Prevalence of mental disorders and torture among Tibetan refugees: A systematic review

BACKGROUND: Many Tibetan refugees flee Tibet in order to escape physical and mental hardships, and to access the freedoms to practice their culture and religion. We aimed to determine the prevalence of mental illnesses within the refugee population and determine the prevalence of previous torture reported within this population. METHODS: We performed a systematic literature search of 10 electronic databases from inception to May 2005. In addition, we searched the internet, contacted all authors of located studies, and contacted the Tibetan Government-in-exile, to locate unpublished studies. We included any study reporting on prevalence of mental illness within the Tibetan refugee populations. We determined study quality according to validation, translation, and interview administration. We calculated proportions with exact confidence intervals. RESULTS: Five studies that met our inclusion criteria (total n = 410). All studies were conducted in North India and 4 were specifically in adult populations. Four studies provided details on the prevalence of torture and previous imprisonment within the populations. The prevalence of post-traumatic stress disorder ranged from 11–23%, anxiety ranged from 25–77%, and major depression ranged from 11.5–57%. CONCLUSION: Our review indicates that the prevalence of serious mental health disorders within this population is elevated. The reported incidence of torture and imprisonment is a possible contributor to the illnesses. Non-government organizations and international communities should be aware of the human rights abuses being levied upon this vulnerable population and the mental health outcomes that may be associated with it

Disturbance and diversity at two spatial scales

The spatial scale of disturbance is a factor potentially influencing the relationship between disturbance and diversity. There has been discussion on whether disturbances that affect local communities and create a mosaic of patches in different successional stages have the same effect on diversity as regional disturbances that affect the whole landscape. In a microcosm experiment with metacommunities of aquatic protists, we compared the effect of local and regional disturbances on the disturbance–diversity relationship. Local disturbances destroyed entire local communities of the metacommunity and required reimmigration from neighboring communities, while regional disturbances affected the whole metacommunity but left part of each local community intact. Both disturbance types led to a negative relationship between disturbance intensity and Shannon diversity. With strong local disturbance, this decrease in diversity was due to species loss, while strong regional disturbance had no effect on species richness but reduced the evenness of the community. Growth rate appeared to be the most important trait for survival after strong local disturbance and dominance after strong regional disturbance. The pattern of the disturbance–diversity relationship was similar for both local and regional diversity. Although local disturbances at least temporally increased beta diversity by creating a mosaic of differently disturbed patches, this high dissimilarity did not result in regional diversity being increased relative to local diversity. The disturbance–diversity relationship was negative for both scales of diversity. The flat competitive hierarchy and absence of a trade-off between competition and colonization ability are a likely explanation for this pattern

Encoding Odorant Identity by Spiking Packets of Rate-Invariant Neurons in Awake Mice

Background: How do neural networks encode sensory information? Following sensory stimulation, neural coding is commonly assumed to be based on neurons changing their firing rate. In contrast, both theoretical works and experiments in several sensory systems showed that neurons could encode information as coordinated cell assemblies by adjusting their spike timing and without changing their firing rate. Nevertheless, in the olfactory system, there is little experimental evidence supporting such model. Methodology/Principal Findings: To study these issues, we implanted tetrodes in the olfactory bulb of awake mice to record the odorant-evoked activity of mitral/tufted (M/T) cells. We showed that following odorant presentation, most M/T neurons do not significantly change their firing rate over a breathing cycle but rather respond to odorant stimulation by redistributing their firing activity within respiratory cycles. In addition, we showed that sensory information can be encoded by cell assemblies composed of such neurons, thus supporting the idea that coordinated populations of globally rateinvariant neurons could be efficiently used to convey information about the odorant identity. We showed that different coding schemes can convey high amount of odorant information for specific read-out time window. Finally we showed that the optimal readout time window corresponds to the duration of gamma oscillations cycles. Conclusion: We propose that odorant can be encoded by population of cells that exhibit fine temporal tuning of spiking activity while displaying weak or no firing rate change. These cell assemblies may transfer sensory information in spikin

Implementing Routine HIV Testing: The Role of State Law

In September 2006, the Centers for Disease Control and Prevention (CDC) recommended routine HIV testing for all Americans aged 13–64, which would eliminate requirements for written consent and pretest counseling as previously required. However, this approach may conflict with state requirements concerning pretest counseling and informed consent for HIV testing. Our survey of state HIV testing laws demonstrates that the majority of states have HIV testing requirements that are inconsistent with the CDC's recommendations. Moreover, states that have recently amended their laws have not eased the requirements for pretest counseling and informed consent. The reasons for the persistence of these legal requirements must be understood to effect policy changes to increase HIV testing

Comparative evidence for a link between Peyer's patch development and susceptibility to transmissible spongiform encephalopathies

BACKGROUND: Epidemiological analyses indicate that the age distribution of natural cases of transmissible spongiform encephalopathies (TSEs) reflect age-related risk of infection, however, the underlying mechanisms remain poorly understood. Using a comparative approach, we tested the hypothesis that, there is a significant correlation between risk of infection for scrapie, bovine spongiform encephalopathy (BSE) and variant CJD (vCJD), and the development of lymphoid tissue in the gut. METHODS: Using anatomical data and estimates of risk of infection in mathematical models (which included results from previously published studies) for sheep, cattle and humans, we calculated the Spearman's rank correlation coefficient, r(s), between available measures of Peyer's patch (PP) development and the estimated risk of infection for an individual of the corresponding age. RESULTS: There was a significant correlation between the measures of PP development and the estimated risk of TSE infection; the two age-related distributions peaked in the same age groups. This result was obtained for each of the three host species: for sheep, surface area of ileal PP tissue vs risk of infection, r(s )= 0.913 (n = 19, P < 0.001), and lymphoid follicle density vs risk of infection, r(s )= 0.933 (n = 19, P < 0.001); for cattle, weight of PP tissue vs risk of infection, r(s )= 0.693 (n = 94, P < 0.001); and for humans, number of PPs vs risk of infection, r(s )= 0.384 (n = 46, P = 0.008). In addition, when changes in exposure associated with BSE-contaminated meat were accounted for, the two age-related patterns for humans remained concordant: r(s )= 0.360 (n = 46, P = 0.014). CONCLUSION: Our findings suggest that, for sheep, cattle and humans alike there is an association between PP development (or a correlate of PP development) and susceptibility to natural TSE infection. This association may explain changes in susceptibility with host age, and differences in the age-susceptibility relationship between host species

Cellular Growth Kinetics Distinguish a Cyclophilin Inhibitor from an HSP90 Inhibitor as a Selective Inhibitor of Hepatitis C Virus

During antiviral drug discovery, it is critical to distinguish molecules that selectively interrupt viral replication from those that reduce virus replication by adversely affecting host cell viability. In this report we investigate the selectivity of inhibitors of the host chaperone proteins cyclophilin A (CypA) and heat-shock protein 90 (HSP90) which have each been reported to inhibit replication of hepatitis C virus (HCV). By comparing the toxicity of the HSP90 inhibitor, 17-(Allylamino)-17-demethoxygeldanamycin (17-AAG) to two known cytostatic compounds, colchicine and gemcitabine, we provide evidence that 17-AAG exerts its antiviral effects indirectly through slowing cell growth. In contrast, a cyclophilin inhibitor, cyclosporin A (CsA), exhibited selective antiviral activity without slowing cell proliferation. Furthermore, we observed that 17-AAG had little antiviral effect in a non-dividing cell-culture model of HCV replication, while CsA reduced HCV titer by more than two orders of magnitude in the same model. The assays we describe here are useful for discriminating selective antivirals from compounds that indirectly affect virus replication by reducing host cell viability or slowing cell growth

Early Markers of Glycaemic Control in Children with Type 1 Diabetes Mellitus

Background: Type 1 diabetes mellitus (T1DM) may lead to severe long-term health consequences. In a longitudinal study, we aimed to identify factors present at diagnosis and 6 months later that were associated with glycosylated haemoglobin (HbA 1c) levels at 24 months after T1DM diagnosis, so that diabetic children at risk of poor glycaemic control may be identified. Methods: 229 children,15 years of age diagnosed with T1DM in the Auckland region were studied. Data collected at diagnosis were: age, sex, weight, height, ethnicity, family living arrangement, socio-economic status (SES), T1DM antibody titre, venous pH and bicarbonate. At 6 and 24 months after diagnosis we collected data on weight, height, HbA 1c level, and insulin dose. Results: Factors at diagnosis that were associated with higher HbA1c levels at 6 months: female sex (p,0.05), lower SES (p,0.01), non-European ethnicity (p,0.01) and younger age (p,0.05). At 24 months, higher HbA1c was associated with lower SES (p,0.001), Pacific Island ethnicity (p,0.001), not living with both biological parents (p,0.05), and greater BMI SDS (p,0.05). A regression equation to predict HbA1c at 24 months was consequently developed. Conclusions: Deterioration in glycaemic control shortly after diagnosis in diabetic children is particularly marked in Pacific Island children and in those not living with both biological parents. Clinicians need to be aware of factors associated wit

Influenza Virus Ribonucleoprotein Complexes Gain Preferential Access to Cellular Export Machinery through Chromatin Targeting

In contrast to most RNA viruses, influenza viruses replicate their genome in the nucleus of infected cells. As a result, newly-synthesized vRNA genomes, in the form of viral ribonucleoprotein complexes (vRNPs), must be exported to the cytoplasm for productive infection. To characterize the composition of vRNP export complexes and their interplay with the nucleus of infected cells, we affinity-purified tagged vRNPs from biochemically fractionated infected nuclei. After treatment of infected cells with leptomycin B, a potent inhibitor of Crm1-mediated export, we isolated vRNP export complexes which, unexpectedly, were tethered to the host-cell chromatin with very high affinity. At late time points of infection, the cellular export receptor Crm1 also accumulated at the same regions of the chromatin as vRNPs, which led to a decrease in the export of other nuclear Crm1 substrates from the nucleus. Interestingly, chromatin targeting of vRNP export complexes brought them into association with Rcc1, the Ran guanine exchange factor responsible for generating RanGTP and driving Crm1-dependent nuclear export. Thus, influenza viruses gain preferential access to newly-generated host cell export machinery by targeting vRNP export complexes at the sites of Ran regeneration

Markers of serotonergic function in the orbitofrontal cortex and dorsal raphé nucleus predict individual variation in spatial-discrimination serial reversal learning.

Dysfunction of the orbitofrontal cortex (OFC) impairs the ability of individuals to flexibly adapt behavior to changing stimulus-reward (S-R) contingencies. Impaired flexibility also results from interventions that alter serotonin (5-HT) and dopamine (DA) transmission in the OFC and dorsomedial striatum (DMS). However, it is unclear whether similar mechanisms underpin naturally occurring variations in behavioral flexibility. In the present study, we used a spatial-discrimination serial reversal procedure to investigate interindividual variability in behavioral flexibility in rats. We show that flexibility on this task is improved following systemic administration of the 5-HT reuptake inhibitor citalopram and by low doses of the DA reuptake inhibitor GBR12909. Rats in the upper quintile of the distribution of perseverative responses during repeated S-R reversals showed significantly reduced levels of the 5-HT metabolite, 5-hydroxy-indoleacetic acid, in the OFC. Additionally, 5-HT2A receptor binding in the OFC of mid- and high-quintile rats was significantly reduced compared with rats in the low-quintile group. These perturbations were accompanied by an increase in the expression of monoamine oxidase-A (MAO-A) and MAO-B in the lateral OFC and by a decrease in the expression of MAO-A, MAO-B, and tryptophan hydroxylase in the dorsal raphé nucleus of highly perseverative rats. We found no evidence of significant differences in markers of DA and 5-HT function in the DMS or MAO expression in the ventral tegmental area of low- vs high-perseverative rats. These findings indicate that diminished serotonergic tone in the OFC may be an endophenotype that predisposes to behavioral inflexibility and other forms of compulsive behavior.This work was supported by Medical Research Council Grants (G0701500; G0802729), a 503 Wellcome Trust Programme Grant (grant number 089589/Z/09/Z), and by a Core Award 504 from the Medical Research Council and the Wellcome Trust to the Behavioural and Clinical 505 21 Neuroscience Institute (MRC Ref G1000183; WT Ref 093875/Z/10/Z). RLB was supported 506 by a studentship from the Medical Research Council. JA was supported by a Fellowship from 507 the Swedish Research Council (350-2012-230). BJ was supported by Fellowships from the 508 AXA Research Fund and the National Health and Medical Research Council of Australia. 509 Financial support from the Fredrik and Ingrid Thuring Foundation is also acknowledged.This is the accepted manuscript. The final version is available from Nature Publishing at http://www.nature.com/npp/journal/vaop/ncurrent/full/npp2014335a.html