Study finds alarming global rise in use of antibiotics
Antibiotic use has surged by 36 percent worldwide in a decade, much of it unwarranted, according to a new study.
12 july 2014--The rise, particularly in countries with a burgeoning middle class, heightens concerns that overuse of antibiotics is leaving more of the world's population vulnerable to drug-resistant bacteria, according to the authors of the analysis, published online Thursday in the journal Lancet Infectious Diseases.
The study provides the most comprehensive long-term view of antibiotic use in 71 countries from 2000 to 2010. It found that the rise in consumption could not be explained by population changes alone and appeared to parallel economic development. A few countries experiencing economic growth - Brazil, Russia, India, China and South Africa - accounted for more than three-quarters of the rise in antibiotic use.
"People are getting richer and can afford antibiotics," said Thomas Van Boeckel, a Princeton University epidemiologist and lead author of the study. "That is not necessarily all bad news. People need access to antibiotics. But there is appropriate use and misuse."
Among the results researchers found most troubling was the sharp rise in consumption of broad-spectrum antibiotics that normally are considered a measure of last resort. Among them are carbapenems, such as ampicillin and amoxicillin; and polymyxins, both often used against enterobacteriaceae, such as salmonella and shigella.
Health care facilities worldwide have struggled with serious outbreaks of carbapenem-resistant enterobacteriaceae, or CRE, as well as methicillin-resistant Staphylococcus aureus, or MRSA.
"If we lose the effectiveness of these drugs, there really isn't much left," Van Boeckel said.
The study was not set up to distinguish inappropriate use of antibiotics, a phenomenon that has been well established by other studies. But some trends in the data suggest that antibiotics may be inappropriately prescribed.
For instance, the authors note, a rise in use of cephalosporins and fluoroquinolones in low- and middle-income countries probably comes in response to acute diarrheal illnesses and to such fever-producing maladies as dengue and chikungunya, even though most of these are caused by viruses, which do not respond to antibiotics.
Higher use of antibiotics also coincides with the influenza virus season, even though they are ineffective as a treament against the flu, Van Boeckel said. "If you look at antibiotic use in the U.S., it's correlated to influenza, and it's not going to do anything for that," he said.
Although overall consumption of antibiotics fell in Europe and the U.S. over the decade studied, largely due to public awareness campaigns, the United States remains a very high consumer of antibiotics on a per-person basis. Per capita consumption also increased substantially in Australia and New Zealand, and all of the high-income Asian countries ranked among the top per capita consumers.
Within Europe, there were sharp differences between two nations of similar economic background. The French use three times the amount of antibiotics as do the Dutch, the study noted. Van Boeckel said authorities in the Netherlands had cut back on antibiotic use in response to a serious outbreak of drug-resistant Staphylococcus bacteria in its hospitals.
In less affluent countries, however, public health authorities appear to be using antibiotics instead of making long-term improvements to sanitation, the authors said. Such a strategy is short-sighted and counterproductive, leaving countries with the same exposure to much more resistant pathogens, they warned.
"It's effective in the short term, but it's going to be a big problem in coming years," Van Boeckel said.
Data were hardest to obtain from countries where overuse of antibiotics appears to be prevalent, Van Boeckel noted. He and co-authors called for international guidelines governing prescription and sale of antibiotics and a uniform system for reporting antibiotic use.
"The more we wait, the more resistance builds up," Van Boekel said.
Friday, July 11, 2014
How antioxidants can accelerate cancers, and why they don't protect against them
Drs. Tuveson and Chandel explain why eating foods rich in antioxidants, as well as taking antioxidant supplements, can actually promote cancer, rather than fight or prevent it, as conventional wisdom suggests. Credit: CSHL
For decades, health-conscious people around the globe have taken antioxidant supplements and eaten foods rich in antioxidants, figuring this was one of the paths to good health and a long life.
11 july 2014--Yet clinical trials of antioxidant supplements have repeatedly dashed the hopes of consumers who take them hoping to reduce their cancer risk. Virtually all such trials have failed to show any protective effect against cancer. In fact, in several trials antioxidant supplementation has been linked with increased rates of certain cancers. In one trial, smokers taking extra beta carotene had higher, not lower, rates of lung cancer.
In a brief paper appearing today in The New England Journal of Medicine, David Tuveson, M.D. Ph.D., Cold Spring Harbor Laboratory Professor and Director of Research for the Lustgarten Foundation, and Navdeep S. Chandel, Ph.D., of the Feinberg School of Medicine at Northwestern University, propose why antioxidant supplements might not be working to reduce cancer development, and why they may actually do more harm than good.
Their insights are based on recent advances in the understanding of the system in our cells that establishes a natural balance between oxidizing and anti-oxidizing compounds. These compounds are involved in so-called redox (reduction and oxidation) reactions essential to cellular chemistry.
Oxidants like hydrogen peroxide are essential in small quantities and are manufactured within cells. There is no dispute that oxidants are toxic in large amounts, and cells naturally generate their own anti-oxidants to neutralize them. It has seemed logical to many, therefore, to boost intake of antioxidants to counter the effects of hydrogen peroxide and other similarly toxic "reactive oxygen species," or ROS, as they are called by scientists. All the more because it is known thatcancer cells generate higher levels of ROS to help feed their abnormal growth.
Drs. Tuveson and Chandel propose that taking antioxidant pills or eating vast quantities of foods rich in antioxidants may be failing to show a beneficial effect against cancer because they do not act at the critical site in cells where tumor-promoting ROS are produced – at cellular energy factories called mitochondria. Rather, supplements and dietary antioxidants tend to accumulate at scattered distant sites in the cell, "leaving tumor-promoting ROS relatively unperturbed," the researchers say.
Quantities of both ROS and natural antioxidants are higher in cancer cells – the paradoxically higher levels of antioxidants being a natural defense by cancer cells to keep their higher levels of oxidants in check, so growth can continue. In fact, say Tuveson and Chandel, therapies that raise the levels of oxidants in cells may be beneficial, whereas those that act as antioxidants may further stimulate the cancer cells. Interestingly, radiation therapy kills cancer cells by dramatically raising levels of oxidants. The same is true of chemotherapeutic drugs – they kill tumor cells via oxidation.
Paradoxically, then, the authors suggest that "genetic or pharmacologic inhibition of antioxidant proteins" – a concept tested successfully in rodent models of lung and pancreatic cancers—may be a useful therapeutic approach in humans. The key challenge, they say, is to identify antioxidant proteins and pathways in cells that are used only by cancer cells and not by healthy cells. Impeding antioxidant production in healthy cells will upset the delicate redox balance upon which normal cellular function depends.
The authors propose new research to profile antioxidant pathways in tumor and adjacent normal cells, to identify possible therapeutic targets.
More information: "The Promise and Perils of Antioxidants for Cancer Patients" appears in The New England Journal of Medicine on July 10, 2014.
Provided by Cold Spring Harbor Laboratory
Thursday, July 10, 2014
Alzheimer's disease: Simplified diagnosis, with more reliable criteria
How many patients receive an incorrect diagnosis of Alzheimer's disease? The answer is a surprisingly high number: over a third! To reduce the number of errors, the diagnostic criteria must be the most reliable possible, especially at the very early stages of the disease. For the last decade, an international team of neurologists, coordinated by Bruno Dubois (Inserm/Pierre and Marie Curie University/AP-HP Joint Research Unit 975) has been working towards this. In the June issue of The Lancet Neurology journal, we see how the researchers have developed a simplified diagnosis based on the most specific criteria of the disease. A challenge primarily for research, but also for clinical practice.
10 july 2014--Alzheimer's disease is a neurodegenerative disease. It is the most common (70%) form of dementia. In France, the number of people with Alzheimer's disease and other forms of dementia is estimated at between 750,000 and one million, and is expected to reach 1.29-1.40 million patients by 2030. Alzheimer's disease results from a loss of neurons. The lesions are caused by an accumulation of some brain proteins. The pathology begins with memory problems. This is followed by problems of orientation in space and in time, behavioural problems and loss of autonomy. However, these symptoms are not specific to Alzheimer's disease. The real challenge is to know how to distinguish this disease from other types of dementia, and establish the diagnosis as reliably and as early as possible.
In 2005, an international group of neurologists, coordinated by Bruno Dubois at Inserm, came together to redefine the diagnostic criteria established in 1984. Until then, it had been necessary to await the death of a patient in order to establish a diagnosis of Alzheimer's disease with certainty by examining the lesions in his/her brain. And in the living, only a probability of disease could be inferred, and only at a late stage, based on a certain threshold of severity of dementia.
In 2007, the international team shattered these concepts. The researchers introduced new diagnostic criteria, particularly biomarkers. These are genuine signatures of the disease, and are present from the initial symptoms (prodromal stage).
The publication of these results constituted a revolution. Researchers then observed that with these new criteria, "36% of their patients included in a therapeutic trial based on previous clinical criteria did not have Alzheimer's disease," reports Bruno Dubois. And although this analysis involved only a subgroup of patients, the implications are serious. Patients did not receive the correct treatment and/or care. And flawed patient selection might have had an impact on the lack of efficacy observed for the new treatment.
Since 2007, many studies have been published. And the international group decided to analyse this literature to make the diagnostic algorithm for Alzheimer's disease simpler and more reliable.
"We have reached the end of the road; we have arrived at the essence, something refined, resulting from an international consensus", indicates Prof. Dubois. The diagnosis of Alzheimer's disease will henceforth rely on "just a couple of clinical-biological criteria for all stages of the disease" (see box).
Most of the time, the diagnosis of Alzheimer's disease is based primarily on a suggestive clinical picture. It is subsequently confirmed or rejected using a biomarker.
As regards the clinical picture, there are three scenarios:
typical cases (80-85% of all cases): impairment of episodic long-term memory (known as amnestic syndrome of the hippocampal type and corresponding to difficulty remembering a list a words, even with clues, for example)
atypical cases (15-20% of cases): atrophy of the posterior part of the cerebral cortex or logopenic aphasia (impairment of verbal memory where the patient inverts the syllables of a word when repeating it, for example), or frontal brain damage (which results in behavioural problems)
preclinical states: asymptomatic at-risk (patients without symptoms, but who are fortuitously discovered to have positive biomarkers during scientific studies), and presymptomatic (with a genetic mutation)
One of the following two biomarkers is required:
in the cerebrospinal fluid (obtained by lumbar puncture): abnormal levels of brain proteins (reduced beta amyloid protein and increased tau protein)
in the brain by PET (positron emission tomography) neuroimaging: elevated retention of amyloid tracer
This simpler and more reliable algorithm is important, primarily for research (therapeutic trials, characterisation of the disease, monitoring of patient cohorts, etc.). Outside of research, the use of biomarkers, which is expensive and/or invasive, currently remains limited to young patients or difficult or complex cases in expert centres.
Provided by Institut National de la Sante et de la Recherche Medicale
Wednesday, July 09, 2014
A healthy lifestyle adds years to life
09 july 2014--Charts for probabilities of surviving the next 10 years for 65 and 75-year-olds with differing health behaviour. Legend: e. g. box top right: a 75-year-old man today who at the start of the study smoked, drank a lot and hardly ate any fruit has a 35 percent probability of surviving the next ten years. E. g. box bottom left: a 65-year-old woman with positive health behaviour in all four areas has a 90 percent probability of still being alive in ten years’ time. Credit: Preventive medicine/UZH
Live longer thanks to fruit, an active lifestyle, limited alcohol and no cigarettes. This is the conclusion of a study by public health physicians at the University of Zurich who documented for the first time the impact of behavioural factors on life expectancy in numbers. The results are to be taken over into prevention and health counselling in primary care.
Cardiovascular diseases (CVDs), cancer, diabetes and chronic respiratory disorders - the incidence of these non-communicable diseases (NCDs) is constantly rising in industrialised countries. The Federal Office of Public Health (FOPH) is, therefore, in the process of developing a national prevention strategy with a view to improving the population's health competence and encouraging healthier behaviour. Attention is focusing, amongst other things, on the main risk factors for these diseases which are linked to personal behaviour – i.e. tobacco smoking, an unhealthy diet, physical inactivity and harmful alcohol consumption.
Against this backdrop Private Docent Brian Martin and his colleagues from the Institute of Social and Preventive Medicine (ISPM) at the University of Zurich have examined the effects of these four factors – both individual and combined – on life expectancy. For the first time the consequences of an unhealthy lifestyle can be depicted in numbers. An individual who smokes, drinks a lot, is physically inactive and has an unhealthy diet has 2.5 fold higher mortality risk in epidemiological terms than an individual who looks after his health. Or to put it positively: "A healthy lifestyle can help you stay ten years' younger", comments the lead author Eva Martin-Diener.
Analysis of data from the Swiss Cohort
For the study the researchers used data from the Swiss National Cohort (SNC). The Zurich public health physicians focussed on CVDs and cancer as they account for the most deaths in Switzerland. The researchers succeeded in correlating data on tobacco consumption, fruit consumption, physical activity and alcohol consumption from 16,721 participants aged between 16 and 90 from 1977 to 1993 with the corresponding deaths up to 2008. The impact of the four forms of behaviour was still visible when biological risk factors like weight and blood pressure were taken into account as well.
"The effect of each individual factor on life expectancy is relatively high", states Eva Martin-Diener. But smoking seems to be the most harmful. Compared with a group of non-smokers, smokers have a 57 percent higher risk of dying prematurely. The impact of an unhealthy diet, not enough sport and alcohol abuse results in an elevated mortality risk of around 15 percent for each factor. "We were very surprised by the 2.5 fold higher risk when all four risk factors are combined", explains Brian Martin. Hence, the probability of a 75-year-old man with all risk factors surviving the next ten years is, for instance, 35 percent, without risk factors 67 percent – for a woman 47 and 74 percent respectively.
Effects only appear in later life
According to Martin an unhealthy lifestyle has above all a long-lasting impact. Whereas high wine consumption, cigarettes, an unhealthy diet and physical inactivity scarcely had any effect on mortality amongst the 45 to 55-year-olds, it does have a visible effect on 65 to 75-year-olds. The probability of a 75-year-old man with none of the four risk factors surviving the next ten years is 67 percent, exactly the same as the risk for a smoker who is ten years younger, doesn't exercise, eats unhealthily and drinks a lot.
The social and public health physicians depict the dependency of life expectancy and the four risk behaviours for the age groups in what are known as survival charts. The impact of individual risk factors and their combined effect on mortality are visible at a glance. "In future, doctors will be able to refer to the easily comprehensible charts when giving health counselling to their patients in primary care", comments Eva Martin-Diener with confidence. "Furthermore, they may also be important for the political discussions of prevention strategies for NCDs."
The study was co-financed by the Swiss Heart Foundation and the Swiss Cancer League. It is an example of how cohort studies can generate relevant results for health policy.
More information: Eva Martin-Diener, Julia Meyer, Julia Braun, Silvan Tarnutzer, David Faeh, Sabine Rohrmann und Brian W. Martin. "The combined effect on survival of four main behavioural risk factors for non-communicable diseases."Preventive Medicine. June, 2014. DOI: 10.1016/j.ypmed.2014.05.023
Provided by University of Zurich
Monday, July 07, 2014
Does cycling increase risk for erectile dysfunction, infertility, or prostate cancer?
08 july 2014--Cycling is a popular activity that offers clear health benefits, but there is an ongoing controversy about whether men who ride have a higher risk of urogenital disorders such as erectile dysfunction, infertility, or prostate cancer. The results of a study of nearly 5,300 male cyclists who participated in the Cycling for Health UK Study are presented in an article in Journal of Men's Health.
"Physicians should discuss the potential risks and health benefits of cycling with their patients, and how it may impact their overall health," says Ajay Nehra, MD, Editor-in-Chief of Journal of Men's Health and Chair, Department of Urology, Director, Men's Health, Rush University Medical Center, Chicago, IL.
Language can help the elderly cope with the challenges of aging, says Stanford professor
Freshman Giselle Tran interviews retired physicist William Frye for Professor Yoshiko Matsumoto's course on the joys and pains of growing older. Linguist Matsumoto studies how language helps the elderly cope with the challenges of aging.
Aging inevitably brings with it a variety of challenges: declining health, changes in work status, the loss of family and friends.
07 july 2014--But in studying the conversations of older people, Stanford linguist Yoshiko Matsumoto discovered "common communication strategies of the elderly that may help them return to their happier, normal lives after experiencing hardship."
A professor of Japanese language and linguistics, Matsumoto through her research not only confirms how certain types of conversation contribute to a sense of well-being, but also offers older people, their families and caregivers potential tools for building resiliency following change.
Matsumoto's most recent work specifically focuses on older women's discourse about the illness or death of their husbands, with particular attention to conversations that also include humor and laughter. "These instances are not uncommon in my data, although they are a surprising combination," Matsumoto says.
Although there have been numerous suggestions about the positive effects of humor and laughter in difficult times, Matsumoto says the actual process of how that is accomplished through verbal interaction is not well understood.
Matsumoto's linguistic analyses of more than 60 hours of recorded conversations illustrate that there is in fact a structure to such discourse. Her findings suggest that by reframing a serious story through an ordinary, or "quotidian," perspective, the women she studied infused their dialogue with cathartic smiles.
When the death of a husband was discussed only as a life-altering event, there was no humor in the conversation. But some speakers reframed similarly painful events with strategic uses of humor and laughter in conversations with friends and acquaintances.
In one instance, a woman jokingly described how she used to chide her husband about his smoking and drinking habits – the very cause of his death. Matsumoto notes that by shifting the narrative perspective from somber to the ordinary, the speaker helped everyone involved regain the feeling of normality.
"Quotidian reframing," as Matsumoto calls the technique, "can function as a useful discourse strategy to relieve tension and let the participants regain the feeling or identity that they consider normal.
The power of the quotidian
Matsumoto conducted her fieldwork in Japan, a country with the world's highest life expectancy and the fastest growing elderly population. It is also where Matsumoto grew up and where her mother, now 84, lives, which gave Matsumoto access to a rich network of groups of elderly women.
Over the course of six months, Matsumoto collected conversations between elderly Japanese women and their friends as they ate, met, worked and socialized in the daily course of their lives. She also interviewed some women and recorded conversations at organizations that facilitate activities for the elderly.
In a detailed study of the recordings, Matsumoto searched for linguistic patterns, finding that a speaker's ability to situate a traumatic event in the context of everyday life experience "seems to be quite effective as a means of emotion regulation."
In one exchange, for example, Matsumoto observed that when a recent widow was calmly recounting her husband's death, she suddenly became animated in describing one of her visits to see him in the hospital. The widow "complained, half laughingly, that her husband told her to shush up when she tried to talk to him, saying he was trying to sleep and she was being too noisy," Matsumoto said.
The widow laughed as she recalled this "ordinary moment" that reminded her of her husband's perpetual complaining during their long relationship.
"By aligning one's identity with that of one's quotidian self through reframing," Matsumoto says, the speaker may "display his or her emotional stability, manipulate the tone of the conversation, manipulate one's self-image, or enhance rapport between the speaker and the listener/audience."
According to Matsumoto, "The quotidian perspective and the quotidian representation of self become important when the situation you are in or the memory you are recounting are extraordinary and psychologically intense."
"This," Matsumoto asserts, "is the power of the quotidian."
One of the most significant things Matsumoto says she discovered is the complexity of emotions and multiple identities that are expressed in casual conversations, which she notes is in "sharp contrast to the findings of previous studies, which were conducted in more controlled, and controlling, environments and in which the identity of the aged seemed more constrained and grim."
New perspectives on aging
Matsumoto notes that although the importance of inter-generational communication is known, her research also illustrates how crucial it is for older people to have casual conversations with people in the same stage of life. Some topics are more difficult to discuss with younger people, a fact that Matsumoto says explains why "older people can feel marginalized in their family conversations."
"As with everyone else, older people need friends," Matsumoto says.
Matsumoto's findings have applications for elder care, where, she says, caregivers can provide environments and space for older adults to casually speak with friends and peers, as opposed to psychotherapy or group therapy.
Caregivers can also create scenarios in which seniors benefit from quotidian reframing by doing away with the "rigid division of caregiver and care recipient" and instead "look for ways to play other roles than those institutionally defined, such as a daughter, a friend or someone who shares the same hobby or interests," Matsumoto suggests.
Making a related point, Matsumoto stresses the importance of "remaining aware that each older person has a continuous personal history" and that "reference to this history may be appreciated by the care recipients, as that would help them to realign themselves with their familiar identity."
Beyond the conversational data previously collected in Japan, Matsumoto will be expanding her examination of quotidian reframing with a cross-cultural comparison between older American women and her Japanese findings. She also plans to extend her research to other conversational narratives of psychologically intense events, such as the Great Eastern Japan Earthquake (March 11, 2011), where she says preliminary observations already suggest that quotidian reframing is used as a mechanism for coping with trauma.
Connecting the generations
Linguistics is one of numerous disciplines that students in Matsumoto's introductory seminar Joys and Pains of Growing Up and Older in Japan study to better appreciate the challenges and pleasures of being a senior citizen, in Japan and other countries.
Through an examination of recent research on aging from fields such as psychology and gerontology, as well as readings of firsthand narrative accounts written by seniors, Matsumoto wants her students to abandon negative stereotypes about the elderly.
At a time when societies across the globe are becoming more sensitive to discrimination, Matsumoto says it's important for students to comprehend that ageism is also a form of prejudice.
Caregivers, young people and even researchers sometimes "project their own understandings and preconceived notions" about aging onto the elderly, says Matsumoto.
For their final project, students are paired with a "senior partner" from the local community. The students record or videotape one or two informal conversations with their partner, which they then edit into narratives about their partner's life.
The goal of the final project, Matsumoto says, is to help students understand the lives of people who are much older than they are and to see that the young and the old face similar challenges of uncertainty and changing identities.
Freshman Giselle Tran met twice with retired physicist William Frye. Tran said Frye shared detailed accounts of his life experiences, which span both World Wars and the Great Depression. "We also discussed why he prefers to live alone, rather than with his children or in a retirement home, as well as his greatest fears and the changes he has experienced while aging," Tran said.
Tran, who expects to pursue a degree in economics and mathematical and computational science, said she "got a sense that the older generation is not completely separate from the rest of society and should not be treated as such. They are not generally as despondent or depressed as the media makes them out to be. They have had amazing experiences that they want to share with others."
Provided by Stanford University
Saturday, July 05, 2014
Understanding and managing chronic pain
Acupuncture, exercise and massage and physical therapy are among the ways to deal with chronic pain that don't require narcotic painkillers, says Nancy Elder, MD, professor of family and community medicine at the University of Cincinnati.
06 july 2014--"A lot of patients think, 'Oh, I hurt a lot, I hurt a lot all the time, the doctor should give me OxyContin and Vicodin,'" says Elder. "I think the most important thing that doctors and patients need to know is there is much we can do to help patients with chronic pain outside of narcotics.
"That doesn't mean narcotics aren't appropriate for some people in certain situations, but there are a whole lot of people that can get better without them," she adds.
Elder says more doctors must have initial conversations with patients to manage expectations in dealing with chronic pain.
"Part of it is understanding the natural course of chronic pain and some of it is understanding the difference between being cured and being able to 'do what I want to do with pain that is manageable,'" says Elder.
"I may not be able to cure somebody of their chronic pain, but I can make them feel a whole lot better and help them do more of the activities they want to do."
Elder says whenever possible, physicians should involve a multimodality team that may include specialists in physical therapy, massage therapy, acupuncture and chiropractic treatment to address chronic pain. Acupuncture may relieve pain caused by conditions such as fibromyalgia, osteoarthritis and back injuries.
Exercise under a doctor's supervision can improve energy levels and mood and relieve chronic pain, while chiropractic treatment may work well in treating certain types of lower back pain, says Elder. Addressing behavioral/mental health is also important when dealing with chronic pain.
"Pain can worsen depression and depression may make chronic pain worse," says Elder.
There are also surgical possibilities and nerve injections that address some types of chronic pain so collaborations with anesthesiologists are also important, says Elder.
"There are medicines besides narcotics to help chronic pain such as antidepressants; even if you are not depressed, they can help," says Elder.
Medicines that were originally developed for epilepsy may have a benefit in chronic pain. Depending on the type of pain, there are even some cardiac medications that are very helpful, explains Elder. "A lot of other medicines from various areas of medicine have also been found to help with chronic pain," she says. "We call them adjuvant medications because they aren't painkillers, but they work to help decrease chronic pain.
"People with chronic pain, both doctors and patients, need to think outside of the opioid/narcotic pain box," Elder says.
Team reduces the size of the human genome to 19,000 genes
Unlike the two protein coding genes shown (top, middle), the gene ACO074091.13 (below) is predicted to produce no protein and is likely to be removed along with an additional 1,700 genes that are currently in the human genome annotation. Credit: CNIO
05 july 2014--How nutrients are metabolised and how neurons communicate in the brain are just some of the messages coded by the 3 billion letters that make up the human genome. The detection and characterisation of the genes present in this mass of information is a complex task that has been a source of ongoing debate since the first systematic attempts by the Human Genome Project more than ten years ago.
A study led by Alfonso Valencia, Vice-Director of Basic Research at the Spanish National Cancer Research Centre (CNIO) and head of the Structural Computational Biology Group, and Michael Tress, researcher at the Group, updates the number of human genes –those that can generate proteins– to 19,000; 1,700 fewer than the genes in the most recent annotation, and well below the initial estimations of 100,000 genes. The work, published in the journal Human Molecular Genetics, concludes that almost all of these genes have ancestors prior to the appearance of primates 50 million years ago.
"The shrinking human genome," that's how Valencia describes the continuous corrections to the numbers of the protein-coding genes in the human genome over the years that has culminated in the approximately 19,000 human genes described in the present work. "The coding part of the genome [which produces proteins] is constantly moving," he adds: "No one could have imagined a few years ago that such a small number of genes could make something so complex."
The scientists began by analysing proteomics experiments; proteomics is the most powerful tool to detect protein molecules. In order to determine a map of human proteins the researchers integrated data from seven large-scale mass spectrometry studies, from more than 50 human tissues, "in order to verify which genes really do produce proteins " says Valencia.
Fewer than ten new genes separate mice and men
The results brought to light just over 12,000 proteins and the researchers mapped these proteins to the corresponding regions of the genome. They analysed thousands of genes that were annotated in the human genome, but that did not appear in the proteomics analysis and concluded: "1,700 of the genes that are supposed to produce proteins almost certainly do not for various reasons, either because they do not exhibit any protein coding features, or because the conservation of their reading frames does not support protein coding ability, "says Tress.
One hypothesis derived from the study is that more than 90% of human genes produce proteins that originated in metazoans or multicellular organisms of the animal kingdom hundreds of millions of years ago; the figure is over 99% for those genes whose origin predates the emergence of primates 50 million years ago.
"Our figures indicate that the differences between humans and primates at the level of genes and proteins are very small," say the researchers. David Juan, author and researcher in the Valencia lab, says that "the number of new genes that separate humans from mice [those genes that have evolved since the split from primates] may even be fewer than ten." This contrasts with the more than 500 human genes with origins since primates that can be found in the current annotation. The researchers conclude: "The physiological and developmental differences between primates are likely to be caused by gene regulation rather than by differences in the basic functions of the proteins in question."
Doing more with less
The sources of human complexity lie more in how genes are used rather than on the number of genes, in the thousands of chemical changes that occur in proteins or in the control of the production of these proteins by non-coding regions of the genome, which comprise 90% of the entire genome and which have been described in the latest findings of the international ENCODE project, a Project in which the Valencia team participates.
The work brings the number of human genes closer to other species such as the nematode worms Caenorhabditis elegans, worms that are just 1mm long, but apparently less complex than humans. But Valencia prefers not to make comparisons: "The human genome is the best annotated, but we still believe that 1,700 genes may have to be re-annotated. Our work suggests that we will have to redo the calculations for all genomes, not only the human genome."
The research results are part of GENCODE, a consortium which is integrated into the ENCODE Project and formed by research groups from around the world, including the Valencia team, whose task is to provide an annotation of all the gene-based elements in the human genome.
"Our data are being discussed by GENCODE for incorporation into the new annotations. When this happens it will redefine the entire mapping of the human genome, and how it is used in macro projects such as those for cancer genome analysis ", says Valencia.
Provided by Centro Nacional de Investigaciones Oncologicas (CNIO)
Friday, July 04, 2014
Vitamin D does not improve glycemic control in prediabetes
04 july 2014—Supplementation with vitamin D does not appear to improve glycemic indices or cardiovascular risk factors in individuals with prediabetes, according to research published online June 19 in Diabetes Care.
Stina Therese Sollid, of the University of Tromsø in Norway, and colleagues randomly assigned 511 individuals with impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) to vitamin D3 or placebo.
At one year, the researchers observed no differences between the vitamin D group and placebo group in measures of glucose metabolism, insulin secretion, or insulin sensitivity. No differences were observed between the groups for blood pressure or serum high-sensitivity C-reactive protein level. Although a small but significant decrease in total and low-density lipoprotein cholesterol levels was observed in the vitamin D group compared with the placebo group, high-density lipoprotein (HDL) cholesterol level decreased, and the change in total/HDL cholesterol ratio was not significant.
"This study shows that vitamin D supplementation does not improve glycemic indices, blood pressure, or lipid status in subjects with IFG and/or IGT," the authors write.
A physician's ability to empathize may be in the genes
03 july 2014—Sensory processing sensitivity (SPS) is associated with increased activation of brain regions involved in awareness, attention, and action planning, according to a study published online June 23 in Brain and Behavior.
Noting that self-report studies show high-SPS individuals are strongly affected by others' moods, Bianca P. Acevedo, Ph.D., from the University of California in Santa Barbara, and colleagues examined theneural correlates of SPS, measured by the standard short-form Highly Sensitive Person (HSP) scale. The functional magnetic resonance imaging study was conducted in 18 participants (10 female) who viewed photos of their romantic partners and of strangers displaying positive, negative, or neutral facial expressions. Thirteen of the 18 participants were scanned twice, one year apart.
The researchers found that HSP scores correlated with increased brain activation in the cingulate and premotor area (involved in attention and action planning) across all conditions. SPS correlated with activation of brain regions involved in awareness, integration of sensory information, empathy, and action planning for happy and sad photo conditions. HSP scores correlated with stronger activation of brain regions involved in awareness, empathy, and self-other processing for partner images and happy facial photos.
"We found that areas of the brain involved with awareness and emotion, particularly those areas connected with empathetic feelings, in the highly sensitive people showed substantially greater blood flow to relevant brain areas than was seen in individuals with low sensitivity during the 12 second period when they viewed the photos," a coauthor said in a statement. "This is physical evidence within the brain that highly sensitive individuals respond especially strongly to social situations that trigger emotions, in this case of faces being happy or sad."
Smartphone app may revolutionize mental health treatment
Mental illness accounts for 90 percent of all reported suicides and places the largest burden of any disease on social and economic infrastructures worldwide, according to the World Health Organization. There is a dire need for support services to assist clinicians in the evaluation and treatment of those suffering from mental illness.
02 july 2014--New technology developed by researchers at Tel Aviv University is poised to transform the way in which patients with mental illnesses are monitored and treated by clinicians. Dr. Uri Nevo, research team engineer Keren Sela, and scientists from TAU's Faculty of Engineering and Sagol School of Neuroscience have developed a new smartphone-based system that detects changes in patients' behavioral patterns, and then transmits them to professionals in real time. It has the potential to greatly improve the response time and efficacy of clinical psychiatrists. By facilitating patient observation through smartphones, the technology also affords patients much-needed independence from hospitals, clinicians—and even family members.
Research on the application was presented in March at the Israel Society for Biological Psychiatry's annual conference. The project won funding from the Israeli Ministry of Economy and was recently chosen as one of four finalist start-up initiatives featured at Israel's leading Entrepreneurship and Innovation 8200 Accelerator Program. The team is currently in talks with other medical centers in Israel and overseas to expand clinical trials.
Using tools already "in the hand"
"The diagnosis of mental health disease is based only on behavioral patterns," said Dr. Nevo. "In some cases, a patient is discharged from the hospital into a vacuum, with no idea how to monitor his or her new state of mind. Because most people own smartphones today, we thought, 'Why not harness the smartphone, a reservoir of daily activities, to monitor behavioral patterns?'
"Bipolar disorder, for example, starts with a manic episode," said Dr. Nevo. "A patient who usually makes five or ten calls a day might suddenly start making dozens of calls a day. How much they talk, text, how many places they visit, when they go to bed and for how long—these are all indicators of mental health and provide important insights to clinicians who want to catch a disorder before it is full blown."
Researchers conducted two Helsinki-approved clinical trials with the cooperation and direction of leading psychiatrists from Geha Mental Health Center and Be'er Ya'acov Mental Health Center. In the trials, the application was installed on the smartphones of 20 patients suffering from bipolar, unipolar/depressive, or schizo-affective disorders, as well as on the phones of 20 healthy participants. Over the course of six months, the app acquired data from patients' phones and sent the information to distant computers, where advanced algorithms analyzed the data to detect changes in patients' sleep, communication, mobility, and vocal patterns. The researchers further developed a visualization system that displayed the summarized information to psychiatrists, providing them with instant insight into the behavioral trends of their patients.
Preserving patient privacy
According to Dr. Nevo, a patient using the app has full control over who has access to the behavioral patterns recorded and analyzed by it. "We take great care to protect the patient's privacy," said Dr. Nevo. "The content of calls and texts is completely ignored and never acquired or recorded, and any identifying parameters of the patient or of his contacts, are irreversibly masked and are obviously not used."
Psychiatrists in the trials reported that the system has already positively affected their interaction with patients, offering a useful objective "window" into the patient's daily routine. One patient who was involved in the clinical trial for only a brief period recently suffered a hospitalization. "If I had kept the app on my phone, you would have immediately noticed the unusual number of phone calls I was making, and this hospitalization could have been prevented," he told his psychiatrist.
"We have a way to go until such a system will be proven effective and adopted by the psychiatric community," said Dr. Nevo. "However, psychiatrists, as well as U.S. federal policymakers in the field, agree that such tools are necessary to improve psychiatric practice."
Provided by Tel Aviv University
Tuesday, July 01, 2014
Nursing home care may be out of reach for many aging 'boomers': study
Price tag for 1 year of institutionalized care is now about $84,000, federal report says.
01 july 2014—With higher rates of illness but fewer adult children to care for them, many of America's baby boom generation may find themselves unable to pay for the nursing home care they need, a new study warns.
Already, a growing number of older Americans are developing chronic diseases but can't cover the costs of long-term care in a nursing facility, the U.S. National Institute on Aging-funded report says.
The statistics represent "an approaching crisis in caregiving," Richard Suzman, director of the NIA's Division of Behavioral and Social Research, said in an agency news release.
"Baby boomers had far fewer children than their parents. Combined with higher divorce rates and disrupted family structures, this will result in fewer family members to provide long-term care in the future," Suzman explained. "This will become more serious as people live longer with conditions such as cancer, heart disease and Alzheimer's."
The analysis of national data revealed that chronic diseases such as high blood pressure, heart disease, lung disease and diabetes rose among older Americans between 1998 and 2008.
By 2008, 41 percent of older adults had three or more chronic conditions, 51 percent had one or two, and only 8 percent had none, according to the NIA-funded Census Bureau study.
While rates of smoking and excessive drinking have fallen among Americans aged 65 and older, the percentage of overweight and obese seniors has risen, the report notes. Between 2003 and 2006, 72 percent of older men and 67 percent of older women were overweight or obese.
Obesity boosts the risk of diabetes, arthritis, mobility problems and even death, according to the report.
The NIA investigation also looked at the costs of nursing home care and older Americans' ability to pay for it. In 2010, the average cost of a private room in a nursing home was $229 a day—or almost $84,000 per year.
However, the NIA team calculated that less than one-fifth of seniors can afford to live in a nursing home for more than three years, and nearly two-thirds can't afford even one year.
Medicare covers short-term nursing home care for older and disabled patients after they've been hospitalized, and Medicaid covers long-term nursing home care for low-income seniors who qualify. In 2006, Medicaid paid for 43 percent of long-term nursing home care.
This all means that "most of the long-term care provided to older people today comes from unpaid family members and friends," Suzman said.
There are currently more than 40 million Americans who are 65 and older, and that number is expected to grow to 83.7 million (one-fifth of the U.S. population) by 2050, according to the study.
"We hope this report will serve as a useful resource to policymakers, researchers, educators, students and the public at large," Enrique Lamas, the Census Bureau's associate director for demographic programs, said in the news release.
Little progress made in reducing health disparities for people with disabilities
Psychological distress in people with disabilities is associated with increased prevalence of other chronic conditions and reduced access to health care and preventive care services, finds a new study in the Journal of Health Care for the Poor and Underserved.
30 jun 2014--The U.S. Department of Health and Human Services' Healthy People series established goals to reduce disparities among people with disabilities, but there has been very little progress toward reaching these goals, says lead author Catherine Okoro, Ph.D., of the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia.
"It's important to find out why there has been so little progress, since the prevention, detection, and treatment of secondary illnesses is critical for health maintenance, halting progression of disability, and helping people with disabilities to participate in life activities," she says.
The study analyzed data from the Behavioral Risk Factor Surveillance System, a telephone survey conducted in 2007 by most state health departments in conjunction with the CDC. Approximately 30 percent of adults with disabilities reported having moderate to serious psychological distress, with over 12 percent reporting serious psychological distress.
Adults who reported having a disability and serious psychological distress had a higher prevalence of seven chronic diseases and conditions—arthritis, asthma,coronary heart disease, diabetes, hypertension, high cholesterol, and stroke—when compared to adults with no psychological distress. Disabled adults with moderate psychological distress also had higher rates of these conditions, with the exception of diabetes.
"We found a strong association between increasing numbers of physical chronic conditions and prevalence of serious psychological distress," Okoro says. "For example, the prevalence of serious psychological distress was about two times as high among those with five to seven chronic conditions compared to those with no conditions."
Adults ages 18 to 64 with disabilities and moderate-to-serious psychological distress were also found to have several barriers to accessing health care. They were more likely to be uninsured and unable to afford care than those with no distress. Researchers found that the use of mental health services increased with the severity of psychological distress, but a larger proportion of older adults with serious psychological distress reported not receiving mental health care when compared to their younger counterparts. "It's possible this may be due to competing health conditions, stigma, or avoidance," Okoro comments.
The study illustrates that a relatively small but highly vulnerable population bears the majority of burden of poor physical and psychological health, says Benjamin Druss, M.D., a psychiatrist at Emory University. "These problems tend to be tangled up with one another so a person who has physical problems tends to be more stressed about their problems—particularly if they can't get health care," he comments. "It's not easy to untangle all these issues, but these individuals should be treated in a holistic way, looking at their mental problems, their physical health, and their psychosocial issues," he adds.
More information: Okoro A, Dhingra SS, and Li C. "A triple play: psychological distress, physical comorbidities, and access and use of health services among US adults with disabilities." J of Health Care for the Poor and Underserved. 2014;(25):814-836.
Provided by Health Behavior News Service
Sunday, June 29, 2014
Aging with HIV and AIDS: A growing social issue
As the first people with HIV grow old, a new study from St. Michael's Hospital questions whether the health care system and other government policies are prepared to meet their complex medical and social needs.
29 jun 2014--In high-income countries such as Canada, 30 per cent of people living with HIV are 50 or older, and many are living into their 60s and 70s. In San Francisco, more than half the people with HIV are over 50.
"It's a positive thing that people are aging with HIV," said Dr. Sean B. Rourke, a neuropsychologist who heads the Neurobehavioural Research Unit at St. Michael's. "This shows that Ontario is doing its job to help people living with HIV have access to the medical systems and antiretroviral medications to keep HIV at bay. But a very significant crisis is looming."
In a study to be published in the July issue of the journal Current Opinion in HIV and AIDS, Dr. Rourke noted that aging for people with HIV may be more challenging than for the general population because of HIV-related stigma, loss of friends and social networks, and the detrimental health effects of the virus and medications taken to combat the virus.
Older people with HIV are more likely to experience mental health and neurocognitive impairments than other people of the same age, as well as more social isolation. A study in the United States found that 94 per cent of people with HIV who were over 50 have at least one other chronic illness, with an average of three conditions.
Pension plans and health care facilities are not designed for, or expecting, people to have these issues at younger ages, Dr. Rourke said. Geriatric physicians are not trained for working with HIV, and those trained for HIV are not trained in geriatrics.
As a large number of people with HIV approach retirement age, policy makers need to develop new policies or adapt the existing ones to improve their social and economic outlook. He said people aging with HIV who are still working may need more time off to take care of themselves or rest breaks during their shifts; reforming retirement benefit programs could allow people with HIV to remain in the workforce as long as possible; retirement homes and long-term facilities need to be more welcoming places for older people living with HIV.
Individuals with HIV continue to live with health consequences that limit their ability to participate in society. This could mean the inability to work or engage in a community. Some people have to remain jobless or in low-paying jobs so they can receive social assistance and government-funded drugs.
Dr. Rourke said a growing body of research is exploring interventions and other coping strategies to minimize the negative impact of aging with HIV, including being proactive and managing treatment appropriately. Eating properly, exercising regularly and taking care of health needs earlier are much more important with a chronic illness like HIV, he said.
Provided by St. Michael's Hospital
Saturday, June 28, 2014
Diet or exercise? "Energy balance" is real key to disease prevention
28 jun 2014—A majority of Americans are overweight or obese, a factor in the rapid rise in common diseases like diabetes, heart disease, cancer, high blood pressure and more. According to a paper published in this month's issue of the official journal of the American College of Sports Medicine (ACSM), energy balance is a viable public health solution to address the obesity epidemic. The paper outlines steps to incorporate energy balance principles into public health outreach in the U.S.
"It is time we collectively move beyond debating nutrition or exercise and focus on nutrition and exercise," said co-author and ACSM member Melinda Manore, Ph.D., R.D., C.S.S.D., FACSM of Oregon State University. "Nutrition and exercise professionals working collaboratively, combined with effective public health messaging about the importance of energy balance, can help America shape up and become healthier."
The paper, published in the July edition of Medicine & Science in Sports & Exercise and in the Journal of the Academy of Nutrition and Dietetics gives the following recommendations:
Integrate energy balance into curriculum and training for both exercise science and nutrition professionals and strengthen collaborative efforts between them
Develop competencies for school and physical education teachers and position them as energy balance advocates
Develop core standards for schools that integrate the dynamic energy balance approach
Work with federally-funded nutrition programs to incorporate energy balance solutions like the Cooperative Extension Service and school lunch programs
Develop messaging and promotional strategies about energy balance that American consumers can understand and apply to their lifestyle
Map out and support existing programs that emphasize energy balance
"Our health professionals are currently working in silos and must work together to educate and promote energy balance as the key to better health" said Manore. "The obesity crisis is one of the greatest public health challenges of our generation. Energy balance can help us work toward a solution so our children aren't saddled with the same health challenges we currently face. "
Scientists establish proof-of-concept for host-directed tuberculosis therapy
M. tuberculosis bacterial colonies. Credit: Centers for Disease Control and Prevention.
27 jun 2014--in a new study published in Nature, scientists describe a new type of tuberculosis (TB) treatment that involves manipulating the body's response to TB bacteria rather than targeting the bacteria themselves, a concept called host-directed therapy. TB remains a major cause of disability and death worldwide as an estimated 8.6 million people fell ill with TB and 1.3 million people died from the disease in 2012, according to the World Health Organization. Although TB is curable, adherence to therapy is difficult as treatment requires taking antibiotic drugs for at least six months and sometimes up to two years. Poor adherence to medication and other factors have resulted in drug-resistant strains, and currently no effective TB vaccine exists.
To address the need for alternative interventions, scientists from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, demonstrated proof-of-concept for a host-directed strategy to treat tuberculosis. They found that interleukin-1, a type of protein that regulates the body's immune response to infection, can help protect the body from TB infection. Their studies in cells and in mice and human patients infected with TB bacteria demonstrated that interleukin-1 induces a mediator, prostaglandin E2 (PGE2), that limits the production of type-I interferons, which are associated with increased TB disease severity.
The scientists found that host-directed immunotherapy using PGE2 and zileuton, a clinically-approved drug typically used to treat asthma, prevented death in TB-infected mice. This strategy could be of particular benefit to people infected with drug-resistant TB strains who have limited options for effective antibiotics because the treatment increased bacterial control and limited disease even in the absence of TB chemotherapy. In principle, this approach is compatible with standard antibiotic regimens, according to the authors. In future studies, NIAID scientists will test adjunct host-directed therapies in TB-infected individuals.
More information: KD Mayer-Barber et al. Host-directed therapy of tuberculosis based on interleukin-1 - type I interferon crosstalk. Nature. DOI: 10.1038/nature13489 (2014).
Provided by NIH/National Institute of Allergy and Infectious Diseases
Thursday, June 26, 2014
Watching too much TV may increase risk of early death in adults
Adults who watch TV for three hours or more each day may double their risk of premature death compared to those who watch less, according to new research published in the Journal of the American Heart Association.
26 jun 2014--"Television viewing is a major sedentary behavior and there is an increasing trend toward all types of sedentary behaviors," said Miguel Martinez-Gonzalez, M.D., Ph.D., M.P.H., the study's lead author and professor and chair of the Department of Public Health at the University of Navarra in Pamplona, Spain. "Our findings are consistent with a range of previous studies where time spent watching television was linked to mortality."
Researchers assessed 13,284 young and healthy Spanish university graduates (average age 37, 60 percent women) to determine the association between three types of sedentary behaviors and risk of death from all causes: television viewingtime, computer time and driving time. The participants were followed for a median 8.2 years. Researchers reported 97 deaths, with 19 deaths from cardiovascular causes, 46 from cancer and 32 from other causes.
The risk of death was twofold higher for participants who reported watching three or more hours of TV a day compared to those watching one or less hours. This twofold higher risk was also apparent after accounting for a wide array of other variables related to a higher risk of death.
Researchers found no significant association between the time spent using a computer or driving and higher risk of premature death from all causes. Researchers said further studies are needed to confirm what effects may exist between computer use and driving on death rates, and to determine the biological mechanisms explaining these associations.
"As the population ages, sedentary behaviors will become more prevalent, especially watching television, and this poses an additional burden on the increased health problems related to aging," Martinez-Gonzalez said. "Our findings suggest adults may consider increasing their physical activity, avoid long sedentary periods, and reduce television watching to no longer than one to two hours each day."
The study cited previous research that suggests that half of U.S. adults are leading sedentary lives.
Provided by American Heart Association
Wednesday, June 25, 2014
USPSTF says evidence doesn't support vitamin D screening
25 jun 2014—Current evidence is insufficient to weigh the benefits and harms of screening for vitamin D deficiency to improve health outcomes in asymptomatic adults, according to a draft evidence report from the U.S. Preventative Service Task Force.
Erin LeBlanc, M.D., from Oregon Health & Science University, and colleagues on behalf of the U.S. Agency for Healthcare Research and Quality conducted a literature search to develop evidence regarding the benefits of vitamin D treatment(with or without calcium) compared with placebo, calcium alone, or no treatment. Included studies evaluated asymptomatic populations from the United States, Canada, and Europe with serum 25(OH)D concentrations of ≤ 30 ng/mL.
The researchers found that in treatment studies, mortality was decreased in those randomized to vitamin D treatment (with or without calcium; 11 studies; pooled RR, 0.83; 95 percent confidence interval [CI], 0.70 to 0.99). However, the risk reduction was limited to studies of older, institutionalized persons (three trials; pooled RR, 0.72; 95 percent CI, 0.56 to 0.94). Vitamin D treatment was not associated with a decreased risk for falling (five studies; pooled RR, 0.84; 95 percent CI, 0.69 to 1.02), but it was associated with fewer falls per person (five studies; pooled RR, 0.66; 95 percent CI, 0.50 to 0.88). There was no association between vitamin D treatment and decreased fracture risk (five studies; pooled RR, 0.98; 95 percent CI 0.82 to 1.16).
"More research is needed to determine vitamin D treatment's effects in younger, non-institutionalized adults and to clarify the subpopulations that are most likely to benefit from treatment," the authors write.
