Understanding psychiatric institutionalization: a conceptual review

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

A Systematic Mapping Approach of 16q12.2/FTO and BMI in More Than 20,000 African Americans Narrows in on the Underlying Functional Variation: Results from the Population Architecture using Genomics and Epidemiology (PAGE) Study

Genetic variants in intron 1 of the fat mass- and obesity-associated (FTO) gene have been consistently associated with body mass index (BMI) in Europeans. However, follow-up studies in African Americans (AA) have shown no support for some of the most consistently BMI-associated FTO index single nucleotide polymorphisms (SNPs). This is most likely explained by different race-specific linkage disequilibrium (LD) patterns and lower correlation overall in AA, which provides the opportunity to fine-map this region and narrow in on the functional variant. To comprehensively explore the 16q12.2/FTO locus and to search for second independent signals in the broader region, we fine-mapped a 646-kb region, encompassing the large FTO gene and the flanking gene RPGRIP1L by investigating a total of 3,756 variants (1,529 genotyped and 2,227 imputed variants) in 20,488 AAs across five studies. We observed associations between BMI and variants in the known FTO intron 1 locus: the SNP with the most significant p-value, rs56137030 (8.3×10-6) had not been highlighted in previous studies. While rs56137030was correlated at r2>0.5 with 103 SNPs in Europeans (including the GWAS index SNPs), this number was reduced to 28 SNPs in AA. Among rs56137030 and the 28 correlated SNPs, six were located within candidate intronic regulatory elements, including rs1421085, for which we predicted allele-specific binding affinity for the transcription factor CUX1, which has recently been implicated in the regulation of FTO. We did not find strong evidence for a second independent signal in the broader region. In summary, this large fine-mapping study in AA has substantially reduced the number of common alleles that are likely to be functional candidates of the known FTO locus. Importantly our study demonstrated that comprehensive fine-mapping in AA provides a powerful approach to narrow in on the functional candidate(s) underlying the initial GWAS findings in European populations

Psychiatric disorder in early adulthood and risk of premature mortality in the 1946 British Birth Cohort

<p>Abstract</p> <p>Background</p> <p>Few studies of the association between psychiatric disorder and premature death have adjusted for key confounders and used structured psychiatric interviews. We aimed to investigate if psychiatric disorder was associated with a higher risk of mortality and whether any excess mortality was due to suicide, or explained by other health or socioeconomic risk factors.</p> <p>Methods</p> <p>We used data from the MRC National Survey of Health and Development, a nationally representative UK birth cohort. 3283 men and women completed the Present State Examination at age 36. The main outcome measure was all-cause mortality before age 60.</p> <p>Results</p> <p>Those with psychiatric disorder at age 36 had a higher risk of death even after adjusting for potential confounders (Hazard ratio = 1.84, 95% C.I. 1.22-2.78). Censoring violent deaths and suicides led to similar results.</p> <p>Conclusions</p> <p>Psychiatric disorder was associated with excess premature mortality not explained by suicide or other health or socioeconomic risk factors.</p

Reducing bias in auditory duration reproduction by integrating the reproduced signal

Duration estimation is known to be far from veridical and to differ for sensory estimates and motor reproduction. To investigate how these differential estimates are integrated for estimating or reproducing a duration and to examine sensorimotor biases in duration comparison and reproduction tasks, we compared estimation biases and variances among three different duration estimation tasks: perceptual comparison, motor reproduction, and auditory reproduction (i.e. a combined perceptual-motor task). We found consistent overestimation in both motor and perceptual-motor auditory reproduction tasks, and the least overestimation in the comparison task. More interestingly, compared to pure motor reproduction, the overestimation bias was reduced in the auditory reproduction task, due to the additional reproduced auditory signal. We further manipulated the signal-to-noise ratio (SNR) in the feedback/comparison tones to examine the changes in estimation biases and variances. Considering perceptual and motor biases as two independent components, we applied the reliability-based model, which successfully predicted the biases in auditory reproduction. Our findings thus provide behavioral evidence of how the brain combines motor and perceptual information together to reduce duration estimation biases and improve estimation reliability

Acquisition of pneumococci specific effector and regulatory Cd4+ T cells localising within human upper respiratory-tract mucosal lymphoid tissue

The upper respiratory tract mucosa is the location for commensal Streptococcus (S.) pneumoniae colonization and therefore represents a major site of contact between host and bacteria. The CD4(+) T cell response to pneumococcus is increasingly recognised as an important mediator of immunity that protects against invasive disease, with data suggesting a critical role for Th17 cells in mucosal clearance. By assessing CD4 T cell proliferative responses we demonstrate age-related sequestration of Th1 and Th17 CD4(+) T cells reactive to pneumococcal protein antigens within mucosal lymphoid tissue. CD25(hi) T cell depletion and utilisation of pneumococcal specific MHCII tetramers revealed the presence of antigen specific Tregs that utilised CTLA-4 and PDL-1 surface molecules to suppress these responses. The balance between mucosal effector and regulatory CD4(+) T cell immunity is likely to be critical to pneumococcal commensalism and the prevention of unwanted pathology associated with carriage. However, if dysregulated, such responses may render the host more susceptible to invasive pneumococcal infection and adversely affect the successful implementation of both polysaccharide-conjugate and novel protein-based pneumococcal vaccines

Activation of the B cell receptor leads to increased membrane proximity of the Igα cytoplasmic domain.

Binding of antigen to the B cell receptor (BCR) induces conformational changes in BCR's cytoplasmic domains that are concomitant with phosphorylation of the immunoreceptor tyrosine-based activation motifs (ITAMs). Recently, reversible folding of the CD3ε and ξ chain ITAMs into the plasma membrane has been suggested to regulate T cell receptor signaling. Here we show that the Igα and Igβ cytoplasmic domains of the BCR do not associate with plasma membrane in resting B cells. However, antigen binding and ITAM phosphorylation specifically increased membrane proximity of Igα, but not Igβ. Thus, BCR activation is accompanied by asymmetric conformational changes, possibly promoting the binding of Igα and Igβ to differently localized signaling complexes

Differences between patients' and clinicians' report of sleep disturbance: a field study in mental health care in Norway

<p>Abstract</p> <p>Background</p> <p>The aims of the study was to assess the prevalence of diagnosed insomnia and the agreement between patient- and clinician-reported sleep disturbance and use of prescribed hypnotic medication in patients in treatment for mental disorders.</p> <p>Methods</p> <p>We used three cross-sectional, multicenter data-sets from 2002, 2005, and 2008. Data-set 1 included diagnostic codes from 93% of all patients receiving treatment in mental health care in Norway (<it>N </it>= 40261). Data-sets 2 (<it>N </it>= 1065) and 3 (<it>N </it>= 1181) included diagnostic codes, patient- and clinician-reported sleep disturbance, and use of prescribed hypnotic medication from patients in 8 mental health care centers covering 10% of the Norwegian population.</p> <p>Results</p> <p>34 patients in data-set 1 and none in data-sets 2 and 3 had a diagnosis of insomnia as a primary or comorbid diagnosis. In data-sets 2 and 3, 42% and 40% of the patients reported sleep disturbance, whereas 24% and 13% had clinician-reported sleep disturbance, and 7% and 9% used hypnotics. Patients and clinicians agreed in 29% and 15% of the cases where the patient or the clinician or both had reported sleep disturbance. Positive predictive value (PPV) of clinicians' evaluations of patient sleep disturbance was 62% and 53%. When the patient reported sleep disturbance as one of their most prominent problems PPV was 36% and 37%. Of the patients who received hypnotic medication, 23% and 29% had neither patient nor clinician-rated sleep disturbance.</p> <p>Conclusion</p> <p>When patients meet the criteria for a mental disorder, insomnia is almost never diagnosed, and sleep disturbance is imprecisely recognized relative to the patients' experience of sleep disturbance.</p

Endangered right whales enhance primary productivity in the bay of fundy

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Marine mammals have recently been documented as important facilitators of rapid and efficient nutrient recycling in coastal and offshore waters. Whales enhance phytoplankton nutrition by releasing fecal plumes near the surface after feeding and by migrating from highly productive, high-latitude feeding areas to low-latitude nutrient-poor calving areas. In this study, we measured NH4 + and PO4 3- release rates from the feces of North Atlantic right whales (Eubalaena glacialis), a highly endangered baleen whale. Samples for this species were primarily collected by locating aggregations of whales in surface- Active groups (SAGs), which typically consist of a central female surrounded by males competing for sexual activity. When freshly collected feces were incubated in seawater, high initial rates of N release were generally observed, which decreased to near zero within 24 hours of sampling, a pattern that is consistent with the active role of gut microflora on fecal particles. We estimate that at least 10% of particulate N in whale feces becomes available as NH4 + within 24 hours of defecation. Phosphorous was also abundant in fecal samples: Initial release rates of PO4 3- were higher than for NH4 +, yielding low N/P nutrient ratios over the course of our experiments. The rate of PO4 3- release was thus more than sufficient to preclude the possibility that nitrogenous nutrients supplied by whales would lead to phytoplankton production limited by P availability. Phytoplankton growth experiments indicated that NH4 + released from whale feces enhance productivity, as would be expected, with no evidence that fecal metabolites suppress growth. Although North Atlantic right whales are currently rare (approximately 450 individuals), they once numbered about 14,000 and likely played a substantial role in recycling nutrients in areas where they gathered to feed and mate. Even though the NH4 + released from fresh whale fecal material is a small fraction of total whale fecal nitrogen, and recognizing the fact that the additional nitrogen released in whale urine would be difficult to measure in a field study, the results of this study support the idea that the distinctive isotopic signature of the released NH4 + could be used to provide a conservative estimate of the contribution of the whale pump to primary productivity in coastal regions where whales congregate