Search Results (5,353)

Background and Objectives: A correct diagnosis of beta-hemolytic group A streptococcus (GAS)-pharyngitis allows the prevention of complications and unnecessary use of antibiotics. The aim of this study was to assess the management of pediatric GAS-pharyngitis in Romanian general practitioners (GPs)’ practice. Material and Methods: a cross-sectional study was conducted using a questionnaire distributed to Romanian GPs. Results: In total, 56 GPs completed the questionnaire, mostly females (83.9%, n = 47) from an urban area (60.7%, n = 34). They treated 5–10 (35.7%) or more than 10 (32.1%) cases of GAS monthly and considered white exudate on tonsils (92.9%, n = 52) to be the most suggestive clinical sign. Of the GPs, 25% (n = 14) used the Centor Criteria, 10.7% (n = 6) performed a rapid antigen detection test, and 42.9% (n = 24) requested throat culture for diagnosis. The younger GPs used the Centor Criteria significantly more often (p = 0.027) than the older ones. Most GPs (69.6%, n = 39) preferred targeted antibiotic therapy. Amoxicillin-clavulanate was the most commonly used antibiotic (55.4%, n = 31). Most GPs preferred oral antibiotics (89%, n = 50) for 10 days (55.4%, n = 31). Conclusions: Antibiotic treatment was initiated mostly based on clinical symptoms and in a short-course therapy. GPs stated that they prefer targeted antibiotic therapy, but they did not use proper diagnostic tools. Full article

Schizophrenia (SCZ) is a debilitating disorder with substantial societal and economic impacts. The clinical high risk of psychosis (CHR-P) state generally precedes the onset of SCZ, offering a window for early intervention. However, treatment guidelines for CHR-P individuals remain contentious, particularly regarding antipsychotic (AP) medications. Although several studies have examined the effects of APs on reducing the risk of conversion to psychosis, the novelty of this narrative review lies in its focus on differentiating APs’ effects on positive and negative symptoms, as well as cognitive functioning, in CHR-P individuals. Evidence suggests that APs may be cautiously recommended for attenuated positive symptoms to stabilize individuals for psychological interventions, but their use in treating negative symptoms is generally discouraged due to limited efficacy and potential side effects. Similarly, the effects of APs on cognitive abilities remain underexplored, with results indicating a lack of significant neurocognitive outcomes. In conclusion, APs’ use in CHR-P patients requires careful consideration due to limited evidence and potential adverse effects. Future research should focus on individual symptom domains and treatment modalities to optimize outcomes in this critical population. Until then, a cautious approach emphasizing non-pharmacological interventions is advisable. Full article

Background/Objective: The most effective strategy for addressing users’ prosthetic needs is a comprehensive clinical assessment that provides a holistic understanding of the individual’s symptoms, health, function, and environmental barriers and facilitators. A standardized evaluation form would provide guidance for a structured approach to comprehensive clinical assessments of people with LLA. The objective of this study was to determine a list of relevant elements to be included in prosthetic evaluation for adults with lower limb amputation. Methods: Three independent focus group discussions were conducted with prosthetists (n = 15), prosthesis users (n = 11), and decision makers (n = 4) to identify all relevant elements that should be included in the clinical assessment of prosthetic services. The final content was then determined using the Delphi technique, with 35 panelists (18 prosthetists and decision makers, and 17 prosthesis users) voting in each round. Results: A total of 91 elements were identified through the focus group, of which 78 were included through the Delphi process. The identified elements are mostly related to the physical health of the prosthesis user (e.g., mobility, pain, and medical information), while others address personal or psychosocial aspects (e.g., activities of daily living, goals, and motivation) or technical aspects (prosthesis-related). Conclusions: Through a Delphi consensus, a list of relevant elements to be included in a prosthetic evaluation was generated. These results will inform the development of a standardized clinical prosthetic assessment form. This form has the potential to improve the quality of clinical evaluations, guide interventions, and enhance the well-being of prosthetic users. Full article

Social trust has been linked to the development and severity of depression, but trust is a complex, multidimensional construct. This study examines the extent to which two distinct forms of trust, general trust and specific trust, predict depressive symptoms. Drawing on longitudinal data from the Directorate of Health’s national surveys conducted in 2007 and 2009, the analysis includes responses from 3211 Icelanders selected through a stratified random sample. Depressive symptoms were assessed using the Depression, Anxiety, and Stress Scale (DASS), while specific trust captured trust in close relationships, and general trust measured broader perceptions of trustworthiness in others. The two forms of trust together explained 7.6% of the variance in depressive symptoms, with specific trust contributing a substantially greater share. Both remained significant predictors after controlling for prior depression and physical health. These findings highlight the protective role of specific trust and suggest that general trust, an indicator of broader social capital, may also help buffer against depression. The results underscore the relevance of trust as a public health resource and support continued research into social determinants of mental health in Iceland. Full article

Background/Objectives: Neuromodulation is under investigation as a possibly effective add-on therapy in Alzheimer’s disease (AD). While transcranial pulse stimulation (TPS) has shown positive short-term effects, long-term effects have not yet been fully explored. This study aims to evaluate the long-term feasibility, safety, and potential cognitive benefits of TPS over one year in patients with Alzheimer’s disease, focusing on domains such as memory, speech, orientation, visuo-construction, and depressive symptoms. Methods: We analyzed preliminary data from the first ten out of thirty-five patients enrolled in a prospective TPS study who completed one year of follow-up and were included in a dedicated long-term database. The protocol consisted of six initial TPS sessions over two weeks, followed by monthly booster sessions delivering 6000 pulses each for twelve months. Patients underwent regular neuropsychological assessments using the Alzheimer Disease Assessment Scale (ADAS), Mini-Mental Status Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Beck Depression Inventory (BDI-II). All adverse events (AEs) were documented and monitored throughout the study. Results: Adverse events occurred in less than 1% of stimulation sessions and mainly included mild focal pain or transient unpleasant sensations, as well as some systemic behavioral or vigilance changes, particularly in patients with underlying medical conditions, with some potentially related to the device’s stimulation as adverse device reactions (ADRs). Cognitive test results showed significant improvement after the initial stimulation cycle (ADAS total improved significantly after the first stimulation cycle (M_pre = 28.44, M_post = 18.56; p = 0.001, d = 0.80, 95% CI (0.36, 1.25)), with stable scores across all domains over one year. Improvements were most notable in memory, speech, and mood. Conclusions: TPS appears to be a generally safe and feasible add-on treatment for AD, although careful patient selection and monitoring are advised. While a considerable number of participants were lost to follow-up for various reasons, adverse events and lack of treatment effect were unlikely primary causes. A multifocal stimulation approach (F-TOP2) is proposed to enhance effects across more cognitive domains. Full article

Diagnosing hypermobility disorders and Ehlers-Danlos syndrome (EDS) in children is challenging due to overlapping features with generalized joint hypermobility (GJH) and the lack of biomarkers. Background/Objectives: This study aims to describe the clinical and genetic features of pediatric EDS patients and identify key comorbidities and correlations. Methods: This is a single-center observational study of patients under 18 diagnosed with suspicion of EDS (2018–2024) at a tertiary pediatric hospital. Diagnoses were made using 2017 criteria. Results: Forty-one patients (46% female; mean age 11.1 ± 2.8 years) were included. Based on 2017 criteria, 61% had hypermobile EDS (hEDS)/hypermobility spectrum disorder (HSD), 22% classical EDS, 7.3% vascular, and 9.7% other subtypes. Musculoskeletal (90.2%), cutaneous (68.3%), and psychiatric (56.1%) symptoms were most frequent. Significant associations included older age with psychiatric symptoms (p = 0.029), Beighton score with dislocations (p = 0.026), and less atrophic scarring in hEDS (p < 0.008). Genetic testing (73% performed) confirmed pathogenic variants (11 novel) in EDS with a known molecular cause. Conclusions: This study proposes a clinically guided approach and diagnostic algorithm for youth hypermobility, emphasizing precision medicine principles, while highlighting the urgent need for further research to identify hEDS biomarkers. Full article

Alzheimer’s disease (AD) is increasingly recognized as a multifactorial disorder driven by a combination of disruptions in proteostasis and organelle communication. The 2020 Lancet commission reported that approximately 10 million people worldwide were affected by AD in the mid-20th century. AD is the most prevalent cause of dementia. By early 2030, the global cost of dementia is projected to rise by USD 2 trillion per year, with up to 85% of that cost attributed to daily patient care. Several factors have been implicated in the progression of neurodegeneration, including increased oxidative stress, the accumulation of misfolded proteins, the formation of amyloid plaques and aggregates, the unfolded protein response (UPR), and mitochondrial–endoplasmic reticulum (ER) calcium homeostasis. However, the exact triggers that initiate these pathological processes remain unclear, in part because clinical symptoms often emerge gradually and subtly, complicating early diagnosis. Among the early hallmarks of neurodegeneration, elevated levels of reactive oxygen species (ROS) and the buildup of misfolded proteins are believed to play pivotal roles in disrupting proteostasis, leading to cognitive deficits and neuronal cell death. The accumulation of amyloid-β (Aβ) plaques and tau neurofibrillary tangles is a characteristic feature of AD. These features contribute to chronic neuroinflammation, which is marked by the release of pro-inflammatory cytokines and chemokines that exacerbate oxidative stress. Given these interconnected mechanisms, targeting stress-related signaling pathways, such as oxidative stress (ROS) generated in the mitochondria and ER, ER stress, UPR, and cytosolic chaperones, represents a promising strategy for therapeutic intervention. This review focuses on the relationship between stress chaperone responses and organelle function, particularly the interaction between mitochondria and the ER, in the development of new therapies for AD and related neurodegenerative disorders. Full article

Coronavirus disease 2019 (COVID-19) causes cardiovascular complications, which contributes to the high mortality rate of the disease. Emerging evidence indicates that aberrant vascular smooth muscle cell (SMC) function is a key driver of vascular disease in COVID-19. While antivirals alleviate the symptoms of COVID-19, it is not known whether these drugs directly affect SMCs. Accordingly, the present study investigated the ability of three approved COVID-19 antiviral drugs to influence SMC function. Treatment of SMCs with remdesivir (RDV), but not molnupiravir or nirmatrelvir, inhibited cell proliferation, DNA synthesis, and migration without affecting cell viability. RDV also stimulated an increase in heme oxygenase-1 (HO-1) expression that was not observed with molnupiravir or nirmatrelvir. The induction of HO-1 by RDV was abolished by mutating the antioxidant responsive element of the promoter, overexpressing dominant-negative NF-E2-related factor-2 (Nrf2), or treating cells with an antioxidant. Finally, silencing HO-1 partly rescued the proliferative and migratory response of RDV-treated SMCs, and this was reversed by carbon monoxide and bilirubin. In conclusion, the induction of HO-1 via the oxidant-sensitive Nrf2 signaling pathway contributes to the antiproliferative and antimigratory actions of RDV by generating carbon monoxide and bilirubin. These pleiotropic actions of RDV may prevent occlusive vascular disease in COVID-19. Full article

Background: Lysosomal storage diseases (LSDs) are a genetically and clinically heterogeneous group of inborn errors of metabolism caused by variants in genes encoding lysosomal hydrolases, membrane proteins, activator proteins, or transporters. These disease-causing variants lead to enzymatic deficiencies and the progressive accumulation of undegraded substrates within lysosomes, disrupting cellular function across multiple organ systems. While classical phenotypes typically manifest in infancy or early childhood with severe multisystem involvement, a combination of advances in molecular diagnostics [particularly next-generation sequencing (NGS)] and improved understanding of disease heterogeneity have enabled the identification of attenuated forms characterised by residual enzyme activity and later-onset presentations. These milder phenotypes often evade early recognition due to nonspecific or isolated symptoms, resulting in significant diagnostic delays and missed therapeutic opportunities. Objectives/Methods: This study characterises the clinical, biochemical, and molecular profiles of 10 adult patients diagnosed with LSDs, all representing attenuated forms, and discusses them alongside a narrative review. Results: Enzyme activity, molecular data, and phenotypic assessments are described to explore genotype–phenotype correlations and identify diagnostic challenges. Conclusions: These findings highlight the variable expressivity and organ involvement of attenuated LSDs and reinforce the importance of maintaining clinical suspicion in adults presenting with unexplained cardiovascular, neurological, ophthalmological, or musculoskeletal findings. Enhanced recognition of atypical presentations is critical to facilitate earlier diagnosis, guide management, and enable cascade testing for at-risk family members. Full article

Background/Objective: Dry eye syndrome affects 16 million Americans with USD 52 billion in annual healthcare costs. With large language models (LLMs) increasingly used for healthcare information, understanding their performance in delivering equitable dry eye guidance across diverse populations is critical. This study aims to evaluate and compare five major LLMs (Grok, ChatGPT, Gemini, Claude.ai, and Meta AI) regarding dry eye syndrome information delivery across different demographic groups. Methods: LLMs were queried using standardized prompts simulating a 62-year-old patient with dry eye symptoms across four demographic categories (White, Black, East Asian, and Hispanic males and females). Responses were analyzed for word count, readability, cultural sensitivity scores (0–3 scale), keyword coverage, and response times. Results: Significant variations existed across LLMs. Word counts ranged from 32 to 346 words, with Gemini being the most comprehensive (653.8 ± 96.2 words) and Claude.ai being the most concise (207.6 ± 10.8 words). Cultural sensitivity scores revealed Grok demonstrated highest awareness for minority populations (scoring 3 for Black and Hispanic demographics), while Meta AI showed minimal cultural tailoring (0.5 ± 0.5). All models recommended specialist consultation, but medical term coverage varied significantly. Response times ranged from 7.41 s (Meta AI) to 25.32 s (Gemini). Conclusions: While all LLMs provided appropriate referral recommendations, substantial disparities exist in cultural sensitivity, content depth, and information delivery across demographic groups. No LLM consistently addressed the full spectrum of dry eye causes across all demographics. These findings underscore the importance for physician oversight and standardization in AI-generated healthcare information to ensure equitable access and prevent care delays. Full article

Temporomandibular disorders (TMDs) encompass a heterogeneous group of musculoskeletal and neuromuscular conditions affecting the temporomandibular joint (TMJ) and masticatory system. Due to academic stress and parafunctional habits, dental students may be particularly vulnerable to TMD. Objective: To determine the prevalence of TMD symptoms and their psychosocial and functional correlates among students at the Faculty of Dental Medicine, UMPh Iasi, Romania, using the diagnostic criteria for TMD (DC/TMD) self-report axis and axis II instruments. Methods: In this cross-sectional survey, 356 volunteer students (66.0% female; mean age, 22.9 ± 3.6 years) out of a total population of 1874 completed an online DC/TMD–based questionnaire. Axis I assessed orofacial pain, joint noises, and mandibular locking. Axis II instruments included the Graded Chronic Pain Scale (GCPS), Jaw Functional Limitation Scale (JFLS-20), Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Oral Behaviors Checklist (OBC). Descriptive statistics summarized frequencies, means, and standard deviations; χ² tests and t-tests compared subgroups by sex; Pearson correlations explored relationships among continuous measures (α = 0.05). Results: A total of 5% of respondents reported orofacial pain in the past 30 days; 41.6% observed TMJ noises; 19.7% experienced locking episodes. Mean JFLS score was 28.3 ± 30.5, with 4.8% scoring > 80 (severe limitation). Mean PHQ-9 was 5.96 ± 5.37 (mild depression); 15.5% scored ≥ 10. Mean GAD-7 was 5.20 ± 4.95 (mild anxiety); 16.0% scored ≥ 10. Mean OBC score was 12.3 ± 8.5; 30.1% scored ≥ 16, indicating frequent parafunctional habits. Symptom prevalence was similar by sex, except temporal headache (43.4% females vs. 24.3% males; p = 0.0008). Females reported higher mean scores for pain intensity (2.09 vs. 1.55; p = 0.0013), JFLS (32.5 vs. 18.0; p < 0.001), PHQ-9 (6.43 vs. 5.16; p = 0.048), and OBC (13.9 vs. 9.7; p = 0.0014). Strong correlation was observed between PHQ-9 and GAD-7 (r = 0.74; p < 0.001); moderate correlations were observed between pain intensity and PHQ-9 (r = 0.31) or GAD-7 (r = 0.30), between JFLS and pain intensity (r = 0.33), and between OBC and PHQ-9 (r = 0.39) (all p < 0.001). Conclusions: Nearly half of dental students reported TMD symptoms, with appreciable functional limitation and psychosocial impact. Parafunctional behaviors and psychological distress were significantly associated with pain and dysfunction. These findings underscore the need for early screening, stress-management interventions, and interdisciplinary care strategies in the dental student population. Full article

(1) Background: Sertoli–Leydig cell tumors (SLCTs) are rare ovarian neoplasms that account for less than 0.5% of all ovarian tumors. They usually affect young women and often present with androgenic symptoms. We report a unique case of a 40-year-old woman diagnosed with both SLCT and clear cell papillary renal cell carcinoma (CCP-RCC), a rare tumor association with unclear pathogenesis. (2) Methods: Both tumors were treated surgically. The diagnostic workup included hormonal testing, imaging studies, and extensive genetic testing, including DICER1 mutation analysis and multiplex ligation-dependent probe amplification (MLPA), as well as the examination of a next-generation sequencing (NGS) panel covering ~280 cancer-related genes. (3) Results: Histopathologic examination confirmed a well-differentiated SLCT and CCP-RCC. No pathogenic variants in DICER1 were identified by WES or MLPA. No clinically relevant changes were found in the extended NGS panel either, so a known hereditary predisposition could be ruled out. The synchronous occurrence of both tumors without genomic alterations could indicate a sporadic event or as yet unidentified mechanisms. (4) Conclusions: This case highlights the importance of a multidisciplinary approach in the management of rare tumor compounds. The exclusion of DICER1 mutations and the absence of genetic findings adds new evidence to the limited literature and underscores the importance of long-term surveillance and further research into potential shared oncogenic pathways. Full article

Autobrewery syndrome is a rare condition characterized by the endogenous fermentation of carbohydrates by gut microbiota, which exceeds the liver’s detoxification capacity and leads to signs and symptoms of acute alcohol intoxication. This condition has significant clinical, social, and legal implications. Beyond the acute effects, the role of excessive endogenous ethanol production in the progression of chronic diseases—particularly liver disease—is still under investigation. In this review, we aim to describe the key clinical features of autobrewery syndrome, identify the main microbial pathogens involved, and explore the potential impact of endogenous ethanol production on the development and progression of chronic liver disease. Although robust data and standardized treatment protocols are currently lacking, we discuss the general principles of management and outline possible therapeutic strategies and future perspectives. Full article

Background/Objectives: Heart transplantation is a life-saving procedure for patients with end-stage heart failure, yet it involves significant psychological and emotional challenges throughout its various stages. International guidelines recommend a multi-professional approach to the care of these patients and a psycho-social assessment for listing. The recommendations focus on content aspects, but not on the psychometric measure to be administered to patients as part of the assessment. Therefore, the purpose of this study is to provide the preliminary results of administering the protocol used by our center, measuring coping strategies, cognitive functioning, quality of life, and psychological distress in a sample of patients who are candidates for and undergo cardiac transplantation, and to observe any variations after the procedure. Methods: We conducted a comprehensive psychological-clinical assessment involving 40 patients, focusing on psychosocial functioning, cognitive reserves, mental health, and coping strategies. Tools such as the Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT), Beck Depression Inventory-II (BDI-II), Montreal Cognitive Assessment (MoCA), General Anxiety Disorder 7 (GAD-7), and Medical Outcomes Survey Short Form 36 (SF-36) were employed to evaluate readiness for transplantation and post-transplant adaptation. Results: Results showed high levels of clinical anxiety (52.5%) and low perceived physical health (98%) before the transplant, while post-operative evaluations indicated reduced anxiety (13.51%) and depressive symptoms (10.81%), along with improved psychological well-being and reintegration into daily life. Conclusions: These results show improvement in physical and cognitive levels, accompanied by a state of enhanced psychological well-being after transplantation. A longitudinal psychological approach, from pre-transplant screening to post-discharge follow-up, is needed to address distress, improve coping mechanisms, and promote treatment adherence. This integrative strategy is critical to improving the quality of life and long-term outcomes for heart transplant recipients. Full article

Sensorimotor integration along the gastrointestinal (GI) tract is crucial for normal gut function yet remains poorly understood in the context of neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD). The genetic tractability of zebrafish allows investigators to generate molecularly defined models that provide a means of studying the functional circuits of digestion in vivo. Optical transparency during development allows for the use of optogenetics and calcium imaging to elucidate the mechanisms underlying GI-related symptoms associated with ASD. The array of commonly reported symptoms implicates altered sensorimotor integration at various points along the GI tract, from the pharynx to the anus. We will examine the reflex arcs that facilitate swallowing, nutrient-sensing, absorption, peristalsis, and evacuation. The high level of conservation of these processes across vertebrates also enables us to explore potential therapeutic avenues to mitigate GI distress in ASD and other NDDs. Full article