Search Results (3,859)

Colorectal cancer (CRC) constitutes a major global health concern, ranking as the third most common cancer and the second leading cause of cancer-related mortality. The current review explores sex-based differences in CRC epidemiology, risk factors, tumor biology, and clinical outcomes. Males exhibit a higher incidence and mortality rate, with left-sided (distal) CRC predominating, while females are more frequently diagnosed with right-sided (proximal) tumors, which tend to be more aggressive and less responsive to conventional chemotherapy. Genetic disparities, including microsatellite instability and X-chromosome tumor suppressor genes, contribute to sex-specific differences in tumor progression and treatment response. Immune variations also influence disease outcomes, with females exhibiting stronger immune surveillance but higher exhaustion markers. Lifestyle factors such as body mass index (BMI), smoking, and hormonal influences further modulate CRC risk. While males are more vulnerable to obesity-related CRC, central obesity (waist-to-hip ratio) emerges as a stronger predictor in females. Additionally, smoking increases CRC risk differentially by tumor location. These findings underscore the importance of sex-specific approaches in CRC prevention, screening, and treatment, advocating for personalized medicine strategies tailored to gender-based biological and clinical distinctions. Full article

The management of acute lymphoblastic leukemia (ALL), the most common pediatric malignancy, critically relies on thiopurine therapy, such as 6-mercaptopurine (6-MP), during the maintenance phase. However, significant inter-individual response variety and high risk of myelosuppression often disrupt therapy efficacy. Pharmacogenetics offer crucial strategies to personalized therapy. While thiopurine methyltransferase (TPMT) was initially the primary focus, the discovery of nudix hydrolase 15 (NUDT15) appears as a more comprehensive determinant of thiopurine intolerance. This review aims to consolidate and critically evaluate the advancement achieved in unraveling the biological mechanism and clinical significance of NUDT15 pharmacogenetics in thiopurine therapy. Foundational studies showed the vital role of NUDT15 in the detoxification of active thiopurines, with common genetic variants (for instance, p. Arg139Cys) significantly disrupting its activity, leading to the accumulation of toxic metabolites. Observational studies consistently associated NUDT15 variants with severe myelosuppression, notably in Asian populations. Recent randomized controlled trials (RCTs) confirmed that NUDT15 genotype-guided dosing effectively reduces thiopurine-induced toxicity without interfering with the therapeutic outcome. Despite these advancements, challenges remain present, including the incomplete characterization of rare variants, limited data in the diverse Asian populations, and the need for standardized integration with metabolite monitoring. In conclusion, NUDT15 pharmacogenetics is essential for improving patient safety and thiopurine dosage optimization in the treatment of ALL. For thiopurine tailored medicine to be widely and fairly implemented, future research should focus on increasing genetic data across different populations, improving the dose adjustment algorithm, and harmonizing therapeutic guidelines. Full article

Oncology physiotherapists frequently provide care for patients experiencing severe immunosuppression. Exercise immunology, the science that studies the effects of exercise on the immune system, is a rapidly evolving field with direct relevance to oncology physiotherapists. Understanding oncology physiotherapists’ perspectives on the subject of immune functioning is essential to explore its possible integration into clinical reasoning. This study aimed to assess the perspectives of oncology physiotherapists concerning immune functioning in oncology physiotherapy. For this qualitative research, semi-structured interviews were performed with Dutch oncology physiotherapists. Results were analyzed via inductive thematic analysis, followed by a validation step with participants. Fifteen interviews were performed. Participants’ ages ranged from 30 to 63 years. Emerging themes were (1) the construct ‘immune functioning’ (definition, and associations with this construct in oncology physiotherapy), (2) characteristics related to decreased immune functioning (in oncology physiotherapy), (3) negative and positive influences on immune functioning (in oncology physiotherapy), (4) tailored physiotherapy treatment, (5) treatment outcomes in oncology physiotherapy, (6) the oncology physiotherapist within cancer care, and (7) measurement and interpretation of immune functioning. In conclusion, oncology physiotherapists play an important role in the personalized and comprehensive care of patients with cancer. They are eager to learn more about immune functioning with the goal of better informing patients about the health effects of exercise and to tailor their training better. Future exercise-immunology research should clarify the effects of different exercise modalities on immune functioning, and how physiotherapists could evaluate these effects. Full article

Background: Breast cancer is the most prevalent malignancy among women globally. In Romania, it is the most frequent form of cancer affecting women, with approximately 12,000 new cases diagnosed annually, and the second most common cause of cancer-related mortality, second only to lung cancer. Methods: This study looked at 79 breast cancer patients from Oltenia, concentrating on epidemiology, histology, diagnostic features, and treatments. Patients were chosen based on inclusion criteria such as histopathologically verified diagnosis, availability of clinical and treatment data, and follow-up information. The analyzed biological material consisted of tissue samples taken from the breast parenchyma and axillary lymph nodes. Even though not the primary subject of this paper, all patients underwent immunohistochemical (IHC) evaluation both preoperatively and postoperatively. Results: We found invasive ductal carcinoma to be the predominant type, while ductal carcinoma in situ (DCIS) and mixed types were rare. We performed cross-tabulations of metastasis versus nodal status and age versus therapy type; none reached significance (all p > 0.05), suggesting observed differences were likely due to chance. A chi-square test comparing surgical interventions (breast-conserving vs. mastectomy) in patients who did or did not receive chemotherapy showed, χ² = 3.17, p = 0.367, indicating that chemotherapy did not significantly influence surgical choice. Importantly, adjuvant chemotherapy and radiotherapy were used at similar rates across age groups, whereas neoadjuvant hormonal (endocrine) therapy was more common in older patients (but without statistical significance). Conclusions: Finally, we discussed the consequences of individualized care and early detection. Romania’s shockingly low screening rate, which contributes to delayed diagnosis, emphasizes the importance of improved population medical examination and tailored treatment options. Also, the country has one of the lowest rates of mammography uptake in Europe and no systematic population screening program. Full article

Nephrotic syndrome (NS) is characterized by proteinuria, hypoalbuminemia, edema, and hyperlipidemia. Apart from the traditional causes of NS, such as minimal change disease, focal segmental glomerulosclerosis, diabetes, infections, malignancies, autoimmune conditions, and nephrotoxic agents, there are also rare causes of NS, whose knowledge is of the utmost importance. The aim of this article was to highlight the less well-known causes that have a significant impact on diagnosis and treatment. Genetic syndromes such as Schimke immuno-osseous dysplasia, familial lecithin-cholesterol acyltransferase deficiency with two clinical variants (fish-eye Disease and the p.Leu364Pro mutation), lead to NS through mechanisms involving podocyte and lipid metabolism dysfunction. Congenital disorders of glycosylation and Nail–Patella Syndrome emphasize the role of deranged protein processing and transcriptional regulation in glomerular injury. The link of NS with type 1 diabetes, though rare, suggests an etiology on the basis of common HLA loci and immune dysregulation. Histopathological analysis, particularly electron microscopy, shows mainly podocyte damage, mesangial sclerosis, and alteration of the basement membrane, which aids in differentiating rare forms. Prompt recognition of these novel etiologies by genetic analysis, renal biopsy, and an interdisciplinary panel is essential to avoid delays in diagnosis and tailored treatment. Full article

Background/Objectives: Strengthening antimicrobial stewardship (AMS) programs is an invaluable intervention in the ongoing efforts to contain the threat of antimicrobial resistance (AMR), particularly in low-resource settings. This study evaluates the impact of the Telementoring, Education, and Advocacy Collaboration initiative for Health through Antimicrobial Stewardship (TEACH AMS), which uses the virtual Extension for Community Healthcare Outcomes (ECHO) learning model to enhance AMS capacity in Kenya, Ghana, and Malawi. Methods: A mixed-methods approach was used, which included attendance data collection, facility-level assessments, post-session and follow-up surveys, as well as focus group discussions. Results: Between September 2023 and February 2025, 77 virtual learning sessions were conducted, engaging 2445 unique participants from hospital-based AMS committees and health professionals across the three countries. Participants reported significant knowledge gain, and data showed facility improvements in two core AMS areas, including the implementation of multidisciplinary ward-based interventions/communications and enhanced monitoring of antibiotic resistance patterns. Along those lines, participants reported that the program assisted them in improving prescribing and culture-based treatments, and also evidence-informed antibiotic selection. The evidence of implementing ward-based interventions was further stressed in focus group discussions, as well as other strengthened practices like point-prevalence surveys, and development or revision of stewardship policies. Substantial improvements in microbiology services were also shared by participants, particularly in Malawi. Other practices mentioned were strengthened multidisciplinary communication, infection prevention efforts, and education of patients and the community. Conclusion: Our findings suggest that a virtual case-based learning educational intervention, providing structured and tailored AMS capacity building, can drive behavior change and strengthen healthcare systems in low resource settings. Future efforts should aim to scale up the engagements and sustain improvements to further strengthen AMS capacity. Full article

Background: Bipolar disorder (BD) is a chronic and disabling psychiatric condition characterized by recurring episodes of mania, hypomania, and depression. Despite the availability of mood stabilizers, antipsychotics, and antidepressants, long-term management remains challenging due to incomplete symptom control, adverse effects, and high relapse rates. Methods: This paper is a narrative review aimed at synthesizing emerging trends and future directions in the pharmacological treatment of BD. Results: Future pharmacotherapy for BD is likely to shift toward precision medicine, leveraging advances in genetics, biomarkers, and neuroimaging to guide personalized treatment strategies. Novel drug development will also target previously underexplored mechanisms, such as inflammation, mitochondrial dysfunction, circadian rhythm disturbances, and glutamatergic dysregulation. Physiological endophenotypes, such as immune-metabolic profiles, circadian rhythms, and stress reactivity, are emerging as promising translational tools for tailoring treatment and reducing associated somatic comorbidity and mortality. Recognition of the heterogeneous longitudinal trajectories of BD, including chronic mixed states, long depressive episodes, or intermittent manic phases, has underscored the value of clinical staging models to inform both pharmacological strategies and biomarker research. Disrupted circadian rhythms and associated chronotypes further support the development of individualized chronotherapeutic interventions. Emerging chronotherapeutic approaches based on individual biological rhythms, along with innovative monitoring strategies such as saliva-based lithium sensors, are reshaping the future landscape. Anti-inflammatory agents, neurosteroids, and compounds modulating oxidative stress are emerging as promising candidates. Additionally, medications targeting specific biological pathways implicated in bipolar pathophysiology, such as N-methyl-D-aspartate (NMDA) receptor modulators, phosphodiesterase inhibitors, and neuropeptides, are under investigation. Conclusions: Advances in pharmacogenomics will enable clinicians to predict individual responses and tolerability, minimizing trial-and-error prescribing. The future landscape may also incorporate digital therapeutics, combining pharmacotherapy with remote monitoring and data-driven adjustments. Ultimately, integrating innovative drug therapies with personalized approaches has the potential to enhance efficacy, reduce adverse effects, and improve long-term outcomes for individuals with bipolar disorder, ushering in a new era of precision psychiatry. Full article

With the arrival of an aging society and the continuous extension of the human lifespan, the quality of life has not improved in a corresponding manner. People’s demand for happiness and health is increasing. As a result, a model emerged that integrates tourism and medical services, which is health tourism. This growing demand has prompted many service providers to see it as a business opportunity and enter the market. Tourism can help travelers release work stress and restore physical and mental balance; meanwhile, health check-ups and disease treatment can help them regain health. Consumers have long favored health and medical tourism because it helps relieve stress and promotes overall well-being. As people age, some consumers experience a gradual decline in physical functions, making it difficult for them to participate in regular travel services provided by traditional travel agencies. Therefore, this study aims to explore the service needs of health and medical tourism customers (tourists/patients) and the interrelationships among these service needs, so that health and medical tourism service providers can develop more customized and diversified services. This study identifies four key drivers of medical tourism services: medical services, medical facilities, tour planning, and hospitality facilities. This study uses the APA (attention and performance analysis) method to assess each dimension and criterion and utilizes the DEMATEL method with the NRM (network relationship map) to identify network relationships. By combining APA and NRM techniques, this study develops the APA-NRM technique to evaluate adoption strategies and identify suitable paths for health tourism services, providing tailored development strategies and recommendations for service providers to enhance the service experience. Full article

Cardiovascular disease (CVD) remains Europe’s leading cause of mortality, responsible for >45% of deaths. Beyond established risk factors (hypertension, diabetes, dyslipidaemia, smoking, obesity), psychosocial elements—depression, anxiety, financial stress, personality traits, and trauma—significantly influence CVD development and progression. Behavioural Cardiology addresses this connection by systematically incorporating psychosocial factors into prevention and rehabilitation protocols. This review examines the HEARTBEAT model, developed by Greece’s first Behavioural Cardiology Unit, which aligns with current European guidelines. The model serves dual purposes: primary prevention (targeting at-risk individuals) and secondary prevention (treating established CVD patients). It is a personalised medicine approach that integrates psychosocial profiling with traditional risk assessment, utilising tailored evaluation tools, caregiver input, and multidisciplinary collaboration to address personality traits, emotional states, socioeconomic circumstances, and cultural contexts. The model emphasises three critical implementation aspects: (1) digital health integration, (2) cost-effectiveness analysis, and (3) healthcare system adaptability. Compared to international approaches, it highlights research gaps in psychosocial interventions and advocates for culturally sensitive adaptations, particularly in resource-limited settings. Special consideration is given to older populations requiring tailored care strategies. Ultimately, Behavioural Cardiology represents a transformative systems-based approach bridging psychology, lifestyle medicine, and cardiovascular treatment. This integration may prove pivotal for optimising chronic disease management through personalised interventions that address both biological and psychosocial determinants of cardiovascular health. Full article

Orofacial pain encompasses a spectrum of disorders ranging from musculoskeletal disorders, such as myofascial pain, and temporomandibular disorders to neuropathic situations, such as trigeminal neuralgia and painful post-traumatic trigeminal neuropathy, and neurovascular pain such as orofacial migraine and cluster orofacial pain. Each require tailored prophylactic pharmacotherapy, such as carbamazepine, gabapentin, pregabalin, amitriptyline, metoprolol, and topiramate. Yet a substantial subset of patients remains refractory. Botulinum toxin type A (BoNT-A) has demonstrated growing efficacy in the treatment of multiple forms of orofacial pain, which covers the whole range of these disorders. We describe the analgesic properties of BoNT-A for each of the three following orofacial pain disorders: neuropathic, myofascial, and neurovascular. Then, we conclude with a section on the neuromodulatory mechanisms of BoNT-A. This lays the basis for the generation of a hypothesis for the segmental therapeutic action of BoNT-A on the whole range of orofacial pain disorders. In addition, the advantage of BoNT-A for providing a safe sustained effect after a single application for chronic pain prophylaxis is discussed, as opposed to the daily use of current conventional prophylactic medications. Finally, we summarize the clinical applications of BoNT-A for chronic orofacial pain therapy. Full article

In many developing African countries, milk safety is often managed through traditional methods such as fermentation or boiling over firewood. While these approaches reduce some microbial risks, they present critical limitations. Firewood dependency contributes to deforestation, depletion of agricultural residues, and loss of soil fertility, which, in turn, compromise environmental health and food security. Solar pasteurization provides a reliable and sustainable method for thermally inactivating pathogenic microorganisms in milk and other perishable foods at sub-boiling temperatures, preserving its nutritional quality. This study aimed to evaluate the thermal and microbial performance of a low-cost solar milk pasteurization system, hypothesized to effectively reduce microbial contaminants and retain milk quality under natural sunlight. The system was constructed using locally available materials and tailored to the climatic conditions of the Savanna ecological zone in West Africa. A flat-plate glass solar collector was integrated with a 0.15 cm thick stainless steel cylindrical milk vat, featuring a 2.2 cm hot water jacket and 0.5 cm thick aluminum foil insulation. The system was tested in Navrongo, Ghana, under ambient temperatures ranging from 30 °C to 43 °C. The pasteurizer successfully processed up to 8 L of milk per batch, achieving a maximum milk temperature of 74 °C by 14:00 GMT. Microbial analysis revealed a significant reduction in bacterial load, from 6.6 × 10⁶ CFU/mL to 1.0 × 10² CFU/mL, with complete elimination of coliforms. These results confirmed the device’s effectiveness in achieving safe pasteurization levels. The findings demonstrate that this locally built solar pasteurization system is a viable and cost-effective solution for improving milk safety in arid, electricity-limited regions. Its potential scalability also opens avenues for rural entrepreneurship in solar-powered food and water treatment technologies. Full article

Background/Objectives: Pituitary tumors account for over 90% of all sellar region masses. However, a spectrum of rare neoplastic, inflammatory, infectious, and vascular lesions—benign and malignant—can arise in the intra- and parasellar compartments and clinically and radiologically mimic PitNETs. We report a cohort of 47 such rare and cystic midline intracranial lesions, emphasizing their distinctive morphological, clinical, and imaging features and the personalized treatment strategies applied. Methods: In this retrospective single-center study, we reviewed all patients treated for suspected PitNETs via transsphenoidal approach between 2015 and 2024. Of 529 surgical cases, we excluded confirmed PitNETs, meningiomas, and classical intradural craniopharyngiomas. Collected data encompassed patient demographics, tumor characteristics, presenting symptoms, extent of resection or medical therapy, endocrine outcomes, and follow-up information. Results: Among all 529 patients who underwent surgical treatment for sellar lesions from 2015 to 2024, 47 cases (8.9%) were identified as rare or cystic masses. Forty-six underwent transsphenoidal resection; one patient with hypophysitis received corticosteroid therapy alone. Presenting symptoms included headache (n = 16), dizziness (n = 5), oculomotor disturbances (n = 2), and visual impairment (n = 17). Endocrine dysfunction was found in 30 patients, 27 of whom required hydrocortisone replacement. Histopathological diagnoses were led by colloid cysts (n = 14) and Rathke’s cleft cysts (n = 11). The remaining 22 cases comprised plasmacytoma, germinoma, lymphoma, pituicytoma, inverted papilloma, metastatic carcinoma, chordoma, nasopharyngeal carcinoma, chloroma, and other rare entities. Preoperative imaging diagnosis proved incorrect in 38% (18/47) of cases, with several lesions initially misidentified as PitNETs. Conclusions: Nearly 9% of presumed PitNETs were rare, often benign or inflammatory lesions requiring distinct management. Most could be safely resected and demonstrated excellent long-term outcomes. Yet, despite advanced imaging techniques, accurate preoperative differentiation remains challenging, with over one-third misdiagnosed. Clinical red flags—such as early hormone deficits, rapid progression or atypical imaging findings—should prompt early interdisciplinary evaluation and, when indicated, image-guided biopsy to avoid unnecessary surgery and ensure tailored therapy. Full article

Neurodevelopmental disorders (NDDs) significantly impact children’s health and development. They pose a substantial burden to families and the healthcare system. Challenges in early identification, accurate and timely diagnosis, and effective treatment persist due to overlapping symptoms, lack of appropriate diagnostic biomarkers, significant stigma and discrimination, and systemic barriers. Generative Artificial Intelligence (GenAI) offers promising solutions to these challenges by enhancing screening, diagnosis, personalized treatment, and research. Although GenAI is already in use in some aspects of NDD management, effective and strategic leveraging of evolving AI tools and resources will enhance early identification and screening, reduce diagnostic processing by up to 90%, and improve clinical decision support. Proper use of GenAI will ensure individualized therapy regimens with demonstrated 36% improvement in at least one objective attention measure compared to baseline and 81–84% accuracy relative to clinician-generated plans, customize learning materials, and deliver better treatment monitoring. GenAI will also accelerate NDD-specific research and innovation with significant time savings, as well as provide tailored family support systems. Finally, it will significantly reduce the mortality and morbidity associated with NDDs. This article explores the potential of GenAI in transforming NDD management and calls for policy initiatives to integrate GenAI into NDD management systems. Full article

This study investigates the mechanical, tribological, and electrochemical behaviour of a novel precipitation-hardenable martensitic alloy produced by selective laser melting (SLM). The alloy was specifically engineered with an optimised composition, free from cobalt and molybdenum, and featuring reduced nickel content (7 wt.%) and 8 wt.% chromium. It has been developed as a cost-effective and sustainable alternative to conventional maraging steels, while maintaining high mechanical strength and a refined microstructure tailored to the steep thermal gradients inherent to the SLM process. Several ageing heat treatments were assessed to evaluate their influence on microstructure, hardness, tensile strength, retained austenite content, dislocation density, as well as wear behaviour (pin-on-disc test) and corrosion resistance (polarisation curves in 3.5%NaCl). The results indicate that ageing at 540 °C for 2 h offers an optimal combination of hardness (550–560 HV), tensile strength (~1700 MPa), microstructural stability, and wear resistance, with a 90% improvement compared to the as-built condition. In contrast, ageing at 600 °C for 1 h enhances ductility and corrosion resistance (Rp = 462.2 kΩ; Ecorr = –111.8 mV), at the expense of a higher fraction of reverted austenite (~34%) and reduced hardness (450 HV). This study demonstrates that the mechanical, surface, and electrochemical performance of this novel SLM-produced alloy can be effectively tailored through controlled thermal treatments, offering promising opportunities for demanding applications requiring a customised balance of strength, durability, and corrosion behaviour. Full article

Enhancing the yield and qualitative traits of horticultural crops without further hampering the environment constitutes an urgent challenge that could be addressed by implementing innovative agronomic tools, such as plant biostimulants. This study investigated the effects of three commercial biostimulants—BIO1 (fulvic/humic acids), BIO2 (leonardite-humic acids), and BIO3 (plant-based extracts)—on leaf ecophysiology, yield, and fruit quality in two raspberry cultivars, ‘Autumn Bliss’ (AB) and ‘Zeva’ (Z), grown in an open-field context, to assess their effectiveness in raspberry cultivation. Experimental activities involved two Research Years (RYs), namely, year 2023 (RY 1) and 2024 (RY 2). Leaf parameters such as chlorophyll, flavonols, anthocyanins, and the Nitrogen Balance Index (NBI) were predominantly influenced by the interaction between Treatment, Year and Cultivar factors, indicating context-dependent responses rather than direct biostimulant effects. BIO2 showed a tendency to increase yield (g plant⁻¹) and berry number plant⁻¹, particularly in RY 2 (417.50 g plant⁻¹, +33.93% vs. control). Fruit quality responses were cultivar and time-specific: BIO3 improved soluble solid content in AB (12.8 °Brix, RY 2, Intermediate Harvest) and Z (11.43 °Brix, +13.91% vs. BIO2). BIO2 reduced titratable acidity in AB (3.12 g L⁻¹) and increased pH in Z (3.02, RY 2) but also decreased °Brix in Z. These findings highlight the potential of biostimulants to modulate raspberry physiology and productivity but underscore the critical role of cultivar, environmental conditions, and specific biostimulant composition in determining the outcomes, which were found to critically depend on tailored application strategies. Full article