Search Results (536)

Background/Objectives: Conventional ketogenic diets, although effective for weight loss, often contain high total and saturated fat intake, which leads to increased low-density lipoprotein cholesterol (LDL-C). Thus, the Healthy Ketogenic Diet (HKD) was developed to address these concerns. It emphasizes calorie restriction, limiting net carbohydrate intake to 50 g per day, prioritizing unsaturated fats, and reducing saturated fat intake. However, adherence to the HKD remains a challenge in urban, time-constrained environments. Therefore, this pilot randomized controlled trial aimed to investigate the effects of Healthy Ketogenic Diet Ready-To-Eat (HKD-RTE) meals (provided for the first month only) versus HKD alone on weight loss and metabolic parameters among overweight adults. Methods: Multi-ethnic Asian adults (n = 50) with a body mass index (BMI) ≥ 27.5 kg/m² were randomized into the HKD-RTE group (n = 24) and the HKD group (n = 26). Both groups followed the HKD for six months, with the HKD-RTE group receiving HKD-RTE meals during the first month. Five in-person workshops and mobile health coaching through the Nutritionist Buddy Keto app helped to facilitate dietary adherence. The primary outcome was the change in body weight at 6 months. Linear regression was performed on the change from baseline for each continuous outcome, adjusting for demographics and relevant covariates. Logistic regression was performed on binary weight loss ≥5%, adjusting for demographics and relevant covariates. Results: In the HKD group, participants’ adherence to the 50 g net carbohydrate target was 15 days, while that in the HKD-RTE group was 19 days over a period of 30 days. Participants’ adherence to calorie targets was 21 days in the HKD group and 23 days in the HKD-RTE. The average compliance with the HKD-RTE meals provided in the HKD-RTE group was 55%. The HKD-RTE group experienced a greater percentage weight loss at 1 month (−4.8 ± 3.0% vs. −1.8 ± 6.2%), although this was not statistically significant. This trend continued up to 6 months, with the HKD-RTE group showing a greater percentage weight reduction (−8.6 ± 6.8% vs. −3.9 ± 8.6%; p = 0.092). At 6 months, the HKD-RTE group had a greater reduction in total cholesterol (−0.54 ± 0.76 mmol/L vs. −0.05 ± 0.56 mmol/L; p = 0.283) and LDL-C (−0.43 ± 0.67 mmol/L vs. −0.03 ± 0.52 mmol/L; p = 0.374) compared to the HKD group. Additionally, the HKD-RTE group exhibited greater reductions in systolic blood pressure (−8.3 ± 9.7 mmHg vs. −5.3 ± 11.0 mmHg), diastolic blood pressure (−7.7 ± 8.8 mmHg vs. −2.0 ± 7.0 mmHg), and HbA1c (−0.3 ± 0.5% vs. −0.1 ± 0.4%) than the HKD group (not statistically significant for any). Conclusions: Both HKD-RTE and HKD led to weight loss and improved metabolic profiles. The HKD-RTE group tended to show more favorable outcomes. Short-term HKD-RTE meal provision may enhance initial weight loss, with sustained long-term effects. Full article

This pilot, randomized, double-blind, placebo-controlled trial investigated the effects of branched-chain amino acids (BCAAs)—provided in a 2:1:1 ratio of leucine:isoleucine:valine—combined with exercise on fatigue, physical performance, and quality of life in older adults. Twenty participants (63% female; BMI: 35 ± 2 kg/m²; age: 70.5 ± 1.2 years) were randomized to 8 weeks of either exercise + BCAAs (100 mg/kg body weight/d) or exercise + placebo. The program included moderate aerobic and resistance training three times weekly. Physical function was assessed using handgrip strength, chair stands, gait speed, VO₂ max, and a 400 m walk. Psychological health was evaluated using the CES-D, Fatigue Assessment Scale (FAS), Insomnia Severity Index (ISI), and global pain, fatigue, and quality of life using a visual analog scale (VAS). Significant group x time interactions were found for handgrip strength (p = 0.03), chair stands (p < 0.01), and 400 m walk time (p < 0.01). Compared to exercise + placebo, exercise + BCAAs showed greater improvements in strength, mobility, and endurance, along with reductions in fatigue (−45% vs. +92%) and depressive symptoms (−29% vs. +5%). Time effects were also observed for ISI (−30%), FAS (−21%), and VAS quality of life (16%) following exercise + BCAA supplementation. These preliminary results suggest that BCAAs combined with exercise may be an effective way to improve physical performance and reduce fatigue and depressive symptoms in older adults. Full article

Background: Type 2 diabetes (T2D) is a growing public health concern, particularly in low- and middle-income countries. Although prediabetes is a major risk factor for T2D, it remains largely underdiagnosed and untreated. Structured lifestyle interventions have proven effective in preventing diabetes, but their feasibility within the Brazilian public health system remains unclear. Methods: This multicenter pilot randomized controlled trial assessed the feasibility of a culturally adapted lifestyle intervention (PROVEN-DIA) across the five regions of Brazil. A total of 220 adults at high risk for T2D were randomized to an intervention group or a control group (usual care) and followed for three months. Both groups received similar educational content on healthy eating and physical activity, but the intervention group participated in a structured and personalized lifestyle program with regular follow-up sessions. The primary outcome was adherence to dietary recommendations, assessed using the BALANCE Index—a validated dietary score (range: 0–40) based on the Brazilian Cardioprotective Diet that classifies foods into color-coded groups according to nutritional quality—along with engagement in moderate-to-vigorous physical activity (MVPA). Secondary outcomes included diet quality (DQIR), anthropometric and metabolic parameters. Results: Feasibility was demonstrated by a 93.2% retention rate (n = 205). There was no significant difference in the primary outcome (simultaneous improvement in diet and MVPA). However, the PROVEN-DIA group exhibited significantly greater improvements in diet quality, with a 2.8-point increase in the BALANCE Index (vs. 0.5 in the control, p = 0.03), and a significant improvement in the DQIR (p < 0.001). No significant differences between groups were observed in MVPA, HbA1C, glycaemia, or body weight. Conclusions: The PROVEN-DIA intervention proved feasible within the Brazilian public health context, resulting in significant improvements in dietary quality among individuals at high risk for T2D. A larger trial with longer follow-up is warranted to evaluate its effectiveness in preventing the progression to diabetes. However, to enhance physical activity outcomes, specific adaptations and targeted strategies may be required to better support participant engagement in exercise. Full article

Objectives: Older adults who worry about not being able to stand up from the floor after a fall, reduce their physical activity, which leads to a higher risk of falling. The Backward Chaining Method (BCM) was developed specifically for this population to safely teach and practice the movement sequence required to stand up from the floor. Our aim is to evaluate the effectiveness of using the BCM to teach older adults how to stand up from the floor, and to determine whether this training has an impact on functional mobility, muscle strength, fear of falling, and life-space mobility. Methods: A total of 26 residents of a long-term care facility were randomly allocated to two groups. Residents in the intervention group (IG, n = 13) participated in a seven-week training program to learn how to stand up from the floor with BCM, in addition to the usual care generally offered in long-term care facilities. The participants in the control group (CG, n = 13) received the usual care alone. The primary outcome measure was functional mobility, assessed by the Timed Up and Go test. Secondary outcome measures included functional lower limb strength, grip strength, fear of falling, and life-space mobility. The outcomes were measured at baseline and after the seven-week intervention period. Results: We found no significant between-group differences in functional mobility, lower limb strength and grip strength; however, IG subjects demonstrated significantly lower fear of falling scores, and significantly higher life-space mobility and independent life-space mobility scores compared to CG subjects after the training program. Conclusions: This study demonstrates that the Backward Chaining Method is a feasible, well-tolerated intervention in a long-term care setting and it may have meaningful benefits, particularly in lessening fear of falling and improving life-space mobility and independent life-space mobility when incorporated into the usual physiotherapy interventions. Full article

Background/Objectives: Aging adults are at an increased risk of depression, anxiety, and poor mood. Research indicates that interacting with companion animals may benefit vulnerable older adults’ mental health. Methods: This study randomly assigned 44 medical inpatients (59+ years) to one of three 20 min daily conditions over 3 days: interactions with a dog and handler (AAI: animal-assisted intervention), handler-only control (CC: conversational control), or usual care (UC). Participants were measured at baseline, daily pre/post-intervention, on day 5 post-intervention, and at 1- and 6-month follow-ups. Results: The results show a significant change in trajectory for the AAI group from pre- to post-intervention for anxiety and mood. Study satisfaction was significantly better in the AAI group than in the UC condition. Depression scores did not change significantly. The effects were not sustained from day 1 to day 5 or to either follow-up. Conclusions: The results suggest that short-term interactions with dogs may provide immediate improvements in anxiety and mood, and dog presence adds value above that of the handler alone. Full article

Background/Objectives: Total knee arthroplasty (TKA) is commonly associated with postoperative muscle atrophy and weakness, while traditional rehabilitation is often limited by pain and patient compliance. Passive blood flow restriction (pBFR) training may offer a safe, low-threshold method to attenuate muscle loss in this early phase. This pilot study examined the feasibility, safety, and early effects of pBFR initiated during hospitalization on muscle mass, swelling, and functional recovery after TKA. Methods: In a prospective, single-blinded trial, 26 patients undergoing primary or aseptic revision TKA were randomized to either a control group (CON: sham BFR at 20 mmHg) or intervention group (INT: pBFR at 80% limb occlusion pressure). Both groups received 50 min daily in-hospital rehabilitation sessions for five consecutive days. Outcomes, including lean muscle mass (DXA), thigh/knee circumference, 6 min walk test (6 MWT), handgrip strength, and patient-reported outcomes, were assessed preoperatively and at discharge, six weeks, and three months postoperatively. Linear mixed models with Bonferroni correction were applied. Results: The INT group showed significant preservation of thigh circumference (p = 0.002), reduced knee swelling (p < 0.001), and maintenance of lean muscle mass (p < 0.01), compared with CON, which exhibited significant declines. Functional performance improved faster in INT (e.g., 6 MWT increase at T3: +23.7%, p < 0.001; CON: −7.2%, n.s.). Quality of life improved in both groups, with greater gains in INT (p < 0.05). No adverse events were reported. Conclusions: Initiating pBFR training on the first postoperative day is feasible, safe, and effective in preserving muscle mass and reducing swelling after TKA. These findings extend prior BFR research by demonstrating its applicability in older, surgical populations. Further research is warranted to evaluate its integration with standard rehabilitation programs and long-term functional benefits. Full article

Background/Objectives: Embryo selection in IVF is traditionally based on morphology, yet many high-quality embryos fail to implant. Preimplantation genetic testing for aneuploidy (PGT-A) using next-generation sequencing (NGS) has been proposed to improve selection by identifying euploid embryos. However, its effectiveness in women of advanced maternal age remains unclear due to limited randomized data. This pilot trial assessed the feasibility of a full-scale RCT comparing PGT-A to morphology-based selection in women aged 35–42. Methods: This single-centre, two-arm parallel RCT (NCT05009745) enrolled women aged 35–42 undergoing IVF/ICSI with ≥3 good-quality day-3 embryos. Participants were randomized (1:1) to either embryo selection by morphology with fresh transfer or PGT-A with frozen transfer of a single euploid embryo. Allocation concealment was achieved via a secure web-based randomization platform; patients and clinicians were unblinded, but the biostatistician remained blinded. The primary outcome was feasibility of recruitment, randomization, and adherence. Results: Between June 2021 and January 2023, 138 women consented (recruitment rate: 55.8%, 95% CI: 49.7–62.0%) and 100 were randomized. Protocol adherence was 94%. Barriers to recruitment included preference for private PGT-A (19%) or fresh transfer (6%). Among biopsied embryos, 51.4% were euploid and 6.6% low-level mosaic. Intention-to-treat analysis showed no significant differences between PGT-A and control groups in clinical pregnancy rate (50% vs. 40%), live birth rate (50% vs. 38%), or miscarriage rate (12% vs. 8%). Cumulative live birth rate after up to three SETs was 72% vs. 52%, respectively (p > 0.05). No multiple pregnancies occurred. Conclusions: RCTs of PGT-A in older women are feasible. A multicentre design with broader inclusion criteria could improve recruitment and allow better assessment of clinical benefit. Full article

Background: Peritoneal stretching from CO₂ insufflation is a primary mechanism of pain associated with laparoscopy. Cyclooxygenase-2 inhibitors are promising anti-inflammatory and analgesic agents. This study aimed to evaluate the effect of celecoxib on postoperative pain reduction and associated changes in peritoneal gene expression after laparoendoscopic single-site (LESS) surgery for benign gynecologic disease. Methods: In this randomized, double-blind, placebo-controlled pilot study, 70 patients were randomly assigned to receive either celecoxib or placebo (400 mg) 40 min before surgery. Peritoneal tissues were collected before and after CO₂ insufflation. We analyzed changes in expressions of prostaglandin I₂ synthase, prostaglandin E synthase (PTGES), PTGES3, aldo-keto reductase family 1 member C1, and 15-hydroxyprostaglandin dehydrogenase (HPGD). Numeric Rating Scale (NRS) pain scores were also compared between groups. Results: A total of 62 patients completed the study: 30 in the celecoxib group and 32 in the placebo group. The mean CO₂ exposure time was 60.4 min. In a quantitative real-time polymerase chain reaction analysis, HPGD mRNA expression significantly increased after surgery in patients exposed to CO₂ for more than 60 min. Patients treated with celecoxib showed a significantly higher rate of grade 3 expression (83.3% vs. 37.5%; p = 0.01) and a level 2 increase in HPGD expression on in situ hybridization (58.3% vs. 12.5%; p = 0.01), despite no significant difference on immunohistochemistry. Moreover, celecoxib effectively reduced NRS pain scores compared to placebo. Conclusions: In this pilot study, celecoxib appeared to reduce postoperative pain and was associated with increased HPGD mRNA expression in the peritoneal tissue of patients with prolonged CO₂ exposure during LESS surgery. These exploratory findings warrant confirmation in larger trials with functional validation of HPGD expression (ClinicalTrials.gov, NCT03391570). Full article

Background: Heart failure (HF) is frequently associated with skeletal muscle wasting, reduced functional capacity, and malnutrition. High-protein diets offer a promising nutritional intervention to improve these outcomes in individuals with HF. Objective: This systematic review evaluated randomized controlled trials of high-protein dietary interventions in HF populations, with emphasis on intervention characteristics, quantitative benefits, and risk of bias. Methods: We conducted a comprehensive search in PubMed, MEDLINE, Embase, and Cochrane CENTRAL from inception to June 2025. Eligible studies enrolled adults (≥18 years) with HF, implemented high-protein regimens (≥1.1 g/kg/day or ~25–30% of energy), and reported on functional capacity, body composition, muscle strength, clinical outcomes, or biochemical markers. Two reviewers independently screened, extracted data, and assessed bias (Cochrane RoB 2). Heterogeneity in dosing, duration, and outcomes precluded meta-analysis; we therefore provide a narrative synthesis. Results: Ten trials (nine randomized controlled trials, one pilot) involving 1080 patients (median n = 38; range 21–652) were included. High-protein interventions yielded mean improvements in six-minute walk distance of +32 ± 14 m, lean body mass gain of +1.6 ± 0.9 kg, and 9 ± 4% enhancement in quality-of-life scores; muscle strength effects varied from −2% to +11%. Two studies reported an 18% reduction in HF readmissions (p < 0.05). The risk-of-bias assessment identified two low-risk, three moderate-risk, and one high-risk study. Key limitations include small sample sizes, varied protein dosing (1.1–1.5 g/kg/day), short follow-up (2–6 months), and outcome heterogeneity. Conclusions: High-protein dietary strategies appear to confer modest, clinically relevant gains in functional capacity, nutritional status, and HF readmission risk. Larger, well-powered trials with standardized dosing and longer follow-up are necessary to establish optimal protein targets, long-term efficacy, and safety. Full article

Objectives: We compared the effects of two active re-warm-up protocols applied during halftime’s last three minutes, after a warm-up, testing, and a simulated first-half match. Methods: Twenty-two professional players from a first Portuguese division club were randomized into two re-warm-up protocols during a simulated match interval: (i) a strength, plyometrics, and balance protocol (SPBP); and (ii) a soccer-specific protocol (SSP). Players were assessed for a 20-m linear sprint and countermovement jump (CMJ) after the warm-up and the re-warm-up. Descriptive statistics and mixed ANOVA were performed, with effect size assessed using partial eta-squared. The Acute Readiness Monitoring Scale (ARMS) questionnaire was administered after the simulated match and re-warm-up and was analyzed using a multifactorial ANOVA. Results: No significant interaction effects were observed (p > 0.05). Comparing pre-match to post-re-warm-up, there was a slight decrease in sprint (significant) and jump performance (non-significant). Additionally, there were no between-protocol differences in perceived readiness (ARMS). Conclusions: After the three-minute re-warm-up protocols, similar results were observed in the 20-m sprint performance, CMJ, and perceived readiness when comparing SPBP and SSP. These re-warm-up protocols (SPBP and SSP) are practical to implement within a 3-min time window, and, given their apparent lack of differences, players’ preferences could be considered. However, the SSP is currently subject to restrictions that limit teams’ access to the field during this period. Future research should compare active re-warm-up protocols with passive controls to more clearly assess their effectiveness. Full article

Background/Objectives: Weight gain is frequently observed during and following breast cancer therapy. Women with overweight/obesity have poorer breast cancer prognoses and are more likely to develop comorbidities. The present study describes the development and qualitative assessment of the acceptability of the NutriLife study, a lifestyle weight management intervention with dietetic counseling and digital tools for breast cancer survivors (BCSs). Methods: The intervention was developed using the Medical Research Council (MRC) framework, informed by a systematic literature review and stakeholder input. Acceptability was assessed using the Theoretical Framework of Acceptability (TFA). A total of 22 BCSs with overweight/obesity participated in focus groups, and 5 dietitians/nutritionists specializing in breast cancer in Greece participated in semi-structured interviews. The data were further analyzed using thematic analysis. Results: Stakeholders assessed the intervention as acceptable across all TFA constructs. The intervention was characterized as supportive, easily adaptable, time-efficient, well-organized, beneficial, and professionally driven, with potential barriers including limited personal time, inadequate digital literacy, insufficient self-care, and lack of commitment. Gradually increasing goals may be helpful and less stressful, while educational resources enhance focus on these objectives, thus encouraging intervention participation. Ensuring confidentiality was perceived as central to promoting health. Conclusions: The evidence-based, co-participatory design of the NutriLife intervention was perceived as acceptable by the participating stakeholders and will be pilot-tested in a randomized controlled trial. Full article

Background: Glioblastoma (GBM IDH-wildtype WHO 2021) is an aggressive central nervous system malignancy with a poor prognosis despite standard therapy. Integrative oncology approaches involving natural compounds have shown potential in preclinical studies to enhance the efficacy of chemoradiotherapy. Methods: This prospective, longitudinal observational pilot study, lacking a randomized control group, followed 72 newly diagnosed glioblastoma patients (diagnosed by histological examination and MGMT promoter molecular study alone, grade 4 glioma patients) treated with the STUPP protocol. This group could voluntarily opt to receive integrative therapy (IT), which included polydatin, curcumin, and Boswellia serrata, in addition to standard care. Survival outcomes were compared between IT-adherent and non-adherent patients. Multivariate Cox regression was employed to adjust for potential confounders, including age, extent of surgical resection, and corticosteroid use. Results: The median overall survival (OS) for the entire cohort was 13.3 months. Patients who adhered to IT (n = 60) had a median OS of 25.4 months, which increased to 34.4 months for those who underwent gross total resection. The non-IT group (n = 12) exhibited a median OS of 10.6 months. Multivariate analysis confirmed that IT adherence and the extent of resection were independent predictors of prolonged survival (p < 0.05). No severe adverse events were reported with IT. Conclusions: Integrative therapy combining polydatin, curcumin, and Boswellia serrata with standard treatment would appear to be associated with prolonged survival in glioblastoma patients, particularly among those who underwent gross total resection. However, the small size of the control group, the absence of randomization, and the inclusion solely of primary glioblastoma limit the generalizability of these findings. These results underscore the need for further investigation through randomized controlled trials. Full article

Aim: This systematic review aims to evaluate the effectiveness of microbiota-modulating interventions (such as probiotics, prebiotics, and fecal microbiota transplantation) in reducing cognitive symptoms, pain, and neuroinflammation in human studies relevant to fibromyalgia (FM). The review will investigate the role of gut–brain axis modulation through these interventions and explore the potential therapeutic benefits for FM management. Materials and Methods: A comprehensive search was conducted in electronic databases including PubMed, Scopus, and the Cochrane Library for studies published from 1 January 2015 to 30 April 2025. Studies were eligible if they were randomized controlled trials (RCTs), pilot studies, or observational studies assessing the impact of microbiota-targeted interventions (probiotics, prebiotics, fecal microbiota transplantation) on cognitive function, pain, or neuroinflammation in patients with FM. Studies were excluded if they involved animal models, lacked relevant outcome measures, or were not peer-reviewed. Although only a subset of the included studies directly involved FM patients, all were selected for their relevance to symptom domains (e.g., pain, cognition, mood) and mechanisms (e.g., neuroinflammation, gut–brain axis dysfunction) that are central to FM. A total of 11 human studies were included in the final qualitative synthesis. Results: Preliminary findings from the included studies suggest that microbiota-targeted interventions, particularly probiotics and prebiotics, show promise in reducing cognitive symptoms, pain, and neuroinflammation in FM patients. Improvements in mood and quality of life were also reported, indicating potential benefits for overall well-being. However, heterogeneity in study designs, sample sizes, and outcome measures limit the ability to draw definitive conclusions. Conclusions: This systematic review highlights the potential of microbiota modulation as a therapeutic strategy for managing FM symptoms, particularly cognitive dysfunction and neuroinflammation. Full article

Background: Parkinson’s disease (PD) presents a significant challenge due to its wide range of motor, non-motor, and treatment-related symptoms. Non-invasive interventions like transcranial magnetic stimulation (TMS) are being explored for potential therapeutic benefits. This study aimed to assess if a high-frequency repetitive TMS protocol (HF-rTMS) consisting of 10 trains of 100 pulses of rTMS at 25 Hz over the motor cortex (M1) at 80% of the resting motor threshold could be effective in treating motor or non-motor symptoms in patients with PD with levodopa-induced dyskinesias. Methods: A randomized, single-blinded, placebo-controlled pilot trial was conducted with eleven PD patients. Nine patients received HF-rTMS, while two received sham stimulation. Patients were exhaustively evaluated using validated clinical scales to assess motor and non-motor symptoms. The study followed a rigorous protocol to avoid bias, with assessments conducted by a neurologist specialized in single-blinded movement disorder. Results: The HF-rTMS group experienced a statistically significant slight worsening in both motor and non-motor symptoms, particularly in the mood/cognition and gastrointestinal domains. However, positive effects were observed in some non-motor symptoms, specifically reduced excessive sweating and weight. No adverse effects were reported. Conclusions: Although HF-rTMS did not produce significant motor improvements, its potential benefit on specific non-motor symptoms, such as autonomic regulation, warrants further investigation. Full article

Multi-agent large language models promise flexible, modular architectures for delivering personalized educational content. Drawing on a pilot randomized controlled trial with middle school students (n = 23), we introduce a two-agent GPT-4 framework in which a Profiler agent infers learner-specific preferences and a Rewrite agent dynamically adapts science passages via an explicit message-passing protocol. We implement structured system and user prompts as inter-agent communication schemas to enable real-time content adaptation. The results of an ordinal logistic regression analysis hinted that students may be more likely to prefer texts aligned with their profile, demonstrating the feasibility of multi-agent system-driven personalization and highlighting the need for additional work to build upon this pilot study. Beyond empirical validation, we present a modular multi-agent architecture detailing agent roles, communication interfaces, and scalability considerations. We discuss design best practices, ethical safeguards, and pathways for extending this framework to collaborative agent networks—such as feedback-analysis agents—in K-12 settings. These results advance both our theoretical and applied understanding of multi-agent LLM systems for personalized learning. Full article