Cummingsmolina4869

Moreover, TLT-1 Fc treatment suppressed B10 polarization via blocking PMA formation. Taking all of these data together, we elucidated that TLT-1 promoted PMA-mediated B10 polarization through enhancing IL-1β, IL-6, and CD40L origin from PMAs, which may provide potential targeting strategies for TB disease treatment.An impaired neutrophil response to pathogenic fungi puts patients at risk for fungal infections with a high risk of morbidity and mortality. Acquired neutrophil dysfunction in the setting of iatrogenic immune modulators can include the inhibition of critical kinases such as spleen tyrosine kinase (Syk). In this study, we used an established system of conditionally immortalized mouse neutrophil progenitors to investigate the ability to augment Syk-deficient neutrophil function against Candida albicans with TLR agonist signaling. LPS, a known immunomodulatory molecule derived from Gram-negative bacteria, was capable of rescuing effector functions of Syk-deficient neutrophils, which are known to have poor fungicidal activity against Candida species. LPS priming of Syk-deficient mouse neutrophils demonstrates partial rescue of fungicidal activity, including phagocytosis, degranulation, and neutrophil swarming, but not reactive oxygen species production against C. albicans, in part due to c-Fos activation. Similarly, LPS priming of human neutrophils rescues fungicidal activity in the presence of pharmacologic inhibition of Syk and Bruton's tyrosine kinase (Btk), both critical kinases in the innate immune response to fungi. In vivo, neutropenic mice were reconstituted with wild-type or Syk-deficient neutrophils and challenged i.p. with C. albicans. In this model, LPS improved wild-type neutrophil homing to the fungal challenge, although Syk-deficient neutrophils did not persist in vivo, speaking to its crucial role on in vivo persistence. Taken together, we identify TLR signaling as an alternate activation pathway capable of partially restoring neutrophil effector function against Candida in a Syk-independent manner.Alternative pathway complement dysregulation with abnormal glomerular C3 deposits and glomerular damage is a key mechanism of pathology in C3 glomerulopathy (C3G). No disease-specific treatments are currently available for C3G. Therapeutics inhibiting complement are emerging as a potential strategy for the treatment of C3G. In this study, we investigated the effects of N-acetylgalactosamine (GalNAc)-conjugated small interfering RNA (siRNA) targeting the C3 component of complement that inhibits liver C3 expression in the C3G model of mice with heterozygous deficiency of factor H (Cfh +/- mice). We showed a duration of action for GalNAc-conjugated C3 siRNA in reducing the liver C3 gene expression in Cfh +/- mice that were dosed s.c. once a month for up to 7 mo. C3 siRNA limited fluid-phase alternative pathway activation, reducing circulating C3 fragmentation and activation of factor B. Treatment with GalNAc-conjugated C3 siRNA reduced glomerular C3d deposits in Cfh +/- mice to levels similar to those of wild-type mice. Ultrastructural analysis further revealed the efficacy of the C3 siRNA in slowing the formation of mesangial and subendothelial electron-dense deposits. The present data indicate that RNA interference-mediated C3 silencing in the liver may be a relevant therapeutic strategy for treating patients with C3G associated with the haploinsufficiency of complement factor H.

Healthcare-associated infections (HCAIs) are a major cause of morbidity and mortality in critically ill children. In critically ill adults, there are data that suggest the use of Selective Decontamination of the Digestive tract (SDD), alongside standard infection control measures reduce mortality and the incidence of HCAIs. SDD-enhanced infection control has not been compared directly with standard infection prevention strategies in the Paediatric Intensive Care Unit (PICU) population. The aim of this pilot study is to determine the feasibility of conducting a multicentre cluster randomised controlled trial (cRCT) in critically ill children comparing SDD with standard infection control.

Paediatric Intensive Care and Infection Control is a parallel group pilot cRCT, with integrated mixed-methods study, comparing incorporation of SDD into infection control procedures to standard care. After a 1-week pretrial ecology surveillance period, recruitment to the cRCT will run for a period of 18 weeks, comprising ( the study, any identifiable data collected and monitoring of medical records. Results will be disseminated via publications in peer-reviewed medical journals.

ISRCTN40310490.

ISRCTN40310490.

This study explores patients' acceptance of obesity as a chronic disease.

Cross-sectional, qualitative study using semistructured phone interviews.

The study was conducted in specialty and primary care clinics from a single central tertiary hospital in Lebanon. Recruitment took place between February and March 2021.

25 adult patients with overweight or obesity were interviewed and the interviews were analysed thematically.

Four themes emerged (1) patients' knowledge and awareness of obesity are based on their own experience; (2) there is ambivalence or conditional acceptance of obesity as a chronic disease; and patients with overweight or obesity perceived (3) that the role of physicians in obesity management is related to complications and (4) that obesity management is as simple as eating less and exercising more.

The study shows the studied population's ambivalence in accepting obesity as a chronic disease. Individuals with overweight or obesity considered the role of the healthcare professional in obesity conditional on morbid obesity and the presence of medical complications of obesity. Findings of this study advocate for educational campaigns about the nature of obesity as a chronic disease and the role of healthcare professionals in obesity management.

The study shows the studied population's ambivalence in accepting obesity as a chronic disease. Individuals with overweight or obesity considered the role of the healthcare professional in obesity conditional on morbid obesity and the presence of medical complications of obesity. Findings of this study advocate for educational campaigns about the nature of obesity as a chronic disease and the role of healthcare professionals in obesity management.

This review aimed to determine the pooled prevalence of preoperative anxiety and its associated factors among patients undergoing surgery in low/middle-income countries (LMICs).

We searched PubMed, SCOPUS, CINAHL, Embase and PsychINFO to identify peer-reviewed studies on the prevalence and factors associated with preoperative anxiety among patients undergoing surgery using predefined eligibility criteria. Studies were pooled to estimate the prevalence of preoperative anxiety using a random-effect meta-analysis model. Heterogeneity was assessed using I² statistics. Funnel plot asymmetry and Egger's regression tests were used to check for publication bias.

Our search identified 2110 studies, of which 27 studies from 12 countries with 5575 participants were included in the final meta-analysis. Of the total 27 studies, 11 used the State-Trait Anxiety Inventory to screen anxiety, followed by the Amsterdam Preoperative Anxiety and Information scale, used by four studies. The pooled prevalence of preoperative anxiety among patients undergoing surgery in LMICs was 55.7% (95% CI 48.60 to 62.93). Our subgroup analysis found that a higher pooled prevalence of preoperative anxiety was found among female surgical patients (59.36%, 95% CI 48.16 to 70.52, I

=95.43, p<0.001) and studies conducted in Asia (62.59%, 95% CI 48.65 to 76.53, I

=97.48, p<0.001).

Our meta-analysis indicated that around one in two patients undergoing surgery in LMICs suffer from preoperative anxiety, which needs due attention. Fimepinostat Routine screening of preoperative anxiety symptoms among patients scheduled for surgery is vital.

CRD42020161934.

CRD42020161934.

It is unclear how pharmacological and non-pharmacological interventions compare with each other in terms of efficacy and tolerability for core symptoms and additional problems in adults with attention-deficit/hyperactivity disorder (ADHD). We aim to conduct the first network meta-analysis (NMA) comparing pharmacological and non-pharmacological interventions (or their combinations) in adults with ADHD.

We will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement for NMAs. We will search a broad set of electronic databases/registries and contact drug companies and experts in the field to retrieve published and unpublished randomised controlled trials (RCTs) (parallel or cross-over) of medications (either licensed or unlicensed) and any non-pharmacological intervention in adults (≥18 years) with ADHD. Primary outcomes will be (1) change in severity of ADHD core symptoms, and (2) acceptability (all-cause discontinuation). Secondary outcomes will include tolerability (drop-out due to side effects) and change in the severity of emotional dysregulation, executive dysfunctions and quality of life. The risk of bias in each individual RCT included in the NMA will be assessed using the Cochrane Risk of Bias tool-version 2. We will evaluate the transitivity assumption comparing the distribution of possible effect modifiers across treatment comparisons. We will perform Bayesian NMA for each outcome with random-effects model in OpenBUGS. Pooled estimates of NMA will be obtained using the Markov Chains Monte Carlo method. We will judge the credibility in the evidence derived from the NMA using the CINeMA tool (which includes assessment of publication bias). We will conduct a series of sensitivity analyses to assess the robustness of the findings.

As this is the protocol for an aggregate-data level NMA, ethical approval will not be required. Results will be disseminated at national/international conferences and in peer-reviewed journals.

CRD42021265576.

CRD42021265576.

Stroke survivors, once in the community, face challenges with their long-term rehabilitation care and present higher levels of loneliness, depression and anxiety than the rest of the population. A community-based performance arts programme, Stroke Odysseys (SO), has been devised to tackle the challenges of living with stroke in the UK. In this study, we aim to evaluate the implementation, impact and experiences of SO for stroke survivors.

Scaling-up Health Arts Programmes Implementation and Effectiveness Research (SHAPER)-SO aims to scale-up SO to 75 participants and 47 stakeholders, while simultaneously evaluating the effectiveness and implementation of the programme. The main research aim is to evaluate the implementation, effectiveness, impact and experiences of a community-based performance arts programme (SO for stroke survivors). This mixed-methods study will evaluate the experience and impact of SO on those participating using mixed methods (interviews, observations and surveys) before and after each stage and carry out non-participant observations during a percentage of the workshops, training and tour. Data will be analysed using quantitative and qualitative approaches. This is a study within the SHAPER programme.

Ethical approval has been granted by the King's College London PNM Research Ethics Panel, REC reference LRS/DP-20/21-21549. Written informed consent will be sought for participants and stakeholders. The results of the study will be reported and disseminated at international conferences and in peer-reviewed scientific journals.

NCT04864470.

NCT04864470.