CRISPR disruption and UK Biobank analysis of a highly conserved polymorphic enhancer suggests a role in male anxiety and alcohol intake.

Excessive alcohol intake is associated with 5.9% of global deaths. However, this figure is especially acute in men such that 7.6% of deaths can be attributed to alcohol intake. Previous studies identified a significant interaction between genotypes of the galanin (GAL) gene with anxiety and alcohol abuse in different male populations but were unable to define a mechanism. To address these issues the current study analysed the human UK Biobank cohort and identified a significant interaction (n = 115,865; p = 0.0007) between allelic variation (GG or CA genotypes) in the highly conserved human GAL5.1 enhancer, alcohol intake (AUDIT questionnaire scores) and anxiety in men. Critically, disruption of GAL5.1 in mice using CRISPR genome editing significantly reduced GAL expression in the amygdala and hypothalamus whilst producing a corresponding reduction in ethanol intake in KO mice. Intriguingly, we also found the evidence of reduced anxiety-like behaviour in male GAL5.1KO animals mirroring that seen in humans from our UK Biobank studies. Using bioinformatic analysis and co-transfection studies we further identified the EGR1 transcription factor, that is co-expressed with GAL in amygdala and hypothalamus, as being important in the protein kinase C (PKC) supported activity of the GG genotype of GAL5.1 but less so in the CA genotype. Our unique study uses a novel combination of human association analysis, CRISPR genome editing in mice, animal behavioural analysis and cell culture studies to identify a highly conserved regulatory mechanism linking anxiety and alcohol intake that might contribute to increased susceptibility to anxiety and alcohol abuse in men

A new challenge for midwives and medical doctors in time of the threat of a mass terrorist attack and a life threatening mass disaster

Purpose:To present the results of research and evaluation study of the legal regulations and rules directly linked and connected to midwives' scope of practice and provide a response on how the professional population of midwives can act as adequate and independent medical providers in the threat of a mass terrorist attack and/or a life-threatening mass disaster event. Materials and methods: The data derives from the Supreme Chamber of Nurses and Midwives in Poland; National Council of Nurses and Midwives in Poland; Gazette of the Republic of Poland, Journal of Laws; curriculum outlines for professional midwifery higher education in Poland; scientific literature, scientific recommendations. The qualitative research method to the data sources in 2018 were used. Results: In the event of a mass terrorist attack and/or a life-threatening mass disaster, the possibility of a pregnant, birthing or postpartum woman and her newborn obtaining proper medical attention from a midwife is questionable. Conclusions:The threat of terrorism in the European Union has grown. A new implications are necessary for policy and practice to keep midwives in their profession to provide adequate quality and quantity of health care in event of a mass terrorist attack and/or a life-threatening mass disaster. In our study we found: a terrorist threat as a gap in the teaching of obstetrics and midwifery; restricted availability of pharmacological agents for use by non-military midwives in event of a terrorist attack and/or a life-threatening mass disaster; lack of authorizations under a midwife license to perform PCD and /or PMCD