Search Results (68)

Clostridium botulinum produces one of the most potent biological toxins and causes botulism, a rare but potentially fatal neuroparalytic disease. In 2014, a foodborne botulism case was reported in Korea, and a strain (CB-2014001) was isolated. Initial characterization identified it as a BoNT/B-producing strain based on mouse bioassay and conventional PCR. However, subsequent genomic analysis revealed the presence of dual BoNT gene clusters, bont/B and bont/F, corresponding to subtypes B5 and F2, respectively. Therefore, we aimed to analyze the genetic characteristics and toxin expression profiles of the isolated strain. The strain showed high sequence identity with Bf-type strains such as CDC 3281 and An436. Functional assays confirmed simultaneous expression of both BoNT/B and /F toxins at 35 °C, and temperature-dependent assays revealed predominant expression of BoNT/F at 30 °C and BoNT/B at 37 °C, indicating that toxin expression is influenced by environmental temperature. These findings highlight the potential for differential pathogenicity based on culture conditions and underscore the importance of developing diagnostic tools capable of detecting multiple bont genes. To our knowledge, this is the first report of a dual-toxin-producing C. botulinum strain associated with foodborne botulism in Korea, providing important insights into botulism diagnosis, treatment strategies, and public health preparedness. Full article

Fibromyalgia, one of the most challenging pains to treat, lacks impartial considerations for diagnosis and useful assessment. The core symptoms are persistent extensive pain accompanied by fatigue, psychological disorders, sleep disturbance, and obesity. This study aims to explore the role of cannabinoid receptor 1 (CB1) on transient receptor potential V1 (TRPV1) signaling pathways in a mouse model of fibromyalgia. This model was subjected to intermittent cold stress (ICS) to induce fibromyalgia, as measured by the nociceptive behavior determined by von Frey and Hargreaves’ tests. Our results showed a lower mechanical threshold (2.32 ± 0.12 g) and thermal latency (4.14 ± 0.26 s) in ICS-induced fibromyalgia mice. The hyperalgesia could be alleviated by 2 Hz electroacupuncture (EA) or by TRPV1 knockout. We found decreased CB1 receptors, upregulated TRPV1, and related kinases in the dorsal root ganglion, spinal cord, hypothalamus, and periaqueductal gray in fibromyalgia mice. EA reversed these effects associated with fibromyalgia, aligning with observations in Trpv1^−/− mice. Peripheral acupoint or the intracerebral ventricle injection of a CB1 agonist significantly attenuated mechanical and thermal hyperalgesia. The EA analgesic effect was reversed by a CB1 antagonist injection, suggesting the involvement of the CB1 signaling pathway. The accurate chemogenetic activation of paraventricular nucleus (PVN), which is a structure of the hypothalamus, initiated fibromyalgia pain. The chemogenetic inhibition of PVN attenuated fibromyalgia pain via the downregulation of TRPV1 pathway. Our discoveries shed light on the involvement of CB1 in the TRPV1 signaling pathway in the effects of EA in fibromyalgia, suggesting its potential as a treatment target. Full article

The endocannabinoid system (ECS) is a complex endocrine network involved in maintaining body homeostasis. It comprises endocannabinoids, their receptors (CB1 and CB2), and the enzymes and transporters responsible for their synthesis and degradation. While the ECS’s role in the nervous system is well established, its functions in other organs and peripheral tissues, including the cardiovascular, gastrointestinal, and reproductive systems, remain incompletely understood. With the increasing use of marijuana, particularly among individuals of reproductive age, concerns have emerged regarding its potential impact on male and female fertility. Phytocannabinoids (∆9tethrahydrocannabinol and cannabidiol), as well as synthetic cannabimimetic drugs, interact with the ECS, influencing sperm and oocyte physiology and reproductive outcomes. Recent research has identified ECS-related biomarkers with potential applications in infertility diagnosis, particularly in assessing male fertility with greater precision. Furthermore, emerging evidence suggests that ECS signaling pathways are involved in epigenetic modifications, which may influence health maintenance, disease susceptibility, and transgenerational inheritance patterns. These findings highlight the therapeutic potential of ECS modulation in reproductive disorders and broader medical applications. This narrative review aims to elucidate the role of the ECS in human reproduction, with a particular focus on the influence of endocannabinoids on gametogenesis. While current research underscores the critical role of the ECS in fertility, further investigations are needed to fully elucidate its underlying mechanisms and its broader implications for reproductive health and therapeutic interventions. Full article

Background and Objectives: Despite ongoing research and evolving diagnostic criteria, progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) remain notoriously difficult to differentiate, largely due to their overlapping clinical presentations and the absence of definitive biomarkers. Materials and Methods: We provide a comprehensive review of cerebrospinal fluid (CSF) biomarkers, which have proven valuable in the diagnosis of other neurodegenerative conditions, and their application to PSP and CBS. Results: The most promising results derive from a combination of biomarkers associated with Parkinson’s disease, Alzheimer’s disease, and neurofilament light chain. Furthermore, CSF proteomics analysis offers valuable insights into the pathogenesis of PSP and CBS and could also contribute to accurate diagnosis. Conclusions: CSF biomarkers hold significant potential for improving the differential diagnosis of PSP and CBS. A stepwise combination approach—starting with CSF α-synuclein and neurofilament light chain, followed by amyloid-β42 and total and phosphorylated tau—may provide clinicians with a practical framework for distinguishing PSP and CBS from other neurodegenerative disorders. To advance this field, future efforts should prioritize large-scale, multicenter studies employing standardized methodologies to enhance the validity and reproducibility of biomarker-based diagnostics. Importantly, considering the frequent pathological overlap between PSP and CBS, future studies would greatly benefit from pathology-confirmed cohorts to ensure diagnostic accuracy and to better delineate biomarker profiles across these challenging conditions. Full article

Background: Homocystinuria caused by cystathionine β-synthase (CBS) deficiency is the most common congenital disorder related to sulfur amino acid metabolism, manifested by neurological, vascular, and connective tissue involvement. Methods: This study analyzed the pathogenic gene and molecular mechanism of two classic homocystinuria families through whole exome sequencing and in vitro experiments including minigene assay and expression analysis. Results: Both probands presented with ectopia lentis, high myopia, and abnormally elevated homocysteine level, but one of them had more severe clinical manifestations, including general growth retardation, mild intellectual disability, and severe pectus excavatum. Their family members were phenotypically normal but presented slightly higher levels of homocysteine in plasma. Whole exome sequencing revealed that the two probands carried c.833T>C (p.Ile278Thr) and c.1359-1G>C, and c.919G>A (p.Gly307Ser) and c.131delT (p.Tle44Thrfs*38) compound heterozygous mutations in the CBS gene, respectively. Bioinformatics and in vitro functional analysis showed that the c.1359-1G>C mutation affects the normal splicing of CBS gene, resulting in the production of two abnormal transcripts and the production of two truncated proteins. One of the c.1359-1G>C splicing events (c.1359_1467del) and c.131delT (p.Tle44Thrfs*38) both lead to a significant decrease in CBS mRNA and protein levels. Conclusions: Accurate diagnosis of patients with homocystinuria is of great importance for timely and effective treatment, as well as for the provision of appropriate genetic counseling and prenatal diagnosis guidance to the affected families. Full article

Background/Objectives: Cesarean birth (CB) is linked to nonspecific low back pain (NSLBP). Different properties of the muscular tissue, including contractile, biomechanical, and viscous properties, may reflect its physiological or pathological condition. This study aimed to measure these properties of lumbar paravertebral muscles (LPVMs) and their relationship with post-CB mothers with moderate-severity NSLBP and match their measurements to those of the controls. Methods: Sixty women were included in this case–control research. They were divided into two equal groups: Group (A) representing cases, consisted of 30 females who experienced CB and complained of moderate-severity NSLBP, and Group (B) representing controls, consisted of 30 healthy females who had never experienced pregnancy with no or mild-severity NSLBP. Results: The statistical analysis between the two groups yielded significant differences in the right and left LPVMs’ tone (p = 0.002 and 0.015), relaxation time (p = 0.002 and 0.022), and creep (p = 0.013 and 0.008), respectively. On the other side, there were non-significant differences in the right and left LPVMs’ stiffness (p = 0.055 and 0.367) and elasticity (p = 0.115 and 0.231), respectively. The regression analysis’s final model indicated a strong overall performance (Nagelkerke: 1.00). Conclusions: The LPVMs of post-CB mothers with moderate-severity NSLBP showed remarkable changes in both contractile and viscous properties: muscle tone notably decreased, while viscosity increased. However, biomechanical properties like stiffness and elasticity showed negligible changes. This fitted regression analysis illustrated the holistic strong effect of LPVMs’ properties as risk factors contributing to post-CB NSLBP, emphasizing their consideration in diagnosis and intervention strategies for such cases. Full article

Background: Fibroblast activation protein (FAP)-targeted theranostic radiopharmaceuticals have shown desired tumor-to-background organ selectivity due to the ubiquitous presence of FAP within the tumor microenvironment. However, suboptimal tumor retention and fast clearance have hindered their use to deliver effective cancer therapies. With well-documented FAP-targeting moieties and linkers appending them to optimal chelators, the development of copper radiopharmaceuticals has attracted considerable interest, given the fact that an ideal theranostic pair of copper radionuclides (⁶⁴Cu: t_1/2 = 12.7 h; 17.4% β⁺; E_β⁺_max = 653 keV and ⁶⁷Cu: t_1/2 = 2.58 d; 100% β⁻; E_β⁻_max = 562 keV) are available. Herein, we report our design, synthesis, and comparative evaluation of monovalent and divalent FAP-targeted theranostic conjugates constructed from our previously reported bifunctional chelator scaffold (BFS) based on 1,4,8,11-tetraaza-bicyclo [6.6.2]hexadecane-4,11-diacetic acid (CB-TE2A), which forms the most stable complex with Cu(II). Methods: After synthesis and characterization, the monovalent and divalent conjugates were radiolabeled with ⁶⁴Cu for in vitro cell assays, followed by in vivo positron emission tomography (PET) imaging evaluation in relevant mouse models. Results: Both ⁶⁴Cu-labeled conjugates showed high in vitro stability and anticipated FAP-mediated cell binding and internalization. The divalent one showed significantly higher FAP-specific tumor uptake than its monovalent counterpart. Conclusions: Our results demonstrate that the BFS-based multivalent approach can be practically used to generate FAP-targeted radiotheranostic agents for effective cancer diagnosis and treatment. Full article

The gold standard for histological acute cellular rejection diagnosis is transbronchial forceps biopsy (FB), but in recent years, transbronchial cryobiopsy (CB) has been increasingly used. This study aims to compare the diagnostic rate and safety of FBs and CBs performed in two different periods. We retrospectively reviewed our case history for the two biopsy procedures: 251 FBs (223 for surveillance purposes and 28 for clinical indication) and 218 consecutive CBs (159 for surveillance purposes and 59 for clinical indication). All biopsies were scored according to the ISHLT criteria. Diagnostic yield was higher in the CB group for all the parameters considered: a grade of acute rejection (AR) was detected in 95.0% vs. 84.5% in the CB vs. FB groups (p < 0.001). The diagnostic rate of airway inflammation was 65.1% vs. 51.8% (p = 0.005), and 89.0% vs. 64.9% (p < 0.001) for chronic rejection. Pneumothorax requiring chest drainage occurred in 4% of the CB group and 3% of the FB group. Moderate and severe bleeding complicated CB and FB procedures in seven (3%) and three cases (1%), respectively. Transbronchial cryobiopsies improved the diagnostic yield in the monitoring of the lung allograft. The complication rate did not increase significantly in CBs vs. FBs. Full article

Primary Ciliary Dyskinesia (PCD) is a rare genetic disorder characterized by alterations in motile cilia function. The diagnosis of PCD is challenging due to the lack of standardized methods in clinical practice. High-speed video microscopy analysis (HSVA) directly evaluates ciliary beat frequency (CBF) in PCD. Recently, open-source ciliary analysis software applications have shown promise in measuring CBF accurately. However, there is limited knowledge about the performance of different software applications, creating a gap in understanding their comparative effectiveness in measuring CBF in PCD. We compared two open-source software applications, CiliarMove (v219) and Cilialyzer (v1.2.1-b3098cb), against the manual count method. We used high-speed videos of nasal ciliary brush samples from PCD RSPH4A-positive (PCD (RSPH4A)) patients and healthy controls. All three methods showed lower median CBF values for patients with PCD (RSPH4A) than in healthy controls. CiliarMove and Cilialyzer identified lower CBF in patients with PCD (RSPH4A), similarly to the manual count. Cilialyzer, CiliarMove, and manual count methods demonstrated statistical significance (p-value < 0.0001) in the difference of median CBF values between patients with PCD (RSPH4A) and healthy controls. Correlation coefficients between the manual count values against both software methods demonstrated positive linear relationships. These findings support the utility of open-source software-based analysis tools. Further studies are needed to validate these findings with other genetic variants and identify the optimal software for accurate CBF measurement in patients with PCD. Full article

Charles Bonnet Syndrome (CBS) is characterized by complex visual hallucinations in individuals with acute vision loss, typically affecting older adults. Most CBS cases are observed in patients with sudden severe visual impairment; however, there are limited reports of CBS occurring in individuals with mild visual deterioration, particularly when confounded by sensory deprivation and social isolation. Here, we report a case of CBS in a female in her early 80s, who experienced vivid visual hallucinations during a period of prolonged social isolation following a hip surgery. Although symptomatology initially presented as delirium and psychosis, the diagnosis of CBS was confirmed after a neuropsychiatric evaluation and ophthalmologic exam, which showed mild deterioration in the patient’s macular degeneration, combined with a social history of reduced independence and increased isolation. The case highlights the lesser-known role of sudden lifestyle changes and reduced cognitive engagement in CBS development in cases of mild visual impairment. It also suggests that cognitive and social stimulation may play a crucial role in CBS management, which has limited reports in the current literature. Full article

Colorectal cancer (CRC) represents a substantial burden on global healthcare, contributing to significant morbidity and mortality worldwide. Despite advances in screening methodologies, its incidence remains high, necessitating continued efforts in early detection and treatment. Neoplastic invasion and metastasis are primary determinants of CRC lethality, emphasizing the urgency of understanding underlying mechanisms to develop effective therapeutic strategies. This study aimed to explore the potential of serum biomarkers in predicting survival outcomes in CRC patients, with a focus on cathepsin B (CB), leukocytic elastase (LE), total sialic acid (TSA), lipid-associated sialic acid (LASA), antitrypsin activity (ATA), C-reactive protein (CRP), and cystatin C (CC). We recruited 185 CRC patients and 35 healthy controls, assessing demographic variables, tumor characteristics, and 7 serum biomarker levels, including (1) CB, (2) LE, (3) TSA, (4) LASA, (5) ATA, (6) CRP, and (7) CC. Statistical analyses included ANOVA with Tukey’s post hoc tests and MANOVA for continuous variables. Student’s t-test was used for dependent samples, while non-parametric tests like Mann–Whitney U and Wilcoxon signed-rank tests were applied for variables deviating from the normal distribution. Categorical variables were assessed using chi-square and Kruskal-Wallis tests. Spearman’s rank correlation coefficient was utilized to examine variable correlations. Survival analysis employed the Kaplan–Meier method with a log-rank test for comparing survival times between groups. Significant associations were observed between CB (p = 0.04), LE (p = 0.01), and TSA (p = 0.008) levels and survival outcomes in CRC patients. Dukes’ classification stages also showed a significant correlation with survival (p = 0.001). However, no significant associations were found for LASA, ATA, CRP, and CC. Multivariate analysis of LE, TSA, and ATA demonstrated a notable correlation with survival (p = 0.041), notwithstanding ATA’s lack of significance in univariate analysis (p = 0.13). CB, LE, and TSA emerged as promising diagnostic markers with prognostic value in CRC, potentially aiding in early diagnosis and treatment planning. Further research is needed to validate these findings and explore additional prognostic indicators. Full article

Knowledge of the precise anatomy and dimensions of the pulp chambers in different teeth allows the odontologist to perform correct diagnosis, as well as treatment planning and monitoring. Clinical practice has introduced cone-beam computed tomography (CB-CT) as a method to evaluate the morphology and dimensions of the pulp chamber. Nevertheless, micro-computed tomography (micro-CT) is regarded as the gold standard in approaching those topics. Here, we have designed an algorithm that takes as input DICOM images from in vivo CB-CT of permanent molars to determine the accuracy of CB-CT for evaluation of pulp chamber volume. The values were compared with those from in vivo CB-CT (rough and expert-manipulated) and ex vivo micro-CT. The relative errors obtained in the volume calculated by the algorithm vs. the volume measured by micro-CT did not exceed 5.7%; additionally, no significant differences were found between algorithm volumes and manipulated CB-CT volumes, while all volumes were different from those obtained with automatic CB-CT software. These data demonstrate that this CB-CT-based volume algorithm may be a reliable technique for evaluation of the pulp chamber volume in permanent molars and can be useful in the diagnosis of pulp diseases, as well as in the planning and monitoring of their treatments. Full article

The gold standard diagnosis of sporotrichosis is the isolation of Sporothrix sp. in culture media, but this is a time-consuming test that is susceptible to contamination and can be affected by the fungal load. Molecular methods such as nested PCR are gaining more ground in the management of several infections as they are tools for the rapid and accurate identification of microorganisms from pure cultures or directly from biological samples. This study aimed to apply a nested PCR molecular protocol for the rapid detection of Sporothrix spp. directly from clinical samples. Thirteen samples—six from skin biopsies, five from skin exudates, and two from conjunctival secretions—were obtained from patients diagnosed with sporotrichosis due to S. brasiliensis. Calmodulin gene sequencing identified all the isolates as S. brasiliensis. Nested PCR was able to detect all the Sporothrix sensu lato directly from clinical samples as well as the CBS 120339 reference strain. The nested PCR protocol stands out as a diagnostic alternative, as it allows the identification of Sporothrix spp. directly from clinical samples without the need for fungal isolation. Full article

Background: Chondroblastoma (CB), a rare benign bone tumor that produces chondrocytes, often develops in the epiphysis or apophysis of children and young adults. The treatment of these rare tumors is complex. The standard treatment protocol involves curettage with local adjuvants and bone graft or cement application. The authors examined 38 CBs to determine risk factors for local recurrence, complications, and functional outcomes following epiphyseal curettage. Methods: Twenty-two girls and sixteen boys aged 10 to 17 years with histologically confirmed chondroblastoma who arrived at our hospital between January 2000 and June 2021 were reviewed retrospectively. Clinical data, radiographic images, histological results, treatment, functional outcomes, and the local recurrence rate were examined—surgical treatment involved total tumor curettage, followed by bone grafting and adjuvant techniques. Local recurrences have also been reported. Results: The most frequently affected site was the proximal femur. Sites of involvement included the proximal femur in 10 (26.3%) cases, the proximal tibia in 8 (20.8%), the humerus in 5 cases (13.2%), the distal tibia in 4 cases (10.5%), the distal femur in 3 cases (7.9%), the supracetabular region in 3 cases (7.9%), the talus in 1 case (2.6%), the calcaneus in 1 case (2.6%), the scapula in 1 case (2.6%), the lumbar spine in 1 case (2.6%), and the iliac bone in 1 (2.6%) patient. The mean follow-up was 144.2 months (24 to 276). The local recurrence rate was 7.9%. The mean Musculoskeletal Tumor Society (MSTS) score was 28.3 points (17 to 30). The mean duration of symptoms at presentation was 5.8 (range, 1 to 28) months. Conclusion: Aggressive curettage and bone grafting resulted in local control and good outcomes in most pediatric patients. In a relatively small proportion of cases, long-term complications and recurrence can occur due to growth plate damage and late diagnosis. In patients admitted to the pediatric clinic with pain, which is often accompanied by localized edema and joint effusion, early detection via advanced radiological scans (X-ray, CT, or MRI) may prevent delays in diagnosis. Full article

(1) Background: Precise diagnosis and early intervention are crucial for toddlers with autism spectrum disorder (ASD) to achieve a better prognosis. This study investigated the efficacy of the Clancy Behavior Scale (CBS) and Modified Checklist for Autism in Toddlers (M-CHAT) in detecting ASD among toddlers under 30 months of age. (2) Methods: A total of 215 toddlers (117 with ASD and 98 with development delays) aged between 18 and 29 months participated in this study. All the primary caregivers of these toddlers were recruited to complete the CBS and M-CHAT. (3) Results: The findings indicated that the accuracy of the CBS and M-CHAT was promising, and the short forms of these two instruments performed better than their full versions. The CBS:9 critical items presented a sensitivity of 0.75 and a specificity of 0.74, while the M-CHAT:14 brief items showed a sensitivity of 0.72 and a specificity of 0.85. (4) Conclusions: The diagnostic accuracy of high-risk ASD toddlers improved via the combination of CBS and M-CHAT, particularly when the information gathered from these two instruments were consistent. The findings may provide implications for enhancing the early detection of ASD. Full article