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Abstract The Proteus effect is a phenomenon found in over 60 studies where people tend to conform behaviorally to their avatars’ identity characteristics, especially in virtual reality. This study extends research on the Proteus effect to consider organization-representing avatars and misogynistic behavioral outcomes. Male participants (N = 141) in a lab experiment embodied a set of pretested avatars which varied in level of association with a university mascot (i.e., color and body type) in a bespoke virtual reality simulation designed to elicit misogynistic behavior. Namely, participants were directed to place a hand on virtual agents’ body parts, including the buttocks (i.e., a transgressive misogynistic act). Time delay in complying with directions to touch the agents’ buttocks served as an implicit measure of resistance to this misogynistic behavior. Results suggest that within moderately masculine body-size avatar users, those who embodied a university-color-associated avatar exhibited more misogynistic behaviors (i.e., faster buttocks-touching). Unexpectedly, this effect of avatar color was not apparent within the hypermasculine body-size avatars, and within the university-associated color condition, hypermasculine body-type was associated with less misogynistic behavior. These findings suggest that organization-representing avatars may induce behavioral conformity to implicit attitudes associated with the organization, such as misogyny.

Abstract Background Prevalence of youth nicotine vaping has increased, heightening concerns around negative health effects. This study aimed to compare self-reported respiratory symptoms among youth by vaping behaviours. Methods Participants (n = 39,214) aged 16–19 from the 2020 and 2021 International Tobacco Control Policy Evaluation Project (ITC) Youth Tobacco and Vaping Surveys (Canada, England, US). Weighted multivariable logistic regression assessed associations between reporting any of five respiratory symptoms in the past week (shortness of breath, wheezing, chest pain, phlegm, cough) and: past 30-day smoking and/or vaping; lifetime/current vaping. Among past-30-day vapers (n = 4644), we assessed associations between symptoms and vaping frequency, use of nicotine salts, usual flavour and device type(s). Results Overall, 27.8% reported experiencing any of the five respiratory symptoms. Compared with youth who had only vaped, those who had only smoked had similar odds of symptoms [adjusted odds ratio, OR (95% confidence interval, CI): 0.97 (0.85–1.10)], those who both smoked and vaped had higher odds [1.26 (1.12–1.42)], and those who had done neither, lower odds [0.67 (0.61–0.72)]. Compared with those who had never vaped, past use, experimentation and current regular or occasional use were all associated with higher odds. Reporting usually using nicotine salts was associated with higher odds of symptoms [1.43 (1.22–1.68)] than non-salt but was often uncertain. Compared with tobacco flavour (including with menthol), menthol/mint and sweets flavours were associated with similar odds; fruit [1.44 (1.07–1.93)], multiple [1.76 (1.30–2.39)] and ‘other’ [2.14 (1.45–3.16)] flavours with higher odds. All device types were associated with similar odds. Conclusions Among youth, vaping was associated with increased reporting of past-week respiratory symptoms. Among those who vaped, some flavour types and potentially nicotine salts were associated with respiratory symptoms.

Background: The military is a male-dominated environment and culture in which women veterans can experience significant institutional prejudice. Transition can be confusing and isolating for women veterans. Group programs are an important source of transition support. However, we know little about the specific group program needs of women veterans. Objectives: To examine mental health and well-being support group programs delivered to women veterans, to understand what they value and find most helpful. Eligibility Criteria: Women military veterans (all types); empirical studies using any design; published between 1990 and 2022; group programs focused on transition issues (such as housing, employment, education, physical health, mental health). Sources of Evidence: Peer-reviewed journals and theses. Charting Methods: Six databases searched: Medline (via Ovid SP), PsycINFO (via Ovid SP), EmCare (via Ovid SP), CINAHL, Scopus, and ProQuest. Results: There was significant heterogeneity across 35 included studies in type of groups, program content and structure, length of sessions, measurement of impact, follow-up, and so forth. Most programs were delivered face to face. Physical health and preventative healthcare were important topics for women veterans, particularly reproductive health, mental health, and chronic pain. Groups that included physical activity, creative arts, and alternative therapies were beneficial to women’s physical and mental health. Strengths-based women-only groups, facilitated by women, that created safe spaces for women veterans to share their experiences, enhanced self-expression, agency, and self-empowerment. This was particularly important for women who had experience military sexual trauma. Conclusion: This review found a small but diverse range of group programs available for women veterans. Many program evaluations were of moderate or low quality and lacked sufficient information to determine whether benefits were sustained over time. No studies involved Australian women veterans. Despite these concerns, this review highlighted several useful lessons that could help inform improved design, delivery, and evaluation of group programs for women veterans.

Abstract Background The National Health Service in England aims to implement tobacco dependency treatment services in all hospitals by 2024. We aimed to assess the uptake of a new service, adapted from the Ottawa Model of Smoking Cessation, and its impact on 6-month quit rates and readmission or death at 1-year follow-up. Methods We conducted a pragmatic service evaluation of a tobacco dependency service implemented among 2067 patients who smoked who were admitted to 2 acute hospitals in London, England, over a 12-month period from July 2020. The intervention consisted of the systematic identification of smoking status, automatic referral to tobacco dependence specialists, provision of pharmacotherapy and behavioural support throughout the hospital stay, and telephone support for 6 months after discharge. The outcomes were (i) patient acceptance of the intervention during admission, (ii) quit success at 6 months after discharge, (iii) death, or (iv) readmission up to 1 year following discharge. Multivariable logistic regression was used to estimate the impact of a range of clinical and demographic variables on these outcomes. Results The majority (79.4%) of patients accepted support at the first assessment. Six months after discharge, 35.1% of successfully contacted patients reported having quit smoking. After adjustment, odds of accepting support were 51–61% higher among patients of all non-White ethnicity groups, relative to White patients, but patients of Mixed, Asian, or Other ethnicities had decreased odds of quit success (adjusted odds ratio (AOR) = 0.32, 95%CI = 0.15–0.66). Decreased odds of accepting support were associated with a diagnosis of cardiovascular disease or diabetes; however, diabetes was associated with increased odds of quit success (AOR = 1.88, 95%CI = 1.17–3.04). Intention to make a quit attempt was associated with a threefold increase in odds of quit success, and 60% lower odds of death, compared to patients who did not intend to quit. A mental health diagnosis was associated with an 84% increase in the odds of dying within 12 months. Conclusions The overall quit rates were similar to results from Ottawa models implemented elsewhere, although outcomes varied by site. Outcomes also varied according to patient demographics and diagnoses, suggesting personalised and culturally tailored interventions may be needed to optimise quit success.

Background The long-term outcomes of COVID-19 hospitalisation in individuals with pre-existing airway diseases are unknown. Methods Adult participants hospitalised for confirmed or clinically suspected COVID-19 and discharged between 5 March 2020 and 31 March 2021 were recruited to the Post-hospitalisation COVID-19 (PHOSP-COVID) study. Participants attended research visits at 5 months and 1 year post discharge. Clinical characteristics, perceived recovery, burden of symptoms and health-related quality of life (HRQoL) of individuals with pre-existing airway disease (i.e., asthma, COPD or bronchiectasis) were compared to the non-airways group. Results A total of 615 out of 2697 (22.8%) participants had a history of pre-existing airway diseases (72.0% diagnosed with asthma, 22.9% COPD and 5.1% bronchiectasis). At 1 year, the airways group participants were less likely to feel fully recovered (20.4% versus 33.2%, p

Objectives A deeper understanding of the lived experiences of Hispanic patients with non-alcoholic fatty liver disease (NAFLD) can help guide the development of behavioural programmes that facilitate NAFLD management. This paper explores Hispanic women’s experiences living with NAFLD.Design, setting, participants We collected brief sociodemographic questionnaires and conducted in-depth interviews with 12 low-income (all had household income ≤USD$55 000 per year) Hispanic women with NAFLD from the Houston area. Transcripts were audio-recorded and transcribed. We developed a coding scheme and used thematic analysis to identify emergent themes, supported by Atlas.ti.Results Participants identified physicians as their main information source on NAFLD but also consulted the internet, family, friends and peers. Many were still left wanting more information. Participants identified family history, sedentary lifestyles, poor diet and comorbid conditions as causes for their NAFLD. Participants also reported emotional distress after diagnosis. Participants experienced both successes and challenges in making lifestyle changes in nutrition and physical activity. Some participants received desired social support in managing NAFLD, although there were conflicting feelings about spousal support.Conclusion Multifaceted programming that improves patient–provider communication, conveys accurate information and enhances social support is needed to support Hispanic women in managing NAFLD.

Abstract Young people experiencing mental health conditions are vulnerable to poorer educational outcomes for many reasons, including: social exclusion, stigma, and limited in-school support. Using a near-complete New Zealand population administrative database, this prospective cohort study aimed to quantify differences in educational attainment (at ages 15–16 years) and school suspensions (over ages 13–16 years), between those with and without a prior mental health condition. The data included five student cohorts, each starting secondary school from 2013 to 2017 respectively (N = 272,901). Both internalising and externalising mental health conditions were examined. Overall, 6.8% had a mental health condition. Using adjusted modified Poisson regression analyses, those with prior mental health conditions exhibited lower rates of attainment (IRR 0.87, 95% CI 0.86–0.88) and higher rates of school suspensions (IRR 1.63, 95% CI 1.57–1.70) by age 15–16 years. Associations were stronger among those exhibiting behavioural conditions, compared to emotional conditions, in line with previous literature. These findings highlight the importance of support for young people experiencing mental health conditions at this crucial juncture in their educational pathway. While mental health conditions increase the likelihood of poorer educational outcomes, deleterious outcomes were not a necessary sequalae. In this study, most participants with mental health conditions had successful educational outcomes.

Abstract Background Rates of diseases and death from tobacco smoking are substantially higher among those with a mental health condition (MHC). Vaping can help some people quit smoking, but little is known about vaping among people with MHCs or psychological distress. We assessed the prevalence and characteristics (heaviness, product type) of smoking and/or vaping among those with and without a history of single or multiple MHC diagnoses and with no, moderate or serious psychological distress. Methods Data from 27,437 adults in Great Britain surveyed between 2020 and 2022. Multinomial regressions analysed associations between smoking, vaping and dual use prevalence, smoking/vaping characteristics and (a) history of a single or multiple MHC and (b) moderate or serious psychological distress, adjusted for age, gender, and socioeconomic status. Results Compared with people who had never smoked, those who currently smoked were more likely to report a history of a single (12.5% vs 15.0%, AOR=1.62, 95% CI=1.46–1.81, p

Community involvement in research is key to translating science into practice, and new approaches to engaging community members in research design and implementation are needed. The Community Scientist Program, established at the MD Anderson Cancer Center in Houston in 2018 and expanded to two other Texas institutions in 2021, provides researchers with rapid feedback from community members on study feasibility and design, cultural appropriateness, participant recruitment, and research implementation. This paper aims to describe the Community Scientist Program and assess Community Scientists' and researchers' satisfaction with the program. We present the analysis of the data collected from 116 Community Scientists and 64 researchers who attended 100 feedback sessions, across three regions of Texas including Northeast Texas, Houston, and Rio Grande Valley between June 2018 and December 2022. Community Scientists stated that the feedback sessions increased their knowledge and changed their perception of research. All researchers (100%) were satisfied with the feedback and reported that it influenced their current and future research methods. Our evaluation demonstrates that the key features of the Community Scientist Program such as follow-up evaluations, effective bi-directional communication, and fair compensation transform how research is conducted and contribute to reducing health disparities.

Abstract Triple negative breast cancer (TNBC) is a disease of poor prognosis, with the majority classified as the basal-like subtype associated with epithelial-mesenchymal transition and metastasis. Because basal breast cancers originate from proliferative luminal progenitor-like cells upon dysregulation of proper luminal differentiation, genes regulating luminal-basal transition are critical to elucidate novel therapeutic targets to improve TNBC outcomes. Herein we demonstrate that the tumor suppressor DEAR1/TRIM62 is a critical regulator of luminal cell fate. DEAR1 loss in human mammary epithelial cells results in significantly enhanced mammosphere formation that is accelerated in the presence of TGF-β/SMAD3 signaling. Mammospheres formed following DEAR1 loss are enriched for ALDH1A1 and CK5 expression, EpCAM−/CD49f+ and CD44high/24low basal-like epithelial cells, indicating that DEAR1 regulates stem/progenitor cell properties and luminal-basal progenitor transition. We show that DEAR1 maintains luminal differentiation as a novel ubiquitin ligase for SNAI2/SLUG, a master regulator driving stemness and generation of basal-like progenitor populations. We also identify a significant inverse correlation between DEAR1 and SNAI2 expression in a 103 TNBC case cohort and show that low DEAR1 expression significantly correlates with young age of onset and shorter time to metastasis, suggesting DEAR1 could serve as a biomarker to stratify early onset TNBCs for targeted stem cell therapies.

Abstract Background Given the importance of the selection process, many medical schools are reviewing their selection criteria. The traditional pathway for post-graduate medicine has been from science-based undergraduate degrees, however some programs are expanding their criteria. In this study we investigated academic success across all years and themes of the Deakin University medical degree, based on the type of degree undertaken prior to admission. We evaluated whether the traditional pathway of biomedical science into medicine should remain the undergraduate degree of choice, or whether other disciplines should be encouraged. Methods Data from 1159 students entering the degree from 2008 to 2016 was collected including undergraduate degree, grade point average (GPA), Graduate Medical Schools Admission Test (GAMSAT) score and academic outcomes during the 4 years of the degree. Z-scores were calculated for each assessment within each cohort and analysed using a one sample t-test to determine if they differed from the cohort average. Z-scores between groups were analysed by 1-way ANOVA with LSD post-hoc analysis correcting for multiple comparisons. Results The majority of students had Science (34.3%) or Biomedical Science (31.0%) backgrounds. 27.9% of students had a Health-related undergraduate degree with smaller numbers of students from Business (3.5%) and Humanities (3.4%) backgrounds. At entry, GPA and GAMSAT scores varied significantly with Biomedical Science and Science students having significantly higher scores than Health students. Health students consistently outperformed students from other disciplines in all themes while Biomedical Science students underperformed. Conclusions Our data suggest that a Health-related undergraduate degree results in the best performance throughout medical school, whereas a Biomedical Science background is associated with lower performance. These findings challenge the traditional Biomedical Science pathway into medicine and suggest that a health background might be more favourable when determining the selection criteria for graduate entry into medicine.

Objectives Electronic vaping devices are being used to consume nicotine and non-nicotine psychoactive drugs. We aimed to determine the pattern and prevalence of using vaping devices for nicotine and/or non-nicotine drug administration in the United Kingdom and how these differ by drug type and individual sociodemographic characteristics. We explored reasons for vaping onset and continuation.Design An online cross-sectional surveyParticipants A convenience sample of adults (aged ≥18 years) in the UK.Primary and secondary outcome measures The primary outcome was prevalence of current use (within the last 30 days) of a vaping device to administer either nicotine or 18 types of non-nicotine drugs. We additionally evaluated reasons for onset and continuation of vaping. Sociodemographic characteristics were compared between the UK general population using census data and those vaping non-nicotine drugs.Results We recruited 4027 participants of whom 1637 (40.7%) had ever used an electronic vaping device; 1495 (37.1%) had ever vaped nicotine and 593 (14.7%) had ever vaped a non-nicotine drug. Overall, 574 (14.3%) currently vaped nicotine and 74 (1.8%) currently vaped a non-nicotine drug. The most common currently vaped non-nicotine drug was cannabis (n=58, 1.4%). For nicotine, people’s modal reasons to start and continue vaping was to quit smoking tobacco. For almost all other drugs, people’s modal reason to start vaping was curiosity and to continue was enjoyment. Compared with the general population, the population who had ever vaped a non-nicotine drug were significantly younger, had more disabilities and fewer identified as white, female, heterosexual or religious.Conclusions A non-trivial number of people report current use and ever use of an electronic vaping device for non-nicotine drug administration. As vaping technology advances and drug consumption changes, understanding patterns of use and associated behaviours are likely to be increasingly important to both users and healthcare professionals.

In New Zealand, international arrivals are quarantined and undergo severe acute respiratory syndrome coronavirus 2 screening; those who test positive are transferred to a managed isolation facility (MIF). Solo traveler A and person E from a 5-person travel group (BCDEF) tested positive. After transfer to the MIF, person A and group BCDEF occupied rooms >2 meters apart across a corridor. Persons B, C, and D subsequently tested positive; viral sequences matched A and were distinct from E. The MIF was the only shared location of persons A and B, C, and D, and they had no direct contact. Security camera footage revealed 4 brief episodes of simultaneous door opening during person A’s infectious period. This public health investigation demonstrates transmission from A to B, C, and D while in the MIF, with airborne transmission the most plausible explanation. These findings are of global importance for coronavirus disease public health interventions and infection control practices.

IntroductionThe classification and management of pulmonary hypertension (PH) is challenging due to clinical heterogeneity of patients. We sought to identify distinct multimorbid phenogroups of patients with PH that are at particularly high-risk for adverse events.MethodsA hospital-based cohort of patients referred for right heart catheterization between 2005-2016 with PH were included. Key exclusion criteria were shock, cardiac arrest, cardiac transplant, or valvular surgery. K-prototypes was used to cluster patients into phenogroups based on 12 clinical covariates.ResultsAmong 5208 patients with mean age 64±12 years, 39% women, we identified 5 distinct multimorbid PH phenogroups with similar hemodynamic measures yet differing clinical outcomes: (1) "young men with obesity", (2) "women with hypertension", (3) "men with overweight", (4) "men with cardiometabolic and cardiovascular disease", and (5) "men with structural heart disease and atrial fibrillation." Over a median follow-up of 6.3 years, we observed 2182 deaths and 2002 major cardiovascular events (MACE). In age- and sex-adjusted analyses, phenogroups 4 and 5 had higher risk of MACE (HR 1.68, 95% CI 1.41-2.00 and HR 1.52, 95% CI 1.24-1.87, respectively, compared to the lowest risk phenogroup 1). Phenogroup 4 had the highest risk of mortality (HR 1.26, 95% CI 1.04-1.52, relative to phenogroup 1).ConclusionsCluster-based analyses identify patients with PH and specific comorbid cardiometabolic and cardiovascular disease burden that are at highest risk for adverse clinical outcomes. Interestingly, cardiopulmonary hemodynamics were similar across phenogroups, highlighting the importance of multimorbidity on clinical trajectory. Further studies are needed to better understand comorbid heterogeneity among patients with PH.

This study explored how frequent gamblers perceive gambling marketing and the role they feel it has in their gambling behaviour. Ten frequent gamblers participated in semi-structured interviews oriented around their experiences of gambling marketing. An interpretative phenomenological analysis of the data led to three overarching themes: exploiting gambling marketing for personal gain; gambling marketing as a test of self-control; and safer gambling messages marketing perceived as ineffective. These themes encapsulated participants' views of gambling marketing as something they could take advantage of to increase their own gambling success. Marketing was also perceived as a test of self-control among self-identified experienced gamblers, although identified as a risk to those who are considered more vulnerable. Finally, safer gambling messages included within marketing was considered ineffective due to perceived insincerity and being seen as an 'afterthought' by marketers. In support of previous research, the current investigation highlights concerning narratives around self-control and perceived risk, as encapsulated within gambling marketing, and these are evident in the perceptions of frequent gamblers. Given gamblers' perceived lack of effectiveness of current safer gambling messages within marketing, future research should explore new avenues for safer gambling promotion.

While linking records across large administrative datasets ["big data"] has the potential to revolutionize empirical social science research, many administrative data files do not have common identifiers and are thus not designed to be linked to others. To address this problem, researchers have developed probabilistic record linkage algorithms which use statistical patterns in identifying characteristics to perform linking tasks. Naturally, the accuracy of a candidate linking algorithm can be substantially improved when an algorithm has access to "ground-truth" examples-matches which can be validated using institutional knowledge or auxiliary data. Unfortunately, the cost of obtaining these examples is typically high, often requiring a researcher to manually review pairs of records in order to make an informed judgement about whether they are a match. When a pool of ground-truth information is unavailable, researchers can use "active learning" algorithms for linking, which ask the user to provide ground-truth information for select candidate pairs. In this paper, we investigate the value of providing ground-truth examples via active learning for linking performance. We confirm popular intuition that data linking can be dramatically improved with the availability of ground truth examples. But critically, in many real-world applications, only a relatively small number of tactically-selected ground-truth examples are needed to obtain most of the achievable gains. With a modest investment in ground truth, researchers can approximate the performance of a supervised learning algorithm that has access to a large database of ground truth examples using a readily available off-the-shelf tool.

Background: Inadequate hand-off communication from hospital to skilled nursing facility (SNF) hinders SNF nurses’ ability to prepare for specific patient needs, including prescriptions for critical medications, such as controlled medications and intravenous (IV) antibiotics, resulting in delayed medication administration. This project aims to improve hand-off communication from hospital to SNF by utilizing a standardized hand-off tool. This project was conducted in an inpatient, 50-bed, post-hospital skilled nursing care unit of a local SNF. The participants included all 32 staff nurses employed by the SNF. Methods: Lewin’s change management theory (CMT) guided this quality improvement (QI) project. Baseline assessment included a one-month chart review of 76 patient charts that was conducted to assess the disparities related to ineffective hand-off and medication delays in the SNF before intervention. The wait time for the availability of prescriptions for controlled medications and IV antibiotics, and delays in medication administration were assessed. Intervention: Multiple randomly selected hospital-to-SNF hand-offs were observed. Semistructured interviews with all staff nurses were conducted using open-ended questions about hand-off structure and process matters. Data gathered from observation and interviews were used to create the standardized hand-off tool used in this project. In-service training on hand-off tool utilization for SNF nurses was conducted. Champions for each shift were cultivated to assist with project implementation. Results: After six weeks of implementation, a chart review of 101 patient charts was conducted to evaluate the effects of the hand-off tool on the wait time on the availability of prescriptions for controlled medications and IV antibiotics, and medication administration. The wait time of prescriptions availability during the hospital-to-SNF transition was decreased by 79% for controlled medications, with an associated 52.9% reduction in late administration, and decreased by 94% for IV antibiotics, with a 77.8% reduction in late administration. Conclusion: The use of standardized hand-off resulted in improved communication during the hospital-to-SNF hand-off and significantly decreased the wait time for the availability of prescriptions for controlled medications and IV antibiotics. Integrating standardized hand-off into the SNF policies can help sustain improved communication, medication management, and patient transition from hospital to SNF.

BackgroundSmoking among sexual and gender minority (SGM) groups, which include lesbian, gay, bisexual, transgender, and queer individuals, has been reported to be highly prevalent. This is attributed to several factors, including minority-specific stress and targeted tobacco marketing. Therefore, this population is at an increased risk for tobacco-related diseases. SMS text messaging programs have been found to be effective for smoking cessation and appeal to traditionally hard-to-reach populations over other interventions. It has also been suggested that targeted and tailored interventions could be more effective among SGM smokers because they can be designed to assure a safe, validating health care environment that enhances receptivity to cessation. ObjectiveThe aim of this study is to develop SmokefreeSGM, a text-based smoking cessation program tailored to and tested among SGM smokers. MethodsThe study consists of three phases, culminating in a feasibility trial. In Phase 1, our research team will collaborate with a Community Advisory Board to develop and pretest the design of SmokefreeSGM. In Phase 2, the tailored text messaging program will be beta tested among 16 SGM smokers. Our research team will use a mixed-methods approach to collect and analyze data from participants who will inform the refinement of SmokefreeSGM. In Phase 3, a feasibility trial will be conducted among 80 SGM smokers either enrolled in SmokefreeSGM or SmokefreeTXT, the original text-based program developed by the National Cancer Institute for the general population. Our research team will examine recruitment, retention, and smoking abstinence rates at 1-, 3-, and 6-month follow-up. Additionally, a qualitative interview will be conducted among 32 participants to evaluate the feasibility and acceptability of the programs (SmokefreeSGM and SmokefreeTXT). ResultsThis study received approval from The University of Texas Health Science Center at Houston Committee for the Protection of Human Subjects to begin research on August 21, 2020. Recruitment for the beta testing of SmokefreeSGM (Phase 2) began in January 2022. We estimate that the feasibility trial (Phase 3) will begin in September 2022 and that results will be available in December 2023. ConclusionsFindings from this research effort will help reduce tobacco-related health disparities among SGM smokers by determining the feasibility and acceptability of SmokefreeSGM, an SGM-tailored smoking cessation intervention. Trial RegistrationClinicalTrials.gov NCT05029362; https://clinicaltrials.gov/ct2/show/NCT05029362 International Registered Report Identifier (IRRID)DERR1-10.2196/42553

Abstract CRISPR–Cas proteins are RNA-guided nucleases used to introduce double-stranded breaks (DSBs) at targeted genomic loci. DSBs are repaired by endogenous cellular pathways such as non-homologous end joining (NHEJ) and homology-directed repair (HDR). Providing an exogenous DNA template during repair allows for the intentional, precise incorporation of a desired mutation via the HDR pathway. However, rates of repair by HDR are often slow compared to the more rapid but less accurate NHEJ-mediated repair. Here, we describe comprehensive design considerations and optimized methods for highly efficient HDR using single-stranded oligodeoxynucleotide (ssODN) donor templates for several CRISPR–Cas systems including S.p. Cas9, S.p. Cas9 D10A nickase, and A.s. Cas12a delivered as ribonucleoprotein (RNP) complexes. Features relating to guide RNA selection, donor strand preference, and incorporation of blocking mutations in the donor template to prevent re-cleavage were investigated and were implemented in a novel online tool for HDR donor template design. These findings allow for high frequencies of precise repair utilizing HDR in multiple mammalian cell lines. Tool availability: https://www.idtdna.com/HDR

Since the first wave of coronavirus disease in March 2020, citizens and permanent residents returning to New Zealand have been required to undergo managed isolation and quarantine (MIQ) for 14 days and mandatory testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As of October 20, 2020, of 62,698 arrivals, testing of persons in MIQ had identified 215 cases of SARS-CoV-2 infection. Among 86 passengers on a flight from Dubai, United Arab Emirates, that arrived in New Zealand on September 29, test results were positive for 7 persons in MIQ. These passengers originated from 5 different countries before a layover in Dubai; 5 had negative predeparture SARS-CoV-2 test results. To assess possible points of infection, we analyzed information about their journeys, disease progression, and virus genomic data. All 7 SARS-CoV-2 genomes were genetically identical, except for a single mutation in 1 sample. Despite predeparture testing, multiple instances of in-flight SARS-CoV-2 transmission are likely.

Abstract Time-of-day effects have been noted in a wide variety of cognitive behavioral tests, and perturbation of the circadian system, either at the level of the master clock in the SCN or downstream, impairs hippocampus-dependent learning and memory. A number of kinases, including the serine-threonine casein kinase 1 (CK1) isoforms CK1δ/ε, regulate the timing of the circadian period through post-translational modification of clock proteins. Modulation of these circadian kinases presents a novel treatment direction for cognitive deficits through circadian modulation. Here, we tested the potential for PF-670462, a small molecule inhibitor of CK1δ/ε, to improve cognitive performance in C57BL/6J mice in an array of behavioral tests. Compared to vehicle-treated mice tested at the same time of the circadian day, mice treated with PF-670462 displayed better recall of contextual fear conditioning, made fewer working memory errors in the radial arm water maze, and trained more efficiently in the Morris Water Maze. These benefits were accompanied by increased expression of activity-regulated cytoskeleton-associated protein (Arc) in the amygdala in response to an acute learning paradigm. Our results suggest the potential utility of CK1δ/ε inhibition in improving time-of-day cognitive performance.

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterised by inflammation of the synovial lining of joints, causing pain, swelling, and stiffness with potential for joint deformity. RA affects about 2.3% of New Zealanders and 2.8% of Māori. Despite pharmacological treatment, people with RA report unmet needs, experiencing unacceptable levels of pain, physical disability, fatigue, and suboptimal mental health. The autoimmune protocol or paleo diet (AIP), popularised in social media, is reportedly used by many with autoimmune disease to manage their symptoms. No clinical trials have tested its efficacy in RA. We report a two-phase design, 12 week intervention; a 4-week control, where participants with RA consumed their usual diet, followed by 8-weeks AIP diet. Participants needed to be on stable medication and supplements for >8 weeks, and an unrestricted diet for inclusion. Participants completed weekly validated questionnaires; RAID (RA Impact of Disease), and RAPID3 (Routine Assessment of Patient Index Data 3). Biometric measures and 3-day diet dairies were taken at baseline and weeks 4, 8 and 12. Post study, a 1-hour interview was conducted with each participant to explore their experience of using the AIP diet. Nine people (7 female, 2 male) completed the study. The mean RAPID3 showed a reduction from baseline to the end of week 12 from 2.53 (Range 0.67–5.33) to 0.99 (Range 0–2.5). Four participants reached a clinically meaningful reduction in RAPID3 of >1.2 and endpoint

Abstract Globally consistent measurements of airborne metal concentrations in fine particulate matter (PM2.5) are important for understanding potential health impacts, prioritizing air pollution mitigation strategies, and enabling global chemical transport model development. PM2.5 filter samples (N ~ 800 from 19 locations) collected from a globally distributed surface particulate matter sampling network (SPARTAN) between January 2013 and April 2019 were analyzed for particulate mass and trace metals content. Metal concentrations exhibited pronounced spatial variation, primarily driven by anthropogenic activities. PM2.5 levels of lead, arsenic, chromium, and zinc were significantly enriched at some locations by factors of 100–3000 compared to crustal concentrations. Levels of metals in PM2.5 and PM10 exceeded health guidelines at multiple sites. For example, Dhaka and Kanpur sites exceeded the US National Ambient Air 3-month Quality Standard for lead (150 ng m−3). Kanpur, Hanoi, Beijing and Dhaka sites had annual mean arsenic concentrations that approached or exceeded the World Health Organization’s risk level for arsenic (6.6 ng m−3). The high concentrations of several potentially harmful metals in densely populated cites worldwide motivates expanded measurements and analyses.

Background: Smokeless tobacco (ST) use is common among youth in South Asia where 85% of the world’s 300 million ST users live and use the most lethal ST forms. Little is known about the impact of tobacco control policies on the youth ST uptake in those countries. We planned to conduct longitudinal surveys among school going adolescents to evaluate existing tobacco control policies on tobacco uptake and use, and a feasibility study for that prospective, observational cohort study. Study objectives: (1) To demonstrate the feasibility of selection, recruitment and retention of schools and of study participants; (2) To assess the feasibility and acceptability of the study procedure and study tool (questionnaire); (3) To evaluate if the questionnaire can assess tobacco uptake and use, and their potential predictors. Methods and analysis: The feasibility study will be conducted in two administrative areas within each of three South Asian countries: Bangladesh, India and Pakistan. We will use both quantitative and qualitative data collection methods. Eight eligible schools will be randomly selected within purposively selected sub-districts from each country. We plan to conduct one baseline and one follow up survey among students of grade 6-8, one year apart. At each time point, data on tobacco uptake and potential predictors will be collected from students via self-administered questionnaires that were designed for the longitudinal study. The qualitative component will be embedded into the study with each round of data collection to assess the acceptability of the study instrument (questionnaire) and data collection methods, via focus group discussions with students and semi-structured interviews with schoolteachers. Recruitment and retention rates, completeness of the questionnaires, frequencies and associations of tobacco use and explanatory variables will be reported. Data gathered from the focus group and interviews will be analysed using the framework approach.

Background/Aims: Therapies aimed at modulating cytokines have been used to treat inflammatory illnesses, such as inflammatory bowel disease. On the other hand, patients may become intolerant, refractory, or present with several side effects. Arthrospira (Spirulina) platensis (SPI) is a blue-green microalga with bioactive molecules that have been evaluated to treat inflammatory diseases. On the other hand, few studies have examined their effects on the production of specific cytokines and the intestinal architecture in dextran sulfate sodium (DSS)-induced colitis. Therefore, this study examined the effects of a treatment using SPI in a murine model of intestinal inflammation. Methods: All mice (C57BL/6 male) were evaluated daily for their food and water intake, bodyweight variations, and clinical signs of disease. Colon inflammation was induced by exposure to DSS for 6 consecutive days. SPI was given orally at 50, 100, and 250 mg/kg/day. ELISA was performed to assess the production of cytokines. Myeloperoxidase and nitric oxide were also investigated. The level of microscopic damage was assessed by staining colon sections with hematoxylin and eosin. Results: SPI attenuated the DSS-induced inflammation, with improvements in the clinical signs and a decrease in the production of inflammatory cytokines, such as tumor necrosis factor-α and interferon-γ. In addition, particularly at 250 mg/kg, SPI attenuated the severity of colitis by modulating the level of mucosal and submucosal cell infiltration, which preserved the epithelial barrier. Conclusions: SPI may be an alternative source of bioactive molecules with immunomodulatory properties, and has great potential to be used in the treatment of inflammatory diseases.

Abstract Background To reduce inequalities between individuals with and without mental health problems, a better understanding is required of triggers and success of quit attempts among the third of smokers with mental health problems. The aim was to assess whether there are differences by mental health status in (i) triggers for quit attempts, (ii) use of evidence-based support (iii) and quit success. Methods Monthly cross-sectional household surveys of representative samples of the adult population in England. In 2016/2017, 40,831 adults were surveyed; 1956 who had attempted to stop smoking cigarettes in the past year were included. Logistic regressions assessed associations between mental health (ever diagnosis, past-year treatment, past-month distress), triggers, support used and quit success, adjusting for sociodemographic and smoking characteristics. Results Concern about future health, current health problems and expense of smoking were the most common triggers overall. For respondents with an ever diagnosis, past-year treatment or serious past-month distress, quit attempts were more frequently triggered by current health problems. Non-evidence-based support and e-cigarettes were used most often, and this did not differ by mental health status. Respondents with an ever diagnosis and moderate or serious distress were less likely to have used non-prescription nicotine replacement therapy (NRT). Respondents with past-year treatment or serious distress were more likely to have used prescription medication/behavioural support. Quit success did not differ by mental health status. Compared with non-evidence-based support, non-prescription NRT conferred no benefit. There was some evidence that prescription medication/behavioural support was beneficial (depending on outcome and adjustment, ORs ranged from 1.46, 95% CI 0.92–2.31, to 1.69, 1.01–2.86). E-cigarettes were associated with higher success rates after adjustment for different indicators of mental health (ORs ranged from 2.21, 1.64–2.98, to 2.25, 1.59–3.18). Conclusions Smokers with mental health problems were more likely to have attempted to quit because of health problems and were more likely to have used gold standard support (medication and behavioural support) than other smokers. E-cigarettes were strongly associated with increased success and were used similarly by those with and without mental health problems, indicating that improved uptake of e-cigarettes for smoking cessation among smokers with mental health problems could help address inequalities.

The coronavirus disease 2019 (COVID-19) pandemic requires urgent implementation of effective community-engaged strategies to enhance education, awareness, and inclusion of underserved communities in prevention, mitigation, and treatment efforts. The Texas Community-Engagement Alliance Consortium was established with support from the United States’ National Institutes of Health (NIH) to conduct community-engaged projects in selected geographic locations with a high proportion of medically underserved minority groups with a disproportionate burden of COVID-19 disease and hospitalizations. The purpose of this paper is to describe the development of the Consortium. The Consortium organized seven projects with focused activities to address COVID-19 clinical and vaccine trials in highly affected counties, as well as critical statewide efforts. Five Texas counties (Bexar, Dallas, Harris, Hidalgo, and Tarrant) were chosen by NIH because of high concentrations of underserved minority communities, existing community infrastructure, ongoing efforts against COVID-19, and disproportionate burden of COVID-19. Policies and practices can contribute to disparities in COVID-19 risk, morbidity, and mortality. Community engagement is an essential element for effective public health strategies in medically underserved minority areas. Working with partners, the Consortium will use community engagement strategies to address COVID-19 disparities.

Background Postnatal mental health problems affect 10–15% of women and can adversely impact on mother-infant interactions and bonding, the mother’s mood, and feelings of competence. There is evidence that attending performing arts activities, such as singing, dancing, and listening to music, may improve maternal mental health with potential for an effect on postnatal depression. Methods A systematic review will be conducted to assess the effect of mother-infant group music classes on postnatal depression compared to standard care, no control or wait list control. Studies will be included that report on postnatal depression. Further outcomes of interest include anxiety, stress, parenting competence, confidence and self-efficacy, perceived social support and mother-infant bonding. Infant and child outcomes measuring cognitive development, behaviour and social and emotional development will be included. Search databases to be used will be Medline, EMBASE, CINAHL, PsycINFO, Scopus, CENTRAL, Web of Science, Maternity and Infant Care and discipline-specific journals for music. The Cochrane’s Template for Intervention description and replication (TIDieR) checklist and guide will be utilised to aid a detailed description, standardised assessment and quality assurance. Risk of bias will be assessed by the authors using the Cochrane Handbook for Systematic Reviews of Interventions risk of bias tool. If sufficient studies are available, meta-analyses will be conducted to combine, compare and summarise the results of the studies for more precise estimates of effects. Where meta-analysis is not possible, results for each individual study will be reported through qualitative narrative data synthesis. Discussion This systematic review will identify and synthesise evidence of the measured effect of postnatal mother-infant interventions involving music on maternal psychological and psychosocial outcomes and infant/child outcomes. Systematic review registration This protocol was registered with Prospero on 18 October 2021 (registration number CRD42021283691). https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021283691.

ObjectiveThe Stress Management and Resilience Training (SMART) program is an evidence-based intervention designed to build resilience in physicians in clinical practice. The objective of the current study was to assess the impact of the SMART program on academic physicians' levels of resilience, subjective happiness, stress, and anxiety, and specifically during the implementation of a new hospital-wide Health Information System (HIS).MethodsA total of 40 physicians in a tertiary care academic hospital were randomized (allocation ratio 1:1) to either the SMART intervention or the control condition. The SMART intervention consisted of one mandatory two-hour in-person workshop and an optional 24-week online program, designed to support the materials delivered in the workshop. Outcome measures were assessed using validated scales administered online at baseline and at 3-months and 6-months follow-up.ResultsAfter adjusting for baseline levels of each outcome, no statistically significant intervention effect was observed for resilience, subjective happiness, stress or anxiety at 3-months or 6-months follow-up. However, physicians in the intervention group demonstrated improvements in resilience, stress and anxiety at follow-up that were within the range of clinically relevant differences.ConclusionsThe findings of this exploratory study provide modest support that the SMART intervention may be beneficial for proactively addressing physician wellness during the implementation of a new HIS and that larger randomized trials are warranted.Trial registrationNCT04384861.

Vaccine hesitancy remains an issue in the United States. This study conducted an online survey [N = 3,013] using the Social Science Research Solution [SSRS] Opinion Panel web panelists, representative of U.S. adults age 18 and older who use the internet, with an oversample of rural-dwelling and minority populations between April 8 and April 22, 2021- as vaccine eligibility opened to the country. We examined the relationship between COVID-19 exposure and socio-demographics with vaccine intentions [eager-to-take, wait-and-see, undecided, refuse] among the unvaccinated using multinomial logistic regressions [ref: fully/partially vaccinated]. Results showed vaccine intentions varied by demographic characteristics and COVID-19 experience during the period that eligibility for the vaccine was extended to all adults. At the time of the survey approximately 40% of respondents were unvaccinated; 41% knew someone who had died of COVID-19, and 38% had experienced financial hardship as a result of the pandemic. The vaccinated were more likely to be highly educated, older adults, consistent with the United States initial eligibility criteria. Political affiliation and financial hardship experienced during the pandemic were the two most salient factors associated with being undecided or unwilling to take the vaccine.

Continental margins host methane seeps, animal falls and wood falls, with chemosynthetic communities that may share or exchange species. The goal of this study was to examine the existence and nature of linkages among chemosynthesis-based ecosystems by deploying organic fall mimics (bone and wood) alongside defaunated carbonate rocks within high and lesser levels of seepage activity for 7.4 years. We compared community composition, density, and trophic structure of invertebrates on these hard substrates at active methane seepage and transition (less seepage) sites at Mound 12 at ~1,000 m depth, a methane seep off the Pacific coast of Costa Rica. At transition sites, the community composition on wood and bone was characteristic of natural wood- and whale-fall community composition, which rely on decay of the organic substrates. However, at active sites, seepage activity modified the relationship between fauna and substrate, seepage activity had a stronger effect in defining and homogenizing these communities and they depend less on organic decay. In contrast to community structure, macrofaunal trophic niche overlap between substrates, based on standard ellipse areas, was greater at transition sites than at active sites, except between rock and wood. Our observations suggest that whale- and wood-fall substrates can function as stepping stones for seep fauna even at later successional stages, providing hard substrate for attachment and chemosynthetic food.

Introduction There is a need to improve breastfeeding support interventions as although many are evidence-based, a sequential increase in breastfeeding rates is not evident. It is crucial to understand why the implementation of evidence-based guidelines in practice does not always translate to positive experiences for women and improve breastfeeding rates. This systematic review aims to synthesise breastfeeding support experiences of trained support providers and their impact on breastfeeding support practices. Methods A strategy was developed to search seven databases including Medline and CINAHL and grey literature for qualitative studies. Studies eligible for inclusion reported professional and trained peer experiences of supporting women to breastfeed. PRISMA guidelines were followed and included studies were quality appraised using the CASP Qualitative Checklist. A thematic synthesis of included studies was undertaken and confidence in the review findings was assessed using the CERQual tool. The study protocol, registered in the International Prospective Register of Systematic Reviews PROSPERO registration number: CRD42020207380, has been peer reviewed and published. Findings A total of 977 records were screened, which identified 18 studies (21 papers) eligible for inclusion comprising 368 participants. Following quality appraisal, all studies were deemed suitable for inclusion. The thematic synthesis resulted in four analytical themes: 1) A personal philosophy of breastfeeding support 2) Teamwork and tensions in practice 3) Negotiating organisational constraints and 4) Encounters with breastfeeding women. Findings demonstrated that a range of experiences influence practice, and practice evolves on continued exposure to such experiences. The potential of each experience to facilitate or inhibit breastfeeding support provision is fluid and context specific. Conclusions Experiences, as named above, are modifiable factors contributing to the development of a philosophy of breastfeeding support based on what the provider believes works and is valuable in practice. Further research is required into the range of factors which underpin context-specific breastfeeding support practice, to improve both women’s experiences and intervention effectiveness.

Waiting lists in mental health services are currently considered too long. Lengthy waits of up to 18 weeks are commonly reported in the UK. Waiting lists have long been associated with a variety of negative psychological responses, however there is little understanding behind young adults’ personal experiences of such delays within mental health services. The current study aimed to explore young adults’ experiences of waiting lists in mental healthcare in the UK. Seven young adults were interviewed in the current study (aged 19–22). Interpretive phenomenological analysis was utilised to explore participant accounts. Three super-ordinate themes were generated: Reliance on Alternative Methods of Support; Inability to Function Sufficiently; and Emergence of Negative Beliefs, Emotions and Thoughts. Participants primarily reported a variety of negative psychological and behavioural consequences associated with waiting lists in mental health services, as well as exacerbated existing physical and psychological health issues. In accordance with the limited number of previous studies, waiting lists are considered by patients to be barriers to mental health support and intervention. Future direction is advised.

RationaleIt has been speculated that shared mechanisms underlie respiratory and cardiovascular diseases (CVD) including systemic inflammation or mutual risk factors. In this context, we sought to examine the associations of CVD-related plasma proteins with lung function as measured by spirometry in a large community-based cohort of adults.MethodsThe study included 5777 Framingham Heart Study participants who had spirometry and measurement of 71 CVD-related plasma proteins. The association of plasma proteins with lung function was assessed cross-sectionally and longitudinally using models accounting for familial correlations. Linear mixed models were used for the following measurements: FEV1%predicted, FVC%predicted, and FEV1/FVC ratio with secondary analyses examining obstructive and restrictive physiology at baseline and their new onset during follow up.Measurements and main resultsAmong the 71 CVD-related plasma proteins, 13 proteins were associated in cross-sectional analyses with FEV1%predicted, 17 proteins were associated with FVC%predicted, and 1 protein was associated with FEV1/FVC. The proteins with the greatest inverse relations to FEV1%predicted and FVC%predicted included leptin, adrenomedullin, and plasminogen activator inhibitor-1; in contrast there were three proteins with positive relations to FEV1%predicted and FVC%predicted including insulin growth factor binding protein 2, tetranectin, and soluble receptor for advanced glycation end products. In longitudinal analyses, three proteins were associated with longitudinal change in FEV1 (ΔFEV1) and four with ΔFVC; no proteins were associated with ΔFEV1/FVC.ConclusionOur findings highlight CVD-related plasma proteins that are associated with lung function including markers of inflammation, adiposity, and fibrosis, representing proteins that may contribute both to respiratory and CVD risk.

African Americans have highest incidence and mortality from obesity-related cancers. Physical activity (PA), minimal alcohol use, and maintaining a low body mass index (BMI) are important cancer prevention behaviors, though there is little research on how these behaviors are associated with one another in African Americans. The purpose of this study is to assess the relationship between PA, alcohol use, and BMI using secondary data from an African American cohort recruited from Houston-area churches. Self-administered questionnaires measured self-reported PA, alcohol use, height, weight, and sociodemographic factors. Univariate and multivariable analyses assessed the relation between PA, alcohol use, BMI, controlling for covariates. Participants (N = 1009) were mostly female (77%), employed (72%), and college graduates (55%). Most (53%) reported both light-to-moderate alcohol use & moderate-to-high levels of PA. There was a statistically significant positive linear association between PA and alcohol use (Pearson’s r = 0.15, p 2 drinks/day men, >1 drink/day women), as compared to an abstainer (Adjusted OR = 1.03, 95%CI 1.01–1.06). There was a statistically significant inverse association between PA and BMI, but no statistically significant association between alcohol use and BMI. In this sample of African Americans, PA and alcohol use were positively associated, mirroring results among Non-Hispanic Whites. However, alcohol use and BMI were not statistically significantly associated. Cancer and obesity prevention for African Americans should stress PA promotion while emphasizing messaging to curtail any associated increases in alcohol use.

Background: We conducted a longitudinal study to estimate immunity produced in response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among university students over seven months. Methods: All participants were attending a public university and resided in Pitt County, North Carolina. University students enrolled weekly for 10 weeks between 26 August 2020 and 28 October 2020, resulting in 136 young adults completing at least one study visit by 17 November 2020. Enrolled students completed an online survey and nasal swab collection at two-week intervals and monthly blood collection between 26 August 2020 and 31 March 2021. Results: Amongst 695 serum samples tested during follow-up, the prevalence of a positive result for anti-nucleocapsid antibodies (N-IgG) was 9.78%. In 22 students with more than one positive N-IgG serum sample, 68.1% of the group lost persistence of N-IgG below the positive threshold over 140 days. Anti-spike IgG antibodies were significantly higher among 11 vaccinated compared to 10 unvaccinated. Conclusions: In healthy young adults, N-IgG wanes below the detectable threshold within five months. S-IgG titer remained consistently elevated months after infection, and significantly increased after vaccination.

Abstract Background The current World Health Organization classification recognises 12 major subtypes of renal cell carcinoma (RCC). Although these subtypes differ on molecular and clinical levels, they are generally managed as the same disease, simply because they occur in the same organ. Specifically, there is a paucity of tools to risk-stratify patients with papillary RCC (PRCC). The purpose of this study was to develop and evaluate a tool to risk-stratify patients with clinically non-metastatic PRCC following curative surgery. Methods We studied clinicopathological variables and outcomes of 556 patients, who underwent full resection of sporadic, unilateral, non-metastatic (T1–4, N0–1, M0) PRCC at five institutions. Based on multivariable Fine-Gray competing risks regression models, we developed a prognostic scoring system to predict disease recurrence. This was further evaluated in the 150 PRCC patients recruited to the ASSURE trial. We compared the discrimination, calibration and decision-curve clinical net benefit against the Tumour, Node, Metastasis (TNM) stage group, University of California Integrated Staging System (UISS) and the 2018 Leibovich prognostic groups. Results We developed the VENUSS score from significant variables on multivariable analysis, which were the presence of VEnous tumour thrombus, NUclear grade, Size, T and N Stage. We created three risk groups based on the VENUSS score, with a 5-year cumulative incidence of recurrence equalling 2.9% in low-risk, 15.4% in intermediate-risk and 54.5% in high-risk patients. 91.7% of low-risk patients had oligometastatic recurrent disease, compared to 16.7% of intermediate-risk and 40.0% of high-risk patients. Discrimination, calibration and clinical net benefit from VENUSS appeared to be superior to UISS, TNM and Leibovich prognostic groups. Conclusions We developed and tested a prognostic model for patients with clinically non-metastatic PRCC, which is based on routine pathological variables. This model may be superior to standard models and could be used for tailoring postoperative surveillance and defining inclusion for prospective adjuvant clinical trials.

The main causes of non-communicable diseases (NCDs), health inequalities and health inequity include consumption of unhealthy commodities such as tobacco, alcohol and/or foods high in fat, salt and/or sugar. These exposures are preventable, but the commodities involved are highly profitable. The economic interests of ‘Unhealthy Commodity Producers’ (UCPs) often conflict with health goals but their role in determining health has received insufficient attention. In order to address this gap, a new research consortium has been established. This open letter introduces the SPECTRUM (Shaping Public hEalth poliCies To Reduce ineqUalities and harM) Consortium: a multi-disciplinary group comprising researchers from 10 United Kingdom (UK) universities and overseas, and partner organisations including three national public health agencies in Great Britain (GB), five multi-agency alliances and two companies providing data and analytic support. Through eight integrated work packages, the Consortium seeks to provide an understanding of the nature of the complex systems underlying the consumption of unhealthy commodities, the role of UCPs in shaping these systems and influencing health and policy, the role of systems-level interventions, and the effectiveness of existing and emerging policies. Co-production is central to the Consortium’s approach to advance research and achieve meaningful impact and we will involve the public in the design and delivery of our research. We will also establish and sustain mutually beneficial relationships with policy makers, alongside our partners, to increase the visibility, credibility and impact of our evidence. The Consortium’s ultimate aim is to achieve meaningful health benefits for the UK population by reducing harm and inequalities from the consumption of unhealthy commodities over the next five years and beyond.

Given that romantic partners play a pivotal role in patients’ survivorship period, integrating partners into survivorship care and broadening the focus of behavioral interventions from the individual (survivor) to the survivor-partner dyad may make healthy lifestyle behaviors more easily adopted and potentially maintained. Understanding the role of dyadic processes in Black survivors is particularly important because their lifestyle behaviors are poor and they have higher cancer-specific and all-cause mortality. To develop an effective dyadic lifestyle behavior intervention for Black survivors, micro-level investigations of interactions between Black survivors and their partners are necessary to pinpoint how survivors and partners facilitate or hinder each other’s lifestyle behaviors in their natural, everyday lives. Accordingly, the objective of the present study is to fill these gaps using ecological momentary assessment to eventually develop more effective lifestyle interventions for Black prostate cancer (PCa) survivors and partners. A total of 120 dyads (i.e., 240 individuals) who are Black adult survivors diagnosed with non-metastatic PCa and their romantic partners will be asked to complete four assessments per day for 14 consecutive days on a smartphone after an initial retrospective survey. Over the 14 days, participants will be asked to complete a brief survey regarding their lifestyle behaviors (physical activity, sedentariness and eating behaviors), contexts of lifestyle behaviors, stress, and coping. Physical activity and sedentary behavior will be assessed via accelerometer; eating behaviors will be assessed with the Automated Self-Administered 24-hour Dietary Assessment Tool. After completing the 14-day assessment, participants will be asked to complete a final retrospective survey. Results of the proposed study will inform the rigorous development of a theory-based dyadic lifestyle intervention in this vulnerable survivorship population with the ultimate goal to improve overall survival and reduce morbidities (for survivors) and reduce cancer incidence (for partners).

Aging is universal, yet characterizing the molecular changes that occur in aging which lead to an increased risk for neurological disease remains a challenging problem. Aging affects the prefrontal cortex (PFC), which governs executive function, learning, and memory. Previous sequencing studies have demonstrated that aging alters gene expression in the PFC, however the extent to which these changes are conserved across species and are meaningful in neurodegeneration is unknown. Identifying conserved, age-related genetic and morphological changes in the brain allows application of the wealth of tools available to study underlying mechanisms in model organisms such as Drosophila melanogaster. RNA sequencing data from human PFC and fly heads were analyzed to determine conserved transcriptome signatures of age. Our analysis revealed that expression of 50 conserved genes can accurately determine age in Drosophila (R2 = 0.85) and humans (R2 = 0.46). These transcriptome signatures were also able to classify Drosophila into three age groups with a mean accuracy of 88% and classify human samples with a mean accuracy of 69%. Overall, this work identifies 50 highly conserved aging-associated genetic changes in the brain that can be further studied in model organisms and demonstrates a novel approach to uncovering genetic changes conserved across species from multi-study public databases.

BackgroundMen are at higher risk for serious complications related to COVID-19 infection than women. More robust immune activation in women has been proposed to contribute to decreased disease severity, although systemic inflammation has been associated with worse outcomes in COVID-19 infection. Whether systemic inflammation contributes to sex differences in COVID-19 infection is not known.Study design and methodsWe examined sex differences in inflammatory markers among 453 men (mean age 61) and 328 women (mean age 62) hospitalized with COVID-19 infection at the Massachusetts General Hospital from March 8 to April 27, 2020. Multivariable linear regression models were used to examine the association of sex with initial and peak inflammatory markers. Exploratory analyses examined the association of sex and inflammatory markers with 28-day clinical outcomes using multivariable logistic regression.ResultsInitial and peak CRP were higher in men compared with women after adjustment for baseline differences (initial CRP: ß 0.29, SE 0.07, p = 0.0001; peak CRP: ß 0.31, SE 0.07, pConclusionsIn a sample of 781 men and women hospitalized with COVID-19 infection, men exhibited more robust inflammatory activation as evidenced by higher initial and peak inflammatory markers, as well as worse clinical outcomes. Better understanding of sex differences in immune responses to COVID-19 infection may shed light on the pathophysiology of COVID-19 infection.

[This corrects the article DOI: 10.1371/journal.pone.0152259.].

IntroductionCOVID-19 is primarily a respiratory illness, and smoking adversely impacts the respiratory and immune systems; this confluence may therefore incentivize smokers to quit. The present study, conducted in four high-income countries during the first global wave of COVID-19, examined the association between COVID-19 and: (1) thoughts about quitting smoking; (2) changes in smoking (quit attempt, reduced or increased smoking, or no change); and (3) factors related to a positive change (making a quit attempt or reducing smoking) based on an adapted framework of the Health Belief Model.MethodsThis cross-sectional study included 6870 adult smokers participating in the Wave 3 (2020) ITC Four Country Smoking and Vaping Survey conducted in Australia, Canada, England, and United States (US). These four countries had varying responses to the pandemic by governments and public health, ranging from advising voluntary social distancing to implementing national and subnational staged lockdowns. Considering these varying responses, and the differences in the number of confirmed cases and deaths (greatest in England and the US and lowest in Australia), smoking behaviours related to COVID-19 may have differed between countries. Other factors that may be related to changes in smoking because of COVID-19 were also explored (e.g., sociodemographics, nicotine dependence, perceptions about personal and general risks of smoking on COVID-19). Regression analyses were conducted on weighted data.ResultsOverall, 46.7% of smokers reported thinking about quitting because of COVID-19, which differed by country (pConclusionsThough nearly half of smokers reported thinking about quitting because of COVID-19, the vast majority did not change their smoking behaviour. Smokers were more likely to try and quit or reduce their smoking if they had greater concern about susceptibility and severity of COVID-19 related to smoking. Smokers in Australia were least likely to reduce or try to quit smoking, which could be related to the significantly lower impact of COVID-19 during the early phase of the pandemic relative to the other countries.

BackgroundMany women stop breastfeeding before they intend to as they cannot overcome breastfeeding difficulties. Breastfeeding support, as an evidence-based intervention by trained lay or professional breastfeeding support providers, can prevent early unintended cessation. Yet some women report dissatisfaction with support and reluctantly stop breastfeeding despite receiving this intervention. Understanding the experiences which shape how support is provided can inform effective implementation of breastfeeding support interventions. This review aims to synthesise experiences of trained breastfeeding support providers in high income settings and how these may influence their breastfeeding support practices.MethodsA qualitative systematic review of trained breastfeeding supporters' experiences of supporting women to breastfeed, as part of a generic healthcare role or focused breastfeeding support role, will be conducted. A systematic search will be performed of the databases: Cumulative Index to Nursing and Allied Health Literature (CINAHL +), MEDLINE ALL, Maternity and Infant Care, EMBASE, APA PsycINFO, Web of Science and Scopus. Title and abstract screening using eligibility criteria will be conducted using Covidence software. Eligible papers will be agreed by the review team following full text screening and reported using PRISMA guidelines. CASP and COREQ tools will assess study methodological quality and quality of reporting. Data will be extracted using a bespoke form and coded, using Excel software for data management. Analysis will involve the three stages of thematic synthesis: initial free coding, development of descriptive and subsequent analytical themes. Confidence in findings will be assessed using the CERQual framework.DiscussionThis review is the first to date to synthesise qualitative evidence on experiences which influence how trained lay and professional providers support women with breastfeeding. Findings will enable deeper understanding of the underpinning mechanisms of breastfeeding support provision and inform the development of tailored interventions to improve breastfeeding rates.Systematic review registrationPROSPERO registration number: CRD42020207380.

The dimensions of patient-centred care include not only clinical effectiveness and patient safety, but, importantly, the preferences of patients as consumers of healthcare services. A total of 249 participants were included in the study, with a balanced population proportional representation by age, gender, ethnicity and geographic region of New Zealand. An online questionnaire was used to identify participants' decision-making process, and what factors and barriers for participants to seek dental treatment. Cross-tabulations, Spearman correlation analysis and Pearson Chi-Square analysis were used for the statistical analyses. Three most common reasons for visit were check-up (77%), clean (57%) and relief of pain 36%). A desire to treat a perceived problem was the most common encouraging factor to seek dental care. Cost was the most common barrier to seeking dental services. The majority of participants attended a private practice (84%), with convenience of location and referral from professionals the most likely to influence their choice. Participants felt the most important trait a dental practitioner could demonstrate was to discuss treatment options with them before any treatment. Dental check-up, teeth cleaning and relief of pain were the most common reasons for patients to choose dental services. Cost and ethnicity of the consumers had a significant impact on how dental services were perceived and sought. Dental practitioners may need to reorientate how they express value of oral health practice, not just in regard to communication with patients, but also with government funding agencies.

In Prion Diseases, misfolding of neuronal prion protein (PrPC) to a pathogenic isomer (PrPSC) is associated with neuronal death. Previous pathological studies have demonstrated increased immunoreactivity of PrPC at Aβ plaques in Alzheimer's Disease, and it has been suggested that this either reflects a role for PrPC in the neuronal response to stress or is a feature of the neuropathogenesis of atypical subtypes of Alzheimer's disease. In this paper we utilised western blotting to examine the molecular characteristics of PrP in frozen Hippocampal tissue from 7 cases of Alzheimer's Disease in which prion protein expression was demonstrated by immunohistochemistry, before using Restriction Fragment Length Polymorphism (RFLP) methodology to define the genotype of the codon 129 polymorphism of PRNP in each case. We observed PrP accumulating as globular structures at A plaques, and within ependymal cells lining the lateral ventricle. Immunohistochemistry also showed that PrPC and Superoxide dismutase-1 where deposited in a similar pattern at Aβ plaques. Western blotting revealed that PrP in Alzheimer's disease is composed of the same 208-residue peptide expressed in non-diseased brain. Quantitative western blot analysis demonstrated increased levels of PrPC in a short duration case of Alzheimer's Disease, while, in the remaining cases, levels of PrPC decreased in parallel with increasing disease duration and decreasing brain mass. RFLP genotyping revealed that all codon 129 genotypes (M/M, M/V, V/V) were represented in our study cohort. Our data suggest that increased levels of PrPC may account for PrP immunoreactivity at plaques in Alzheimer's disease, and that PrP deposition is not restricted to certain atypical subtypes of Alzheimer's disease.

Although a number of lifestyle interventions have been developed for cancer survivors, the extent to which they are effective for African American men with cancer is unclear. Given that African American men have the highest prostate cancer burden and the lack of proven interventions, this study developed a culturally-tailored lifestyle intervention for African American men with prostate cancer and their partners that aimed to improve healthy lifestyle behaviors (physical activity and healthy eating) and quality of life. The aim of the present study is to provide a detailed overview of the model-based process of intervention adaptation. Based on the IM Adapt approach (Highfield et al., 2015) and Typology of Adaptation (Davidson et al., 2013), the present study adapted existing, evidence-based interventions to address African American prostate cancer survivors’ and their partners’ potential unmet needs including anxiety/uncertainty about cancer progression, communication between partners, cultural sensitivity, and concordance/discordance of motivation and behaviors between partners. The intervention adaptation was a comprehensive and fluid process. To the best knowledge of the author, this is the first couple-based lifestyle intervention specifically developed for African American men with prostate cancer. The present study will be highly informative to future investigators by providing flexible and detailed information regarding lifestyle intervention adaptation for racial/ethnic minority men with prostate cancer and their partners.

Introduction There are no disease-modifying treatments for Parkinson’s disease (PD). We undertook the first drug screen in PD patient tissue and idntified ursodeoxycholic acid (UDCA) as a promising mitochondrial rescue agent. The aims of this trial are to determine safety and tolerability of UDCA in PD at 30 mg/kg, confirm the target engagement of UDCA, apply a novel motion sensor-based approach to quantify disease progression objectively, and estimate the mean effect size and its variance on the change in motor severity.Methods and analysis This is a phase II, two-centre, double-blind, randomised, placebo-controlled trial of UDCA at a dose of 30 mg/kg in 30 participants with early PD. Treatment duration is 48 weeks, followed by an 8-week washout phase. Randomisation is 2:1, drug to placebo. Assessments are performed at baseline, week 12, 24, 36, 48 and 56. The primary outcome is safety and tolerability. Secondary outcomes will compare the change between baseline and week 48 using the following three approaches: the Movement Disorders Society Unified Parkinson’s Disease Rating Scale Part 3 in the practically defined ‘OFF’ medication state; confirmation of target engagement, applying 31Phosphorus MR Spectroscopy to assess the levels of ATP and relevant metabolites in the brain; and objective quantification of motor impairment, using a validated, motion sensor-based approach. The primary outcome will be reported using descriptive statistics and comparisons between treatment groups. For each secondary outcome, the change from baseline will be summarised within treatment groups using summary statistics and appropriate statistical tests assessing for significant differences. All outcomes will use an intention-to-treat analysis population.Ethics and dissemination This trial has been approved by the East of England – Cambridgeshire and Hertfordshire Research Ethics committee. Results will be disseminated in peer-reviewed journals, presentations at scientific meetings and to patients in a lay-summary format.Trial registration number NCT03840005.

Obesity remains a public health issue, especially for Blacks (or African Americans). Obesity is thought to reflect a complex interaction of socioenvironmental, biological, and cognitive factors. Yet, insufficient attention has been given to psychosocial factors like social cohesion within the African American community. Using multivariable linear regression, we examined the association between social cohesion, measured by the Social Cohesion and Trust scale, and body mass index (BMI) with cross-sectional data (n = 1467) from a cohort study (2008–2009). Greater social cohesion was associated with lower BMI (b = -0.88; 95% CI: −1.45, −0.32) in an unadjusted model. The association was strengthened after further adjusting for relevant covariates (i.e., individual-level sociodemographic factors, health behaviors, and depressive symptoms) (b = -1.26; 95% CI: −1.94, −0.58). Future research should examine potential mechanisms underlying the association between social cohesion and BMI with longitudinal data. In the meantime, obesity prevention and intervention measures should consider promoting social ties and bonds to lower BMI in African American communities.