Despite affecting up to 70% of HIV-positive patients and being the leading cause of dementia in patients under 40 years, the molecular mechanisms involved in the onset of HIV-associated neurocognitive disorders (HAND) are not well understood. To address this, we performed SILAC-based quantitative proteomic analysis on HIV-Tat treated SH-SY5Y neuroblastoma cells. Isolated protein was fractionated by SDS-PAGE and analyzed by nLC-MS/MS on an Orbitrap Velos. Using MaxQuant, we identified and quantified 3077 unique protein groups, of which 407 were differentially regulated. After applying an additional standard deviation-based cutoff, 29 of these were identified as highly significantly and stably dysregulated. GO term analysis shows dysregulation in both protein translation machinery as well as cytoskeletal regulation that have both been implicated in other dementias. In addition, several key cytoskeletal regulatory proteins such as ARHGEF17, the Rho GTPase, SHROOM3, and CMRP1 are downregulated. Together, these data demonstrate that HIV-Tat can dysregulate neuronal cytoskeletal regulatory proteins that could lead to the major HAND clinical manifestation-synapse loss.

ClinicalTrials.gov identifier: NCT00300313​​.

The question posed to the panelists on the first panel is: How has McDonnell affected prosecutors’ ability to police public corruption? What can politicians and lobbyists do and what can prosecutors prosecute?

No significant increase in the rate of serious infection was observed in LT recipients with PSC-IBD during exposure to anti-TNF therapy.

Moral emotions elicited in response to others' suffering are mediated by empathy and affect how we respond to their pain. South Africa provides a unique opportunity to study group processes given its racially divided past. The present study seeks insights into aspects of the moral brain by investigating behavioral and functional MRI responses of White and Black South Africans who lived through apartheid to in- and out-group physical and social pain. Whereas the physical pain task featured faces expressing dynamic suffering, the social pain task featured victims of apartheid violence from the South African Truth and Reconciliation Commission to elicit heartfelt emotion. Black participants' behavioral responses were suggestive of in-group favoritism, whereas White participants' responses were apparently egalitarian. However, all participants showed significant in-group biases in activation in the amygdala (physical pain), as well as areas involved in mental state representation, including the precuneus, temporoparietal junction (TPJ) and frontal pole (physical and social pain). Additionally, Black participants reacted with heightened moral indignation to own-race suffering, whereas White participants reacted with heightened shame to Black suffering, which was associated with blunted neural empathic responding. These findings provide ecologically valid insights into some behavioral and brain processes involved in complex moral situations.

<b>Background</b>Although childhood adversities are known to predict increased risk of post-traumatic stress disorder (PTSD) after traumatic experiences, it is unclear whether this association varies by childhood adversity or traumatic experience types or by age.<b>Aims</b>To examine variation in associations of childhood adversities with PTSD according to childhood adversity types, traumatic experience types and life-course stage.<b>Method</b>Epidemiological data were analysed from the World Mental Health Surveys (<i>n</i> = 27 017).<b>Results</b>Four childhood adversities (physical and sexual abuse, neglect, parent psychopathology) were associated with similarly increased odds of PTSD following traumatic experiences (odds ratio (OR) = 1.8), whereas the other eight childhood adversities assessed did not predict PTSD. Childhood adversity-PTSD associations did not vary across traumatic experience types, but were stronger in childhood-adolescence and early-middle adulthood than later adulthood.<b>Conclusions</b>Childhood adversities are differentially associated with PTSD, with the strongest associations in childhood-adolescence and early-middle adulthood. Consistency of associations across traumatic experience types suggests that childhood adversities are associated with generalised vulnerability to PTSD following traumatic experiences.

Children in the DCHS develop in a context typical of many communities in South Africa and other LMICs. There is a critical need for research in LMICs to elucidate underlying factors that inform risk for, and resilience to, poor developmental outcomes in infants born into high-risk communities. Such work may inform effective intervention strategies appropriate to this context.

The association between psychosocial factors and disability is less clear. This study investigated the biological and psychosocial (employment and psychological distress) factors associated with level of disability in an adult sample in South Africa. Data were analysed from a cross-sectional survey among adults aged 18-64 (n = 4974). Multiple linear regression was used to investigate the associations of the selected variables with disability. The mean percentage score on the WHODAS scale of disability was 5.31% (95% CI: 4.74-5.88). Age (p < 0.001) and race (p = 0.0002) were significantly associated with disability, and history of stroke (β = 7.19, 95% CI: 3.19-11.20) and heart-related conditions (β = 2.08, 95% CI: [0.23-3.93) showed positive associations. Of the psychosocial variables, psychological distress (β = 10.49 [8.63-12.35]) showed a strong positive association while employment (-1.62 [-2.36 to -0.88]) showed a negative association with disability. The association between demographic factors, medical conditions and increased disability confirms the findings in the literature. The finding that psychological distress is associated with increased disability has not been frequently reported. This study highlights specific psychosocial targets that may be usefully addressed by health policies and interventions in order to improve disability management.

There is a putative causal relationship between genetically determined female body shape and PTSD, which could be mediated by evolutionary mechanisms involved in human sexual behaviors.

There is not sufficient good-quality evidence available to determine the effects of risperidone compared with other antipsychotics in people with a dual diagnosis. Few trials compared risperidone with first-generation agents, leading to limited applicability to settings where access to second-generation agents is limited, such as in low- and middle-income countries. Moreover, heterogeneity in trial design and measurement of outcomes precluded the use of many trials in our analyses. Future trials in this area need to be sufficiently powered but also need to conform to consistent methods in study population selection, use of measurement scales, definition of outcomes, and measures to counter risk of bias. Investigators should adhere to CONSORT guidelines in the reporting of results.