Search Results (53,472)

Background and objectives: Frontotemporal dementia (FTD) is a heterogeneous neurodegenerative disorder with autosomal dominant forms most often linked to MAPT, GRN, and C9orf72. We aimed to evaluate the prevalence of pathogenic variants in these genes in a hospital-based cohort of FTD patients assessed at a tertiary referral center in southeastern Serbia. Methods: We studied 58 consecutive patients with FTD spectrum syndromes evaluated at a tertiary referral center. All underwent standardized neurological, neuropsychological, and imaging assessments, and family history was recorded. Genetic testing included validated assays for C9orf72 repeat expansions and next-generation sequencing of MAPT and GRN. Results: Women comprised 53.45% of the cohort. The mean age was 67.88 years, with mean onset at 61.70 years. Behavioral variant FTD predominated (75.87%), while language forms were less frequent. Positive family history was present in 16 patients (27.59%). Pathogenic variants were identified in three individuals (5.17%): two unrelated carriers of the intronic MAPT mutation c.1920+16C>T and one patient with a C9orf72 expansion. No GRN variants were detected. Mutation frequency was 18.75% in familial cases, while none were found among sporadic patients (p = 0.018). Four of nine relatives were asymptomatic MAPT mutation carriers. Conclusions: This first genetic study of FTD in southeastern Serbia revealed a lower mutation frequency than in Northern and Western Europe, but similar to cohorts from Southeastern Europe. The detection of MAPT c.1920+16C>T in two unrelated families extends the geographic range of this splice-site variant and underscores the importance of systematic genetic testing and larger collaborative studies in the Balkans. Full article

Background/Objectives: Vestibulodynia is the prevalent form of vulvodynia, causing burning, irritation, rawness, and dyspareunia sensations. This sensory abnormality suggests sensitization to neuropathic pain. Methods: This was a randomized double-blind trial involving patients who applied a 5% cannabidiol gel with myrcene or a placebo to their vulvar vestibule for 60 days, assessing changes in dyspareunia, pain, and vestibular cotton swab test scores on a 0–10-point VAS scale. Results: This study enrolled 40 women, with 20 in the active treatment group and 20 in the placebo group. All symptoms improved in both groups, but the active treatment group showed a greater reduction in VAS scores for pain and swab tests. However, dyspareunia improved significantly more in the active treatment group. Conclusions: Cannabidiol’s positive effects on vestibulodynia patients can be attributed to its antinociceptive and anti-inflammatory properties. It desensitizes transient vanilloid receptor potential channels subtype 1, which are found in peripheral C-fiber nociceptors and mast cells. The results also suggest that myrcene, a terpene found in cannabis, can inhibit peripheral sensitization exerted by cannabidiol. Full article

Background: The aim of this study is to investigate the prevalence of the retromolar canal (RMC) and retromolar foramen (RMF) using cone-beam computed tomography (CBCT), and to evaluate the course and anatomical structure of the RMC. Methods: The study group consisted of CBCT images of 1008 subjects (541 females and 467 males). The prevalence and types of the RMC, as well as the frequency of the RMF, were analyzed according to age and sex. A significance level of 0.05 was accepted for all statistical analyses. Results: According to the findings, 575 (57.0%) RMCs and 298 (29.5%) RMFs were identified in 1008 subjects. Bilateral RMCs were observed in 327 subjects (32.4%), while unilateral RMCs were present in 248 subjects (24.6%). When 2016 retromolar regions were examined, a total of 902 RMCs and 400 RMFs were identified. No statistically significant difference was observed between the right and left retromolar regions or between sexes regarding the overall prevalence of RMCs (p > 0.05). The most frequently observed RMC type was Type A1, and a statistically significant difference was found between RMC types and sex. Conclusions: This study suggested that the RMC is a common anatomical variation that may have surgical relevance. Due to the presence of a neurovascular bundle passing through it, both the RMC and RMF should be considered in surgical and anesthetic procedures involving the retromolar region. CBCT is a reliable tool for detecting these structures and assessing their morphology. Full article

RNA-based therapeutics offer transformative potential for treating devastating diseases. However, current RNA delivery technologies face significant hurdles, including inefficient tissue targeting, insufficient selectivity, and severe side effects, leading to the termination of many clinical trials. This review critically assesses the landscape of RNA-derived medicines, examining world-renowned mRNA vaccines (Spikevax, BNT162b2/Comirnaty) and RNA-based therapeutics like Miravirsen (anti-miR-122). It details the composition and clinical trial results of numerous modified short RNA drugs (e.g., siRNAs, miRNA mimetics/inhibitors) targeting various conditions. Prospects for RNA-based medicines are analysed for diseases with substantial societal impact, such as cancer, autoimmune disorders, and infectious diseases, with a focus on evolving delivery methods, including lipid nanoparticles, viral vectors, and exosomes. RNA-mediated macrophage reprogramming emerges as a promising strategy, potentially enhancing both delivery and clinical efficacy. This review highlights that while approved RNA therapies primarily target rare diseases due to delivery limitations, novel approaches in RNA modification, targeted delivery systems, and enhanced understanding of molecular mechanisms are crucial for expanding their application to prevalent diseases and unlocking their full therapeutic potential. Full article

Objective: To determine the prevalence of mood and eating disorders, chronotype, and social jetlag in a cohort of women with polycystic ovarian syndrome (PCOS). Methods: A total of 70 patients, 35 with PCOS and 35 healthy controls, aged between 18 and 40 years, were included in the study. PCOS was diagnosed according to the Rotterdam criteria. Five different questionnaires, namely the “Morningness–Eveningness Questionnaire (MEQ)”, “Social Jetlag Status (SJL)”, “Night Eating Questionnaire (NEQ)”, “Beck Depression Inventory (BDI)”, and “Beck Anxiety Inventory (BAI)”, were administered to patients with and without PCOS, and the “total questionnaire scores” of both groups were compared. Results: In addition to BMI (p = 0.004), serum insulin (p < 0.001), HOMAIR (p < 0.001), total testosterone (p = 0.006), DHEAS (p = 0.004), and LH (p < 0.001) levels were significantly higher in women with PCOS than in the controls. BAI (p = 0.006), BDI (p = 0.007), and NEQ (p = 0.013) scores of participants with PCOS were significantly higher than those in the control group, while MEQ scores were significantly lower than those in the control group (p = 0.005). When categorized according to the total test scores, the number of individuals with moderate and severe anxiety was significantly higher in the PCOS group than in the control group (p = 0.030). Morningness was significantly lower in the PCOS group than in the control group, whereas eveningness was higher than that in the control group (p = 0.013). There was no difference between the PCOS and control groups in terms of the number of individuals with SJL ≥ 2 h and night eating disorders. The NEQ score was positively correlated with BAI, BMI, insulin, and HOMA-IR. Both the BDI and BAI scores were positively correlated with BMI, HOMA-IR, and total testosterone levels. Conclusions: PCOS can lead to mood, appetite, and circadian rhythm issues through variations in chronotype. PCOS-related endocrine, metabolic, and adiposity factors influence mood, eating habits, and chronotype disorders. Full article

Heart failure (HF) is a complex clinical syndrome characterized by impaired cardiac function and maladaptive neurohormonal activation, representing one of the leading causes of morbidity, hospitalization, and mortality worldwide. Both its incidence and prevalence continue to rise, largely as a consequence of population aging and the increasing burden of cardiovascular risk factors. The pathogenesis of HF is multifactorial, involving a dynamic interplay between inflammation and neurohormonal activation, ultimately leading to cardiac remodeling, diastolic dysfunction, and impaired cardiac output. In this context, numerous biomarkers have been investigated for diagnosis and prognosis utility in patients with HF. According to their underlying pathophysiological mechanisms, biomarkers in HF can be broadly categorized as indicators of inflammation, oxidative stress, cardiac remodeling, myocardial stress, neurohormonal activation, and cardiomyocyte injury. This review summarizes current knowledge on the pathophysiological basis of HF and highlights the diagnostic and prognostic relevance of circulating biomarkers, emphasizing their role in linking disease mechanisms with clinical management. Full article

Background/Objectives: The glymphatic system is a recently characterized glial-dependent waste clearance pathway in the brain, which makes use of perivascular spaces for cerebrospinal fluid exchange. Diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) offers a non-invasive method for estimating perivascular flow, but its biological specificity and susceptibility to methodological variation, particularly head position during MRI acquisition, remain as threats to the validity of this technique. This study aimed to assess the prevalence of current DTI-ALPS practices, evaluate the impact of head orientation on ALPS index calculation, and propose a novel computational approach to improve measurement validity. Methods: We briefly reviewed DTI-ALPS literature to determine the use of head-orientation correction strategies. We then analyzed diffusion MRI data from 172 participants in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) to quantify the influence of head orientation on ALPS indices computed using the conventional Unrotated-ALPS, a vecrec-corrected ALPS, and the new LD-ALPS method proposed within. Results: A majority of studies employed Unrotated-ALPS, which does not correct for head orientation. In our sample, Unrotated-ALPS values were significantly associated with absolute head pitch (r₁₆₉ = −0.513, p < 0.001), indicating systematic bias. This relationship was eliminated using either vecreg or LD-ALPS. Additionally, LD-ALPS showed more sensitivity to cognitive status as measured by Mini-Mental State Examination scores. Conclusions: Correcting for head orientation is essential in DTI-ALPS studies. The LD-ALPS method, while computationally more demanding, improves the reliability and sensitivity of perivascular fluid estimates, supporting its use in future research on aging and neurodegeneration. Full article

The prevalence of probiotic-labeled products with no evidence of improved health outcomes associated with their consumption has perturbed both the trust of clinicians and the public perception of microbial therapeutics. While probiotics are clearly defined as live microorganisms that, when administered in adequate amounts, confer a health benefit on the host, it is often ignored in the microbial marketplace. Many products including household cleaners, cosmetics, and pet foods attach probiotic to their labels without supplying viable strains, clinically effective doses, or proven outcomes. Evidence from metagenomic studies and compositional analyses suggest that many probiotics on the market are mischaracterized or mislabeled, a problem that is only exacerbated by weak regulatory standards. In contrast, there are a limited collection of strain-specific interventions such as Lactobacillus rhamnosus GG, L. rhamnosus GR1, Saccharomyces boulardii, and Escherichia coli Nissle 1917 that have demonstrated beneficial effects in randomized clinical trials. Considering that the consumption of commercial probiotics often lacks measurable health benefits, it is unreasonable to group proven microbial therapeutics under the same umbrella term of “probiotic”. This paper proposes a strict enforcement of semantic distinction: reserving “probiotics” for less regulated microbial-rich products whereas microbe-containing products that have demonstrated clinical benefit following robust regulatory oversight should be considered for reclassification. Full article

Background/Objectives: Pediatric foreign body (FB) ingestion is a common clinical problem that frequently necessitates time-sensitive decisions regarding esophagogastroduodenoscopy (EGDS). Although established high-risk criteria guide the indication for EGDS, coins—despite their high prevalence—are not uniformly classified as high-risk FBs. In this study, we aimed to delineate epidemiology and endoscopic outcomes and to identify predictors of EGDS. Methods: We retrospectively reviewed cases of children younger than 15 years presenting to an urban emergency department (ED) with suspected or confirmed FB ingestion between 2014 and 2020. After applying exclusion criteria, 757 patients remained for analysis. Data abstracted included demographic characteristics, presenting symptoms, type and location of FB, ED length of stay (EDLOS), and whether EGDS was performed along with its outcomes. Multivariable logistic regression was used to identify predictors of EGDS, including age group, sex, symptom presence, established high-risk criteria, and type of FB (coin, button battery, magnet). Results: Among 757 children (median age 17.0 months; 54.0% male), 55.2% were asymptomatic. EGDS was performed in 47 of the 757 children (6.2%), with a success rate of 74.5% (35/47). Among EGDS cases, the most common foreign bodies were coins (29.8%), button batteries (27.7%), and magnets (17.0%). In multivariable models, established high-risk criteria were the dominant determinant of EGDS (adjusted OR ≈ 179.4; 95% CI, 29.9–1075.8; p < 0.001). Compared with button batteries, coin ingestion was independently associated with EGDS (adjusted OR ≈ 7.26; 95% CI, 1.07–49.31; p = 0.042). Conclusions: Established high-risk criteria were the primary determinant of EGDS, and coin ingestion showed a possible independent association with EGDS; these findings suggest that coin ingestion may warrant consideration as a potential high-risk factor when determining whether endoscopy is indicated. Full article

Raw meat-based diets (RMBDs) have gained popularity over the past few years. However, there is growing concern about their safety. The study objective was to evaluate the prevalence and characteristics of the pathogens Salmonella spp., Listeria monocytogenes, Yersinia enterocolitica, and Campylobacter spp. in frozen commercially sold RMBDs. One hundred raw meat-based diet products (meat originating from Switzerland, Germany, Austria, Spain, Scandinavia, South Africa, and Australia) were purchased online or in local stores and identified using culture-based methods. Isolates were further characterized by phenotypic and whole genome sequencing-based methods. In total, 11% (n = 11) of the samples tested positive for Salmonella spp., 41% (n = 41) for L. monocytogenes, 58% (n = 58) for Y. enterocolitica, and 3% (n = 3) for Campylobacter spp. Other than for Salmonella, there are no legal regulations concerning contamination of RMBDs with these zoonotic pathogens. The results of our study show that it is indicated to reconsider the requirements for the microbiological quality of RMBDs and to further raise awareness regarding the risks of handling and feeding RMBDs. Full article

Background/Objectives: Thyroid hormone deficiency may impair bone metabolism, but its mandibular impact remains uncertain. We aimed to compare the prevalence of altered Mandibular Cortical Index (MCI; C2–C3) and Panoramic Mandibular Index (PMI) on digital panoramic radiographs in adult women with primary hypothyroidism versus euthyroid controls, considering age and key clinical covariates. To our knowledge, this is the first study out of Spain addressing this question. Methods: This is a cross-sectional study (September 2021–June 2024) of 179 white women recruited at a university clinic. Cases were on L-thyroxine for ≥6 months, with TSH > 4.5 mIU/L and normal FT4; controls were euthyroid and untreated. Demographics, reproductive history, and BMI were recorded. Panoramic radiographs (Ratograph EVO 3D; 72 kV, 6 mA, 14.4 s) were analysed; MCI was graded (Klemetti C1–C3) distal to the mental foramen; PMI and mandibular cortical width (MCW) were measured bilaterally. Results: Women with hypothyroidism showed higher BMI and a greater number of years since menopause; age was slightly higher, but the difference was not significant. MCI distribution did not differ between groups (C3 and C2–C3, both p > 0.45). PMI (left/right) was similar (p = 0.253/0.160). Left MCW was higher in hypothyroidism in a crude analysis (4.86 ± 0.98 vs. 4.46 ± 0.94 mm; p = 0.039), but lost significance after age adjustment (adjusted p = 0.191); right MCW showed no differences. Total tooth loss tended to be higher (p = 0.055) without conclusive evidence. Conclusions: In this cohort, primary hypothyroidism was not associated with a differential mandibular cortical pattern by MCI or PMI; the crude MCW difference was explained by age. These Spain-based data refine heterogeneous prior findings and indicate that, in women treated for hypothyroidism, mandibular cortical metrics largely resemble those of their euthyroid peers. Longitudinal and multicentre studies are warranted to clarify trajectories and enhance generalisability. Full article

The aim of this study was to explore the prevalence of acute and overuse injuries, as well as risk factors, training load and well-being, in male and female youth padel players. Using a cross-sectional design, data were collected from 104 players (aged 15–20) via a web-based form. Players reported injuries, exposure and rating of perceived exertion (RPE), demographics (age and sex), and perceived well-being. Overuse injury severity was scored per body region (0–25), yielding a total possible score of 125. A total of six acute and 49 overuse injuries were recorded, corresponding to a prevalence of 0.53 injuries per player during a one-week recall period. Most injuries affected the knee, while the foot and lower leg had the highest severity scores (median = 44). Female players reported slightly higher stress levels (median 3) than males (median 2: p = 0.01), though no other well-being or training load differences were found. Injured players had significantly higher total wellness scores, indicating worse well-being, compared to non-injured players (median 10 vs. 9, p = 0.03). In conclusion, overuse injuries, particularly to the knee, were most common. Higher perceived stress and poorer wellness scores may be linked to injury risk, underlining the importance of monitoring well-being in youth padel athletes. Full article

Background: Granulomatous mastitis (GM) is a rare, chronic inflammatory breast condition with poorly understood etiology and variable clinical presentation. The efficacy of corticosteroid therapy in reducing recurrence remains controversial, particularly in Middle Eastern populations where the condition appears more prevalent. This study aimed to describe the demographic and clinical characteristics of patients with GM, evaluate the efficacy of corticosteroid therapy in reducing recurrence rates, and identify risk factors associated with disease recurrence. Methods: A retrospective cohort analysis was conducted on 56 patients diagnosed with GM between 2003 and 2020 at a single tertiary referral center. Patients were stratified into two groups based on steroid use (n = 14 with steroids and n = 42 without steroids). Results: The mean age of the cohort was 46.3 ± 13.2 years, with no significant differences in baseline characteristics between the steroid and non-steroid groups. The most common presentation was a breast mass (32.69%), often associated with abscess formation (25%). Core biopsy was the primary diagnostic tool used (51.79%). Recurrence of GM occurred in 10 patients (18%) overall: 7 patients (17%) in the non-steroid group and 3 patients (21%) in the steroid group. The difference in recurrence rates between the treatment groups was not statistically significant (HR = 1.40, 95% CI:0.30–6.52, p = 0.671). A history of infection (HR = 5.85, 95% CI: 1.60–21.44, p = 0.008) and hormonal disorders (hyperprolactinemia in one patient) (HR = 13.90, 95% CI: 1.43–135.52, p = 0.024) were significantly associated with recurrence. Conclusions: GM remains diagnostically challenging with an 18% recurrence rate in our cohort. We observed no statistically significant reduction in recurrence with corticosteroids, though our analysis was limited by sample size. These findings suggest that targeted management of these conditions may be beneficial in GM patients, though larger multicenter studies are needed to confirm these associations and establish standardized treatment protocols. Full article

Objective: The purpose of this study was to investigate the knowledge, attitudes, and practices (KAPs), including ageism, of rehabilitation service providers regarding older adults with substance use disorders to examine the association between KAPs and ageism on the knowledge of rehabilitation providers and confidence in treating this population. Methods: An online survey was developed to assess providers’ familiarity with geriatric substance use disorders, attitudes towards aging, and perceived barriers to treatment. The survey included the Expectations Regarding Aging (ERA-12) tool to measure ageist attitudes. Data was collected from 25 rehabilitation healthcare providers across rehabilitation centers in North Carolina. Descriptive statistics and ERA-12 scoring were used to analyze the results. Results: Most (52.0%) respondents reported slight or moderate familiarity with specific risk factors for substance use disorders associated with older adults, and participants most commonly expressed ambivalence (48.0% indicated they were neither satisfied nor dissatisfied) with their training on this demographic. Barriers included a lack of specialized training, limited availability of age-appropriate treatment programs, and resistance to change. Negative attitudes towards aging and substance use disorders were prevalent among respondents. Providers indicated a need for enhanced education, clinical guidelines, and access to geriatric-trained professionals. Discussion: The findings highlight a critical need for specialized training for rehabilitation providers to improve care for older adults with substance use disorders. Addressing ageism, increasing awareness, and enhancing provider education are essential to improving treatment outcomes. Implementing targeted training programs and specialized resources could significantly enhance the quality of care for this underserved population. Full article

African horse sickness (AHS) is an arthropod-borne, severe equid disease caused by African horse sickness virus (AHSV). AHSV has high mortality and is endemic to sub-Saharan Africa. It has been classified into nine distinct serotypes (AHSV-1 to AHSV-9) based on VP2 immunogenicity. The AHS outbreak in Thailand in 2020, caused by AHSV-1, marked the first occurrence of this disease in Southeast Asia. It posed a substantial threat to the security of the equine industry in the nations across the region. To ensure the emergency reserve for AHS prevention and control, the AHSV strain imported to China from abroad over 60 years ago was characterized in this study. The strain was passaged in mice and then blind-passaged in Vero cells. The plaque purification method was then used to purify the strain and obtain its cell-adapted version, named AHSV/C. Neutralization tests confirmed that the virus belongs to AHSV-1. Whole-genome sequencing revealed that AHSV/C was highly homologous to AHSV-1 isolate 1180, with over 95% homology of major antigenic protein VP2, as compared to other AHSV-1 strains, including the prevalent strain in Thailand. In the mouse models, AHSV/C exhibited no clinical signs or histopathological lesions, suggesting low virulence and safety. This research for the first time characterized the in vitro growth characteristics and viral subtypes of the AHSV in China, determined its complete whole-genome sequence, and evaluated its safety using a mouse model. It provides crucial experimental materials and scientific foundations for the development of diagnostic methods and vaccines against AHSV-1. Full article