Learning from our mothers: examining the role of intergenerational knowledge transfer in advancing gender equity among Sri Lankan youth

Background In a 2013 survey, over half of Sri Lankan men and women expressed gender-inequitable attitudes that equated masculinity with violence, and femininity with obedience to men. High rates of gender-inequitable attitudes are a community-level risk factor for gender-based violence including rape and intimate partner violence. In Sri Lanka, public health practitioners focused on reducing the health disparities resulting from gender inequity need to better understand the processes by which gender-inequitable attitudes develop and how to prevent them. The goal of this research was to identify potential points of intervention at which appropriate programmes and policies could most effectively cultivate gender-equitable attitudes among young people in Sri Lanka. Methods Over 9 months in 2016 and 2017, we interviewed more than 30 young adults in Sri Lanka to understand how their experiences helped them to develop their own gender identity, as well as to understand and respond to gender norms. Their responses were analysed using a grounded theory approach to explore which factors have most influenced the processes of gender norm learning, acceptance, or rejection throughout Sri Lankan young adults’ lives. Findings Many interviews focused on the impact of elder family members on the interviewee\u27s perception and acceptance of gender norms. Many young adults who did not agree with gender-inequitable norms reported receiving advice from their parents or other elder relatives to disregard norms and pursue their own non-conforming interests. In one example, many non-working mothers insisted on their daughters working and becoming financially independent. Interpretation Young people in Sri Lanka are repeatedly confronted by gender-inequitable attitudes in school, the media, politics, and society at large. However, family members can support youth to develop gender equitable attitudes and behaviours within this gender-inequitable society. Harnessing elders’ positive wishes for their offspring\u27s future may prove essential to advancing gender equity in the next generation of Sri Lankan adults. Even from gender-inequitable roles, parents may still support gender equity, and could be encouraged through public health interventions to support their children in realising their full potential. Elder family members are an untapped public health resource for advancing gender equity and reducing its related health disparities among Sri Lankan youth

n-3 polyunsaturated fatty acid effects on inflammatory mediator activity and intracellular signalling pathways in chondrocyte metabolism

Previous studies have shown that supplementation of n-3 polyunsaturated fatty acids (PUFAs) has a beneficial effect on reducing the expression and activity of degradative enzymes and inflammatory factors known to cause damage and destruction of cartilage in arthritic diseases. The aims of this thesis was to use a well-established in vitro model of cartilage degradation to further these studies and to investigate how n-3 PUFAs effect the expression of inflammatory factors at a proteomic level and to use specific inhibitors to identify possible signalling pathways involved in cartilage metabolism. The results of this thesis research indicate that n-3 PUFAs abrogate IL-1-induced cyclooxygenase-2 (COX-2) mRNA expression, protein levels and activity, measured as PGE2 production, in both normal bovine and human osteoarthritis articular cartilage chondrocytes. These studies were followed by the use of a simple array system to analyse the expression of several marker genes from different signalling pathways after IL-1 exposure, plus or minus n-3 PUFA supplementation. This led us to identify three possible pathways involved in IL-1-induced cartilage catabolism and inflammation. These were analysed further with the use of specific inhibitors to ascertain whether the inhibition profiles were similar to those seen by n-3 PUFAs. Two main pathways, the extracellular signal-regulated kinase (ERK) pathway and NFkappaB pathway were identified. Further analysis using the ERK pathway inhibitor, U0126, showed that it decreased IL-1-induced glycosaminoglycan release from the tissue, endogenous aggrecanase activity, ADAMTS-4 (but not ADAMTS-5) mRNA levels, MMP-3 and MMP-13 mRNA levels, COX-2 message, protein levels and PGE2 production in a manner similar to that seen with n-3 PUFA supplementation. Collectively, these results suggest that n-3 PUFAs may be directing their effects through the ERK pathway

Mutations in multidomain protein MEGF8 identify a Carpenter syndrome subtype associated with defective lateralization

Carpenter syndrome is an autosomal-recessive multiple-congenital-malformation disorder characterized by multisuture craniosynostosis and polysyndactyly of the hands and feet; many other clinical features occur, and the most frequent include obesity, umbilical hernia, cryptorchidism, and congenital heart disease. Mutations of RAB23, encoding a small GTPase that regulates vesicular transport, are present in the majority of cases. Here, we describe a disorder caused by mutations in multiple epidermal-growth-factor-like-domains 8 (MEGF8), which exhibits substantial clinical overlap with Carpenter syndrome but is frequently associated with abnormal left-right patterning. We describe five affected individuals with similar dysmorphic facies, and three of them had either complete situs inversus, dextrocardia, or transposition of the great arteries; similar cardiac abnormalities were previously identified in a mouse mutant for the orthologous Megf8. The mutant alleles comprise one nonsense, three missense, and two splice-site mutations; we demonstrate in zebrafish that, in contrast to the wild-type protein, the proteins containing all three missense alterations provide only weak rescue of an early gastrulation phenotype induced by Megf8 knockdown. We conclude that mutations in MEGF8 cause a Carpenter syndrome subtype frequently associated with defective left-right patterning, probably through perturbation of signaling by hedgehog and nodal family members. We did not observe any subject with biallelic loss-of function mutations, suggesting that some residual MEGF8 function might be necessary for survival and might influence the phenotypes observed

Prevalence and clinical characteristics of non-malignant CT detected incidental findings in the SUMMIT lung cancer screening cohort

BACKGROUND: Pulmonary and extrapulmonary incidental findings are frequently identified on CT scans performed for lung cancer screening. Uncertainty regarding their clinical significance and how and when such findings should be reported back to clinicians and participants persists. We examined the prevalence of non-malignant incidental findings within a lung cancer screening cohort and investigated the morbidity and relevant risk factors associated with incidental findings. We quantified the primary and secondary care referrals generated by our protocol. METHODS: The SUMMIT study (NCT03934866) is a prospective observational cohort study to examine the performance of delivering a low-dose CT (LDCT) screening service to a high-risk population. Spirometry, blood pressure, height/weight and respiratory history were assessed as part of a Lung Health Check. Individuals at high risk of lung cancer were offered an LDCT and returned for two further annual visits. This analysis is a prospective evaluation of the standardised reporting and management protocol for incidental findings developed for the study on the baseline LDCT. RESULTS: In 11 115 participants included in this analysis, the most common incidental findings were coronary artery calcification (64.2%) and emphysema (33.4%). From our protocolised management approach, the number of participants requiring review for clinically relevant findings in primary care was 1 in 20, and the number potentially requiring review in secondary care was 1 in 25. CONCLUSIONS: Incidental findings are common in lung cancer screening and can be associated with reported symptoms and comorbidities. A standardised reporting protocol allows systematic assessment and standardises onward management

Prevalence, risk factors, and treatments for post-COVID breathlessness:a systematic review and meta-analysis

Persistent breathlessness >28 days after acute COVID-19 infection has been identified as a highly debilitating post-COVID symptom. However, the prevalence, risk factors, mechanisms and treatments for post-COVID breathlessness remain poorly understood. We systematically searched PubMed and Embase for relevant studies published from 1 January 2020 to 1 November 2021 (PROSPERO registration number: CRD42021285733) and included 119 eligible papers. Random-effects meta-analysis of 42 872 patients with COVID-19 reported in 102 papers found an overall prevalence of post-COVID breathlessness of 26% (95% CI 23-29) when measuring the presence/absence of the symptom, and 41% (95% CI 34-48) when using Medical Research Council (MRC)/modified MRC dyspnoea scale. The pooled prevalence decreased significantly from 1-6 months to 7-12 months post-infection. Post-COVID breathlessness was more common in those with severe/critical acute infection, those who were hospitalised and females, and was less likely to be reported by patients in Asia than those in Europe or North America. Multiple pathophysiological mechanisms have been proposed (including deconditioning, restrictive/obstructive airflow limitation, systemic inflammation, impaired mental health), but the body of evidence remains inconclusive. Seven cohort studies and one randomised controlled trial suggested rehabilitation exercises may reduce post-COVID breathlessness. There is an urgent need for mechanistic research and development of interventions for the prevention and treatment of post-COVID breathlessness

Understanding the limits to generalizability of experimental evolutionary models.

Post print version of article deposited in accordance with SHERPA RoMEO guidelines. The final definitive version is available online at: http://www.nature.com/nature/journal/v455/n7210/abs/nature07152.htmlGiven the difficulty of testing evolutionary and ecological theory in situ, in vitro model systems are attractive alternatives; however, can we appraise whether an experimental result is particular to the in vitro model, and, if so, characterize the systems likely to behave differently and understand why? Here we examine these issues using the relationship between phenotypic diversity and resource input in the T7-Escherichia coli co-evolving system as a case history. We establish a mathematical model of this interaction, framed as one instance of a super-class of host-parasite co-evolutionary models, and show that it captures experimental results. By tuning this model, we then ask how diversity as a function of resource input could behave for alternative co-evolving partners (for example, E. coli with lambda bacteriophages). In contrast to populations lacking bacteriophages, variation in diversity with differences in resources is always found for co-evolving populations, supporting the geographic mosaic theory of co-evolution. The form of this variation is not, however, universal. Details of infectivity are pivotal: in T7-E. coli with a modified gene-for-gene interaction, diversity is low at high resource input, whereas, for matching-allele interactions, maximal diversity is found at high resource input. A combination of in vitro systems and appropriately configured mathematical models is an effective means to isolate results particular to the in vitro system, to characterize systems likely to behave differently and to understand the biology underpinning those alternatives

An Autoethnographic Study of Interprofessional Education Partnerships

Background: Thiis qualitative longitudinal study describes an Interprofessional Education (IPE) collaboration between a public university with medical and pharmacy schools and a private, non-affiliated university with a nursing school. The study explores the dynamics of the IPE partnership and lessons learned over a three-year period in which members of the collaborative directed three IPE simulations.Methods and Findings: An autoethnographic inquiry technique was used to interview eight collaborators who designed and implemented a large-scale IPE simulation for approximately 300 students and 100 faculty members annually for three years. Two, 90-minute group narrative interviews were conducted and audio recorded for transcription and analysis. Five themes emerged: Natural Collaboration, Shared Vision and Commitment, Integrations and Synergy, All Hands on Deck, and Lasting Foundations. Collaborators agreed the joint effort was a positive experience with multidimensional returns on investment. They applied teamwork competencies to build the partnership, develop the IPE simulation, and overcome implementation challenges.Conclusions: Thiis article provides readers with the opportunity to learn from those who have been intimately involved in the design and implementation of a large-scale IPE collaboration to enhance the shared learning process for health students and faculty. Findings highlight the complexity of building an IPE collaborative and the necessity to build partnerships with facilitators committed to communication

Pavlovian influences on learning differ between rats and mice in a counter-balanced Go/NoGo judgement bias task

Judgement bias tests of animal affect and hence welfare assume that the animal's responses to ambiguous stimuli, which may herald positive or negative outcomes, are under instrumental control and reflect 'optimism' or 'pessimism' about what will happen. However, Pavlovian control favours responses (e.g. approach or withdrawal) according to the valence associated with a stimulus, rather than the anticipated response outcomes. Typically, positive contexts promote action and approach whilst negative contexts promote inhibition or withdrawal. The prevalence of Go-for-reward (Go-pos) and NoGo-to-avoid-punishment (NoGo-neg) judgement bias tasks reflects this Pavlovian influence. A Pavlovian increase or decrease in activity or vigour has also been argued to accompany positive or negative affective states, and this may interfere with instrumental Go or NoGo decisions under ambiguity based on anticipated decision outcomes. One approach to these issues is to develop counter-balanced Go-pos/NoGo-neg and Go-neg/NoGo-pos tasks. Here we implement such tasks in Sprague Dawley rats and C57BL/6J mice using food and air-puff as decision outcomes. We find striking species/strain differences with rats achieving criterion performance on the Go-pos/NoGo-neg task but failing to learn the Go-neg/NoGo-pos task, in line with predictions, whilst mice do exactly the opposite. Pavlovian predispositions may thus differ between species, for example reflecting foraging and predation ecology and/or baseline activity rates. Learning failures are restricted to cues predicting a negative outcome; use of a more powerful air-puff stimulus may thus allow implementation of a fully counter-balanced task. Rats and mice achieve criterion faster than in comparable automated tasks and also show the expected generalisation of responses across ambiguous tones. A fully counter-balanced task thus offers a potentially rapidly implemented and automated method for assessing animal welfare, identifying welfare problems and areas for welfare improvement and 3Rs Refinement, and assessing the effectiveness of refinements