A global phylogenomic analysis of the shiitake genus Lentinula.

Lentinula is a broadly distributed group of fungi that contains the cultivated shiitake mushroom, L. edodes. We sequenced 24 genomes representing eight described species and several unnamed lineages of Lentinula from 15 countries on four continents. Lentinula comprises four major clades that arose in the Oligocene, three in the Americas and one in Asia-Australasia. To expand sampling of shiitake mushrooms, we assembled 60 genomes of L. edodes from China that were previously published as raw Illumina reads and added them to our dataset. Lentinula edodes sensu lato (s. lat.) contains three lineages that may warrant recognition as species, one including a single isolate from Nepal that is the sister group to the rest of L. edodes s. lat., a second with 20 cultivars and 12 wild isolates from China, Japan, Korea, and the Russian Far East, and a third with 28 wild isolates from China, Thailand, and Vietnam. Two additional lineages in China have arisen by hybridization among the second and third groups. Genes encoding cysteine sulfoxide lyase (lecsl) and γ-glutamyl transpeptidase (leggt), which are implicated in biosynthesis of the organosulfur flavor compound lenthionine, have diversified in Lentinula. Paralogs of both genes that are unique to Lentinula (lecsl 3 and leggt 5b) are coordinately up-regulated in fruiting bodies of L. edodes. The pangenome of L. edodes s. lat. contains 20,308 groups of orthologous genes, but only 6,438 orthogroups (32%) are shared among all strains, whereas 3,444 orthogroups (17%) are found only in wild populations, which should be targeted for conservation.

Is parental unemployment associated with increased risk of adverse childhood experiences? A systematic review and meta-analysis.

BACKGROUND: Unemployment has adverse consequences for families and can put children at risk of harm. This study presents a systematic review and meta-analysis of global evidence on associations between parental unemployment and adverse childhood experiences (ACEs). METHODS: Systematic literature searches across four databases identified cross-sectional, cohort or case-control studies measuring associations between parental employment and individual or cumulative ACEs in children. Available risk estimates were extracted and pooled odds ratios calculated using random-effects models. RESULTS: Of 60 included studies, 37 provided risk estimates suitable for pooling across seven ACE types. Paternal/any parental unemployment was associated with a 29% increased risk of sexual abuse, 54% increased risk of neglect, 60% increased risk of physical abuse and around 90% increased risk of child maltreatment and parental mental illness. No associations were found between maternal unemployment and ACEs. Pooling estimates from representative general population studies also identified increased risk of child maltreatment with paternal/any parental unemployment (82%) but not maternal unemployment. CONCLUSIONS: Children who grow up with parental unemployment can be at increased risk of ACEs. A combination of socioeconomic measures to increase employment opportunities and parental support targeting fathers and mothers may help break multigenerational cycles of abuse and deprivation.

Measuring changes in adult health and well-being during the COVID-19 pandemic and their relationship with adverse childhood experiences and current social assets: a cross-sectional survey.

BACKGROUND: Adverse childhood experiences (ACEs) can impact mental and physical health, leaving people with less resilience to health challenges across the life-course. This study examines whether individuals' levels and changes in levels of mental health, physical health and sleep quality reported across the first year of the COVID-19 pandemic are associated with ACEs and moderated by social assets such as having trusted family and friends. METHODS: A cross-sectional household telephone survey in England (a North West local authority) and Wales (nationally) using landline and mobile numbers stratified by health areas, deprivation quintile and age group and supplemented by an online survey. Data were collected from 4,673 English and Welsh residents aged ≥ 18 years during national COVID-19 restrictions (December 2020 to March 2021). Measures included nine types of ACE; self-reported mental health, physical health and sleep quality at time of survey (in pandemic) and one-year earlier (pre-pandemic); numbers of trusted family members and friends, knowledge of community help; and COVID-19 infection. RESULTS: ACEs were strongly related to moving into poorer mental health, physical health, and sleep categories during the pandemic, with likelihoods more than doubling in those with ≥ 4 ACEs (vs. 0). ACEs were also associated with increased likelihood of moving out of poorer health and sleep categories although this was for a much smaller proportion of individuals. Individuals with more trusted family members were less likely to move into poorer health categories regardless of ACE counts. CONCLUSIONS: ACEs are experienced by large proportions of populations and are associated with poorer health even in non-pandemic situations. However, they also appear associated with greater vulnerability to developing poorer health and well-being in pandemic situations. There is a minority of those with ACEs who may have benefited from the changes in lifestyles associated with pandemic restrictions. Connectedness especially with family, appears an important factor in maintaining health during pandemic restrictions.

Parental technoference and adolescents' mental health and violent behaviour: a scoping review.

PURPOSE: The term 'technoference' refers to habitual interferences and disruptions within interpersonal relationships or time spent together due to use of electronic devices. Emerging evidence suggests associations between parental technoference and young people's mental health and violent behaviours. This scoping review sought to summarise the existing literature. METHODS: A scoping review was undertaken across six databases (APA PsycINFO, MEDLINE, ASSIA, ERIC, Social Sciences Premium Collection, SciTech Premium). Searches included articles examining the association between parental technoference and adolescent mental health and violent behaviours. All included studies provided empirical findings. RESULTS: Searches retrieved 382 articles, of which 13 articles met the eligibility criteria. A narrative approach was applied to synthesise the eligible findings. Across all studies, adolescent perceptions of parental technoference were negatively associated to adolescent mental health and positively related to adolescent violent behaviours. Parental cohesion and mental health were identified as significant mediating factors. CONCLUSION: Findings suggest that parents should be aware of the environment in which they use electronic devices as their use can potentially, directly and indirectly, influence adolescent mental health and violent behaviours. Further research into the potential caveats of parental technoference could support the development of evidence-informed guidelines for parental management of electronic devices.

Global phylogeny of the Shiitake mushroom and related Lentinula species uncovers novel diversity and suggests an origin in the Neotropics.

Lentinula (Basidiomycota, Agaricales) includes the most widely cultivated mushroom in the world, Lentinula edodes, also known as shiitake (Japanese) or xiang-gu (Chinese). At present, nine species are recognized in the genus, based on morphology, mating criteria, and geographic distribution. However, analyses of internal transcribed spacers (ITS) of ribosomal RNA genes have suggested that there are cryptic lineages. We analyzed a global-scale phylogenetic dataset from 325 Lentinula individuals from 24 countries in Asia-Australasia and the Americas plus Madagascar, with 325 sequences of ITS, 80 LSU sequences, and 111 sequences of translation elongation factor (tef1-α) genes. We recovered 15 independent lineages (Groups 1-15) that may correspond to species. Lineages in Asia-Australasia (Groups 1-5) and the Americas plus Madagascar (Groups 6-15) formed sister clades. Four lineages are represented only by sequences from single individuals and require further molecular sampling, including L. aff. raphanica (Group 7), L. ixodes (Group 8), L. boryana (Group 12), and L. aff. aciculospora (Group 14). Groups 1 and 5 are here referred to L. edodes and L. aff. edodes, respectively. However, these groups most likely represent the same species and are only recognized as (unsupported) monophyletic lineages by maximum likelihood analyses of ITS alone. Other putative species resolved here include L. lateritia (Group 2), L. novae-zelandieae (Group 3), L. aff. lateritia (Group 4), L. raphanica (Group 6), L. aff. detonsa (Group 9), L. detonsa (Group 10), L. guzmanii sp. nov. (Group 11), L. aciculospora (Group 13), and L. madagasikarensis (Group 15). Groups 9-12 represent the "L. boryana complex". Molecular clock and historical biogeographic analyses suggest that the most recent common ancestor (MRCA) of Lentinula can be placed in the middle Oligocene, ca. 30 million years ago (Ma), and had a likely presence in neotropical America. The MRCA of Lentinula in the Americas and Madagascar lived ca. 22 Ma in the Neotropics and the MRCA of Lentinula in Asia-Australasia lived ca. 6 Ma in Oceania. Given the current knowledge about plate tectonics and paleoclimatic models of the last 30 Myr, our phylogenetic hypothesis suggests that the extant distribution of Lentinula is likely to have arisen, in large part, due to long-distance dispersal. Lentinula collections include at least four dubious taxa that need further taxonomic studies: L. reticeps from the USA (Ohio); L. guarapiensis from Paraguay; Lentinus puiggarii from Brazil (São Paulo); and "L. platinedodes" from Vietnam. Approximately ten of the fifteen Groups are reported on Fagaceae, which appears to be the ancestral substrate of Lentinula.

Decision support-tools for early detection of infection in older people (aged> 65 years): a scoping review.

BACKGROUND: Infection is more frequent, and serious in people aged > 65 as they experience non-specific signs and symptoms delaying diagnosis and prompt treatment. Monitoring signs and symptoms using decision support tools (DST) is one approach that could help improve early detection ensuring timely treatment and effective care. OBJECTIVE: To identify and analyse decision support tools available to support detection of infection in older people (> 65 years). METHODS: A scoping review of the literature 2010-2021 following Arksey and O'Malley (2005) framework and PRISMA-ScR guidelines. A search of MEDLINE, Cochrane, EMBASE, PubMed, CINAHL, Scopus and PsycINFO using terms to identify decision support tools for detection of infection in people > 65 years was conducted, supplemented with manual searches. RESULTS: Seventeen papers, reporting varying stages of development of different DSTs were analysed. DSTs largely focussed on specific types of infection i.e. urine, respiratory, sepsis and were frequently hospital based (n = 9) for use by physicians. Four DSTs had been developed in nursing homes and one a care home, two of which explored detection of non- specific infection. CONCLUSIONS: DSTs provide an opportunity to ensure a consistent approach to early detection of infection supporting prompt action and treatment, thus avoiding emergency hospital admissions. A lack of consideration regarding their implementation in practice means that any attempt to create an optimal validated and tested DST for infection detection will be impeded. This absence may ultimately affect the ability of the workforce to provide more effective and timely care, particularly during the current covid-19 pandemic.

The use of mobile phone applications to enhance personal safety from interpersonal violence - an overview of available smartphone applications in the United Kingdom.

BACKGROUND: Interpersonal violence has devastating implications for individuals, families, and communities across the globe, placing a significant burden on health, justice, and social welfare systems. Smartphone technology may provide a platform for violence prevention interventions. However, evidence on the availability and user experience of smartphone applications aimed to prevent violence is underexplored. METHODS: Systematic searches of available smartphone applications marketed for personal safety and violence prevention on the Apple Store (IOS) and Google Play (Android) in the United Kingdom were run in May 2021. Relevant applications were downloaded, with data on user reviews and ratings extracted. Included applications were categorised according to their features and functions. Online user reviews were rated according to their sentiment (positive, negative, neutral) and thematically analysed. RESULTS: Of 503 applications, 86 apps met review criteria. Only 52 (61%) apps offered full functionality free of charge. Over half (52%) of apps were targeted towards the general population, with 16% targeting women and 13% targeting families. App functionality varied with 22% providing an alarm, 71% sending alerts to pre-designated contacts, 34% providing evidence capture and 26% offering educational information. Overall, 71% of applications had a user rating of four or above. For 61 apps a total of 3,820 user reviews were extracted. Over half (52.4%) of reviews were rated as having a positive sentiment, with 8.8% neutral and 38.8% negative. Key themes across user reviews included positive consequences of app use, technical and usage issues including app reliability, dissatisfaction with the financial cost of some app features and personal data and ethical issues. CONCLUSIONS: Reviews suggest that users find apps for personal safety and violence prevention useful. However, individuals also report them being unreliable, not working as described and having features that others may exploit. Findings have implications for the development of policy on apps to improve personal safety, especially given recent national policy (e.g. UK) discussions about their utility. Without the regulation or accreditation of such technology for quality assurance and reliability, emphasis needs to be placed on ensuring user safety; otherwise vulnerable individuals may continue to place reliance on untested technology in potentially dangerous circumstances.

An evaluation of a short film promoting kindness in Wales during COVID-19 restrictions #TimeToBeKind.

BACKGROUND: In response to successive COVID-19 restrictions in Wales, the Welsh ACE Support Hub launched the #TimeToBeKind campaign in March 2021. The campaign used a short film broadcast on national television and promoted on social media to encourage behaviour change for kindness. We evaluated the #TimeToBeKind campaign film to identify whether watching the film would result in increased intention to act in ways that promote kindness to others and if intentions were associated with being emotionally affected by the film. METHODS: A mixed methods evaluation was employed, using a short online survey and interaction with the film on the Twitter social media platform. The online survey measured public (n = 390) attitudes towards the film including feelings invoked, and behavioural intentions for acts of kindness as a result of viewing the film. Tweets which interacted with the film (n = 59; likes, re-tweets or comments), and tweet sentiment (positive, negative, or neutral) towards the film were also explored. RESULTS: The majority of participants reported positive attitudes to the film and agreed that they understood the campaign message (91.8%). 67.9% reported that the film made them feel upset or sad and for 22.6% the film resonated with their lockdown experience. As a result of seeing the film, 63.6% reported intentions to be kinder to others, 65.6% intended to try and help other members of their community, and 70.5% were more likely to check in on friends, family and neighbours. A higher proportion of individuals who were emotionally affected by the film (e.g. upset or sad, hopeful or encouraged, gained something positive) and those for whom the film resonated with their lockdown experience reported increased kindness behavioural intentions as a result of seeing the film. CONCLUSIONS: Film can be an effective tool to promote behaviour change for kindness. Films that provoke strong emotional reactions can still be perceived positively and lead to behaviour change. With the COVID-19 pandemic accelerating a move online for many, the findings of the present evaluation are relevant to how public health messaging can adapt and utilise this space to target individuals and promote behaviour change.

The public health impact of loneliness during the COVID-19 pandemic.

BACKGROUND: Social distancing measures have been effective in mitigating the spread of COVID-19; however, they have imposed a significant burden on population mental health and well-being. This study aimed to identify factors associated with loneliness during the COVID-19 pandemic, and to describe the relationship between loneliness and the risk of worsening health outcomes and behaviours. METHODS: Data for 8,960 adults were drawn from a national cross-sectional survey undertaken in Wales between January and June 2021. Participants self-reported changes to health and behaviour since the start of the pandemic. Logistic regression was used to identify factors associated with loneliness, and the impact of loneliness on self-reported changes in physical health, physical fitness, mental health, weight, alcohol consumption and social relations in comparison with pre-pandemic experiences. RESULTS: Groups most at risk of loneliness were those aged < 35 years, women (odds ratio [95% confidence interval]: 1.86 [1.70-2.05]), those with chronic health conditions (1.43 [1.29-1.58]) and the unemployed (2.18 [1.76-2.70]). Loneliness was a strong predictor of worsening health outcomes and behaviours, with those reporting often feeling lonely being at increased odds of worsening physical health (3.29 [2.80-3.86]), physical fitness (2.22 [1.90-2.60]), mental health (8.33 [6.95-9.99]), weight (1.39 [1.19-1.62]), alcohol consumption (1.37 [1.12,-1.66]) and social relations (2.45 [2.07-2.89]) during the pandemic. CONCLUSION: This study established an association between loneliness and self-reported worsening health during the pandemic, and identified factors increasing the risk of loneliness. The effect that social control measures have on loneliness should influence the design of future public health policy.

The impact of behavioural risk factors on communicable diseases: a systematic review of reviews.

BACKGROUND: The coronavirus (COVID-19) pandemic has highlighted that individuals with behavioural risk factors commonly associated with non-communicable diseases (NCDs), such as smoking, harmful alcohol use, obesity, and physical inactivity, are more likely to experience severe symptoms from COVID-19. These risk factors have been shown to increase the risk of NCDs, but less is known about their broader influence on communicable diseases. Taking a wide focus on a range of common communicable diseases, this review aimed to synthesise research examining the impact of behavioural risk factors commonly associated with NCDs on risks of contracting, or having more severe outcomes from, communicable diseases. METHODS: Literature searches identified systematic reviews and meta-analyses that examined the association between behavioural risk factors (alcohol, smoking, illicit drug use, physical inactivity, obesity and poor diet) and the contraction/severity of common communicable diseases, including infection or associated pathogens. An a priori, prospectively registered protocol was followed (PROSPERO; registration number CRD42020223890). RESULTS: Fifty-three systematic reviews were included, of which 36 were also meta-analyses. Reviews focused on: tuberculosis, human immunodeficiency virus, hepatitis C virus, hepatitis B virus, invasive bacterial diseases, pneumonia, influenza, and COVID-19. Twenty-one reviews examined the association between behavioural risk factors and communicable disease contraction and 35 examined their association with communicable disease outcomes (three examined their association with both contraction and outcomes). Fifty out of 53 reviews (94%) concluded that at least one of the behavioural risk factors studied increased the risk of contracting or experiencing worse health outcomes from a communicable disease. Across all reviews, effect sizes, where calculated, ranged from 0.83 to 8.22. CONCLUSIONS: Behavioural risk factors play a significant role in the risk of contracting and experiencing more severe outcomes from communicable diseases. Prevention of communicable diseases is likely to be most successful if it involves the prevention of behavioural risk factors commonly associated with NCDs. These findings are important for understanding risks associated with communicable disease, and timely, given the COVID-19 pandemic and the need for improvements in future pandemic preparedness. Addressing behavioural risk factors should be an important part of work to build resilience against any emerging and future epidemics and pandemics.

STOP-sexual violence: evaluation of a community-based nightlife worker awareness raising bystander training programme.

BACKGROUND: Preventing sexual violence in nightlife environments is a pervasive issue across many countries. This study explored the associated impact of a nightlife worker sexual violence awareness raising/bystander training programme (STOP-SV) on trainees' sexual violence myth acceptance and readiness and confidence to intervene. METHODS: : Pre- and post-test (n = 118), and 3-month follow-up (n = 38) trainee surveys were implemented across three countries (Czech Republic, Portugal and Spain). Paired-sample tests examined changes across time-periods in participants' myth acceptance (e.g. unwanted sexual advances are a normal part of a night out), and readiness and confidence to intervene. Multi-nominal regression was used to examine the relationship between the change in pre-to-post-training scores and trainee characteristics. RESULTS: Compared to pre-training, post-training participants were significantly (P < 0.01) less likely to agree with sexual violence myths, and more likely to be ready and confident to intervene. In bi-variate and multi-variate analyses, we found no significant associations between the change in pre-to-post-training scores and trainee characteristics. Analyses of the small follow-up sub-sample illustrated some positive changes at the post-training and follow-up time-periods (i.e. reduction in sexual violence myth acceptance). CONCLUSION: This exploratory study suggests that the STOP-SV training programme was associated with a decrease in trainees' acceptance of sexual violence myths, and an increase in their readiness and confidence to intervene. Our findings support the case for further implementation and evaluation of awareness raising/bystander programmes for nightlife workers that aim to prevent and respond to sexual violence.

Secret lifestyles of pyrophilous fungi in the genus Sphaerosporella.

PREMISE: Pyrophilous fungi form aboveground fruiting structures (ascocarps) following wildfires, but their ecology, natural history, and life cycles in the absence of wildfires are largely unknown. Sphaerosporella is considered to be pyrophilous. This study explores Sphaerosporella ascocarp appearance following a rare 2016 wildfire in the Great Smoky Mountains National Park (GSMNP), compares the timing of ascocarp formation with recovery of Sphaerosporella DNA sequences in soils, and explores the association of Sphaerosporella with post-fire Table Mountain pine (Pinus pungens) seedlings. METHODS: Burned sites in the GSMNP were surveyed for pyrophilous fungal ascocarps over 2 years. Ascocarps, mycorrhizae, and endophyte cultures were evaluated morphologically and by Sanger sequencing of the nuclear ribosomal ITS gene region (fungal barcode; Schoch et al., 2012). DNA from soil cores was subjected to Illumina sequencing. RESULTS: The timing and location of post-fire Sphaerosporella ascocarp formation was correlated with recovery of Sphaerosporella DNA sequences in soils. Genetic markers (fungal barcode) of Sphaerosporella were also recovered from mycorrhizal root tips and endophyte cultures from seedlings of Pinus pungens. CONCLUSIONS: This study demonstrates that Sphaerosporella species, in the absence of fire, are biotrophic, forming both mycorrhizal and endophytic associations with developing Pinus pungens seedlings and may persist in nature in the absence of wildfire as a conifer symbiont. We speculate that Sphaerosporella may fruit only after the host plant is damaged or destroyed and that after wildfires, deep roots, needle endophytes, or heat-resistant spores could serve as a source of soil mycelium.

Public acceptability of public health policy to improve population health: A population-based survey.

BACKGROUND: For public health policies to be effective, it is critical that they are acceptable to the public as acceptance levels impact success rate. OBJECTIVE: To explore public acceptance of public health statements and examine differences in acceptability across socio-demographics, health behaviours (physical activity, diet, binge drinking and smoking), health status and well-being. METHOD: A cross-sectional survey was conducted with a nationally representative sample (N = 1001) using a random stratified sampling method. Face-to-face interviews were conducted at homes of residents in Wales aged 16+ years. Individuals reported whether they agreed, had no opinion, or disagreed with 12 public health statements. RESULTS: More than half of the sample were supportive of 10 out of 12 statements. The three statements with the greatest support (>80% agreement) reflected the importance of: a safe and loving childhood to becoming a healthy adult, schools teaching about health, and healthier foods costing less. Individuals who engaged in unhealthy behaviours were less likely to agree with some of the statements (eg 39.8% of binge drinkers agreed alcohol adverts should be banned compared to 57.6% of those who never binge drink; P < .001). CONCLUSIONS: Findings show an appetite for public health policies among the majority of the public. The relationship between supporting policies and engaging in healthy behaviours suggests a feedback loop that is potentially capable of shifting both public opinion and the opportunities for policy intervention. If a nation becomes healthier, this could illicit greater support for stronger policies which could encourage more people to move in a healthier direction.

Understanding the association between self-reported poor oral health and exposure to adverse childhood experiences: a retrospective study.

BACKGROUND: Adverse childhood experiences, including physical, sexual or emotional abuse, can have detrimental impacts on child and adult health. However, little research has explored the impact that such early life experiences have on oral health. This study examines whether experiencing adverse childhood experiences before the age of 18 years is associated with self-reported poor dental health in later life. METHODS: Using stratified random probability sampling, a household survey (N = 5307; age range 18-69 years) was conducted in the South of England (Hertfordshire, Luton and Northamptonshire). Data were collected at participants' homes using face-to-face interviews. Measures included exposure to nine adverse childhood experiences, and two dental outcomes: tooth loss (> 8 teeth lost due to dental caries or damage) and missing or filled teeth (direct or indirect restorations; > 12 missing or filled teeth). RESULTS: Strong associations were found between exposure to childhood adversity and poor dental health. The prevalence of tooth loss was significantly higher (8.3%) in those with 4+ adverse childhood experiences compared to those who had experienced none (5.0%; p < 0.05). A similar relationship was found for levels of missing or filled teeth (13.4%, 4+ adverse childhood experiences; 8.1%, none; p < 0.001). Exposure to 4+ adverse childhood experiences was associated with a higher level of tooth loss and restorations at any age, compared to individuals who had not experienced adversity. Demographically adjusted means for tooth loss increased with adverse childhood experience count in all age groups, rising from 1.0% (18-29 years) and 13.0% (60-69 years) in those with none, to 3.0% and 26.0%, respectively in those reporting 4+. CONCLUSIONS: Exposure to childhood adversity could be an important predictive factor for poor dental health. As oral health is an important part of a child's overall health status, approaches that seek to improve dental health across the life-course should start with safe and nurturing childhoods free from abuse and neglect. Given the growing role that dental professionals have in identifying violence and abuse, it seems appropriate to raise awareness in the field of dentistry of the potential for individuals to have suffered adverse childhood experiences, and the mechanisms linking childhood adversity to poor dental health.

Stem cell factor and granulocyte colony-stimulating factor promote brain repair and improve cognitive function through VEGF-A in a mouse model of CADASIL.

Cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy (CADASIL) is a cerebral small vascular disease caused by NOTCH3 gene mutation in vascular smooth muscle cells (VSMCs), leading to ischemic stroke and vascular dementia. To date, the pathogenesis of CADASIL remains poorly understood, and there is no treatment that can slow the progression of CADASIL. Using a transgenic mouse model of CADASIL (TgNotch3R90C), this study reveals novel findings for understanding CADASIL pathogenesis that decreased cerebral vascular endothelial growth factor (VEGF/VEGF-A) is linked to reduced cerebral blood vessel density. Reduced endothelial cell (EC) proliferation and angiogenesis are seen in TgNotch3R90C mouse brain-isolated ECs. Decreased dendrites, axons, and synapses in the somatosensory and motor cortex layer 2/3 and in the hippocampal CA1, and reduced neurogenesis in both the subventricular zone and subgranular zone occur in 15-month-old TgNotch3R90C mice. These reductions in neuron structures, synapses, and neurogenesis are significantly correlated to decreased cerebral vasculature in the corresponding areas. Impaired spatial learning and memory in TgNotch3R90C mice are significantly correlated with the reduced cerebral vasculature, neuron structures, and synapses. Repeated treatment of stem cell factor and granulocyte colony-stimulating factor (SCF+G-CSF) at 9 and 10 months of age improves cognitive function, increases cerebral VEGF/VEGF-A, restores cerebral vasculature, and enhances regeneration of neuronal structures, synaptogenesis and neurogenesis in TgNotch3R90C mice. Pretreatment with Avastin, an angiogenesis inhibitor by neutralizing VEGF-A, completely eliminates the SCF+G-CSF-enhanced cognitive function, vascular and neuronal structure regeneration, synaptogenesis and neurogenesis in TgNotch3R90C mice. SCF+G-CSF-enhanced EC proliferation and angiogenesis in TgNotch3R90C mouse brain-isolated ECs are also blocked by Avastin pretreatment. These data suggest that SCF+G-CSF treatment may repair Notch3R90C mutation-damaged brain through the VEGF-A-mediated angiogenesis. This study provides novel insight into the involvement of VEGF/VEGF-A in the pathogenesis of CADASIL and sheds light on the mechanism underlying the SCF+G-CSF-enhanced brain repair in CADASIL.

Ideal, expected and perceived descriptive norm drunkenness in UK nightlife environments: a cross-sectional study.

BACKGROUND: Drunkenness is common in nightlife environments and studies suggest it can be considered both desirable and normal by nightlife users. We aimed to compare UK nightlife users' ideal levels of drunkenness to their expected drunkenness on a night out and their perceptions of descriptive nightlife norms. METHODS: A cross-sectional survey with nightlife patrons (n = 408, aged 18-35) in three cities. Using a scale from 1 (completely sober) to 10 (very drunk), participants rated: personal drunkenness at survey; expected drunkenness on leaving nightlife; perceived descriptive drunkenness norm in the city's nightlife; and ideal personal drunkenness. Analyses were limited to those who had or were intending to consume alcohol. RESULTS: Almost half of participants (46.8%) expected to get drunker than their reported ideal level on the night of survey, rising to four fifths of those with the highest levels of expected drunkenness. 77.9% rated typical nightlife drunkenness ≥8 but only 40.9% expected to reach this level themselves and only 23.1% reported their ideal drunkenness as ≥8. Higher expected drunkenness was associated with higher ideal drunkenness, higher perceived drunkenness norm and later expected home time. CONCLUSIONS: Nightlife users' perceptions of typical drunkenness in nightlife settings may be elevated and many of the heaviest drinkers are likely to drink beyond their ideal level of drunkenness. Findings can support emerging work to address cultures of intoxication in nightlife environments and suggest that interventions to correct misperceptions of normal levels of nightlife drunkenness may be of benefit.

Adverse childhood experiences, childhood relationships and associated substance use and mental health in young Europeans.

BACKGROUND: Adverse childhood experiences (ACEs) can increase risks of health-harming behaviours and poor health throughout life. While increases in risk may be affected by resilience resources such as supportive childhood relationships, to date few studies have explored these effects. METHODS: We combined data from cross-sectional ACE studies among young adults (n = 14 661) in educational institutions in 10 European countries. Nine ACE types, childhood relationships and six health outcomes (early alcohol initiation, problem alcohol use, smoking, drug use, therapy, suicide attempt) were explored. Multivariate modelling estimated relationships between ACE counts, supportive childhood relationships and health outcomes. RESULTS: Almost half (46.2%) of participants reported ≥1 ACE and 5.6% reported ≥4 ACEs. Risks of all outcomes increased with ACE count. In individuals with ≥4 ACEs (vs. 0 ACEs), adjusted odds ratios ranged from 2.01 (95% CIs: 1.70-2.38) for smoking to 17.68 (95% CIs: 12.93-24.17) for suicide attempt. Supportive childhood relationships were independently associated with moderating risks of smoking, problem alcohol use, therapy and suicide attempt. In those with ≥4 ACEs, adjusted proportions reporting suicide attempt reduced from 23% with low supportive childhood relationships to 13% with higher support. Equivalent reductions were 25% to 20% for therapy, 23% to 17% for problem drinking and 34% to 32% for smoking. CONCLUSIONS: ACEs are strongly associated with substance use and mental illness. Harmful relationships are moderated by resilience factors such as supportive childhood relationships. Whilst ACEs continue to affect many children, better prevention measures and interventions that enhance resilience to the life-long impacts of toxic childhood stress are required.

Adverse childhood experiences and sources of childhood resilience: a retrospective study of their combined relationships with child health and educational attendance.

BACKGROUND: Adverse childhood experiences (ACEs) including maltreatment and exposure to household stressors can impact the health of children. Community factors that provide support, friendship and opportunities for development may build children's resilience and protect them against some harmful impacts of ACEs. We examine if a history of ACEs is associated with poor childhood health and school attendance and the extent to which such outcomes are counteracted by community resilience assets. METHODS: A national (Wales) cross-sectional retrospective survey (n = 2452) using a stratified random probability sampling methodology and including a boost sample (n = 471) of Welsh speakers. Data collection used face-to-face interviews at participants' places of residence. Outcome measures were self-reported poor childhood health, specific conditions (asthma, allergies, headaches, digestive disorders) and school absenteeism. RESULTS: Prevalence of each common childhood condition, poor childhood health and school absenteeism increased with number of ACEs reported. Childhood community resilience assets (being treated fairly, supportive childhood friends, being given opportunities to use your abilities, access to a trusted adult and having someone to look up to) were independently linked to better outcomes. In those with ≥4 ACEs the presence of all significant resilience assets (vs none) reduced adjusted prevalence of poor childhood health from 59.8 to 21.3%. CONCLUSIONS: Better prevention of ACEs through the combined actions of public services may reduce levels of common childhood conditions, improve school attendance and help alleviate pressures on public services. Whilst the eradication of ACEs remains unlikely, actions to strengthen community resilience assets may partially offset their immediate harms.

Exploring practices and perceptions of alcohol use during pregnancy in England and Sweden through a cross-cultural lens.

Background: Qualitative studies have aimed to understand why some women continue to drink during pregnancy; however, there is a lack of comparative cross-cultural research. We aimed to explore perceptions and practices of alcohol use during pregnancy in England and Sweden. Methods: Semi-structured interviews were conducted with 21 parents in Merseyside, England and 22 parents in Örebro County, Sweden. Interviews were audio recorded, transcribed verbatim and translated. Data were analyzed using thematic analysis. Results: The majority of women in both countries abstained from alcohol when they found out they were pregnant, despite alcohol being part of many social contexts before pregnancy. Nine of the seventeen English women drank at some point during pregnancy, typically on special occasions. Most parents felt women should modify their alcohol intake when they become mothers, though several English parents argued that responsible motherhood did not necessarily equate to abstinence. Swedish parents held strong opinions against drinking during pregnancy and argued that any amount of alcohol could harm the foetus. English parents' opinions were divided; some were skeptical of whether low to moderate drinking was associated with risks. Conclusions: Practices and attitudes towards alcohol use during pregnancy and views on foetal rights and responsibilities of pregnant women differed in England and Sweden. Shared social norms around drinking may be shaped within the policy context of pregnancy drinking guidelines, determining whether women consume alcohol or not.

Does continuous trusted adult support in childhood impart life-course resilience against adverse childhood experiences - a retrospective study on adult health-harming behaviours and mental well-being.

BACKGROUND: Adverse childhood experiences (ACEs) including child abuse and household problems (e.g. domestic violence) increase risks of poor health and mental well-being in adulthood. Factors such as having access to a trusted adult as a child may impart resilience against developing such negative outcomes. How much childhood adversity is mitigated by such resilience is poorly quantified. Here we test if access to a trusted adult in childhood is associated with reduced impacts of ACEs on adoption of health-harming behaviours and lower mental well-being in adults. METHODS: Cross-sectional, face-to-face household surveys (aged 18-69 years, February-September 2015) examining ACEs suffered, always available adult (AAA) support from someone you trust in childhood and current diet, smoking, alcohol consumption and mental well-being were undertaken in four UK regions. Sampling used stratified random probability methods (n = 7,047). Analyses used chi squared, binary and multinomial logistic regression. RESULTS: Adult prevalence of poor diet, daily smoking and heavier alcohol consumption increased with ACE count and decreased with AAA support in childhood. Prevalence of having any two such behaviours increased from 1.8% (0 ACEs, AAA support, most affluent quintile of residence) to 21.5% (≥4 ACEs, lacking AAA support, most deprived quintile). However, the increase was reduced to 7.1% with AAA support (≥4 ACEs, most deprived quintile). Lower mental well-being was 3.27 (95% CIs, 2.16-4.96) times more likely with ≥4 ACEs and AAA support from someone you trust in childhood (vs. 0 ACE, with AAA support) increasing to 8.32 (95% CIs, 6.53-10.61) times more likely with ≥4 ACEs but without AAA support in childhood. Multiple health-harming behaviours combined with lower mental well-being rose dramatically with ACE count and lack of AAA support in childhood (adjusted odds ratio 32.01, 95% CIs 18.31-55.98, ≥4 ACEs, without AAA support vs. 0 ACEs, with AAA support). CONCLUSIONS: Adverse childhood experiences negatively impact mental and physical health across the life-course. Such impacts may be substantively mitigated by always having support from an adult you trust in childhood. Developing resilience in children as well as reducing childhood adversity are critical if low mental well-being, health-harming behaviours and their combined contribution to non-communicable disease are to be reduced.