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Neurological Sciences : Official... Jun 2024Variations in the UBQLN2 gene are associated with a group of diseases with X-linked dominant inheritance and clinical phenotypes of amyotrophic lateral sclerosis (ALS)...
Variations in the UBQLN2 gene are associated with a group of diseases with X-linked dominant inheritance and clinical phenotypes of amyotrophic lateral sclerosis (ALS) and/or frontal temporal lobe dementia (FTD). Cases with UBQLN2 variations have been rarely reported worldwide. The reported cases exhibit strong clinical heterogeneity. Here, we report two adult-onset cases with UBQLN2 variations in Han Chinese. Whole exome sequencing revealed the hemizygous P506S (c.1516C > T) and the heterozygous P509S variation (c.1525C > T), both of which were located within the hotspot mutation region. The patient with the P506S variation was a 24-year-old male. The clinical feature was spastic paraplegia without lower motor neuron damage. The patient's mother was an asymptomatic heterozygote carrier with skewed X-chromosome inactivation. The patient with the P509S variation was a 63-year-old female. Clinical features included ALS and parkinsonism. F-fluorodopa PET-CT revealed presynaptic dopaminergic deficits in bilateral posterior putamen. These cases further highlight the clinical heterogeneity of UBQLN2 cases.
PubMed: 38943019
DOI: 10.1007/s10072-024-07674-7 -
Communications Biology Jun 2024Clear cell renal cell carcinoma (ccRCC) is the most prevalent form of renal cancer, accounting for over 75% of cases. The asymptomatic nature of the disease contributes...
Clear cell renal cell carcinoma (ccRCC) is the most prevalent form of renal cancer, accounting for over 75% of cases. The asymptomatic nature of the disease contributes to late-stage diagnoses and poor survival. Highly vascularized and immune infiltrated microenvironment are prominent features of ccRCC, yet the interplay between vasculature and immune cells, disease progression and response to therapy remains poorly understood. Using droplet-based single-cell RNA sequencing we profile 50,236 transcriptomes from paired tumor and healthy adjacent kidney tissues. Our analysis reveals significant heterogeneity and inter-patient variability of the tumor microenvironment. Notably, we discover a previously uncharacterized vasculature subpopulation associated with epithelial-mesenchymal transition. The cell-cell communication analysis reveals multiple modes of immunosuppressive interactions within the tumor microenvironment, including clinically relevant interactions between tumor vasculature and stromal cells with immune cells. The upregulation of the genes involved in these interactions is associated with worse survival in the TCGA KIRC cohort. Our findings demonstrate the role of tumor vasculature and stromal cell populations in shaping the ccRCC microenvironment and uncover a subpopulation of cells within the tumor vasculature that is associated with an angiogenic phenotype.
Topics: Humans; Carcinoma, Renal Cell; Kidney Neoplasms; Single-Cell Analysis; Tumor Microenvironment; Gene Expression Profiling; Phenotype; Gene Expression Regulation, Neoplastic; Endothelial Cells; Transcriptome; Epithelial-Mesenchymal Transition; Male; Female
PubMed: 38942917
DOI: 10.1038/s42003-024-06478-x -
British Dental Journal Jun 2024Introduction Impacted mandibular third molars can be asymptomatic or cause some pathologies, such as distal caries and odontogenic cysts and tumours. This study...
Introduction Impacted mandibular third molars can be asymptomatic or cause some pathologies, such as distal caries and odontogenic cysts and tumours. This study investigates the prevalence of distal caries of the mandibular second molar adjacent to the mesioangular or horizontally partially erupted mandibular third molar and its relationship regarding decayed, missing and filled teeth (DMFT) risk group, age, side (left-right) and sex.Methods The study included patients who had an appointment for mesioangular or horizontally positioned and partially erupted mandibular third molar surgery. Before the surgery, the DMFT score, age, sex and side were recorded. After extraction, the second molar was clinically examined for distal caries. The prevalence of distal caries and the correlation between the DMFT risk group, age, sex and side were determined.Results The study was conducted on 514 patients and involved 639 teeth. Men and patients in the moderate- or high-risk group are significantly prone to developing distal caries of the second molar. No statistically significant relationship exists regarding age group, side and position.Conclusion Sex and DMFT risk groups affect the prevalence of distal caries in second molars adjacent to the mesioangular or horizontally partially erupted third molars. The prophylactic extraction should be considered in men and patients in the moderate- or high-risk group.
Topics: Humans; Male; Female; Dental Caries; Molar, Third; Cross-Sectional Studies; Risk Factors; Adult; Mandible; Molar; Prevalence; Young Adult; Adolescent; Middle Aged; Tooth, Impacted; DMF Index; Tooth Extraction; Sex Factors
PubMed: 38942867
DOI: 10.1038/s41415-024-7508-3 -
Scientific Reports Jun 2024Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, causes a spectrum of symptoms ranging from mild upper to severe lower...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, causes a spectrum of symptoms ranging from mild upper to severe lower respiratory tract infections. However, the dynamics of nucleocapsid (N) protein antigenemia and RNAemia are not fully understood. We conducted a cohort study involving 117 patients with clinically confirmed COVID-19, focusing on the kinetics of antigenemia and RNAemia and their association with various clinical characteristics. The patients had a median age of 66.0 years (52.0-79.0 years), with a gender distribution of 46.2% male and 53.8% female. Antigenemia reached 100% in fatal cases during the first week after admission. The sensitivity/specificity of antigenemia for diagnosis were 64.7%/73.0% at admission, 69.1%/100% in Week 1, and 66.3%/100% in Week 2. Additionally, the rates of antigenemia in asymptomatic patients were 27.3% upon admission and 22.0% in Week 1, respectively; however, no antigenemia was in samples collected in Week 2. Viral RNAemia was not detected in asymptomatic patients, but RNAemia viral loads were elevated in fatal cases. Kaplan-Meier survival curves demonstrated a higher mortality rate when antigenemia concentrations were elevated in the follow-up samples (P = 0.005). Our study provides a comprehensive analysis of the kinetics of viral N-protein antigenemia and RNAemia according to disease severity and clinical classification. Our findings suggest that highest concentrations of antigenemia in fatal cases occur in the first week after admission, indicating that early elevated antigenemia may serve as a marker of mortality risk.
Topics: Humans; Male; COVID-19; Female; Middle Aged; Aged; SARS-CoV-2; RNA, Viral; Severity of Illness Index; Antigens, Viral; Coronavirus Nucleocapsid Proteins; Cohort Studies; Phosphoproteins
PubMed: 38942808
DOI: 10.1038/s41598-024-65489-0 -
Journal of Vascular Surgery Jun 2024Outcomes for weekend surgical interventions are associated with higher rates of mortality and complications compared to weekday interventions. While prior investigations...
OBJECTIVE
Outcomes for weekend surgical interventions are associated with higher rates of mortality and complications compared to weekday interventions. While prior investigations have reported the 'weekend effect' for carotid endarterectomy (CEA), this association remains unclear for Transcarotid Artery Revascularization (TCAR) and Transfemoral Carotid Artery Stenting (TFCAS). We investigated the weekend effect for all three carotid revascularization methods.
METHODS
We queried the Vascular Quality Initiative (VQI) for patients undergoing CEA, TCAR, and TFCAS between 2016-2022. Chi-square and logistic regression modeling analyzed outcomes including in-hospital stroke, death, MI, and 30-day mortality by weekend vs. weekday intervention. Backward stepwise regression was utilized to identify significant confounding variables and were ultimately included in each final logistic regression model. Logistic regression of outcomes was substratified by symptomatic status. Secondary multivariable analysis compared outcomes between the three revascularization methods by weekend vs. weekday interventions.
RESULTS
155,962 procedures were analyzed including 103,790 CEA, 31,666 TCAR and 20,506 TFCAS. Of these, 1988 CEA, 246 TCAR and 820 TFCAS received weekend interventions. Logistic regression demonstrated no significant differences for TCAR, and increased odds of in-hospital stroke/death/MI for CEA [OR:1.31,(1.04-1.65)] and TFCAS [OR:1.46,(1.09-1.96)] weekend procedures. Asymptomatic TCAR patients had nearly triple the odds of 30-day mortality [OR:2.85,(1.06-7.68), P=0.038]. Similarly, odds of in-hospital death were nearly tripled for asymptomatic CEA [OR:2.89,(1.30-6.43), P=0.009] and asymptomatic TFCAS [OR:2.78,(1.34-5.76), P=0.006] patients. Secondary analysis demonstrated that CEA and TCAR had no significant differences for all outcomes. TFCAS was associated with increased odds of stroke and death compared to CEA and TCAR.
CONCLUSION
In this observational cohort study, we found that weekend carotid revascularization is associated with increased odds of complications and mortality. Furthermore, asymptomatic weekend patients perform worse in the CEA and TFCAS procedural groups. Among the three revascularization methods, TFCAS is associated with the highest odds of perioperative stroke and mortality. As such, our findings suggest that TFCAS procedures should be avoided over the weekend, in favor of CEA or TCAR. In patients who are poor candidates for CEA, TCAR offers the lowest morbidity and mortality for weekend procedures.
PubMed: 38942398
DOI: 10.1016/j.jvs.2024.06.163 -
Journal of Forensic and Legal Medicine Jun 2024Pheochromocytoma is a neuroendocrine tumor that secretes catecholamines; excessive catecholamine secretion can lead to pheochromocytoma crisis (PCC), a rare and...
Pheochromocytoma is a neuroendocrine tumor that secretes catecholamines; excessive catecholamine secretion can lead to pheochromocytoma crisis (PCC), a rare and life-threatening condition. Sibutramine, a serotonin and norepinephrine reuptake inhibitor, was previously used for obesity treatment but is now banned due to its cardiovascular side effects. Although fatalities related to PCC and adverse events associated with sibutramine have been frequently reported individually, there is no documented literature addressing PCC-induced by sibutramine. Here we report a rare case of fatal sibutramine-induced PCC in a previously asymptomatic young female with undiagnosed pheochromocytoma. The 25-year-old patient took a weight-loss pill containing sibutramine for the first time and subsequently experienced nausea, vomiting, chest tightness, and other symptoms. She went to hospital about 6 hours after taking the pill but died approximately 4 hours later despite the resuscitation efforts. An autopsy revealed a pheochromocytoma in the right adrenal gland. The cause of death was attributed to sibutramine-induced PCC. To our knowledge, this is the first report to document the occurrence of sibutramine-induced PCC.
PubMed: 38941912
DOI: 10.1016/j.jflm.2024.102711 -
Bioprocess and Biosystems Engineering Jun 2024The most prevalent form of inflammatory bowel disease (IBD), ulcerative colitis (UC), is characterized by persistent inflammation of the colorectal mucosa. It is...
The most prevalent form of inflammatory bowel disease (IBD), ulcerative colitis (UC), is characterized by persistent inflammation of the colorectal mucosa. It is asymptomatic, whereas Crohn's disease (CD) causes patchy lesions in the gastrointestinal tract. Men and women suffer equally from ulcerative colitis, which usually strikes in the second and third decades of life and becomes more common in senior citizens. In the present study, we produced zinc oxide nanoparticles using the natural herbal plant, Cassia alata. Zinc oxide nanoparticles have remarkable antimicrobial and antitumor benefits in the field of biomedical science. Furthermore, the synthesized zinc oxide nanoparticles (ZnO NPs) were characterized using UV, XRD, FTIR, and SEM analyses. The XRD analysis confirmed the crystallite nature and purity of the synthesized nanoparticles. Zinc oxide nanoparticles with a uniform size and partially agglomerated morphology were verified by SEM analysis. We investigated the protective effects of environmentally friendly zinc oxide nanoparticles in dextran sodium sulfate-induced ulcerative colitis mouse models. Green synthesized Cassia alata zinc oxide nanoparticles (CA ZnO NPs) reversed weight loss, disease activity index, colon shortening, and colon histological damage. Zinc oxide nanoparticles reduce hypersensitivity, oxidative stress, and inflammation, and protect the mucosal layer. Green synthesized CA ZnO NPs demonstrated protection against dextran sodium sulfate-induced ulcerative colitis via anti-inflammatory activity.
PubMed: 38942827
DOI: 10.1007/s00449-024-03047-8 -
Journal of Neurosurgery. Pediatrics Jun 2024An association between blunt head trauma and cerebral venous sinus thrombosis (CVST) has been recognized, but its symptoms are nonspecific and the duration of symptoms...
OBJECTIVE
An association between blunt head trauma and cerebral venous sinus thrombosis (CVST) has been recognized, but its symptoms are nonspecific and the duration of symptoms remains unclear. Anticoagulation therapy is not considered necessary in most cases of traumatic CVST; however, this is controversial. The aim of this study was to describe the clinical characteristics and outcomes of children with CVST after isolated head trauma.
METHODS
The records of pediatric patients with isolated head trauma admitted for observation at 3 medical centers between January 2018 and May 2023 were reviewed retrospectively. CVST was diagnosed on MR venography (MRV). Clinical presentation, therapeutic management, and outcomes were evaluated in patients who had follow-up MRV.
RESULTS
Of 260 pediatric patients with head trauma admitted to the 3 hospitals, 26 patients underwent MRV and 8 (30.8%) were diagnosed with CVST. One patient was treated with heparin, while the others received conservative treatment. All patients were discharged home asymptomatic. MRV performed during follow-up displayed complete recanalization in all cases, except for 1 case with partial recanalization. The median hospital stay was longer in patients with CVST than in those without CVST (9.5 vs 3.0 days, p = 0.001).
CONCLUSIONS
The length of stay of pediatric patients with traumatic CVST was prolonged compared with those without CVST, but most patients had good outcomes with spontaneous recanalization following conservative treatment.
PubMed: 38941650
DOI: 10.3171/2024.4.PEDS24109 -
Head and Neck Pathology Jun 2024Myoepithelioma is a benign salivary gland tumor. Central myoepitheliomas are very rare. The aim of this report was to describe a case of maxillary myoepithelioma. A...
Myoepithelioma is a benign salivary gland tumor. Central myoepitheliomas are very rare. The aim of this report was to describe a case of maxillary myoepithelioma. A 14-year-old female patient presented with an multilocular lesion in the anterior maxilla, with nearly 8 months of duration. The lesion was asymptomatic, and the patient's dental history was unremarkable. The diagnostic hypothesis was an odontogenic tumor. Biopsy specimen consisted of nests of plasmacytoid cells in a myxoid stroma without duct formation. No cellular atypia or bone and cartilage formation were noted. The neoplastic cells were positive for Pan-cytokeratin, S100, CK7, and CK8. The final diagnosis was myoepithelioma. The patient was treated by surgical excision followed by bone curettage, and no signs of recurrence were found after 8 years of treatment.
Topics: Humans; Female; Myoepithelioma; Adolescent; Maxillary Neoplasms; Biomarkers, Tumor
PubMed: 38940938
DOI: 10.1007/s12105-024-01665-y -
Medical & Biological Engineering &... Jun 2024The prevalence of epidemics has been studied by researchers in various fields. In the last 2 years, the outbreak of COVID-19 has affected the health, economy, and...
The prevalence of epidemics has been studied by researchers in various fields. In the last 2 years, the outbreak of COVID-19 has affected the health, economy, and industry of communities around the world and has caused the death of millions of people. Therefore, many researchers have tried to model and control the prevalence of this disease. In this article, the new SQEIAR model for the spread of the COVID-19 disease is provided, which, compared to previous models, explores the effects of additional interventions on the outbreak and incorporates a wider range of variables and parameters to enhance its accuracy and alignment with reality. These modifications in the model lead to a more rapid eradication and control of the disease. This model includes six variables of the group of susceptible, quarantined, exposed, symptomatic, asymptomatic, and recovered individuals and includes three control inputs such as quarantine of susceptible, vaccination, and treatments. In order to minimize symptomatic infectious individuals and susceptible individuals and also to reduce treatment, vaccination, and quarantine costs, an optimal control approach using the Deep Deterministic Policy Gradient (DDPG) method has been applied to the system. This algorithm is applied to the model in different cases of control inputs, and for each case, optimal control inputs are obtained. In the following, the number of deaths due to the disease and the total number of symptomatic infectious individuals for each of these optimal control cases has been calculated. The results of the implemented control structure demonstrated a reduction of 60% in the number of deaths and 74% in the number of symptomatically infected individuals compared to the uncontrolled model. Finally, to test the performance of the control system, noise was applied to the system in various ways, including three methods: applying noise to observer variables, applying noise to control inputs, and applying uncertainty to model parameters. Therefore, we found that this control system was robust and performed well in different conditions despite the disturbance.
PubMed: 38940880
DOI: 10.1007/s11517-024-03153-5