Adverse Childhood Experiences among Adults in North Carolina, USA: Influences on Risk Factors for Poor Health across the Lifespan and Intergenerational Implications.

Adverse childhood experiences (ACEs) are a critical determinant and predictor of health across the lifespan. The Appalachian region of the United States, particularly the central and southern portions, experiences worse health outcomes when compared to the rest of the nation. The current research sought to understand the cross-sectional relationships between ACEs, social determinants of health and other health risk factors in one southcentral Appalachian state. Researchers used the 2012 and 2014 North Carolina Behavioral Risk Factor Surveillance System (BRFSS) for analyses. An indicator variable of Appalachian county (n = 29) was used to make comparisons against non-Appalachian counties (n = 71). Analyses further examined the prevalence of ACEs in households with and without children across Appalachian and non-Appalachian regions, and the effects of experiencing four or more ACEs on health risk factors. There were no statistically significant differences between Appalachian and non-Appalachian counties in the prevalence of ACEs. However, compared with adults in households without children, those with children reported a higher percentage of ACEs. Reporting four or more ACEs was associated with higher prevalence of smoking (prevalence ratio [PR] = 1.56), heavy alcohol consumption (PR = 1.69), overweight/obesity (PR = 1.07), frequent mental distress (PR = 2.45), and food insecurity (PR = 1.58) in adjusted models and with fair or poor health only outside Appalachia (PR = 1.65). Residence in an Appalachian county was independently associated with higher prevalence of food insecurity (PR = 1.13). Developing programs and implementing policies aimed at reducing the impact of ACEs could improve social determinants of health, thereby helping to reduce health disparities.

Pharmacotherapeutics of capecitabine and trastuzumab in the treatment of metastatic breast cancer.

Metastatic HER2-positive breast cancer is an incurable disease with a poor prognosis. This article presents a critical appraisal of two treatments commonly used in the treatment of metastatic HER2-positive breast cancer: the oral chemotherapy drug, capecitabine, and the monoclonal antibody, trastuzumab. What follows is a critical discussion of the pharmacotherapeutics of capecitabine and trastuzumab, which considers their use both as single agents and as a combination regimen in the treatment of metastatic breast cancer. The implications of side effects of these drugs are discussed, both individually and in combination, as are the challenges these bring to the prescriber. The article evaluates the use of these agents and concludes that the combination of capecitabine and trastuzumab is an attractive treatment option for patients and for the prescriber.

Adult Food Security and the Relationship with Adverse Childhood Experiences Among Residents of Appalachian North Carolina.

Introduction: The Appalachian region has worse health outcomes than the remainder of the United States. These disparities are often linked to the underlying social and environmental determinants of health. Adverse childhood experiences (ACEs) are associated with poor health outcomes across the lifespan and have a significant impact on future social determinants as an adult, including food security status. Purpose: To explore the relationships between ACEs and food security among adults in the Appalachian counties of North Carolina and make comparisons with the rest of the state. Methods: Researchers used North Carolina's 2012 Behavioral Risk Factor Surveillance System data; namely, the ACEs optional module which includes 11 items related to experiences respondents had before the age of 18 and a single item from the Social Context optional module to classify food security status. The sample was divided into three age categories (18-44, 45-64, and 65 and older) for statistical comparisons as well as by the indicator for Appalachian county. Using Stata 15, weighted logistic regression was utilized for examining relationships between variables. Results: ACEs were a statistically significant predictor of food insecurity across all respondents; each additional ACE was associated with a 13-21% increase in the odds of food insecurity, depending on age group. However, living in an Appalachian county was only a predictor for those age 45-64. Implications: These findings highlight the long-term effects of childhood experiences on food security generally, and in Appalachia particularly for middle-aged adults. Reducing ACEs could reduce food insecurity and improve health in the region.

Fork pausing allows centromere DNA loop formation and kinetochore assembly.

De novo kinetochore assembly, but not template-directed assembly, is dependent on COMA, the kinetochore complex engaged in cohesin recruitment. The slowing of replication fork progression by treatment with phleomycin (PHL), hydroxyurea, or deletion of the replication fork protection protein Csm3 can activate de novo kinetochore assembly in COMA mutants. Centromere DNA looping at the site of de novo kinetochore assembly can be detected shortly after exposure to PHL. Using simulations to explore the thermodynamics of DNA loops, we propose that loop formation is disfavored during bidirectional replication fork migration. One function of replication fork stalling upon encounters with DNA damage or other blockades may be to allow time for thermal fluctuations of the DNA chain to explore numerous configurations. Biasing thermodynamics provides a mechanism to facilitate macromolecular assembly, DNA repair, and other nucleic acid transactions at the replication fork. These loop configurations are essential for sister centromere separation and kinetochore assembly in the absence of the COMA complex.

Enrichment of dynamic chromosomal crosslinks drive phase separation of the nucleolus.

Regions of highly repetitive DNA, such as those found in the nucleolus, show a self-organization that is marked by spatial segregation and frequent self-interaction. The mechanisms that underlie the sequestration of these sub-domains are largely unknown. Using a stochastic, bead-spring representation of chromatin in budding yeast, we find enrichment of protein-mediated, dynamic chromosomal cross-links recapitulates the segregation, morphology and self-interaction of the nucleolus. Rates and enrichment of dynamic crosslinking have profound consequences on domain morphology. Our model demonstrates the nucleolus is phase separated from other chromatin in the nucleus and predicts that multiple rDNA loci will form a single nucleolus independent of their location within the genome. Fluorescent labeling of budding yeast nucleoli with CDC14-GFP revealed that a split rDNA locus indeed forms a single nucleolus. We propose that nuclear sub-domains, such as the nucleolus, result from phase separations within the nucleus, which are driven by the enrichment of protein-mediated, dynamic chromosomal crosslinks.

Being hostile towards mentorship is a mistake.

Reflect for a moment on how you got to where you are today in terms of your professional development. No matter where you have ended up, you didn't do it alone. All the people you worked with influenced how you practise, and you owe them a debt.

Assessment matters-mentors need support in their role.

BACKGROUND: In the UK the Nursing and Midwifery Council (NMC) standards to support learning and assessment in practice state that mentors are responsible and accountable for the assessment of pre-registration nursing students in practice. This study was undertaken to explore mentors' experience of assessing nursing students in practice post implementation of the NMC standards. METHOD: Five focus groups were conducted with mentors (N=35) who had assessed adult pre-registration nursing students in the previous 12 months. The focus groups were recorded, transcribed and analysed to generate categories. RESULTS: Five categories were identified from the data: Changing roles and responsibilities; Exploring the past to understand the present; Just knowing; The odds; Time to mentor. The findings highlighted that mentors were aware of their role and responsibility for the assessment of students in practice. However, many felt this was a new responsibility and role in which they lacked experience. Some existing mentors felt that they may not have had the necessary preparation to effectively assess students in practice and identified their need for support. CONCLUSION: Given that mentors are expected to be competent assessors of students in practice and protect the public through gate-keeping professional registration, this study suggests that serious consideration should be given to how mentors are prepared and the ongoing support and education they receive in assessment.