Medical sciences (Basel, Switzerland)最新文献

Background: Chronic pain affects nearly one in five adults worldwide and remains a major healthcare burden due to its persistence, multidimensional impact, and resistance to conventional therapies. The opioid crisis has further highlighted the urgent need for safer and more effective alternatives. Psilocybin, a serotonergic psychedelic compound, has re-emerged as a potential therapeutic option for chronic pain given its effects on neuroplasticity, neuroinflammation, and emotional regulation.

Methods: This narrative review synthesized evidence from published preclinical and clinical studies. The focus was on the mechanisms of action of psilocybin, animal models of neuropathic and inflammatory pain, and early human trials exploring its effects on pain, mood, and quality of life.

Results: Preclinical studies demonstrated that psilocybin promotes synaptogenesis via BDNF-TrkB signalling, modulates 5-HT2A receptor activity, and reduces neuroinflammatory processes, leading to persistent analgesic and anxiolytic effects. Animal models of chemotherapy-induced neuropathy and inflammatory pain showed long-lasting antinociceptive responses. Clinical studies, though limited, reported improvements in depression, anxiety, resilience, and quality of life in patients with advanced cancer and chronic conditions, with preliminary evidence of analgesic benefit.

Conclusions: Psilocybin shows promise as a multidimensional therapy for chronic pain, addressing both sensory and affective components. However, ethical issues, safety concerns, and regulatory barriers necessitate careful management, and robust randomized controlled trials are essential to confirm efficacy and guide clinical translation.

Background/Objectives: Epilepsy is a major neurological disorder associated with significant comorbidity and treatment challenges. In low- and middle-income countries, access to newer antiseizure medications (ASMs) remains limited, and prescription patterns often rely on older agents. This study aimed to characterize national prescribing patterns of ASMs among patients with epilepsy in Kazakhstan from 2021 to 2023. Methods: We conducted a retrospective observational study using de-identified electronic health record data from the Unified National Electronic Health System of Kazakhstan. All patients with an ICD-10 diagnosis of epilepsy (G40) and at least one ASM prescription during 2021-2023 were included. Prescription frequencies, therapy type, and chronic polytherapy levels were analyzed. Associations between therapy type, age, and comorbidity status were determined. Results: A total of 54,274 patients were identified (median age 42 years; interquartile range (IQR) 31-57). Monotherapy predominated: 61.7% remained on monotherapy, 18.5% remained on polytherapy, and 19.8% had mixed exposure. Carbamazepine and valproic acid were most frequently prescribed (64.3% and 45.6% of patients, respectively). Among those with chronic medication data (n = 15,752), nervous-system drugs were common (70.1%), led by psycholeptics (49.7%); frequently dispensed agents included chlorpromazine (n = 5991), clozapine (n = 1875), and risperidone (n = 1642). Cardiovascular agents were recorded in 37.2% (acetylsalicylic acid n = 4056; atorvastatin n = 2235), and diabetes drugs in 12.1% (metformin n = 1430). Conclusions: Epilepsy treatment in Kazakhstan remains dominated by older broad-spectrum ASMs, while the use of lamotrigine and levetiracetam is steadily increasing. The frequent co-prescription of psychotropic and cardiometabolic drugs underscores the need for coordinated, multidisciplinary care and continued monitoring of prescribing patterns to enhance treatment safety and effectiveness.

Breast cancer continues to rank among the most common and complex cancers worldwide. A promising approach is the direct delivery of drugs to cancer cells via specially designed nanocarriers that can target specific receptors on their surface, like folate receptors. When combined with other therapies, these functionalized nanocarriers can increase the effectiveness of treatment by more precisely targeting cancer cells than traditional methods that rely on passive targeting. Folate receptors are glycoproteins with four isoforms, for which both laboratory and animal models have shown encouraging results in research. The numerous chemical methods for attaching folic acid (FA) and enhancing drug delivery in folic acid-modified nanocarriers for breast cancer are examined in this review. Additionally, it examines how these smart carriers combine chemotherapy with alternative therapies like photodynamic therapies and state-of-the-art theranostics. The review highlights how important it is to carry out comprehensive testing to ensure that these innovations can successfully move from the lab to real clinical settings, even though the potential is evident.

Background: Traditional tumor markers used in testicular cancer diagnosis, such as alpha-fetoprotein (AFP), beta-human chorionic gonadotropin (hCG), and lactate dehydrogenase (LDH), present limitations due to variable expression across tumor subtypes. Inflammatory markers derived from complete blood count (CBC), along with C-reactive protein (CRP), have emerged as potential adjuncts for diagnosis and prognosis. This study aimed to evaluate the diagnostic and prognostic utility of CBC-derived inflammatory indices and CRP in patients with testicular cancer.

Methods: We retrospectively analyzed testicular cancer patients, assessing baseline CBC parameters, inflammatory ratios (including neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR], and systemic immune-inflammation index [SII]), and CRP levels. Their diagnostic accuracy was compared with classical tumor markers, while prognostic implications were assessed through survival outcomes and disease progression.

Results: Inflammatory markers, particularly NLR and SII, demonstrated significant associations with tumor burden and advanced disease stage. Elevated CRP levels correlated with poorer prognostic features and worse outcomes. While classical tumor markers remained essential in diagnosis and staging, the integration of inflammatory indices provided additional discriminatory power, especially in patients with normal or equivocal AFP and hCG values.

Conclusions: CBC-derived inflammatory markers and CRP represent promising, cost-effective, and easily accessible tools that complement classical tumor markers in testicular cancer. They offer both diagnostic and prognostic value, particularly in cases where traditional biomarkers are insufficient. Prospective multicenter studies are warranted to validate these findings and incorporate inflammatory indices into routine clinical algorithms for testicular cancer management.

This study examined whether the triglyceride-to-high-density lipoprotein cholesterol (TG/HDL-C) ratio is associated with cardiovascular and all-cause mortality among non-diabetic patients undergoing hemodialysis. From June 2017 to December 2023, patients followed until December 2024 were categorized into two groups based on their baseline TG/HDL-C ratio: those with a high TG/HDL-C ratio (>3.29) and those with a non-elevated TG/HDL-C ratio (≤3.29). The association between TG/HDL-C ratio and CV and all-cause mortality was examined by univariate and multivariate Cox regression analyses. Of the 138 patients, 43 were categorized into the high TG/HDL-C ratio group and 95 into the non-elevated TG/HDL-C ratio group. The non-elevated TG/HDL-C ratio group had significantly increased cardiovascular survival rates of 1, 3, and 5 years (97.8% vs. 85.2%, 96.2% vs. 70.0%, and 87.0% vs. 52.2%, respectively; p < 0.05) and overall survival rates of 1, 3, and 5 years (95.8% vs. 79.1%, 89.6% vs. 62.9%, and 73.9% vs. 40.7%, respectively; p < 0.05). In the proportional hazards model, a high TG-HDL ratio was an independent predictor of cardiovascular mortality (hazard ratio [HR]: 6.799; 95% confidence interval [CI]: 2.276-20.313; p = 0.001) and all-cause mortality (HR: 2.88; 95% CI: 1.16-7.17; p = 0.023). A high TG/HDL-C ratio was associated with CV and overall mortality in non-diabetic HD patients. Further research will be required to explore changes in the serum TG/HDL-C ratio, assess lipoprotein profiles, and determine their outcomes in this group.

Background: Abdominal aortic aneurysm (AAA) is a multifactorial vascular disease with limited therapeutic options, as no pharmacological treatments currently exist to mitigate the progression of small AAAs. Quality of life (QoL) has emerged as a valuable supplementary metric for assessing the efficacy of pharmacological interventions. This study evaluated QoL scores of MetAAA trial patients on metformin therapy compared to those with placebo intake. Methods: Overall, 54 patients with AAA were included in the MetAAA trial (ClinicalTrials.gov-Identifier:NCT03507413) and randomized to either metformin or placebo treatment. All participants were asked to complete three established and validated (in total 659 longitudinally collected) QoL questionnaires: (1) the 36-Item Short Form Health Survey (SF-36), (2) the Aneurysm Symptom Rating Questionnaire (ASRQ), and (3) the Aneurysm-Dependent Quality of Life questionnaire (ADQoL). Results: A superior health-related QoL was found in metformin-treated AAA patients compared to enrolled AAA patients receiving a placebo. In detail, AAA patients undergoing metformin treatment showed a superior overall current QoL score (p = 0.038), general health perception (p = 0.013), improved physical functioning (p = 0.004), and increased energy/lower fatigue scores (p = 0.008). Furthermore, fewer limitations due to cognitive distress (p = 0.001) and lower limb function (p = 0.021) were detected. Other QoL subscales did not show statistical significance. Inflammatory blood parameters suggest that while systemic inflammation may have some impact on perceived QoL, the relationship is largely limited. Conclusions: In patients with small AAA, metformin led to a limited improvement in health-related QoL compared to a placebo.

Background: A systematic exercise programme using low-cost virtual reality devices can help maintain and improve postural control in older adults. This study aimed to evaluate the effectiveness of two different exergame programme modalities: telerehabilitation (TR) and face-to-face (FF).

Methods: A randomised controlled trial was conducted with 16 participants aged 65 to 75. Both groups completed an 18-session exergame intervention over six weeks, with the TR group (exposure) receiving remote sessions and the FF group having in-person (control) sessions with a physiotherapist. Assessments were carried out at baseline, at weeks 2, 4, and 6, with two follow-ups at weeks 8 and 10. Centre of Pressure (CoP) measures in tasks: eyes open (EO), eyes closed (EC), medial-lateral (ML) weight-shifting exergame and anterior-posterior (AP) weight-shifting exergame, and clinical tests were used to evaluate postural control.

Results: TR and FF significantly reduced the CoP_Sway-area during EC (TR: p < 0.01; FF: p = 0.01) at 6 weeks and only FF demonstrated a significant reduction during EO (p < 0.01). Post hoc analysis revealed that TR maintained a significant reduction in the secondary outcomes of the CoP at 8 and 10 weeks, while FF did not sustain these effects over time. Between-group comparisons revealed a greater effect of TR in CoP_Sway-area, and secondary outcomes during the AP weight-shifting task (p < 0.01) at 6 weeks, whereas the FF had a greater effect in secondary CoP outcomes during the ML weight-shifting task (p < 0.01) at 6 weeks.

Conclusion: Both six-week exergame programmes were equally effective at improving postural control. Given the observed specific effects of TR and FF delivery, physiotherapists can consider either modality to suit individual needs and access, or as a complementary approach to maintain and improve postural control in older adults.

Background: Obesity and insomnia are prevalent public health issues with shared behavioral and physiological pathways. However, their interplay remains understudied in occupational cohorts. Obesity and insomnia are prevalent public health issues with shared behavioral and physiological pathways. However, their interplay remains understudied in occupational cohorts. This study aimed to evaluate the associations of sociodemographic factors, lifestyle habits, and insomnia severity with multiple obesity indices in a large population of Spanish workers. Methods: We conducted a cross-sectional analysis of 84,898 workers (2021-2024). Data were obtained from annual occupational health assessments conducted across multiple Spanish regions between 2020 and 2024. Insomnia severity was assessed using the Insomnia Severity Index (ISI), dietary quality using the 14-item Mediterranean Diet Adherence Screener (MEDAS-14), and physical activity using the International Physical Activity Questionnaire-Short Form (IPAQ-SF). Adiposity was measured using Body Mass Index (BMI), waist-to-height ratio (WtHR), the Clínica Universidad de Navarra-Body Adiposity Estimator (CUN-BAE), and the Metabolic Score for Visceral Fat (METS-VF). Multivariable logistic regression models were used to examine associations adjusted for age, sex, education, and occupational social class. Results: Higher ISI scores were significantly and independently associated with elevated adiposity across all indices, with the strongest association observed for METS-VF (odds ratio = 1.19, 95% CI 1.14-1.25, p < 0.001). Women showed higher mean CUN-BAE and METS-VF values than men (CUN-BAE: 37.4 ± 6.2 vs. 25.6 ± 6.4; p < 0.001; METS-VF: 5.7 ± 0.7 vs. 6.4 ± 0.6; p < 0.001), despite lower BMI (25.3 ± 4.8 vs. 26.8 ± 4.3; p < 0.001). Lower physical activity (OR = 5.70; 95% CI 4.91-6.50), poor adherence to the Mediterranean diet (OR = 3.29; 95% CI 2.88-3.70), smoking (OR = 1.29; 95% CI 1.22-1.36), and lower occupational class (Class III: OR = 1.77; 95% CI 1.56-1.97) were also significantly associated with higher obesity markers. Associations were more pronounced among women and participants with severe insomnia symptoms. Conclusions: Insomnia severity, sociodemographic disadvantage, and unhealthy behaviors (low physical activity, poor diet, smoking) were all independent correlates of general and visceral adiposity. The findings underscore the need for comprehensive workplace health programs that integrate sleep quality assessment, dietary improvement, and physical activity promotion to prevent obesity and its metabolic consequences.

The study of incretins spans more than a century and has revealed their essential role in glucose homeostasis and metabolic regulation. This understanding has led to the development of incretin receptor agonists as highly effective pharmacological agents for the treatment of such cardiometabolic diseases as type 2 diabetes and obesity, showing substantial benefits in glycemic control, body weight reduction, and cardiometabolic outcomes. However, their use is limited by adverse events, most commonly gastrointestinal intolerance, along with ongoing safety concerns regarding pancreatic, renal, and ophthalmologic effects. Although incretin-based therapies have fundamentally reshaped the management of diabetes and obesity, continued innovation in drug design and delivery holds promise for expanding their applicability, improving patient adherence, and reinforcing their role as a cornerstone of metabolic disease management and beyond. This review summarizes the historical development, molecular design, and clinical relevance of incretin-based therapies, with particular emphasis on approved agents used in current clinical practice.

Background/objectives: Postmenopausal women face an elevated risk of sarcopenia and functional decline, yet the distinct roles of type 2 diabetes mellitus (T2DM) and physical inactivity in these outcomes remain unclear. This study aimed to investigate the independent and combined associations of T2DM and physical activity on sarcopenia and functional performance in postmenopausal women.

Methods: This was a cross-sectional study of 175 postmenopausal women stratified by T2DM status and physical activity level (active ≥150 min/week vs. insufficiently active). Body composition was assessed via dual-energy X-ray absorptiometry, muscle strength by handgrip dynamometry, and functional performance by gait speed. Sarcopenia was diagnosed using the Asian Working Group for Sarcopenia 2019 criteria. Binary logistic regression calculated odds ratios (ORs) for adverse outcomes.

Results: Physical inactivity was the strongest predictor of functional decline, with insufficiently active women showing nearly four-fold increased odds of slow gait speed (<1.0 m/s) compared to active counterparts (OR: 3.93; 95% CI: 1.24-12.45). While T2DM appeared protective against sarcopenia in unadjusted analysis, multivariate adjustment revealed obesity (OR: 4.97; 95% CI: 1.62-15.20) and T2DM (OR: 3.80; 95% CI: 1.59-9.08) as independent sarcopenia predictors.

Conclusions: Distinct associational profiles emerged for sarcopenia and functional decline in postmenopausal women. While T2DM and obesity are independently associated with sarcopenia through metabolic mechanisms, physical inactivity emerged as the strongest predictor of functional impairment. These findings support targeted interventions: metabolic optimization for muscle mass preservation and structured physical activity, particularly resistance training, for maintaining functional independence in this high-risk population.