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Mary P Martinasek,1 Linda M Gibson-Young,2 Janiece N Davis,3 Robert J McDermott41Public Health Department of Health Sciences and Human Performance, University of Tampa, Kennedy Boulevard, Tampa, FL, 2College of Nursing and Health Sciences, Texas A&M University: Corpus Christi, Corpus Christi, TX, 3Department of Health – Palm Beach County, West Palm beach, FL, 4Department of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USABackground: Given the increasing evidence of its negative health effects, including contributions to both infectious and chronic diseases, waterpipe tobacco smoking raises public health concerns beyond even those presented by traditional smoking. Methods: Identification of Clean Indoor Air Acts (CIAAs) from each of the 50 United States and District of Columbia were retrieved and examined for inclusion of regulatory measures where waterpipe tobacco smoking is concerned. Several instances of exemption to current CIAAs policies were identified. The cumulative policy lens is presented in this study. Results: States vary in their inclusion of explicit wording regarding CIAAs to the point where waterpipe tobacco smoking, unlike traditional smoking products, is excluded from some legislation, thereby limiting authorities’ ability to carry out enforcement. Conclusion: Consistent, comprehensive, and unambiguous legislative language is necessary to prevent establishments where waterpipe tobacco smoking occurs from skirting legislation and other forms of regulatory control. Stricter laws are needed due to the increasing negative health impact on both the smoker and the bystander. Actions at both the federal and state levels may be needed to control health risks, particularly among youth and young adult populations.Keywords: health policy, waterpipe tobacco, hookah smoking, tobacco regulation

Between 15% and 25% of children and adolescents seen in pediatric primary care have a behavioral health disorder with significant psychopathology, high functional impairment, and frequent psychiatric diagnostic comorbidity. Because child psychiatry services are frequently unavailable, primary care clinicians are frequently left managing these children without access to child psychiatry consultation. We describe Targeted Child Psychiatric Services (TCPS), a new model of pediatric primary clinician-child psychiatry collaborative care, and describe program utilization and characteristics of children referred over the first 18 months of the program using a retrospective chart review. The TCPS model can serve a large number of pediatric primary care practices and provide collaborative help with the evaluation and treatment of complex attention deficit hyperactivity disorder, depression, anxiety disorders, and pediatric psychopharmacology. [ABSTRACT FROM AUTHOR]

Background: Mood disorders, including unipolar and bipolar depression, contribute significantly to the global burden of disease. Psychological therapy is considered a gold standard non-pharmacological treatment for managing these conditions; however, a growing body of evidence also supports the use of lifestyle therapies for these conditions. Despite some clinical guidelines endorsing the application of lifestyle therapies as a first-line treatment for individuals with mood disorders, there is limited evidence that this recommendation has been widely adopted into routine practice. A key obstacle is the insufficient evidence on whether lifestyle therapies match the clinical and cost effectiveness of psychological therapy, particularly for treating those with moderate to severe symptoms. The HARMON-E Trial seeks to address this gap by conducting a non-inferiority trial evaluating whether a multi-component lifestyle therapy program is non-inferior to psychological therapy on clinical and cost-effectiveness outcomes over 8-weeks for adults with major depressive disorder and bipolar affective disorder., Methods: This trial uses an individually randomised group treatment design with computer generated block randomisation (1:1). Three hundred and seventy-eight adults with clinical depression or bipolar affective disorder, a recent major depressive episode, and moderate-to-severe depressive symptoms are randomised to receive either lifestyle therapy or psychological therapy (adjunctive to any existing treatments, including pharmacotherapies). Both therapy programs are delivered remotely, via a secure online video conferencing platform. The programs comprise an individual session and six subsequent group-based sessions over 8-weeks. All program aspects (e.g. session duration, time of day, and communications between participants and facilitators) are matched except for the content and program facilitators. Lifestyle therapy is provided by a dietitian and exercise physiologist focusing on four pillars of lifestyle (diet, physical activity, sleep, and substance use), and the psychological therapy program is provided by two psychologists using a cognitive behavioural therapy approach. Data collection occurs at baseline, 8-weeks, 16-weeks, and 6 months with research assistants blinded to allocation. The primary outcome is depressive symptoms at 8 weeks, measured using the Montgomery-Åsberg Depression Rating Scale (MADRS) (minimal clinically important difference = 1.6). A pre-specified within-trial economic evaluation will also be conducted., Discussion: Should lifestyle therapy be found to be as clinically and cost effective as psychological therapy for managing mood disorders, this approach has potential to be considered as an adjunctive treatment for those with moderate to severe depressive symptoms., Trial Registration: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12622001026718, registered 22nd July 2022., Protocol Version:  4.14, 26/06/2024., (© 2024. The Author(s).)

Background: We conducted the first non-inferiority, randomised controlled trial to determine whether lifestyle therapy is non-inferior to psychotherapy with respect to mental health outcomes and costs when delivered via online videoconferencing., Methods: An individually randomised, group treatment design with computer-generated block randomisation was used. Between May 2021-April 2022, 182 adults with a Distress Questionnaire-5 score = ≥8 (indicative depression) were recruited from a tertiary mental health service in regional Victoria, Australia and surrounds. Participants were assigned to six 90-min sessions over 8-weeks using group-based, online videoconferencing comprising: (1) lifestyle therapy (targeting nutrition, physical activity) with a dietitian and exercise physiologist (n = 91) or (2) psychotherapy (Cognitive Behavioural Therapy) with psychologists (n = 91). The primary outcome was Patient Health Questionnaire-9 (PHQ-9) depression at 8-weeks (non-inferiority margin ≤2) using Generalised Estimating Equations (GEE). Cost-minimisation analysis estimated the mean difference in total costs from health sector and societal perspectives. Outcomes were assessed by blinded research assistants using Computer Assisted Telephone Interviews. Results are presented per-protocol (PP) and Intention to Treat (ITT) using beta coefficients with 95% Confidence Intervals (CIs)., Findings: The sample was 80% women (mean: 45-years [SD:13.4], mean PHQ-9:10.5 [SD:5.7]. An average 4.2 of 6 sessions were completed, with complete data for n = 132. Over 8-weeks, depression reduced in both arms (PP: Lifestyle (n = 70) mean difference:-3.97, 95% CIs:-5.10, -2.84; and Psychotherapy (n = 62): mean difference:-3.74, 95% CIs:-5.12, -2.37; ITT: Lifestyle (n = 91) mean difference:-4.42, 95% CIs: -4.59, -4.25; Psychotherapy (n = 91) mean difference:-3.82, 95% CIs:-4.05, -3.69) with evidence of non-inferiority (PP GEE β:-0.59; 95% CIs:-1.87, 0.70, n = 132; ITT GEE β:-0.49, 95% CIs:-1.73, 0.75, n = 182). Three serious adverse events were recorded. While lifestyle therapy was delivered at lower cost, there were no differences in total costs (health sector adjusted mean difference: PP AUD$156 [95% CIs -$182, $611, ITT AUD$190 [95% CIs -$155, $651] ]; societal adjusted mean difference: PP AUD$350 [95% CIs:-$222, $1152] ITT AUD$ 408 [95% CIs -$139, $1157]., Interpretation: Remote-delivered lifestyle therapy was non-inferior to psychotherapy with respect to clinical and cost outcomes. If replicated in a fully powered RCT, this approach could increase access to allied health professionals who, with adequate training and guidelines, can deliver mental healthcare at comparable cost to psychologists., Funding: This trial was funded by the Australian Medical Research Future Fund (GA133346) under its Covid-19 Mental Health Research Grant Scheme., Competing Interests: This trial was funded by the National Health and Medical Research Council’s (NHMRC) Medical Research Future Fund–COVID-19 Mental Health Research Australian Government Department of Health (GA133346). AO is supported by a NHMRC Emerging Leader 2 Fellowship (2009295). FNJ is supported by an NHMRC Investigator Grant (#1194982). FNJ has received fellowship funding support from the National Health and Medical Research Council (#1194982) and payment or honorariums for lectures, presentations, speakers bureaus, manuscript writing, or educational events from the Malaysian Society of Gastroenterology and Hepatology, JNPN Congress, American Nutrition Association, Personalised Nutrition Summit, and American Academy of Craniofacial Pain, is a Scientific Advisory Board member of Dauten Family Centre for Bipolar Treatment Innovation (unpaid) and Zoe Nutrition (unpaid), has written two books for commercial publication on the topic of nutritional psychiatry and gut health, and is the principal investigator for the MicroFit Study. She is Director of the Food & Mood Centre, Deakin University, which has received research funding support from Be Fit Food, Bega Dairy and Drinks, and the a2 Milk Company and philanthropic research funding support from the Waterloo Foundation, Wilson Foundation, the JTM Foundation, the Serp Hills Foundation, the Roberts Family Foundation, and the Fernwood Foundation. SR is supported by an NHMRC Investigator Grant (2017506). MB is supported by a NHMRC Senior Principal Research Fellowship and Leadership 3 Investigator grant (1156072 and 2017131). MTey is supported by a NHMRC Emerging Leadership Fellowship (APP1195335). JS is supported by core funding to the Australian Centre for Behavioural Research in Diabetes provided by the collaboration between Diabetes Victoria and Deakin University. VV is supported by the Rural Health Multidisciplinary Training program. SMah has received funding from Education in Nutrition to provide a professional development presentation and Red Island Olive Oil for social media promotion. MMor has received research grants related to antimicrobial stewardship, discharge medication, consulting fees from Primary Health Networks of Gold Coast and Western Australia related to Primary Sense software. Australian Health Policy Collaboration, RACGP, Australian Department of Health and Aged Care (DoHAC), conference support from RACGP various as chair of Expert Committee for Quality Care, participation in DSMBs for Primary Sense and DoHAC and is a member of Arthritis Australia and Bond University Boards. The contents of the published material are solely the responsibility of the individual authors and do not reflect the views of the funding bodies. The authors have no interests to declare., (© 2024 The Authors.)

Context: The best practice for cleaning wrestling mats is using a residual disinfectant with continued antibacterial action. Recently available wash-in silver additives claim to confer a residual effect to fabric., Objective: To test the efficacy of laundering with a wash-in silver additive in reducing exposure of athletes to potentially infectious microbes on apparel., Design: 4-part Controlled Laboratory Study/Parallel Group Comparison Study: (1) To test whether fabrics in athletic clothing would be affected differently, we applied bacteria to control fabrics washed in detergent alone and test counterparts washed in detergent plus wash-in silver additive. Bacteria were applied to fabrics, extracted, plated, incubated, and counted. (2) To see if wash-in silver affected various bacteria differently, we washed cotton t-shirts with detergent alone or with detergent plus wash-in silver. We applied four bacterial species commonly found in the wrestling environment. Bacteria were extracted, plated, incubated, and counted. (3) To see if wash-in silver was effective in reducing bacterial contamination during practice, 32 collegiate wrestlers paired off with one wearing a test silver-treated t-shirt, and their partner wearing a control shirt. Wrestler rotations exposed shirts to 2, 4 or 8 wrestlers. Identical swatches of fabric were cut from the t-shirts. Bacteria were extracted, plated, incubated, and counted. (4) We simulated prolonged/repeated bacterial exposure as occurs during tournaments by applying bacteria directly to silver-treated and untreated singlet material repeatedly over time. Test samples were taken at regular intervals to see if bacterial growth was inhibited by the presence of the silver nanoparticles. Bacteria were extracted, plated, incubated, and counted., Setting: Laboratory and practice., Participants: Collegiate D3 Wrestling Team., Main Outcome Measure(s): Wash-in silver would be considered effective if statistically significant reduction in bacterial count was observed at 95% confidence., Results: Wash-in silver reduced bacterial growth at low levels of contamination but did not significantly reduce bacterial growth at levels seen during contact sport competitions. This was true for all bacterial species and all fabrics tested., Conclusions: The environmental and potential health risks in using a wash-in silver nanoparticle laundry additive in the wash cycle for clothing worn by wrestlers outweigh any potential infection control benefits to these athletes. We do not currently recommend adopting wash-in silver treatment as part of the laundering regimen for wrestling programs until further testing of alternate methods of silver impregnation into sports fabrics has been investigated.

Background: As the global population ages, there has been a growing incidence of neurodegenerative diseases such as Alzheimer's. More recently, studies exploring the relationship between dietary patterns and neuroimaging outcomes have received particular attention. This systematic literature review provides a structured overview of the association between dietary and nutrient patterns on neuroimaging outcomes and cognitive markers in middle-aged to older adults. A comprehensive literature search was conducted to find relevant articles published from 1999 to date using the following databases Ovid MEDLINE, Embase, PubMed, Scopus and Web of Science. The inclusion criteria for the articles comprised studies reporting on the association between dietary patterns and neuroimaging outcomes, which includes both specific pathological hallmarks of neurodegenerative diseases such as Aβ and tau and nonspecific markers such as structural MRI and glucose metabolism. The risk of bias was evaluated using the Quality Assessment tool from the National Heart, Lung, and Blood Institute of the National Institutes of Health. The results were then organized into a summary of results table, collated based on synthesis without meta-analysis. After conducting the search, 6050 records were extracted and screened for eligibility, with 107 eligible for full-text screening and 42 articles ultimately being included in this review. The results of the systematic review indicate that there is some evidence suggesting that healthy dietary and nutrient patterns were associated with neuroimaging measures, indicative of a protective influence on neurodegeneration and brain ageing. Conversely, unhealthy dietary and nutrient patterns showed evidence pointing to decreased brain volumes, poorer cognition and increased Aβ deposition. Future research should focus on sensitive neuroimaging acquisition and analysis methods, to study early neurodegenerative changes and identify critical periods for interventions and prevention., Systematic Review Registration: PROSPERO registration no, CRD42020194444)., Competing Interests: Conflicts of Interest The authors report no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The use of omega-3 polyunsaturated fatty acid (ω-3 PUFA) supplements is increasingly common among middle-aged and older adults. Users of ω-3 PUFA supplements often report using such supplements to support cognitive health, despite mixed findings reported within the ω-3 PUFA literature. To date, very few studies have explored cognitive effects in distinctly middle-aged (40 to 60 years) adults, and none have examined the acute effects (in the hours following a single dose) on cognitive performance. The current study evaluated whether a single dose of ω-3 PUFA (4020 mg docosahexaenoic acid and 720 mg eicosapentaenoic acid) influences cognitive performance and cardiovascular function in middle-aged males. Cognitive performance and cardiovascular function were assessed before and 3.5-4 h after consumption of a high dose of ω-3 PUFA (DHA + EPA) or placebo, incorporated into a standardized meal (i.e., single serve of Greek yogurt). In this study of middle-aged males, no significant differential treatment effects were observed for cognitive performance. However, a significant reduction in aortic systolic blood pressure (pre-dose to post-dose) was apparent following consumption of the ω-3 PUFA (DHA + EPA) treatment (mean difference = -4.11 mmHg, p = 0.004) but not placebo (mean difference = -1.39 mmHg, p = 0.122). Future replication in a sample comprising females, as well as patients with hypertension, is merited.

Background: Previous randomized controlled trials examining cognitive and mood effects of combination multivitamin supplements in healthy, non-clinical adults have reported mixed results. One purported explanation for this is that the dietary status of participants at the start of supplement interventions may influence the magnitude of the effect of supplementation. Methods: In this study, we evaluated the effect of a multinutrient formula containing B group vitamins, Bacopa monniera and Ginkgo biloba on memory, attention, mood and biochemical markers of nutrient status in middle-aged adults ( M = 52.84 years, n = 141) with 'optimal' and 'sub-optimal' diets over 12 weeks. We hypothesised that active supplementation would differentially improve memory and attention in those with a 'sub-optimal' diet. Results: Mixed model, repeated measures analysis revealed that, in comparison to placebo, active treatment was associated with significant increases in B vitamin status (B1, B6, B12). Regarding behavioural outcomes there was no significant benefit to memory ( F (1, 113.51) = 0.53, p = 0.470) nor attention ( F (1,113.77) = 1.89, p = 0.171) in the whole cohort. Contrary to our hypothesis, there was a significant beneficial effect of supplementation on attentional performance in individuals with an 'optimal' diet prior to supplementation ( F (1,57.25) = 4.94, p = 0.030). In the absence of a main effect of supplementation across the entire cohort, there were also a number of significant three-way interactions (treatment by time by diet group) detected in secondary outcomes including lower state anxiety and mental fatigue in those with an 'optimal' diet. Conclusion: These findings suggest that the cognitive benefit of B vitamin and herbal supplementation may be dependent on diet quality, supporting the concepts of 'co-nutrient optimisation' and interdependency of nutrients. This warrants further investigation. This study advocates characterising the diet of participants prior to supplementation as it may influence the effect of a nutraceutical intervention.

Adherence to different dietary patterns has been linked to the development of cognitive decline; yet little is known about whether this relationship is present in middle age. The current study aimed to explore the relationship between different dietary patterns, cognitive performance, and potential cardio-metabolic mechanisms for this relationship. Participants were recruited using a diet screening tool to ensure that the cohort had a range of diet quality ranging from relatively poor to relatively healthy. In a sample of 141 middle-aged adults (age: M = 52.84 years, SD = 6.87 years), multiple 24 h diet recalls were collected and used to score adherence to the Mediterranean diet, dietary approaches to stop hypertension (DASH) diet, and Mediterranean-DASH diet intervention for neurodegenerative delay (MIND) diet. Metabolic risk was assessed using the metabolic syndrome severity score (MetSSS) and arterial stiffness. Cognitive performance was assessed using the Swinburne University Computerized Cognitive Assessment Battery (SUCCAB). Adherence to the MIND diet was significantly related to Stroop Processing domain (β = 0.19, p = 0.035). None of the dietary patterns were significantly related to MetSSS or arterial stiffness. However, adherence to the DASH diet was significantly associated with two cardio-metabolic measures including lower augmentation index (β = -0.17, p = 0.032) and lowered cholesterol (β = -0.18, p = 0.041). Interestingly, two cardio-metabolic risk factors were also associated with better cognitive performance: MetSSS (β = 0.21, p = 0.010) and waist circumference (β = 0.22, p = 0.020). Together these findings suggest that diet in middle age may be important for cognitive functioning and cardio-metabolic risk. However, more research is needed in the form of randomized controlled trials to confirm the direction of these relationships., Competing Interests: AS, DW, and AP have received research funding honoraria and conference support and consultancy from the nutrition industry. AP has previously served as a member of the Scientific Advisory Panel for Swisse Wellness Pty Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gauci, Young, Arnoldy, Scholey, White, Lassemillante, Meyer and Pipingas.)

Context: Diet plays a critical role in cognitive integrity and decline in older adults. However, little is known about the relationship between diet and cognitive integrity in middle age., Objective: To investigate the relationship between dietary patterns in healthy middle-aged adults and neurocognition both in middle age and later in life., Data Sources: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, the following electronic databases were searched: Web of Science, Scopus, PubMed, and PsychInfo., Data Extraction: Data from eligible articles was extracted by 2 reviewers., Data Analysis: Articles included in the systematic review were synthesized (based on the synthesis without meta-analysis reporting guidelines) and assessed for quality (using the Joanna Briggs Institute checklist for randomized controlled trials, cohort studies, and cross-sectional studies) by 2 reviewers., Results: Of 1558 studies identified, 34 met the eligibility criteria for inclusion. These comprised 9 cross-sectional studies, 23 longitudinal or prospective cohort studies, and 2 randomized controlled trials. Findings were mixed, with some studies reporting a significant positive relationship between adherence to various "healthy" dietary patterns and neurocognition, but others reporting no such relationship., Conclusion: This systematic review demonstrated that adherence to the Mediterranean diet and other healthy dietary patterns in middle age can protect neurocognition later in life., Systematic Review Registration: PROSPERO registration no. CRD42020153179., (© The Author(s) 2021. Published by Oxford University Press on behalf of the International Life Sciences Institute.)

Background: There is increasing recognition of the substantial burden of mental health disorders at an individual and population level, including consequent demand on mental health services. Lifestyle-based mental healthcare offers an additional approach to existing services with potential to help alleviate system burden. Despite the latest Royal Australian New Zealand College of Psychiatrists guidelines recommending that lifestyle is a 'first-line', 'non-negotiable' treatment for mood disorders, few such programs exist within clinical practice. Additionally, there are limited data to determine whether lifestyle approaches are equivalent to established treatments. Using an individually randomised group treatment design, we aim to address this gap by evaluating an integrated lifestyle program (CALM) compared to an established therapy (psychotherapy), both delivered via telehealth. It is hypothesised that the CALM program will not be inferior to psychotherapy with respect to depressive symptoms at 8 weeks., Methods: The study is being conducted in partnership with Barwon Health's Mental Health, Drugs & Alcohol Service (Geelong, Victoria), from which 184 participants from its service and surrounding regions are being recruited. Eligible participants with elevated psychological distress are being randomised to CALM or psychotherapy. Each takes a trans-diagnostic approach, and comprises four weekly (weeks 1-4) and two fortnightly (weeks 6 and 8) 90-min, group-based sessions delivered via Zoom (digital video conferencing platform). CALM focuses on enhancing knowledge, behavioural skills and support for improving dietary and physical activity behaviours, delivered by an Accredited Exercise Physiologist and Accredited Practising Dietitian. Psychotherapy uses cognitive behavioural therapy (CBT) delivered by a Psychologist or Clinical Psychologist, and Provisional Psychologist. Data collection occurs at baseline and 8 weeks. The primary outcome is depressive symptoms (assessed via the Patient Health Questionnaire-9) at 8 weeks. Societal and healthcare costs will be estimated to determine the cost-effectiveness of the CALM program. A process evaluation will determine its reach, adoption, implementation and maintenance., Discussion: If the CALM program is non-inferior to psychotherapy, this study will provide the first evidence to support lifestyle-based mental healthcare as an additional care model to support individuals experiencing psychological distress., Trial Registration: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12621000387820 , Registered 8 April 2021., (© 2022. The Author(s).)

DILI is a major cause of attrition in drug development with over 1000 FDA-approved drugs known to potentially cause DILI in humans. Unfortunately, DILI is often not detected until drugs have reached clinical stages, risking patients' safety and leading to substantial losses for the pharma industry. Taking into account that standard 2D models have limitations in detecting DILI it is essential to develop in vitro models that are more predictive to improve data translatability. To understand causality and mechanistic aspects of DILI in detail, a human liver MPS consisting of human primary liver parenchymal and non-parenchymal cells (NPCs) and cultured in 3D microtissues on an engineered scaffold under perfusion has been developed. Cryopreserved primary human hepatocytes (PHHs) and Kupffer cells (HKCs) were cocultured as microtissues in the MPS platform for up to two weeks, and each compound of interest was repeatably dosed onto liver microtissues at seven test concentrations for up to four days. Functional liver-specific endpoints were analyzed (including clinical biomarkers such as alanine aminotransferase, ALT) to evaluate liver function. Acute and chronic exposure to compounds of various DILI severities can be assessed by comparing responses to single and multi-dosed microtissues. The methodology has been validated with a broad set of severe and mildly hepatotoxic compounds. Here we show the data for pioglitazone and troglitazone, well-known hepatotoxic compounds withdrawn from the market for causing liver failures. Overall, it has been shown that the liver MPS model can be a useful tool to assess DILI and its association with changes in hepatic function. The model can additionally be used to assess how novel compounds behave in distinct patient subsets and how toxicity profiles may be affected by liver disease states (e.g., viral hepatitis, fatty liver disease).

Background: Cognitive decline is influenced by various factors including diet, cardiovascular disease, and glucose control. However, the combined effect of these risk factors on cognitive performance is yet to be fully understood., Objective: The current study aimed to explore the inter-relationship between these risk factors and cognitive performance in older adults at risk of future cognitive decline., Methods: The sample comprised 163 (Age: M = 65.23 years, SD = 6.50) participants. Food Frequency Questionnaire data was used to score diet quality and adherence to the Western Style Diet (WSD) and Prudent Style Diet (PSD). Glucose control was gauged by serum levels of glycated hemoglobin (HbA1c) and arterial stiffness was measured using carotid to femoral pulse wave velocity. Cognitive performance was assessed using two subtests of the Swinburne University Computerized Cognitive Assessment Battery (SUCCAB) and Rey's Verbal Learning Test (RVLT)., Results: Diet quality, adherence to the WSD or PSD, and glucose control were not significantly related to cognitive outcomes. However, a significant negative association was found between arterial stiffness and the spatial working memory subtest of SUCCAB (β= -0.21, p < 0.05). Arterial stiffness also significantly interacted with the PSD to impact total recall (F change (1,134) = 5.37, p < 0.05) and the composite score of RVLT (F change (1,134) = 4.03, p < 0.05)., Conclusion: In this sample of older adults at risk of cognitive decline, diet alone was not found to predict cognitive performance; however, it was found to moderate the relationship between arterial stiffness and cognition.

Background: Beta-casein is a major protein in cow's milk, of which A1 and A2 are the most frequent variants. Recent evidence implicates A1 beta-casein consumption in mechanisms that are of potential importance to mental health, yet its possible effects on psychological endpoints remains unknown. The primary aim of the study is to evaluate the comparative effects of consumption of dairy products containing A2 beta-casein versus conventional dairy (i.e. containing both A1 and A2 beta-casein) on symptoms of psychological distress in women with low mood., Methods: 'The Moo'D Study' is a 16-week, superiority, 1:1 parallel group, triple-blinded, randomised controlled trial. Ninety women with low mood (Patient Health Questionnaire score ≥ 5) will be randomised to consume either A2 beta-casein only or conventional dairy products. The primary outcome, symptoms of psychological distress, will be measured by the 21-item Depression, Anxiety and Stress Scale. Secondary outcomes will include symptoms of depression, anxiety and stress, severity of low mood, cognition, gut microbiota composition, gut symptomatology, markers of immune function, gut inflammation, systemic metabolites, endothelial integrity and oxidative stress, body composition, perceived wellbeing, sleep, quality of life, resource use and cost-effectiveness., Discussion: This study will advance our understanding of the possible impact of milk proteins on psychological distress in women as well as elucidate mechanisms underpinning any association. Given dairy products form a substantial component of traditional and Western diets, the implications of these findings are likely to be of clinical and public health importance., Trial Registration: The trial protocol has been prospectively registered with the Australia and New Zealand Clinical Trials Registry, ACTRN12618002023235 . Registered on 17 December 2018., (© 2021. The Author(s).)

Non-alcoholic steatohepatitis (NASH) is a common form of chronic liver disease characterised by lipid accumulation, infiltration of immune cells, hepatocellular ballooning, collagen deposition and liver fibrosis. There is a high unmet need to develop treatments for NASH. We have investigated how liver fibrosis and features of advanced clinical disease can be modelled using an in vitro microphysiological system (MPS). The NASH MPS model comprises a co-culture of primary human liver cells, which were cultured in a variety of conditions including+/- excess sugar, fat, exogenous TGFβ or LPS. The transcriptomic, inflammatory and fibrotic phenotype of the model was characterised and compared using a system biology approach to identify conditions that mimic more advanced clinical disease. The transcriptomic profile of the model was shown to closely correlate with the profile of patient samples and the model displayed a quantifiable fibrotic phenotype. The effects of Obeticholic acid and Elafibranor, were evaluated in the model, as wells as the effects of dietary intervention, with all able to significantly reduce inflammatory and fibrosis markers. Overall, we demonstrate how the MPS NASH model can be used to model different aspects of clinical NASH but importantly demonstrate its ability to model advanced disease with a quantifiable fibrosis phenotype., (© 2021. The Author(s).)

Background: Dirofilaria immitis, a globally distributed filarial parasite of dogs, is known to cause serious or fatal cardiopulmonary disease. Client-owned dogs were enrolled in a clinical field study in the USA to evaluate the clinical effectiveness and field safety of an orally administered combination investigational product (IP) containing milbemycin oxime and lotilaner (Credelio ® Plus) as compared to a control product (CP) for the prevention of heartworm disease when administered monthly for 11 consecutive months., Methods: In this 11-month field study, 319 dogs ≥ 8 weeks old confirmed to be heartworm-negative were enrolled from eight geographically distinct US veterinary clinics, including sites in the southern USA and Mississippi River Valley. The dogs were treated with either the IP combination product at 0.75-1.53 mg/kg milbemycin oxime and 20-41.5 mg/kg lotilaner (n = 159) or the CP (Sentinel ® Flavor Tabs ® ; milbemycin oxime/lufenuron) at the label-recommended dose rate (n = 158.) On day 330, effectiveness was evaluated in each dog using antigen and microfilarial (modified Knott's) testing to assess the establishment of any patent adult heartworm infections., Results: All dogs treated with the IP combination product and the CP tested negative (100% prevention) for heartworm infection on day 330. The IP combination product tablets containing milbemycin oxime and lotilaner were well tolerated based on the safety assessments in all treated dogs., Conclusions: This multi-site clinical study using client-owned dogs demonstrated that monthly use of flavored, chewable tablets containing a combination of milbemycin oxime and lotilaner administered orally under end use conditions is safe for dogs. None of the enrolled dogs developed heartworm infections. Eleven consecutive monthly treatments of the IP provided 100% prevention of heartworm disease caused by D. immitis.

Background: The ascarid, Toxocara canis, is a common and important zoonotic intestinal nematode parasite that infects dogs globally. An effective treatment that kills any pre-patent stages of immature T. canis could additionally reduce or eliminate the development of patent infections that can result in clinical disease in infected dogs and would further reduce environmental contamination of eggs. Two randomized, blinded, GCP-compliant, pivotal laboratory dose confirmation studies were conducted to assess the effectiveness and safety of a new novel combination of lotilaner and milbemycin oxime tablets (Credelio Plus) administered orally to dogs that were experimentally infected with immature (L4 or immature adult [L5]) stages of T. canis., Methods: The commercial tablet formulation of Credelio Plus ® was administered in a time frame relative to inoculation with infective eggs. This allowed for effectiveness to be assessed against each specific immature stage of T. canis. In each study, dogs were randomized and allocated to one of four treatment groups. Each treatment group contained ten dogs that had been experimentally inoculated on Day 0 with infective T. canis eggs and then were dosed once on Day 14 or Day 24 using either placebo tablets or Credelio Plus tablets (IP) to provide minimum dosages of 0.75 mg/kg of milbemycin oxime and 20 mg/kg of lotilaner. All dogs were necropsied 5 or 6 days after their respective treatment. At necropsy, all nematodes recovered from the gastrointestinal tract were counted by species and stage., Results: In both dose confirmation studies using geometric mean worm counts, effectiveness of Credelio Plus was ≥ 98.6% and ≥ 96.8% against L4 larval stage T. canis and immature adult [L5] T. canis in both studies, respectively., Conclusions: These studies demonstrated that the Credelio Plus combination tablet administered orally to dogs was highly efficacious against experimental infections with L4 and immature adult [L5] stages of T. canis.

Many researchers have identified the issue of self-selection bias hindering the ability to detect nutrient effects in healthy populations. However, it appears that no effort has been made to mitigate this potential design flaw. By recruiting individuals on the basis of pre-trial dietary intake, the Memory and Attention Supplementation Trial aimed to capture a cohort of participants with a wide variety of dietary intake, thus increasing the likelihood of a diverse range of nutrient status. This perspective specifically examines the profile of these trial volunteers and in doing so, we present the first empirical evidence of self-selection bias when recruiting healthy volunteers for a randomized controlled trial of a nutrient-based supplement. These findings support the anecdotal proposal that traditional recruitment methods inherently attract trial volunteers who are vastly unrepresentative of the population and threatens the generalizability of this field of research. Alternative approaches to recruitment, including a-priori screening for baseline diet quality and nutrient status, are discussed as essential design recommendations to ensure accurate interpretation of nutrient effects within the context of baseline participant characteristics., (Copyright © 2020 Young, Gauci, Scholey, White and Pipingas.)

The purpose of the current study was to investigate the impact of job demands on health and work outcomes among Malaysian workers. We hypothesized that job demands (i.e., emotional demands and physical demands) would predict future work-related burnout and work engagement, in turn affecting sleep problems and job performance (in-role, extra-role). A longitudinal two-wave survey was conducted among Malaysian workers and valid data from 345 participants were analyzed using structural equation modeling. The results revealed that work-related burnout predicts sleep problems while work engagement increased employees' job performance over time. Overall, the current study highlights the importance of specific job demands (i.e., emotional demands and physical demands) that specifically affect health-related behavior and work-related behavior among workers., (© 2020 The Institute of Psychology, Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.)

Evidence for diet quality representing a modifiable risk factor for age-related cognitive decline and mood disturbances has typically come from retrospective, cross-sectional analyses. Here a diet screening tool (DST) was used to categorize healthy middle-aged volunteers ( n = 141, 40-65 years) into "optimal" or "sub-optimal" diet groups to investigate cross-sectional associations between diet quality, cognitive function, and mood. The DST distinguished levels of nutrient intake as assessed by Automated Self-Administered 24-h dietary recall and nutrient status, as assessed by blood biomarker measures. Compared with the "sub-optimal" group, the "optimal" diet group showed significantly higher intake of vitamin E ( p = 0.007), magnesium ( p = 0.001), zinc ( p = 0.043) and fiber ( p = 0.015), higher circulating levels of vitamin B6 ( p = 0.030) and red blood cell folate ( p = 0.026) and lower saturated fatty acids ( p = 0.012). Regarding psychological outcomes, the "optimal" diet group had significantly better Stroop processing than those with a "sub-optimal" diet ( p = 0.013). Regression analysis revealed that higher DST scores were associated with fewer mood disturbances ( p = 0.002) and lower perceived stress ( p = 0.031), although these differences were not significant when comparing "optimal" versus "sub-optimal" as discrete groups. This study demonstrates the potential of a 20-item diet screen to identify both nutritional and psychological status in an Australian setting.

Objective: Childhood asthma is complex and poor management of childhood asthma is the leading health reason for pediatric emergency department visits, hospitalizations and missed school days for school-aged children. The purpose of this study was to explore caregiver perceptions of home management of childhood asthma in school-aged children who have been hospitalized for asthma. Methods: Using qualitative descriptive design with in-depth interviews, we aimed to explore family caregiver perceptions of managing asthma in school-aged children between 5 and 12 years of age. Results: Data were collected from 17 participants; however, two transcripts were incomplete due to interruption in interview from medical team. The sample consisted of 15 families with child age mean of 8 years, and diagnosed with asthma at 2 years and 8 months. Four experts with asthma and research design analyzed all transcripts and six clear themes emerged. These themes included family or caregiver burden, care coordination, certainty or uncertainty continuum, effort to control, sign or symptom recognition, and trigger recognition. In this article, we defined each theme and identify specific statements from families on daily life when affected by childhood asthma. Conclusions: The findings of this study confirm and extend results from other studies of caregivers who have school-aged children diagnosed with asthma. This study found that families play a vital role in management of asthma on a daily basis and families often assess the overall management of asthma by all child relations throughout the day. Clinical implications are highlighted within each theme.

Background: Electronic nicotine-delivery systems have been increasing in prevalence among young adults. Although these devices are marketed to aid in quit smoking, young adults who do not smoke traditional cigarettes are using these devices. This study explored associations between individuals' quit type (ie, no plans to quit, plans to quit, or quit > 6 months ago) and perceived health status, perception of harm compared to cigarettes, perception of secondhand vapor harm, and reasons for first use., Methods: We utilized a cross-sectional study design using a 33-item electronic survey questionnaire. The total sample size was 2,792. Out of these the ENDS users were 1,217. The survey was distributed to university students in 5 areas in 3 countries: the United States (ie, Florida, Alabama, and Illinois), Germany (ie, Hamburg) and South Africa (ie, Potchefstroom)., Results: Quantitative data analysis indicated that, regardless of quit status, there was a general lack of knowledge regarding secondhand vapor effects. Additionally, young adults are utilizing these products primarily due to peer influence and stress relief. Harm perception may factor into quit attempts using electronic nicotine-delivery systems., Conclusions: Education provided by respiratory therapists (and to respiratory therapy students) would be valuable as they inform patients and communities of the scholarly literature on vaping devices., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2020 by Daedalus Enterprises.)

Aim: High-throughput phenotypic screens have emerged as a promising avenue for small-molecule drug discovery. The challenge faced in high-throughput phenotypic screens is target deconvolution once a small molecule hit is identified. Chemogenomics libraries have emerged as an important tool for meeting this challenge. Here, we investigate their target-specificity by deriving a 'polypharmacology index' for broad chemogenomics screening libraries., Methods: All known targets of all the compounds in each library were plotted as a histogram and fitted to a Boltzmann distribution, whose linearized slope is indicative of the overall polypharmacology of the library., Results & Conclusion: Comparison of libraries clearly distinguished the most target-specific library, which might be assumed to be more useful for target deconvolution in a phenotypic screen., Competing Interests: Financial & competing interests disclosure T Cardozo and K Felsovalyi are co-founders of GeneCentrix, Inc. This work was supported by NIH award R43LM012577 (to K Felsovalyi and L Young), R44DA050376 (to J Fuller) and RC2LM010994 (to T Cardozo). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript., (© 2020 Timothy Cardozo.)

A systematic review and meta-analysis was undertaken to examine and quantify the effects of B vitamin supplementation on mood in both healthy and 'at-risk' populations. A systematic search identified all available randomised controlled trials (RCTs) of daily supplementation with ≥3 B group vitamins with an intervention period of at least four weeks. Random effects models for a standardized mean difference were used to test for overall effect. Heterogeneity was tested using the I 2 statistic. Eighteen articles (16 trials, 2015 participants) were included, of which 12 were eligible for meta-analysis. Eleven of the 18 articles reported a positive effect for B vitamins over a placebo for overall mood or a facet of mood. Of the eight studies in 'at-risk' cohorts, five found a significant benefit to mood. Regarding individual facets of mood, B vitamin supplementation benefited stress ( n = 958, SMD = 0.23, 95% CI = 0.02, 0.45, p = 0.03). A benefit to depressive symptoms did not reach significance ( n = 568, SMD = 0.15, 95% CI = -0.01, 0.32, p = 0.07), and there was no effect on anxiety ( n = 562, SMD = 0.03, 95% CI = -0.13, 0.20, p = 0.71). The review provides evidence for the benefit of B vitamin supplementation in healthy and at-risk populations for stress, but not for depressive symptoms or anxiety. B vitamin supplementation may particularly benefit populations who are at risk due to (1) poor nutrient status or (2) poor mood status.

Environmental changes alter the diversity and structure of communities. By shifting the range of species traits that will be successful under new conditions, environmental drivers can also dramatically impact ecosystem functioning and resilience. Above and belowground communities jointly regulate whole-ecosystem processes and responses to change, yet they are frequently studied separately. To determine whether these communities respond similarly to environmental changes, we measured taxonomic and trait-based responses of plant and soil microbial communities to four years of experimental warming and nitrogen deposition in a temperate grassland. Plant diversity responded strongly to N addition, whereas soil microbial communities responded primarily to warming, likely via an associated decrease in soil moisture. These above and belowground changes were associated with selection for more resource-conservative plant and microbe growth strategies, which reduced community functional diversity. Functional characteristics of plant and soil microbial communities were weakly correlated (P = 0.07) under control conditions, but not when above or belowground communities were altered by either global change driver. These results highlight the potential for global change drivers operating simultaneously to have asynchronous impacts on above and belowground components of ecosystems. Assessment of a single ecosystem component may therefore greatly underestimate the whole-system impact of global environmental changes.

Despite decades of clinical use and research, the mechanism of action (MOA) of antidepressant medications remains poorly understood. Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are the most commonly prescribed antidepressants-atypical antidepressants such as bupropion have also proven effective, while exhibiting a divergent clinical phenotype. The difference in phenotypic profiles presumably lies in the differences among the MOAs of SSRIs/SNRIs and bupropion. We integrated the ensemble of bupropion's affinities for all its receptors with the expression levels of those targets in nervous system tissues. This "combined target tissue" profile of bupropion was compared to those of duloxetine, fluoxetine, and venlafaxine to isolate the unique target tissue effects of bupropion. Our results suggest that the three monoamines-serotonin, norepinephrine, and dopamine-all contribute to the common antidepressant effects of SSRIs, SNRIs, and bupropion. At the same time, bupropion is unique in its action on 5-HT3AR in the dorsal root ganglion and nicotinic acetylcholine receptors in the pineal gland. These unique tissue-specific activities may explain unique therapeutic effects of bupropion, such as pain management and smoking cessation, and, given melatonin's association with nicotinic acetylcholine receptors and depression, highlight the underappreciated role of the melatonergic system in bupropion's MOA.

Protein aggregation is linked with the onset of several neurodegenerative disorders, including Parkinson's disease (PD), which is associated with the aggregation of α-synuclein (αSyn). The structural mechanistic details of protein aggregation, including the nature of the earliest protein-protein interactions, remain elusive. In this study, we have used single molecule force spectroscopy (SMFS) to probe the first dimerization events of the central aggregation-prone region of αSyn (residues 71-82) that may initiate aggregation. This region has been shown to be necessary for the aggregation of full length αSyn and is capable of forming amyloid fibrils in isolation. We demonstrate that the interaction of αSyn 71-82 peptides can be studied using SMFS when inserted into a loop of protein L, a mechanically strong and soluble scaffold protein that acts as a display system for SMFS studies. The corresponding fragment of the homolog protein γ-synuclein (γSyn), which has a lower aggregation propensity, has also been studied here. The results from SMFS, together with native mass spectrometry and aggregation assays, demonstrate that the dimerization propensity of γSyn 71-82 is lower than that of αSyn 71-82 , but that a mixed αSyn 71-82 : γSyn 71-82 dimer forms with a similar propensity to the αSyn 71-82 homodimer, slowing amyloid formation. This work demonstrates the utility of a novel display method for SMFS studies of aggregation-prone peptides, which would otherwise be difficult to study., (© 2018 The Authors Protein Science published by Wiley Periodicals, Inc. on behalf of The Protein Society.)

Skp2 is a member of the F-box family of proteins that serve as substrate-specific adaptors in Skp1-CUL1-ROC1-F-box (SCF) E3 ubiquitin ligases. Skp2 (Fbxl1) directly binds to the tumor suppressor p27 in the context of the SCF Skp2 E3 ubiquitin ligase to ubiquitylate and target-phosphorylated p27 for proteasomal degradation. As p27 is a powerful suppressor of growth in a variety of cells, and as Skp2 is also overexpressed in many human cancers, Skp2 is considered an oncogene and an intriguing drug target. However, despite 20 years of investigation, a valid chemical inhibitor of Skp2-mediated degradation of p27 has not been identified. Recently, an increasing number of compounds designed to have this bioactivity have been reported. Here, we conduct a meta-analysis of the evidence regarding bioactivity, structure, and medicinal chemistry in order to evaluate and compare these Skp2 inhibitor compounds. Despite chemically diverse compounds with a wide array of Skp2-mediated p27 ubiquitylation inhibition properties reported by several independent groups, no current chemical probe formally qualifies as a validated pharmaceutical hit compound. This finding suggests that our knowledge of the structural biochemistry of the Skp2-p27 complex remains incomplete and highlights the need for novel modes of inquiry.

To evaluate comparative efficiency of traditional vs automated colony counting methods, cultures of Escherichia coli (ATCC 25945), Staphylococcus epidermidis (ATCC 12225), Streptococcus pyogenes (ATCC19615) and Streptococcus pneumoniae (ATCC49619) were prepared as pure cultures and mixed cultures at 0·5 McFarland standard and serial dilutions were performed. Plates were inoculated in triplicate with 50, 125, 250 and 500 colony forming units and counted by four researchers, visually and using each of the automated counters. Colony count and counting time were recorded. The pattern of efficiency for all bacterial species was similar: plates with low counts were accurate and quick to count for all methods, with an increase in time and a decrease in accuracy and precision as counts rose. Higher counts of single round colonies required less time and had greater precision with automated counters than human visual counting counts with no loss of accuracy; however, counts were reduced in accuracy and increased in time for species with less regular morphology or when plates had mixed species. Surprisingly, a free phone application was only slightly less precise and more time consuming than the high-end professional counter indicating that automation may be achievable at lower cost than expected., Significance and Impact of the Study: Colony quantification is essential in clinical and research settings as well as pedagogy at the college level. Human visual (HV) counting, the most common method, is time consuming and fraught with errors. The time, accuracy and precision of HV counting were compared to a high-end professional automated counter, an inexpensive phone application and a free phone application. Low cost benefits of increased speed and accuracy with automated counting are maximized when counting single round colonies; but much reduced if colonies have irregular morphology or demonstrate haemolysis., (© 2018 The Society for Applied Microbiology.)

The international community has advocated the adoption of climate-smart agriculture (CSA) as lower-income countries deal with the negative consequences of climate change. Scaling up such policies, practices, and programs successfully will require support from a variety of local stakeholders. Such support requires alignment between CSA solutions and the problem understandings of stakeholders. However, problem understandings can differ across individuals, stakeholder groups, and geographic areas. Consequently, we examine understandings of climate problems and socioeconomic and infrastructure problems related to agriculture among different stakeholder groups in Uganda and Senegal. We operationalized and measured these problem understandings following the detailed guidance of the political will and public will approach for analyzing social change. Semi-structured interviews elicited stakeholder-generated lists of problems for each group. Limited quantification of problem understandings and their relative importance or "ripeness" demonstrates how contexts might shape opportunities for CSA.