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Effectiveness of transcranial direct current stimulation with and without positive mood induction on worry and transdiagnostic cognitive-emotional processes: A randomized controlled trial.

The present study investigated the effectiveness of transcranial direct current stimulation (tDCS), with and without positive mood induction, on worry and key transdiagnostic cognitive-emotional processes, including attentional bias, working memory, problem solving, and emotion regulation, in individuals with high levels of worry. This single-blind randomized controlled trial included 45 individuals with high levels of worry. After a structured clinical interview, participants were randomly assigned, with gender balancing, to one of three groups: (1) tDCS alone, (2) tDCS combined with positive mood induction, or (3) a sham control group. Outcome measures were administered at three time points (pretest, posttest, and one-month follow-up) and assessed attentional bias (Dot Probe Task), working memory (1-back task), problem solving (Tower of London task), emotion regulation (Gross's Emotion Regulation Questionnaire), and worry severity (Penn State Worry Questionnaire; PSWQ). Repeated-measures ANOVA showed that both active groups (tDCS alone and tDCS + positive mood induction) significantly improved attentional bias, worry, working memory, problem solving, and emotion regulation compared to controls (p < 0.05). The combined intervention produced significantly greater gains than tDCS alone in working memory, problem solving, emotion regulation (p < 0.05), and reductions in attentional bias and worry (p < 0.001). All effects persisted at one-month follow-up (p < 0.05). tDCS reduces worry and attentional bias and enhances cognition and emotion regulation in individuals with high levels of worry. The combined intervention produced larger and more sustained improvements than tDCS alone across the assessed behavioral outcomes. These findings support further investigation of combining tDCS with structured positive mood induction while the mechanisms underlying the additional benefits remain to be established.

Humans

Educational Effects of Electronic Documents and Videos on Parents' Responses to Acute Illness in Young Children: A Randomized Controlled Trial.

AIM: This study compared changes associated with electronic document-based and video-based education for parents responding to acute illness in young children, focusing on self-reported knowledge, anxiety, and satisfaction. METHODS: A randomized controlled trial with pre- and post-intervention measurements was conducted among 140 adults in Japan who self-reported raising a child under 3&#x2009;years of age and having experienced their child's acute illness. Participants were assigned to an electronic document group or a video group (n&#x2009;=&#x2009;70 each). Self-reported knowledge was assessed using a researcher-developed questionnaire, and anxiety was measured using the State-Trait Anxiety Inventory. Pre-post changes and between-group differences in change scores were examined. RESULTS: Total self-reported knowledge scores increased significantly in both groups (p&#x2009;<&#x2009;0.01), with no significant between-group difference. The video group showed significant improvements in items related to symptoms requiring attention at home and information sources, whereas the electronic document group improved in items related to symptoms requiring medical consultation and emergency calls. State and trait anxiety did not change significantly in either group. Satisfaction was high in both groups. CONCLUSIONS: Both educational formats may support parents' learning about responses to acute illness in young children, although appropriate formats may differ according to the educational content. Information provision alone may have limited effects on anxiety; therefore, future parent education should incorporate interactive and reassurance-focused approaches. TRIAL REGISTRATION: UMIN-CTR: UMIN000056457.

Humans

Effects of strength and balance training on the structure of the aging brain.

BACKGROUND: While it is established that motor training induces structural changes in the brains of young adults, structural adaptations in aging brains are less studied. METHODS: This randomized controlled study investigated the impact of long-term strength and balance training on the structural plasticity in 60 elderly adults (64 - 82 years old, 70.6 &#xb1; 4.7) using multi-modal neuroimaging. We compared the effects of three months of strength training to balance training of the same duration and to a passive control group. Voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) were used to assess grey matter (GM) and white matter (WM) plasticity. White matter tract integrity (WMTI) modelling was employed to explore the microstructural underpinnings of white matter alterations. RESULTS: We found that strength training was associated with changes in diffusion metrics consistent with white matter microstructural remodeling, specifically increased extra-axonal axial diffusivity in the bilateral inferior fronto-occipital and longitudinal fasciculi. Additionally, both balance and strength training mitigated reductions in axonal water fraction in the splenium of the corpus callosum and the right posterior corona radiata observed in the control group. CONCLUSION: These results underscore the potential relevance of strength and balance training to induce beneficial neural plasticity by counteracting aging-related demyelination in the corpus callosum and highlight the specific role of strength training in facilitating white matter reorganization in key transmission fiber pathways.

Humans

The radiographic effect of cage subsidence on neuroforamina after anterior cervical discectomy and fusion.

STUDY DESIGN: Retrospective Cohort Study. OBJECTIVE: The objective of this study is to investigate the effect of cage subsidence on neuroforaminal area after anterior cervical discectomy and fusion (ACDF) utilizing computed tomography (CT). SUMMARY OF BACKGROUND DATA: Restoration of disc height via implantation of an interbody device provides an indirect decompression of the cervical neuroforamina. Interbody cage subsidence is a potential postoperative occurrence, but the effect of this on neuroforaminal area has yet to be characterized. METHODS: A retrospective review was conducted of patients who underwent one- to four-levels of ACDF utilizing an interbody device with anterior plating. Cage subsidence, neuroforaminal area, height and width were measured on CT scans preoperatively and at least 6&#xa0;months postoperatively. Levels with a cumulative sum of cranial and caudal subsidence greater than 4&#xa0;mm were classified as severely subsided, while levels with cumulative subsidence less than 4&#xa0;mm were classified as non-severely subsided. RESULTS: A total of 83 patients (151 levels) were included in this retrospective analysis. Average endplate subsidence was 3.2&#xa0;&#xb1;&#xa0;1.9&#xa0;mm. Non-severely subsided levels demonstrated a greater perioperative increase in neuroforaminal area (7.9 vs 2.1&#xa0;mm2, p&#xa0;<&#xa0;0.001), neuroforaminal height (1.1 vs 0.4&#xa0;mm, p&#xa0;<&#xa0;0.001) and neuroforaminal width (0.7 vs 0.1&#xa0;mm, p&#xa0;<&#xa0;0.001) compared to severely subsided levels. Interbody subsidence significantly predicted a decreased change in neuroforaminal height, width and area (p&#xa0;<&#xa0;0.001). Severe subsidence was associated with an increased rate of pseudarthrosis, but similar reoperation rates and recurrent neurologic deficits between the two groups. CONCLUSIONS: Severe subsidence of interbody cages after an ACDF was associated with a decreased perioperative change in neuroforaminal dimensions. This decrease in the size of the neuroforamen may reduce the effect of indirect decompression of the nerve root.

Humans

Efficacy, tolerability, and threshold effect of atropine eye drops for myopia control: A systematic review and dose-response meta-analysis.

Atropine is an emerging therapy for myopia, yet the optimal concentration for prescription remains uncertain. We searched PubMed, Embase, Web of Science, Cochrane Library, World Health Organization International Clinical Trials, and ClinicalTrials.gov registry platforms. We included the randomized clinical trials (RCTs) that compared any dose of atropine against a placebo in myopic children. Among 3566 studies assessed, we identified 33 eligible RCTs involving 6301 children aged 4-18 years, with 10 different concentrations and a mean follow-up time of 19.5&#x202f;&#xb1;&#x202f;12.3 months. A nonlinear relationship was observed between atropine dosage and treatment efficacy (P&#x202f;<&#x202f;0.001). Compared to placebo groups, the mean differences in reducing annual spherical equivalent refraction progression for atropine concentrations of 0.01%, 0.02%, 0.03%, 0.04%, and 0.05% were 0.21 diopters (D) (95% CI, 0.13-0.28), 0.35 D (95% CI, 0.23-0.46), 0.42 D (95% CI, 0.28-0.56), 0.45 D (95% CI, 0.30-0.60), and 0.46 D (95% CI, 0.32-0.61) respectively For higher concentrations, the estimates were 0.49 D (95% CI, 0.34-0.63) for 0.1% and 0.99 D (95% CI, 0.66-1.31) for 1%, although these were based on fewer and smaller trials. Higher doses of atropine were associated with decreased amplitude of accommodation (P&#x202f;=&#x202f;0.02), increased pupil diameters (P&#x202f;=&#x202f;0.01) and a higher frequency of photophobia (P&#x202f;=&#x202f;0.02). Our findings suggest that the increase in treatment efficacy with higher concentrations may plateau beyond a certain range, and that the current practice of increasing atropine concentrations for children who show inadequate responses to lower doses should be confined to a specific concentration range. This analysis is limited by the number, design heterogeneity, and sample sizes of available trials for higher concentrations, and by the frequent lack of pre-intervention refractive history in included studies. Therefore, estimates-particularly for doses exceeding 0.1%-should be interpreted with caution.

Humans

Cross-kingdom dynamics of the subgingival bacteriome and mycobiome: A pilot study on the effects of a novel HA-H&#x2082;O&#x2082;-Glycine formulation to treat periodontitis.

OBJECTIVES: Traditional periodontal therapy primarily focuses on bacterial biofilm control; however, recent evidence also suggests a critical role for the oral mycobiome. This study evaluated the clinical and ecological impact of a novel mouthwash formulation containing hyaluronic acid (HA), hydrogen peroxide (H2O2), and glycine on periodontal patients METHODS: This prospective, randomized split-mouth trial included 13 adult participants with periodontitis treated with HA-H2O2-glycine formula (BMG0703A) used twice a day for seven days. Subgingival plaque samples were collected from periodontal pocket and healthy control sites at baseline (T0) and one-week post-treatment (T1). Microbial and fungal communities were characterized using Next-Generation Sequencing (NGS) of the 16S rRNA and ITS2 regions. Linear Mixed Models (LMM) and Spearman correlation were used to assess taxonomic shifts and cross-kingdom relationships. RESULTS: Sequencing revealed a promising ecological shift: the bacteriome shifted from anaerobic dominance (Olsenella, Peptostreptococcus) toward a health-associated aerobic profile, with Rothia near-doubling (11.91% to 22.68%). The mycobiome underwent a "normalization" effect: Candida abundance decreased significantly (22.8% to 9.1%), while fungal Shannon diversity in pockets returned to healthy-site levels. Inter-kingdom analysis identified antagonistic relationships between expanding commensal bacteria and opportunistic fungi, suggesting that the intervention may help re-establish a protective bacterial niche. CONCLUSIONS: The HA-H2O2-glycine formulation seems to facilitate a rapid, cross-kingdom modulation of the subgingival niche. By reducing anaerobic pathogens and normalizing the mycobiome it appear to induce short-term changes, suggesting potential as adjunctive strategy in periodontal management. CLINICAL SIGNIFICANCE: The present work underlines the possible cross-Kingdom effects of a novel compound.

Humans

The Effect of Game-Based Virtual Reality Rehabilitation and Its Impact on Upper Extremity Function After Arthroscopic Rotator Cuff Repair: A Randomized Controlled Trial.

BACKGROUND: Arthroscopic rotator cuff repair (ARCR) often results in prolonged recovery and limited shoulder function. Conventional physical therapy rehabilitation programs require sustained patient engagement; however, adherence is frequently low. Game-based virtual reality (VR) offers an interactive and engaging environment that may enhance rehabilitation outcomes. OBJECTIVE: To evaluate the effect of a game-based VR program on the function of the upper limb in patients following ARCR. METHODS: A randomized controlled trial was conducted with patients who underwent ARCR. Participants were randomized into two groups: game-based VR or conventional rehabilitation. Outcomes were evaluated using the Disabilities of the Arm, Shoulder and Hand score, pain severity by the Numerical Pain Rating Scale, range of motion measures, and muscle strength testing. Assessments were performed at baseline and at 6 weeks and 12 weeks post surgery. RESULTS: Results have shown significant within-group improvements in pain, function, range of motion, and isometric muscle strength across all time points (P < 0.05). Between-group analysis revealed greater improvements in pain, function, flexion range, and abduction and external rotation strength in the experimental group at both time points (P < 0.05). Abduction range improved significantly only at 12 weeks (P = 0.02), whereas external rotation range showed no significant difference between groups at either time point (P > 0.05). CONCLUSION: The findings indicate that integrating game-based VR rehabilitation provides additional benefits over conventional therapy in improving pain and upper extremity function following ARCR. These findings support the use of VR as an effective alternative to the conventional rehabilitation for postoperative rehabilitation.

Humans

Proteomic insights into the immunomodulatory effects of Ca/Sr co-doped sol-gel coatings for titanium implants.

Ionic functionalization of biomaterial coatings has emerged as a powerful strategy to regulate early host responses at the implant interface. However, how combined Ca/Sr incorporation governs the adsorbed proteome and downstream immune signaling remains poorly understood. This study analyses, employing in vitro tests and proteomics, the effect of adding Sr and Ca to Si-based coatings designed to bioactivate Ti implants. Hybrid Si-based coatings were synthesized by the sol-gel route with a fixed Ca content (0.5&#x202f;wt%) and increasing Sr contents (0.5, 1.0, 1.5&#x202f;wt%), and their physicochemical properties, ion release kinetics, and hydrolytic stability were characterized. The coatings remained highly crosslinked despite Ca/Sr incorporation, whereas the highest Sr content increased hydrolytic degradation to around 70% after 56 days. Proteomic analysis identified 183 adsorbed proteins, of which 56 were differentially adsorbed on Ca/Sr-coatings, mainly associated with immune and coagulation pathways. In vitro, RAW 264.7 showed increased gene expression of TNF-&#x3b1; and TGF-&#x3b2;; with an enhanced TNF-&#x3b1; secretion by the addition of Ca and Sr. In parallel, MC3T3-E1 indicated that Ca/Sr-coatings were not cytotoxic and did not impair cell proliferation. However, ALP activity was reduced in the co-doped groups, indicating that the immunomodulatory effects induced by Ca/Sr incorporation were not accompanied by enhanced early osteogenic differentiation. The Ca/Sr combination induced alterations in the adsorption of immune-related proteins, which correlated with the in vitro findings. The deeper insight into how Ca/Sr mixtures modulate protein adsorption on biomaterial surfaces may be key to understanding the immunomodulatory capacity of these bioactive cations.

Animals

Effects of phenylephrine and norepinephrine with restrictive infusion on oxygenation during one-lung ventilation for lung surgery: a randomized controlled trial.

OBJECTIVE: This study compared&#xa0;the effects of norepinephrine or phenylephrine combined with restrictive infusion on the oxygenation during thoracoscopic one-lung ventilation (OLV). METHODS: Ninety patients were randomly divided into three groups: the norepinephrine group (Group N), the phenylephrine group (Group P), and the control group (Group C). Arterial partial pressure of oxygen (PaO2) and intrapulmonary shunt fraction (Qs/Qt) were measured with patients in lateral positions during two-lung ventilation (TLV) at 10&#x2009;min (T1), and during OLV at 15&#x2009;min (T2) and 45&#x2009;min (T3). Lung tissue samples were analyzed for endothelin and COX-2 levels after surgery. RESULTS: At T3, Group P had significantly higher PaO2 and lower Qs/Qt than Groups N and C (all p&#x2009;<&#x2009;0.05), with no significant differences between Groups N and C (all p&#x2009;>&#x2009;0.05). Compared to T1, Groups N and C showed significantly lower PaO2 and higher Qs/Qt at T2 and T3 (all p&#x2009;<&#x2009;0.05), with no significant differences in PaO2 and Qs/Qt at T3 compared with T2 (all p&#x2009;>&#x2009;0.05). Group P patients had lower PaO2 and higher Qs/Qt at T2 and T3 compared to T1 (all p&#x2009;<&#x2009;0.05), but at T3, PaO2 increased and Qs/Qt decreased compared to T2 (all p&#x2009;<&#x2009;0.05). Lung tissue levels of endothelin and COX-2 were significantly elevated in group P compared to groups N and C (all p&#x2009;<&#x2009;0.05). CONCLUSION: Combining phenylephrine with restrictive infusion during OLV improved oxygenation by increasing PaO2, decreasing Qs/Qt, and raising endothelin and COX-2 levels in lung tissue, thereby enhancing the HPV effect.

Humans

The effects of mindfulness-based cognitive therapy in the psychological and physical health of cancer patients: A systematic review and meta-analysis.

PURPOSE: No prior systematic review has specifically evaluated the efficacy of mindfulness-based cognitive therapy (MBCT) in improving both psychological and physical outcomes among cancer populations. This study aims to assess MBCT's effects on cancer patients' mental and physical health. METHOD: Following PRISMA guidelines and with PROSPERO registration (CRD42023453581), we systematically searched PubMed, Cochrane CENTRAL, Embase, and Web of Science for randomized controlled trials (RCTs) were searched up to June 2026. Eligible trials enrolled adults (&#x2265; 18&#xa0;years) with any cancer type/stage, compared MBCT delivered per standard manual against non-MBCT controls, and reported at least one validated measure of distress, depression, or anxiety; secondary outcomes included fatigue, quality of life, and mindfulness skills. Two reviewers independently selected studies, extracted data, and assessed risk of bias using the Cochrane tool; random-effects meta-analyses were performed in Stata 16. RESULTS: 11 RCTs comprising 1122 participants (mean age 54.8&#xa0;years; 91% female) were included. MBCT produced large, significant reductions in psychological distress (SMD&#xa0;=&#xa0;-0.81, 95% CI-1.27 to-0.40), depression (SMD&#xa0;=&#xa0;-0.95, 95% CI -1.40 to-0.49), and anxiety (SMD&#xa0;=&#xa0;-0.86, 95% CI -1.22 to-0.51). It also markedly decreased fatigue (SMD&#xa0;=&#xa0;-0.83, 95% CI-1.10 to-0.56), improved quality of life (SMD&#xa0;=&#xa0;0.56, 95% CI 0.22-0.88), and enhanced mindfulness skills (SMD&#xa0;=&#xa0;0.76, 95% CI 0.59-0.92). CONCLUSIONS: This meta-analysis is the first to exclusively synthesize RCT evidence of standardized MBCT in cancer care, demonstrating significant dual benefits for emotional and physical well-being while providing strong support for integrating MBCT into comprehensive oncology rehabilitation.

Humans

Rotavirus vaccine effectiveness against rotavirus and acute gastroenteritis mortality: an analysis of pooled case-control studies from the MNSSTER-V dataset.

BACKGROUND: Rotavirus accounts for an estimated 25% of diarrhoea deaths in children under 5 years globally, and more than 140 countries have included rotavirus vaccines in their routine national infant vaccination programmes. We aimed to calculate rotavirus vaccine effectiveness against rotavirus-positive and all-cause acute gastroenteritis deaths. METHODS: The Multi-National Subpopulations Study to Evaluate Rotavirus Vaccines (MNSSTER-V) dataset combines child-level data from test-negative case-control studies of rotavirus vaccine effectiveness that enrolled children under 5 years of age seeking care for acute gastroenteritis at hospitals or emergency departments in 24 countries between July 1, 2007, and Aug 24, 2023. Children were included in this study if they were: younger than 5 years, met the acute gastroenteritis case definition (had at least three episodes of diarrhoea in a 24-h period, had non-bloody and non-chronic diarrhoea, and were enrolled within 7 days of diarrhoea onset), met vaccine card quality metrics, had vaccine delivery dates if the child was reported to have received a rotavirus vaccine, and had a reported outcome of death or discharge. In-hospital acute gastroenteritis deaths were characterised, and rotavirus vaccine effectiveness against all-cause and rotavirus-positive acute gastroenteritis mortality was calculated using an unconditional logistic regression model with adjustment for national under-5 mortality strata and child's age. Vaccine effectiveness analyses against all-cause and rotavirus-positive acute gastroenteritis mortality were restricted to children aged at least 3 months who received any routine vaccines from countries reporting at least one acute gastroenteritis death. FINDINGS: From the MNSSTER-V dataset, we included 27&#x2008;252 children younger than 5 years enrolled from 22 countries; outcomes of patients were not available for two countries. At least one in-hospital acute gastroenteritis death was reported from 16 countries including 21&#x2008;522 children; in total, 183 all-cause acute gastroenteritis deaths and 25 rotavirus-positive deaths were reported. Among children aged at least 3 months who had received any routine vaccines, receiving at least one dose of a rotavirus vaccine had an adjusted vaccine effectiveness of 75&#xb7;8% (95% CI 28&#xb7;4 to 91&#xb7;8; n=13&#x2008;630) against rotavirus-positive acute gastroenteritis mortality and 20&#xb7;8% (-47&#xb7;0 to 57&#xb7;3; n=20&#x2008;005) against all-cause acute gastroenteritis mortality. INTERPRETATION: Rotavirus vaccines are effective in preventing rotavirus-positive acute gastroenteritis mortality. Continued efforts to improve vaccine delivery could help to reduce acute gastroenteritis mortality due to rotavirus worldwide. FUNDING: None.

Humans

Effects of multistrain probiotic supplementation on hepatic function and anthropometric parameters in patients with metabolic dysfunction-associated steatotic liver disease: a double-blind, randomized controlled trial.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly prevalent on a global scale. The gut microbiota is integral to its pathogenesis, prompting extensive research into microbiota modulation as a potential adjunctive therapeutic strategy. AIM: The study aimed to evaluate the effect of multistrain probiotics supplementation on hepatic function in patients with MASLD in a double-blind, randomized, controlled trial. The primary outcomes were changes in Fibrosis-4 index (FIB-4) and fatty liver index (FLI). Secondary outcomes included changes in anthropometric parameters, selected biochemical markers, and other liver-related indices. METHODS: A total of 64 patients with MASLD were randomly assigned to two groups receiving either placebo (C) or a probiotic mixture (PRO) containing the following bacterial strains: 50% Lactococcus lactis Rosell-1058, 25% Lacticaseibacillus casei Rosell-215, 12.5% Lactobacillus helveticus Rosell-52, 12.5% Bifidobacterium bifidum Rosell-71 for 12 wk. RESULTS: Significant group &#xd7; time interactions were observed for FIB-4 (Q = 0.007), with reduction in the PRO group and increase in the C group (-0.05 vs. 0.10; P = 0.002). No significant interaction was found for FLI (Q = 0.942). Significant group &#xd7; time interactions were also observed for aspartate aminotransferase (-2.87 vs. 1.87 U/L; Q = 0.003) and APRI (-0.03 vs. 0.02; Q = 0.001), favoring the PRO group (P < 0.001 for both). No significant changes were observed in anthropometric parameters, glucose levels, or lipid profile. CONCLUSIONS: In patients with MASLD, the 12-wk probiotic supplementation had a modest but statistically significant effect on FIB-4, aspartate aminotransferase, and APRI, with no significant effect on FLI or anthropometric and metabolic parameters. These findings suggest that this probiotic formulation may have potential benefits for liver function in MASLD. However, long-term studies incorporating imaging-based and histological endpoints are required to determine the clinical significance of these findings.

Humans

Effects of acute inflammatory challenge on anhedonia and social reward processing: A randomized controlled trial of endotoxin.

Anhedonia is a core feature of depression that reflects reward system dysfunction. Acute inflammatory challenge has been shown to induce transient anhedonia and reward processing deficits, but its effects on distinct components of social reward processes remain poorly understood. This randomized, double-blind, placebo-controlled study evaluated anhedonia and social reward responsivity following acute inflammatory challenge. Low-dose endotoxin (0.8&#x202f;ng/kg body weight; n&#x202f;=&#x202f;18) or placebo (same volume of 0.9% saline; n&#x202f;=&#x202f;22) was administered to female adults (ages 25-44). Anhedonia (Snaith-Hamilton Pleasure Questionnaire) and blood samples for cytokine assessment were collected pre-infusion and 2 and 4&#x202f;h post-infusion. Social reward motivation (wanting to engage in a social task) was assessed at a baseline eligibility visit and 2&#x202f;h post-infusion. Sensitivity to positive social cues (attentional bias toward and recognition of happy faces) was assessed pre-infusion and 2&#x202f;h post-infusion. Results showed that endotoxin increased anhedonic symptoms (p&#x202f;=&#x202f;.005) and decreased social motivation by 2&#x202f;h post-infusion (p&#x202f;=&#x202f;.001); within the endotoxin condition, changes in both outcomes were associated with increases in TNF-&#x3b1; (p's&#x202f;<&#x202f;.04). A significant condition-by-time interaction for happy-face recognition (p&#x202f;=&#x202f;.011) was driven by increased accuracy in the placebo (p&#x202f;=&#x202f;.04) but not endotoxin (p&#x202f;=&#x202f;.43) condition. Endotoxin administration did not affect attentional bias toward happy faces. Findings suggest that acute inflammatory challenge induces anhedonia and reduces social motivation, with more limited effects on sensitivity to positive social cues, highlighting specific reward-related pathways through which immune activation may contribute to inflammation-associated depression. Future work could examine whether immune-related changes in social motivation contribute to motivational deficits in depression.

Humans

Effect of atenolol versus ivabradine on heart rate variability in patients of schizophrenia with clozapine-induced tachycardia: a randomized controlled trial.

BACKGROUND: A third of schizophrenia cases are resistant to antipsychotics, where clozapine is the only FDA-approved medication. Clozapine use is often limited by intolerable adverse effects. Persistent tachycardia occurs in approximately 25-54% patients receiving clozapine. Heart rate variability (HRV) is a non-invasive, clinically relevant marker of autonomic nervous system functioning. Atenolol and Ivabradine are usually prescribed for clozapine-induced tachycardia (CIT), although evidence guiding their optimal use remains limited. AIM: This study aimed to compare the effects of atenolol versus ivabradine on HRV in patients with treatment-resistant schizophrenia (TRS) receiving clozapine. METHODS: This open-label randomised clinical trial, conducted at a tertiary-care center over 20 months, involved TRS patients on clozapine for more than three months and having persistent tachycardia. Twenty patients received atenolol 25mg once-daily, while twenty received ivabradine 5mg twice-daily for two months. The primary outcome was the change in the frequency domain of HRV, while the secondary outcomes were time-domains, central and peripheral blood pressure, pulse rate and treatment-emergent adverse events (TEAE). RESULTS: While both drugs significantly reduced pulse-rates (atenolol: -20.56&#xb1;13.00, p<0.001; ivabradine: -21.855&#xb1;12.873, p<0.001). Within-group analysis showed that, the atenolol group had significant improvements in high-frequency [HF] power (p=0.048) and LF/HF ratio (p=0.044), along with a non-significant trend towards increased total power (p=0.053); no significant within-group changes were observed in the ivabradine group. CONCLUSION: No significant between-group differences in HRV parameters were established between atenolol and ivabradine. Ivabradine could be a viable option in patients where atenolol is either contraindicated or not tolerated. Future larger multicentric studies are needed for greater generalisability. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT06505668.

Humans

Systematic Review on the Effectiveness of Photobiomodulation Therapy on Enhancing Musculoskeletal Rehabilitation Outcomes after Total Knee and Hip Arthroplasty.

BACKGROUND: Total knee and hip arthroplasty (TKA/THA) effectively alleviate chronic pain and improve joint function and quality of life. However, postoperative recovery is often hindered by pain, edema, restricted range of motion (ROM), and muscle weakness, necessitating structured physical rehabilitation. Photobiomodulation Therapy (PBMT) has been proposed as an adjunct modality to enhance rehabilitation outcomes. This systematic review evaluates the efficacy of PBMT in reducing postoperative pain and edema as well as improving ROM and functional performance compared with placebo or standard physical therapy in post-arthroplasty patients. METHODS: A systematic search of PubMed, ProQuest, ScienceDirect, and Google Scholar was conducted from inception to May 31, 2025. Only prospective controlled trials assessing PBMT effects on postoperative pain, swelling, ROM, or functional performance following TKA or THA were included. Case reports, uncontrolled studies, and trials focusing on unrelated outcomes were excluded. Article selection involved title, abstract, and full-text screening, with additional studies identified through reference lists. The review is registered in PROSPERO (CRD420251123169). RESULTS: Four randomized controlled trials (RCTs; n = 133 participants) met the inclusion criteria, three studies focused on TKA, and one study examined THA. PBMT significantly improved postoperative pain and edema reduction in three trials, while two studies demonstrated enhanced ROM and functional outcomes compared with control or placebo interventions. PEDro scores ranged from 8 to 10, indicating moderate-to-high methodological quality. CONCLUSIONS: PBMT shows promising short-term benefits in reducing postoperative pain and swelling and improving functional performance after knee or hip arthroplasty. However, due to heterogeneity in treatment parameters and limited high-quality trials, conclusive evidence remains insufficient. Future large-scale RCTs with standardized PBMT parameters and extended follow-up are warranted to confirm its clinical efficacy.

Humans

Effects of extended problem-based learning interventions on undergraduate nursing education: A systematic review.

OBJECTIVE: Exploring the effects of long-term PBL (problem-based learning) intervention on undergraduate nursing students. METHODS: The article retrieved literature from CINAHL Complete, Academic Search Complete, Web of Science, PubMed, EMBASE, OVID, and Cochrane Library up to January 2025. Studies had to meet all of these criteria: (1) They used a randomized controlled trial (RCT) and quasi-experimental design. (2) The PBL pedagogy intervention lasted 4&#xa0;weeks or longer. (3) The participants were undergraduate nursing students. (4) They reported primary outcomes. These included critical thinking, problem-solving skills and self-directed learning. Two researchers screened articles, extracted data, and assessed quality independently using blinding. They used Cochrane ROB2 for RCTs and ROBINS-I for quasi-experimental studies to judge bias risk. Meta-analysis was performed using RevMan 5.4 software. For continuous variables, standardized mean difference (SMD) and 95% confidence interval were calculated. Heterogeneity was assessed by I2 statistic. When I2&#xa0;>&#xa0;50%, sensitivity analysis was conducted. The source of heterogeneity was explored by excluding studies one by one. The primary outcomes included standardized critical thinking, problem-solving, and self-directed learning assessment results. RESULTS: A total of 11 randomized controlled trials and quasi-experimental studies were retrieved and included for meta-analysis. The experimental group significantly outperformed the control group in critical thinking, problem-solving, and self-directed learning, with differences being statistically significant (P&#xa0;&#x2264;&#xa0;0.05). However, high heterogeneity was observed. After sensitivity analysis, the heterogeneity was reduced and the results remained statistically significant, indicating that the findings were not solely dependent on the excluded studies.

Problem-Based Learning

Post-intervention effectiveness of a computerized personalized cognitive stimulation program adapted according to cognitive reserve in older adults without cognitive impairment in Primary Care: A randomized clinical trial.

BACKGROUND: Cognitive reserve may influence responsiveness to cognitive interventions, yet it is rarely used to tailor computerized stimulation. OBJECTIVE: To evaluate the effectiveness of a computerized cognitive stimulation program personalized according to cognitive reserve on cognition, reserve-related activities, and digital competence in community-dwelling older adults without cognitive impairment in Primary Care. METHODS: In this randomized clinical trial, 102 adults aged &#x2265;65 years with normal cognitive performance were recruited from three primary care centers in Zaragoza, Spain, and stratified by cognitive reserve level before random allocation to intervention or control. The intervention comprised digital literacy sessions followed by 8 weeks of home-based computerized cognitive stimulation tailored to participants' cognitive reserve profiles and life history. Controls received a single group-based health education session focused on maintaining everyday cognitive activity. Outcomes were assessed at baseline and post-intervention using global cognition (MEC-35), the Cognitive Reserve Questionnaire, the Mobile Device Proficiency Questionnaire-16, and domain-specific neuropsychological tests. A total of 100 participants completed the final evaluation and were included in complete-case analyses. RESULTS: Compared with controls, the intervention group showed greater adjusted post-intervention improvements in global cognition (MEC-35 between-group difference: 1.8 points) and several cognitive measures, including temporal orientation, calculation, attention, praxis, verbal fluency, processing speed, executive functions, and verbal learning. CRQ scores and digital competence also improved, with small-to-large effect sizes. CONCLUSIONS: A computerized cognitive stimulation program adapted according to cognitive reserve appears feasible in Primary Care and may improve cognition, engagement in reserve-related activities, and digital competence in older adults without cognitive impairment.

Humans

Effectiveness of an AI-based home exercise app for rehabilitation of rotator cuff-related shoulder pain: A randomized controlled trial.

BACKGROUND: Rotator cuff-related shoulder pain contributes to disability and healthcare use. Although therapeutic exercise is first-line treatment, limited supervision and adherence may reduce its effectiveness; digital rehabilitation with real-time feedback may address these limitations. OBJECTIVES: To evaluate the effectiveness of adding a digital rehabilitation program to standard physiotherapy on pain, function, fear-avoidance beliefs, and healthcare utilization. DESIGN: Single-center, assessor-blinded, randomized controlled trial with two parallel groups. METHOD: Forty-six adults (mean age 59 years) with rotator cuff-related shoulder pain were randomized to 12 weeks of conventional physiotherapy or physiotherapy plus an AI-based digital rehabilitation program using computer vision for real-time feedback and performance monitoring. Outcomes were assessed at baseline and at 2, 4, and 12 weeks. Pain intensity (NPRS) was primary outcome; secondary outcomes included upper limb function (QuickDASH), fear-avoidance beliefs (FABQ), and post-intervention healthcare utilization. Analyses followed an intention-to-treat approach. RESULTS: Pain reduction exceeded the MCID (1.3) at 4 and 12 weeks. Between-group differences favoured the intervention at Weeks 2 and 4 (MD -0.7; 95% CI -1.13 to -0.14 and MD -1.01; 95% CI -1.8 to -0.2, respectively). Upper limb function improved more at Week 4 (MD -7.3; 95% CI -12.3 to -2.2). FABQ scores decreased more at Week 12 (MD -7.6; 95% CI -14 to -0.5). Fewer participants in the experimental group required post-intervention healthcare (3 vs 10; p&#x202f;=&#x202f;0.02). CONCLUSION: Adding AI-based home exercise app to conventional treatment improve pain and may improve function and reduce healthcare utilization in rotator cuff-related shoulder pain.

Humans