Search Results (1,577)

Background/Objectives: Extracellular vesicles (EVs) play a key role in intercellular communication by transferring miRNAs and other macromolecules between cells. Understanding how diet and exercise modulate the release and content of skeletal muscle (SM)-derived EVs could lead to novel therapeutic strategies to prevent age-related muscle decline and other chronic diseases, such as sarcopenia. This review aims to provide an overview of the role of EVs in muscle function and to explore how nutritional and physical interventions can optimise their release and function. Methods: A literature review of studies examining the impact of exercise and nutritional interventions on MS-derived EVs was conducted. Major scientific databases, including PubMed, Scopus and Web of Science, were searched using keywords such as ‘extracellular vesicles’, ‘muscle’, ‘exercise’, ‘nutrition’ and ‘sarcopenia’. The selected studies included randomised controlled trials (RCTs), clinical trials and cohort studies. Data from these studies were synthesised to identify key findings related to the release of EVs, their composition and their potential role as therapeutic targets. Results: Dietary patterns, specific foods and supplements were found to significantly modulate EV release and composition, affecting muscle health and metabolism. Exercise-induced changes in EV content were observed after both acute and chronic interventions, with a marked impact on miRNAs and proteins related to muscle growth and inflammation. Nutritional interventions, such as the Mediterranean diet and omega-3 fatty acids, have also shown the ability to alter EV profiles, suggesting their potential to improve cardiovascular health and reduce inflammation. Conclusions: EVs are emerging as critical mediators of the beneficial effects of diet and exercise on muscle health. Both exercise and nutritional interventions can modulate the release and content of MS-derived EVs, offering promising avenues for the development of novel therapeutic strategies targeting sarcopenia and other muscle diseases. Future research should focus on large-scale RCT studies with standardised methodologies to better understand the role of EVs as biomarkers and therapeutic targets. Full article

Background: Severe atopic dermatitis (AD) is a complex disease requiring systemic treatment. This study aimed to assess the effectiveness of combined therapy consisting of dupilumab and sublingual dust mite allergen immunotherapy (SLIT-HDM) in patients with severe AD and HDM allergies. Methods: Patients diagnosed with severe AD were included in this randomised, placebo-controlled, double-blind 12-month trial; they received SLIT for HDMs and/or dupilumab for 12 months and were compared with patients on cyclosporine. The primary outcomes for the treatment arms were changes in the Eczema Area and Severity Index (EASI), body surface area (%BSA), and Investigator Global Assessment (IsGA) over 12 months. The secondary outcomes were the proportion of patients who achieved IsGA success and reduced medication scores. Results: Significant improvements were observed in all analysed groups after 12 months of therapy based on the EASI, %BSA, and IsGA. However, the most substantial changes were observed in the groups treated with dupilumab or a combination of SLIT-HDM and dupilumab. Additionally, the proportion of patients who achieved an IsGA reduction was significantly greater in the group receiving combination therapy than in the other groups (9/14 [64% of the group receiving SLIT-HDM] vs. 11/14 [73% of the group receiving dupilumab] vs. 15/17 [88% of the group receiving dupilumab and SLIT-HDM] vs. 7/13 [53% of the group receiving cyclosporine]) (p < 0.05). Conclusions: In patients with severe AD and HDM allergies, combination treatment with dupilumab and allergen immunotherapy for HDMs may increase the therapeutic benefit over treatment with these methods separately. Full article

(1) Background: The World Health Organisation (WHO) categorises moxifloxacin and levofloxacin as Group A drugs, which should be prioritised in the treatment of rifampicin-resistant tuberculosis. We compare their relative efficacy and safety using data from the STREAM trial; (2) Methods: Marginal structural models were used to balance differences in the baseline characteristics of participants receiving the STREAM control regimen containing either moxifloxacin or levofloxacin as this was not a randomised comparison. The difference in proportions between regimens was estimated for favourable outcome, any grade 3/4 adverse event, QTcF increase to ≥500 ms, QTcF increase from baseline by at least 60 ms, and any grade 3/4 adverse event excluding QT events, using weighted analyses; (3) Results: In efficacy analyses (n = 123), the weighted risk difference (moxifloxacin—levofloxacin, wRD) for a favourable outcome was −0.045 (−0.213, 0.123), p = 0.60. Similarly, estimates from the safety analyses (n = 127) showed no evidence of a difference between the fluoroquinolones, other than a suggestion of fewer QTcF increases from baseline on levofloxacin (wRD 0.160 (−0.026, 0.346), p = 0.091); (4) Conclusions: In this small dataset, we found no statistically significant difference in key efficacy or safety outcomes between the moxifloxacin- and levofloxacin-containing regimens; there was a suggestion that QTcF increases from baseline were fewer on levofloxacin. Full article

Given the high prevalence of overweight and obesity amongst educators, this study investigated the feasibility of the 16-week Health4LIFE weight loss intervention for primary school educators living with overweight/obesity in low-income settings in Cape Town, South Africa. The research comprised two sub-studies, a pilot randomised controlled trial testing the intervention (10 intervention, n = 79 and 10 control schools, n = 58), and an investigation of the perceptions of participating educators and principals. Feasibility outcomes included reach, applicability, acceptability, implementation integrity, and a hypothesis-generating signal of effect on lifestyle factors and weight. The intervention consisted of a wellness day, weight loss manual, and text messages. Results indicated acceptable reach, with positive feedback on intervention components from principals and educators. Implementation was largely successful, though three schools dropped out due to scheduling issues. Barriers included interruption of teaching time and busy school schedules. The intervention group (n = 42) showed favourable shifts in belief patterns, stages of change, and lifestyle behaviours, with a trend towards weight loss. Control group (n = 43) changes were limited to dietary intake. The triangulation of results supported the intervention’s feasibility in terms of primary and secondary outcomes. Recommendations for enhancement include adding in-person follow-up sessions and an app-based element to potentially increase impact on lifestyle indicators and weight loss. Full article

Maximising the potential benefit of resistance exercise (RE) programs by ensuring optimal recovery is an important aim of exercise prescription. Despite this, research surrounding recovery from RE in older adults is limited and inconsistent. The following randomised controlled trial was designed to investigate the efficacy of milk consumption for improving recovery from RE in older adults. However, the study encountered various challenges that may be applicable to similar studies. These include recruitment issues, a lack of measurable perturbations in muscle function following RE, and potential learning effects amongst participants. Various considerations for exercise research have arisen from the data which could inform the design of future studies in this area. These include (i) recruitment—consider ways in which the study design could be altered to aid recruitment or allow a longer recruitment period; (ii) learning effects and familiarisation—consider potential learning effects of outcome measures and adjust familiarisation accordingly; (iii) identify, validate and optimise protocols for outcome measures that are applicable for the specific population; (iv) adjust the exercise protocol according to the specific aims of the study (e.g., are you replicating a usual exercise bout or is the intent to cause large amounts of muscle damage?). Full article

Childhood overweight/obesity (OV/OB) is a major public health problem in Western countries, often accompanied with comorbidities (e.g., hypertension and insulin resistance) (i.e., metabolically unhealthy obesity—MUO). Among diet-related risk factors of OV/OB risk and MUO, meal patterns remain limitedly studied. The aim of this systematic review was to explore associations between meal patterns and the risk of childhood OV/OB and MUO in children/adolescents aged 2–19 years. Longitudinal studies and randomised controlled trials from PUBMED and Scopus published between January 2013 and April 2024 were retrieved. Twenty-eight studies were included, all of which reported on OV/OB risk, with none on MUO risk. Regular consumption of breakfast (n = 3) and family meals (n = 4) and avoiding dining while watching TV (n = 4) may be protective factors against childhood OV/OB, whereas meal skipping (primarily breakfast; n = 4) may be a detrimental factor. Mixed effects of meal frequency on OV/OB risk were observed; no effects of frequency of lunch or of fast-food consumption and of meals served at school were found. There was insufficient evidence to support the role of other patterns (meal timing, eating in other social contexts). Meals were mainly participant-identified, leading to increased heterogeneity. Research focusing on childhood MUO and the use of harmonised definitions regarding the assessment of meal patterns are highly warranted. Full article

Background/Objectives: Dendrimer-based astodrimer sodium nasal spray was assessed for its ability to reduce SARS-CoV-2 load in outpatients with COVID-19, which remains a severe illness for vulnerable groups. Methods: This was a randomised, double-blind, placebo-controlled clinical investigation evaluating the efficacy of astodrimer nasal spray in reducing SARS-CoV-2 viral burden in the nasopharynx of outpatients with COVID-19. Non-hospitalised adults with SARS-CoV-2 infection were randomised 1:1 to astodrimer or placebo four times daily from Day 1 to Day 7. Nasopharyngeal swabs for SARS-CoV-2 load determination were self-obtained daily from Day 1 to Day 8. The primary endpoint was an area under the curve of SARS-CoV-2 RNA copies/mL through Day 8 (vAUC_d1–8). The primary analysis population was the modified intent-to-treat population (mITT: all randomised participants exposed to the study treatment who had at least one post-baseline viral load determination). Safety analyses included all randomised participants exposed to the study treatment. Study registration: ISRCTN70449927; Results: 231 participants were recruited between 9 January and 20 September 2023. The safety population comprised 109 and 113 participants randomised to astodrimer and placebo, respectively, with 96 and 101 participants in the mITT. Astodrimer sodium nasal spray reduced the SARS-CoV-2 burden (vAUC_d1–8) vs. placebo in non-hospitalised COVID-19 patients aged 16 years and over (−1.2 log₁₀ copies/mL × Day). The reduction in SARS-CoV-2 load was statistically significant in those aged 45 years and older (−3.7, p = 0.017) and the effect increased in older age groups, including in those aged 65 years and older (−7.3, p = 0.005). Astodrimer sodium nasal spray increased the rate of viral clearance and helped alleviate some COVID-19 symptoms, especially loss of sense of smell. Overall, 31 participants (14%) had ≥1 adverse event (AE). Four AEs were deemed possibly related to treatment. Most AEs were of mild severity and occurred at similar rates in both treatment arms. Conclusions: Astodrimer nasal spray reduces viral burden and accelerates viral clearance, especially in older populations, and is well tolerated. Full article

Malaria poses a significant threat to pregnant women in sub-Saharan Africa, necessitating effective interventions like the intermittent preventive treatment of malaria in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP). However, challenges persist in the uptake and effectiveness of this intervention. This scoping review aims to explore IPTp-SP uptake in African countries, identify influencing factors, and assess its effectiveness in preventing malaria and adverse outcomes in pregnancy. This scoping review follows Arksey and O’Malley’s framework, employing the PRISMA-ScR guidelines for reporting. Searches were conducted in PubMed, Embase, Scopus, JSTOR, Web of Science, Google Scholar, and ProQuest, focusing on studies post-2000 published in the English language. The search produced 15,153 records, of which 104 full-text records were eligible and 101 papers were included in this review. The findings suggest varying IPTp-SP uptake rates, spanning from 5.3% to 98.9%, with their effectiveness supported by longitudinal studies, randomised controlled-trials (RCTs), cross-sectional surveys, and mixed-method studies. IPTp-SP demonstrates efficacy in reducing malaria during pregnancy, placental parasitaemia, and anaemia episodes, alongside improved birth outcomes. Common adverse effects of IPTp-SP include prematurity and low birth weight. Facilitators of IPTp-SP uptake include education and ANC attendance, while commonly reported barriers included inadequate knowledge and healthcare system challenges. The findings also suggest adverse effects such as prematurity, low birth weight, and maternal and perinatal mortality associated with IPTp-SP uptake. It is vital to strengthen antenatal care services by integrating comprehensive counselling on IPTp-SP and address healthcare system challenges. Community engagement, women’s empowerment, and context-specific interventions are necessary for promoting IPTp-SP uptake and improving maternal and neonatal health outcomes in Africa. Full article

Background: The coronary slow flow phenomenon (CSFP) is an angiographic finding characterised by the delayed passage of contrast through the coronary arteries, despite the absence of obstructive coronary artery disease (defined as less than 50% narrowing of the vessel lumen). Patients with the CSFP experience recurrent angina, for which there are limited evidence-based therapies. Ticagrelor may serve as an effective anti-anginal therapy for these patients by increasing adenosine levels, which could alleviate coronary microvascular dysfunction and its associated angina due to its vasodilatory properties. This study aimed to determine the anti-anginal efficacy of ticagrelor 90 mg taken twice daily on spontaneous angina episodes in patients with refractory angina (i.e., episodes ≥3/week despite two anti-anginals) and documented CSFP. Methods: In a randomised, double-blind, placebo-controlled, cross-over trial, the anti-anginal efficacy of a 4-week ticagrelor therapy regimen was evaluated in 20 patients with refractory angina (mean age 61.5 ± 10.5 years; 40% women) who had documented slow coronary flow. The primary endpoint was the frequency of angina episodes, recorded using an angina diary. Secondary endpoints included the duration and severity of angina episodes, consumption of short-acting nitrates, and health status evaluations using the Seattle Angina Questionnaire (SAQ) and the Short Form-36 (SF-36) indices. Results: During the four weeks of therapy, ticagrelor did not significantly improve angina symptoms compared to the placebo (placebo 25.7 (16.7)) vs. ticagrelor 19.8 (18.1), p > 0.05). Furthermore, it did not impact other patient-related outcome measures, including angina severity, duration, frequency of prolonged angina episodes, nitrate consumption, or the SAQ/SF-36 health outcome indices. No serious adverse events related to the study drug were observed. Conclusions: In patients with documented CSFP who were unresponsive to standard anti-anginal therapy, ticagrelor did not reduce the frequency of spontaneous angina episodes or the consumption of nitrates. Further confirmation of the potential benefits of this therapy may be obtained through a larger clinical trial. Full article

The review examines the long-term impact of community psychiatric care on improving the quality of life of people with schizophrenia. It addresses the global burden of this disorder and the need for effective community-based care strategies. A systematic literature search was conducted in databases such as CINAHL, Medline, Web of Science, Sage and ScienceDirect, with the search lasting until March 2024 and following the PRISMA guidelines. The inclusion criteria targeted studies that addressed the long-term effects of community mental health care for people aged 18 years and older with schizophrenia and included both quantitative and qualitative research designs. Studies unrelated to the research question or with significant methodological flaws were excluded. The risk of bias was assessed using GRADE and GRADECERqual, in addition to critical appraisal using the Joanna Briggs Institute (JBI) checklists. Independent screening and data extraction was performed, with results summarised by thematic analysis. In total, 11 studies met the inclusion criteria and included cross-sectional, cohort, qualitative and randomised controlled trial designs. The results showed that community psychiatric care significantly improves the quality of life, well-being and social integration of people with schizophrenia. Effective interventions identified include psychoeducation, cognitive behavioural therapy, social skills training and individualised care plans. However, challenges such as limited resources, labour shortages and social stigma, particularly in low-income neighbourhoods, were also identified. This study highlights the importance of continuous, personalised, multidisciplinary community-based care for sustainable mental health outcomes. Further research is recommended to investigate the long-term impact and strategies to overcome implementation challenges. Full article

Background: Stage IIIA-N2 non-small cell lung cancer (NSCLC) poses a significant clinical challenge, with low survival rates despite advances in therapy. The lack of a standardised treatment approach complicates patient management. This study utilises real-world data from Guy’s Thoracic Cancer Database to analyse patient outcomes, identify key predictors of overall survival (OS) and disease-free survival (DFS), and address the limitations of randomised controlled trials. Methods: This observational, single-centre, non-randomised study analysed 142 patients diagnosed with clinical and pathological T1/2 N2 NSCLC who received curative treatment from 2015 to 2021. Patients were categorised into three groups: Group A (30 patients) underwent surgery for clinical N2 disease, Group B (54 patients) had unsuspected N2 disease discovered during surgery, and Group C (58 patients) received radical chemoradiation or radiotherapy alone (CRT/RT) for clinical N2 disease. Data on demographics, treatment types, recurrence, and survival rates were analysed. Results: The median OS for the cohort was 31 months, with 2-year and 5-year OS rates of 60% and 30%, respectively. Group A had a median OS of 32 months, Group B 36 months, and Group C 25 months. The median DFS was 18 months overall, with Group A at 16 months, Group B at 22 months, and Group C at 17 months. Significant predictors of OS included ECOG performance status, lymphovascular invasion, and histology. No significant differences in OS were found between treatment groups (p = 0.99). Conclusions: This study highlights the complexity and diversity of Stage IIIA-N2 NSCLC, with no single superior treatment strategy identified. The findings underscore the necessity for personalised treatment approaches and multidisciplinary decision-making. Future research should focus on integrating newer therapeutic modalities and conducting multi-centre trials to refine treatment strategies. Collaboration and ongoing data collection are crucial for improving personalised treatment plans and survival outcomes for Stage IIIA-N2 NSCLC patients. Full article

Background: Current management of mild-to-moderate ulcerative colitis (UC) involves monitoring clinical markers of disease activity, such as stool frequency (SF) and rectal bleeding (RB), and adjusting treatment accordingly. Our aim was to assess whether targeting treatment based on faecal calprotectin (FC) levels (treat-to-target; T2T) provides greater UC disease control versus a symptom-based approach. Methods: This was a pragmatic, randomised (1:1) controlled study of patients with mild-to-moderate UC (global Mayo score 2–6) treated with ≤2.4 g/day 5-aminosalicylic acid that compared the effectiveness of two management strategies with (interventional arm) and without (reference arm) FC home monitoring over 12 months of follow-up. Treatment was optimised in the interventional arm using FC values and clinical symptoms (PRO-2), while the reference arm used only PRO-2. Results: 193 patients completed the study. No significant difference was found for the primary endpoint (Mayo Endoscopic Subscore [MES] = 0 at 12 months). A numerical advantage for the interventional arm over the reference arm for the primary endpoint (37.0% vs. 33.4%, respectively) and for MES ≤ 1, RB = 0, and SF ≤ 1 at 12 months was found following imputation for missing data. The composite endpoint of MES = 0, RB = 0, and SF ≤ 1 at 12 months was achieved at a significantly higher rate in the interventional arm than the reference arm (effect size [ES]: 0.17, 95% CI 0.02–0.32; p < 0.05). A similar result was obtained for MES ≤ 1, RB = 0 and SF ≤ 1 (ES: 0.22; 95% CI 0.07–0.37; p < 0.05). Conclusions: T2T using FC monitoring was effective in patients with mild-to-moderate UC at 12 months. Further longer-term studies are required to confirm the results. Full article

High dose bolus cholecalciferol supplementation has been associated with falls and fracture, and this does not appear to be due to hypercalcaemia. The primary aim of this study was to determine the change in free vitamin D and metabolites after high dose bolus supplementation. This was a single centre, double-blinded, randomised, controlled trial of three different oral bolus doses of vitamin D₃ (50,000 IU, 150,000 IU, and 500,000 IU) in otherwise healthy, vitamin D deficient (total 25-hydroxylated vitamin 25(OH)D < 30 nmol/L) postmenopausal women. Thirty-three women were randomized to one of the three treatment groups. Twenty-seven vitamin D sufficient (25(OH)D > 50 nmol/L) postmenopausal women were recruited as a concurrent control group. Participants attended five study visits over three months. We measured total 25(OH)D₃ and free 25(OH)D, total and free 1,25(OH)₂D, parathyroid hormone, fibroblast-growth factor-23, serum calcium, ionised calcium, urinary calcium excretion, and bone turnover markers (procollagen I N-propeptide (PINP), serum C-telopeptides of type I collagen (CTX-I) and Osteocalcin (OC)). We assessed muscle strength and function with grip strength and a short physical performance battery. Postural blood pressure and aldosterone:renin ratio (ARR) was also measured. Total 25(OH)D₃ and free 25(OH)D increased in response to dose, and there were proportionate increases in total and free metabolites. Treatment did not affect serum calcium, postural blood pressure, ARR, or physical function. Bone turnover markers increased transiently one week after administration of 500,000 IU. High dose bolus cholecalciferol supplementation does not cause disproportionate increases in free vitamin D or metabolites. We did not identify any effect on blood pressure regulation or physical function that would explain increased falls after high dose treatment. A transient increase in bone turnover markers one week after a 500,000 IU bolus suggests that very high doses can have acute effects on bone metabolism, but the clinical significance of this transient increase is uncertain. Full article

Introduction: Apraxia is a neurological disorder that is common after a stroke and impairs the planning and execution of movements. In the rehabilitation field, virtual reality (VR) presents new opportunities and offers advantages to both rehabilitation teams and individuals with neurological conditions. Indeed, VR can stimulate and improve cognitive reserve and abilities, including executive function, and enhance the patient’s emotional status. Aim: The objective of this research is to determine the effectiveness of VR in improving praxis skills and behavioural functioning in individuals with severe stroke. Methods: A total of 20 stroke patients were enrolled from February 2022 to March 2023 and divided by the order of their recruitment into two groups: the experimental group (EG: n = 10) received training to improve their praxis skills using VR whereas the control one (CG: n = 10) received the same amount of standard training. All patients underwent an evaluation using a psychometric battery that consisted of the Hamilton Rating Scale for Depression (HRS-D), Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB), Spinnler and Tognoni test, and De Renzi and Faglioni test. Valuations were performed before rehabilitation (T0) and after its completion (T1). Results: Both groups demonstrated significant improvements post-intervention. The EG showed a greater enhancement in their MMSE scores (p = 0.002), and reductions in both ideomotor and constructive apraxia (p = 0.002 for both), compared to the CG. The VR-based training also resulted in significant improvements in their depression symptoms (HRSD scores improved, p = 0.012 in EG vs. p = 0.021 in CG). Conclusions: This pilot study suggests that VR could help reduce cognitive, constructive apraxia and ideomotor apraxia symptoms caused by stroke injury. Full article