Search Results (455)

The global population is ageing due to increased life expectancy, and the prevalence of diabetes is proportionally increasing. With advancing age, diabetes in older people is a complex condition due to associated morbidities and geriatric syndromes. As a result, the management of diabetes in old age is challenging. Due to the wide heterogeneity of older people, diabetes management in this age group should be personalised. While strict targets are accepted in fit individuals, relaxed targets should be considered in patients with multiple morbidities and a high risk of hypoglycaemia. The development of frailty changes the metabolic profile of older people, and their insulin resistance and diabetes trajectory, which will have an impact on the choice of glucose-lowering agents and the goals of therapy. For example, intensive therapy, the use of SGLT-2 inhibitors and GLP-1RA, and tight targets should be continued in frail, sarcopenic, obese individuals due to their increased insulin resistance and cardiovascular risk. On the other hand, relaxed targets and deintensification of therapy should be considered in anorexic, malnourished, frail individuals with significant weight loss due to their low insulin resistance, low prevalence of cardiovascular risk factors, and high risk of hypoglycaemia. Annual reviews of older people with diabetes should include screening for frailty, depression and dementia for early diagnosis, and appropriate interventions. The introduction of continuous glucose monitoring is increasingly used in older people with diabetes and has the potential to reduce the incidence of hypoglycaemia. With the expectation of a continued increase in the prevalence of older people with diabetes, the use of mobile health may allow care delivery on a wider scale without the need for face-to-face appointments. In addition, there is a promising scope for artificial intelligence to achieve better diabetes outcomes. Future research is still required to expand the use of these technologies in older age groups. Full article

Background: Pediatric cancer is a highly stressful and potentially traumatic condition affecting physical health, emotional well-being, developmental trajectories, and family functioning. Hospitalization and intensive treatments often exacerbate emotional distress and symptom burden, negatively impacting quality of life (QoL). Integrating psychosocial and expressive interventions into pediatric oncology care is increasingly recognized as essential. Clay therapy is a multisensory, hands-on creative intervention that may promote emotional regulation, coping, and a sense of agency in hospitalized children. Objectives: This prospective pilot study evaluated the effects of clay therapy on emotional and physical well-being in pediatric oncology patients and explored potential indirect effects on caregivers’ emotional status. Methods: From December 2023 to December 2024, forty hospitalized children with onco-hematological diseases and one parent per patient were enrolled. Each child participated in a one-hour clay therapy workshop led by a professional ceramist. Emotional outcomes were assessed before (T0) and immediately after (T1) the intervention using the Visual Analog Scale (VAS) and the ArtsObs observational scale. Physical symptoms, including pain, fatigue, and nausea, were also evaluated. Results: Following clay therapy, children showed statistically significant improvements across all VAS emotional domains, independent of age and gender. ArtsObs assessments confirmed a significant increase in observed mood, with high levels of relaxation and engagement; female patients demonstrated greater mood improvement than males. Significant reductions in pain, fatigue, and nausea were also observed. Parents exhibited a significant improvement in mood following their child’s participation. Conclusions: These findings suggest that clay therapy is feasible and could be an effective supportive intervention in pediatric oncology, benefiting both emotional and physical well-being. Its integration into multidisciplinary, family-centered care models may enhance QoL during hospitalization and provide holistic support for children with cancer and their families. Full article

Obesity is a chronic, highly prevalent disease affecting nearly one-third of the global population and represents a major independent risk factor for heart failure (HF), particularly heart failure with preserved ejection fraction (HFpEF). Excess adiposity—especially visceral and epicardial adipose tissue (EAT)—acts as an active endocrine and immune organ, promoting chronic low-grade inflammation, oxidative stress, endothelial dysfunction, and adverse myocardial remodeling. Expanded EAT exerts both paracrine inflammatory effects and mechanical constraint on the myocardium, contributing to diastolic dysfunction, microvascular impairment, atrial arrhythmogenesis, and elevated filling pressures despite preserved systolic function. Evidence demonstrates a dose–response relationship between increasing body mass index and incident HF. Clinically, obesity-related HFpEF is characterized by concentric left ventricular hypertrophy, impaired relaxation, increased plasma volume, reduced exercise tolerance, and relatively low natriuretic peptide levels, complicating diagnosis. HF management includes traditional treatment with diuretics, renin-angiotensin system inhibitors, β-blockers, mineralocorticoid receptor antagonists, and angiotensin receptor-neprilysin inhibitors. These agents widely remain foundational as they primarily target hemodynamic and neurohormonal pathways in HF. In contrast, sodium–glucose cotransporter 2 inhibitors consistently reduce HF hospitalizations across the ejection fraction spectrum, while glucagon-like peptide-1 receptor agonists and dual incretin therapies (e.g., tirzepatide) promote substantial weight loss, improve symptoms, and demonstrate promising anti-remodeling effects in obesity-related HFpEF. Recognizing obesity-driven HF as a distinct cardiometabolic entity supports an integrated therapeutic strategy combining structured weight reduction with guideline-directed HF polypharmacotherapy to address both hemodynamic burden and upstream adiposity-related mechanisms. Full article

Background: Children with β-thalassemia major (β-TM) survive longer due to advances in transfusion and chelation therapy; however, cardiovascular complications have emerged as a leading cause of long-term morbidity. Chronic hemolysis, oxidative stress, and iron overload may promote early endothelial dysfunction and premature vascular aging, yet their impact on myocardial deformation in pediatric patients remains incompletely characterized. Objectives: To evaluate subclinical myocardial dysfunction and arterial stiffness in children with β-TM and to investigate hemolysis-related changes in asymmetric dimethylarginine (ADMA) and L-arginine as biomarkers of endothelial dysfunction in relation to cardiovascular involvement. Methods: Twenty-four children with β-TM and 20 age-matched healthy controls were included. Cardiac structure and myocardial deformation were assessed by conventional echocardiography, tissue Doppler imaging, and speckle-tracking strain analysis. Arterial stiffness was evaluated using oscillometric pulse wave analysis and bilateral carotid intima–media thickness (CIMT). Serum ADMA and L-arginine levels were measured, and hemoglobin, reticulocyte count, and ferritin levels were recorded. Results: Children with β-thalassemia major demonstrated significantly increased arterial stiffness compared with controls, including higher PWV (4.61 ± 0.37 vs. 4.38 ± 0.31), AIx@75 (augmentation index at 75 bpm) (28.5 ± 8.34 vs. 22.8 ± 6.51), left CIMT [0.45 (0.39–0.51) vs. 0.41 (0.38–0.46)], and right CIMT [0.43 (0.39–0.54) vs. 0.40 (0.34–0.46)]. In addition, patients exhibited reduced global longitudinal strain (−19.3 ± 2.91 vs. −21.84 ± 1.91), prolonged isovolumetric relaxation time [53 (37–71) vs. 45 (37–55)], and elevated E/Em (8.44 ± 2.19 vs. 6.92 ± 1.10). ADMA levels were significantly higher in patients (0.54 ± 0.19 vs. 0.39 ± 0.22) and were positively associated with reticulocyte counts and inversely correlated with hemoglobin levels. In addition, both ADMA and ferritin levels were positively correlated with arterial stiffness indices and left ventricular filling pressures. Conclusions: Children with β-thalassemia major exhibit features suggestive of early cardiovascular aging, including impaired myocardial deformation, diastolic involvement, and increased arterial stiffness. The observed association between ADMA levels and markers of hemolysis, vascular stiffness, and myocardial deformation highlights the potential involvement of endothelial dysfunction in premature myocardial–vascular remodeling. These findings suggest that ADMA may serve as a promising biomarker for early cardiovascular risk in pediatric β-thalassemia major; however, further longitudinal and multi-center studies are needed to confirm its clinical utility for risk stratification. Full article

Stress states are increasing with global urbanization, but evidence on the physiological impact of urban blue-space exposure remains limited compared to green spaces. In this randomized within-subject crossover study, we examined the physiological effects of seascape viewing from the 29th floor of an office building in 44 healthy young adults. Each participant underwent visual stimulation with a seascape window view (blue space) and a blind-covered window (control) for 90 s each after a 60 s rest. Prefrontal cortex activity was recorded using near-infrared spectroscopy, and the left–right difference (LRD) in Δoxy-Hb concentrations was used as an indicator. Autonomic nervous system activity was assessed using heart rate variability, and psychological outcomes were measured using a semantic differential scale and the Profile of Mood States—2 short form. Seascape viewing significantly increased LRD, indicating left-dominant prefrontal activation relative to the control. It also increased comfort and relaxation and improved mood states. Correlation analyses showed that LRD was positively correlated with comfort and relaxation. These findings suggest that intentional window-view design, including exposure to high-rise blue-space views, represents a promising environmental approach to support occupants’ well-being and provide practical implications for window-view design and operation in high-rise office environments. Full article

Background: Tinnitus, the perception of sound in the absence of an external source, is a prevalent condition that can substantially affect physical and mental health. Although tinnitus is not typically curable, it is often manageable with structured, multidisciplinary care. This pilot research describes the Sensation–Emotion–Cognition (SEC) model, a practical audiological framework developed by Danesh et al. that targets three core dimensions of the tinnitus experience. Methods: We integrate findings from an exploratory retrospective cohort and a prospective expansion study. The SEC protocol included sound therapy, counseling and relaxation training, and cognitive behavioral therapy (CBT) delivered through either unguided, module-based internet CBT, clinician-guided module-based internet CBT, or six therapist-led CBT sessions. The objective was to evaluate whether this multifactorial approach is associated with reductions in tinnitus-related distress. Results: In this prospective study, preliminary results from 16 participants who completed the study were associated with significant pre–post changes in tinnitus-related outcomes: 4C management confidence increased from M = 30.38 to 60.19 (p < 0.001; Cohen’s dz = 1.04), and SAD-T emotional distress decreased from M = 4.75 to 2.38 (p = 0.001; Cohen’s dz = 0.99). Conclusions: These findings suggest the potential value of an integrated management strategy; however, given the single-group pre–post design and attrition, the results should be interpreted as exploratory and warrant confirmation in larger controlled trials. Full article

One of the most popular food supplements among the Canary population for the treatment of insomnia and mild anxiety is Valeriana officinalis L. (valerian), whose organ of use is the root. However, this plant is susceptible to the accumulation of certain metals, and a daily multi-dose treatment may be a dosage indication/regimen as multidose therapy. Therefore, there is an interest in determining its content of metals (Cd, Pb, Al, Cr, Cu, Li, Ni, Sr, Mo, Zn, Co, Fe, B, Mn, V, Ba, K, Na, Mg, Ca) to establish the possible toxicological risk of its consumption. The concentrations were determined by inductively coupled plasma optical emission spectrometry (ICP-OES) in a total of 23 samples (8 fragmented, 7 crushed, 8 pulverized). The Cd limit set by the European Pharmacopoeia (0.1 mg/kg) is more than doubled in six samples. The results showed that Pinisan (0.11 mg/kg), the EnRelax^® pill (0.12 mg/kg), the EnRelax^® infuser (0.13 mg/kg), Kneipp (0.15 mg/kg), Milvus (0.16 mg/kg) and one of the market samples (0.23 mg/kg) all exceed this parameter. However, the use of valerian root as a herbal plant or food supplement at therapeutic doses and in all studied dosages does not pose a toxicological risk based on the Estimated Daily Intake (EDI) of metals. Full article

This review examines biodegradable polymer-based core–shell nanoformulations encapsulating essential oils for acne treatment through the lens of physicochemical design and controlled delivery mechanisms. Acne is a common inflammatory skin disorder closely associated with sebum overproduction and microbial imbalance, while conventional therapies, although effective, may present long-term side effects. Increasing attention has therefore turned to sustainable dermatological materials derived from eco-friendly polymers combined with naturally active compounds. Recent advances show that core–shell nanostructures fabricated from biodegradable polymers function as physicochemically engineered carriers for volatile essential oils. They enhance their stability and protect them from premature degradation. They also enable controlled release governed by diffusion, polymer relaxation, interfacial interactions, and degradation kinetics. This review highlights how polymer chemistry, interfacial properties, particle morphology, and processing routes determine encapsulation efficiency, release profiles, and skin permeation behaviour. Particular emphasis is placed on structure–property–function relationships, including mass transport phenomena, thermodynamic compatibility between polymers and essential oils, surface charge, wettability, and nanostructure architecture, which collectively influence bioavailability and therapeutic performance. By integrating concepts from polymer physical chemistry, colloid and interface science, and drug delivery kinetics, these sustainable nanoformulations emerge as promising platforms for acne and sebum control. Overall, essential oil-loaded biodegradable polymeric core–shell systems represent a sustainable and scientifically grounded approach to acne management, although further physicochemical characterization, in vivo validation, and consideration of cost, technical challenges, and current limitations are required to support clinical translation. Full article

Older adults with multiple diseases are likely to be prescribed multiple medications including anticholinergic agents, which are frequently prescribed to manage conditions such as overactive bladder and chronic obstructive pulmonary disease and Parkinson’s disease. Overactive bladder (OAB) has been the subject of increased disease awareness and is a common and significant cause of reduced quality of life, particularly in the elderly. The selective β₃ adrenoceptor agonist, mirabegron was developed for the pharmacological treatment of OAB. Mirabegron has been shown to exert off-target effects on various functional proteins such as muscarinic receptors in rat tissues. This agent may relax the detrusor muscle by activating β₃ adrenoceptors and also antagonizing muscarinic receptors. Mirabegron and antimuscarinics exerted additive effects on muscarinic receptor binding and relaxant responses of cholinergic contractions of the detrusor muscle. Mirabegron excreted in human urine appears to directly attenuate muscarinic receptor-mediated functions in the bladder. Combination therapy of mirabegron and solifenacin in patients with OAB may enhance not only their therapeutic effects on OAB, but also increase the risk of anticholinergic adverse effects. Therefore, the safety of concomitant use of mirabegron and other drugs such as antimuscarinics for elderly patients needs to be carefully considered. Full article

Arterial stiffness encompasses the global structural and functional modifications that induce progressively increased vascular rigidity, whether associated with pathological cardiovascular or metabolic alterations or not. This narrative review highlights the comparative effects of physical exercise practices, current drug treatments, and approaches based on the use of medicinal plants on arterial stiffness, due to metabolic and/or blood pressure disorders. This review would provide up-to-date information for further experimental and clinical studies concerning the prevention/therapy of high glucose levels and vascular remodelling. Indeed, it is known that physical activities can reduce high blood glucose and blood pressure, allowing the prevention of arterial stiffness. Concerning conventional drugs, some are used to treat arterial stiffness, but their effectiveness is generally limited to treating components of the disease. Eighteen medicinal plant species, belonging to fourteen different botanical families, have potential activities against arterial stiffness in preclinical and/or clinical studies. Several plant extracts reduced the parameters implicated in vascular stiffness, such as the Pulse Wave Velocity, the Augmentation Index, and the Cardio–Ankle Vascular Index. Some plant extracts reduced arterial stiffness by primarily lowering glycemia and/or blood pressure in animal models, which has also been confirmed in humans. By reducing arterial stiffness, plant extracts or derived bioactive compounds not only improved vascular relaxation by enhancing Nitric Oxide production and/or antioxidant defences, but also inhibited inflammation-induced aortic remodelling and promoted elastin neo-synthesis. Polyphenols have often been identified as the main effective compounds involved in these beneficial effects. However, only a few studies explained the mechanisms associated. Full article

Introduction: Massage therapy delivers structured mechanosensory input that can influence brain function, yet the central mechanisms and potential for neuroplastic change have not been synthesized across neuroimaging modalities. This mechanistic review integrates evidence from electroencephalography (EEG), functional MRI (fMRI), and functional near-infrared spectroscopy (fNIRS) to map how massage alters human brain activity acutely and over time and to identify signals of longitudinal adaptation. Materials and Methods: We conducted a scoping, mechanistic review informed by PRISMA/PRISMA-ScR principles. PubMed/MEDLINE, Cochrane Library, Google Scholar, and ResearchGate were queried for English-language human trials (January 1990–July 2025) that (1) delivered a practitioner-applied manual massage (e.g., Swedish, Thai, shiatsu, tuina, reflexology, myofascial techniques) and (2) measured brain activity with EEG, fMRI, or fNIRS pre/post or between groups. Non-manual stimulation, structural-only imaging, protocols, and non-English reports were excluded. Two reviewers independently screened and extracted study, intervention, and neuroimaging details; heterogeneity precluded meta-analysis, so results were narratively synthesized by modality and linked to putative mechanisms and longitudinal effects. Results: Forty-seven studies met the criteria: 30 EEG, 12 fMRI, and 5 fNIRS. Results: Regarding EEG, massage commonly increased alpha across single sessions with reductions in beta/gamma, alongside pressure-dependent autonomic shifts; moderate pressure favored a parasympathetic/relaxation profile. Connectivity effects were state- and modality-specific (e.g., reduced inter-occipital alpha coherence after facial massage, preserved or reorganized coupling with hands-on vs. mechanical delivery). Frontal alpha asymmetry frequently shifted leftward (approach/positive affect). Pain cohorts showed decreased cortical entropy and a shift toward slower rhythms, which tracked analgesia. Somatotopy emerged during unilateral treatments (contralateral central beta suppression). Adjuncts (e.g., binaural beats) enhanced anti-fatigue indices. Longitudinally, repeated programs showed attenuation of acute EEG/cortisol responses yet improvements in stress and performance; in one program, BDNF increased across weeks. In preterm infants, twice-daily massage accelerated EEG maturation (higher alpha/beta, lower delta) in a dose-responsive fashion; the EEG background was more continuous. In fMRI studies, in-scanner touch and reflexology engaged the insula, anterior cingulate, striatum, and periaqueductal gray; somatotopic specificity was observed for mapped foot areas. Resting-state studies in chronic pain reported normalization of regional homogeneity and/or connectivity within default-mode and salience/interoceptive networks after multi-session tuina or osteopathic interventions, paralleling symptom improvement; some task-based effects persisted at delayed follow-up. fNIRS studies generally showed increased prefrontal oxygenation during/after massage; in motor-impaired cohorts, acupressure/massage enhanced lateralized sensorimotor activation, consistent with use-dependent plasticity. Some reports paired hemodynamic changes with oxytocin and autonomic markers. Conclusions: Across modalities, massage reliably modulates central activity acutely and shows convergent signals of neuroplastic adaptation with repeated dosing and in developmental windows. Evidence supports (i) rapid induction of relaxed/analgesic states (alpha increases, network rebalancing) and (ii) longer-horizon changes—network normalization in chronic pain, EEG maturation in preterm infants, and neurotrophic up-shifts—consistent with trait-level recalibration of stress, interoception, and pain circuits. These findings justify integrating massage into rehabilitation, pain management, mental health, and neonatal care and motivate larger, standardized, multimodal longitudinal trials to define dose–response relationships, durability, and mechanistic mediators (e.g., connectivity targets, neuropeptides). Full article

Background: Prospective trials provide robust evidence for prostate cancer (PCa) treatment but often include highly selective populations, limiting generalizability. Real-world data (RWD) can address these gaps and inform personalized care. Objectives: This study aimed to evaluate treatment-free survival (TFS) and secondary treatment sequences after initial curative therapy for PCa using electronic health record (EHR) data and to analyze associated medication profiles. Methods: We studied 3024 patients treated with radical prostatectomy (RP), brachytherapy (BT), or curative radiotherapy (RT) at Erasmus MC (2009–2023), the Netherlands. Outcomes included TFS, treatment sequences, and medication patterns across treatment lines. Results: Median age at diagnosis was 65 years (IQR 61–69) for RP, 68 (62–73) for BT, and 72 (68–76) for RT. At 10 years, TFS was 89% (95% CI: 84.9–94.1) for BT, 85% (95% CI: 83–87) for RT, and 71% (95% CI: 65.7–75.8) for RP. Most patients remained treatment-free, but up to five treatment lines occurred, mainly in patients with low comorbidity scores. Medication profiles reflected treatment-related morbidity: alpha-blocker use increased after BT and RT, while bladder relaxants were common after RP. Comorbidity-related medication use remained low among patients undergoing multiple sequenced treatments. Conclusions: These findings highlight the real-world application of multiple secondary treatments after different primary curative therapy options for PCa and associated comorbidity and medication use patterns. They confirm the durability and long-term effectiveness of curative treatments in real-world PCa care. By combining treatment trajectories and medication profiles, RWD provides insights for personalized counseling, helping clinicians and patients anticipate long-term treatment needs, and enabling informed decisions aligned with health status and preferences. Full article

Back pain in horses is a frequent musculoskeletal issue that affects performance and welfare. Magnetotherapy has been proposed as a complementary, non-invasive treatment to reduce pain and support soft tissue recovery, but studies in horses remain limited. This pilot study aimed to evaluate the effects of low-frequency pulsed magnetic field therapy on horses with hypersensitivity to palpation along the longissimus dorsi muscle. Four recreational horses participated in a 10-session magnetotherapy program, with changes assessed using palpation, neck flexibility tests, heart rate measurements and thermal imaging. Results showed a reduction in pain sensitivity and muscle tension, particularly in the withers, thoracic, lumbar and sacral regions. Heart rate decreased after treatment, which may indicate a relaxing effect. Thermal imaging confirmed that magnetotherapy did not increase surface temperature, confirming its non-thermal nature. No adverse effects or swelling were observed in any of the horses. These findings provide preliminary data from this pilot study, suggesting that magnetotherapy may be a beneficial adjunct in the treatment of back pain in horses, promoting relaxation and pain relief without inducing tissue heating. Further research on larger populations with a negative control group is needed to validate these findings and support broader clinical application. Full article

Background: An anterior cruciate ligament (ACL) rupture is one of the most psychologically demanding injuries in professional sport. This study aimed to describe a structured psychological intervention conducted during the rehabilitation process following an ACL rupture in a professional female futsal player. Methods: A single-case longitudinal design was implemented with three phases (pre-test, intervention, post-test) across a 12-month rehabilitation period. Psychological assessment was conducted at four key points: initial evaluation, rehabilitation follow-up, medical discharge, and three- and six-month follow-ups. The battery included perfectionism (FMPS), anxiety (STAI), depression (BDI-II), mental health indicators (DASS-21, GHQ-12), sleep quality (PSQI), pain perception and catastrophizing (VAS, PCS), mood states (POMS), psychological readiness for return to play (PRIA-RS), and perceived intervention effectiveness. The program consisted of 15 individual sessions plus a follow-up, combining cognitive–behavioral therapy principles, mindfulness-based techniques (relaxation, body scan, visualization), cognitive restructuring, sleep hygiene, goal setting, problem-solving, and emotional expression strategies. Results: Progressive and sustained improvements were observed in mood states and pain catastrophizing, along with enhanced sleep quality, psychological readiness, and reintegration into competition. Improved overall mental health indicators were also observed, supporting adherence to rehabilitation and return-to-play confidence. Conclusions: This case highlights the relevance of structured psychological intervention as an integral component of injury rehabilitation in professional athletes with ACL rupture, supporting its inclusion in multidisciplinary care and future research to optimize recovery and prevent maladaptive outcomes. Full article

Objective: In this study, we aimed to determine the most significant risk factors for 5-year mortality in patients with paroxysmal and persistent drug-refractory tachysystolic atrial fibrillation after undergoing atrioventricular node ablation (AVNA) in combination with the implantation of a permanent three-chamber pacemaker with an implantable cardioverter–defibrillator function (CRT-D). Methods: This prospective single-center cohort study included 101 patients with chronic heart failure (mean age 62 ± 15.5 years; 70.3% male) with paroxysmal or persistent drug-refractory atrial fibrillation who underwent atrioventricular node ablation and CRT-D implantation. All patients received optimal medical therapy before and after undergoing the procedure. Predictors of 5-year mortality were assessed using exploratory machine-learning methods, including random forest and Shapley additive explanations. Results: During 5-year follow-up, 13 cardiovascular deaths were recorded. Five key predictors of mortality were identified: left ventricular ejection fraction, 6 min walk distance, mean pulmonary artery pressure, systolic relaxation coefficient, and degree of mitral regurgitation. The exploratory predictive model showed high accuracy (92%) in terms of classifying the outcomes. Conclusions: Atrioventricular node ablation (AVNA) combined with CRT-D was associated with the observed long-term clinical outcomes observed in patients with drug-refractory tachysystolic atrial fibrillation. The exploratory machine learning analysis identified key mortality-associated factors, which may support future efforts in personalized risk stratification and hypothesis generation. The combination of AVNA and CRT-D was associated with the observed long-term outcomes in this real-world cohort. Full article