Search Results (397)

The treatment landscape of metastatic hormone-sensitive prostate cancer (mHSPC) has transformed significantly with the advent of triplet therapy involving androgen deprivation therapy (ADT), docetaxel, and androgen receptor signalling inhibitors (ARSIs). While clinical guidelines increasingly support early intensification, real-world practice remains challenged by patient heterogeneity, evolving evidence, and limited consensus on treatment sequencing. This narrative review integrates evidence from landmark trials, clinical guidelines, and expert insights from oncologists managing mHSPC in India. Findings affirm that triplet therapy, particularly with darolutamide, improves survival in high-volume disease and underscores the need for personalized treatment based on disease burden, comorbidities, and genomic profiles. The review also highlights gaps in real-world data, sequencing strategies, and biomarker-driven therapy, reinforcing the need for precision medicine and locally relevant evidence to guide treatment. Ultimately, optimizing mHSPC management requires harmonizing guideline-based approaches with individualized, real-world decision making to improve patient outcomes. Full article

Background/Objectives: Androgen deprivation therapy (ADT) is widely used to manage prostate cancer (PC), but the emergence of treatment resistance remains a major clinical challenge. Although the GST family has been implicated in drug resistance, the specific role of GSTM5 remains poorly understood. This study investigates whether GSTM5, alone or in combination with clinical variables, can improve patient stratification based on the risk of early treatment resistance. Methods: In silico analyses were performed to examine GSTM5’s role in protein interactions, molecular pathways, and gene expression. The rs3768490 polymorphism was genotyped in 354 patients with PC, classified by ADT response. Descriptive analysis and logistic regression models were applied to evaluate associations between genotype, clinical variables, and ADT response. GSTM5 expression related to the rs3768490 genotype and ADT response was also analyzed in 129 prostate tissue samples. Results: The T/T genotype of rs3768490 was significantly associated with a lower likelihood of early ADT resistance in both individual (p = 0.0359, Odd Ratios (OR) = 0.18) and recessive models (p = 0.0491, OR = 0.21). High-risk classification according to D’Amico was strongly associated with early progression (p < 0.0004; OR > 5.4). Combining genotype and clinical risk improved predictive performance, highlighting their complementary value in stratifying patients by treatment response. Additionally, GSTM5 expression was slightly higher in T/T carriers, suggesting a potential protective role against ADT resistance. Conclusions: The T/T genotype of rs3768490 may protect against ADT resistance by modulating GSTM5 expression in PC. These preliminary findings highlight the potential of integrating genetic biomarkers into clinical models for personalized treatment strategies, although further studies are needed to validate these observations. Full article

Background: Congenital anosmia (CA) is a rare condition characterized by a lifelong inability to perceive odors, which significantly affects daily life and may be linked to broader neurodevelopmental alterations. This study aimed to investigate structural brain differences in patients with CA using MRI, focusing on gray matter (GM) and white matter (WM) changes and their implications for neurodevelopment. Methods: This retrospective study included 28 patients with CA and 28 age- and gender-matched healthy controls. Patients with CA were diagnosed at a single medical center between 1 January 2001 and 30 August 2024. Controls were randomly selected from an imaging database and had no history of olfactory dysfunction. Brain Magnetic Resonance Imaging (MRI)was analyzed using volumetric analysis in SPM12.GM and WM volumes were quantified across 11 anatomical brain regions based on theWFU_PickAtlas toolbox, including frontal, temporal, parietal, occipital, limbic, sub-lobar, cerebellum (anterior/posterior), midbrain, the pons, and the frontal–temporal junction. Left–right hemispheric comparisons were also conducted. Results: Patients with CA exhibited significantly smaller GM volumes compared to healthy controls (560.6 ± 114.7 cc vs. 693.7 ± 96.3 cc, p < 0.001) but larger WM volumes (554.2 ± 75.4 cc vs. 491.1 ± 79.7 cc, p = 0.015). Regionally, GM reductions were observed in the frontal (131.9 ± 33.7 cc vs. 173.7 ± 27.0 cc, p < 0.001), temporal (81.1 ± 18.4 cc vs. 96.5 ± 14.1 cc, p = 0.001), parietal (52.4 ± 15.2 cc vs. 77.2 ± 12.4 cc, p < 0.001), sub-lobar (57.8 ± 9.7 cc vs. 68.2 ± 10.2 cc, p = 0.001), occipital (39.1 ± 13.0 cc vs. 57.8 ± 8.9 cc, p < 0.001), and midbrain (2.0 ± 0.5 cc vs. 2.3 ± 0.4 cc, p = 0.006) regions. Meanwhile, WM increases were notable in the frontal(152.0 ± 19.9 cc vs. 139.2 ± 24.0 cc, p = 0.027), temporal (71.5 ± 11.5 cc vs. 60.8 ± 9.5 cc, p = 0.001), parietal (75.8 ± 12.4 cc vs. 61.9 ± 11.5 cc, p < 0.001), and occipital (58.7 ± 10.3 cc vs. 41.9 ± 7.9 cc, p < 0.001) lobes. A separate analysis of the left and right hemispheres revealed similar patterns of reduced GM and increased WM volumes in patients with CA across both sides. An exception was noted in the right cerebellum-posterior, where patients with CA showed significantly greater WM volume (5.625 ± 1.667 cc vs. 4.666 ± 1.583 cc, p = 0.026). Conclusions: This study demonstrates widespread structural brain differences in individuals with CA, including reduced GM and increased WM volumes across multiple cortical and sub-lobar regions. These findings suggest that congenital olfactory deprivation may impact brain maturation beyond primary olfactory pathways, potentially reflecting altered synaptic pruning and increased myelination during early neurodevelopment. The involvement of the cerebellum further implies potential adaptations beyond motor functions. These structural differences may serve as potential neuroimaging markers for monitoring CA-associated cognitive or emotional comorbidities. Full article

Sleep is crucial to overall health and plays a significant role in skin function. While the circadian rhythm has been extensively researched for its impact on the body’s optimal functioning, the skin also possesses an independent circadian system that serves many important functions. Sleep disruptions or deprivation can significantly affect skin conditions, by compromising the skin barrier and impairing processes such as collagen production, cellular repair, and wound healing. Given the commonality of sleep disturbances, it is crucial to understand the connection between sleep, circadian regulation, and skin health. This is particularly important in understudied populations, such as those with occupational sleep disruption and individuals with hormone-related conditions like PCOS and menopause. Bidirectional relationships have been established between sleep and several inflammatory skin conditions, including atopic dermatitis, psoriasis, rosacea, and hidradenitis suppurativa. While acne is influenced by sleep, the reverse relationship, how acne affects sleep quality, has not been well established. Chronic sleep disruption can increase cortisol levels and oxidative stress, both of which contribute to skin aging and the progression of autoimmune skin conditions, including systemic lupus erythematosus. As sleep is a modifiable risk factor, it is crucial to consider therapeutic options and interventions to prevent or alleviate skin conditions. This review discusses various therapeutic approaches, including melatonin, L-Theanine, Magnesium-L-threonate, Inositol, Cinnamomi cortex, nervous system regulation, and proper sleep hygiene. These therapeutic options have been studied for their impact on sleep, and importantly, several have been evaluated for their utility as adjuncts for treating skin conditions. Overall, the relationship between sleep and skin health is clear, and incorporating sleep-focused therapeutic interventions offers potential to improve both sleep quality and skin health in individuals with a variety of skin conditions. Full article

Transcranial direct current stimulation (tDCS) can modulate cortical excitability in a polarity-specific manner, yet identical protocols often produce inconsistent outcomes across sessions or individuals. This narrative review proposes that much of this variability arises from the brain’s intrinsic temporal landscape. Integrating evidence from chronobiology, sleep research, and non-invasive brain stimulation, we argue that tDCS produces reliable, polarity-specific after-effects only within a circadian–homeostatic “window of efficacy”. On the circadian (Process C) axis, intrinsic alertness, membrane depolarisation, and glutamatergic gain rise in the late biological morning and early evening, whereas pre-dawn phases are marked by reduced excitability and heightened inhibition. On the homeostatic (Process S) axis, consolidated sleep renormalises synaptic weights, widening the capacity for further potentiation, whereas prolonged wakefulness saturates plasticity and can even reverse the usual anodal/cathodal polarity rules. Human stimulation studies mirror this two-process fingerprint: sleep deprivation abolishes anodal long-term-potentiation-like effects and converts cathodal inhibition into facilitation, while stimulating at each participant’s chronotype-aligned (phase-aligned) peak time amplifies and prolongs after-effects even under equal sleep pressure. From these observations we derive practical recommendations: (i) schedule excitatory tDCS after restorative sleep and near the individual wake-maintenance zone; (ii) avoid sessions at high sleep pressure or circadian troughs; (iii) log melatonin phase, chronotype, recent sleep and, where feasible, core temperature; and (iv) consider mild pre-heating or time-restricted feeding as physiological primers. By viewing Borbély’s two-process model and allied metabolic clocks as adjustable knobs for plasticity engineering, this review provides a conceptual scaffold for personalised, time-sensitive tDCS protocols that could improve reproducibility in research and therapeutic gain in the clinic. Full article

Background: Sleep is a fundamental component of health, and deprivation has been linked to numerous adverse outcomes, including reduced academic and occupational performance, greater risk of accidents, and increased susceptibility to chronic diseases and premature mortality. Dietary and lifestyle behaviors are increasingly recognized as key determinants of sleep quality. Women are particularly susceptible to sleep disturbances due to hormonal fluctuations and psychosocial factors. However, women remain underrepresented in sleep research. This study aims to examine the associations between sleep quality, nutrition, and lifestyle in a large cohort of Spanish women. Methods: A cross-sectional study was conducted with 785 women aged 18–64. Participants completed the Pittsburgh Sleep Quality Index (PSQI) and the NutSo-HH questionnaire on dietary and lifestyle behaviors. Descriptive analyses, correlation matrices, Gaussian Graphical Models, and Principal Component Analyses were used to assess relationships between variables. Results: More than half of the participants rated their sleep quality as good or very good, although over 30% experienced frequent nighttime awakenings. Poor sleep quality was significantly associated with higher alcohol consumption, lower vegetable and white fish intake, and lower levels of physical activity. Diets rich in ultra-processed foods correlated moderately with subjective poor sleep and daytime dysfunction. However, no strong associations were found between stimulant consumption, late meals, or dietary patterns (e.g., Mediterranean diet) and sleep. Self-perceived health emerged as a protective factor, while nocturnal lifestyles were linked to longer sleep latency and fragmented sleep. Conclusions: In adult women, better sleep quality is linked to healthy dietary choices, regular physical activity, and a positive perception of general health. In contrast, alcohol use and irregular lifestyles are associated with poor sleep. Individual variability and cultural adaptation may moderate the impact of some traditionally harmful behaviors. Personalized, multidimensional interventions are recommended for promoting sleep health in women. Full article

This paper reports findings on the social patterning of dog bite injuries in Scotland and discusses their implications for prevention policies. Previous studies have shown evidence of social inequalities in dog bites in other countries, but this analysis provides new evidence about Scotland. Three sources of health record data are used (NHS 24 (telephone) records, accident and emergency department records, and hospital admissions records). The records span the period of 2007–2019 and combine information on 59,111 health records involving injuries caused by dogs (from 48,599 different individuals). The results are presented, summarising the volume of dog bite injuries across time periods by the age of respondents, the location of the incident, and the Scottish Index of Multiple Deprivation categorisation for their locality. The results suggest consistent patterns of social inequality in injuries caused by dogs. We argue that the most important finding concerns the higher risk for people from more deprived areas, and we discuss mechanisms that might lie behind the patterns and how policies might respond to them. Existing policies focus on the breed of dog and punitive strategies, but we argue that different approaches are more likely to be effective in addressing a socially stratified public health issue. Full article

Work-related well-being is an important research topic, as it is linked to various aspects of individuals’ lives, including job performance. To measure it effectively, unobtrusive sensors are desirable to minimize the burden on employees. Because there is a lack of consensus on the definitions of well-being in the psychological literature in terms of its dimensions, our work begins by proposing a conceptualization of well-being based on the refined definition of health provided by the World Health Organization. We focus on reviewing the existing literature on the unobtrusive measurement of well-being. In our literature review, we focus on affect, engagement, fatigue, stress, sleep deprivation, physical comfort, and social interactions. Our initial search resulted in a total of 644 studies, from which we then reviewed 35, revealing a variety of behavioral markers such as facial expressions, posture, eye movements, and speech. The most commonly used sensory devices were red, green, and blue (RGB) cameras, followed by microphones and smartphones. The methods capture a variety of behavioral markers, the most common being body movement, facial expressions, and posture. Our work serves as an investigation into various unobtrusive measuring methods applicable to the workplace context, aiming to foster a more employee-centric approach to the measurement of well-being and to emphasize its affective component. Full article

Background/Objectives: Alzheimer’s disease (AD) is a progressive neurodegenerative condition whose growing prevalence has become an increasingly important public health concern as the population ages. The lack of a definitive cure elevates the importance of identifying risk factors that are crucial for prevention efforts. Hypertension (HTN) and obesity have emerged as two highly widespread, interrelated conditions that have independently been associated with AD risk. Despite extensive research into AD pathology, the impact of obesity in a hypertensive population is not well explored. This study aims to investigate how obesity and blood pressure control within a hypertensive population may interact with genomic risk and environmental factors to influence AD incidence. Methods: A retrospective cohort of matched AD and normal patients diagnosed with HTN and taking anti-HTN drugs (n = 1862) from the All of Us database was analyzed. In this hypertensive cohort, obesity was significantly associated with increased AD risk. Genome-wide association studies (GWASs) were conducted on hypertensive AD individuals (n = 1030) and identified six single nucleotide variants (SNVs) that were associated with AD development in this population. Results: Obesity and Area Deprivation Index, a measure of socioeconomic status, were significantly associated with elevated AD risk within the hypertensive cohort. GWAS analysis identified six SNVs significantly associated with AD development among the hypertensive cohort. Conclusions: Our findings suggest that among hypertensive individuals, comorbid obesity and the Area Deprivation Index confer greater AD risk. These results highlight the critical need for obesity prevention and management strategies as part of Alzheimer’s risk reduction efforts. Full article

Poverty is a major concern worldwide, and so its eradication represents the first Sustainable Development Goal. Moreover, quality education and decent working conditions are among the factors that seem to reduce poverty, a detail also observed in the current research. The current study aimed to determine poverty and educational levels along with work conditions within the 11 EU Member States located in Central and Eastern Europe using 2023 Eurostat data. To identify them, two techniques were implemented: cluster analysis and the TOPSIS method. The first is used to determine similarities and differences between countries, and the second is used with the purpose of achieving a ranking of the countries based on the 10 indicators designed to examine the three SDGs investigated. Among the results discovered, the clear differentiation of Romania and Bulgaria compared to the other countries was observed for most of the indicators analysed, especially for the people in severe material and social deprivation, as well as the share of individuals having at least basic digital skills. Thus, by applying both methods, the grouping of Romania and Bulgaria is obvious, with these countries being characterised by the poorest performances within the analysed countries. At the opposite end of the scale was Slovenia, which presented the lowest values of the indicators intended to define poverty for the year evaluated, standing out among the countries with the best results for most of the indicators included in the analysis. Full article

Background/Objectives: The management of localized prostate cancer with regional lymph node involvement (N1M0) presents significant clinical challenges. While once considered indicative of systemic disease, improved imaging and evolving treatment paradigms have redefined node-positive disease as potentially curable. This systematic review aims to assess current evidence regarding treatment modalities and outcomes for patients with localized N1M0 prostate cancer. Methods: A systematic review was conducted to identify studies evaluating therapeutic strategies for N1M0 prostate cancer. Eligible studies included randomized controlled trials, retrospective analyses, and consensus guidelines. Treatment approaches reviewed included radical prostatectomy (RP) with pelvic lymph node dissection (PLND), whole pelvic radiotherapy (WPRT), prostate-only radiotherapy (PORT), androgen deprivation therapy (ADT), and metastasis-directed therapy (MDT), including stereotactic body radiotherapy (SBRT). Key outcomes included overall survival (OS), biochemical recurrence-free survival (bRFS), disease-free survival (DFS), and treatment-related toxicity. Results: Multimodal approaches—particularly the combination of ADT with WPRT or adjuvant radiotherapy following RP—were associated with improved survival outcomes. Patients with limited nodal burden and undetectable postoperative prostate-specific antigen (PSA) levels derived the most benefit. The use of prostate-specific antigen membrane positron-emission tomography/computed tomography (PSMA PET/CT) enhanced detection and guided MDT in oligorecurrent disease. SBRT, simultaneous integrated boost (SIB), and hypofractionated regimens demonstrated promising efficacy with acceptable toxicity profiles. Conclusions: Node-positive localized prostate cancer is optimally managed with individualized, multidisciplinary strategies. Combining systemic and locoregional treatments improves outcomes in selected patients. Ongoing prospective studies are warranted to refine patient selection, optimize treatment sequencing, and integrate novel imaging and systemic agents. Full article

NAD⁺ is a fundamental molecule participating as a redox cofactor in several metabolic reactions and has a neuroprotective role associated with oxidate stress. Despite its critical role, NAD⁺ levels sharply decline with age, contributing to the pathogenesis of aging-related diseases. Supplementation with nicotinamide riboside (NR), also known as a form of vitamin B3, a biochemical precursor of NAD⁺, may replenish this depletion. Background/Objectives: Mounting evidence suggests that dietary supplementation with NR, a form of vitamin B3 and a biochemical precursor of NAD⁺, enhances NAD⁺ bioavailability and prevents the detrimental effects on sleep, cognitive function, mitochondrial function, and insulin sensitivity. However, there is a paucity of studies focused on how NR administration affects sleep patterns. This narrative review summarizes the current state of scientific knowledge on the effects of nicotinamide riboside supplementation on sleep. Results: Pre-clinical studies indicate that NR enhances the performance of the clock genes BMAL1 and PER2, and ameliorates chronic sleep deprivation-induced cognitive impairment, potentially by alleviating oxidative stress and mitochondrial impairment in microglia. NR supplementation also increased REM sleep and reduced NREM sleep by approximately 17%. In human studies, NR improved sleep efficiency in young and middle-aged male individuals with insomnia. It also improved sleep quality and reduced fatigue and drowsiness in older adults. More research is warranted to understand the impacts of NR on sleep for women. Conclusions: NR supplementation is a reliable and effective alternative to boost NAD⁺ levels and may ameliorate sleep patterns. Full article

Background: Standard treatment for patients with early-stage estrogen receptor-positive (ER+) breast cancer often includes sequential adjuvant radiation and endocrine therapies. Unfortunately, ~1/3 of patients eventually experience disease recurrence, partly due to residual disease in the form of drug-tolerant persister cancer cells. The anti-cancer efficacy of radiation therapy is partly attributable to the production of oxyradicals that damage biomolecules. We previously showed that endocrine therapy increases mitochondrial content in ER+ breast cancer cells; we postulated that this may also increase oxidative stress. Methods: Herein, we tested the efficacy of concurrent endocrine and radiation therapies, including both conventional (CDR) and ultra-high dose rate (UHDR) radiation. Results: We found that estrogen deprivation and radiation inhibit cell growth, induce apoptosis, and force cells into an oxidatively stressed state. DNA damage was almost exclusive to cells treated with the combination of endocrine and radiation therapy. Radiation slowed tumor growth in two xenograft models, and combination with estrogen deprivation prolonged the time to regrowth in ZR75-1 tumors. Conclusions: These findings indicate that simultaneous treatment with endocrine and radiation therapies can be advantageous, warranting further evaluation to identify tumor features predictive of response to individual and combination treatments. Full article

The article seeks to read the contribution of religious practices in prison education within the broader framework of spirituality as a search for meaning in life. It argues that religious engagement can foster cognitive and emotional development, providing inmates with a sense of purpose, community, and resilience that supports their reintegration into society. In light of an exceptional and extremely significant experience with APAC in Brazil’s police-free prison model, the authors aim to highlight the nexus between spirituality and re-education in contexts of deprivation and restriction of personal liberty. Indeed, the APAC (Association for the Protection and Assistance of the Convicted) model, central to this study, emphasizes nonviolent coexistence, responsibility, and spiritual care as part of its rehabilitative framework, with a significant reduction in recidivism rates and costs compared to traditional prisons. The model’s approach, grounded in a collective sense of responsibility and spirituality, aligns with Viktor Frankl’s and Paulo Freire’s theories on meaning and liberation, illustrating how spirituality can transform prison environments and promote social justice. The study concludes that spirituality in prisons not only aids individual redemption but also calls for structural changes to support reintegration, marking a shift towards a more human-centered penitentiary system. Full article

Objectives: To evaluate how a 10-day multi-stressor field-training course—combining high physical and psycho-emotional demands, caloric restriction, and severe sleep deprivation—affects systemic oxidative/antioxidative status and biomarkers of nucleic-acid and skeletal-muscle damage in trained military cadets. Methods: Seventy-five healthy cadets (8 women, 67 men; 22–34 y) completed the course. Standardised operational rations (700–800 kcal day⁻¹) and two 20 min tactical naps per 24 h were enforced. Pre- and post-course venous blood was collected after an overnight fast. Plasma superoxide-dismutase activity (SOD), reduced and oxidised glutathione (GSH, GSSG), malondialdehyde (MDA), and hydrogen peroxide (H₂O₂) were quantified by colourimetric/fluorometric assays; 8-hydroxy-2-deoxyguanosine (8-OHdG) and myoglobin were measured by ELISA. The oxidative-stress index (OSI) was calculated as GSSG·GSH⁻¹. Within-subject differences were assessed with Wilcoxon signed-rank tests; associations between biomarker changes were explored by Spearman correlation. Results: After training, GSH (+175%, p < 0.001) and GSSG (+32%, p < 0.001) rose significantly, whereas SOD (−19%, p = 0.002), H₂O₂ (−20%, p = 0.015), MDA (−50%, p < 0.001), 8-OHdG (−23%, p < 0.001), and OSI (−47%, p < 0.001) declined. Myoglobin remained unchanged (p = 0.603). Reductions in MDA correlated inversely with increases in GSSG (rₛ = −0.25, p = 0.041), while H₂O₂ changes correlated positively with GSSG (rₛ = 0.25, p = 0.046), indicating a glutathione-driven adaptive response. Conclusions: Ten consecutive days of vigorous, calorie- and sleep-restricted field training elicited a favourable redox adaptation characterised by enhanced glutathione-mediated antioxidant capacity and lower circulating oxidant concentrations, without evidence of DNA or skeletal-muscle damage. The data suggest that, in physically prepared individuals, prolonged multi-stressor exposure can strengthen endogenous antioxidant defences rather than precipitate oxidative injury. Full article