The role of cranial CT in the investigation of meningitis

More patients with meningitis are undergoing CT and the number of inappropriate requests are increasing. There are few abnormal CT scans presenting a contraindication for lumbar puncture and the majority of these patients usually have clinical signs to suggest raised intracranial pressure

A Transposon in Comt Generates mRNA Variants and Causes Widespread Expression and Behavioral Differences among Mice

Background: Catechol-O-methyltransferase (COMT) is a key enzyme responsible for the degradation of dopamine and norepinephrine. COMT activity influences cognitive and emotional states in humans and aggression and drug responses in mice. This study identifies the key sequence variant that leads to differences in Comt mRNA and protein levels among mice, and that modulates synaptic function and pharmacological and behavioral traits. Methodology/Principal Findings: We examined Comt expression in multiple tissues in over 100 diverse strains and several genetic crosses. Differences in expression map back to Comt and are generated by a 230 nt insertion of a B2 short interspersed element (B2 SINE) in the proximal 39 UTR of Comt in C57BL/6J. This transposon introduces a premature polyadenylation signal and creates a short 39 UTR isoform. The B2 SINE is shared by a subset of strains, including C57BL/6J

Catechol-O-Methyltransferase Val158Met Polymorphism Associates with Individual Differences in Sleep Physiologic Responses to Chronic Sleep Loss

Val158Met polymorphism was a novel marker in healthy adults of differential vulnerability to chronic partial sleep deprivation (PSD), a condition distinct from total sleep loss and one experienced by millions on a daily and persistent basis. allelic frequencies were higher in whites than African Americans.-related treatment responses and risk factors for symptom exacerbation

Mortality Risk Prediction by an Insurance Company and Long-Term Follow-Up of 62,000 Men

Background: Insurance companies use medical information to classify the mortality risk of applicants. Adding genetic tests to this assessment is currently being debated. This debate would be more meaningful, if results of present-day risk prediction were known. Therefore, we compared the predicted with the observed mortality of men who applied for life insurance, and determined the prognostic value of the risk assessment. Methods: Long-term follow-up was available for 62,334 male applicants whose mortality risk was predicted with medical evaluation and they were assigned to five groups with increasing risk from 1 to 5. We calculated all cause standardized mortality ratios relative to the Dutch population and compared groups with Cox's regression. We compared the discriminative ability of risk assessments as indicated by a concordance index (c). Results: In 844,815 person years we observed 3,433 deaths. The standardized mortality relative to the Dutch male population was 0.76 (95 percent confidence interval, 0.73 to 0.78). The standardized mortality ratios ranged from 0.54 in risk group 1 to 2.37 in group 5. A large number of risk factors and diseases were significantly associated with increased mortality. The algorithm of prediction was significantly, but only slightly better than summation of the number of disorders and risk factors (c-index, 0.64 versus 0.60, P,0.001). Conclusions: Men applying for insurance clearly had better survival relative to the general population. Readily available medical evaluation enabled accurate prediction of the mortality risk of large groups, but the deceased men could not have been identified with the applied prediction method

Copy number elevation of 22q11.2 genes arrests the developmental maturation of working memory capacity and adult hippocampal neurogenesis

Working memory capacity, a critical component of executive function, expands developmentally from childhood through adulthood. Anomalies in this developmental process are seen in individuals with autism spectrum disorder (ASD), schizophrenia and intellectual disabilities (ID), implicating this atypical process in the trajectory of developmental neuropsychiatric disorders. However, the cellular and neuronal substrates underlying this process are not understood. Duplication and triplication of copy number variants of 22q11.2 are consistently and robustly associated with cognitive deficits of ASD and ID in humans, and overexpression of small 22q11.2 segments recapitulates dimensional aspects of developmental neuropsychiatric disorders in mice. We capitalized on these two lines of evidence to delve into the cellular substrates for this atypical development of working memory. Using a region- and cell-type-selective gene expression approach, we demonstrated that copy number elevations of catechol-O-methyl-transferase (COMT) or Tbx1, two genes encoded in the two small 22q11.2 segments, in adult neural stem/progenitor cells in the hippocampus prevents the developmental maturation of working memory capacity in mice. Moreover, copy number elevations of COMT or Tbx1 reduced the proliferation of adult neural stem/progenitor cells in a cell-autonomous manner in vitro and migration of their progenies in the hippocampus granular layer in vivo. Our data provide evidence for the novel hypothesis that copy number elevations of these 22q11.2 genes alter the developmental trajectory of working memory capacity via suboptimal adult neurogenesis in the hippocampus.Peer reviewe

Kazakhstan Gulag heritage: dark tourism and selective interpretation

Kazakhstan holds some of the most significant Gulag heritage sites; however, tourism research remains limited. This article introduces analysis of contrasting sites and considers how some have been developed and others ignored. Selectivity in interpretation is linked to societal amnesia and the collective trauma experienced by the population of Kazakhstan. The article reaffirms the politicization of heritage in this emergent nation

Association between Catechol-O-Methyltrasferase Val108/158Met Genotype and Prefrontal Hemodynamic Response in Schizophrenia

BACKGROUND:"Imaging genetics" studies have shown that brain function by neuroimaging is a sensitive intermediate phenotype that bridges the gap between genes and psychiatric conditions. Although the evidence of association between functional val108/158met polymorphism of the catechol-O-methyltransferase gene (COMT) and increasing risk for developing schizophrenia from genetic association studies remains to be elucidated, one of the most topical findings from imaging genetics studies is the association between COMT genotype and prefrontal function in schizophrenia. The next important step in the translational approach is to establish a useful neuroimaging tool in clinical settings that is sensitive to COMT variation, so that the clinician could use the index to predict clinical response such as improvement in cognitive dysfunction by medication. Here, we investigated spatiotemporal characteristics of the association between prefrontal hemodynamic activation and the COMT genotype using a noninvasive neuroimaging technique, near-infrared spectroscopy (NIRS). METHODOLOGY/PRINCIPAL FINDINGS:Study participants included 45 patients with schizophrenia and 60 healthy controls matched for age and gender. Signals that are assumed to reflect regional cerebral blood volume were monitored over prefrontal regions from 52-channel NIRS and compared between two COMT genotype subgroups (Met carriers and Val/Val individuals) matched for age, gender, premorbid IQ, and task performance. The [oxy-Hb] increase in the Met carriers during the verbal fluency task was significantly greater than that in the Val/Val individuals in the frontopolar prefrontal cortex of patients with schizophrenia, although neither medication nor clinical symptoms differed significantly between the two subgroups. These differences were not found to be significant in healthy controls. CONCLUSIONS/SIGNIFICANCE:These data suggest that the prefrontal NIRS signals can noninvasively detect the impact of COMT variation in patients with schizophrenia. NIRS may be a promising candidate translational approach in psychiatric neuroimaging