A novel drug based on capsaicin, the compound that gives chili peppers their spicy burn, caused long term weight loss and improved metabolic health in mice eating a high fat diet, in new studies from the University of Wyoming School of Pharmacy. The drug, Metabocin, was designed to slowly release capsaicin throughout the day so it can exert its anti-obesity effect without producing inflammation or adverse side effects.

"We observed marked improvements in blood sugar and cholesterol levels, insulin response, and symptoms of fatty liver disease," reported Dr. Baskaran Thyagarajan, lead investigator, describing how Metabocin reversed many damaging effects of the high fat diet. He presented the results this week at the annual meeting of the Society for the Study of Ingestive Behavior, the leading international conference of experts on food and fluid intake.

The research team developed Metabocin, which can be taken orally, to target receptors called TRPV1 (transient receptor potential vanilloid subfamily 1) that are found in high numbers in fat cells. Stimulating the TRPV1 receptors causes white fat cells to start burning energy instead of storing it, which, in theory, should cause weight loss. An important question for the researchers was whether the drug remains effective when used long term, and whether adverse effects would outweigh its benefits. The mice in this experiment remained on the drug for 8 months, maintaining the weight loss with no evidence of safety problems. Additional ongoing experiments will see how long that can be maintained.

"It proved safe and was well tolerated by the mice," Thyagarajan concluded. "Developing Metabocin as a potent anti-obesity treatment shows promise as part of a robust strategy for helping people struggling with obesity."

Although these results may give some people the idea to eat more spicy food to lose weight, that would not work as intended. Most of the capsaicin in spicy food is not well absorbed into the body so it would not produce these effects. The researchers specifically modified the capsaicin in Metabocin for proper absorption and sustained release.

Obesity is a growing public health concern, resulting in metabolic diseases including type 2 diabetes, hypertension, atherosclerosis and heart diseases. Currently one in three individuals world-wide is either overweight or obese. Exercise and diet are the standard recommendation, but those are difficult for most people to maintain in the long term, and rebound weight gain usually occurs. The Wyoming researchers advocated for continuing to pursue medical options that stay effective in the long term to counter obesity and its metabolic impacts, to assist people seeking to maintain a healthier weight.

Patients with persistent facial pain are costing the economy more than £3,000 each per year, new research has revealed.

Experts at Newcastle University, UK, say introducing an electronic referral system to speed up diagnosis and treatment is likely to improve quality of life and save money.

The team has assessed the hidden costs of people suffering from long-term face and mouth pain that wasn't caused by toothache.

Findings, published today in the Journal of Dental Research, show patients' out-of-pocket costs are more than £650 a year, including prescription charges and travel expenses to and from appointments.

Meanwhile, costs to employers can be almost £2,500 every 12 months, due to aspects such as absenteeism and workers' loss of productivity as a result of dealing with pain.

Screening patients

This research adds weight to growing evidence that there is a need to screen patients with a Graded Chronic Pain Scale (GCPS) to ensure those most severely affected receive specialist care quickly.

A previous study, by the same team at Newcastle University, showed that a well-established graded pain scale could help reduce costs by providing a better structured system of care.

Justin Durham, Professor of Orofacial Pain and Deputy Dean of Clinical Medicine, at Newcastle University, led the two-year study which was funded by the National Institute for Health Research.

He said: "Our research shows that people have to go around the proverbial 'mulberry bush', visiting lots of different healthcare professionals to even get close to obtaining a diagnosis never mind beginning treatment for their condition.

"A better and more defined care pathway would improve care for those with persistent facial pain and help reduce their costs and those to the economy."

It is estimated that 7% of the population have Persistent Orofacial Pain (POFP), including temporomandibular disorders, phantom tooth pain, burning mouth syndrome, trigeminal neuralgia and atypical facial pain.

This research has revealed how patients attend a large number of appointments with different healthcare professionals but fail to obtain effective diagnosis or treatment plan quickly.

Professor Durham added: "Persistent facial pain is like having toothache every day of the week and, therefore, understandably has a profound and debilitating impact on people's lives, and our research has highlighted the hidden costs of this condition."

Data collected

Experts asked 200 patients suffering long-term face and or mouth pain to complete questionnaires every six months for two years to assess how individuals used the NHS for their pain.

The team collected the costs of the care patients received, such as what the NHS paid to provide medication, surgery or other treatments, how much patients paid out of their own pockets and how their condition affected their ability to work.

Within a six month period, participants reported an average of nine healthcare appointments, and those employed reported missing almost two days off work. This absenteeism equates to an average employer cost of £174 per person per six-months.

While the findings suggest that most study participants were unlikely to have a large number of days off work because of their pain, they did report experiencing pain while working for nearly 35 days in a six-month period, during which they noted a decrease in their productivity whilst at work that could cost employers more than £1,000.

Professor Durham said: "We're calling for the introduction of an electronic referral system which uses a Graded Chronic Pain Scale - a simple seven item questionnaire.

"This scale would be a reliable way to determine who to fast-track to specialists and who should begin care immediately at their dentists or GP, meaning direct referrals would be made electronically to the best service local to the patient rather than relying on healthcare professionals' knowledge of who manages persistent facial pain in their locality."

Further research is expected to focus on how care pathways can be designed to better meet the needs of patients.

In partnership with the British Dental Association, the Newcastle University team is helping dentists and GPs manage persistent facial pain by setting up study days for next year.

Peter Dyer, Chair of the British Dental Association's Central Committee for Hospital Dental Staff, said: "Dentists working in hospitals will have seen patients who have failed to get priority, some on the verge of suicide in the face of unmanageable pain.

"This important research is a timely reminder that facial pain carries a huge personal and financial cost, and patients need not face barriers securing care.

"When so many people have been laid low by this condition GPs and high street dentists need a clear pathway to ensure patients can get the right treatment, when they need it."

Patient's story

Father-of-two Joe Buckham's life was turned upside down when he began to get severe facial pain a decade ago.

The extraction of a wisdom tooth left the former school teacher in agony as he suffered a fractured jaw during the procedure and a subsequent bone infection.

Mr Buckham was pushed from pillar to post as healthcare professionals struggled to identify the problem despite extensive tests, scans and investigations.

He spent a lot of money on hospital trips, including return train fares to a specialist in Oldham up to eight times, and private treatment, such as acupuncture and sports massage therapy.

It was not until he was referred to Professor Justin Durham, an Honorary Consultant Oral Surgeon at Newcastle upon Tyne Hospitals NHS Foundation Trust, that his problem was unearthed.

The 52-year-old has received treatment at Newcastle Hospitals' orofacial pain referral service and is on medication to help him deal with the pain.

The foster carer, of Rowlands Gill, Gateshead, said: "I believe had I been given the correct treatment quicker than I was, then I would have continued to work as a teacher.

"Sadly I had to retire because I couldn't do the job due to the seriousness of the pain - even things such as heat and antibiotics make it much worse.

"The pain I get in my face is severe and it can be very debilitating, sometimes it's so bad I just want to lie in a darkened room.

"Persistent facial pain is a hidden condition as no-one can see the problem and people don't understand it's so serious that it can ruin lives and you're stuck with it forever.

"The specialist service in Newcastle is fantastic and the research being done into facial pain is very much welcomed to help raise awareness of the condition.

"I feel that if medical healthcare professionals were able to use a Graded Chronic Pain Scale it would help ensure patients like me got the best treatment as soon as possible."

An independent inquiry by the Nuffield Council on Bioethics has concluded that editing the DNA of a human embryo, sperm, or egg to influence the characteristics of a future person ('heritable genome editing') could be morally permissible. If that is to happen, a number of measures would need to be put in place first to ensure that genome editing proceeds in ways that are ethically acceptable.

The technique of genome editing - the deliberate alteration of a targeted DNA sequence in a living cell - could theoretically be used in assisted reproduction to alter the DNA of a human embryo, before it is transferred to the womb. This is not currently lawful in the UK, but could, in time, become available as an option for parents who wish to influence the genetic characteristics of their future child (for example, to exclude a heritable disease or a predisposition to cancer in later life). The Council says that the possibilities raised by this radical new approach to reproductive choices could have significant implications for individuals and for all of society, and there must be action now to support public debate and to put in place appropriate governance.

The new report, Genome editing and human reproduction: social and ethical issues, sets out the range of ethical issues that arise in relation to the prospect of genome editing becoming available as a reproductive option for prospective parents.

The Council recommends that two overarching principles should guide the use of 'heritable genome editing interventions' for them be ethically acceptable:

they must be intended to secure, and be consistent with, the welfare of the future person; and

they should not increase disadvantage, discrimination or division in society

The Council further recommends that heritable genome editing interventions should be permitted only when:

there has been a sufficient opportunity for broad and inclusive public debate about its use and possible implications

further research has been carried out to establish standards of clinical safety

the risks of adverse effects for individuals, groups and society as a whole have been appropriately assessed and measures are in place to monitor and review these

It adds that, if it were to be permitted, it should be:

strictly regulated (by the HFEA in the UK)

introduced only in the context of a clinical study, with monitoring of the long-term effects on individuals and groups

licensed on a case-by-case basis

Further recommendations

In addition to these measures, the Council recommends the establishment of an independent body in the UK to promote broad and inclusive societal debate on heritable genome editing interventions and related scientific and medical developments.

Noting the international scope of research, the international mobility of knowledge, technology, and people, and the differences in values among jurisdictions, it says that countries across the world should work with international human rights institutions such as the Council of Europe and UNESCO to promote international dialogue and governance of heritable genome editing interventions.

Professor Karen Yeung, Chair of the working party and Professor of Law, Ethics, and Informatics at the University of Birmingham, said:

"There is potential for heritable genome editing interventions to be used at some point in the future in assisted human reproduction, as a means for people to secure certain characteristics in their children. Initially, this might involve preventing the inheritance of a specific genetic disorder. However, if the technology develops it has potential to become an alternative strategy available to parents for achieving a wider range of goals.

Whilst there is still uncertainty over the sorts of things genome editing might be able to achieve, or how widely its use might spread, we have concluded that the potential use of genome editing to influence the characteristics of future generations is not unacceptable in itself. However, the possibilities it raises could have significant impacts on individuals, families and on society. It is important that governments and public authorities step up and address these possibilities before people start asking to use this technology. Therefore, we urge the government to invest in supporting and encouraging broad and inclusive public debate, and put in place the governance measures that we need to ensure this promising technology is not used against the public interest."

Other reproductive options that are currently available to prospective parents who face the possibility of passing on an inherited genetic disorder, which genome editing might be considered alongside, include pre-implantation genetic diagnosis, which involves testing embryos for genetic characteristics and selecting one/s with preferred characteristics.

Although the UK is one of the countries that permits research on human embryos, the law does not currently permit genome editing interventions on embryos that are to be placed in a womb. The law would therefore have to be changed in order to allow the use of genome editing embryos, sperm or eggs for reproduction.

The Council's report sets out the ethical considerations raised by the prospect of heritable genome editing interventions in relation to the interests of the people who would be affected by its use, of others in society who may be indirectly affected, and of human beings in general. One of the main reasons heritable genome editing interventions are controversial is that changes may be passed on to future generations.

Professor Dave Archard, Chair of the Nuffield Council on Bioethics said:

"Huge advances are happening in genomics research, and whilst we have to acknowledge that genes alone do not shape a person, the possibility of using genome editing in reproduction to secure or avoid a characteristic in a child offers a radically new approach that is likely to appeal to some prospective parents.

There may be good reasons for allowing some parental preferences to be met, but we need to be careful that the use of genome editing to help parents to exercise these preferences doesn't increase social disadvantage, discrimination or division and that close attention is paid to the welfare of those involved, especially any child born as a result."

Children with autism have structural and functional abnormalities in the brain circuit that normally makes social interaction feel rewarding, according to a new study from the Stanford University School of Medicine.

The study, which will be published July 17 in Brain, documented deficits in children with autism in a crucial reward circuit, called the mesolimbic reward pathway, that's buried deep within the brain. The degree of abnormality in this pathway predicted the degree of social difficulty in individual children with autism, the study found.

The findings help clarify which of several competing theories best explains the social impairments seen in children with autism. The discoveries, made via MRI brain scans, support the social motivation theory of autism, which proposes that social interaction is inherently less appealing to people who have the disorder.

"It's the first time we have had concrete brain evidence to support this theory," said the study's lead author, Kaustubh Supekar, PhD, a research scientist at Stanford's Translational Neurosciences Incubator. Disrupting the mesolimbic reward pathway in mice reduces their social behavior, prior research has shown, but no one knew how closely the pathway was tied to social skills in people. "This is the first neurobiological evidence in children that this mechanism might explain their social impairments," Supekar said.

"Human social cognition is complex," said the study's senior author, Vinod Menon, PhD, professor of psychiatry and behavioral sciences. "We were surprised we could trace deficits in social skills to a very simple, almost primordial circuit."

A vicious cycle

The brain difference could launch a vicious cycle that makes it hard for children with autism to acquire complex social skills, according to the researchers.

"Social interaction is usually inherently rewarding. If it's not rewarding enough to a child with autism, that could have cascading effects on other brain systems," said Menon, who is the Rachael L. and Walter F. Nichols, MD, Professor. In order to develop social-communication skills and the ability to infer others' thoughts and feelings, children must interact with other people. If they don't find those interactions rewarding, they seek fewer opportunities to develop complex social skills, he said. "Our findings suggest that this is a brain system that should be targeted early in clinical treatments," he added.

Children with autism have difficulty with social interaction and communication, and show repetitive behaviors and restricted interests. The Centers for Disease Control and Prevention estimates the developmental disorder affects 1 in 59 children.

To conduct the study, the researchers collected MRI brain scans of 40 children with autism and 44 children without autism. They examined brain wiring in 24 children with autism and 24 children who didn't have it, and functional connections in the brain in 16 children with autism and 20 children without the disorder as they looked at social or nonsocial images -- pictures of faces or of scenery -- while having their brains scanned.

The team also conducted MRI scans of brain wiring on an additional 17 children with the disorder and 17 children without it to see if the results from the first groups could be replicated in a second, independent cohort. All of the children studied were 8-13 years old. Children with autism had their diagnosis confirmed by standard clinical testing for the disorder, and all children had their IQ tested.

The density of nerve-fiber tracts in the mesolimbic reward pathway was lower in children with autism than in those without; there were no differences between the children with and without autism when researchers examined an emotion-related brain pathway as a control. Among the children who had autism, lower density of nerve-fiber tracts was linked to greater social impairment on a standard clinical evaluation of their social skills. The results were the same in the second, independent cohort of children the team studied. Children with autism also had weaker functional connections in the mesolimbic reward pathway than did typically developing children. The degree of functional deficit was also correlated to social impairment.

Findings could aid search for treatments

The research provides a useful link between prior work in animal models of autism and human data, the researchers said, and is especially strong because the findings were replicated in two groups of research participants. Next, the researchers want to determine whether the same brain deficits can be detected in younger children with autism.

The discovery also provides a good starting point for future studies of autism treatments. Some existing, effective autism therapies use various rewards to help children engage in social interaction, but it is not known if those treatments strengthen the brain's social reward circuits.

"It would be exciting to conduct a clinical intervention study to determine whether the structural and functional integrity of this pathway can be altered through a reward-based learning paradigm," Menon said.