Search Results (3,577)

Crimean–Congo hemorrhagic fever (CCHF) is a zoonotic viral disease endemic to parts of Africa, Asia and southeastern Europe. Bulgaria is one of the few European countries with the consistent annual reporting of human CCHF cases. This study provides a descriptive overview of 24 confirmed CCHF cases in Bulgaria between 2015 and 2024. Laboratory confirmation was performed by an enzyme-linked immunosorbent assay (ELISA) and/or real-time reverse transcriptase polymerase chain reaction (RT-qPCR) testing. Common findings included fever, fatigue, gastrointestinal symptoms, thrombocytopenia, leukopenia, liver dysfunction and coagulopathy. Two fatal cases were recorded. Two samples collected in 2016 and 2024 were subjected to whole-genome sequencing. Phylogenetic analysis showed that both strains clustered within the Turkish branch of the Europe 1 genotype and shared high genetic similarity with previous Bulgarian strains, as well as strains from neighboring countries. These findings suggest the long-term persistence of a genetically stable viral lineage in the region. Continuous molecular and clinical surveillance is necessary to monitor the evolution and public health impact of CCHFV in endemic areas. Full article

Background: Meniere’s disease is characterized by a triad of vertigo episodes, fluctuating hearing loss, and tinnitus. The disease is followed by a loss of quality of life in patients, with the severity depending on the individual and the stage of the disease. Since there are no quantitatively validated tests that connect all elements of the disease, the only source of subjective data that can be analyzed is the disease diary and questionnaires, among which the MDPOSI (Meniere’s Disease Patient-Oriented Symptom-Severity Index) stands out as a designated quality-of-life assessment tool. This study aims to evaluate the differences in the questionnaire depending on the clinical characteristics of the disease. Methods: The study recruited 60 patients, with clinical variables including age, gender, disease laterality, caloric testing results, and PTA results, the presence of spontaneous nystagmus, pathological values of calorimetric testing, or rotatory chair testing abnormalities. Results: The appearance of spontaneous nystagmus showed a significant association with worse hearing threshold values at 500 Hz (p = 0.036, OR 4.416) and higher. Worse SRT scores correlated with Q1 (p = 0.011), Q2 (p = 0.028), Q4 (p = 0.045), Q5 (p = 0.013), and the total MDPOSI score (p = 0.008, 0.339). Multivariate analysis showed that a higher total value of the MDPOSI questionnaire was statistically significantly associated with older age (p = 0.042) and spontaneous nystagmus (p = 0.037). Conclusions: There is a correlation between the clinical characteristics of Meniere’s disease and the MDPOSI questionnaire, making it useful for assessing quality of life and disease progression. Full article

Objectives: Topical lubricants are the fundamental treatment for dry eye disease (DED). However, the molecular mechanisms underlying their efficacy remain unknown. Here, the protective effects of Thealoz^® Duo with 3% trehalose and 0.15% hyaluronic acid are investigated in DED patients by a longitudinal clinical study and subsequent elucidation of the tear proteome and cell signaling changes. Methods: Participants were classified as moderate to severe DED (DRY, n = 35) and healthy (CTRL, n = 23) groups. Specific DED subgroups comprising evaporative (DRYlip) and aqueous-deficient with DRYlip (DRYaqlip) were also classified. Only DED patients received Thealoz^® Duo. All participants were clinically examined before (day 0, T1) and after the application of Thealoz^® Duo at day 28 (T2) and day 56 (T3). Next, 174 individual tear samples from all groups at three time-points were subjected to proteomics analysis. Results: Clinically, Thealoz^® Duo significantly improved the ocular surface disease index at T2 vs. T1 (DRY, p = 1.4 × 10⁻²; DRYlip, p = 9.2 × 10⁻³) and T3 vs. T1 (DRY, p = 2.1 × 10⁻⁵; DRYlip, p = 1.2 × 10⁻⁴), and the tear break-up time at T3 vs. T1 (DRY, p = 3.8 × 10⁻²; DRYlip, p = 1.4 × 10⁻²). Thealoz^® Duo significantly ameliorated expression of inflammatory response proteins (p < 0.05) at T3, which was observed at T1 (DRY, p = 3.4 × 10⁻⁴; DRYlip, p = 7.1 × 10⁻³; DRYaqlip, p = 2.7 × 10⁻⁸). Protein S100-A8 (S100A8), Alpha-1-antitrypsin (SERPINA1), Annexin A1 (ANXA1), and Apolipoprotein A-I (APOA1) were found to be significantly reduced in all the DED subgroups. The application of Thealoz^® Duo showed the therapeutic characteristic of the anti-inflammatory mechanism by promoting the expression of (Metalloproteinase inhibitor 1) TIMP1 in all the DED subgroups. Conclusions: Thealoz^® Duo substantially improved the DED symptoms and restored the functionality of the tear lipid layer to near normal in DRYlip and DRY patients by ameliorating inflammation. Notably, this study unravels the novel mechanistic alterations underpinning the healing effects of Thealoz^® Duo in DED subgroups in a time-dependent manner, which supports the improvement in corresponding clinical attributes. Full article

Background/Objectives: Breast cancer was the leading cause of malignant tumors among women in 2022. About two-thirds of breast cancer cases are hormone-receptor-positive. In these patients, aromatase inhibitors are a mainstay of treatment, but associated musculoskeletal symptoms can negatively affect patient compliance. Aromatase-inhibitor-induced carpal tunnel syndrome represents one of the main causes of aromatase inhibitor discontinuation, with a non-compliance rate of up to 67%, potentially leading to increased cancer mortality. This study investigates estrogen receptor expression in aromatase-inhibitor-induced carpal tunnel syndrome tissues, in order to better define its etiopathogenesis and derive preventive or therapeutic measures that can improve aromatase inhibitor patient compliance. To our knowledge, there is no study on this subject in the literature. Methods: Between 2023 and 2024, we recruited 14 patients at the Jewish Hospital of Rome, including seven patients with aromatase-inhibitor-induced carpal tunnel syndrome (study group) and seven with postmenopausal idiopathic carpal tunnel syndrome (control group). Each patient was evaluated based on a clinical visit, a questionnaire, instrumental exams, and serum hormone dosages and were treated with open carpal tunnel release surgery, during which transverse carpal ligament and flexor tenosynovium samples were collected. For immunohistochemical experiments, sections were treated with anti-estrogen receptor α and anti-estrogen receptor β antibodies. Results: The immunohistochemical features in the study and control groups were similar, demonstrating that tissues affected by aromatase-inhibitor-induced carpal tunnel syndrome are targets of direct estrogen action and that estrogen deprivation is correlated with disease etiogenesis. Surgery was effective in patient treatment. Conclusions: Aromatase-inhibitor-induced carpal tunnel syndrome represents a newly defined form of the disease. This syndrome represents one of the main causes of aromatase inhibitor discontinuation, due to its negative impact on the patient’s quality of life. The identification by clinicians of aromatase inhibitor use as a possible risk factor for carpal tunnel syndrome development is of essential importance, as early diagnosis and prompt management can improve patient compliance and overall breast cancer treatment outcomes. Full article

Background/Objectives: Cancer is a complex disease that affects patients’ nutritional and psychological status. This study aimed to assess the nutritional status of patients diagnosed with lung and gastrointestinal system cancers and evaluate its association with anthropometric measurements, nutrient intake, and psychological symptoms. Methods: This cross-sectional study was conducted with 180 patients with lung and gastrointestinal system cancers. Data were collected face-to-face by a questionnaire that included the Subjective Global Assessment-(SGA), Cachexia Assessment Criteria, 24 h Food Consumption Record, and Symptom Checklist-90-Revised-(SCL-90-R). Some anthropometric measurements were collected. Results: Body Mass Index (BMI) was found to be significantly lower (p < 0.001) in SGA-B (moderately malnourished) and SGA-C (severely malnourished) compared to those in SGA-A (well-nourished). The calf circumference was significantly lower (p = 0.002) in SGA-C compared to those in SGA-A and SGA-B. The mean SGA scores were found to be higher in cachexia-diagnosed participants (p < 0.001). The energy intake of SGA-C was significantly lower than SGA-A and SGA-B (p < 0.001). In addition, the energy intake of SGA-B was lower than SGA-A (p < 0.001). The protein intake of SGA-C was lower than SGA-A and SGA-B (p < 0.001). The protein intake of SGA-B was lower than SGA-A (p < 0.001). Regarding the intake of vitamins A, C, E, B1, and B6 and carotene, folate, potassium, magnesium, phosphorus, iron, and zinc, SGA-B and SGA-C were significantly lower than SGA-A (p < 0.001). Additionally, only phobic anxiety was found to be significantly higher in SGA-B than in SGA-A (p: 0.024). Conclusions: As the level of malnutrition increased, a reduction in some nutrient intake and anthropometric measurements was observed. No significant difference was found in any psychological symptoms except phobic anxiety. With this in mind, it is important that every cancer patient, regardless of the stage of the disease, is referred to a dietitian from the time of diagnosis. Full article

Objective: This study aimed to improve the understanding of the lives of patients with chronic neuropathic pain planned for invasive motor cortex stimulation (iMCS) and assess their expectations towards this intervention and its impact. Methods: Semi-structured face-to-face interviews were conducted until saturation of data was reached. Patients were recruited from one university medical center in the Netherlands. All interviews were audio-recorded, transcribed verbatim, and subjected to thematic analysis using iterative and inductive coding by two researchers independently. Results: Fifteen patients were included (11 females; mean age 63 ± 9.4 yrs). Analysis of the coded interviews revealed seven themes: (1) the consequences of living with chronic neuropathic pain; (2) loss of autonomy and performing usual activities; (3) balancing energy and mood; (4) intimacy; (5) feeling understood and accepted; (6) meaning of life; and (7) the expectations of iMCS treatment. Conclusions: This is the first qualitative study that describes the suffering of patients with chronic neuropathic pain, and their expectations prior to invasive brain stimulation. Significant themes in the lives of patients with chronic pain have been brought to light. The findings strengthen communication between physicians, caregivers, and patients. Practice Implications: The insights gathered from the interviews create a structured framework for comprehending the values and expectations of patients living with central pain and reveal the impact of symptoms due to the central pain. This knowledge improves the communication between physicians and caregivers on one side and the patient on the other side. Furthermore, the framework enhances the capacity for shared decision-making, particularly in managing expectations related to iMCS. Full article

Background/Objectives: Schizophrenia exhibits symptoms linked to the hippocampus and parahippocampal gyrus. This includes the entorhinal cortex (ERC) and perirhinal cortex (PRC) as anterior parts, along with the posterior segment known as the parahippocampal cortex (PHC). However, recent research has detailed atlases based on cytoarchitectural characteristics and the hippocampus divided into four subregions: cornu ammonis (CA), dentate gyrus (DG), subiculum (SUB), and hippocampal–amygdaloid transition (HATA). This study aimed to explore the functional connectivity (FC) changes between these hippocampal subregions and the parahippocampal gyrus structures (ERC, PRC, and PHC) as well as between hippocampal subregions and various functional brain networks in schizophrenia. Methods: In total, 50 individuals with schizophrenia and 50 matched healthy subjects were examined using resting state functional magnetic resonance imaging (rs-fMRI). Results: The results showed alterations characterized by increases and decreases in the strength of the positive connectivity between the parahippocampal gyrus structures and the four hippocampal subregions when comparing patients with schizophrenia with healthy subjects. Alterations were observed among the hippocampal subregions and functional brain networks, as well as the formation of new connections and absence of connections. Conclusions: There is strong evidence that the different subregions of the hippocampus have unique functions and their connectivity with the parahippocampal cortices and brain networks are affected by schizophrenia. Full article

Objectives: To investigate the reliability and validity of the Singer Reflux Symptom Score (sRSS), a new patient-reported outcome questionnaire documenting the severity of reflux symptoms in singing voice is proposed. Methods: Amateur and professional singers consulting the European Reflux Clinic for laryngopharyngeal reflux disease (LPRD) symptoms and findings were prospectively recruited from January 2022 to February 2023. The diagnosis was based on a Reflux Symptom Score (RSS) > 13 and Reflux Sign Assessment (RSA) > 14. A control group of asymptomatic singer subjects was recruited from the University of Mons. The sRSS was rated within a 7-day period to assess test–retest reliability. Internal consistency was measured using Cronbach’s α in patients and controls. A correlation analysis was performed between sRSS and Singing Voice Handicap Index (sVHI) to evaluate convergent validity. Responsiveness to change was evaluated through pre- to post-treatment sRSS changes. The sRSS threshold for suggesting a significant impact of LPRD on singing voice was determined by receiver operating characteristic (ROC) analysis. Results: Thirty-three singers with suspected LPRD (51.5% female; mean age: 51.8 ± 17.2 years) were consecutively recruited. Difficulty reaching high notes and vocal fatigue were the most prevalent LPRD-related singing complaints. The sRSS demonstrated high internal consistency (Cronbach-α = 0.832), test–retest reliability, and external validity (correlation with sVHI: r = 0.654; p = 0.015). Singers with suspected LPRD reported a significant higher sRSS compared to 68 controls. sRSS item and total scores significantly reduced from pre-treatment to 3 months post-treatment except for the abnormal voice breathiness item. ROC analysis revealed superior diagnostic accuracy for sRSS (AUC = 0.971) compared to sRSS-quality of life (AUC = 0.926), with an optimal cutoff at sRSS > 38.5 (sensitivity: 90.3%; specificity: 85.0%). Conclusions: The sRSS is a reliable and valid singer-reported outcome questionnaire for documenting singing symptoms associated with LPRD leading to personalized management of Singers. Future large-cohort studies are needed to evaluate its specificity for LPRD compared to other vocal fold disorders in singers. Full article

Eosinophilic Granulomatosis with Polyangiitis (EGPA) is a rare systemic vasculitis with eosinophilic inflammation and variable clinical presentations. Although skin manifestations are frequent, current classification criteria do not include them, which may underestimate their diagnostic value. This prospective observational study aimed to assess systemic and skin involvement as well as eosinophilia, anti-neutrophil cytoplasmic antibody (ANCA), and Anti-nuclear antibodies (ANA) serum levels in 20 EGPA patients followed for one year at the University Hospital of Messina, Italy, before starting Mepolizumab, 300 mg. Eosinophilia, ANCA status, systemic and skin involvement were also evaluated at 6 and 12 months; a literature review on these data supplements our findings. Skin involvement was present in 55% of patients, including purpura, urticarial vasculitis, angioedema, maculopapular rash, and nodules, mostly in ANCA-negative patients, though purpura was more frequent in ANCA-positive cases but without any statistically significant correlation. ANAs were present in 50% of patients, together with ANCA in two subjects and without in eight. Mepolizumab significantly reduced eosinophil levels, BVASs, and corticosteroid dependence, with notable improvement in skin symptoms. In conclusion, skin manifestations are common in EGPA and may represent useful indicators of disease activity. Their integration with ANCA status, eosinophil counts, and positivity to other autoantibodies could enhance diagnostic and monitoring strategies identifying different clusters of EGPA patients even if the small sample size limits the generalizability of the findings. Full article

(1) Insulin-like growth factor-1 (IGF-1) is a neurotrophin with anti-inflammatory properties. Neuroinflammation and stress activate peripheral immune mechanisms, which may contribute to the development of depression and anxiety in sporadic Alzheimer’s disease (sAD). This study aims to evaluate whether intracerebroventricular (ICV) premedication with IGF-1 in a rat model of streptozotocin (STZ)-induced neuroinflammation can prevent the emergence of anhedonia and anxiety-like behavior by impacting the peripheral inflammatory responses. (2) Male Wistar rats were subjected to double ICVSTZ (total dose: 3 mg/kg) and ICVIGF-1 injections (total dose: 2 µg). We analyzed the level of anhedonia (sucrose preference), anxiety (elevated plus maze), peripheral inflammation (hematological and cytometric measurement of leukocyte populations, interleukin (IL)-6), and corticosterone concentration at 7 (very early stage, VES), 45 (early stage, ES), and 90 days after STZ injections (late stage, LS). (3) We found that ICVIGF-1 administration reduces behavioral symptoms: anhedonia (ES and LS) and anxiety (VES, ES), and peripheral inflammation: number of leukocytes, lymphocytes, T lymphocytes, monocytes, granulocytes, IL-6, and corticosterone concentration (LS) in the rat model of sAD. (4) The obtained results demonstrate beneficial effects of central IGF-1 administration on neuropsychiatric symptoms and peripheral immune system activation during disease progression in the rat model of sAD. Full article

Despite growing evidence supporting the efficacy of LSD-assisted psychotherapy in treating major depressive disorder (MDD), identifying reliable psychopharmacological biomarkers remains necessary. Oxytocin, a neuropeptide implicated in social bonding and flexibility, is a promising candidate due to its release following serotonergic psychedelic administration in healthy individuals; however, its dynamics in psychiatric populations are currently unexplored. This observational pilot study aimed to characterize salivary oxytocin dynamics during a single LSD-assisted psychotherapy session in our patients with treatment-resistant MDD. Participants received 100 or 150 µg LSD, and salivary oxytocin was measured at baseline, 60, 90, and 180 min post-LSD. Concurrently, participants rated subjective drug intensity (0–10 scale) at 60, 90, and 180 min. A linear mixed model revealed significant variation of oxytocin levels over time. Perceived psychedelic intensity also significantly varied over time. This supports oxytocin as a potential biomarker. Larger, controlled trials are warranted to replicate these findings and clarify the mechanistic links between oxytocin dynamics and clinical outcomes, including changes in depressive symptoms and mental flexibility. Full article

Alzheimer’s disease (AD) is the most common cause of cognitive decline. Among the various susceptibility genes, the gene of apolipoprotein E (APOE) is probably the most important. It may be present in three allelic forms, termed ε2, ε3 and ε4, and the most common genotype is the ε3/ε3. Recently, it has been observed that subjects with the ε4/ε4 genotype may show near-full penetrance of AD biology (pathology and biomarkers), leading to the suggestion that ε4 homozygosity may represent a distinct genetic type of AD. The aim of the present study was to investigate the role of ε4 homozygosity or heterozygosity in the presence or absence of the AD biomarker profile in patients with cognitive disorders in the Greek population. A total of 274 patients were included in the study. They underwent APOE genotyping and cerebrospinal fluid (CSF) biomarker profiling. The presence of ε4 was associated with a lower age of symptom onset and decreased amyloid biomarkers (irrespective to AD or non-AD profiles), and predicted the presence of an AD profile by a positive predictive value approaching 100%. In conclusion, the ε4 allele has a significant effect on the risk and clinical parameters of cognitive impairment and AD in the Greek population, while the ε4/ε4 genotype may be highly indicative of the (co)existence of AD in cognitively impaired patients. Full article

Background/Objectives: Huntington’s disease (HD) is a neurodegenerative disorder involving the basal ganglia and is characterized by psychiatric, cognitive, and movement dysfunction, including gait and balance impairment. Given the limited efficacy of pharmacological treatments for HD motor symptoms, nonpharmacological approaches like rhythmic auditory stimulation are being explored. This study aims to describe walking performance in people with HD during rhythmic auditory stimulation using external musical cues and internal singing cues. Methods: Individuals in the manifest stage of HD performed walking in four conditions: (1) comfortable pace, (2) cognitive dual task, (3) musical cue (music was played aloud), and (4) singing cue (participants sang aloud). Sensors measured cadence, velocity, stride length, and variability. Relationships between change in cadence and motor and cognitive measures were explored. Results: While no direct measurements of synchronization were performed, limiting our interpretation, neither the external musical cue nor the singing cue significantly improved walking performance. Both cues increased variability, similar to what was observed during the dual task. Greater subjective balance confidence and better cognitive performance were associated with positive cadence change during cueing. Conclusions: Musical cues may be too cognitively demanding for individuals with Huntington’s disease as they worsen gait variability without increasing gait speed, cadence, or stride length. Although global cognition and perceived balance confidence were related to the ability to increase cadence, very few people were able to increase their cadence during either cue. Therefore, the results do not support the use of musical cues to improve gait for individuals with Huntington’s disease. Full article

Background: Uvulopalatopharyngoplasty (UPPP) and expansion sphincter pharyngoplasty (ESP) are two standard surgical procedures for the treatment of snoring and obstructive sleep apnea. In a retrospective clinical trial, we compared the two surgical techniques regarding objective sleep parameters and patients’ reported outcomes. Materials and Methods: Patients treated with UPPP or ESP between January 2016 and February 2020 were included in this retrospective clinical trial. Pre- and postoperative AHI, BMI, and smoking habits were recorded. Subjective improvement was assessed by the ESS score and symptom relief reported by patients and their bed partners. Results: Between 2016 and 2020, 114 patients were included in the study, 74 patients suffered from OSA, and 30 patients had non-apnoeic snoring (AHI < 5/h). No preoperative sleeping studies were available in 10 patients (10/114; 9%). Based on the findings during drug-induced sedation endoscopy, most patients received an ESP (71/114, 62%), and 43 patients received a UPPP (43/114, 38%). Additionally, in 52/114 (46%), radio frequency ablation of the tongue base was performed if DISE revealed retrolingual collapse. ESP reduced AHI from 21.1 ± 10.8/h to 13.3 ± 12.1/h (p = 0.04), whereas UPPP caused a non-significant decrease in the AHI from 25.0 ± 13.8/h to 18.2 ± 14.6/h (p = 0.6). A minor secondary bleeding was observed in 32 patients, which was effectively treated with electrocautery or conservative therapy (32/114). This was more common in the ESP group (22/71; 31%) than in the UPPP group (10/43; 23%). Postoperative need for analgesics was higher in the ESP group than in the UPPP group. The ESS score showed no significant improvement after UPPP or ESP (p = 0.3), but subjective improvement in snoring was reported by 87/114 (76%) patients. Conclusion: AHI reduction was significantly higher in the ESP patient group than in the UPPP group. ESP patients had a slightly higher rate of minor secondary bleeding and postoperative need for analgesics than UPPP patients. Full article

Asthma is the leading chronic condition in children and adolescents, requiring continuous monitoring to effectively prevent and manage symptoms. Symptom monitoring can guide timely and effective self-management actions by children and their parents and inform treatment decisions by healthcare providers. This paper examines two conventional monitoring methods, including symptom-based and peak expiratory flow (PEF) monitoring, reviews early efforts to quantify respiratory symptoms, and introduces an emerging sensor-based mHealth approach. Although symptom-based monitoring is commonly used in clinical practice, its adequacy is a concern due to its subjective nature, as it primarily relies on individual perception. PEF monitoring, while objective, has shown weak correlations with actual asthma activity or lung function and suffers from suboptimal adherence among youth. To enhance objectivity in symptom monitoring, earlier efforts focused on quantifying respiratory symptoms by harnessing mechanical equipment. However, the practicality of these methods for daily use is limited due to the equipment’s bulkiness and the time- and labor-intensive nature of data processing and interpretation. As an innovative alternative, sensor-based mHealth devices have emerged to provide automatic, objective, and continuous monitoring of respiratory symptoms. These wearable technologies offer promising potential to overcome the issues of perceptual inaccuracy and poor adherence associated with conventional methods. However, many of these devices are still in developmental or testing phases, with limited data on their clinical efficacy, usability, and long-term impact on self-management behaviors. Future research and robust clinical trials are warranted to establish their role in asthma monitoring and management and improving asthma outcomes in children and adolescents. Full article