Science 23 May 2008:
Vol. 320. no. 5879, pp. 1074 - 1077
Differential Rescue of Light- and Food-Entrainable Circadian Rhythms
When food is plentiful, circadian rhythms of animals are powerfully entrained by the light-dark cycle. However, if animals have access to food only during their normal sleep cycle, they will shift most of their circadian rhythms to match the food availability. We studied the basis for entrainment of circadian rhythms by food and light in mice with targeted disruption of the clock gene Bmal1, which lack circadian rhythmicity. Injection of a viral vector containing the Bmal1 gene into the suprachiasmatic nuclei of the hypothalamus restored light-entrainable, but not food-entrainable, circadian rhythms. In contrast, restoration of the Bmal1 gene only in the dorsomedial hypothalamic nucleus restored the ability of animals to entrain to food but not to light. These results demonstrate that the dorsomedial hypothalamus contains a Bmal1-based oscillator that can drive food entrainment of circadian rhythms.

Science 23 May 2008:
Vol. 320. no. 5879, pp. 1092 - 1095
The Right and the Good: Distributive Justice and Neural Encoding of Equity and Efficiency
Distributive justice concerns how individuals and societies distribute benefits and burdens in a just or moral manner. We combined distribution choices with functional magnetic resonance imaging to investigate the central problem of distributive justice: the trade-off between equity and efficiency. We found that the putamen responds to efficiency, whereas the insula encodes inequity, and the caudate/septal subgenual region encodes a unified measure of efficiency and inequity (utility). Notably, individual differences in inequity aversion correlate with activity in inequity and utility regions. Against utilitarianism, our results support the deontological intuition that a sense of fairness is fundamental to distributive justice but, as suggested by moral sentimentalists, is rooted in emotional processing. More generally, emotional responses related to norm violations may underlie individual differences in equity considerations and adherence to ethical rules.

Nature 453, - (2008) p441
Parkinson's researchers join forces with gene tester

Nature 453, - (2008) p446
Language: The language barrier
Some researchers think that the evolution of languages can be understood by treating them like genomes — but many linguists don't want to hear about it. Emma Marris reports. Consider a word as it tumbles through history: khun, a Nepali word for blood. In the early twentieth century, the word fell all too often from the lips of the Gurkhas, a Nepalese brigade in the British Army, in songs describing the horror of the First World War.

Nature 453, 456-457 (22 May 2008)
Science & Music: Lost in music
Music provides unique opportunities for understanding both brain and culture. But globalization means that time is running out, warns David Huron, for the quest to encounter the range of possible musical minds.

JAMA  Vol. 299 No. 19, May 21, 2008    
Percutaneous Closure of Patent Foramen Ovale and Atrial Septal Defect
To the Editor: In their Research Letter, Dr Opotowsky and colleagues reported an increase in percutaneous closure of interatrial defects. There are a number of points that we believe need to be considered in interpreting the data presented in their article.Patent foramen ovale (PFO) and atrial septal defect (ASD) were classified together in the analysis, so specific comment on the indication for closure should be cautious. In addition, the observation that the rate of interatrial shunt closure has increased disproportionate to coronary revascularization following the introduction of stents needs to be viewed in context. This is due in part to far fewer PFO/ASD closures being performed in comparison with coronary revascularization at the commencement of the relevant periods. This increase is also likely to be magnified by significant improvements in equipment, devices, operator training, and lesion identification.

JAMA Vol. 299 No. 19, May 21, 2008     
Percutaneous Closure of Patent Foramen Ovale and Atrial Septal Defect—Reply
In Reply: We agree with the main assertions made by Drs Bhindi and Ormerod. The data available did not allow for distinction between PFO and ASD, and any comment on indications for the procedure must be qualified. The relative increase in the rate of coronary revascularization procedures was included to provide general perspective; direct comparison between these procedures is limited.
In terms of PFO closure, we agree that management decisions for PFO must be individualized and that certain characteristics of PFO may help predict the risk of a neurological event. Some observational data suggest that certain atrial septal characteristics predict higher stroke risk, although there are conflicting reports. Given the potential for selection and ascertainment bias in these studies (eg, echocardiographers may "look harder" to make a diagnosis of PFO in patients with cryptogenic stroke), data must be interpreted with caution.

JAMA. 2008;299(19):2261-2263.
Studies, Reports Say Botulinum Toxins May Have Effects Beyond Injection Site
Scientists and investigators are probing the possibility that botulinum toxins may migrate from the site of injection and may cause unintended effects including weakening adjacent muscles.
As the myriad clinical uses for botulinum toxins continue to expand, scientists examining their mechanism of action in animal models have demonstrated that these neurotoxins may have a measurable effect on muscles adjacent to the injection site. They also have identified pathways by which the toxins may travel in the nervous system and cause distant neurological effects. The findings have emerged as the US Food and Drug Administration (FDA) investigates reports of adverse reactions in patients treated with botulinum toxin that suggest spread of toxin beyond the injection site.

JAMA. 2008;299(19):2267.
Parkinson Disease
Independent findings from 2 teams of scientists in Europe and North America suggest that using cell transplants to compensate for the destruction of dopamine-producing neurons in patients with Parkinson disease may be compromised because the disease is an ongoing process that can also affect the transplanted cells (Kordower JH et al. Nat Med. 10.1038/nm1747; Li J-Y et al. Nat Med. 10.1038/nm1746 [both published online ahead of print April 6, 2008]).

BMJ  2008;336:1094 (17 May
Nuffield Council seeks views on ethics of caring for people with dementia
Patients, carers, and families affected by dementia and health professionals are being asked to contribute to a consultation on the ethical dilemmas of managing the disease.
The Nuffield Council on Bioethics, a UK independent body that examines ethical issues raised by new developments in biology and medicine, has launched the consultation this week to gather the views and experiences of people who face the challenges of dementia. Its aim is to develop recommendations to support people in the decisions they make every day.

BMJ  2008;336:1094-1095 (17 May
UK lags behind similar countries in stroke services
Services in the United Kingdom for stroke patients are lagging behind those in other developed nations, a new report says, and targets are now being called into question.
The Health Foundation, an independent body that works to improve the quality of health care in the United Kingdom, has published a report that brings together data on performance of services with evidence of what works and the cost implications of stroke.

BMJ  2008;336:1121-1123 (17 May), doi:10.1136/bmj.39548.738368.BE (published 14 May 2008)
Effects of different regimens to lower blood pressure on major cardiovascular events in older and younger adults: meta-analysis of randomised trials
Objective To quantify the relative risk reductions achieved with different regimens to lower blood pressure in younger and older adults.
Design Meta-analyses and meta-regression analyses used to compare the effects on the primary outcome between two age groups (<65 v 65 years). Evidence for an interaction between age and the effects of treatment sought by fitting age as a continuous variable and estimating overall effects across trials.
Main outcome measures Primary outcome: total major cardiovascular events.
Results 31 trials, with 190 606 participants, were included. The meta-analyses showed no clear difference between age groups in the effects of lowering blood pressure or any difference between the effects of the drug classes on major cardiovascular events (all P0.24). Neither was there any significant interaction between age and treatment when age was fitted as a continuous variable (all P>0.09). The meta-regressions also showed no difference in effects between the two age groups for the outcome of major cardiovascular events (<65 v 65; P=0.38).
Conclusions Reduction of blood pressure produces benefits in younger (<65 years) and older (65 years) adults, with no strong evidence that protection against major vascular events afforded by different drug classes varies substantially with age.

The Lancet Vol: 371 Issue: 9625, May 17 - 23 2008
From drugs to delirium
In July, 2007, at around 0740 h, a 36-year-old man was brought to our emergency department by his father, with whom he lived. Since his teens, the patient had misused several drugs, often concurrently: cough mixture, cannabis, zopiclone and other sleeping tablets, and a mixture of ketamine and ecstasy. He had been admitted to our psychiatric unit five times in the preceding 6 years: three times for drug-induced psychosis, and twice for detoxification. His admissions were becoming more frequent. The patient's father said that, on this occasion, the patient had suddenly become confused, at around 0640 h. He had wandered out of the toilet without his trousers or underpants on, and had knelt on the floor, his body resting against his bed. He had inappropriate and scanty speech. His father did not know what drugs the patient had been taking recently—other than zopiclone, which was prescribed.

NEJM Volume 358:2231-2239  May 22, 2008  Number 21
Effect of Gene Therapy on Visual Function in Leber's Congenital Amaurosis
Early-onset, severe retinal dystrophy caused by mutations in the gene encoding retinal pigment epithelium–specific 65-kD protein (RPE65) is associated with poor vision at birth and complete loss of vision in early adulthood. We administered to three young adult patients subretinal injections of recombinant adeno-associated virus vector 2/2 expressing RPE65 complementary DNA (cDNA) under the control of a human RPE65 promoter. There were no serious adverse events. There was no clinically significant change in visual acuity or in peripheral visual fields on Goldmann perimetry in any of the three patients. We detected no change in retinal responses on electroretinography. One patient had significant improvement in visual function on microperimetry and on dark-adapted perimetry. This patient also showed improvement in a subjective test of visual mobility. These findings provide support for further clinical studies of this experimental approach in other patients with mutant RPE65. (ClinicalTrials.gov number, NCT00643747 [ClinicalTrials.gov] .)

NEJM Volume 358:2240-2248  May 22, 2008  Number 21
Safety and Efficacy of Gene Transfer for Leber's Congenital Amaurosis
Leber's congenital amaurosis (LCA) is a group of inherited blinding diseases with onset during childhood. One form of the disease, LCA2, is caused by mutations in the retinal pigment epithelium–specific 65-kDa protein gene (RPE65). We investigated the safety of subretinal delivery of a recombinant adeno-associated virus (AAV) carrying RPE65 complementary DNA (cDNA) (ClinicalTrials.gov number, NCT00516477 [ClinicalTrials.gov] ). Three patients with LCA2 had an acceptable local and systemic adverse-event profile after delivery of AAV2.hRPE65v2. Each patient had a modest improvement in measures of retinal function on subjective tests of visual acuity. In one patient, an asymptomatic macular hole developed, and although the occurrence was considered to be an adverse event, the patient had some return of retinal function. Although the follow-up was very short and normal vision was not achieved, this study provides the basis for further gene therapy studies in patients with LCA.

NEJM Volume 358:2282-2284  May 22, 2008  Number 21
Preliminary Results of Gene Therapy for Retinal Degeneration
In this issue of the Journal, two groups of investigators — Bainbridge et al. and Maguire et al. — describe the first results of separate clinical trials investigating the short-term safety and preliminary efficacy of gene therapy for Leber's congenital amaurosis. Both groups present short-term data (12 months and 5 months, respectively) on three patients with Leber's congenital amaurosis in each study; the patients were enrolled in trials of recombinant adeno-associated viral delivery of the human retinal pigment epithelium-specific 65-kDa protein gene (RPE65), which was administered as a subretinal injection during vitrectomy.

NEJM Volume 358:2298  May 22, 2008  Number 21
Neurogenic Orthostatic Hypotension
To the Editor: In his Clinical Practice article on neurogenic orthostatic hypotension, Freeman (Feb. 7 issue) notes that the definition of orthostatic hypotension encompasses a drop in blood pressure during the first 3 minutes of standing. He states that when evaluating a patient, however, the blood pressure should be measured with the patient in the supine position and at least 3 minutes after the patient stands up. These two statements appear to contradict each other.