Read more]]> Mental health is a tricky branch of medicine – psychiatrists deal with significant diagnostic and research challenges, and some patients struggle with the stigma they may face socially due to having a mental disorder. In a bid to educate the public about psychiatric conditions, Mental Health Awareness Week, which this year runs from 13th–19th May, is focusing on raising awareness about how exercise can positively affect mental health. In fact, there is increasing focus on modifying key lifestyle factors as primary prevention strategies for mental health disorders, and in a recent opinion article published in BMC Medicine, Felice Jacka and colleagues argue that depression and anxiety should be ranked amongst prevalent medical conditions affected by poor diet and physical inactivity. In another opinion article, Almudena Sanchez-Villegas and Miguel Martínez-Gonzalez discuss how diet may help prevent depression, and recommend that observational studies and clinical trials need to be carried out to confirm the association.

Psychiatry is also very topical this week due to the imminent release of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) by the American Psychiatric Association. This has been undergoing revision for some time, and although greatly anticipated, has also led to much debate, with some arguing that the DSM-5 should not be heralded as the ultimate guide in diagnosing psychiatric disorders. To focus on the many controversies in this area of medicine, a new article collection, Current Controversies in Psychiatry, has been published in BMC Medicine to address the current challenges in psychiatry from diagnosis to co-morbidities.

As Michael Berk discusses in an editorial to launch our article collection, the debate on diagnostic categories in mental health based on DSM-5 is disproportionate to what the changes will actually mean. He highlights that while the modifications in diagnostic criteria are useful, the limitations should also be kept in perspective amongst clinicians and regulators, and warns that adhering too tightly to imperfect criteria will hamper progress in research.

In a debate article, Ian Hickie and colleagues argue that the diagnostic criteria can be improved by developing new approaches that identify pathways underlying the illnesses rather than using broad categories to describe psychiatric disorders. However, in another debate article, Victoria Cosgrove and Trisha Suppes highlight that boundaries between the diagnosis of bipolar disorder I, schizophrenia and schizoaffective disorder are preserved in the DSM-5 criteria, as there is not yet enough data to justify a continuous model of psychosis.

It should be noted that the DSM diagnoses are based on consensus guided by clinical symptoms, and are not derived from any quantifiable research measures. Another closely related diagnostic guideline is the tenth edition of the International Classification of Diseases (ICD-10) developed by the WHO, which is also undergoing revision (the ICD-11 is due for release in 2015); some argue that the two sets of guidelines, although developed for use by different branches of health professionals, suffer from similar limitations.

In an attempt to produce a more informative set of diagnostic guidelines, the National Institute of Mental Health (NIMH) launched the Research Domain Criteria (RDoC) project in 2009, which aims to incorporate genetics, neuroimaging and cognitive science to develop a new classification system. In a debate article, Bruce Cuthbert and Thomas Insel argue that future psychiatric nosologies will be informed by the RDoC, which will help achieve precision medicine for mental disorders. Thomas Insel expands on this project further in his NIMH blog. The move towards focusing on a more personalized approach to psychiatric research is also highlighted in a review article by Charles Nemeroff and colleagues, where the genetics, epigenetics, biomarkers, treatment response and environmental factors of mood disorders and schizophrenia are discussed, with particular emphasis on the impact of neuroimaging on personalized medicine in psychiatry.

The patient’s perspective in all this should also not be forgotten, and as Dan Stein and Katherine Phillips point out, the fifth DSM revision incorporated public feedback for the first time. Stein and Phillips both worked as part of the subgroup for the obsessive compulsive and related disorders criteria, and in a commentary describe the importance of taking patient opinion into account.

One thing that cannot be underestimated is the impact psychiatric conditions have on overall health. In particular, depression has been associated with obesity and cardiovascular diseases (CVD), and in a review article Brenda Penninx and colleagues examine the biological pathways and the dysregulation between depressive symptoms and somatic health. Additionally, Peter de Jonge and colleagues argue that although there is a link between coronary heart disease (CHD) and depression, this association is confounded by heterogeneity, such that depression is a non-causal risk factor for CHD. However, Kenneth Freedland and Robert Carney dispute that depression predicts CHD but admit that better methods are required to ascertain whether depression is a causal risk factor for CHD, which could help determine treatment strategies for CVD prevention.

Further articles will be added to this series to focus on some of the controversies and open questions in psychiatry, so keep an eye out for developments in our article collection. In the meantime, we wish you good mental health!

The problem of antibiotic resistance, recently described as “apocalyptic” by Sally Davies, Chief Medical Officer of the UK, is getting worse and cannot be expected to get better quickly. In a Question and Answer article in BMC Biology, Gerard Wright explains the reasons for the worsening situation, and why, despite the acute need, there are few new antibiotics on the horizon.

Antibiotic resistance is a natural and ancient phenomenon, and the emergence and spread of resistance in human pathogens inevitable, he argues, though widespread clinical and agricultural use of antibiotics makes it much worse; and the problem can only be met by the development of new drugs.

The point that antibiotic resistance predates our development of antibiotic drugs was ...

Read more]]>

The problem of antibiotic resistance, recently described as “apocalyptic” by Sally Davies, Chief Medical Officer of the UK, is getting worse and cannot be expected to get better quickly. In a Question and Answer article in BMC Biology, Gerard Wright explains the reasons for the worsening situation, and why, despite the acute need, there are few new antibiotics on the horizon.

Antibiotic resistance is a natural and ancient phenomenon, and the emergence and spread of resistance in human pathogens inevitable, he argues, though widespread clinical and agricultural use of antibiotics makes it much worse; and the problem can only be met by the development of new drugs.

The point that antibiotic resistance predates our development of antibiotic drugs was made in an earlier Q&A in which Wright explored the mechanisms and origins of antibiotic resistance – it is prevalent in bacteria that live in the environment, for example in the soil microbes from which almost all of our antibiotic products are derived. He can now cite a more recent study confirming that the resistance genes we see in human pathogens are the same as those found in environmental bacteria, presumably as a defence against antibiotic products of their microbial neighbours – the very same products that are exploited by us for antimicrobial drugs. And the antiquity of resistance is illustrated by his own recent finding of resistance genes in the microbial community of a cave sealed from the surface 4 million years ago. The news that multi-resistant bugs have been found on American supermarket shelves thus clearly does not necessarily (as pointed out by the US FDA) imply a disease outbreak in the making – pathogens do not have a monopoly of resistance genes.

So if antibiotic resistance genes are everywhere, and can spread easily – what can we do about it? Wright’s answer, to which he has effectively devoted his career, is to keep discovering new antibiotics, or new ways to make old ones effective again. The problem here, he explains, IS manmade. Not a shortage of good ideas, or new compounds with drug potential, but a regulatory and incentive structure that is ill adapted to support the development of these drugs and get them quickly to the pharmacy. Perhaps most important is a bias towards the development of broad spectrum drugs, which has served the industry well in the past, but which limits the number of suitable lead compounds and – it can be argued – has helped promote both the spread of resistance and undesirable side-effects such as antibiotic-induced colitis, due to an indiscriminate effect on the patient’s microbiome.

Despite his conclusion that things will get worse before they can get better again, Wright points to some glimmers of hope. The Generate Antibiotic Incentives Now (GAIN) Act passed in in the US in 2012 has special provisions for antibiotics against resistant bacteria as well as measures designed to help fast-track new drugs. More recently, further reforms to clinical trial requirements have been proposed by the pharmaceutical industry. There are already some drugs that are benefiting from the GAIN Act, including two new drugs that will treat Clostridium difficile, bacteria that are notoriously causing complications after treatment with broad-spectrum antibiotics in a hospital setting.

Seventy years after antibiotics were first brought to market, it is hard to imagine where we would be if they cease to be effective. The erosion of their efficacy is ongoing, but Wright gives us reason to believe that the inevitable problem of resistance can be successfully met.

BioMed Central welcomes the HRA proposals ‘to make the registration of clinical trials within an agreed timeframe a condition of ethics ...

Read more]]> International Clinical Trials Day is celebrated around the world on the 20 May to commemorate the day in 1747 when James Lind started one of the very first trials in history. It provides an opportunity to raise awareness about the importance of clinical research in healthcare and to encourage involvement in clinical trials. It is timely that the recently created Health Research Authority (HRA) – whose mission is ‘to protect and promote the interests of patients and the public in health research’ - has announced its plans to increase transparency and reporting of clinical trials in the UK.

BioMed Central welcomes the HRA proposals ‘to make the registration of clinical trials within an agreed timeframe a condition of ethics approval’ and ‘to work with publishers to dispel the myths and perceptions about the difficulties in publishing results’.

Services for trial registration are already widely available. Under the aegis of the World Health Organization which has developed standards for trial registration, a growing number of registers worldwide help researchers reduce wasteful duplication of research and the potential for patients to be put at unnecessary risk in redundant trials.

In the absence of national legislation that would mandate public registration, responsibility for registration and results reporting ultimately lies with investigators and their sponsors or employers. A growing number of health research funders make public registration a condition of their grant application process. Ethical approval is another stage in the research cycle where public registration could be mandated and the HRA proposal to that effect is a step in the right direction.

BioMed Central has acknowledged that public registration (declaration of existence of research) can be seen as the first step towards transparency and future dissemination of health research outcomes. We administer the ISRCTN trial register which will list both trials awaiting ethical approval and trials with full ethical approval.

Traditional subscription journals often need to be extremely selective about what they can publish and less exciting results from trials can be excluded for reasons of space. Open access journals do not have these space constraints: BioMed Central journals welcome the publication of negative or inconclusive results which are essential in order to get the full picture of the research which has been carried out in any specific field. We publish a number of trials-related journals, including Trials, Systematic Reviews and the Journal of  Negative Results in BioMedicine which focuses on articles that ‘promote the discussion of unexpected, controversial, provocative and/or negative results in the context of current tenets’. The journal BMC Research Notes aims ‘to reduce the loss suffered by the research community when results remain unpublished because they do not form a sufficiently complete story to justify the publication of a full research article’. All journals in the BioMed Central medical portfolio encourage and/or demand adherence to established guidelines on trial reporting, such as CONSORT for trial results, SPIRIT for trial protocols, PRISMA for systematic reviews.  They all require that authors register their trials in a recognised register and provide the relevant reference, whether it is the ISRCTN number or the trial identifier used by another of the WHO-vetted registers.

BioMed Central supports this announcement and we look forward to working with the HRA.

Posted on behalf of Helene Faure

Ahead of the release of DSM-5, Molecular Autism has published commentaries from the labs of Catherine Lord and Fred Volkmar, both world leaders in autism and the autism phenotype, offering their perspectives on the new DSM-5 criteria for the autism spectrum.

The commentary by Lord’s group is broadly positive about the changes on the basis that they recognize core symptoms of autism spectrum disorders, as well as clinical features that are not specific to autism spectrum ...

Read more]]> This month, we will see the release of DSM-5, the fifth edition of the American Psychiatry Association’s Diagnostic and Statistical Manual of Mental Disorders, and perhaps one of the most anticipated events this year for those in the mental health field.

Ahead of the release of DSM-5, Molecular Autism has published commentaries from the labs of Catherine Lord and Fred Volkmar, both world leaders in autism and the autism phenotype, offering their perspectives on the new DSM-5 criteria for the autism spectrum.

The commentary by Lord’s group is broadly positive about the changes on the basis that they recognize core symptoms of autism spectrum disorders, as well as clinical features that are not specific to autism spectrum disorders. In contrast, Volkmar’s group raises some concern about DSM-5, in light of evidence that some high-functioning individuals will no longer meet diagnostic criteria for autism spectrum disorders, thereby becoming ineligible for services and treatment. They also question the removal of the subgroup of Asperger syndrome in this new edition of the manual as too extreme a move, as its symptoms will instead fall under the new single category termed “autism spectrum disorder”. Simon Baron-Cohen and Joseph Buxbaum, the Editors-in-Chief of Molecular Autism, have commented on this debate in an accompanying Editorial.

The DSM is used in a number of countries and is still hugely influential despite its controversy. However, on 29th April, the National Institute of Mental Health (NIMH) – the world’s biggest mental health research funder – announced that it was withdrawing its support of DSM-5 and would be “re-orienting its research away from DSM categories.” This is on the premise that, although the editions have provided “reliability” in ensuring that clinicians use the same terms in the same ways, they lack “validity”. As an alternative approach, the NIMH has launched the Research Domain Criteria (RDoC) project with the aim of transforming diagnosis by incorporating imaging, genetics, cognitive science, and other levels of information to pave the way for a new classification system.

DSM-5 has also been met with criticisms from the British Psychological Society, which recommends a change from using “diagnostic frameworks” to a description based specifically on an individual’s experienced problems.

What these changes will mean for the diagnosis of autism spectrum disorders in the decades to come remains to be seen. Follow the debate on Twitter at #DSM5.

Elizabeth Bal
Senior Journal Development Editor, BioMed Central

This Sunday, May 12th, marks Fibromyalgia Awareness Day, which aims to increase public awareness of the disease, and educate patients and the medical community. This year, Fibromyalgia Awareness Day coincides with the publication of Canadian guidelines for the diagnosis and management of ...

Read more]]> Fibromyalgia is a chronic widespread pain disorder, estimated to affect one in 20 people worldwide. It causes pain throughout the body, and often patients experience simultaneous conditions including fatigue and sleep problems, headaches and irritable bowel and bladder problems. After osteoarthritis, it is the second most common disorder observed by rheumatologists, yet there is no known cause or cure. The persistent and debilitating nature of the disorder can have a devastating effect on peoples’ lives.

This Sunday, May 12th, marks Fibromyalgia Awareness Day, which aims to increase public awareness of the disease, and educate patients and the medical community. This year, Fibromyalgia Awareness Day coincides with the publication of Canadian guidelines for the diagnosis and management of fibromyalgia in adults. The authors recommend that improved quality of life is the main treatment outcome, achieved by alleviating pain or the most troublesome symptom(s).

Alcohol, fibromyalgia, and quality of life
A study published in March in Arthritis Research & Therapy surveyed patients with fibromyalgia to examine the association between alcohol and their severity of symptoms and quality of life. It suggests that low and moderate drinkers have better scores for physical function, ability to work, the number of work days missed, fatigue and pain than people who abstained. The Mayo Clinic researchers suspect that alcohol’s ability to raise γ-aminobutyric acid (GABA) levels in the central nervous system might be accountable for these results.

Lifestyle effects were further assessed by Bjersing and colleagues in a recent trial that examined the long-term effects of aerobic exercise on fatigue in lean, overweight and obese women with fibromyalgia. Results show that exercise reduces fatigue in all patients, with the effect achieved earlier in lean patients and associated with increased levels of the adipokine resistin.

Mechanisms and management of fibromyalgia
With new developments continually arising from fibromyalgia research, Arthritis Research & Therapy has commissioned a review series that will explore the latest hot topics including the pain-prone phenotype, animal model studies in fibromyalgia and why the syndrome is important to rheumatologists. To be notified of publication of these articles, you can sign up for article alerts from Arthritis Research & Therapy here.

The researchers surveyed almost half a million mosquitoes from varied habitats including savannah grassland, semi-arid Acacia thorn bushes, and mangrove swamps, and sequenced the genomes of the viruses they found. 83 different viruses were found, both known and unknown species that cause disease in humans and livestock. Predominant virus families were alphaviruses, flaviviruses and orthobunyaviruses; ...

Read more]]> Mosquito borne viruses are a major cause of mortality and morbidity, especially in the developing world. As warmer weather increases the habitat for these disease vectors the problem is spreading to the developed world. A five-year study published today in Virology Journal shows for the first time the extent of mosquito-borne viruses (known as arboviruses) in diverse regions of Kenya.

The researchers surveyed almost half a million mosquitoes from varied habitats including savannah grassland, semi-arid Acacia thorn bushes, and mangrove swamps, and sequenced the genomes of the viruses they found. 83 different viruses were found, both known and unknown species that cause disease in humans and livestock. Predominant virus families were alphaviruses, flaviviruses and orthobunyaviruses; pathogenic West Nile virus, Ndumu, Sindbis, Bunyamwera, Pongola and Usutu virus were all found in diverse locations. Of particular interest was the isolation of Ngari virus, associated with hemorrhagic fever in northern Kenya in the late 1990s, from two sites in Kenya.

The authors, from United States Army Medical Research Unit, Kenya, Kenya Medical Research Institute, and the International Centre for Insect Physiology and Ecology in Nairobi, also found two previously unknown viruses, one with similarities to the newly discovered Chaoyang virus in China, and two more related to Quang Binh virus.

This study provides a hugely important resource for public health professionals in East Africa, identifying the habitat of these viruses and their insect vectors for the first time. Professor Linfa Wang, Editor-in-Chief of Virology Journal and an expert in emerging infectious diseases commented that “this important study highlights the need for on-going surveillance in animals and insect vectors, in order to prepare for potential virus outbreaks in humans.”

The Sherpas are a group known to perform extraordinarily well at altitude.  The team record the physiological responses of healthy individuals in this extreme environment – low oxygen levels at high altitude – and apply this research to patients in intensive care.  This is very much in line with the Extreme Physiology & Medicine’s objectives, outlined in its launch editorial, to explore boundary physiology and translate research findings into a clinical setting.

Mike provided this update:

“All our recruited subjects have now been ...

Read more]]> Two months into a research expedition to Mount Everest, Extreme Physiology & Medicine Editor-in-Chief Mike Grocott, reports from the trip.  Researchers on the Xtreme Everest 2 expedition are comparing Sherpa and “lowlander” physiology.

The Sherpas are a group known to perform extraordinarily well at altitude.  The team record the physiological responses of healthy individuals in this extreme environment – low oxygen levels at high altitude – and apply this research to patients in intensive care.  This is very much in line with the Extreme Physiology & Medicine’s objectives, outlined in its launch editorial, to explore boundary physiology and translate research findings into a clinical setting.

Mike provided this update:

“All our recruited subjects have now been tested at Everest Base Camp.  We still have a few days of investigator testing, but once this is complete we will start to decommission the Base Camp laboratory.  The team have done a brilliant job under often difficult conditions.”

The Xtreme Everest 2 team are keeping the wider world updated with a lively blog, twitter feed and plenty of pictures.

Other expedition core  team members include Extreme Physiology & Medicine Deputy Section Editors Dan Martin, Denny Levett and Phil Hennis, and other Editorial Board members are represented in the science and advisory teams too.

The project doesn’t finish at the end of the expedition in Nepal.  Expedition leader Dan Martin praised the efforts of everyone involved in the mission and highlighted the next steps:

“We cannot express enough our thanks to all our volunteer subjects and the fantastic team for making this unique experiment possible.  Collecting this data in the field is the beginning of a long journey of translation into the clinical environment that we hope will ultimately lead to improved care of critically ill patients.”

A new thematic series from Longevity & Healthspan focuses primarily on one aspect of aging; cellular senescence. The series, edited by Professors John M Sedivy and Jan M van Deursen, recently published an Editorial highlighting our current understanding of the mechanisms of cellular senescence and explains the need for continued study of this growing area of research.

The Editorial describes how cellular senescence can be triggered by many intrinsic and extrinsic stimuli, from activation of oncogenes to nutrient imbalances. In any case, ...

Read more]]> The biology of aging is becoming an increasingly popular area of research; both life-limiting age-related diseases and the mechanisms underlying  a longer healthy lifespan are intriguing to researchers and the public alike.

A new thematic series from Longevity & Healthspan focuses primarily on one aspect of aging; cellular senescence. The series, edited by Professors John M Sedivy and Jan M van Deursen, recently published an Editorial highlighting our current understanding of the mechanisms of cellular senescence and explains the need for continued study of this growing area of research.

The Editorial describes how cellular senescence can be triggered by many intrinsic and extrinsic stimuli, from activation of oncogenes to nutrient imbalances. In any case, it is known that p52 or retinoblastoma tumor suppressor proteins, or both, are activated via central signalling pathways and this is responsible for initiating and maintaining the cellular senescent state. In addition to understanding the mechanisms leading to cellular senescence, our knowledge of the senescent cell phenotype has also grown considerably; we now know that a typical senescent cell displays genotoxic stress, secretes specific inflammatory cytokins and contains a certain type of facultative heterochromatin.

The solid connection between cellular senescence and organismal aging requires further study. Therapeutically, there may be large implications for senescent cells; if  there is an accumulation of senescent cells as we age and they are also present at sites of age-associated pathologies, perhaps removal of these cells would help to improve healthy lifespan.

It is these topics that the Cellular Senescence and Aging thematic aims to address. Pre-submission enquires on all areas relating to cellular senescence and aging are welcome and should be sent to editorial@longevityandhealthspan.com. To stay up to date with publications in Longevity & Healthspan, sign up to receive article alerts here.

Streamed live online from the Royal Society of Medicine, London, MSF Scientific Day is a unique opportunity to showcase medical and scientific research carried out in MSF programmes around the world. Presenting and debating the findings from our research is vital to improve the quality of our humanitarian programmes and, by streaming the event online, we hope to engage the wider humanitarian and global health community in this discussion.

The agenda for this year’s MSF Scientific Day has now been finalised. The keynote speech by international health expert, co-founder of the Gapminder Foundation and TED talks alumnus

Read more]]> This year BioMed Central is pleased to be sponsoring MSF Scientific Day.

Streamed live online from the Royal Society of Medicine, London, MSF Scientific Day is a unique opportunity to showcase medical and scientific research carried out in MSF programmes around the world. Presenting and debating the findings from our research is vital to improve the quality of our humanitarian programmes and, by streaming the event online, we hope to engage the wider humanitarian and global health community in this discussion.

The agenda for this year’s MSF Scientific Day has now been finalised. The keynote speech by international health expert, co-founder of the Gapminder Foundation and TED talks alumnus Hans Rosling on the synergy and conflict between research and advocacy will be followed by a panel discussion on the impact of MSF’s research which will prove to be a lively and topical discussion on the importance of research and research visibility.

Other highlights include:
• Treatment in conflict and emergency settings including TB in Somalia and hepatitis E in South Sudan
• New approaches to preventing malaria in Mali and Chad, cholera vaccination in an outbreak in Guinea, and preventing malnutrition in Niger by cash transfer and food supplementation
• Challenges for MSF including the introduction of a medical error reporting system and parenteral artesunate for severe malaria
• The role of social media and health looking at the effect of MDR-TB patients blogging about their experiences

Get involved in the debate by following @MSF_UK on Twitter and using the #MSFSci hashtag or pop along to the BioMed Central stand at the event!

RNA binding proteins and their recognition elements within the transcriptome
The issue will focus on RNA binding proteins (RBPs), and the RNA molecules and motifs to which they bind: it is this RNA landscape, sculpted by RBPs, that we believe to be a particularly exciting and fast-moving area of research at the present time.

Read more]]> Genome Biology is very pleased to announce the Guest Editors of our special issue on the RBPome as John Rinn and Jernej Ule. The issue will be published in late 2013.

RNA binding proteins and their recognition elements within the transcriptome
The issue will focus on RNA binding proteins (RBPs), and the RNA molecules and motifs to which they bind: it is this RNA landscape, sculpted by RBPs, that we believe to be a particularly exciting and fast-moving area of research at the present time.

John Rinn

Jernej Ule