-senior author Karen E. Duff, PhD, professor of pathology and cell biology (in psychiatry and in the Taub Institute for Research on Alzheimer's Disease and the Aging Brain) at CUMC and at the New York State Psychiatric Institute.
In the study, the researchers used a high-resolution variant of fMRI to map metabolic defects in the brains of 96 adults enrolled in the Washington Heights-Inwood Columbia Aging Project (WHICAP). All of the adults were free of dementia at the time of enrollment.
"Dr. Richard Mayeux's WHICAP study enables us to follow a large group of healthy elderly individuals, some of whom have gone on to develop Alzheimer's disease," said Dr. Small. "This study has given us a unique opportunity to image and characterize patients with Alzheimer's in its earliest, preclinical stage."
The 96 adults were followed for an average of 3.5 years, at which time 12 individuals were found to have progressed to mild Alzheimer's disease. An analysis of the baseline fMRI images of those 12 individuals found significant decreases in cerebral blood volume (CBV) — a measure of metabolic activity — in the LEC compared with that of the 84 adults who were free of dementia.
A second part of the study addressed the role of tau and APP in LEC dysfunction. While previous studies have suggested that entorhinal cortex dysfunction is associated with both tau and APP abnormalities, it was not known how these proteins interact to drive this dysfunction, particularly in preclinical Alzheimer's.
To answer this question, explained first author Usman Khan, an MD-PhD student based in Dr. Small's lab, the team created three mouse models, one with elevated levels of tau in the LEC, one with elevated levels of APP, and one with elevated levels of both proteins. The researchers found that the LEC dysfunction occurred only in the mice with both tau and APP.
The study has implications for both research and treatment. "Now that we've pinpointed where Alzheimer's starts, and shown that those changes are observable using fMRI, we may be able to detect Alzheimer's at its earliest preclinical stage, when the disease might be more treatable and before it spreads to other brain regions," said Dr. Small. In addition, say the researchers, the new imaging method could be used to assess the efficacy of promising Alzheimer's drugs during the disease's early stages.
Source:Columbia University Medical Center

Why is Laughter Not Always the Best Medicine? A Serious Take on Laughter

Laughter may not be the best medicine, after all. The Christmas issue of British Medical Journal (BMJ), one of the world's oldest and most prestigious medical journals, takes a hard and serious take on laughter. Laugh related dangers range from asthma attacks to strokes, says the article. Laughter is not purely beneficial. The harms it can cause are immediate and dose related, the risks being highest for Homeric (uncontrollable) laughter," the authors wrote.

The authors delved deep into researches related to laughter that were published between 1946 and 2013; an analysis was drawn from nearly 5000 studies.

Harms
Psychological harms:

Laughter weakens resolve and promotes your preference for certain brands. Hence it is better for doctors to be sceptical of those cheer laden witty drug reps.

Laughter may not be that good for the heart:

Hearty laughter can cause syncope, due to neurological changes. It can lead to conduction abnormalities and arrhythmias. 'Laughing fit to burst can cause cardiac rupture,' observes BMJ. There has been a reported case of death after intense sustained laughter in a woman with a condition known as long QT syndrome.

Respiratory harms:

Laugher may provoke inhalation of foreign bodies. It sometimes triggers attacks of asthma. Pilgaard-Dahl syndrome is a rare condition in which middle aged smokers can develop a condition called pneumothorax. Exhaled air flow during laughter can disseminate infections.

Harms to the nervous system:

Laughter can trigger cataplexy, i.e. sudden loss of muscle tone. It may precipitate headaches. In one recorded case, 'a woman with a patent foramen ovale laughed uproariously for three minutes, became aphasic, and had a cerebral infarct.''

Harms to the digestive system:

Laughter is an unusual precipitant of Boerhaave's syndrome, i.e. spontaneous rupture of the food pipe. It may also make hernia protrude.

Laughter is thus not as light as we think. A strong laughter may dislocate your jaw; it can cause stress incontinence.

Gelastic seizures manifest by laughing, thus laughter can be pathological.

Benefits

Don't panic anyway, laughter also has a brighter side. Laughter can increase pain thresholds. Laughter prevents heart attacks; it is good for blood vessels. Authors also note that laughter induced by a clown improved lung function in patients with the lung condition called chronic obstructive pulmonary disease.

'A day of merriment consumes over 8360 kJ (2000 kcal), improves glycaemic control, and cures obesity'. Laughter has obstetric benefits; would-be-mothers undergoing treatment for infertility benefitted from the entertainment provided clown, dressed as a chef de cuisine.

The ENT benefits may be deduced from this line, "A surgeon proceeded to read [to me] the diverting history of 'The Lady Rohesia' [from The Ingoldsby Legends], and how she was cured of her quinsy... The story caused me to laugh, and this led to the bursting of the [tonsillar] abscess, and to my cure without the use of cold steel."

The latest revelations 'refute the proposition that laughter can only be beneficial.' Well, now we have been warned decently well about the risks of outbursts of laughter!

Reference: Laughter and MIRTH (Methodical Investigation of Risibility, Therapeutic and Harmful): narrative synthesis. BMJ 2013;347:f7274


 

Study Develops Method for DNA Extraction from the Saliva After Stroke Using Magnetic Nanoparticles

A risk factor for stroke is the C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene. Studies have report a higher C677T homozygosity frequency in Chinese than in Europeans. Usually, the detection of genetic diseases is rather complicated on a large scale owing to the invasive sampling and a cumbersome DNA extraction process.
In a study by Dr. Li Yi and team from Peking University Shenzhen Hospital in China, DNA from stroke patients and healthy controls was extracted from the saliva using a magnetic nanoparticles-based method and from the blood using conventional methods. Real-time PCR results revealed that the C677T polymorphism was genotyped by PCR using DNA extracted from both saliva and blood samples. The genotype results were confirmed by gene sequencing, and results for saliva and blood samples were consistent. Therefore, this noninvasive magnetic nanoparticles-based method using saliva samples could be used to screen for the MTHFR C677T polymorphism in target populations. Source:This study was published in the Neural Regeneration Research (Vol. 8, No. 32, 2013).