Search Results (5,103)

Objective: This study was conducted to examine the relationship between ruminative thinking styles and suicide probability in individuals presenting to the emergency department with suspected alcohol and substance intoxication/use, and to investigate whether these variables differ according to various demographic characteristics. Methods: The sample of this descriptive study consisted of 45 cases presenting to the emergency departments of two hospitals in eastern Turkey. Data were collected using a Sociodemographic Data Form, the Rumination Scale, and the Suicide Probability Scale. Descriptive statistics, Pearson correlation, independent samples t-test, and Linear Regression analysis were used for data analysis. Results: Of the participants, 66.7% were male and 44.4% were in the 18–23 age group. A positive and moderately significant relationship was found between rumination and suicide probability (r = 0.441; p = 0.001). Regression analysis revealed that rumination explained 34% of the variance in the suicide probability. Furthermore, suicide probability scores of those using non-alcohol or multiple substances were significantly higher than those using only alcohol (p = 0.025). Conclusions: Ruminative thinking is a significant associated factor of suicide risk in patients with alcohol and substance use disorders presenting to the emergency department. It is recommended that cognitive assessments of these patients be conducted during clinical processes and that multiple-substance users, in particular, should be closely monitored for suicide risk. Full article

Lung adenocarcinoma (LUAD) remains the leading cause of mortality worldwide, while asthma is the most prevalent chronic disease affecting individuals of all ages. The shared airway involvement in these global health concerns results in exposure to common risk factors, suggesting a potential overlap in their genetic background. Given the roles oxidative stress and chronic inflammation play in both LUAD and asthma, we aimed to investigate similarities in their molecular mechanisms and to explore whether these shared transcriptomic signatures may prove useful for potential drug repurposing hypotheses by analyzing relevant transcriptomic datasets. This analysis identified a set of genes and co-expression interactions shared between asthma and LUAD, suggesting potential common molecular mechanisms underlying both diseases. Specifically, DNAJC3, APOBEC3G, and PRDX4 were highlighted as potential common molecular mediators underlying both diseases, offering correlative evidence for shared pathways. These genes may represent key molecular links connecting the pathogenic processes of asthma and LUAD. The transcriptomic profiles of asthma and lung cancer datasets reveal common molecular interactions, suggesting potential shared biological mechanisms between the two diseases. These findings provide a computational framework that may guide future studies investigating therapeutic associations and possible drug–gene relationships in lung adenocarcinoma and asthma. Full article

Background/Objectives: This study examined the association between self-reported walking pace and subclinical hypothyroidism (SCH) in relation to atherosclerotic status, as both walking pace and SCH have been linked to an increased risk of all-cause mortality and cardiovascular disease. The vascular network underlying atherosclerotic processes may help explain this relationship. Methods: This was a cross-sectional study involving 1719 Japanese with normal thyroid function (free triiodothyronine [T3] and free thyroxine [T4] levels within the normal range). Since all individuals who participated in this study had free T3 and free T4 levels within the normal range, those with elevated TSH levels (>4.01 μIU/mL) were classified as having SCH. Self-reported faster walking pace was identified based on the participants’ responses to whether they perceived themselves as walking faster than their peers of the same age and sex. Logistic regression models were used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for SCH. Results: Of the study participants, 166 had atherosclerosis and 98 had SCH. Among individuals without atherosclerosis, a self-reported faster walking pace was significantly inversely associated with SCH but not among those with atherosclerosis. The sex and age-adjusted ORs (95% CIs) of SCH for self-reported faster walking pace were 0.58 (0.37, 0.91) for those without atherosclerosis and 2.35 (0.75, 7.36) for those with atherosclerosis. Atherosclerosis showed a significant interaction with the association between SCH and self-reported faster walking pace, with sex- and age-adjusted p-values of 0.027. These associations persisted, even after adjusting for potential confounding factors. Conclusions: Self-reported faster walking pace is inversely associated with SCH in individuals without atherosclerosis but not in those with atherosclerosis. Atherosclerosis status may influence the association between SCH and self-reported faster walking pace. Full article

Multiple sclerosis (MS) is a neuro-inflammatory disease characterized by demyelination in the central nervous system (CNS). Although a substantial endogenous capacity for remyelination has been demonstrated, this process is frequently incomplete and exhibits marked intra- and inter-individual heterogeneity. Several factors influence the extent of spontaneous myelin regeneration, including age, sex, disease course, and lesion localization. Oligodendrocytes (OL), derived from oligodendrocyte progenitor cells (OPCs), are the principal myelinating cells of the CNS. The regenerative cascade involves several key stages, including OPC activation, recruitment, differentiation into oligodendrocytes (OL), and myelin deposition. This process is orchestrated in a spatiotemporal manner by a complex interplay of intracellular signaling pathways, genetic determinants, and dynamic microenvironmental cues, which together balance inhibitory and pro-remyelinating influences. Several lines of evidence indicate that chronically demyelinated axons are vulnerable to degeneration, whereas successful remyelination may confer neuroprotection. These observations underscore remyelination as a promising neuroprotective therapeutic target for preventing or slowing disability progression in MS, a condition in which gradual neuroaxonal degeneration is believed to underlie irreversible disability progression. In this review, we aim to bridge the gap between fundamental biological mechanisms of remyelination and their clinical relevance. We examine recent advances in in vivo techniques for assessing remyelination and discuss how these measures correlate with clinical and disability outcomes. In addition, we review recent clinical trials of remyelination-promoting therapies and analyze the challenges that have limited their advancement beyond phase II. Overall, we seek to provide a comprehensive overview of the remyelination process from bench to bedside, highlighting both the obstacles and the therapeutic potential of remyelination strategies in MS. Full article

Appropriate dose adjustment of renally eliminated medicines is central to safe pharmacotherapy in patients with chronic kidney disease; yet, in European primary care, it is systematically undermined not by lack of knowledge, but by structural misalignment between laboratory reporting, regulatory product information, and clinical guidelines. This Perspective argues that the core barrier to optimal renal dose adjustment is a mismatch between routinely reported indexed eGFR and dosing requirements based on absolute renal function, compounded by persistent regulatory reliance on the Cockcroft–Gault equation despite its known limitations. We show how these structural inconsistencies, together with patient-related factors such as frailty, ageing, and body size, generate uncertainty at the point of prescribing and contribute to persistent variability in dosing decisions. To address this challenge, we propose a structured, context-aware renal dosing framework designed for routine primary care. The framework integrates regulatory guidance, multiple methods of renal function estimation, and patient-specific modifiers into a stepwise decision process. Clinical vignettes illustrate how divergent renal function estimates and regulatory requirements can lead to different dosing decisions in everyday practice. By reframing renal dose adjustment as a context-driven clinical process rather than a purely equation-based task, this Perspective highlights the need for regulatory alignment and pragmatic decision tools to improve prescribing quality in patients with chronic kidney disease. Full article

Background/Objectives: Embryo implantation is a highly regulated, multistep process requiring precise synchronization between a developmentally competent blastocyst and a receptive endometrium. Despite advances in reproductive medicine, implantation failure remains a major limiting factor in assisted reproductive technology (ART), particularly in cases of recurrent implantation failure (RIF). This review aims to summarize current knowledge on the molecular, cellular, and immunological mechanisms governing embryo–endometrial interaction and to evaluate contemporary strategies for optimizing implantation outcomes. Methods: This narrative review synthesizes the current literature on embryo implantation, including studies addressing uterine receptivity, etiological factors contributing to implantation failure, and emerging diagnostic and therapeutic approaches. The review integrates findings from molecular biology, clinical ART practices, and bioengineering-based models. Key areas include transcriptomic tools such as endometrial receptivity analysis, time-lapse imaging, artificial-intelligence-based embryo selection, and advanced in vitro models (e.g., microfluidic “womb-on-a-chip” systems and three-dimensional embryo–endometrial platforms). The literature was identified through major biomedical databases, following a structured but non-systematic approach. Results: Implantation success is dependent on a complex interplay of hormonal regulation, gene expression, immune modulation, and embryo quality. Disruption of uterine receptivity during the window of implantation is a critical contributor to infertility and RIF. Multiple factors—including genetic abnormalities, maternal age, lifestyle influences, immunological imbalance, uterine pathology, and chronic endometrial conditions—are implicated in implantation failure. Emerging technologies, such as AI-assisted embryo selection, transcriptomic profiling, and advanced in vitro implantation models, provide enhanced insight into implantation dynamics and offer potential for improved clinical outcomes. Conclusions: Advances in understanding embryo implantation and the development of innovative diagnostic and therapeutic technologies hold significant promise for improving reproductive success. However, further research, validation, and standardization are required before these approaches can be fully integrated into routine clinical practice. A more personalized and mechanism-based approach to implantation may ultimately enhance ART outcomes and reduce the burden of infertility. Full article

This study introduces a comprehensive framework for understanding sustainable online shopping preferences, validated using survey data collected in Serbia and Slovenia in 2025 (n = 572), thereby enhancing its generalizability. The primary aim of this research is to examine the extent to which specific environmental, social, and economic indicators influence decision-making processes for online purchasing and delivery. A detailed quantitative analysis was conducted using a structured questionnaire that included a wide range of variables related to online shopping behaviors and delivery preferences. The findings indicate that preferences for sustainability are inherently complex and multifaceted, shaped by critical factors such as environmental concerns, social responsibility, trust, skepticism towards sustainability claims, willingness to pay (WTP), and price sensitivity. Demographic variables, particularly gender and age, show consistent links to preferences for environmental considerations and corporate social responsibility (CSR), while income impacts trust-related behaviors and WTP. Furthermore, the analysis distinguishes between two distinct decision-making approaches: a value-driven sustainability cluster represented by EcoIndex, SocialIndex, and WTPIndex, and a cost-minimization strategy focused on price sensitivity (PriceIndex), with trust acting as a related yet separate factor (CredibilityIndex). Overall, this study emphasizes that a range of interconnected dimensions significantly shape sustainable online shopping preferences. The study was conducted in two developing European countries. Additionally, the findings highlight the need to address universal market barriers, such as price sensitivity, information asymmetry, and consumer skepticism. In a business context, they underscore the importance of adopting advanced analytical methods to enhance decision-making and optimize sustainable business strategies. Full article

Background: Parenting stress is a known risk factor for children’s social anxiety, yet the mediating and moderating mechanisms underlying this relationship remain underexplored, particularly regarding gene–environment interactions. This quantitative, cross-sectional study, grounded in diathesis-stress and family process theories, examined whether maladaptive parenting mediates the link between parenting stress and children’s social anxiety, and whether FKBP5 gene variation moderates this mediation. Methods: A sample of 1774 fourth- to sixth-grade students (aged 10–14 years) and their parents participated. Parenting stress and maladaptive parenting were parent-reported, children’s social anxiety was self-reported, and children’s FKBP5-related cumulative genetic score was derived from four SNPs (rs4713916, rs1360780, rs3800373, rs9296158). Moderated mediation analyses were conducted. Results: Parenting stress was significantly and positively associated with children’s social anxiety. Maladaptive parenting partially mediated this relationship. The FKBP5 showed a marginally significant moderating effect, with simple slope analysis suggesting parenting stress was more strongly associated with child social anxiety among children with higher genetic risk. No moderating effect was found for the path from maladaptive parenting to social anxiety. Conclusions: Parenting stress is associated with children’s social anxiety both directly and indirectly through maladaptive parenting, with FKBP5-related cumulative genetic risk potentially moderating the direct effect. These findings offer preliminary evidence that may inform preventive interventions targeting parenting stress, although replication is needed. Full article

Background: Background breast features are frequently noted in pathology reports alongside invasive breast cancer but rarely factor into prognosis or treatment decisions. Their relationship to tumor characteristics and patient outcomes remains incompletely characterized. Methods: We conducted a retrospective cohort study of 7603 patients with Stage I–III invasive breast cancer (diagnosed 1991–2022, age < 80 years) from the Joint Breast Cancer Registry in Singapore. Natural language processing (NLP) was applied to 9754 free-text pathology reports to extract co-existing background breast features, with accuracy validated by dual-reviewer assessment of 200 reports. Because background features are most reliably assessed on excision specimens, the primary analytic cohort comprised 3988 patients with available excision pathology reports. Unsupervised hierarchical clustering grouped extracted features into three categories. Associations with tumor characteristics were assessed with multinomial logistic regression and ten-year overall survival by Cox proportional hazards models (median follow-up 9.6 years; 620 deaths). Results: Here, we show that NLP-based extraction of background breast features from routine pathology reports achieves an accuracy of over 90% across features. Lobular neoplasia and benign proliferative changes are associated with less aggressive tumor characteristics, whereas early neoplastic and papillary lesions are more prevalent in HER2-enriched and luminal B tumor subtypes. Benign proliferative changes are associated with better survival in age- and year-adjusted models (hazard ratio 0.91, 95% CI 0.86–0.97), but this association is attenuated after adjustment for stage and subtype. Conclusions: NLP-enabled extraction of background breast features from pathology text is feasible at scale. These features reflect tumor biology but do not independently add prognostic information beyond established clinical variables. Full article

Inflammaging is defined as chronic low-grade inflammation associated with aging and is increasingly recognized as a dynamic and mechanistically driven biological process rather than a state adequately described by circulating biomarkers alone. Traditional inflammatory markers alone, including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and C-reactive Protein (CRP), fail to capture the complexity, tissue specificity, and causal architecture of inflammaging. Recent experimental evidence has demonstrated that diverse upstream drivers, including immunosenescence, gut microbiome dysbiosis, metabolic dysfunction, and cellular senescence, converge on a limited number of central inflammatory hubs, including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, GMP–AMP synthase–stimulator of interferon genes (cGAS–STING), Janus kinase/signal transducer and activator of transcription (JAK/STAT), and p38 mitogen-activated protein kinase (p38 MAPK) signaling. These mechanistic nodes represent promising therapeutic targets, potentially modifiable biological processes, and support the emerging concept of ‘druggable inflammaging’, whereby senotherapeutics, inflammasome inhibitors, innate immune modulators, and metabolic interventions may actively modify aging-associated inflammatory biology rather than simply monitor it through biomarkers. This review highlights a paradigm shift from biomarker-based assessment toward mechanism-based intervention, where inflammaging can be characterized as a modifiable biological process and a central target for precision pharmacological strategies in aging-related diseases. Full article

Background/Objectives: Bone tissue undergoes continuous remodelling processes that are closely controlled by mechanical stimuli and metabolic as well as inflammatory factors. Although the beneficial effects of regular physical activity on skeletal health are well documented, the response of bone turnover markers to a single maximal intensity exercise—particularly depending on training level—still remains ambiguous. The aim of the study was to assess the effect of a single physical exercise unit at maximum intensity on changes in selected biochemical markers specific for bone tissue, connective tissue remodelling and systemic stress response in young men. Methods: The study comprised 34 healthy men aged 20–25 years, divided into two groups: experimental (training, n = 15) and control (non-training, n = 19). The test was performed on a mechanical treadmill with a gradually increasing load (until subjective feeling of fatigue). Blood samples were collected before and 60 min following the test, and then assessed for the concentration of selected bone turnover markers, including bone-specific alkaline phosphatase (BSP), C-terminal telopeptide of type I collagen (CTX-I), deoxypyridinoline (DPD), hydroxyproline (GEN HYP) and haptoglobin (HPT). Results: In the group of training individuals, a significant decrease in BSP concentration was observed after physical exercise (p = 0.003). CTX-I concentration was significantly lower in training individuals compared to their non-training peers, regardless of measurement time (p < 0.001). Furthermore, a significant increase in GEN HYP concentration was observed after exercise in both groups (p = 0.033). For the remaining analysed markers, including DPD and HPT, no significant changes were demonstrated post-exercise. Conclusions: A single bout of maximal intensity exercise induces short-term, marker-specific changes in bone turnover dependent on training level, which reflect an early metabolic response of the musculoskeletal system rather than direct structural adaptation of the bone tissue. Full article

Background/Objectives: Excess weight and dyslipidemia are health conditions growing worldwide in children, including indigenous populations. The concern is their related comorbidities, which could appear at an early age. Given limited information on Seri children, this study aimed to evaluate the prevalence of excess weight and dyslipidemia, and to identify factors associated with BMI-for-age Z-score and dyslipidemia. Methods: This cross-sectional study was conducted among Seri children aged 3–11 years. For prevalence analysis, the BMI-for-age Z-score was calculated as an indicator of excess weight. Dyslipidemia was assessed only in school-age children. Information was collected on potential associated variables, including maternal nutritional status, children’s sleep behaviors, physical activity, diet, and cardiovascular health, as well as household characteristics such as the modernity index and food insecurity. Results: A total of 154 Seri children were evaluated. Among preschoolers, 18.8% were classified at risk of overweight. In school-age children, the combined prevalence of overweight and obesity was 32.8%. Maternal BMI and weight, the modernity index, and being a boy were positively associated with the BMI-for-age Z-score, whereas having food insecurity, cardiovascular health score, and sleep time were negatively associated. Dyslipidemia prevalence was 46.1% among school-age Seri children. Having dyslipidemia was positively associated with maternal BMI, percentage of energy intake from ultra-processed products, paternal occupation as a merchant, and child age, and negatively associated with the number of remunerative maternal economic activities. Conclusions: These findings provide evidence on the prevalence of excess weight and dyslipidemia and their associated factors among Seri children and may inform future research and health strategies in Seri and other vulnerable populations. Full article

Intervertebral disc disease remains the most common spinal pathology in dogs and is characterized by degeneration of the intervertebral disc, primarily through chondroid metaplasia of the nucleus pulposus. Current histological grading systems for disc degeneration do not include inflammation, despite its potential relevance in clinical presentation through extradural swelling and compression. In this retrospective study, surgically removed disc extrusion material from 74 dogs was histologically processed and evaluated using a semi-quantitative grading system for disc degeneration and inflammation. A high prevalence of chondroid metaplasia was observed, frequently accompanied by inflammatory infiltrates, hemorrhage, and necrosis. A significant positive correlation (correlation coefficient = 0.636, p < 0.001) was found between the degree of degeneration and the intensity of inflammation. Notably, thoracolumbar extrusions exhibited significantly higher inflammatory scores than cervical cases. In Dachshunds, more severe neurological deficits were associated with lower histological degeneration scores, indicating that neurological severity depends on multiple interacting factors that may differ between breeds. No significant associations were identified with age, sex, breed, body weight, neurological localization, or lesion severity in other groups. These findings suggest that inflammation is an active component in the pathophysiology of intervertebral disc disease. Incorporating inflammatory grading into histological grading systems could refine functional outcome predictions and guide therapeutic decisions. Full article

Background: Inhibitory processes in the nervous system are traditionally conceptualized as suppressive mechanisms; however, their fundamental role is the refinement and optimization of sensory information. In nociception, this function is mediated by the descending pain inhibitory system (DPIS), which modulates nociceptive transmission at multiple hierarchical levels. Biological sex and gender-related factors significantly influence these inhibitory pathways, yet they are often overlooked in clinical frameworks. Methods: A narrative review was conducted using PubMed, MEDLINE, and Scopus databases, focusing on studies published between 2010 and 2025. Search terms included “descending pain inhibitory system,” “nociplastic pain,” “aging,” “sex differences,” “gender,” and “gut–brain axis.” Approximately 30 key references were synthesized. Results: The DPIS enhances the precision of nociceptive signals through mechanisms analogous to lateral inhibition. In chronic and nociplastic pain, this refinement process is impaired, leading to “sensory blurring.” Aging exacerbates these changes through neurochemical depletion and neuroinflammation. Crucially, this decline follows sex-specific trajectories; estrogen depletion in post-menopausal females accelerates the loss of monoaminergic inhibitory reserves, while gender-related sociocultural stressors can further disrupt top-down executive control. Additionally, alterations in the gut–brain axis signaling—modulated by sex-specific gut microbiota profiles—further disrupt inhibitory control. Conclusions: Chronic pain may be conceptualized as a disorder of sensory refinement rather than excessive nociceptive input. Inclusion of sex and gender as biological variables is essential for precision pain management. Therapeutic strategies should focus on restoring inhibitory precision through both central and systemic approaches, tailored to the patient’s hormonal and physiological profile. Full article

Background: Adverse event reporting is a critical component of patient safety systems; however, nurses’ engagement in reporting is influenced not only by reporting procedures but also by broader organizational characteristics of the nursing practice environment. Although previous studies have examined reporting behaviors in various healthcare settings, limited evidence is available regarding how organizational factors influence nurses’ perceptions of adverse event reporting in post-Soviet primary healthcare systems. Objective: To examine the relationship between the nursing practice environment and nurses’ perceived benefits of adverse event reporting in primary healthcare settings in Kazakhstan and to explore the underlying factor structure of the nursing practice environment within this context. Methods: A cross-sectional survey was conducted among 468 primary healthcare nurses from six major cities in Kazakhstan. Participants were recruited through professional and educational networks using a targeted convenience sampling strategy. The nursing practice environment was assessed using the Revised Professional Practice Environment (RPPE) scale, while attitudes toward adverse event reporting were measured using the Reporting of Clinical Adverse Events Scale (RoCAES), focusing on the perceived benefits of reporting dimension. Exploratory factor analysis was performed to identify the underlying structure of the RPPE scale. Associations between EFA-derived factors and perceived benefits of adverse event reporting were examined using Spearman correlation analysis and multivariable logistic regression with adjustment for age, gender, city, and professional position. Results: Exploratory factor analysis identified three dimensions of the nursing practice environment: Professional Motivation and Teamwork, Interprofessional Conflict and Workplace Relationships, and Staffing Adequacy. Spearman correlation analysis demonstrated significant associations between all three factors and perceived benefits of adverse event reporting. Factor 1 (Professional Motivation and Teamwork) showed the strongest negative correlation with the outcome (r = −0.562, p < 0.001), followed by Factor 3 (Staffing Adequacy) (r = −0.434, p < 0.001), whereas Factor 2 (Interprofessional Conflict and Workplace Relationships) demonstrated a positive correlation (r = 0.227, p < 0.001). In the multivariable logistic regression model adjusted for age, gender, city, and professional position, Factor 1 was negatively associated with favorable perceptions of adverse event reporting (OR = 0.389, p < 0.001), whereas Factor 2 demonstrated a positive association (OR = 1.763, p = 0.002). Factor 3 and demographic variables were not statistically significant. Conclusions: The findings suggest that nurses’ perceptions of the benefits of adverse event reporting are influenced by multiple dimensions of the nursing practice environment. Exploratory factor analysis identified three organizational dimensions—Professional Motivation and Teamwork, Interprofessional Conflict and Workplace Relationships, and Staffing Adequacy—that were associated with reporting perceptions. After adjustment for demographic characteristics, Professional Motivation and Teamwork and Interprofessional Conflict and Workplace Relationships remained independently associated with perceived benefits of adverse event reporting, whereas demographic factors did not demonstrate significant associations. These findings highlight the importance of organizational conditions, communication processes, and professional engagement in shaping nurses’ attitudes toward adverse event reporting. Efforts to strengthen patient safety reporting systems should therefore extend beyond reporting procedures alone and include broader organizational strategies aimed at improving communication, teamwork, and supportive work environments within primary healthcare settings. Full article