ANO10 c.1150_1151del is a founder mutation causing autosomal recessive cerebellar ataxia in Roma/Gypsies

A recent report (Vermeer et al. in Am J Hum Genet 87:813-819, 2010) implicated for the first time the ANO10 gene in the genetic basis of autosomal recessive cerebellar ataxias. One of the three described families were Roma/Gypsies from Serbia, where the affected individuals were homozygous for the truncating p.Leu384fs mutation and displayed distinct phenotypic features (Vermeer et al. in Am J Hum Genet 87:813-819, 2010). Based on the history and population genetics of the Roma/Gypsies, we hypothesised that p.Leu384fs could be another founder mutation in this population, whose identification in a larger number of genetically homogeneous patients will contribute to defining the phenotypic spectrum of the disorder. Here, we describe additional patients from neighbouring Bulgaria, outlining invariable ANO10-ataxia features and confirming global intellectual decline as part of the phenotype resulting from complete Anactomin 10 deficit.     

A Functional Polymorphism under Positive Evolutionary Selection in ADRB2 is Associated with Human Intelligence with Opposite Effects in the Young and the Elderly

Comparative genomics offers a novel approach to unravel the genetic basis of complex traits. We performed a two stage analysis where genes ascertained for enhanced protein evolution in primates are subsequently searched for the presence of non-synonymous coding SNPs in the current human population at amino acid sites that differ between humans and chimpanzee. Positively selected genes among primates are generally presumed to determine phenotypic differences between humans and chimpanzee, such as the enhanced cognitive ability of our species. Amino acid substitutions segregating in humans at positively selected amino acid sites are expected to affect phenotypic differences among humans. Therefore we conducted an association study in two family based cohorts and one population based cohort between cognitive ability and the most likely candidate gene among the five that harbored more than one such polymorphism. The derived, human-specific allele of the beta-2 adrenergic receptor Arg16Gly polymorphism was found to be the increaser allele for performance IQ in the young, family based cohort but the decreaser allele for two different measures of cognition in the large Scottish cohort of unrelated individuals. The polymorphism is known to affect signaling activity and modulation of beta-2 adrenergic signaling has been shown to adjust memory consolidation, a trait related to cognition. The opposite effect of the polymorphism on cognition in the two age classes observed in the different cohorts resembles the effect of ADRB2 on hypertension, which also has been reported to be age dependent. This result illustrates the relevance of comparative genomics to detect genes that are involved in human behavior. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. Edited by Tatiana Foroud.     

Low-income, ethnically diverse consumers' perspective on health information exchange and personal health records

We surveyed low-income, ethnically diverse consumers regarding their attitudes towards providers' use of electronic health information exchange (HIE) and consumer use of HIE through personal health records (PHRs). Amongst respondents (n=214), 48% had an annual household income below $15,000 and 62% spoke a language other than English at home. A majority indicated that they supported providers' use of HIE (61%). Support for providers' use of HIE was independently associated with consumer willingness to permit health care providers other than their primary care doctor to view their electronic medical record information (odds ratio (OR)=2.92, 95% confidence interval (CI)=1.31-6.50) and beliefs that electronic health record use would improve quality of care (OR=2.70, 95% CI=1.18-6.18). Seventy-eight percent would potentially use PHRs. Potential PHR use was independently associated with Internet usage rates, (OR=4.46, 95% CI=1.77-11.22), belief that PHR use would improve their understanding of their own healthcare (OR=3.12, 95% CI=1.27-7.67) and comfort with sharing PHR data with their primary care doctor (OR=2.79, 95% CI=1.09-7.11). Low-income, ethnically diverse consumers affected by interoperable health information technology (IT) initiatives largely support using PHRs and HIE, provided these systems demonstrate benefits and address the privacy and security of their electronic health information. Although we found interest in PHRs comparable or higher than nationally representative populations, support for HIE was lower, and thus efforts will need to be made to engage low-income and ethnically diverse consumers to participate in interoperable health IT initiatives.     

Using the model of resource and time-based triage (MORTT) to guide scarce resource allocation in the aftermath of a nuclear detonation

Conventional triage algorithms assume unlimited medical resource availability. After a nuclear detonation, medical resources are likely to be particularly limited, suggesting that conventional triage algorithms need to be rethought. To test various hypotheses related to the prioritization of victims in this setting, we developed the model of resource- and time-based triage (MORTT). This model uses information on time to death, probability of survival if treated and if untreated, and time to treat various types of traumatic injuries in an agent-based model in which the time of medical practitioners or materials can be limited. In this embodiment, MORTT focuses solely on triage for surgical procedures in the first 48 hours after a nuclear detonation. MORTT determines the impact on survival based on user-selected prioritization of victims by severity or type of injury. Using MORTT, we found that in poorly resourced settings, prioritizing victims with moderate life-threatening injuries over victims with severe life-threatening injuries saves more lives and reduces demand for intensive care, which is likely to outstrip local and national capacity. Furthermore, more lives would be saved if victims with combined injury (ie, trauma plus radiation >2 Gy) are prioritized after nonirradiated victims with similar trauma.     

Posttransplant lymphoproliferative disorder associated with an Epstein-Barr-related virus in cynomolgus monkeys

BACKGROUND: Human posttransplant lymphoproliferative disorder (PTLD) has been shown to be associated with Epstein-Barr virus (EBV) infection. Primate animal models of PTLD and the use of molecular markers in its diagnosis have not been reported. This study was designed to evaluate the frequency, pathology, and molecular characteristics of PTLD in cynomolgus kidney allograft recipients. METHODS: Over a 5-year period (January 1995 to November 2000), 160 primate renal transplants were performed at the Massachusetts General Hospital (MGH). Of these, all cases (n=9) that developed PTLD were included. H&E stained paraffin sections of all available tissue samples from the cases were evaluated for the presence of PTLD. Immunoperoxidase staining for T cells (CD3), B cells (CD20), kappa and lambda light chains as well as EBV nuclear antigens (EBNA2) and latent membrane proteins (EBV LMP-1) was done on paraffin sections using standard immunohistochemical (IHC) methods. In situ hybridization for EBV encoded RNA (EBER) was performed in all tissue samples with atypical lymphoid proliferations, using a novel EBER nucleotide probe based on consensus gene sequences from EBV and the related herpes lymphocryptoviruses (LCV) infecting baboons and rhesus macaques. RESULTS: Of 160 consecutive primate renal transplants performed at MGH, 5.6% developed PTLD 28-103 days after transplantation. In all cases, the lymph nodes were involved and effaced by an atypical polymorphous lymphoid proliferation of EBER+ B cells, diagnostic for PTLD. Focal staining for EBNA-2 was noted in tumor cells. In 67% (six of nine) the PTLD infiltrates were present in extra nodal sites, notably liver (56%), lung (44%), heart (44%), renal allograft (44%), and native kidney (22%). The spleen was involved by PTLD in all four animals that had not undergone a pretransplant splenectomy. The PTLD morphology was similar in all cases and predominantly of the polymorphous type, however, some of these showed areas that appeared minimally polymorphous. No cases of monomorphic PTLD were seen. CONCLUSIONS: By in situ hybridization, expression of the RNA product, homologous for EBV-encoded RNA (EBER) was identified in the PTLD tumor cells of all cases, indicating latent primate EBV- related infection. This report identifies a novel animal model of EBV associated PTLD in the setting of kidney transplantation, with valuable implications for managing and understanding human PTLD and oncogenesis.     

Placebo Effects of Edible Cannabis: Reported Intoxication Effects at a 30-Minute Delay

Previous research has demonstrated the ability of non-active smoked cannabis cigarettes to induce subjective effects of intoxication (i.e., placebo effect). No studies have been conduced to test whether edible forms of cannabis, which are associated with a significant delay in onset of effect, are able to induce a placebo effect. In the present study, 20 participants were told that they would receive an edible cannabis lollipop containing a high dose of tetrahydrocannabinol (THC), but were instead given a placebo control. Measures of intoxication and mood were taken at baseline, 30 minutes, and 60 minutes post-ingestion of the placebo lollipop. Results of four repeated-measures ANOVAs found significant and quadratic changes across time in cannabis (ARCI m-scale) intoxication (F(2,18) = 4.90, p = .01, η² = .22) and negative mood (F(2,18) = 3.99, p = .05, η² = .19). Changes in positive mood and the overall measure of general intoxication (ARCI) failed to reach significance. The present study provides preliminary evidence that a placebo effect can be induced with inert edible agents when participants are told that they are receiving active THC. This is the first known study to demonstrate an edible cannabis intoxication placebo effect.     

Limitations of liver surface US in the diagnosis of cirrhosis.

Ultrasound (US) of the liver surface with a high-frequency, small-parts, short-focused probe has been proposed as a method of diagnosing cirrhosis. US of the liver was performed in 50 consecutive patients undergoing diagnostic liver biopsy to assess the clinical usefulness of this noninvasive procedure in diagnosing hepatic cirrhosis. Eight patients had histologically proved cirrhosis, and 42 had no histologic evidence of cirrhosis. Seven of the eight patients with cirrhosis had a normal liver surface at US, and five of the 42 patients without cirrhosis had an abnormal liver surface. US of the liver surface with this probe was not reliable in this heterogeneous patient population.