The effects of nitrate-rich beetroot juice supplementation on nonverbal executive function in healthy recreationally active females

Nitrate-rich beetroot juice (BR) supplementation has been reported to preserve executive function (i.e. decision making and reaction time) before and after a simulated soccer match in recreationally active males, which may be due to enhanced cerebral blood flow. However, the literature examining the physiological response following BR ingestion in females is scarce, which hampers the extrapolation of results since physiological sex-differences may exist. Therefore, the purpose of this study was to assess if BR ingestion influenced executive function in an unfatigued and fatigued state in healthy recreationally active females. In a double-blind, randomized crossover design, 20 females consumed 140 mL of concentrated BR or nitrate-depleted placebo juice (PL) approximately 2.5 hours prior to each experimental visit. The Delis-Kaplan Executive Function (D-KEF) test, used for assessing higher-level cognitive function, was administered before and after completing a high-intensity intermittent running protocol. The D-KEF test involved 3 x 60-s conditions evaluating various cognitive tasks. A two-way repeated measures analysis of variance was conducted (n=15) and revealed no significant differences in executive function between PL (PRE: 15.27 ± 32.71 vs. POST: 16.93 ± 1.44) and BR (PRE: 15.80 ± 2.65 vs. POST: 16.60 ± 1.88). These preliminary data suggest that acute BR ingestion does not have an influence on processing and creative thinking of nonverbal executive function in an unfatigued or fatigued state in healthy recreationally active females, although importantly, the study is still in progress

The Effects of Acute Beetroot Juice Ingestion on Exercise and Cognitive Performance in Female Athletes

Nitrate-rich beetroot juice can enhance intense exercise performance which is attributed to enhanced skeletal muscle contractility. However, limited data exist in females and it is unknown whether dietary nitrate has an ergogenic effect in this population. PURPOSE: To investigate the potential effects of acute nitrate ingestion on a battery of exercise performance and cognitive tests before and after fatiguing intermittent running exercise. METHODS: Fifteen female team-sport athletes were assigned in a randomized, double-blind, crossover design to consume nitrate-rich beetroot juice (BR; 12 mmol of nitrate) and nitrate-depleted beetroot juice (PL; 0.10 mmol of nitrate) 2.5 h prior to performing the exercise protocol, with a washout period of 7 days between trials. Running 10 m and 20 m sprint split times, sprint reaction time, upper- and lower-body power, handgrip strength, and cognitive flexibility were measured before and after the Yo-Yo intermittent recovery level 1 (Yo-Yo IR1) test, during which performance and rate of perceived exertion were recorded. RESULTS: There were no significant differences in any performance outcome or cognitive flexibility (P \u3e 0.05). CONCLUSION: These findings indicate that acute nitrate ingestion does not influence performance in sprints, intermittent running, power, strength, or cognitive function in young adult female team-sport athletes

REFOCUS: developing a recovery focus in mental health services in England

Background: Recovery in mental health services is defined as living a satisfying, hopeful, and contributing life even with any limitations caused by illness. An evidence base for understanding and supporting recovery is needed.Objectives: To carry out a programme of linked research studies to understand how mental health services can promote recovery.Design: A two phase, mixed methods study. Phase 1 (theory) involved seven systematic reviews (develop a conceptual framework for recovery; establish its cross-cultural validity; develop a recovery practice framework; review measures of recovery measures; recovery support measures; strengths measures; staff understanding of recovery), development and evaluation of three new measures (INSPIRE for recovery support; IOM for individualised measurement of recovery; SAFE for feasibility assessment), evaluation of existing recovery measure (QPR), national survey, three qualitative studies (conceptual framework validation, staff recoveryoriented practice, black service users), and development of a new manualised REFOCUS intervention. Phase 2 involved a two-site cluster randomised controlled trial of the REFOCUS intervention, with a nested secondary outcome study, process and economic evaluation, interrupted time series analysis, sub-group analysis of black service users, and outcomes comparison. The impact of PPI on the programme was also empirically evaluated.Setting: Six mental health Trusts in England.Participants: 741 community mental health service users, 1,169 mental health staff and 54 expert stakeholders.Interventions: The manualised team-level REFOCUS intervention to increase support for personal recovery.Main outcome measures: Survey: Recovery Self Assessment (RSA). Trial: Questionnaire about the Process of Recovery (QPR), Client Satisfaction Questionnaire (CSQ).Results: Phase 1: the conceptual framework for recovery identified characteristics, stages and processes of recovery. It was cross-culturally valid and applicable to current service users. The recovery practice framework identified four domains of recovery support. INSPIRE, SAFE and IOM were developed and evaluated. The national survey identified differences between team managers (n=22), workers (n=120) and service users (n=108), and found higher recovery orientation was associated with improved recovery. The REFOCUS intervention has two elements: recovery promoting relationships and working practices. Phase 2: the 27-team trial involving 403 service users (297 at follow-up) showed no differences on primary outcomes of QPR (adjusted difference 0.63, 95%CI: -1.4 to 2.3, p=.55), but secondary outcomes of functioning (adjusted difference 5.90, 95%CI 2.6 to 9.2,

REFOCUS: developing a recovery focus in mental health services in England

Background: Recovery in mental health services is defined as living a satisfying, hopeful, and contributing life even with any limitations caused by illness. An evidence base for understanding and supporting recovery is needed. Objectives: To carry out a programme of linked research studies to understand how mental health services can promote recovery. Design: A two phase, mixed methods study. Phase 1 (theory) involved seven systematic reviews (develop a conceptual framework for recovery; establish its cross-cultural validity; develop a recovery practice framework; review measures of recovery measures; recovery support measures; strengths measures; staff understanding of recovery), development and evaluation of three new measures (INSPIRE for recovery support; IOM for individualised measurement of recovery; SAFE for feasibility assessment), evaluation of existing recovery measure (QPR), national survey, three qualitative studies (conceptual framework validation, staff recoveryoriented practice, black service users), and development of a new manualised REFOCUS intervention. Phase 2 involved a two-site cluster randomised controlled trial of the REFOCUS intervention, with a nested secondary outcome study, process and economic evaluation, interrupted time series analysis, sub-group analysis of black service users, and outcomes comparison. The impact of PPI on the programme was also empirically evaluated. Setting: Six mental health Trusts in England. Participants: 741 community mental health service users, 1,169 mental health staff and 54 expert stakeholders. Interventions: The manualised team-level REFOCUS intervention to increase support for personal recovery. Main outcome measures: Survey: Recovery Self Assessment (RSA). Trial: Questionnaire about the Process of Recovery (QPR), Client Satisfaction Questionnaire (CSQ). Results: Phase 1: the conceptual framework for recovery identified characteristics, stages and processes of recovery. It was cross-culturally valid and applicable to current service users. The recovery practice framework identified four domains of recovery support. INSPIRE, SAFE and IOM were developed and evaluated. The national survey identified differences between team managers (n=22), workers (n=120) and service users (n=108), and found higher recovery orientation was associated with improved recovery. The REFOCUS intervention has two elements: recovery promoting relationships and working practices. Phase 2: the 27-team trial involving 403 service users (297 at follow-up) showed no differences on primary outcomes of QPR (adjusted difference 0.63, 95%CI: -1.4 to 2.3, p=.55), but secondary outcomes of functioning (adjusted difference 5.90, 95%CI 2.6 to 9.2, p<.001) and staff-rated unmet need (adjusted difference -0.80, 95%CI -1·6 to -0·7, p=.03) did improve. Implementation was mixed, and higher-participating teams had higher staff-rated pro-recovery behaviour change (adjusted difference -0·4, 95%CI -0·7 to -0·2, p=·001) and patients had higher QPR Interpersonal scores (adjusted difference -1·6, 95%CI -2·7 to -0·5, p=·005) at follow-up. Intervention-group patients incurred £1,062 (95%CI -£1,103 to £3,017) lower adjusted costs. Black service users did not show improved recovery or satisfaction. Service users who experienced the intervention reported benefits. Conclusions: The REFOCUS intervention has been modified following its evaluation. The REFOCUS Programme provides a theory base for recovery research

Burkholderia Type VI Secretion Systems Have Distinct Roles in Eukaryotic and Bacterial Cell Interactions

Bacteria that live in the environment have evolved pathways specialized to defend against eukaryotic organisms or other bacteria. In this manuscript, we systematically examined the role of the five type VI secretion systems (T6SSs) of Burkholderia thailandensis (B. thai) in eukaryotic and bacterial cell interactions. Consistent with phylogenetic analyses comparing the distribution of the B. thai T6SSs with well-characterized bacterial and eukaryotic cell-targeting T6SSs, we found that T6SS-5 plays a critical role in the virulence of the organism in a murine melioidosis model, while a strain lacking the other four T6SSs remained as virulent as the wild-type. The function of T6SS-5 appeared to be specialized to the host and not related to an in vivo growth defect, as ΔT6SS-5 was fully virulent in mice lacking MyD88. Next we probed the role of the five systems in interbacterial interactions. From a group of 31 diverse bacteria, we identified several organisms that competed less effectively against wild-type B. thai than a strain lacking T6SS-1 function. Inactivation of T6SS-1 renders B. thai greatly more susceptible to cell contact-induced stasis by Pseudomonas putida, Pseudomonas fluorescens and Serratia proteamaculans—leaving it 100- to 1000-fold less fit than the wild-type in competition experiments with these organisms. Flow cell biofilm assays showed that T6S-dependent interbacterial interactions are likely relevant in the environment. B. thai cells lacking T6SS-1 were rapidly displaced in mixed biofilms with P. putida, whereas wild-type cells persisted and overran the competitor. Our data show that T6SSs within a single organism can have distinct functions in eukaryotic versus bacterial cell interactions. These systems are likely to be a decisive factor in the survival of bacterial cells of one species in intimate association with those of another, such as in polymicrobial communities present both in the environment and in many infections

Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts infectivity and fusogenicity

The SARS-CoV-2 Omicron BA.1 variant emerged in 20211 and has multiple mutations in its spike protein2. Here we show that the spike protein of Omicron has a higher affinity for ACE2 compared with Delta, and a marked change in its antigenicity increases Omicron’s evasion of therapeutic monoclonal and vaccine-elicited polyclonal neutralizing antibodies after two doses. mRNA vaccination as a third vaccine dose rescues and broadens neutralization. Importantly, the antiviral drugs remdesivir and molnupiravir retain efficacy against Omicron BA.1. Replication was similar for Omicron and Delta virus isolates in human nasal epithelial cultures. However,&nbsp;in lung cells and gut cells, Omicron demonstrated lower replication. Omicron spike protein was less efficiently cleaved compared with Delta. The differences in replication were mapped to the entry efficiency of the virus on the basis&nbsp;of spike-pseudotyped&nbsp;virus assays. The defect in entry of Omicron pseudotyped virus to specific cell types effectively correlated with higher cellular RNA expression of TMPRSS2, and deletion of TMPRSS2 affected Delta entry to a greater extent than Omicron. Furthermore, drug inhibitors targeting specific entry pathways3 demonstrated that the Omicron spike inefficiently uses the cellular protease TMPRSS2, which promotes cell entry through plasma membrane fusion, with greater dependency on cell entry through the endocytic pathway. Consistent with suboptimal S1/S2 cleavage and inability to use TMPRSS2, syncytium formation by the Omicron spike was substantially impaired compared with the Delta spike. The less efficient spike cleavage of Omicron at S1/S2 is associated with a shift in cellular tropism away from TMPRSS2-expressing cells, with implications for altered pathogenesis

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Development and Psychometric Properties of a New Questionnaire to Assess Mental Health and Concerning Behaviors in Children and Young People with Autism Spectrum Disorder (ASD):The Assessment of Concerning Behavior (ACB) Scale

Although 70% of autistic children and young people meet criteria for co-occurring psychiatric conditions, there are few screening measures specifically for autistic individuals. We describe the development and validation of the Assessment of Concerning Behavior (ACB), an instrument co-developed with the autistic community to assess mental health and problematic/risky behaviors. Items include descriptions to facilitate symptom recognition by autistic people, and carers/professionals. The ACB was completed by 255 parents, 149 autistic children and young people and 30 teachers. Internal consistency, stability and validity was assessed. The ACB parent-version fit a two-factor model (internalizing and externalizing problems) and showed adequate test–retest reliability, internal consistency and construct validity. The ACB is a promising new measure for research and clinical use in autism

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts infectivity and fusogenicity

The SARS-CoV-2 Omicron BA.1 variant emerged in 20211 and has multiple mutations in its spike protein2. Here we show that the spike protein of Omicron has a higher affinity for ACE2 compared with Delta, and a marked change in its antigenicity increases Omicron’s evasion of therapeutic monoclonal and vaccine-elicited polyclonal neutralizing antibodies after two doses. mRNA vaccination as a third vaccine dose rescues and broadens neutralization. Importantly, the antiviral drugs remdesivir and molnupiravir retain efficacy against Omicron BA.1. Replication was similar for Omicron and Delta virus isolates in human nasal epithelial cultures. However, in lung cells and gut cells, Omicron demonstrated lower replication. Omicron spike protein was less efficiently cleaved compared with Delta. The differences in replication were mapped to the entry efficiency of the virus on the basis of spike-pseudotyped virus assays. The defect in entry of Omicron pseudotyped virus to specific cell types effectively correlated with higher cellular RNA expression of TMPRSS2, and deletion of TMPRSS2 affected Delta entry to a greater extent than Omicron. Furthermore, drug inhibitors targeting specific entry pathways3 demonstrated that the Omicron spike inefficiently uses the cellular protease TMPRSS2, which promotes cell entry through plasma membrane fusion, with greater dependency on cell entry through the endocytic pathway. Consistent with suboptimal S1/S2 cleavage and inability to use TMPRSS2, syncytium formation by the Omicron spike was substantially impaired compared with the Delta spike. The less efficient spike cleavage of Omicron at S1/S2 is associated with a shift in cellular tropism away from TMPRSS2-expressing cells, with implications for altered pathogenesis