Health and well-being of serving and ex-serving UK Armed Forces personnel: protocol for the fourth phase of a longitudinal cohort study.

INTRODUCTION: This is the fourth phase of a longitudinal cohort study (2022-2023) to investigate the health and well-being of UK serving (Regulars and Reservists) and ex-serving personnel (veterans) who served during the era of the Iraq and Afghanistan conflicts. The cohort was established in 2003 and has collected data over three previous phases including Phase 1 (2004-2006), Phase 2 (2007-2009) and Phase 3 (2014-2016). METHODS AND ANALYSIS: Participants are eligible to take part if they completed the King's Centre for Military Health Research Health and Wellbeing Cohort Study at Phase 3 (2014-2016) and consented to be recontacted (N=7608). Participants will be recruited through email, post and text message to complete an online or paper questionnaire. Data are being collected between January 2022 and September 2023. Health and well-being measures include measures used in previous phases that assess common mental disorders, post-traumatic stress disorder (PTSD) and alcohol misuse. Other areas of interest assess employment, help-seeking and family relationships. New topics include the impact of the British withdrawal from Afghanistan in 2021, complex PTSD (C-PTSD), illicit drug use, gambling and loneliness. Analyses will describe the effect size between groups deployed to Iraq and/or Afghanistan or not deployed, and those who are currently in service versus ex-service personnel, respectively, reporting prevalences with 95% CIs, and ORs with 95% CI. Multivariable logistic and multiple linear regression analyses will be conducted to assess various health and well-being outcomes and associations with risk and protective factors. ETHICS AND DISSEMINATION: Ethical approval has been granted by the Ministry of Defence Research Ethics Committee (Ref: 2061/MODREC/21). Participants are provided with information and agree to a series of consent statements before taking part. Findings will be disseminated to UK Armed Forces stakeholders and international research institutions through stakeholder meetings, project reports and scientific publications.

Nerve growth factor in cancer cell death and survival.

One of the major challenges for cancer therapeutics is the resistance of many tumor cells to induction of cell death due to pro-survival signaling in the cancer cells. Here we review the growing literature which shows that neurotrophins contribute to pro-survival signaling in many different types of cancer. In particular, nerve growth factor, the archetypal neurotrophin, has been shown to play a role in tumorigenesis over the past decade. Nerve growth factor mediates its effects through its two cognate receptors, TrkA, a receptor tyrosine kinase and p75NTR, a member of the death receptor superfamily. Depending on the tumor origin, pro-survival signaling can be mediated by TrkA receptors or by p75NTR. For example, in breast cancer the aberrant expression of nerve growth factor stimulates proliferative signaling through TrkA and pro-survival signaling through p75NTR. This latter signaling through p75NTR promotes increased resistance to the induction of cell death by chemotherapeutic treatments. In contrast, in prostate cells the p75NTR mediates cell death and prevents metastasis. In prostate cancer, expression of this receptor is lost, which contributes to tumor progression by allowing cells to survive, proliferate and metastasize. This review focuses on our current knowledge of neurotrophin signaling in cancer, with a particular emphasis on nerve growth factor regulation of cell death and survival in cancer.

The increased incidence of the RET p.Gly691Ser variant in French-Canadian vesicoureteric reflux patients is not replicated by a larger study in Ireland.

The p.Gly691Ser variant of the RET protein, resulting from the 'A' allele of the SNP rs1799939 in exon 11 of the RET gene, was recently found to be present in a high proportion of primary vesicoureteric reflux (pVUR) patients in Quebec. We have determined the genotype of this SNP in 221 unrelated index cases of pVUR from the Irish population, in 190 full siblings of 160 of the index cases, and in 592 healthy controls. We found no significant difference in genotype or allele frequencies in patients and controls, and no tendency of affected siblings to share the same genotype. We also found no difference in the presence of additional phenotypic features such as duplex kidneys, between patients with and without the 'A' allele, and no difference in grade of reflux. We find no evidence of any influence of RET SNP rs1799939 on pVUR phenotype.