Search Results (2,414)

Essential hypertension is a leading cause of chronic kidney disease (CKD) and is frequently complicated by hypertensive nephropathy, characterized by nephroangiosclerosis and increased intrarenal vascular resistance, assessable by renal resistive index (RRI). Oxidative stress and endothelial dysfunction contribute to CKD progression, and the Mediterranean diet (MD) has been associated with a more favorable oxidative and endothelial profile, although data linking diet to renal microcirculation in hypertensive nephropathy remain limited. The aim of this study is to evaluate the relationship between RRI, oxidative stress, endothelial function, and adherence to the Mediterranean diet in patients with essential hypertension and hypertensive nephropathy. We performed a cross-sectional single-center study and we enrolled 99 patients with essential hypertension, hypertensive nephropathy, and CKD stages G1–G4 (KDIGO). All patients underwent laboratory testing, measurement of oxidative stress markers (sNOX2-dp, H₂O₂) and endothelial function (NO), renal ultrasound with interlobar RRI assessment, and PREDIMED questionnaire for MD adherence. A significant direct correlation was observed between RRI and oxidative stress markers (sNOX2-dp and H₂O₂) (p = 0.002, r = 0.302; p = 0.002, r = 0.322), while a significant inverse correlation was found between RRI and the endothelial function marker (NO) (p = 0.013, r = −0.302). The correlation between RRI and PREDIMED questionnaire scores did not reach statistical significance, but there was a trend toward an inverse association (p = 0.06, r = −0.18). In addition, a significant inverse correlation was observed between RRI and eGFR (p = 0.005, r = −0.27), consistent with published data. We also found a significant inverse correlation between sNOX2-dp and PREDIMED scores (p = 0.034, r = −0.21); no statistically significant correlations with H₂O₂ and NO were observed in this analysis. Higher intrarenal vascular resistance is associated with heightened oxidative stress, impaired endothelial function, and lower eGFR. Adherence to the Mediterranean diet is linked to lower NOX2-mediated oxidative stress, supporting a potential association between higher MD adherence and lower NOX2-related oxidative stress. These findings are hypothesis-generating and require confirmation in adequately powered longitudinal and interventional studies before any clinical inference on CKD progression can be made. Full article

Background: Gustatory dysfunction represents an underrecognized complication that may influence dietary behaviors and metabolic control. Previous investigations have suggested alterations in taste in patients with diabetes, yet the relationship between disease duration and specific taste modalities remains incompletely characterized. Aim: This study aimed to (i) compare orosensory detection thresholds for lipid and sweet tastes between patients with recent type 2 diabetes mellitus (rT2DM) (duration ≤ 5 years) and chronic type 2 diabetes mellitus (cT2DM) (duration > 5 years), and (ii) determine whether diabetes duration is associated with alterations in chemosensory function in a North African population. Methods: A cross-sectional comparative pilot study was conducted at the National Institute of Nutrition and Food Technology in Tunis, Tunisia, from April to June 2021. Sixty-seven patients with type 2 diabetes mellitus (T2DM) receiving oral antidiabetic medication were recruited through systematic sampling and divided into two groups: rT2DM (n = 30, duration ≤ 5 years) and cT2DM (n = 37, duration > 5 years). Orosensory detection thresholds for lipid taste were assessed using eight ascending concentrations of linoleic acid ranging from 0.018 to 12 mmol/L. In contrast, sweet taste thresholds were evaluated using a sucrose concentration series ranging from 0.01 to 5 mmol/L. The three-alternative forced-choice method with an ascending-concentration presentation was employed for both taste modalities. Detection thresholds were defined as the lowest concentration at which participants correctly identified the taste quality. Results: Patients with cT2DM exhibited significantly elevated orosensory detection thresholds compared to those with rT2DM for both taste modalities tested. The median linoleic acid detection threshold was 6.000 mmol/L in cT2DM versus 0.058 mmol/L in rT2DM (p < 0.001), representing a 107-fold increase in detection threshold. For sweet taste, the median sucrose detection threshold was 1.0 mmol/L in cT2DM compared with 0.5 mmol/L in rT2DM (p < 0.001), indicating a 2-fold increase in the threshold. In the overall patient cohort, the duration of diabetes was positively correlated with both fat taste perception thresholds (r = 0.657, p < 0.001) and sweet taste perception thresholds (r = 0.466, p < 0.001). However, when analyses were performed by diabetes duration-based subgroups, these correlations were observed only for fat taste perception in cT2DM, with no statistically significant correlations found in rT2DM. In multivariate linear regression analyses adjusted for age, body mass index, and sex/gender, the duration of diabetes remained independently associated with fat and sweet taste perception. Conclusions: Extended T2DM duration is associated with substantial elevations in orosensory detection thresholds for both lipid and sweet tastes in a North African population. These findings suggest that disease chronicity may contribute to chemosensory impairment, potentially influencing dietary preferences and metabolic control in patients with diabetes. Full article

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. The kidney is among the organs most susceptible to sepsis-induced injury, and acute kidney injury frequently develops in this context, thereby markedly increasing mortality in affected patients. With continued advances in research, a more comprehensive understanding has been achieved regarding the clinical risk factors, pathophysiological mechanisms, therapeutic responses, and renal recovery processes associated with sepsis-associated acute kidney injury (SA-AKI). These advances have strengthened the capacity for prevention, early detection, and effective management of SA-AKI. Despite this progress, substantial gaps remain in the overall understanding of SA-AKI pathogenesis, including the complex interplay among pathophysiological mechanisms and the extensive cross-regulation of multiple signaling pathways. Consequently, SA-AKI remains a major clinical challenge and imposes a substantial global healthcare burden. There is therefore an urgent need for further research to elucidate the underlying mechanisms of SA-AKI and to identify more effective therapeutic strategies. Unlike previous reviews that primarily focused on individual mechanisms or isolated therapeutic targets, the present review synthesizes the most recent evidence on SA-AKI. Particular emphasis is placed on its pathogenic processes, associated molecular mechanisms and signaling pathways, and emerging therapeutic targets. Special attention is given to the hierarchical relationships among distinct mechanisms during disease progression and their implications for clinical translation. This review aims to inform clinical practice and to identify future research directions, thereby providing valuable insights for both researchers and clinicians in this field. Full article

Cellular senescence, mitochondrial dysfunction, and cumulative oxidative stress (OS) are the main causes of the progressive decreases in oocyte and sperm quality that define reproductive age. There is growing evidence that these processes are controlled by systemic variables, such as metabolites produced from the gut microbiome and extracellular vesicle (EV)-mediated intercellular communication, rather than being exclusively regulated at the tissue level. Antioxidant enzymes, regulatory microRNAs, and bioactive lipids that regulate mitochondrial redox balance, mitophagy, and inflammatory signaling are transported by EVs derived from reproductive organs, stem cells, immune cells, and the gut microbiota. Concurrently, microbiome-derived metabolites such as urolithin A, short-chain fatty acids, and polyphenol derivatives enhance mitochondrial quality control, activate antioxidant pathways, and suppress senescence-associated secretory phenotypes. This narrative review integrates the most recent research on the relationship between redox homeostasis, mitochondrial function, gut microbiota activity, and EV signaling in the context of male and female reproductive aging. We propose an emerging gut–EV–mitochondria axis as a unified framework through which systemic metabolic and antioxidant signals affect gamete competence, reproductive tissue function, and fertility longevity. Finally, we discuss therapeutic implications, including microbiome modulation, EV-based interventions, and senotherapeutic strategies, highlighting key knowledge gaps and future research directions necessary for clinical translation. Full article

Background/Objectives: Speech difficulties are an early and disabling manifestation of Parkinson’s disease (PD), affecting communication and quality of life. This study aimed to examine demographic, clinical, dopaminergic imaging and cerebrospinal fluid (CSF) correlates of speech difficulties in early PD, comparing treatment-naïve and levodopa-treated patients. Methods: A cross-sectional analysis was conducted using data from the Parkinson’s Progression Markers Initiative (PPMI). The sample included 376 treatment-naïve and 133 levodopa-treated early PD participants. Speech difficulties were defined by Movement Disorder Society—Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III, with Item 3.1 ≥ 1. Group comparisons and binary logistic regression identified predictors among demographic, clinical, dopaminergic and CSF biomarker variables, including [¹²³I]FP-CIT specific binding ratios (SBRs). All analyses were cross-sectional, and findings reflect associative relationships rather than treatment effects or causal mechanisms. Results: Speech difficulties were present in 44% of treatment-naïve and 57% of levodopa-treated participants. In both cohorts, higher MDS-UPDRS Part III ON scores—reflecting greater motor severity—and lower mean putamen SBR values were significant independent predictors of speech impairment. Age was an additional predictor in the treatment-naïve group. No significant differences were found in CSF biomarkers (α-synuclein, amyloid-β, tau, phosphorylated tau). These findings indicate that striatal dopaminergic loss, particularly in the putamen, and motor dysfunction relate to early PD-related speech difficulties, whereas CSF neurodegeneration markers do not differentiate affected patients. Conclusions: Speech difficulties in early PD are primarily linked to dopaminergic and motor dysfunction rather than global neurodegenerative biomarker changes. Longitudinal and multimodal studies integrating acoustic, neuroimaging, and cognitive measures are warranted to elucidate the neural basis of speech decline and inform targeted interventions. Full article

Objective: Visceral adipose tissue is a primary driver of insulin resistance and dysglycemia in type 2 diabetes (T2D), yet its clinical assessment remains challenging. This study aimed to validate neck circumference (NC) as a novel, practical anthropometric biomarker for estimating visceral fat area (VFA) and identifying metabolic risk in a T2D cohort, facilitating its integration into public health and primary care screening strategies. Methods: In a cross-sectional study of 1139 T2D patients, we collected data on NC, biochemical parameters (fasting plasma glucose, hemoglobin A1c, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides), and precisely measured VFA and subcutaneous fat area (SFA) via bioelectrical impedance analysis (Omron HDS-2000). We employed Pearson’s correlation and multivariate logistic regression to analyze the relationship between NC and metabolic indicators. Receiver operating characteristic (ROC) curve analysis was used to establish sex-specific NC cut-off values for predicting abnormal VFA. Results: The cohort comprised 687 (60.3%) males and 452 (39.7%) females. NC demonstrated strong positive correlations with VFA (p < 0.001), as did body mass index (BMI), waist–hip ratio (WHR), and SFA. In males, NC was further positively correlated with key metabolic biomarkers including fasting insulin, Insulin Resistance Index, triglycerides, and creatinine. ROC analysis identified NC > 39.5 cm for males and >35.5 cm for females as the optimal cut-off points for detecting abnormal visceral adiposity, highlighting its diagnostic utility. Conclusions: NC serves as a highly accessible and effective biomarker for visceral adiposity and associated metabolic dysfunction in patients with T2D. The established sex-specific cut-off values provide a simple, non-invasive tool for risk stratification in clinical and public health settings, enabling early intervention and improved management of metabolic disease. Full article

Background/Objectives: Major Depressive Disorder (MDD) affects over 280 million people worldwide and is a leading cause of disability. Emotional blunting—characterized by a numbing or flattening of emotions—is a significant yet often underrecognized symptom that impairs daily functioning and interpersonal relationships in patients with MDD. It remains unclear whether emotional blunting results primarily from the disorder itself or from antidepressant treatments, especially selective serotonin reuptake inhibitors (SSRIs) and serotonin–norepinephrine reuptake inhibitors (SNRIs). Vortioxetine, a multimodal antidepressant approved for MDD, may help alleviate emotional blunting by modulating neurotransmitters differently than SSRIs. This study investigates the severity of emotional blunting among Hong Kong MDD patients and explores the changes in this symptom with the use of vortioxetine, while also considering anhedonia as a related dimension of reward processing. Methods: This naturalistic, longitudinal observational study in Hong Kong enrolled adults (aged 18 and above) clinically diagnosed with MDD who were initiating vortioxetine treatment for emotional blunting. Patient inclusion was based on independent prescribing decisions by psychiatrists, with informed consent obtained. Data collection comprised one intake interview and the administration of four self-report questionnaires—ODQ, PHQ-9, PDQ-D, SDS, MFI, and SHAPS—at baseline, week 1, week 4, and week 8. Demographic and clinical history data were also recorded. Questionnaires were completed online or via phone, over a study duration of approximately two months. Results: The prevalence of emotional blunting, estimated by the proportion of patients with an ODQ score at or above the clinical cut-off (≥50), was 91.9% at baseline, decreasing to 85.5% at week 1, 77.7% at week 4, and 73.3% at week 8. Significant improvements were also observed in depressive symptoms, cognitive dysfunction, functional impairment, pleasure experience, and fatigue. Conclusions: In this naturalistic observational cohort of patients with MDD who were prescribed vortioxetine, self-reported emotional blunting, depressive symptoms, cognitive dysfunction, functional impairment, and fatigue decreased over eight weeks. Anhedonia scores (SHAPS) decreased to non-significant levels, and clinician-rated Clinical Global Impression scores confirmed a significant reduction in illness severity. Full article

Cardiovascular disease (CVD) is increasingly recognized as a significant comorbidity in people living with HIV (PWH), contributing to increased morbidity and mortality. Epidemiological studies indicate that PWH have a 1.2–2-fold higher risk of myocardial infarction (MI) and other CVD events compared to HIV-negative individuals. While the mechanisms underlying HIV-associated CVD are not fully understood, they are likely to include a combination of cardiovascular-related adverse effects of HIV medications, vascular dysfunction caused by HIV-induced monocyte activation, and cytokine secretion, in addition to existing comorbidities and lifestyle choices. This comprehensive review examines the complex relationship between HIV infection and CVD, highlighting key pathophysiological mechanisms such as chronic immune activation, inflammation, endothelial dysfunction, and the role of antiretroviral therapy (ART) in promoting cardiovascular risk. Alongside conventional risk factors such as smoking, hypertension, and dyslipidemia, HIV-specific elements, especially metabolic abnormalities associated with ART, significantly contribute to the development of CVD. Prevention strategies are crucial, focusing on the early identification and management of cardiovascular risk factors as well as optimizing ART regimens to minimize adverse metabolic effects. Clinical guidelines now recommend routine cardiovascular risk assessment in PWH, emphasizing aggressive management tailored to their unique health profiles. However, challenges exist in fully understanding the cardiovascular outcomes in this population. Future research directions include exploring the role of inflammation-modulating therapies and refining sustainable prevention strategies to mitigate the growing burden of CVD in PWH. Full article

Psychological stress is increasingly investigated as a potentially modifiable factor in male infertility, in part through oxidative stress. This narrative review synthesizes mechanistic and translational evidence linking stress-related neuroendocrine activation and coping behaviors with redox imbalance in the male reproductive tract. Chronic activation of the hypothalamic–pituitary–adrenal axis and sympathetic outflow elevates glucocorticoids and catecholamines. In controlled animal stress paradigms, this is accompanied by suppression of the hypothalamic–pituitary–gonadal axis and by immune and metabolic changes that favor reactive oxygen species generation. The resulting oxidative stress may reduce Leydig cell steroidogenesis, impair testicular and epididymal function, and induce lipid peroxidation, mitochondrial dysfunction, and sperm DNA fragmentation. In such models, these lesions, together with apoptosis of germ and supporting cells, are associated with lower sperm concentration, reduced motility, compromised viability, and diminished fertilizing potential. Overall, preclinical animal studies using defined stress paradigms provide experimental evidence consistent with causal effects of stress on oxidative injury and reproductive impairment in preclinical settings. Human studies linking perceived stress, anxiety/depression, and disturbed sleep to adverse semen parameters and oxidative biomarkers are summarized. However, the human evidence is predominantly associative, and the available studies are cross sectional and remain vulnerable to residual confounding and reverse causality. Potential effect modifiers, including smoking, alcohol use, and circadian disruption, are also discussed as contributors to heterogeneity across clinical studies. Standardized assessment of stress biology and redox status, longitudinal designs aligned with spermatogenic timing, and well-powered intervention trials are needed to define dose–response relationships and support individualized prevention and care. Full article

Background/Objectives: Respiratory dysfunction in Parkinson’s disease (PD) is frequently underrecognized, particularly when resting oxygen saturation is preserved. Dynamic stress testing, however, may reveal exercise-induced oxygen desaturation, reflecting a latent functional respiratory impairment. The relationship between exertional oxygen desaturation and cognitive performance in PD remains insufficiently explored. Objective: To investigate the association between exercise-induced oxygen desaturation and global cognitive performance in patients with PD, and to explore the contribution of pulmonary gas exchange impairment assessed by diffusing capacity of the lung for carbon monoxide (DLCO). Methods: This prospective, cross-sectional, single-center observational study with consecutive enrollment included 50 patients with idiopathic Parkinson’s disease undergoing multidisciplinary respiratory evaluation following neurological assessment. Participants underwent cognitive evaluation using the Romanian version of the Montreal Cognitive Assessment (MoCA), pulmonary function testing including DLCO and total lung capacity (TLC), and a supervised 6-min walk test (6MWT) with continuous pulse oximetry. Exercise-induced oxygen desaturation was defined as a decrease in SpO₂ of ≥4% from baseline. Correlation analyses and multivariable regression models were applied. Results: Exercise-induced oxygen desaturation was frequent, with 60% of patients exhibiting a ≥4% decrease in SpO₂ during the 6MWT. Greater desaturation was significantly associated with lower MoCA scores (Spearman’s r = −0.383, p = 0.006). No significant associations were found between exertional desaturation and resting pulmonary function parameters, including DLCO and TLC. In multivariable analysis, lower MoCA score and levodopa–carbidopa intestinal gel treatment independently predicted greater oxygen desaturation during exercise. Conclusions: Exercise-induced oxygen desaturation is common in patients with PD despite preserved resting oxygenation and is associated with poorer cognitive performance. These findings suggest that exertional desaturation may reflect a dynamic functional impairment and may be associated with increased physiological vulnerability. Functional exercise testing with oxygen saturation monitoring may provide complementary information beyond resting pulmonary assessments. Full article

Background/Objectives: Craniopharyngiomas (CPs) are rare, generally benign tumors predominantly located in the sellar and suprasellar regions, associated with significant morbidity and complex surgical management. Despite high overall survival rates, patients frequently experience complications including visual impairment, pituitary dysfunction, diabetes insipidus (DI), and hypothalamic syndrome. Among these, hypothalamic obesity (HO) represents one of the most clinically challenging sequelae, often occurring early, lacking standardized medical treatment, and leading to substantial comorbidity and reduced quality of life. This study reports a single-center experience focusing on the relationship between skull base anatomy, surgical approach selection, and endocrinological outcomes. Methods: A retrospective analysis was conducted on patients diagnosed with CPs who underwent surgery by a dedicated team at our Department from January 2014 to January 2024. The approaches used were endoscopic (ER) and transcranial (TR). Preoperative imaging (volumetric MRI and CT scans) was analyzed using 3DSlicer (open-source software) for anatomical modeling of the tumor and skull base. Clinical outcomes were evaluated through follow-up assessments by a team of neuroendocrinologists. Data on BMI changes, DI onset, and hypopituitarism were collected. Statistical analyses consisted of descriptive comparisons and exploratory regression models. Results: Of 18 patients reviewed, 14 met the inclusion criteria. Larger sphenoid sinus volumes were associated with selection of an endoscopic endonasal approach (p = 0.0351; AUC = 0.875). In ER cases, the osteotomy area was directly related to tumor volume, independent of other anatomical parameters. Postoperatively, a significant increase in BMI (22.39 vs. 26.65 kg/m²; p = 0.0049) and in the incidence of DI (three vs. nine cases; p-value 0.0272) was observed. No clear differential association between surgical approach and endocrinological outcomes emerged in this cohort. Conclusions: Quantitative assessment of skull base anatomy using 3D modeling may support surgical approach selection in patients with craniopharyngiomas, particularly in identifying anatomical settings favorable to endoscopic endonasal surgery. Endocrinological outcomes appeared more closely related to tumor characteristics and hypothalamic involvement than to the surgical route itself. These findings support the role of individualized, anatomy-informed surgical planning within a multidisciplinary framework. Full article

Background: Visual dysfunction resulting from damage to the optic nerve and retinal neurons represents a significant concern in the postoperative management of childhood-onset craniopharyngioma (CP) survivors. The study aims to evaluate the influence of clinical parameters assessed in patients before and after neurosurgery of CP on peripapillary retinal nerve fiber layer (RNFL) thickness results, using optical coherence tomography (OCT) as early markers of compressive neuropathy. Methods: This study retrospectively examined 73 eyes from 38 individuals diagnosed with CP and 64 eyes from 32 healthy controls matched for age and sex. All patients in the study group underwent a complete endocrine examination before and after surgery. Moreover, all participants in both groups underwent a thorough ophthalmological examination and OCT imaging. The average RNFL thickness was analyzed, along with the RNFL in the superior and inferior sectors and in eight peripapillary sectors around the optic nerve. Clinical variables were analyzed to assess how they relate to alterations in RNFL thickness within specific sectors. Results: After surgery, the peripapillary RNFL thickness was much lower in the CP group than in the healthy control group. Preoperative factors significantly affecting RNFL reduction are as follows: age below 5 years at the time of diagnosis, birth in the country, optic disc oedema, delayed puberty, arginine vasopressin deficiency (AVD), growth hormone deficiency (GHD), hyperprolactinemia, and the degree of preoperative hypothalamic involvement. Moreover, syndrome of inappropriate secretion of antidiuretic hormone (SIADH), as well as the end of AVD, memory disorder and hyperfagia after surgery, correlated with damage to RNFL. Conclusions: CP causes significant thinning of the RNFL, which demonstrates the tumor’s impact on the visual pathway. Monitoring optic nerve damage and assessing outcomes after surgery can be performed effectively using OCT. Additionally, the relationship between RNFL thickness in specific areas and clinical indicators can provide vital information for diagnosing and monitoring. This highlights their usefulness in forecasting visual results. As a result, ongoing RNFL assessments should be part of the long-term management of CP patients to improve visual outlook and identify ongoing or remaining damage. Full article

Introduction: Traumatic brain injury (TBI) is a complex condition that may lead to alterations in cerebral hemodynamics. Impairment of cerebral autoregulatory mechanisms, as well as autonomic dysfunction, has been associated with worse patient outcomes after TBI. Aims: The purpose of this narrative review is to synthesize current evidence on impaired cerebral autoregulation, autonomic dysfunction, and their relationship with intracranial pressure in TBI. Findings: Initial studies examining waveform data have found that impaired cerebral autoregulation and autonomic dysfunction are present in a high proportion of patients after TBI. These are distinct but closely related phenomena, with current evidence suggesting a bidirectional relationship. Conclusions: Impaired cerebral autoregulation and autonomic dysfunction are closely associated. The intersection of these mechanisms is a potential target for intervention to improve patient outcomes after TBI. Additional research is needed to further characterize this relationship. Full article

The nasal microbiome represents a complex and dynamic microbial ecosystem that contributes to mucosal defense, epithelial homeostasis, immune regulation, and olfactory function. Increasing evidence indicates that this microbial community actively interacts with host physiology, while alterations in its composition are associated with chronic inflammation, oxidative stress, and olfactory impairment. Such changes have been reported in conditions including chronic rhinosinusitis, allergic rhinitis, and post-viral anosmia. Beyond local effects, chronic nasal inflammation has been hypothesized to influence neuroinflammatory processes and protein aggregation pathways involving α-synuclein and tau, potentially linking nasal microbial imbalance to neurodegenerative mechanisms. However, current evidence remains largely indirect and does not support a causal relationship. This narrative review summarizes current clinical and immunological evidence on the role of the nasal microbiome in olfactory function and dysfunction, highlighting limitations of existing studies and outlining future research directions. Full article