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In recent decades, 'whole school' approaches to improving health have gained traction, based on settings-based health promotion understandings which view a setting, its actors and processes as an integrated 'whole' system with multiple intervention opportunities. Much less is known about 'whole institution' approaches to improving health in tertiary education settings. We conducted a scoping review to describe both empirical and non-empirical (e.g. websites) publications relating to 'whole settings', 'complex systems' and 'participatory'/'action' approaches to improving the health of students and staff within tertiary education settings. English-language publications were identified by searching five academic and four grey literature databases and via the reference lists of studies read for eligibility. We identified 101 publications with marked UK over-representation. Since the 1970s, publications have increased, spanning a gradual shift in focus from 'aspirational' to 'conceptual' to 'evaluative'. Terminology is geographically siloed (e.g., 'healthy university' (UK), 'healthy campus' (USA)). Publications tend to focus on 'health' generally rather than specific health dimensions (e.g. diet). Policies, arguably crucial for cascading systemic change, were not the most frequently implemented intervention elements. We conclude that, despite the field's evolution, key questions (e.g., insights into who needs to do what, with whom, where and when; or efficacy) remain unanswered. [ABSTRACT FROM AUTHOR]

Highlights: [•] This review highlights a therapeutic approach that overcomes KRAS mutations. [•] An analysis that confronts impairing targets with impairing physiological processes. [•] Highlighting alternative routes to apoptosis. [Copyright &y& Elsevier]

Objective: To evaluate and compare the inflammatory response and mediators in the endometrium of patients with hydrosalpinges compared with normal controls. Design: Retrospective case-control study. Setting: Urban medical center. Patient(s) and Intervention(s): Hysterectomy samples were identified as being affected by hydrosalpinx or salpingitis (n = 30) and were age-matched with control samples (n = 30). Interventions: Fallopian tube and endometrial slides were analyzed for leukocytes and immunohistochemical techniques performed for cytokines (interleukin-2 [IL-2]). Main Outcome Measure(s): Evaluate and compare the endometrial inflammatory response (leukocytes and cytokines) from samples affected and non-affected by hydrosalpinx and salpingitis. Result(s): Examination of tubal and endometrial slides with hydrosalpinx demonstrated a statistically significant increase in the number of overall inflammatory cells. High-intensity immunohistochemical staining for IL-2 was demonstrated in 7.4% of controls versus 65% of cases. Conclusion(s): A defined, identifiable, local response to hydrosalpingeal fluid has been demonstrated in the endometrium. This response consists of statistically significant elevations of leukocytes and IL-2. An inflammatory endometrial response may be an independent contributor to the decreased reproductive outcome observed in patients with hydrosalpinges. [Copyright &y& Elsevier]

Cancer therapies based on drugs designed to interfere with specific targets within the molecular circuitry of cancer cells are currently under intense experimentation. Our strategy is based on the use of a naturally occurring immunomolecule which can selectively kill cancer cells, based on its ability to exploit genetic differences between normal and cancer cells. The βGBP cytokine has previously been shown to negatively regulate the cell cycle by blocking cells in late S phase. In tumour cells, but not in normal cells, the S phase block has been shown to be followed by apoptosis. Mechanisms involved in S phase arrest have been pinpointed to downregulation of signalling and altered expression of cell cycle controller proteins, including E2F1, a transcription factor with ability to play a part in apoptosis. Here we discuss the use of βGBP within the context of cancer surveillance and cancer therapeutics focussing on E2F1 as one mechanistic aspect relevant to βGBP’s selective induction of programmed cell death in cancer. [Copyright &y& Elsevier]

Policy PointsIncome is thought to impact a broad range of health outcomes. However, whether income inequality (how unequal the distribution of income is in a population) has an additional impact on health is extensively debated.Studies that use multilevel data, which have recently increased in popularity, are necessary to separate the contextual effects of income inequality on health from the effects of individual income on health.Our systematic review found only small associations between income inequality and poor self‐rated health and all‐cause mortality. The available evidence does not suggest causality, although it remains methodologically flawed and limited, with very few studies using natural experimental approaches or examining income inequality at the national level. Context: Whether income inequality has a direct effect on health or is only associated because of the effect of individual income has long been debated. We aimed to understand the association between income inequality and self‐rated health (SRH) and all‐cause mortality (mortality) and assess if these relationships are likely to be causal. Methods: We searched Medline, ISI Web of Science, Embase, and EconLit (PROSPERO: CRD42021252791) for studies considering income inequality and SRH or mortality using multilevel data and adjusting for individual‐level socioeconomic position. We calculated pooled odds ratios (ORs) for poor SRH and relative risk ratios (RRs) for mortality from random‐effects meta‐analyses. We critically appraised included studies using the Risk of Bias in Nonrandomized Studies – of Interventions tool. We assessed certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework and causality using Bradford Hill (BH) viewpoints. Findings: The primary meta‐analyses included 2,916,576 participants in 38 cross‐sectional studies assessing SRH and 10,727,470 participants in 14 cohort studies of mortality. Per 0.05‐unit increase in the Gini coefficient, a measure of income inequality, the ORs and RRs (95% confidence intervals) for SRH and mortality were 1.06 (1.03‐1.08) and 1.02 (1.00‐1.04), respectively. A total of 63.2% of SRH and 50.0% of mortality studies were at serious risk of bias (RoB), resulting in very low and low certainty ratings, respectively. For SRH and mortality, we did not identify relevant evidence to assess the specificity or, for SRH only, the experiment BH viewpoints; evidence for strength of association and dose–response gradient was inconclusive because of the high RoB; we found evidence in support of temporality and plausibility. Conclusions: Increased income inequality is only marginally associated with SRH and mortality, but the current evidence base is too methodologically limited to support a causal relationship. To address the gaps we identified, future research should focus on income inequality measured at the national level and addressing confounding with natural experiment approaches. [ABSTRACT FROM AUTHOR]

Summary: Optimal sleep, both in terms of duration and quality, is important for adolescent health. However, young people's sleeping habits have worsened over recent years. Access to and use of interactive electronic devices (e.g., smartphones, tablets, portable gaming devices) and social media have become deep‐rooted elements of adolescents' lives and are associated with poor sleep. Additionally, there is evidence of increases in poor mental health and well‐being disorders in adolescents; further linked to poor sleep. This review aimed to summarise the longitudinal and experimental evidence of the impact of device use on adolescents' sleep and subsequent mental health. Nine electronic bibliographical databases were searched for this narrative systematic review in October 2022. Of 5779 identified unique records, 28 studies were selected for inclusion. A total of 26 studies examined the direct link between device use and sleep outcomes, and four reported the indirect link between device use and mental health, with sleep as a mediator. The methodological quality of the studies was generally poor. Results demonstrated that adverse implications of device use (i.e., overuse, problematic use, telepressure, and cyber‐victimisation) impacted sleep quality and duration; however, relationships with other types of device use were unclear. A small but consistent body of evidence showed sleep mediates the relationship between device use and mental health and well‐being in adolescents. Increasing our understanding of the complexities of device use, sleep, and mental health in adolescents are important contributions to the development of future interventions and guidelines to prevent or increase resilience to cyber‐bullying and ensure adequate sleep. [ABSTRACT FROM AUTHOR]

In recent decades, the use of conditionality backed by benefit sanctions for those claiming unemployment and related benefits has become widespread in the social security systems of high-income countries. Critics argue that sanctions may be ineffective in bringing people back to employment or indeed harmful in a range of ways. Existing reviews largely assess the labour market impacts of sanctions but our understanding of the wider impacts is more limited. We report results from a scoping review of the international quantitative research evidence on both labour market and wider impacts of benefit sanctions. Following systematic search and screening, we extract data for 94 studies reporting on 253 outcome measures. We provide a narrative summary, paying attention to the ability of the studies to support causal inference. Despite variation in the evidence base and study designs, we found that labour market studies, covering two thirds of our sample, consistently reported positive impacts for employment but negative impacts for job quality and stability in the longer term, along with increased transitions to non-employment or economic inactivity. Although largely relying on non-experimental designs, wider-outcome studies reported significant associations with increased material hardship and health problems. There was also some evidence that sanctions were associated with increased child maltreatment and poorer child well-being. Lastly, the review highlights the generally poor quality of the evidence base in this area, with few studies employing research methods designed to identify the causal impact of sanctions, especially in relation to wider impacts. [ABSTRACT FROM AUTHOR]

Objective: To assess efficacy and safety of a single-dose vaginal clindamycin gel for bacterial vaginosis treatment.Methods: We conducted a double-blind, placebo-controlled, randomized study comparing clindamycin gel with placebo (2:1 ratio). Entry required clinical diagnosis of bacterial vaginosis, that is, all four Amsel's criteria, without other genital infections. Nugent scores of 7-10 were required for efficacy assessment, per updated 2019 U.S. Food and Drug Administration guidance. Patients were evaluated at screening, day 7-14, and day 21-30 (test of cure). Clinical cure was defined as resolution of three of four Amsel's criteria. Bacteriologic cure was defined as Nugent score lower than 4. Therapeutic cure was both clinical and bacteriologic cure. Primary outcome was clinical cure at the test-of-cure visit. Secondary endpoints were clinical cure at day 7-14, and bacteriologic and therapeutic cures at day 7-14 and test of cure. A sample size of 188 patients in the clindamycin group compared with 94 patients in the placebo group had 90% power to detect statistically significant difference (P=.05, 2-tailed).Results: Participants were seen between July 9, 2020, and November 12, 2020. Of 307 randomized women, 56.0% were Black and 88.3% reported one or more previous bacterial vaginosis episodes. In the modified intention-to-treat population, 70.5% of patients in the clindamycin group and 35.6% in the placebo group achieved clinical cure at test of cure (primary outcome) (difference of 34.9, 95% CI 19.0-50.8), as did 77.5% of patients in the clindamycin group and 42.6% of patients in the placebo group in the per-protocol population (difference of 34.9, 95% CI 17.0-52.7). Statistically significant differences between groups were seen for all secondary endpoints. Clinical cure rate in patients in the clindamycin group with more than three bacterial vaginosis episodes in the prior year was 70.0%. Approximately 15% (15.3%) of patients in the clindamycin group experienced one or more treatment-emergent adverse events related to study treatment, as did 9.7% of patients in the placebo group. The most frequent treatment-related, treatment-emergent adverse event was vulvovaginal candidiasis.Conclusion: A new, single-dose clindamycin vaginal gel was highly effective, with excellent safety, in women disproportionately affected by bacterial vaginosis, with Nugent scores of 7-10 at study entry.Funding Source: The study was funded by Daré Bioscience, Inc.Clinical Trials Registration: ClinicalTrials.gov, NCT04370548. [ABSTRACT FROM AUTHOR]

Abstract: Regulatory T cells (Tregs) and beta-galactoside-binding protein (βGBP), a regulatory protein often found expressed at sites of immunological privilege, have similar functions. Their presence affects the outcome of harmful autoimmunity and cancers, including experimental autoimmune encephalomyelitis and malignant gliomas. Here we report a novel pathway by which Tregs express and utilize βGBP to control CD8+ T cell responses partially activating TCR signaling but blocking PI3K activity. As a result, this leads to a loss of p21ras, ERK and Akt activities despite activation of TCR proximal signals, such as phosphorylation of CD3ζ, Zap70, Lat and PKCθ. Although non-processive TCR signaling often leads to cell anergy, Tregs/βGBP did not affect cell viability. Instead, βGBP/Tregs transiently prevented activation of CD8+ T cells with self-antigens, while keeping their responses to xenogeneic antigens unaffected. [Copyright &y& Elsevier]

Background: Summer learning loss has been the subject of longstanding concern among researchers, the public and policy makers. The aim of the current research was to investigate inequality changes in children's mental health and cognitive ability across the summer holidays.Methods: We conducted linear and logistic regression analysis of mental health (borderline-abnormal total difficulty and prosocial scores on the strengths and difficulties questionnaire (SDQ)) and verbal cognitive ability (reading, verbal reasoning or vocabulary) at ages 7, 11 and 14, comparing UK Millennium Cohort Study members who were interviewed before and after the school summer holidays. Inequalities were assessed by including interaction terms in the outcome models between a discrete binary variable with values representing time periods and maternal academic qualifications. Coefficients of the interaction terms were interpreted as changes from the pre- to post-holiday period in the extent of inequality in the outcome between participants whose mothers had high or low educational qualifications. Separate models were fitted for each age group and outcome. We used inverse probability weights to allow for differences in the characteristics of cohort members assessed before and after the summer holidays.Results: Mental health (borderline/abnormal SDQ total and prosocial scores) at ages 7 and 14 worsened and verbal cognitive ability scores at age 7 were lower among those surveyed after the summer holidays. Mental health inequalities were larger after the holidays at age 7 ([OR = 1.4; 95%CI (0.6, 3.2) and 14: [OR = 1.5; 95%CI (0.7, 3.2)], but changed little at age 11 (OR = 0.9; 95%CI (0.4, 2.6)]. There were differences in pro-social behaviours among those surveyed before/after the school holidays at age 14 [OR = 1.2; 95%CI (0.5, 3.5)] but not at age 7 or 11. There was little change in inequalities in verbal cognitive ability scores over the school holidays [Age 7: b = 1.3; 95%CI (- 3.3, 6.0); Age 11: b = - 0.7; 95%CI (- 4.3, 2.8); Age 14: b = - 0.3; 95%CI (- 1.0, 0.4)].Conclusion: We found inequalities in mental health and cognitive ability according to maternal education, and some evidence or worsening mental health and mental health inequalities across school summer holidays. We found little evidence of widening inequalities in verbal cognitive ability. Widespread school closures during the COVID-19 restrictions have prompted concerns that prolonged closures may widen health and educational inequalities. Management of school closures should focus on preventing or mitigating inequalities that may arise from differences in the support for mental health and learning provided during closures by schools serving more or less disadvantaged children. [ABSTRACT FROM AUTHOR]

Background: Behavioural weight management programmes are effective in assisting people with overweight or obesity to lose excess body weight. Yet, many still struggle to attain their weight loss goals in such programmes. Little is understood about the factors which impact success in these programmes. Synthesising this data will allow for theory to be developed on how to improve success in such programmes. The main aim of this review will be to extract and synthesise the barriers and facilitators of successful weight loss during participation of behavioural weight loss programmes in adults living with overweight and obesity. Methods: A systematic search of MEDLINE, Embase, PsycINFO, The Cochrane Library and CINAHL will be performed from inception onwards. Studies will also be sought by contacting experts in the field, reference and website searching. Studies will be eligible if the participants are adults living with obesity (population) undertaking or recently completed behavioural weight loss programmes (intervention) with the primary focus of weight loss (outcome). The primary outcomes will be amount of weight lost and information on barriers and/or facilitators to success. The secondary outcomes will be reasons or factors related to attrition and adherence and behaviour change techniques used in programmes. Two reviewers will screen citations and full-text data. Reviewer 1 will screen all, and reviewer 2 will screen a random 50% of articles. Data extraction will be completed by reviewer 1, and 10% will be checked by the research team. Potential conflicts will be resolved through discussion. Data will be synthesised and described narratively to show the characteristics of each study, levels of success and barriers and facilitators during programme participation. A thematic approach will be taken, and themes will be coded against the levels of the socioecological model. Quantitative data will be extracted and categorised according to these themes and presented alongside the qualitative data. Discussion: Our findings can be used to inform how weight loss programmes can be improved to facilitate success in those at risk of failure. Results will be published in a peer-reviewed journal. Systematic review registration: (PROSPERO CRD42019148158 ) [ABSTRACT FROM AUTHOR]

Background: Current approaches aimed at inducing immunogenic cell death (ICD) to incite an immune response against cancer neoantigens are based on the use of chemotherapeutics and other agents. Results are hampered by issues of efficacy, combinatorial approaches, dosing and toxicity. Here, we adopted a strategy based on the use of an immunomolecule that overcomes pharmachemical limitations.Methods: Cytofluorometry, electron microscopy, RT-PCR, western blotting, apotome immunofluorescence, MLR and xenografts.Results: We report that an ICD process can be activated without the use of pharmacological compounds. We show that in Kras-mut/TP53-mut colorectal cancer cells the 15 kDa βGBP cytokine, a T cell effector with onco-suppressor properties and a potential role in cancer immunosurveillance, induces key canonical events required for ICD induction. We document ER stress, autophagy that extends from cancer cells to the corresponding xenograft tumours, CRT cell surface shifting, ATP release and evidence of dendritic cell activation, a process required for priming cytotoxic T cells into a specific anticancer immunogenic response.Conclusions: Our findings provide experimental evidence for a rationale to explore a strategy based on the use of an immunomolecule that as a single agent couples oncosuppression with the activation of procedures necessary for the induction of long term response to cancer. [ABSTRACT FROM AUTHOR]

Background: Several systematic reviews have reviewed the evidence relating to nature on aspects of children and adolescent's health and wellbeing; however, none have looked at the associations or effectiveness of attending nature-based early childhood education (ECE). The main objective is to systematically review and synthesise the evidence to determine if nature-based ECE enhances children's health, wellbeing and development. Methods: We will search the following electronic databases (from inception onwards): MEDLINE, Scopus, PsycINFO, ERIC, SportDiscus, Australian Education Index, British Education Index, Child Development and Adolescent studies, and Applied Social Sciences Index and Abstracts. Grey literature will be identified searching dissertations and reports (e.g. Open Grey, Dissertations Theses Database [ProQuest], and Google Scholar). All types of studies (quantitative and qualitative) conducted in children (aged 2–7 years old) attending ECE who had not started education at primary or elementary school will be included. The exposure of interest will be nature-based ECE settings that integrate nature into their philosophy and/or curriculum and environment. The outcomes of interest will be all aspects of the child's physical, cognitive, social and emotional health wellbeing and development. Two reviewers will independently screen full-text articles. The study methodological quality (or bias) will be appraised using appropriate tools. If feasible, a meta-analysis will be conducted using a random-effect model for studies similar in exposure and outcome. Where studies cannot be included in a meta-analysis, findings will be summarised based on the effect directions and a thematic analysis will be conducted for qualitative studies. Discussion: This systematic review will capture the state of the current literature on nature-based ECE for child health, wellbeing and development. The results of this study will be of interest to multiple audiences (including researchers and policy makers). Results will be published in a peer-reviewed journal. Gaps for future research will be identified and discussed. Systematic review registration: PROSPERO CRD42019152582 [ABSTRACT FROM AUTHOR]

Background: Despite a decline in child and adult smoking prevalence, young people who smoke (even occasionally) can rapidly become addicted to nicotine, with most adult smokers initiating smoking before they are 18. Schools have long been a popular setting to deliver youth smoking prevention interventions, but evidence of the effectiveness of school-based prevention programmes is mixed, and outcomes vary by the type of programme delivered. Existing systematic reviews that explore the factors contributing to the success or failure of school-based smoking prevention programmes often exclude qualitative studies, due to a focus on intervention effectiveness which qualitative research cannot answer. Instead, qualitative research is focussed on the experiences and perceptions of those involved in the programmes. This systematic review will address this gap by updating a 2009 review to examine qualitative studies. The aim is to generate deeper insight to help target resources which have the potential to save lives by preventing smoking initiation among children and young people. Methods: This systematic review will be searching the following databases: the Cochrane Library, MEDLINE, EMBASE, PsycINFO, HMIC, ERIC, ASSIA, Web of Science and CINAHL. In order to identify additional references, we will consult the reference lists of a sample of systematic reviews and search relevant organizational websites in order to identify appropriate grey literature. The search strategy will include key words and database-specific subject headings relating to smoking, children and young people, health promotion and school. Authors will independently screen, assess data quality and extract data for synthesis. Study findings will be synthesised thematically using ‘best-fit framework syntheses’. This allows for an existing set of themes to be used as a starting point to map or code included studies. These themes are then adapted as coding takes place to accommodate new emerging themes. Discussion: This review will focus on qualitative studies that seek to examine the barriers and facilitators to the delivery of school-based smoking prevention programmes in order to inform the design of future theory-based interventions in schools to prevent children and young people from smoking. Systematic review registration: PROSPERO CRD42014015483 [ABSTRACT FROM AUTHOR]