Search Results (172)

Polyneuropathy is a common condition that limits the quality of life among patients with primary Sjögren disease (pSjD). Somatic sensory fiber neuropathy involving small myelinated (A-δ) and unmyelinated C fibers may precede the development of sicca syndrome. The cutaneous silent period (CSP) is an inhibitory spinal reflex that can be used as a tool for evaluating the dysfunction of A-δ fibers. This study sought to examine CSP parameters, and their correlates, in patients with pSjD vs. healthy controls. We recruited 134 consecutive patients with a diagnosis of pSjD, of whom 109 subjects were included in the analysis. Electrodiagnostic tests comprised a nerve conduction study (NCS) and CSP analysis, alongside laboratory tests and questionnaires (the ESSPRI and SF-36). The examination of the healthy control (HC) group consisted of 113 NCSs and CSP studies. NCS tests of the median nerve in both groups were within the normal range. Statistical analysis revealed a significant difference in CSP duration (p < 0.001), S1 latency (p < 0.001) and S2 latency (p < 0.001) between the pSjD and HC groups. We observed prolonged CSP duration in approximately 38% of patients with pSjD and prolonged S2 latency in 18.35%. Small A-delta fiber neuropathy was diagnosed in 38% (41 subjects) patients. A regression analysis of CSP parameters indicated an association between the age of patients and PM Scl-75 antibodies (ab) levels in the pSjD cohort. As a new, noninvasive method of assessing A-δ nerve fibers, CSP was found to have a relation to the age and PM Scl-75 antibodies in patients with pSjD. The utility and sensitivity of CSP as a test for screening A-δ fiber function require further investigation in large cohorts of the pSjD population. Full article

Background and Objectives: This systematic review synthesized somatic and psychosocial determinants of postpartum sexual dysfunction (PSD) during the first 12 months after childbirth. Methods: Following PRISMA 2020 guidelines, we searched PubMed, Web of Science, and Scopus from inception to 4 August 2025 without language limits for the indexed records. Eligible studies enrolled postpartum women (≤12 months) and reported validated sexual outcomes (FSFI/FSFI-6, PISQ-12), dyspareunia, or sexual activity, examining breastfeeding, partner support/body image, perineal trauma/instrumentation, or postpartum perineal/musculoskeletal pain. Two reviewers independently screened and extracted data; risk of bias was assessed with a modified Newcastle–Ottawa Scale. Results: Of 1127 records screened, 15 studies were included. Perineal morbidity and early pain consistently tracked with worse sexual outcomes; assisted vaginal birth increased 6-month dyspareunia odds (OR 2.5). Breastfeeding was often associated with lower early sexual function and higher dyspareunia (6-month dyspareunia OR 4.4), with attenuation by 12 months. Higher partner/family support and more positive body image correlated with better FSFI scores. Heterogeneity in timing, measures, and adjustment precluded meta-analysis; results were narratively synthesized. Conclusions: Perineal trauma and early pain are dominant risk signals; breastfeeding-related symptoms exert early and context-dependent effects; psychosocial resources are protective. Full article

Major depression (MD) is a condition characterised by persistent sadness and apathy, sometimes accompanied by changes in sleep, appetite, and energy levels. It is highly heterogeneous, and depressive subtypes exhibit differing symptom profiles and patterns of brain activity. Background/Objectives: Currently, there are no physiological diagnostic means to detect depression or depressive subtypes. An emerging biomarker may be the electroencephalogram (EEG) band, gamma, due to the role of this frequency in reward processing and cognition. The aim of this work was to complete an exploratory study to investigate the interaction between gamma band power, depression, and four depressive subtypes. Methods: A correlative study between resting-state gamma band power and individual scores on the Zung Self-rating Depression Scale (SDS) was completed using exact standardised low-resolution electromagnetic tomography (eLORETA) using EEG data from a community sample of 100 participants, including not depressed and depressed participants, and four depressive subtypes (anhedonia-, cognitive- and somatic-depression and depressed mood). Results: There was no significant positive correlation between gamma band power and overall depression score. However, there was a significant positive correlation between anhedonia and gamma band power, predominantly in the left anterior cingulate cortex, which may be consistent with dysfunctional reward processing, a characteristic of anhedonia. Additional areas of significance included the posterior cingulate cortex and left middle and superior frontal cortex. Conclusions: These results provide preliminary support for neurophysiological indicators of depressive subtypes and may help inform diagnosis and treatment guidance for depression and depressive subtypes in the future. Full article

Corneal endothelial dysfunction is a leading cause of vision impairment globally, traditionally managed through donor-dependent keratoplasty procedures. However, limitations in donor tissue availability, surgical complexity, and long-term graft survival have prompted the development of cell-based regenerative therapies. Among these, corneal endothelial cells (CECs) injection therapy has emerged as a minimally invasive alternative, offering the potential to restore endothelial function. This review provides a comprehensive analysis of recent advances in bioengineering strategies for CECs therapy, including cell sourcing from donor tissue, pluripotent stem cells, and transdifferentiated somatic cells; optimization of culture conditions and substrates; and delivery protocols that enhance cell adhesion and survival. We further examine clinical trial outcomes and propose future directions for clinical translation. The convergence of cell biology, biomaterials engineering, and translational medicine positions CECs injection therapy as a transformative solution to corneal blindness. Full article

Background: Multiple System Atrophy (MSA) is a rapidly progressing neurodegenerative movement disorder characterized by autonomic failure, parkinsonism, and cerebellar ataxia. While its non-motor symptoms are well-documented, personality features in MSA remain underexplored. This study characterizes the personality traits of non-demented patients with MSA and explores their association with clinical variables. Methods: Twenty-six patients with MSA were assessed using the Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF). Dementia was excluded by Montreal Cognitive Assessment. Descriptive statistics and non-parametric analyses were conducted to examine clinical, demographic, and MMPI-2-RF variables. Results: Patients commonly showed elevated scores in somatic domains: Somatic Complaints (39%), Malaise (58%), and Neurological Complaints (85%), as well as in internalizing emotional traits: Low Positive Emotions (39%), Introversion (46%), Suicidal Ideation (46%), and Hopelessness (54%). Externalizing behavioral traits were absent, with only 4–8% of patients showing elevations in aggression or behavioral dysfunction. Strong correlations were found between somatic and emotional traits (r = 0.656, p < 0.001), and between Neurological Complaints and disease duration (r = 0.662, p < 0.001). Conclusions: This exploratory study reveals a distinct personality pattern in MSA, characterized by marked suicidal ideation, emotional vulnerability with internalizing coping, and absence of externalizing behaviors. These features highlight the need for suicide risk screening, interventions to alleviate psychological suffering, and tailored multidisciplinary care. Larger, longitudinal studies are warranted to confirm these preliminary results and clarify whether these traits reflect premorbid personality, early disease manifestations, or secondary responses, as well as their prognostic and clinical relevance. Full article

Background/Objectives: Personality traits in patients with cluster headache (CH) remain understudied compared to migraine patients. This could help improve diagnosis, identify comorbidities, and provide more personalized management of CH. This study aimed to characterize the personality profiles of patients with CH and compare them with those of patients with migraine. Methods: This cross-sectional, case–control observational study was conducted at a tertiary hospital’s headache unit (May–August 2024). Patients with CH were compared with migraine patients and healthy controls. Demographic and clinical data were collected, and the Minnesota Multiphasic Personality Inventory-3 (MMPI-3) was administered. Results: The study included 28 CH patients (17 with episodic and 11 with chronic CH), 55 migraine patients (34 with episodic migraine and 21 with chronic migraine), and 54 healthy controls. Both patient groups reported significantly more somatic and cognitive complaints than controls (p < 0.05). Compared to controls, the migraine group exhibited greater emotional dysfunction, social avoidance, demoralization, introversion, and social anxiety (p < 0.05), while the CH group showed greater impulsivity (p < 0.05). Directly comparing patient groups, migraine patients displayed greater social avoidance, emotional dysfunction, demoralization, and introversion than the CH group (p < 0.05). CH patients also showed a non-significant trend towards behavioral disinhibition, hypomania, a favorable self-image, juvenile conduct problems, substance abuse, and aggressiveness. Patients with CH did not present a higher risk of suicide compared to migraine patients. Conclusions: This study identified distinct personality profiles: Migraine patients exhibited greater emotional and interpersonal dysfunction (internal distress and withdrawal), while CH patients exhibited greater externalizing behavioral dysfunction, predominantly involving impulsivity. Full article

Background: Endometriosis is a chronic, estrogen-dependent inflammatory and immunological disease, with chronic pain being its predominant clinical manifestation. This condition significantly impairs quality of life and is frequently associated with depressive and anxiety symptoms, further exacerbating social and occupational dysfunction in affected women. The aim of this study was to assess the relationship between chronic pain in patients with endometriosis and the severity of depressive symptoms. Methods: A retrospective analysis was conducted on the medical records of 60 women of reproductive age treated at the Tomaszewski Medical Center in Białystok between 2023 and 2024. Pain intensity was evaluated using the Visual Analogue Scale (VAS) and the McGill Pain Questionnaire, while depressive symptoms were assessed with the Beck Depression Inventory (BDI). Results: Statistical analyses included the Student t-test, Wilcoxon signed-rank test, chi-square test, and Shapiro–Wilk test, with significance set at p < 0.05. Pain intensity was significantly higher during menstruation (M = 7.23) compared to non-menstrual phases of the cycle (M = 4.55; p < 0.001). Accompanying symptoms included sleep disturbances, reduced activity, and gastrointestinal complaints. Depressive symptoms were also more severe during menstruation (M = 30.12) than during the rest of the cycle (M = 22.15; p < 0.001). A significant association between pain severity and depressive symptoms was observed during menstruation (χ²(4) = 12.89; p = 0.012), but not outside this phase. Conclusions: (1) Pain in endometriosis is chronic and cyclic in nature. (2) Depressive symptoms are common but may be masked by nonspecific somatic complaints. (3) Pain intensity strongly correlates with the severity of depressive disorders, particularly during menstruation. (4) The coexistence of depression significantly impairs patient functioning. (5) Effective management of endometriosis should integrate gynecological treatment with psychological support and psychiatric care when necessary. Full article

Gulf War illness (GWI) is a multi-symptom disorder affecting veterans of the Persian Gulf operations. Persistent neuroendocrine dysregulation contributes to impairing cognitive capacity and generates anxiety-like behavior. Effective treatments for this illness are challenging due to compromised metabolism, increased oxidative stress and neuroinflammation, perpetuated by chronic stress and hypothalamic–pituitary–adrenal (HPA) axis dysfunction. This neuroinflammation can be alleviated with synthetic antagonistic analogs of the growth hormone-releasing hormone (GHRH) through modulation of the HPA axis. We evaluated the efficacy of the GHRH antagonist analog, MIA-690, against cognitive impairment and anxiety-like behavior in GWI. Mice exposed to an experimental GWI model involving corticosterone (CORT) and diisopropylfluorophosphate (DFP), followed by CORT and lipopolysaccharide (LPS), received a daily subcutaneous dose of 10 μg of MIA-690 for 10 days. Assessments of spatial memory, recognition capacity, somatic health, anxiety and innate survival were carried out, combining the Morris water maze (MWM), novel object recognition (NORT), grip strength (GST), and open field (OFT) tests. Learning efficiency was selectively enhanced in females using the MWM. There were no significant differences in the recall capacity and performance on the OFT, NOR, and GST tasks. Our findings suggest that the MIA-690 dosage is sufficient to improve learning deficits in experimental GWI exposures. 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

Background and Objectives: Toe walking (TW) is frequently observed in children with Autism Spectrum Disorder (ASD), yet its clinical significance and association with comorbid conditions remain poorly understood. This study aimed to examine the prevalence of TW in a large Italian cohort of children with ASD and to explore its association with ASD severity, sleep disturbances, feeding behaviors, and gastrointestinal symptoms. Materials and Methods: A total of 289 children with ASD and 289 typically developing controls (TDC), matched for age and sex, were evaluated in a multicentric observational study. TW was assessed during neurodevelopmental evaluations. Sleep quality was assessed using the Sleep Disturbance Scale for Children (SDSC), feeding behaviors via the Brief Autism Mealtime Behavior Inventory (BAMBI), and gastrointestinal symptoms through clinical reporting. Statistical analyses included Chi-square tests, Mann–Whitney U tests, Spearman correlations, and logistic regressions. Results: TW was significantly more prevalent in the ASD group (27.3%) than in TDC (5.5%, p < 0.0001). Within the ASD group, TW occurred in 50.5% of children with Level 3 severity but was absent in Levels 1 and 2 (p < 0.0001). Males exhibited TW more frequently than females. Children with TW had higher SDSC scores (ρ = 0.33, p < 0.0001), though no subscale independently predicted TW. Constipation was reported in 100% of children with Level 3 ASD and was strongly correlated with SDSC total scores (ρ = 0.58, p < 0.0001). The Disorders of Arousal (DA) subscale emerged as an independent predictor of constipation (β = 0.184, p = 0.019). Conclusions: TW in ASD appears to be a marker of greater neurodevelopmental severity and is associated with sleep disturbances and gastrointestinal dysfunction. These findings support the hypothesis that TW may reflect broader dysfunctions involving the gut–brain axis, sensory processing, and motor control. The routine clinical assessment of TW should include the evaluation of sleep and somatic symptoms to better understand the multisystemic nature of ASD phenotypes. Full article

Background: Depression is a mental disorder characterized by a combination of somatic and cognitive disturbances, in which a predominantly sad or irritable mood significantly interferes with the patient’s functioning. This condition can affect individuals of all ages and socioeconomic backgrounds. Currently, various studies are exploring a possible association between oral dysbiosis and depression—an increasingly relevant topic, as confirmation of such a relationship could position the oral microbiota as a potential etiological or diagnostic factor for depression, given its accessibility and ease of analysis. Aim: To present a qualitative synthesis of studies addressing how oral dysbiosis influences the onset of depression, as well as the importance of controlling this alteration of the oral microbiota to aid in the prevention of the disease. Materials and Methods: The PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) outline the procedures to be followed for conducting this systematic review. The article search was carried out on 22 May 2025, across the PubMed, Scopus, Scielo, and The Cochrane Library databases, using terms related to “depression” and “oral dysbiosis”. Studies published within the last 10 years that addressed the potential association between oral dysbiosis, and depression were included. Furthermore, the quality of the studies was assessed using various tools depending on their design: the Newcastle–Ottawa Scale (NOS) was applied to case-control and cohort studies; the Joanna Briggs Institute (JBI) critical appraisal checklist was used for cross-sectional studies; and experimental studies were evaluated using SYRCLE’s Risk of Bias Tool. Results: A total of eleven studies were included in this systematic review. The findings suggest the presence of alterations in the oral microbiota of patients with depression, particularly in terms of composition, structure, and diversity. A reduction in alpha diversity—an indicator of local microbial balance—was observed, along with an increase in beta diversity, indicating greater inter-individual variability, which may be associated with inflammatory processes or immunological dysfunctions. Some studies reported differing results, which may be attributable to methodological variability regarding study design, or the populations sampled. Conclusions: This systematic review suggests that the oral microbiome could be considered a diagnostic biomarker and therapeutic target for depression, as the analyzed studies demonstrate a significant association between oral microbiome dysbiosis and this mental disorder. However, the methodological heterogeneity among the studies highlights the need for further research to confirm this potential relationship. Full article

Background and objectives: Duloxetine is widely used for the treatment of major depressive disorder (MDD), generalized anxiety disorder (GAD), and various types of neuropathic pain. While its efficacy is well documented in clinical trials, less is known about how it is perceived and utilized in routine psychiatric practice. To address this knowledge gap, we conducted a cross-sectional observational study involving 80 psychiatrists from Spain to assess real-world clinical attitudes toward duloxetine. Methods: Participants completed a 20-item multiple-choice questionnaire that examined familiarity, perceived efficacy in multiple conditions (MDD, GAD, neuropathic pain, somatization, and quality of life), and perspectives on tolerability, safety, adherence, and overall satisfaction. Results: Survey results indicated that a large majority of psychiatrists frequently prescribe duloxetine, particularly for patients with MDD and comorbid chronic pain. Notably, 94% rated it as either “more effective” or “much more effective” for diabetic peripheral neuropathic pain. Psychiatrists reported a high perceived efficacy of duloxetine: 94% rated it as “more effective” or “much more effective” for diabetic peripheral neuropathy, and 93% gave similarly positive ratings for general neuropathic pain. For somatization, 70% found it “effective” or “very effective”, and 83% observed improvements in quality of life for many of their patients. Psychiatrists generally reported favorable perceptions of duloxetine’s tolerability profile: 97.5% rated it as the antidepressant associated with the least weight gain, and 82.5% perceived fewer sexual side effects compared to other options. Sedation and gastrointestinal side effects were generally considered mild or less severe. In terms of treatment adherence, 69% rated it as “better” or “much better” than other antidepressants, and 80% found its combination with other antidepressants to be “favorable” or “very favorable”. Overall satisfaction was high, with 99% of psychiatrists reporting being either “satisfied” or “very satisfied” with its use. The side effect profile was generally viewed as manageable, with low perceived rates of weight gain, sedation, and sexual dysfunction. Furthermore, 96% of respondents expressed a willingness to recommend duloxetine to their colleagues. Conclusions: Psychiatrists reported highly favorable attitudes toward duloxetine, viewing it as a flexible treatment option in routine care. However, these findings reflect clinicians’ subjective perceptions rather than objective clinical outcomes and should be interpreted accordingly. Full article

Background: Post-concussion syndrome (PCS) and Functional Neurological Disorder (FND), including Functional Cognitive Disorder (FCD), are two frequently encountered but diagnostically complex conditions. While PCS is conceptualized as a sequela of mild traumatic brain injury (mTBI), FND/FCD encompasses symptoms incompatible with recognized neurological disease, often arising in the absence of structural brain damage. Yet, both conditions exhibit considerable clinical overlap—particularly in the domains of cognitive dysfunction, emotional dysregulation, and symptom persistence despite negative investigations. Objective: This review critically examines the shared and divergent features of PCS and FND/FCD. We explore their respective epidemiology, diagnostic criteria, and risk factors—including personality traits and trauma exposure—as well as emerging insights from neuroimaging and biomarkers. We propose the “Functional Overlay Model” as a clinical tool for navigating diagnostic ambiguity in patients with persistent post-injury symptoms. Results: PCS and FND/FCD frequently share features such as subjective cognitive complaints, fatigue, anxiety, and heightened somatic vigilance. High neuroticism, maladaptive coping, prior psychiatric history, and trauma exposure emerge as common risk factors. Neuroimaging studies show persistent network dysfunction in both PCS and FND, with overlapping disruption in fronto-limbic and default mode systems. The Functional Overlay Model helps to identify cases where functional symptomatology coexists with or replaces an initial organic insult—particularly in patients with incongruent symptoms and normal objective testing. Conclusions: PCS and FND/FCD should be conceptualized along a continuum of brain dysfunction, shaped by injury, psychology, and contextual factors. Early recognition of functional overlays and stratified psychological interventions may improve outcomes for patients with persistent, medically unexplained symptoms after head trauma. This review introduces the Functional Overlay Model as a novel framework to enhance diagnostic clarity and therapeutic planning in patients presenting with persistent post-injury symptoms. Full article

Striking belief distortions may accompany various disorders of awareness that are predominantly associated with right hemispheric cerebral dysfunction. Distortions may range on a continuum of pathological severity, from the unawareness of paralysis in anosognosia for hemiplegia, to a more startling disturbance in denial of paralysis where belief may starkly conflict with reality. The patients’ beliefs about their limitations typically represent attempts to make sense of limitations or to impart meaning to incongruous facts. These beliefs are often couched in recollections from past memories or previous experience, and are hard to modify even given new information. Various explanations of unawareness have been suggested, including sensory, cognitive, monitoring and feedback operations, feedforward mechanisms, disconnection theories, and hemispheric asymmetry hypotheses, along with psychological denial, to account for the curious lack of awareness in anosognosia and other awareness disorders. This paper addresses these varying explanations of the puzzling beliefs regarding hemiparesis in anosognosia. Furthermore, using the multi-dimensional nature of unawareness in anosognosia as a model, some startling belief distortions in other right-hemisphere associated clinical syndromes are also explored. Other neurobehavioral disturbances, though perhaps less common, reflect marked psychopathological distortions. Startling disorders of belief are notable in somatic illusions, non-recognition or delusional misattribution of limb ownership (asomatognosia, somatoparaphrenia), or delusional identity (Capgras syndrome) and misidentification phenomena. Difficulty in updating beliefs as a source of unawareness in anosognosia and other awareness disorders has been proposed. Processes of belief development are considered to be patterns of thought, memories, and experience, which coalesce in a sense of the bodily and personal self. A common consequence of such disorders seems to be an altered representation of the self, self-parts, or the external world. Astonishing nonveridical beliefs about the body, about space, or about the self, continue to invite exploration and to stimulate fascination. Full article

DNA-deaminase AID plays a pivotal role in adaptive immunity, antibody diversification and epigenetic regulation. AID catalyzes cytidine deamination in immunoglobulin genes, facilitating somatic hypermutation (SHM), class-switch recombination (CSR) and gene conversion (GC). However, the dysregulation of AID activity can lead to oncogenic mutations and immune disorders such as hyper-IgM syndrome type 2 (HIGM2). At present the number of studies investigating the role of AID polymorphic variants in the promotion of pathology is low. The current review examines the structural and functional aspects of AID, focusing on the impact of amino acid substitutions—both natural polymorphisms and artificial mutations—on its catalytic activity, substrate binding and interactions with regulatory proteins. Additionally, a bioinformatic analysis of single-nucleotide polymorphisms of AID deposited in the dbSNP database was performed. SNPs leading to amino acid substitutions in the primary protein structure were analyzed. The bioinformatic analysis of SNPs in the AID gene predicts that among 208 SNPs causing amino acid substitutions in the primary protein structure, 62 substitutions may have significant negative impact on the functioning of AID. The integration of computational predictions with experimental data underscores the importance of AID regulation in maintaining immune homeostasis and highlights potential markers for immune-related pathologies. This comprehensive analysis provides insights into the molecular mechanisms of AID dysfunction and its implications for disease. Full article