An International, Multidisciplinary Consensus Set of Patient-Centered Outcome Measures for Substance-Related and Addictive Disorders.

Background: In 1990, the United States' Institute of Medicine promoted the principles of outcomes monitoring in the alcohol and other drugs treatment field to improve the evidence synthesis and quality of research. While various national outcome measures have been developed and employed, no global consensus on standard measurement has been agreed for addiction. It is thus timely to build an international consensus. Convened by the International Consortium for Health Outcomes Measurement (ICHOM), an international, multi-disciplinary working group reviewed the existing literature and reached consensus for a globally applicable minimum set of outcome measures for people who seek treatment for addiction. Methods: To this end, 26 addiction experts from 11 countries and 5 continents, including people with lived experience (n = 5; 19%), convened over 16 months (December 2018-March 2020) to develop recommendations for a minimum set of outcome measures. A structured, consensus-building, modified Delphi process was employed. Evidence-based proposals for the minimum set of measures were generated and discussed across eight videoconferences and in a subsequent structured online consultation. The resulting set was reviewed by 123 professionals and 34 people with lived experience internationally. Results: The final consensus-based recommendation includes alcohol, substance, and tobacco use disorders, as well as gambling and gaming disorders in people aged 12 years and older. Recommended outcome domains are frequency and quantity of addictive disorders, symptom burden, health-related quality of life, global functioning, psychosocial functioning, and overall physical and mental health and wellbeing. Standard case-mix (moderator) variables and measurement time points are also recommended. Conclusions: Use of consistent and meaningful outcome measurement facilitates carer-patient relations, shared decision-making, service improvement, benchmarking, and evidence synthesis for the evaluation of addiction treatment services and the dissemination of best practices. The consensus set of recommended outcomes is freely available for adoption in healthcare settings globally.

Present-day thermal and water activity environment of the Mars Sample Return collection.

The Mars Sample Return mission intends to retrieve a sealed collection of rocks, regolith, and atmosphere sampled from Jezero Crater, Mars, by the NASA Perseverance rover mission. For all life-related research, it is necessary to evaluate water availability in the samples and on Mars. Within the first Martian year, Perseverance has acquired an estimated total mass of 355 g of rocks and regolith, and 38 µmoles of Martian atmospheric gas. Using in-situ observations acquired by the Perseverance rover, we show that the present-day environmental conditions at Jezero allow for the hydration of sulfates, chlorides, and perchlorates and the occasional formation of frost as well as a diurnal atmospheric-surface water exchange of 0.5-10 g water per m2 (assuming a well-mixed atmosphere). At night, when the temperature drops below 190 K, the surface water activity can exceed 0.5, the lowest limit for cell reproduction. During the day, when the temperature is above the cell replication limit of 245 K, water activity is less than 0.02. The environmental conditions at the surface of Jezero Crater, where these samples were acquired, are incompatible with the cell replication limits currently known on Earth.

UPDATE trial: investigating the effects of ultra-processed versus minimally processed diets following UK dietary guidance on health outcomes: a protocol for an 8-week community-based cross-over randomised controlled trial in people with overweight or obesity, followed by a 6-month behavioural intervention.

INTRODUCTION: Obesity increases the risk of morbidity and mortality. A major driver has been the increased availability of ultra-processed food (UPF), now the main UK dietary energy source. The UK Eatwell Guide (EWG) provides public guidance for a healthy balanced diet but offers no UPF guidance. Whether a healthy diet can largely consist of UPFs is unclear. No study has assessed whether the health impact of adhering to dietary guidelines depends on food processing. Furthermore, our study will assess the impact of a 6-month behavioural support programme aimed at reducing UPF intake in people with overweight/obesity and high UPF intakes. METHODS AND ANALYSIS: UPDATE is a 2×2 cross-over randomised controlled trial with a 6-month behavioural intervention. Fifty-five adults aged ≥18, with overweight/obesity (≥25 to <40 kg/m2), and ≥50% of habitual energy intake from UPFs will receive an 8-week UPF diet and an 8-week minimally processed food (MPF) diet delivered to their home, both following EWG recommendations, in a random order, with a 4-week washout period. All food/drink will be provided. Participants will then receive 6 months of behavioural support to reduce UPF intake. The primary outcome is the difference in weight change between UPF and MPF diets from baseline to week 8. Secondary outcomes include changes in diet, waist circumference, body composition, heart rate, blood pressure, cardiometabolic risk factors, appetite regulation, sleep quality, physical activity levels, physical function/strength, well-being and aspects of behaviour change/eating behaviour at 8 weeks between UPF/MPF diets, and at 6-month follow-up. Quantitative assessment of changes in brain MRI functional resting-state connectivity between UPF/MPF diets, and qualitative analysis of the behavioural intervention for feasibility and acceptability will be undertaken. ETHICS AND DISSEMINATION: Sheffield Research Ethics Committee approved the trial (22/YH/0281). Peer-reviewed journals, conferences, PhD thesis and lay media will report results. TRIAL REGISTRATION NUMBER: NCT05627570.

The impact of the cost of living crisis and food insecurity on food purchasing behaviours and food preparation practices in people living with obesity.

Lower income households are at greater risk of food insecurity and poor diet quality than higher income households. In high-income countries, food insecurity is associated with high levels of obesity, and in the UK specifically, the cost of living crisis (i.e., where the cost of everyday essentials has increased quicker than wages) is likely to have exacerbated existing dietary inequalities. There is currently a lack of understanding of the impact of the current UK cost of living crisis on food purchasing and food preparation practices of people living with obesity (PLWO) and food insecurity, however this knowledge is critical in order to develop effective prevention and treatment approaches to reducing dietary inequalities. Using an online survey (N = 583) of adults residing in England or Scotland with a body mass index (BMI) of ≥30 kg/m2, participants self-reported on food insecurity, diet quality, perceived impact of the cost of living crisis, and their responses to this in terms of food purchasing behaviours and food preparation practices. Regression analyses found that participants adversely impacted by the cost of living crisis reported experiencing food insecurity. Additionally, food insecurity was associated with use of specific purchasing behaviours (i.e., use of budgeting, use of supermarket offers) and food preparation practices (i.e., use of energy-saving appliances, use of resourcefulness). Exploratory analyses indicated that participants adversely impacted by the cost of living crisis and who used budgeting had low diet quality, whereas use of meal planning was associated with high diet quality. These findings highlight the fragility of food budgets and the coping strategies used by PLWO and food insecurity during the cost of living crisis. Policy measures and interventions are urgently needed that address the underlying economic factors contributing to food insecurity, to improve access to and affordability of healthier foods for all.

Real-world data of a digitally enabled, time-restricted eating weight management program in public sector workers living with overweight and obesity in the United Kingdom: A service evaluation of the Roczen program.

Introduction: The health of the United Kingdom workforce is key; approximately 186 million days are lost to sickness each year. Obesity and type 2 diabetes (T2D) remain major global health challenges. The aim of this retrospective service evaluation was to assess the impact of a digitally enabled, time-restricted eating (TRE) intervention (Roczen Program, Reset Health Ltd) on weight and other health-related outcomes. Methods: This service evaluation was conducted in people living with overweight/obesity, with 89% referred from public sector employers. Participants were placed on a TRE, low-carbohydrate, moderate protein plan delivered by clinicians and mentors with regular follow up, dietary guidance, goal setting, feedback, and social support. Results: A total of 660 members enrolled and retention was 41% at 12 months. The majority were female (73.2%), 58.9% were of White ethnicity, with a mean (SD) age of 47.5 years (10.1), and a body mass index of 35.0 kg/m2 (5.7). Data were available for 82 members at 12-month. At 12-month, members mean actual and percentage weight loss was -9.0 kg (7.0; p < 0.001) and -9.2% (6.7, p < 0.001) respectively and waist circumference reduced by -10.3 cm (10.7 p < 0.001), with 45.1% of members achieving ≥10% weight loss. Glycated hemoglobin was significantly improved at 6 months in people living with T2D (-11 mmol/mol [5.7] p = 0.012). Binge eating score significantly reduced (-4.4 [7.0] p = 0.006), despite cognitive restraint increasing (0.37 [0.6] p = 0.006). Conclusion: Our service evaluation showed that the Roczen program led to clinically meaningful improvements in body weight, health-related outcomes and eating behaviors that were sustained at 12-month.

Digital adaptation of the Standing up for Myself intervention in young people and adults with intellectual disabilities: the STORM feasibility study.

Background: Stigma contributes to the negative social conditions persons with intellectual disabilities are exposed to, and it needs tackling at multiple levels. Standing Up for Myself is a psychosocial group intervention designed to enable individuals with intellectual disabilities to discuss stigmatising encounters in a safe and supportive setting and to increase their self-efficacy in managing and resisting stigma. Objectives: To adapt Standing Up for Myself to make it suitable as a digital intervention; to evaluate the feasibility and acceptability of Digital Standing Up for Myself and online administration of outcome measures in a pilot; to describe usual practice in the context of the coronavirus disease 2019 pandemic to inform future evaluation. Design: Adaptation work followed by a single-arm pilot of intervention delivery. Setting and participants: Four third and education sector organisations. Individuals with mild-to-moderate intellectual disabilities, aged 16+, members of existing groups, with access to digital platforms. Intervention: Digital Standing Up for Myself intervention. Adapted from face-to-face Standing Up for Myself intervention, delivered over four weekly sessions, plus a 1-month follow-up session. Outcomes: Acceptability and feasibility of delivering Digital Standing Up for Myself and of collecting outcome and health economic measures at baseline and 3 months post baseline. Outcomes are mental well-being, self-esteem, self-efficacy in rejecting prejudice, reactions to discrimination and sense of social power. Results: Adaptation to the intervention required changes to session duration, group size and number of videos; otherwise, the content remained largely the same. Guidance was aligned with digital delivery methods and a new group member booklet was produced. Twenty-two participants provided baseline data. The intervention was started by 21 participants (four groups), all of whom were retained at 3 months. Group facilitators reported delivering the intervention as feasible and suggested some refinements. Fidelity of the intervention was good, with over 90% of key components observed as implemented by facilitators. Both facilitators and group members reported the intervention to be acceptable. Group members reported subjective benefits, including increased confidence, pride and knowing how to deal with difficult situations. Digital collection of all outcome measures was feasible and acceptable, with data completeness ≥ 95% for all measures at both time points. Finally, a picture of usual practice has been developed as an intervention comparator for a future trial. Limitations: The pilot sample was small. It remains unclear whether participants would be willing to be randomised to a treatment as usual arm or whether they could be retained for 12 months follow-up. Conclusions: The target number of groups and participants were recruited, and retention was good. It is feasible and acceptable for group facilitators with some training and supervision to deliver Digital Standing Up for Myself. Further optimisation of the intervention is warranted. Future work: To maximise the acceptability and reach of the intervention, a future trial could offer the adapted Digital Standing Up for Myself, potentially alongside the original face-to-face version of the intervention. Study registration: This study was registered as ISRCTN16056848. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme (NIHR award ref: 17/149/03) and is published in full in Public Health Research; Vol. 12, No. 1. See the NIHR Funding and Awards website for further award information.

People with intellectual disabilities (or 'learning disabilities' in United Kingdom language) are more likely to experience poor physical and mental health than the general population. Stigma (negative stereotypes, prejudice and discrimination) has been linked to lower self-esteem, quality of life, and mental and physical ill health. Efforts to empower people with intellectual disabilities themselves to challenge stigma with a view to improving well-being, health and self-esteem are lacking. In 2017, we developed Standing Up for Myself, a brief group-based programme for people with mild-to-moderate intellectual disabilities aged 16+ to address this gap. As this study got underway, face-to-face meetings were suspended due to the coronavirus disease 2019 pandemic. We used the opportunity to assess whether Standing Up for Myself could be delivered through web-based meetings. We adapted Standing Up for Myself for digital delivery, with close input from advisors with intellectual disabilities and experienced group facilitators. We then tested the digital version in charity and education settings to evaluate if Digital Standing Up for Myself could be delivered as planned and how acceptable it was to group facilitators and participants. Four groups, with a total of 22 members, signed up to try Digital Standing Up for Myself. One participant dropped out before starting Standing Up for Myself, and the other 21 continued until the end of the programme. Retention and attendance were good; participants on average attended four of the five sessions. Ninety per cent of the core programme requirements were fully delivered as detailed in the Digital Standing Up for Myself manual. Problems with technology were manageable, although facilitators found using the Standing Up for Myself Wiki platform (an online platform for storage and sharing of resources) difficult, particularly when sharing video content. Facilitators felt acceptable levels of privacy were achieved and there were no reports of undue distress. All facilitators and many group members said they would recommend Digital Standing Up for Myself to others. Group members shared how the programme benefitted them, noting increased awareness about disabilities, and for some increased confidence, pride and independence. Some had learnt how to stand up for themselves and manage difficult situations and took pride in this. Completing outcome and health cost measures via web-based meetings was acceptable and data were largely fully complete and useable.

Nutrients or processing? An analysis of food and drink items from the UK National Diet and Nutrition Survey based on nutrient content, the NOVA classification and front of package traffic light labelling.

UK front of package labelling (FOPL) informs consumers on the nutrient content of food. However, FOPL does not consider food processing, and with the UK government being urged to act on ultra-processed food (UPF), whether UPF should be added to FOPL is unclear. This study compared food and drink in the UK National Diet and Nutrition Survey (NDNS) Intake24 database based on FOPL, nutrient content and NOVA classification, to understand whether UPF are covered by dietary recommendations for foods high in fat, salt and sugar. NDNS items were coded into minimally processed food (MPF), processed culinary ingredients, processed food and UPF according to the NOVA classification and FOPL traffic lights. UPF contained greater energy, fat, saturated fat (SF), total sugar (TS) and salt than MPF. UPF had a greater odds of containing red FOPL and an unhealthier overall FOPL score (OR:4·59 (95 % CI: 3·79, 5·57); OR:7·0 (95 % CI: 6·1, 8·2), respectively) and lower odds of containing green FOPL (OR:0·05 (95 % CI: 0·03, 0·10)), compared with MPFs. For items with no red FOPL, UPF still contained greater energy, fat, SF, TS and salt than MPF. However, several UPF have healthier FOPL scores. UPF had an unhealthier nutritional profile and FOPL score than MPF. For items with no red FOPL, UPF still had an unhealthier profile than MPF, with a higher energy density. Importantly, not all UPF were unhealthy according to FOPL. These results indicate partial overlap between FOPL, nutrient content and NOVA classification of UK food and drink products, with implications for UK food and drink labelling.

Does a Ketogenic Diet Have a Place Within Diabetes Clinical Practice? Review of Current Evidence and Controversies.

Carbohydrate restriction has gained increasing popularity as an adjunctive nutritional therapy for diabetes management. However, controversy remains regarding the long-term suitability, safety, efficacy and potential superiority of a very low carbohydrate, ketogenic diet compared to current recommended nutritional approaches for diabetes management. Recommendations with respect to a ketogenic diet in clinical practice are often hindered by the lack of established definition, which prevents its capacity to be most appropriately prescribed as a therapeutic option for diabetes. Furthermore, with conflicted evidence, this has led to uncertainty amongst clinicians on how best to support and advise their patients. This review will explore whether a ketogenic diet has a place within clinical practice by reviewing current evidence and controversies.

Improvements in Sperm Motility Following Low- or High-Intensity Dietary Interventions in Men With Obesity.

INTRODUCTION: Obesity increases risks of male infertility, but bariatric surgery does not improve semen quality. Recent uncontrolled studies suggest that a low-energy diet (LED) improves semen quality. Further evaluation within a randomized, controlled setting is warranted. METHODS: Men with obesity (18-60 years) with normal sperm concentration (normal count) (n = 24) or oligozoospermia (n = 43) were randomized 1:1 to either 800 kcal/day LED for 16 weeks or control, brief dietary intervention (BDI) with 16 weeks' observation. Semen parameters were compared at baseline and 16 weeks. RESULTS: Mean age of men with normal count was 39.4 ± 6.4 in BDI and 40.2 ± 9.6 years in the LED group. Mean age of men with oligozoospermia was 39.5 ± 7.5 in BDI and 37.7 ± 6.6 years in the LED group. LED caused more weight loss than BDI in men with normal count (14.4 vs 6.3 kg; P < .001) and men with oligozoospermia (17.6 vs 1.8 kg; P < .001). Compared with baseline, in men with normal count total motility (TM) increased 48 ± 17% to 60 ± 10% (P < .05) after LED, and 52 ± 8% to 61 ± 6% (P < .0001) after BDI; progressive motility (PM) increased 41 ± 16% to 53 ± 10% (P < .05) after LED, and 45 ± 8% to 54 ± 65% (P < .001) after BDI. In men with oligozoospermia compared with baseline, TM increased 35% [26] to 52% [16] (P < .05) after LED, and 43% [28] to 50% [23] (P = .0587) after BDI; PM increased 29% [23] to 46% [18] (P < .05) after LED, and 33% [25] to 44% [25] (P < .05) after BDI. No differences in postintervention TM or PM were observed between LED and BDI groups in men with normal count or oligozoospermia. CONCLUSION: LED or BDI may be sufficient to improve sperm motility in men with obesity. The effects of paternal dietary intervention on fertility outcomes requires investigation.

Veteran Caretaker Perspectives of the Need for Childcare Assistance During Health Care Appointments.

PURPOSE: In 2020, Congress passed legislation to establish the national Veterans Child Care Assistance Program (VCAP) targeting eligible veterans receiving care through the Veterans Health Administration (VA). This needs assessment describes the childcare needs of veteran caretakers of young children and explores the implications of inadequate childcare on health care engagement. METHODS: Survey data were collected from 2,000 VA users with dependent children; data were analyzed using standard descriptive statistics. Qualitative data were collected from 19 veterans through focus groups and analyzed using rapid thematic analysis. FINDINGS: More than 75% of veterans surveyed indicated that they required childcare assistance during health care appointments and 73% reported barriers to finding childcare. Prominent barriers included the high cost of childcare and not having a trusted source of childcare. Nearly 58% of survey respondents reported missed or canceled VA health care appointments due to childcare challenges. Furthermore, 35% of surveyed veterans reported that their children had accompanied them to an appointment in the past year. Among these veterans, 59% brought their children into the exam room. Focus group participants discussed how having children present during their health care appointments hampered communication with health care providers. CONCLUSIONS: Veterans report that lack of childcare keeps them from attending and remaining focused on the provider during their health care visits, which could compromise quality of care. As one of the only health systems in the United States that will offer childcare assistance, VCAP presents an opportunity to improve health care access and quality by reducing missed appointments and suboptimal care.

Exogenous abscisic acid treatment regulates protein secretion in sorghum cell suspension cultures.

Drought stress adversely affects plant growth, often leading to total crop failure. Upon sensing soil water deficits, plants switch on biosynthesis of abscisic acid (ABA), a stress hormone for drought adaptation. Here, we used exogenous ABA application to dark-grown sorghum cell suspension cultures as an experimental system to understand how a drought-tolerant crop responds to ABA. We evaluated intracellular and secreted proteins using isobaric tags for relative and absolute quantification. While the abundance of only ~ 7% (46 proteins) intracellular proteins changed in response to ABA, ~32% (82 proteins) of secreted proteins identified in this study were ABA responsive. This shows that the extracellular matrix is disproportionately targeted and suggests it plays a vital role in sorghum adaptation to drought. Extracellular proteins responsive to ABA were predominantly defense/detoxification and cell wall-modifying enzymes. We confirmed that sorghum plants exposed to drought stress activate genes encoding the same proteins identified in the in vitro cell culture system with ABA. Our results suggest that ABA activates defense and cell wall remodeling systems during stress response. This could underpin the success of sorghum adaptation to drought stress.

Linkage of the Avon Longitudinal Study of Parents and Children (ALSPAC) to Avon & Somerset Police regional police records.

This data note describes a new resource for crime-related research: the Avon Longitudinal Study of Parents and Children (ALSPAC) linked to regional police records. The police data were provided by Avon & Somerset Police (A&SP), whose area of responsibility contains the ALSPAC recruitment area. In total, ALSPAC had permission to link to crime records for 12,662 of the 'study children' (now adults, who were born in the early 1990s).  The linkage took place in two stages: Stage 1 involved the ALSPAC Data Linkage Team establishing the linkage using personal identifiers common to both the ALSPAC participant database and A&SP records using deterministic and probabilistic methods. Stage 2 involved A&SP extracting attribute data on the matched individuals, removing personal identifiers and securely sharing the de-identified records with ALSPAC. The police data extraction took place in July 2021, when the participants were in their late 20s/early 30s. This data note contains details on the resulting linked police records available. In brief, electronic police records were available from 2007 onwards. In total, 1757 participants (14%) linked to at least one police record for a charge, offence 'taken into consideration', caution, or another out of court disposal. Linked participants had a total of 6413 records relating to 6283 offences. Almost three quarters of the linked participants were male. The most common offence types were violence against the person (22% of records), drug offences (19%), theft (17%) and public order offences (11%). This data note also details important issues that researchers using the local police data should be aware of, including the importance of defining an appropriate denominator, completeness, and biases affecting police records.

Heterologous production of the insecticidal pea seed albumin PA1 protein by Pichia pastoris and protein engineering to potentiate aphicidal activity via fusion to snowdrop lectin Galanthus nivalis agglutinin; GNA).

BACKGROUND: New bioinsecticides with novel modes of action are urgently needed to minimise the environmental and safety hazards associated with the use of synthetic chemical pesticides and to combat growing levels of pesticide resistance. The pea seed albumin PA1b knottin peptide is the only known proteinaceous inhibitor of insect vacuolar adenosine triphosphatase (V-ATPase) rotary proton pumps. Oral toxicity towards insect pests and an absence of activity towards mammals makes Pa1b an attractive candidate for development as a bioinsecticide. The purpose of this study was to investigate if Pichia pastoris could be used to express a functional PA1b peptide and if it's insecticidal activity could be enhanced via engineering to produce a fusion protein comprising the pea albumin protein fused to the mannose-specific snowdrop lectin (Galanthus nivalis agglutinin; GNA). RESULTS: We report the production of a recombinant full-length pea albumin protein (designated PAF) and a fusion protein (PAF/GNA) comprised of PAF fused to the N-terminus of GNA in the yeast Pichia pastoris. PAF was orally toxic to pea (Acyrthosiphon pisum) and peach potato (Myzus persicae) aphids with respective, Day 5 LC50 values of 54 µM and 105 µM derived from dose-response assays. PAF/GNA was significantly more orally toxic as compared to PAF, with LC50 values tenfold (5 µM) and 3.3-fold (32 µM) lower for pea and peach potato aphids, respectively. By contrast, no phenotypic effects were observed for worker bumble bees (Bombus terristrus) fed PAF, GNA or PAF/GNA in acute toxicity assays. Confocal microscopy of pea aphid guts after pulse-chase feeding fluorescently labelled proteins provides evidence that enhanced efficacy of the fusion protein is attributable to localisation and retention of PAF/GNA to the gut epithelium. In contact assays the fusion protein was also found to be significantly more toxic towards A. pisum as compared to PAF, GNA or a combination of the two proteins. CONCLUSIONS: Our results suggest that GNA mediated binding to V-type ATPase pumps acts to potentiate the oral and contact aphicidal activity of PAF. This work highlights potential for the future commercial development of plant protein-based bioinsecticides that offer enhanced target specificity as compared to chemical pesticides, and compatibility with integrated pest management strategies.

Safety and Efficacy of Liraglutide, 3.0 mg, Once Daily vs Placebo in Patients With Poor Weight Loss Following Metabolic Surgery: The BARI-OPTIMISE Randomized Clinical Trial.

Importance: Metabolic surgery leads to weight loss and improved health, but these outcomes are highly variable. Poor weight loss is associated with lower circulating levels of glucagon-like peptide-1 (GLP-1). Objective: To assess the efficacy and safety of the GLP-1 receptor agonist, liraglutide, 3.0 mg, on percentage body weight reduction in patients with poor weight loss and suboptimal GLP-1 response after metabolic surgery. Design, Setting, and Participants: The Evaluation of Liraglutide 3.0 mg in Patients With Poor Weight Loss and a Suboptimal Glucagon-Like Peptide-1 Response (BARI-OPTIMISE) randomized placebo-controlled trial recruited adult patients at least 1 year after metabolic surgery who had experienced 20% or less body weight loss from the day of surgery and a suboptimal nutrient-stimulated GLP-1 response from 2 hospitals in London, United Kingdom, between October 2018 and November 2019. Key exclusion criteria were type 1 diabetes; severe concomitant psychiatric, gastrointestinal, cardiac, kidney or metabolic disease; and use of insulin, GLP-1 receptor analogues, and medication that can affect weight. The study period was 24 weeks followed by a 4-week follow-up period. Last participant follow-up was completed in June 2020. All participants and clinical study personnel were blinded to treatment allocation. Of 154 assessed for eligibility, 70 met trial criteria and were included in the study, and 57 completed follow-up. Interventions: Liraglutide, 3.0 mg, once daily or placebo as an adjunct to lifestyle intervention with a 500-kcal daily energy deficit for 24 weeks, on a 1:1 allocation by computer-generated randomization sequence, stratified by surgery type (Roux-en-Y gastric bypass [RYGB] or sleeve gastrectomy [SG]) and type 2 diabetes status. Main Outcome and Measures: The primary outcome was change in percentage body weight from baseline to the end of the 24-week study period based on an intention-to-treat analysis. Participant safety was assessed through monitoring of biochemical parameters, including kidney and liver function, physical examination, and assessment for adverse events. Results: A total of 70 participants (mean [SD] age, 47.6 [10.7] years; 52 [74%] female) with a poor weight loss response following RYGB or SG were randomized to receive 3.0-mg liraglutide (n = 35) or placebo (n = 35). All participants received at least 1 dose of the trial drug. Eight participants discontinued treatment (4 per group), and 2 in the 3.0-mg liraglutide group and 1 in the placebo group were lost to follow-up. Due to COVID-19 restrictions, 3 participants in the 3.0-mg liraglutide group and 7 in the placebo group were unable to attend their final in-person assessment. Estimated change in mean (SD) percentage body weight from baseline to week 24 was -8.82 (4.94) with liraglutide, 3.0 mg (n = 31), vs -0.54 (3.32) with placebo (n = 26). The mean difference in percentage body weight change for liraglutide, 3.0 mg, vs placebo was -8.03 (95% CI, -10.39 to -5.66; P < .001). Adverse events, predominantly gastrointestinal, were more frequent with liraglutide, 3.0 mg (28 events [80%]), than placebo (20 events [57%]). There were no serious adverse events and no treatment-related deaths. Conclusion and Relevance: These findings support the use of adjuvant liraglutide, 3.0 mg, for weight management in patients with poor weight loss and suboptimal GLP-1 response after metabolic surgery. Trial Registration: ClinicalTrials.gov Identifier: NCT03341429.

Impact of nutritional-behavioral and supervised exercise intervention following bariatric surgery: The BARI-LIFESTYLE randomized controlled trial.

OBJECTIVE: The study's aim was to investigate the impact of a 12-month adjunctive lifestyle intervention on weight loss and health outcomes after bariatric surgery. METHODS: A total of 153 participants (78.4% females; mean [SD], age 44.2 [10.6] years; BMI 42.4 [5.7] kg/m2 ) were randomized to intervention (n = 79) and control (n = 74). The BARI-LIFESTYLE program combined 17 nutritional-behavioral tele-counseling sessions plus once-weekly supervised exercise for 12 weeks. The primary outcome was percentage weight loss at 6 months post surgery. Secondary outcomes included body composition, physical activity levels, physical function and strength, health-related quality of life, depressive symptomatology, and comorbidities. RESULTS: Longitudinal analysis of the entire cohort showed significant reductions in body weight, fat mass, fat-free mass, and bone mineral density at the total hip, femoral neck, and lumbar spine (all p < 0.001). The 6-minute walk test, sit-to-stand test, health-related quality of life, and depressive symptomatology improved significantly (all p < 0.001). The time spent in moderate-to-vigorous physical activity and sedentary behavior remained the same as before surgery (both p > 0.05). There was no significant difference in the primary outcome between the intervention versus control (20.4% vs. 21.2%; mean difference = -0.8%; 95% CI: -2.8 to 1.1; p > 0.05) and no between-group differences in secondary outcomes. CONCLUSIONS: An adjunctive lifestyle program implemented immediately after surgery had no favorable impact upon weight loss and health outcomes.

Independent Membrane Binding Properties of the Caspase Generated Fragments of the Beaded Filament Structural Protein 1 (BFSP1) Involves an Amphipathic Helix.

BACKGROUND: BFSP1 (beaded filament structural protein 1) is a plasma membrane, Aquaporin 0 (AQP0/MIP)-associated intermediate filament protein expressed in the eye lens. BFSP1 is myristoylated, a post-translation modification that requires caspase cleavage at D433. Bioinformatic analyses suggested that the sequences 434-452 were α-helical and amphipathic. METHODS AND RESULTS: By CD spectroscopy, we show that the addition of trifluoroethanol induced a switch from an intrinsically disordered to a more α-helical conformation for the residues 434-467. Recombinantly produced BFSP1 fragments containing this amphipathic helix bind to lens lipid bilayers as determined by surface plasmon resonance (SPR). Lastly, we demonstrate by transient transfection of non-lens MCF7 cells that these same BFSP1 C-terminal sequences localise to plasma membranes and to cytoplasmic vesicles. These can be co-labelled with the vital dye, lysotracker, but other cell compartments, such as the nuclear and mitochondrial membranes, were negative. The N-terminal myristoylation of the amphipathic helix appeared not to change either the lipid affinity or membrane localisation of the BFSP1 polypeptides or fragments we assessed by SPR and transient transfection, but it did appear to enhance its helical content. CONCLUSIONS: These data support the conclusion that C-terminal sequences of human BFSP1 distal to the caspase site at G433 have independent membrane binding properties via an adjacent amphipathic helix.

Systematic review of the barriers and facilitators to dietary modification in people living with type 2 diabetes and pre-diabetes from South Asian ethnic populations.

AIMS: Lifestyle and dietary modification are effective in the prevention and management of Type 2 diabetes Mellitus (T2DM). However, South Asian (SA) populations living in Western countries have low adherence rates to healthcare advice and experience poor diabetes control and clinical outcomes compared with the general population. This systematic review aimed to summarise the barriers and facilitators of dietary modification within people from South Asian (SA) ethnicity with T2DM or pre-diabetes. METHODS: A systematic search of PubMed, Web of Science and Scopus generated 3739 articles, of which seven were included. Qualitative and quantitative data were inputted utilising COVIDENCE. Qualitative data were analysed by thematic analysis. RESULTS: Thematic analysis identified three facilitators: (1) cultural sensitivity, (2) health education and (3) support networks. Barriers include (1) healthcare inequity, (2) cultural insensitivity, (3) social pressures, (4) misconceptions and (5) time constraints. Good access to health care and motivation were the most common facilitators discussed. Misconceptions on T2DM management and cultural insensitivity contributed to the majority of barriers discussed. CONCLUSIONS: Culturally tailored interventions could improve adherence to diet modification in people with T2DM from SA ethnicity. Interventions involving the application of social media to challenge intergenerational stigmas and misinformation, distributing culturally appropriate resources and providing diets tailored to the SA palate could help.

The implications of defining obesity as a disease: a report from the Association for the Study of Obesity 2021 annual conference.

Unlike various countries and organisations, including the World Health Organisation and the European Parliament, the United Kingdom does not formally recognise obesity as a disease. This report presents the discussion on the potential impact of defining obesity as a disease on the patient, the healthcare system, the economy, and the wider society. A group of speakers from a wide range of disciplines came together to debate the topic bringing their knowledge and expertise from backgrounds in medicine, psychology, economics, and politics as well as the experience of people living with obesity. The aim of their debate was not to decide whether obesity should be classified as a disease but rather to explore what the implications of doing so would be, what the gaps in the available data are, as well as to provide up-to-date information on the topic from experts in the field. There were four topics where speakers presented their viewpoints, each one including a question-and-answer section for debate. The first one focused on the impact that the recognition of obesity could have on people living with obesity regarding the change in their behaviour, either positive and empowering or more stigmatising. During the second one, the impact of defining obesity as a disease on the National Health Service and the wider economy was discussed. The primary outcome was the need for more robust data as the one available does not represent the actual cost of obesity. The third topic was related to the policy implications regarding treatment provision, focusing on the public's power to influence policy. Finally, the last issue discussed, included the implications of public health actions, highlighting the importance of the government's actions and private stakeholders. The speakers agreed that no matter where they stand on this debate, the goal is common: to provide a healthcare system that supports and protects the patients, strategies that protect the economy and broader society, and policies that reduce stigma and promote health equity. Many questions are left to be answered regarding how these goals can be achieved. However, this discussion has set a good foundation providing evidence that can be used by the public, clinicians, and policymakers to make that happen.

Mortality, Cardiovascular, and Medication Outcomes in Patients With Myocardial Infarction and Underweight in a Meta-Analysis of 6.3 Million Patients.

Although most of the current evidence on myocardial infarction focuses on obesity, there is growing evidence that patients who are underweight have unfavorable prognosis. This study aimed to explore the prevalence, clinical characteristics, and prognosis of this population at risk. Embase and Medline were searched for studies reporting outcomes in populations who were underweight with myocardial infarction. Underweight and normal weight were defined according to the World Health Organization criteria. A single-arm meta-analysis of proportions was used to estimate the prevalence of underweight in patients with myocardial infarction, whereas a meta-analysis of proportions was used to estimate the odds ratio of all-cause mortality, medications prescribed, and cardiovascular outcomes. Twenty-one studies involving 6,368,225 patients were included, of whom 47,866 were underweight. The prevalence of underweight in patients with myocardial infarction was 2.96% (95% confidence interval 1.96% to 4.47%). Despite having fewer classical cardiovascular risk factors, patients who were underweight had 66% greater hazard for mortality (hazard ratio 1.66, 95% confidence interval 1.44 to 1.92, p <0.0001). The mortality of patients who were underweight increased from 14.1% at 30 days to 52.6% at 5 years. Nevertheless, they were less likely to receive guideline-directed medical therapy. Relative to subjects with normal weight, Asian populations who were underweight had greater mortality risks than those of their Caucasian counterparts (p = 0.0062). In conclusion, in patients with myocardial infarction, those who were underweight tend to have poorer prognostic outcomes. A lower body mass index is an independent predictor of mortality, which calls for global efforts in addressing this modifiable risk factor in clinical practice guidelines.