A Mendelian randomization study of genetic liability to post-traumatic stress disorder and risk of ischemic stroke.

Observational studies have shown an association between post-traumatic stress disorder (PTSD) and ischemic stroke (IS) but given the susceptibility to confounding it is unclear if these associations represent causal effects. Mendelian randomization (MR) facilitates causal inference that is robust to the influence of confounding. Using two sample MR, we investigated the causal effect of genetic liability to PTSD on IS risk. Ancestry-specific genetic instruments of PTSD and four quantitative sub-phenotypes of PTSD, including hyperarousal, avoidance, re-experiencing, and total symptom severity score (PCL-Total) were obtained from the Million Veteran Programme (MVP) using a threshold P value (P) of <5 × 10-7, clumping distance of 1000 kilobase (Mb) and r2 < 0.01. Genetic association estimates for IS were obtained from the MEGASTROKE consortium (Ncases = 34,217, Ncontrols = 406,111) for European ancestry individuals and from the Consortium of Minority Population Genome-Wide Association Studies of Stroke (COMPASS) (Ncases = 3734, Ncontrols = 18,317) for African ancestry individuals. We used the inverse-variance weighted (IVW) approach as the main analysis and performed MR-Egger and the weighted median methods as pleiotropy-robust sensitivity analyses. In European ancestry individuals, we found evidence of an association between genetic liability to PTSD avoidance, and PCL-Total and increased IS risk (odds ratio (OR)1.04, 95% Confidence Interval (CI) 1.007-1.077, P = 0.017 for avoidance and (OR 1.02, 95% CI 1.010-1.040, P = 7.6 × 10-4 for PCL total). In African ancestry individuals, we found evidence of an association between genetically liability to PCL-Total and reduced IS risk (OR 0.95 (95% CI 0.923-0.991, P = 0.01) and hyperarousal (OR 0.83 (95% CI 0.691-0.991, P = 0.039) but no association was observed for PTSD case-control, avoidance, or re-experiencing. Similar estimates were obtained with MR sensitivity analyses. Our findings suggest that specific sub-phenotypes of PTSD, such as hyperarousal, avoidance, PCL total, may have a causal effect on people of European and African ancestry's risk of IS. This shows that the molecular mechanisms behind the relationship between IS and PTSD may be connected to symptoms of hyperarousal and avoidance. To clarify the precise biological mechanisms involved and how they may vary between populations, more research is required

Basic science of osteoarthritis

Osteoarthritis (OA) is a prevalent, disabling disorder of the joints that affects a large population worldwide and for which there is no definitive cure. This review provides critical insights into the basic knowledge on OA that may lead to innovative end efficient new therapeutic regimens. While degradation of the articular cartilage is the hallmark of OA, with altered interactions between chondrocytes and compounds of the extracellular matrix, the subchondral bone has been also described as a key component of the disease, involving specific pathomechanisms controlling its initiation and progression. The identification of such events (and thus of possible targets for therapy) has been made possible by the availability of a number of animal models that aim at reproducing the human pathology, in particular large models of high tibial osteotomy (HTO). From a therapeutic point of view, mesenchymal stem cells (MSCs) represent a promising option for the treatment of OA and may be used concomitantly with functional substitutes integrating scaffolds and drugs/growth factors in tissue engineering setups. Altogether, these advances in the fundamental and experimental knowledge on OA may allow for the generation of improved, adapted therapeutic regimens to treat human OA.(undefined

Evaluation of mid-level management training in immunisation in the African Region

Objective: The Mid-Level Management (MLM) training course provides managers of immunisation programmes with new, advanced skills in planning, management, monitoring and evaluation. An evaluation was conducted of the MLM training courses held between 2000 and 2004 in the African Region, in order to assess its effectiveness and impact, and its contribution to the management of the Extended Programme on Immunisation (EPI) at country level.Methods: Evaluation methods included: a desk review of the MLM course reports, WHO/AFRO MLM modules and reference documents; interviews with MLM course participants, facilitators, supervisors, Ministry of Health officials and country-based partners; focus group discussions; and questionnaires.Results: During 2000-2004, eleven MLM courses were held and 642 participants were trained. Of the 151 course participants interviewed, 85% rated the course as very useful and 15% as useful. Modules on new vaccines, immunisation safety, cold chain and vaccine management, communication and problem solving were most appreciated. According to supervisors, the MLM training has contributed to significant improvements in the performance of the staff after attending the MLM course. Using DTP3 as an indicator, immunisation coverage in the African Region increased from 49% in 1991 to 53% in 2001 and 69% in 2004.Conclusions: The MLM training has increased the performance of the trained staff and therefore contributed to the improvement of EPI coverage in the African Region. However, MLM training remains a predominantly vertical event and should be harmonised with other health training programmes for various levels of the health system

Electroencephalography and psychological assessment datasets to determine the efficacy of a low-cost, wearable neurotechnology intervention for reducing Post-Traumatic Stress Disorder symptom severity

The datasets described here comprise electroencephalography (EEG) data and psychometric data freely available on data.mendeley.com. The EEG data is available in .mat formatted files containing the EEG signal values structured in two-dimensional (2D) matrices, with channel data and trigger information in rows, and samples in columns (having a sampling rate of 250Hz). Twenty-nine female survivors of the 1994 genocide against the Tutsi in Rwanda, underwent a psychological assessment before and after an intervention aimed at reducing Post-Traumatic Stress Disorder (PTSD) symptom severity. Three measures of trauma and four measures of wellbeing were assessed using empirically validated standardised assessments. The pre- and post- intervention psychometric data were analysed using non-parametric statistical methods and the post-intervention data were further evaluated according to diagnostic assessment rules to determine clinically relevant improvements for each group. The participants were assigned to a control group (CG, n = 9), a motor-imagery group (MI, n = 10), and a neurofeedback group (NF, n = 10). Participants in the latter two groups received Brain-Computer Interface (BCI) based training as a treatment intervention over a sixteen-day period, between the pre- and post- clinical interviews. The training involved presenting feedback visually via a videogame, based on real-time analysis of the EEG recorded data during the BCI-based treatment session. Participants were asked to regulate (NF) or intentionally modulate (MI) brain activity to affect/control the game

Leukocyte methylomic imprints of exposure to the genocide against the Tutsi in Rwanda: a pilot epigenome-wide analysis

Aim & methods: We conducted a pilot epigenome-wide association study of women from Tutsi ethnicity exposed to the genocide while pregnant and their resulting offspring, and a comparison group of women who were pregnant at the time of the genocide but living outside of Rwanda.Results: Fifty-nine leukocyte-derived DNA samples survived quality control: 33 mothers (20 exposed, 13 unexposed) and 26 offspring (16 exposed, 10 unexposed). Twenty-four significant differentially methylated regions (DMRs) were identified in mothers and 16 in children. Conclusions: In utero genocide exposure was associated with CpGs in three of the 24 DMRs: BCOR, PRDM8 and VWDE, with higher DNA methylation in exposed versus unexposed offspring. Of note, BCOR and VWDE show significant correlation between brain and blood DNA methylation within individuals, suggesting these peripherally derived signals of genocide exposure may have relevance to the brain. Lay abstract The 1994 Rwandan genocide against ethnic Tutsi has been associated with adverse mental health outcomes in survivors decades later, but the molecular mechanisms that contribute to this association remain poorly characterized. Epigenetic mechanisms such as DNA methylation regulate gene function and change in response to life experiences. We identified differentially methylated regions (DMRs) in genocide-exposed versus unexposed mothers and children. In utero genocide exposure was linked with methylation differences in three maternal DMRs, with higher methylation in exposed offspring. Two of three DMRs show correlation between brain and blood methylation within individuals, suggesting that peripherally derived signals of genocide exposure may be relevant to the brain. en

Community engagement in epigenomic and neurocognitive research on post-traumatic stress disorder in Rwandans exposed to the 1994 genocide against the Tutsi: lessons learned

Epigenomic and neurocognitive studies have provided new perspectives on post-traumatic stress disorder and its intergenerational transmission. This article outlines the lessons learned from community engagement (CE) in such research on Rwandan genocide survivors. A strong trauma-related response was observed within the research project-targeted community (genocide survivors) during explanation of the project. CE also revealed privacy concerns, as community members worried that any leakage of genetic/(epi)genomic data could affect not only themselves but also their close relatives. Adopting a culture of CE in the process of research implementation enables the prioritization of targeted community needs and interests. Furthermore, CE has stimulated the development of mental healthcare interventions, which married couples can apply to protect their offspring and thus truly break the cycle of inherited vulnerability. Studies of how human genes are affected by the environment (epigenomic studies) have provided new perspectives on post-traumatic stress disorder and its intergenerational transmission. This article describes the lessons learned from community engagement (CE) in this type of research in a Rwandan genocide-exposed population. A strong trauma-related response was observed within the community while explaining the project. CE also revealed the participants' privacy concerns related to leakage of genetic/(epi)genomic data that could also affect their close relatives. Adopting a culture of CE in the process of research implementation enables the prioritization of community needs and interests. CE has furthermore stimulated the development of preventive interventions for married couples to protect their offspring and thus truly break the cycle of inherited vulnerability. en