Search Results (1,426)

Objective: This study assessed the blood-pressure effects of various exercise regimens in middle-aged and older adults with type 2 diabetes, considering baseline levels, to clarify dose–response relationships for personalized exercise guidance. Methods: We conducted a dose–response network meta-analysis. Systematic searches were performed in Web of Science, EMBASE, PubMed and Cochrane Library. Baseline blood pressure was modelled as an explanatory variable via meta-regression. Thirty-six eligible RCTs of physical-activity interventions in older adults with type 2 diabetes reporting blood-pressure outcomes were included. Results: In stage 1–2 hypertension, mind–body activities were associated with the greatest systolic blood-pressure reduction and appear to be the most effective intervention based on available evidence. For diastolic blood pressure, combined aerobic-resistance training was effective in stage 1 hypertension. Dose–response analysis indicated that clinically meaningful reductions occur at modest volumes (668 and 657 MET-min/week for systolic and diastolic pressures, respectively), aligning with the lower end of international activity guidelines. Conclusions: Individualized exercise prescription based on baseline blood pressure may offer a useful non-pharmacological strategy for hypertension management in older adults with type 2 diabetes. By quantifying the required activity dose, this work provides an evidence base for integrating structured exercise into precision care for this high-risk population. Full article

Background: Peripheral neuropathy is a common and clinically heterogeneous neurological condition caused by metabolic, inflammatory, toxic, or traumatic factors and is associated with sensory deficits, neuropathic pain, motor impairment, and reduced functional capacity. Management remains challenging and often requires multimodal therapeutic approaches, as pharmacological monotherapy frequently provides incomplete symptom control. Objective: This narrative review explores the conceptual rationale for combining galantamine with iontophoresis and Black Sea brine-based therapy as a potential multimodal strategy for peripheral neuropathy management. Main Findings: Galantamine, a reversible acetylcholinesterase inhibitor and positive allosteric modulator of nicotinic acetylcholine receptors, has demonstrated neuroprotective, neuromodulatory, and anti-inflammatory properties in experimental settings. Iontophoresis may provide a non-invasive method for targeted local drug delivery while reducing systemic exposure. Black Sea brine, widely used in Bulgarian balneological and rehabilitation practice, has been associated with improved circulation, pain reduction, and neuromuscular support. The reviewed evidence suggests biologically plausible complementary mechanisms; however, no direct clinical studies evaluating the combined intervention were identified. Limitations: Current evidence is indirect and derived from separate investigations of galantamine, iontophoresis, and brine-based therapy, as well as heterogeneous historical and regional sources. Therefore, the proposed combination should be considered hypothesis-generating rather than evidence-established. Conclusions: The combination of galantamine, iontophoresis, and Black Sea brine represents a potentially interesting multimodal concept for peripheral neuropathy rehabilitation. Well-designed preclinical and clinical studies are required to determine safety, feasibility, optimal treatment parameters, and therapeutic efficacy. Full article

Background: The global increase in life expectancy has led to a higher prevalence of age-related cognitive decline, highlighting the need for effective non-pharmacological interventions. This systematic review aimed to evaluate the potential effects of olive oil, particularly its bioactive compounds and fatty acid profile, on cognitive function in adults Methods: A comprehensive literature search was conducted in PubMed, Scopus, and EBSCO in accordance with PRISMA 2020 guidelines, including peer-reviewed studies published in English between 2015 and 2025. A total of six studies met the inclusion criteria and were included in the final qualitative synthesis, comprising five randomized controlled trials and one prospective cohort study. Risk of bias was assessed using the Cochrane Risk of Bias tool (RoB 2) and the Newcastle–Ottawa Scale. Results: The findings suggest that consumption of extra virgin olive oil (EVOO), particularly high-phenolic varieties, may be associated with improvements in cognitive domains such as memory, attention, executive function, and global cognition. However, the evidence is derived from a limited number of heterogeneous studies with relatively small sample sizes. Most of the available data relate to high-phenolic EVOO and olive-derived bioactive compounds, while studies directly examining the role of fatty acid composition remain limited. Proposed mechanisms include reduced blood–brain barrier permeability, enhanced brain functional connectivity, and the neuroprotective effects of compounds such as hydroxytyrosol and oleuropein. Conclusions: While the findings suggest potential cognitive benefits of EVOO, the current evidence remains preliminary and insufficient to establish causality. Therefore, results should be interpreted with caution. Further large-scale, well-designed randomized controlled trials are required to confirm these associations and clarify the specific contributions of fatty acids and bioactive compounds. Full article

Neurodegenerative diseases are among the most consequential disorders of later life, not only because of their increasing prevalence, rising from approximately 1–2% at age 65 to over 30% by age 85, but also because they develop within the broader clinical context of ageing, multimorbidity, frailty, and polypharmacy. In older adults, these conditions rarely present as isolated and static diagnostic entities; rather, they unfold as dynamic clinical trajectories involving the progressive interaction of cognitive decline, behavioural-neuropsychiatric symptoms, and extrapyramidal-motor dysfunction. In this review, we propose a trajectory-based framework for the interpretation and management of major neurodegenerative disorders in later life, including Alzheimer’s disease, frontotemporal dementia, Parkinson’s disease and Parkinson’s disease dementia, dementia with Lewy bodies, and vascular cognitive impairment. Building on a conceptual model organized around three major symptom spheres: cognitive, behavioural-neuropsychiatric, and extrapyramidal-motor, we argue that each disorder can be understood according to the relative predominance and temporal evolution of these domains. Alzheimer’s disease is typically cognition-led, frontotemporal dementia behaviour-led, and Parkinsonian syndromes motor-led, whereas dementia with Lewy bodies shows early multidomain convergence across all three spheres simultaneously. Vascular and mixed dementias follow more heterogeneous trajectories shaped by lesion burden, network disruption, and copathology. This framework has direct implications for diagnosis, prognostic stratification, and treatment selection, because interventions targeting one sphere may destabilize another and generate prescription cascades, delirium, or functional decline. We further discuss how biomarker-based diagnosis, disease-modifying therapies, non-pharmacological interventions, multidisciplinary care, deprescribing strategies, and palliative planning can be integrated within a trajectory-based approach. Interpreting neurodegeneration through clinical trajectories rather than diagnostic labels alone offers a more realistic and therapeutically useful model for precision geriatric neurology across the full course of disease. Full article

Postoperative nausea and vomiting (PONV) remain a leading preventable perioperative complication despite advances in anesthetic and surgical care, significantly affecting recovery within Enhanced Recovery After Surgery (ERAS) pathways. ERAS protocols provide a structured, multidisciplinary framework for perioperative optimization; however, variability in the implementation of PONV prevention strategies persists. This narrative review synthesizes current evidence on perioperative strategies for PONV prevention within ERAS pathways, focusing on patient risk stratification, multimodal pharmacologic prophylaxis, anesthetic techniques, and adjunctive non-pharmacologic interventions. We evaluate validated risk prediction tools, including the Apfel score, and highlight the importance of individualized prophylactic strategies based on patient, surgical, and anesthetic risk factors. Multimodal antiemetic regimens, opioid-sparing anesthesia, total intravenous anesthesia (TIVA), and regional techniques are discussed as key components of perioperative management. In addition, non-pharmacologic interventions such as optimized fluid therapy, early mobilization, and supportive perioperative care are reviewed as integral elements of ERAS-based recovery pathways. Complementing existing consensus guidelines, this review provides a practical, workflow-based framework spanning preoperative risk assessment, intraoperative decision-making, and postoperative monitoring for direct application within ERAS protocols. Full article

Background: Obesity often affects kidney health. Irisin, a myokine released during exercise, may exert renoprotective effects. This study examined the effects of swimming-induced irisin on kidney health in obese rats. Materials and methods: Sixty male rats were divided into four groups: control non-trained, obese non-trained, control trained, and obese trained. Obesity was induced using a high-fat diet, and an 8-week swimming program was implemented. Measurements included body and kidney weights, renal function markers (serum urea, creatinine, and urinary albumin), lipid profile, fasting glucose, insulin, and HOMA-IR. Levels of skeletal muscle irisin and PGC-1α were measured by ELISA, and citrate synthase activity was assessed spectrophotometrically. Renal tissue analysis included phospho-AMPKα1 (measured by ELISA), Complex I activity, ATP, Malondialdehyde (MDA), superoxide dismutase (SOD) activity (measured spectrophotometrically), and PGC-1α mRNA expression (qRT-PCR). Renal tissues were examined under a light microscope for histopathological evaluation, followed by semi-quantitative scoring of glomerular and tubulointerstitial lesions, morphometric analysis of glomerular tuft area, and a composite score of cleaved caspase-3 immunoexpression. Results: Exercise increased skeletal muscle levels of irisin, PGC-1α, and citrate synthase activity. It also activated renal AMPK, improved mitochondrial function, increased PGC-1α mRNA levels, and reduced renal oxidative stress, as evidenced by decreased malondialdehyde (MDA) levels and restored superoxide dismutase (SOD) activity in obese rats. These changes were associated with improved renal function, reduced tubular injury and apoptosis in obese rats, partial restoration of the glomerular tuft area, lower lesion scores, and reduced cleaved caspase-3 immunoexpression. Conclusions: These findings suggest that irisin may mediate the renoprotective effects of exercise through the AMPK–PGC-1α pathway, highlighting swimming as a beneficial non-pharmacological intervention and supporting a potential adjunct role for irisin in managing obesity-related CKD. Full article

Background/Objectives: To evaluate the association between adjunct tendon vibration and changes over 12 months in dual-energy X-ray absorptiometry (DXA)-derived bone mineral density (BMD) T-score and bone turnover markers in older adults with osteoporosis receiving standard care in a non-randomised controlled cohort study. Methods: This 12-month prospective non-randomised controlled cohort study included 100 adults aged ≥60 years with DXA-confirmed osteoporosis recruited from orthopaedic clinics in the Greater Thessaloniki area. Fifty participants received adjunct tendon vibration therapy in addition to usual care, while 50 received usual care alone. Usual care consisted of calcium and vitamin D supplementation. The primary outcome was post-intervention BMD T-score, analysed using analysis of covariance (ANCOVA) adjusted for baseline T-score. Secondary outcomes included changes in bone turnover markers and calcium/phosphate metabolism. Sensitivity analysis was conducted using a linear mixed-effects model with repeated BMD measurements. Results: Baseline characteristics were comparable between groups. Over 12 months, the intervention group showed greater improvement in BMD T-score than controls (median change 0.90 [0.70–1.00] vs. −0.10 [−0.10–0.10], p < 0.001). The adjusted between-group difference was 0.871 (95% CI 0.773–0.968; p < 0.001). Results remained consistent after adjustment for age and sex. The mixed-effects model confirmed a significant group × time interaction (β = 0.922, 95% CI 0.806–1.038; p < 0.001). Bone resorption markers decreased more in the intervention group. The magnitude of the observed BMD improvement (~0.9 T-score units) is notable for a non-pharmacological intervention and should be interpreted cautiously. Conclusions: Adjunct tendon vibration was associated with a more favourable BMD trajectory and changes in bone turnover markers in older adults with osteoporosis receiving standard care. Given the non-randomised design and potential residual confounding, these findings should be interpreted as associative rather than causal. Full article

Background/Objectives: The gut microbiome is a critical regulator of host metabolism, immunity, and the gut–brain axis. Exercise is a promising non-pharmacological modulator of microbial ecology, yet human evidence remains heterogeneous and the translational gap persists. This narrative review synthesizes mechanisms, human and animal evidence, and future directions for the exercise–gut microbiome axis. Methods: PubMed, Scopus, Web of Science, and SID were searched for articles published between January 2000 and February 2025. Keywords included exercise, physical activity, gut microbiome, gut microbiota, short-chain fatty acids, and gut–muscle axis. From 218 initial records, 89 original studies (47 human, 42 animal) met inclusion criteria and were critically appraised. Results: Exercise modulates the gut microbiome via splanchnic hypoperfusion, hyperthermia, altered transit time, and immune-mediated barrier regulation. Moderate-intensity continuous training consistently increases alpha diversity and enriches butyrate-producing taxa (Faecalibacterium prausnitzii, Roseburia hominis) and mucin-degrading Akkermansia muciniphila. High-intensity interval training transiently increases intestinal permeability in untrained individuals but, following adaptation, stimulates butyrate production via lactate cross-feeding metabolism—a recent breakthrough. Effects are transient and reversible upon detraining. Animal models establish causality through fecal microbiota transplantation; human randomized controlled trials demonstrate modest, intensity-dependent, and highly individualistic responses. Emerging evidence supports the gut–muscle axis in sarcopenia and personalized exercise prescription guided by microbiome profiling. Conclusion: Exercise shows promise as a low-cost modulator of the gut microbiome for enriching health-associated taxa and improving metabolic outcomes. Definitive evidence linking exercise-induced microbial shifts to enhanced athletic performance in humans remains lacking. Future research requires diet-controlled randomized controlled trials with ≥12-week interventions, shotgun metagenomics, and mechanistic validation of the gut–muscle axis in humans. Full article

Background: The neonatal period involves rapid physiological adaptation and high vulnerability to painful stimuli, especially in NICU-admitted infants. Neonates have the neurophysiological capacity for nociception, and repeated pain exposure may impair neurodevelopment. Non-pharmacological interventions, particularly oral sucrose and breast milk, are widely used as first-line analgesic strategies due to their safety and efficacy. However, heterogeneity in existing studies requires evidence synthesis. Methods: A systematic review following PRISMA guidelines was conducted to assess the effectiveness of sucrose and breast milk in neonatal pain reduction. PubMed, Scopus, CINAHL, and Web of Science were searched for randomized controlled trials published between 2019 and 2024. Studies involving neonates undergoing painful procedures and receiving sucrose, breast milk, or both were included. Data extraction and risk of bias assessment were performed independently. Due to heterogeneity in interventions and outcomes, a narrative synthesis was conducted. Results: Thirteen randomized controlled trials were included. Both sucrose and breast milk consistently reduced neonatal pain scores and physiological indicators such as heart rate and oxygen saturation. Sucrose showed rapid, short-term analgesia mediated by endogenous opioid pathways, while breast milk provided additional sensory, nutritional, and emotional benefits that support mother–infant bonding. Multimodal approaches, including kangaroo care, non-nutritive sucking, and swaddling, enhanced analgesic effects. Heterogeneity in protocols and assessment tools limited comparability across studies. Conclusions: Sucrose and breast milk are safe and effective non-pharmacological interventions for neonatal pain management. Their incorporation into standardized multimodal protocols is recommended to optimize analgesia and promote humanized neonatal care. Further research is needed to standardize dosing and evaluate long-term outcomes. Full article

Background/Objectives: The efficacy of topical therapies in dermatology is often limited by the barrier function of the stratum corneum, which restricts drug penetration. Iontophoresis is a non-invasive transdermal delivery technique that uses a low-intensity electrical current to enhance the transport of charged and polar molecules across the skin. It has emerged as a strategy to improve local drug bioavailability while minimizing systemic exposure. We systematically reviewed the clinical evidence on the efficacy, safety, and pharmacologic performance of iontophoresis-assisted topical drug delivery in dermatologic diseases. Methods: This systematic review followed PRISMA guidelines and was prospectively registered in PROSPERO (CRD420251234877). PubMed, Embase, Web of Science, CENTRAL, and ClinicalTrials.gov were searched through 19 November 2025 without language restrictions. Records were screened against predefined eligibility criteria, and data were extracted on study design, participants, dermatologic indications, intervention/comparator, iontophoresis parameters, efficacy outcomes, and adverse events. The risk of bias was assessed using RoB 2 for randomized trials and the JBI checklist for non-randomized studies. Because of substantial clinical and methodological heterogeneity, the findings were synthesized narratively and no meta-analysis was performed. Results: Twenty-one studies published between 1990 and 2025 met the inclusion criteria, including 15 randomized and 6 non-randomized studies. Investigated conditions included psoriasis, eczema, melasma, post-inflammatory hyperpigmentation, herpes labialis, onychomycosis, chronic ulcers, systemic sclerosis-related digital ulcers, acne scarring, and actinic keratosis. Across studies, findings were mixed. The most consistent signals of benefit were observed in pigmentary disorders and infectious diseases, whereas results were more heterogeneous in inflammatory dermatoses and some studies did not show superiority over active comparators. Tolerability was generally favorable, with adverse events limited to mild, reversible local reactions such as erythema, tingling, burning, or transient irritation. No serious treatment-related adverse events were reported. Conclusions: Iontophoresis may represent a useful non-invasive delivery-enhancement strategy in selected dermatologic settings, particularly when topical efficacy is limited by anatomical or physicochemical barriers. However, heterogeneity in protocols, formulations, outcomes, and clinical indications limits direct comparison and does not support broad conclusions of efficacy across all dermatologic conditions. Larger, standardized trials are needed to clarify its therapeutic role, long-term efficacy, and indication-specific benefit. Full article

Background/Objectives: The placement of central venous access devices, including peripherally inserted central catheters (PICCs) and PICC-PORTs, is a routine procedure in oncology care. Usually associated with limited physical pain, these procedures may nevertheless generate significant anxiety and negatively influence the overall procedural experience. Virtual reality (VR) has emerged as a non-pharmacological intervention capable of modulating attentional and emotional responses during medical procedures; however, evidence in adult oncology patients undergoing vascular access placement remains scarce. The aim of this study is to evaluate the effect of VR on an oncological patient’s overall procedural experience. Methods: This manuscript outlines the design and methodology of a prospective, single-centre randomised controlled trial. Adult oncology patients scheduled for PICC/PICC-PORT placement are randomised to receive standard care alone or standard care combined with an immersive VR intervention delivered via a head-mounted display during the procedure under pragmatic, real-world clinical conditions. The primary outcome is a composite patient-reported procedural experience endpoint, assessed through a non-aggregated framework encompassing procedural anxiety, comfort, satisfaction and procedural tolerability. Procedural anxiety constitutes the main quantitative driver; the remaining domains are analysed as individual component dimensions and interpreted jointly to contextualise the overall experience. Secondary outcomes include procedural pain, physiological parameters and procedural characteristics. A mixed-methods approach integrates quantitative assessment with qualitative phenomenological analysis. Results: The study is expected to provide methodological and clinical insight into the role of immersive VR in improving procedural experience and support future multicentre trials. Conclusions: This trial will contribute to the expanding field of digital and immersive health technologies by evaluating VR as a patient-centred adjunct intervention in oncological procedural care using a predefined patient-reported experience-based primary endpoint. The protocol has been submitted to ClinicalTrials.gov with the registration number NCT07384741. Full article

Background: Effective pain management is crucial during orthodontic treatments with fixed appliances, to ensure adequate patient compliance and to avoid treatment discontinuation. Photobiomodulation approaches, including Low Level Laser Therapy (LLLT) has received substantial attention, due to its potential as an effective, non-pharmacological analgesic modality, however, evidence pertaining to its efficacy is controversial. Our present study aims to evaluate the efficacy of LLLT vs. placebo, following placement of orthodontic elastic separators (ESs) in adult patients treated with fixed orthodontic appliances. Methods: A randomized, double-blind, split-mouth study was carried out, where n = 31 volunteers (18 male and 13 female; aged between 19 and 32 years) were enrolled. ESs were placed at the mesial and distal surfaces of the first permanent molars in both quadrants of lower, as well as upper jaws. Based on the assigned intervention, the four quadrants were divided as follows: three quadrants received LLLT treatment—using a 980 nm wavelength GaAlAs diode laser, with 0.1–0.2 W—according to three treatment regimes, i.e., regime 1 (R1): 6 J, continuous mode, R2: 12 J, continuous mode, and R3: 6 J, pulsed mode; while placebo treatment (P) was applied in the fourth quadrant. A questionnaire with a visual analogue scale (VAS; 0–100) was used for pain assessment (spontaneous pain and pain on mastication), scored directly after separation and after 6, 24, 48 and 72 h of both laser and placebo treatment application. Results: After the 24 h mark, significant differences were detected between the pain readings of LLLT-treated and placebo quadrants, both in resting position and during mastication (p < 0.05); pain readings were highest for R2, P, while lowest for R3 quadrants in resting position, and at R1 during mastication, respectively. Conclusions: Although findings of our study are exploratory in nature, they suggest that a single application of LLLT might be effective in reducing pain caused by ES placement, especially in the vulnerable 24 h following separation. Trial registration: clinicaltrials.gov ID NCT07456709 (date of registration: 2 March 2026, retrospectively registered). Full article

GJB2-associated hearing loss is the most common form of non-syndromic hereditary deafness worldwide. However, it exhibits significant heterogeneity in terms of both clinical presentation and biological basis. This review focuses on mechanism-oriented therapeutic strategies for GJB2-associated hearing loss, investigating how different types of GJB2 variants correspond to distinct clinical phenotypes and underlying pathogenic mechanisms, and aims to determine appropriate treatments. Current evidence suggests that GJB2-associated hearing loss is not solely caused by channel dysfunction resulting from gap junction defects, but rather the result of multiple pathological processes, including impaired GJB2 transcriptional regulation, cochlear developmental abnormalities, sensory epithelial degeneration and secondary damage pathways such as inflammation. Consequently, emerging therapeutic approaches can be viewed as interventions targeting specific mechanisms, including gene therapy, restoration of protein transport and pharmacological modulation of damage to the cochlear microenvironment. Overall, this review highlights the importance of aligning therapeutic strategies with specific GJB2 variants, underlying pathogenic mechanisms, and the developmental window during which cochlear injury remains biologically reversible. Full article

Background: Periodontitis affects approximately 7–11% of the global adult population in its severe forms and has been epidemiologically associated with cardiovascular, cardiometabolic, and neurodegenerative diseases. Low-grade chronic inflammation represents the unifying mechanism; however, an integrative framework connecting the oral cavity, the gut, and the brain into a single mechanistic continuum is lacking. Objective: This narrative review, conducted with structured (but non-systematic) elements and PRISMA-2020 style reporting used solely as a transparency tool, synthesizes current evidence on the oral–gut–brain axis. A comprehensive literature search was conducted in PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar (2000–March 2026), yielding 159 included studies after structured screening and eligibility assessment. The review focuses on: the molecular mechanisms by which periodontal dysbiosis may disrupt intestinal homeostasis and contribute to neuroinflammation; the role of salivary and intestinal biomarkers as monitoring tools for the entire axis; and emerging pharmacological opportunities targeting this tripartite pathway. Results: Periodontal pathogens, particularly Porphyromonas gingivalis (P. gingivalis) and Fusobacterium nucleatum, have been detected ectopically in the gut and are associated with reduced tight junction protein expression and altered Firmicutes/Bacteroidetes ratios in preclinical and observational studies. These perturbations have been associated with increased blood–brain barrier (BBB) permeability, microglial activation, and amyloid-beta (Aβ) accumulation, although causal directionality in humans remains to be established. Salivary biomarkers (MMP-8, IL-1β, IL-6, BDNF) and intestinal biomarkers (short-chain fatty acids, calprotectin) reflect systemic inflammatory burden and offer potential for non-invasive screening. Conclusions: The oral–gut–brain axis provides a plausible unifying framework for understanding comorbidity among periodontal, cardiometabolic, and neurodegenerative diseases; however, current evidence is predominantly associative, and mechanistic extrapolation from preclinical models requires validation in longitudinal human studies. Salivary biomarkers may serve as candidate first-line tools for systemic risk assessment, and pharmacological interventions targeting this axis represent promising investigational directions warranting further clinical evaluation. Full article

Mineralocorticoid receptor antagonists (MRAs) are the cornerstone of the management of heart failure and chronic kidney disease. A well-known adverse event, hyperkalemia, is associated with fatal arrhythmia and discontinuation of MRA. Our narrative review discusses the personalized treatment of MRAs, focusing on the pharmacological profile and drug–drug interactions to address safety concerns related to hyperkalemia. Clinicians should scrupulously monitor potassium levels, especially during dose titration, and review each patient’s medication list. Cytochrome P450 3A4 (CYP3A4) inhibitors are pharmacokinetic precipitators that interact with most MRAs, except spironolactone, and adversely affect the risk of hyperkalemia, although suggestive evidence is scarce. Potassium-elevating drugs synergistically increase serum potassium levels when co-administered with an MRA (e.g., renin-angiotensin aldosterone inhibitors, co-trimoxazole, non-steroidal anti-inflammatory drugs, calcineurin inhibitors, and β blockers). Additional approaches include correction of metabolic acidosis using sodium bicarbonate, potassium-lowering therapy using loop and thiazide diuretics, and sodium-glucose cotransporter 2 inhibitors. Novel potassium binders enable patients to receive the maximum-tolerated MRA with fewer gastrointestinal side effects. Individualized interventions for hyperkalemia risk are important in treatment using MRA. Full article