Physiological and Molecular Outcomes of Chronic Post-Weaning Folate Deficiency

Folate is an essential B vitamin that serves as a primary one-carbon carrier in a number of essential cellular reactions; among these reactions are synthesis of purines, thymidylate, and methionine. As a result of these synthesis reactions, folate plays a key role in regulating nucleic acid metabolism, amino acid metabolism, maintenance of DNA stability, and production of S-adenosylmethionine for methylation of nucleic acids, neurotransmitters, phospholipids, histones, and other proteins. As such, folate deficiency is associated with a number of adverse outcomes including various cancers, cardiovascular disease, and cognitive defects. Despite mandatory folate fortification in grains in many developed countries, a number of people groups remain at risk for folate deficiency due to various disease conditions and lifestyle choices such as smoking and alcoholism, many of which arise in early adulthood and persist for the remainder of life. Using a mouse model of folate deficiency beginning post-weaning and persisting through the duration of the adult life, we examine the outcome of chronic folate deficiency in two key tissues: the hippocampus and the liver. The hippocampus was chosen as a tissue of focus due to its central role in cognition. The liver was chosen as the second tissue of focus because of its central role in folate storage and metabolism. Folate deficient mice exhibited memory deficits beginning in early adulthood and persisting through late adulthood. These deficits were linked to differential expression of a number of hippocampal genes in a tissue-specific manner, and enrichment of several transcription factor binding sites were found to be associated with the differentially expressed genes. These genes may represent targets for understanding and treating diseases associated with cognitive decline, such as Alzheimer’s disease. Further, significant site-specific changes in methylation of promoter regions of hepatic genes were observed; however, no significant changes in gene expression were determined, both by global expression analysis using microarrays and by specific expression analysis of a number of tumor suppressor genes by quantitative PCR. Since promoter methylation is often inversely related to gene expression, the lack of expression changes was surprising. This may indicate that many of the differentially methylated promoter regions do not significantly impact gene expression. Gad1, a tumor suppressor gene associated with liver cancer, exhibited significant promoter hypermethylation in response to folate deficiency. Bisulfite sequencing of portions of the Gad1 promoter region showed differential methylation patterns that may indicate that methylation downstream of the transcription start site of this gene has a greater impact on gene expression that methylation in upstream promoter regions. Together, these results show a relative resiliency of the liver in resisting adverse outcomes of chronic folate deficiency, such as differential expression of tumor suppressor genes, despite significant changes in methylation. The mechanisms by which the liver so propitiously resists negative outcomes of this methyl donor deficiency may serve as a template for treating this deficiency in less resilient tissues by comparing liver-specific pathways to similar pathways in other tissues

Raising awareness of Asperger’s Syndrome amongst coaches and athletes: the power of virtual support networks

The Virtual Alliance for sport technology (V.A.S.T) is an online tool utilised by a community of experts and practitioners to facilitate the generation and sharing of knowledge in order to promote inclusion in sport. The principal aim of the present study was to utilise this platform to create and evaluate an online teaching resource to provide support for coaches working with athletes with Asperger’s Syndrome. At present little information is provided by National governing bodies about Asperger’s, and as a consequence many athletes can be marginalised in sports provision. A methods-driven evaluative framework was adopted in order to assess the impact of the web-tool. Gantt timelines and a programme theory were produced prior to the project, and programme processes were evaluated throughout. Website impact was assessed via triangulation of statistical analysis regarding website usage with interviews conducted with network users. Results were interpreted using a figurational framework to investigate how information about the web-tool was disseminated and transformed through virtual networks of interdependencies which linked participants diagnosed with Asperger syndrome, their coaches and the online community. Results gained from this project are expected to highlight how web-based platforms have the capability to bring together otherwise marginalised groups with virtual networks of sports experts, athletes and practitioners. The implications of these results will increase awareness of participants with Asperger’s syndrome within sport and provide coaches, athletes and policy makers with information that will enable them to effectively teach and support sports participants with Asperger’s syndrome in an athlete-centric manner

Counseling Problems that Accompany the Diagnosis of Mental Retardation

This is a report of a descriptive study in which a random sample of fifty out of four hundred returned questionnaires from parents with a mentally retarded child were analyzed. The foci of analysis were: (1) parental attitudes toward the child; (2) the changes experienced by the family as affected by birth order and sex of the mentally retarded child; (3) how the diagnosis was accomplished; and (4) how in their opinion services during this diagnostic period could be improved. The data revealed that: (1) protectiveness toward the child is the predominant parental response; (2) negative changes are probably twice as high with an only child who is retarded; (3) male retardates are somewhat more disruptive than are female; (4) diagnosis must be individualized; however, generalizations which can be made include: understandable language, patience, empathy, and above all honesty

The Home Environment Interview and associations with energy balance behaviours and body weight in school-aged children - a feasibility, reliability, and validity study.

BACKGROUND: The home environment is thought to influence children's weight trajectories. However, few studies utilise composite measures of the home environment to examine associations with energy balance behaviours and weight. The present study aimed to adapt and update a comprehensive measure of the obesogenic home environment previously developed for pre-schoolers, and explore associations with school-aged children's energy balance behaviours and weight. METHODS: Families from the Gemini cohort (n = 149) completed the Home Environment Interview (HEI) via telephone when their children were 12 years old. The HEI comprises four composite scores: one for each domain (food, activity and media) of the environment, as well as a score for the overall obesogenic home environment. The primary caregiver also reported each child's height and weight (using standard scales and height charts), diet, physical activity and sedentary screen-based behaviours. A test-retest sample (n = 20) of caregivers completed the HEI a second time, 7-14 days after the initial interview, to establish test-retest reliability. RESULTS: Children (n = 298) living in 'higher-risk' home environments (a 1 unit increase in the HEI obesogenic risk score) were less likely to consume fruits (OR; 95% CI = 0.40; 0.26-0.61, p < 0.001), and vegetables (0.30; 0.18-0.52, p < 0.001), and more likely to consume energy-dense snack foods (1.71; 1.08-2.69, p = 0.022), convenience foods (2.58; 1.64-4.05, p < 0.001), and fast foods (3.09; 1.90-5.04, p < 0.001). Children living in more obesogenic home environments also engaged in more screen-time (β (SE) = 4.55 (0.78), p < 0.001), spent more time playing video games (β (SE) = 1.56 (0.43), p < 0.001), and were less physically active (OR; 95% CI = 0.57; 0.40-0.80, p < 0.01). Additionally, there was a positive association between higher-risk overall home environment composite score and higher BMI-SDS (β (SE) = 0.23 (0.09), p < 0.01). This finding was mirrored for the home media composite (β (SE) = 0.12 (0.03), p < 0.001). The individual home food and activity composite scores were not associated with BMI-SDS. CONCLUSION: Findings reveal associations between the overall obesogenic home environment and dietary intake, activity levels and screen-based sedentary behaviours, as well as BMI in 12 year olds. These findings suggest that the home environment, and in particular the home media environment, may be an important target for obesity prevention strategies

Effectiveness of a national quality improvement programme to improve survival after emergency abdominal surgery (EPOCH): a stepped-wedge cluster-randomised trial

Background: Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for these patients. Methods: We did a stepped-wedge cluster-randomised trial of patients aged 40 years or older undergoing emergency open major abdominal surgery. Eligible UK National Health Service (NHS) hospitals (those that had an emergency general surgical service, a substantial volume of emergency abdominal surgery cases, and contributed data to the National Emergency Laparotomy Audit) were organised into 15 geographical clusters and commenced the QI programme in a random order, based on a computer-generated random sequence, over an 85-week period with one geographical cluster commencing the intervention every 5 weeks from the second to the 16th time period. Patients were masked to the study group, but it was not possible to mask hospital staff or investigators. The primary outcome measure was mortality within 90 days of surgery. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN80682973. Findings: Treatment took place between March 3, 2014, and Oct 19, 2015. 22 754 patients were assessed for elegibility. Of 15 873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 patients in the usual care group and 7374 in the QI group. Eight patients in the usual care group and nine patients in the QI group were not included in the analysis because of missing primary outcome data. The primary outcome of 90-day mortality occurred in 1210 (16%) patients in the QI group compared with 1393 (16%) patients in the usual care group (HR 1·11, 0·96–1·28). Interpretation: No survival benefit was observed from this QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. Future QI programmes should ensure that teams have both the time and resources needed to improve patient care. Funding: National Institute for Health Research Health Services and Delivery Research Programme

Effectiveness of a national quality improvement programme to improve survival after emergency abdominal surgery (EPOCH): a stepped-wedge cluster-randomised trial

BACKGROUND: Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for these patients. METHODS: We did a stepped-wedge cluster-randomised trial of patients aged 40 years or older undergoing emergency open major abdominal surgery. Eligible UK National Health Service (NHS) hospitals (those that had an emergency general surgical service, a substantial volume of emergency abdominal surgery cases, and contributed data to the National Emergency Laparotomy Audit) were organised into 15 geographical clusters and commenced the QI programme in a random order, based on a computer-generated random sequence, over an 85-week period with one geographical cluster commencing the intervention every 5 weeks from the second to the 16th time period. Patients were masked to the study group, but it was not possible to mask hospital staff or investigators. The primary outcome measure was mortality within 90 days of surgery. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN80682973. FINDINGS: Treatment took place between March 3, 2014, and Oct 19, 2015. 22 754 patients were assessed for elegibility. Of 15 873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 patients in the usual care group and 7374 in the QI group. Eight patients in the usual care group and nine patients in the QI group were not included in the analysis because of missing primary outcome data. The primary outcome of 90-day mortality occurred in 1210 (16%) patients in the QI group compared with 1393 (16%) patients in the usual care group (HR 1·11, 0·96-1·28). INTERPRETATION: No survival benefit was observed from this QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. Future QI programmes should ensure that teams have both the time and resources needed to improve patient care. FUNDING: National Institute for Health Research Health Services and Delivery Research Programme

Investigation of hospital discharge cases and SARS-CoV-2 introduction into Lothian care homes

Background The first epidemic wave of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Scotland resulted in high case numbers and mortality in care homes. In Lothian, over one-third of care homes reported an outbreak, while there was limited testing of hospital patients discharged to care homes. Aim To investigate patients discharged from hospitals as a source of SARS-CoV-2 introduction into care homes during the first epidemic wave. Methods A clinical review was performed for all patients discharges from hospitals to care homes from 1st March 2020 to 31st May 2020. Episodes were ruled out based on coronavirus disease 2019 (COVID-19) test history, clinical assessment at discharge, whole-genome sequencing (WGS) data and an infectious period of 14 days. Clinical samples were processed for WGS, and consensus genomes generated were used for analysis using Cluster Investigation and Virus Epidemiological Tool software. Patient timelines were obtained using electronic hospital records. Findings In total, 787 patients discharged from hospitals to care homes were identified. Of these, 776 (99%) were ruled out for subsequent introduction of SARS-CoV-2 into care homes. However, for 10 episodes, the results were inconclusive as there was low genomic diversity in consensus genomes or no sequencing data were available. Only one discharge episode had a genomic, time and location link to positive cases during hospital admission, leading to 10 positive cases in their care home. Conclusion The majority of patients discharged from hospitals were ruled out for introduction of SARS-CoV-2 into care homes, highlighting the importance of screening all new admissions when faced with a novel emerging virus and no available vaccine

SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant

Associations between the home environment and childhood weight change: a cross-lagged panel analysis.

BACKGROUND: The obesogenic quality of the home environment is hypothesised to play an important role in children's weight development but few prospective studies have investigated relationships between the home environment and adiposity across childhood. OBJECTIVE: To investigate the continuity and stability of the home environment from ages 4 to 12, and bi-directional relationships between the home environment and BMI-SDS from ages 4 to 12. METHODS: Parents from the Gemini cohort completed the Home Environment Interview (HEI), a comprehensive measure of the obesogenic home environment, when their children were aged 4 and 12 (n = 149 families, n = 298 children). The obesogenic home environment was measured using four composite scores capturing the food, activity, media environments, and the overall home environment. Child weights and heights were used to calculate BMI-SDS. Continuity was assessed with Pearson's correlations between scores at each time point, and stability by changes in mean scores over time. Cross-lagged analyses were performed (HEI composites at age 4 to BMI-SDS at age 12 and the reverse) to measure the magnitude and direction of associations. RESULTS: The home environment showed moderate-to-high continuity from ages 4 to 12 (r = 0.30-0.64). The overall home environment (r = 0.21, p < 0.01) and media composites (r = 0.23, p < 0.01) were cross-sectionally associated with child BMI-SDS at age 12, but not at age 4. Longitudinally, the home media environment at age 4 predicted increases in child BMI-SDS at age 12 (β; 95% CI = 0.18; 0.08,0.28, p < 0.01). No associations were observed for the reverse path, or the remaining composites (the overall, food and activity) in either direction. CONCLUSION: This study provides evidence that the obesogenic home environment tracks across childhood and highlights the importance of the early home media environment for child weight development. The findings provide insight into key aspects of the home environment that could be targeted when developing obesity treatment or prevention strategies

Recoverable resources from pot ale and spent wash from Scotch whisky production.

Scotch Whisky is an important global commodity which generates extensive co-product known as pot ale or spent wash (> 10 L co-product per L whisky). Whilst this is often used as fertiliser or animal feed, a proportion requires disposal resulting in cost to the distillery along with the negative impact on the carbon footprint due to transportation. This study examined the composition of the soluble fraction of pot ale from twenty-two distilleries in Scotland in order to assess the potential for resource recovery and transition to a more circular economy. The results reinforced previous studies, demonstrating that pot ale is an excellent source of protein with a potential for recovery >150, 000 t per annum in Scotland based on Whisky production data. Lactic acid, an important industrial platform chemical, was the major organic acid produced with concentrations ranging from 0.3 to 6.6 g L−1, representing a potential opportunity for recovery for applications such as manufacture of biodegradable polylactic acid for plastics (> 15,000 t per annum based on mean values). Other important platform chemicals, succinic acid and lysine were also identified and considered in sufficient amounts for future use. Pot ale was also shown to contain significant amounts of critical raw materials, magnesium and phosphate, which could be reclaimed for use in fertiliser/feed supporting the development of a new circular economy whilst at the same time reducing the burden of mining and transportation on the environment. The data in this study demonstrated a potential 13.8 kt recoverable phosphate per annum representing more than half of the annual fertiliser consumption in Scotland. Whisky co-products can contribute to sustainable energy, food and platform chemicals with the added value that metal concentrations are not sufficiently high to prevent its utilisation