The Notch-PDGFRß axis suppresses brown adipocyte progenitor differentiation in early post-natal mice.

De novo brown adipogenesis holds potential in combating the epidemics of obesity and diabetes. However, the identity of brown adipocyte progenitor cells (APCs) and their regulation have not been extensively explored. Here, through in vivo lineage tracing and mouse modeling, we observed that platelet-derived growth factor receptor beta (PDGFRß)+ pericytes give rise to developmental brown adipocytes but not to those in adult homeostasis. By contrast, T-box 18 (TBX18)+ pericytes contribute to brown adipogenesis throughout both developmental and adult stages, though in a depot-specific manner. Mechanistically, Notch inhibition in PDGFRß+ pericytes promotes brown adipogenesis by downregulating PDGFRß. Furthermore, inhibition of Notch signaling in PDGFRß+ pericytes mitigates high-fat, high-sucrose (HFHS)-induced glucose and metabolic impairment in mice during their development and juvenile phases. Collectively, these findings show that the Notch/PDGFRß axis negatively regulates developmental brown adipogenesis, and its repression promotes brown adipose tissue expansion and improves metabolic health.

Structures and Biological Activities of Secondary Metabolites from Xylaria spp.

The fungus genus Xylaria is an important source of drug discoveries in scientific fields and in the pharmaceutical industry due to its potential to produce a variety of structured novel and bioactive secondary metabolites. This review prioritizes the structures of the secondary metabolites of Xylaria spp. from 1994 to January 2024 and their relevant biological activities. A total of 445 new compounds, including terpenoids, nitrogen-containing compounds, polyketides, lactones, and other classes, are presented in this review. Remarkably, among these compounds, 177 compounds show various biological activities, including cytotoxic, antimicrobial, anti-inflammatory, antifungal, immunosuppressive, and enzyme-inhibitory activities. This paper will guide further investigations into the structures of novel and potent active natural products derived from Xylaria and their potential contributions to the future development of new natural drug products in the agricultural and medicinal fields.

Correlation between symptoms and cognitive function changes in patients with primary insomnia and pathways in gut microbiota.

Background: Primary insomnia (PI) refers to syndromes of difficulty falling asleep, poor sleep quality, early awakening, and difficulty falling asleep after waking up. Although there have been numerous studies, the specific etiology and pathogenesis of PI are still misunderstanding. In recent years, the gut microbiota has been proved to be involved in the metabolism of many mental disorders. But the specific mechanisms of its involvement in PI have not been fully elucidated. This study aims to explore the relationship between the gut microbiota and the symptoms, cognitive function changes in PI. Methods: In this study, the gut microbiota of PI patients and healthy controls was profiled by performing stool 16s rRNA gene sequencing. The co-occurrence network was constructed by using Weight Gene Co-expression Network Analysis (WGCNA) algorithm. The correlation between gut microbiota associated pathways and traits in PI were predicted. Results: WGCNA results demonstrated several Operational Taxonomic Units (OTU) modules are correlated to symptoms. By using PICRUSt2 software, we predicted the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of microbiota in modules. For instance, sleep efficiency may be correlated with the presence of Insulin signaling pathway, Flavonoid biosynthesis, Ascorbate and aldarate metabolism, Nitrotoluene degradation, Biotin metabolism, RNA polymerase and Chlorocyclohexane and chlorobenzene degradation. Total sleep time may be correlated with the presence of Tyrosine metabolism, Propanoate metabolism, Carbon fixation pathways in prokaryotes, Carotenoid biosynthesis, Systemic lupus erythematosus, Nitrotoluene degradation and Biosynthesis of unsaturated fatty acids. The severity of insomnia may be correlated with Insulin signaling pathway, Flavonoid biosynthesis, Ascorbate and aldarate metabolism, Nitrotoluene degradation, Biotin metabolism and RNA polymerase. Change of name score in Montreal Cognitive Assessment (MoCA) may be correlated with Tyrosine metabolism, Propanoate metabolism, Carbon fixation pathways in prokaryotes, Carotenoid biosynthesis, Systemic lupus erythematosus, Nitrotoluene degradation, Biosynthesis of unsaturated fatty acids, Apoptosis, Steroid hormone biosynthesis, Geraniol degradation, Protein digestion and absorption and Bisphenol degradation in Gut Microbiota (GM). Conclusion: This study revealed the potential relationships between gut microbiota and PI. By using pathway prediction and enrichment analysis, we concluded many metabolic pathways may associated with some important traits of insomnia patients, including sleep efficiency, severe insomnia, total sleep time and change of name score in MoCA. The metabolic pathways include Insulin signaling pathway, Flavonoid biosynthesis, Ascorbate and aldarate metabolism, Nitrotoluene degradation, Biotin metabolism, RNA polymerase and Chlorocyclohexane, chlorobenzene degradation, Tyrosine metabolism, Propanoate metabolism, Carbon fixation pathways in prokaryotes, Carotenoid biosynthesis, Systemic lupus erythematosus, Biosynthesis of unsaturated fatty acids, Apoptosis, Steroid hormone biosynthesis, Geraniol degradation, Protein digestion and absorption and Bisphenol degradation.Our study demonstrated that PI patients demonstrate significant changes in gut microbiota, which will help delineate the relationship between gut microbiota and syndromes of PI.

The clinical outcome of COVID-19 is strongly associated with microbiome dynamics in the upper respiratory tract.

OBJECTIVES: The respiratory tract is the portal of entry for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although a variety of respiratory pathogens other than SARS-CoV-2 have been associated with severe cases of COVID-19 disease, the dynamics of the upper respiratory microbiota during disease the course of disease, and how they impact disease manifestation, remain uncertain. METHODS: We collected 349 longitudinal upper respiratory samples from a cohort of 65 COVID-19 patients (cohort 1), 28 samples from 28 recovered COVID-19 patients (cohort 2), and 59 samples from 59 healthy controls (cohort 3). All COVID-19 patients originated from the earliest stage of the epidemic in Wuhan. Based on a modified clinical scale, the disease course was divided into five clinical disease phases (pseudotimes): "Healthy" (pseudotime 0), "Incremental" (pseudotime 1), "Critical" (pseudotime 2), "Complicated" (pseudotime 3), "Convalescent" (pseudotime 4), and "Long-term follow-up" (pseudotime 5). Using meta-transcriptomics, we investigated the features and dynamics of transcriptionally active microbes in the upper respiratory tract (URT) over the course of COVID-19 disease, as well as its association with disease progression and clinical outcomes. RESULTS: Our results revealed that the URT microbiome exhibits substantial heterogeneity during disease course. Two clusters of microbial communities characterized by low alpha diversity and enrichment for multiple pathogens or potential pathobionts (including Acinetobacter and Candida) were associated with disease progression and a worse clinical outcome. We also identified a series of microbial indicators that classified disease progression into more severe stages. Longitudinal analysis revealed that although the microbiome exhibited complex and changing patterns during COVID-19, a restoration of URT microbiomes from early dysbiosis toward more diverse status in later disease stages was observed in most patients. In addition, a group of potential pathobionts were strongly associated with the concentration of inflammatory indicators and mortality. CONCLUSION: This study revealed strong links between URT microbiome dynamics and disease progression and clinical outcomes in COVID-19, implying that the treatment of severe disease should consider the full spectrum of microbial pathogens present.

Diabetes distress as mediators of loneliness and health promotion behaviour: a cross-sectional study.

OBJECTIVES: The purpose of this study was to explore whether diabetes distress mediated the relationship between loneliness and health promotion in older adults with diabetes. DESIGN: A cross-sectional study. SETTING: The study was conducted at three tertiary hospitals in Changsha, Hunan Province, China. PARTICIPANTS: The sample included 140 patients with diabetes (65 years and older, mean age 72.6 years, SD=4.6). METHODS: We employed path models to analyse data on diabetes distress, loneliness and health promotion behaviours. We collected diabetes distress, loneliness and health promotion behaviour with self-reported questionnaires including the Diabetes Distress Scale, the University of California at Los Angeles (UCLA) Loneliness Scale and the Elderly Health Promotion Scale from January 2022 to October 2022. Mediation analysis was performed by SPSS V.26.0's PROCESS macro. RESULT: The findings of this study indicated diabetes distress acted as a mediator between loneliness and health promotion behaviour. According to bootstrapping results, the total effect of loneliness on health promotion behaviour was significantly negative (ß=-0.312, p=0.006). Loneliness significantly and negatively correlated with diabetes distress (ß=-0.043, p<0.001), while diabetes distress significantly and negatively correlated with health promotion behaviours (ß=-2.724, p=0.008). Both the indirect effect and the direct effect of loneliness on health promotion behaviour were significant. CONCLUSION: Our study illustrated that loneliness was negatively associated with health promotion behaviours, and diabetes distress acted as a mediator in this relationship. It is suggested that healthcare providers should prioritise the identification and management of diabetes distress in older patients with diabetes who experience loneliness to improve health promotion behaviours and optimise disease management outcomes.

The role of the symbiotic microecosystem in cancer: gut microbiota, metabolome, and host immunome.

The gut microbiota is not just a simple nutritional symbiosis that parasitizes the host; it is a complex and dynamic ecosystem that coevolves actively with the host and is involved in a variety of biological activities such as circadian rhythm regulation, energy metabolism, and immune response. The development of the immune system and immunological functions are significantly influenced by the interaction between the host and the microbiota. The interactions between gut microbiota and cancer are of a complex nature. The critical role that the gut microbiota plays in tumor occurrence, progression, and treatment is not clear despite the already done research. The development of precision medicine and cancer immunotherapy further emphasizes the importance and significance of the question of how the microbiota takes part in cancer development, progression, and treatment. This review summarizes recent literature on the relationship between the gut microbiome and cancer immunology. The findings suggest the existence of a "symbiotic microecosystem" formed by gut microbiota, metabolome, and host immunome that is fundamental for the pathogenesis analysis and the development of therapeutic strategies for cancer.

Hippocampal subfield volumes in mild cognitive impairment and alzheimer's disease: a systematic review and meta-analysis.

The hippocampus is a complex structure that consists of several subfields with distinct and specialized functions. Although numerous studies have been performed to explore hippocampal atrophy at the sub-regional level in mild cognitive impairment (MCI) and Alzheimer's disease (AD), the results have been inconsistent especially for whether and which subfields can be served as the most potential biomarkers in MCI and AD. Herein, we used a meta-analytic approach to synthesize the extant literatures on hippocampal subfields in MCI and AD through PubMed, Web of Science, and Embase (PROSPERO CRD42021257586). As a result, a total of twenty studies using Freesurfer 5 and Freesurfer 6 were included in this investigation. These studies revealed that at the sub-regional level, hippocampal subfield volume reductions in MCI and AD were not restricted to specific subfields, and subiculum and presubiculum had the largest z-scores across most comparisons. However, none of the subfield performed much better in discriminating MCI and HC, AD and MCI, AD and HC as compared to whole hippocampus volume. These results suggested that we should explore the changes in the hippocampal subfields in subtypes of MCI or even at an earlier stage, that is subjective cognitive impairment.

Mechanism of action of buckwheat quercetin in regulating lipid metabolism and intestinal flora via Toll-like receptor 4 or nuclear factor κB pathway in rats on a high-fat diet.

OBJECTIVES: Buckwheat quercetin (QUE) was used as a dietary supplement to investigate the mechanism of QUE on the regulation of lipid metabolism and intestinal flora in hyperlipidemic rats. METHODS: Here, using a high-fat diet-induced hyperlipidemia model, the intervention was carried out by gavage of QUE at doses of 50, 100, and 200 mg/kg. Serum lipid levels, liver biochemical parameters, and histopathologic changes in the liver and intestinal microorganisms were measured in rats by enzyme-linked immunosorbent assay, hematoxylin-eosin, and high-throughput sequencing, respectively. RESULTS: Our results found that QUE, at a dose of 200 mg/kg, significantly reduced body weight, liver index, and lipid levels in rats (P < 0.05); improved hepatic oxidative stress; and repaired liver injury. In addition, the upregulation of beneficial bacteria, such as christensenellaceae and Bifidobacterium, in the organism increased the content of short-chain fatty acids, thus interfering with intestinal pH and improving the intestinal environment, while downregulating the relative abundance of Proteobacteria and Eubacterium_coprostanoligenes_group, and regulating the overproduction of butyrate. The real-time fluorescence quantitative polymerase chain reaction results found that QUE inhibited the expression of Toll-like receptor 4 (TLR4) and nuclear factor κB (NF-κB) mRNA content and blocked the activation of the TLR4/NF-κB signaling pathway, thus affecting the downregulation of lipid levels and restoring intestinal homeostasis. CONCLUSIONS: A QUE dose of 200 mg/kg may improve lipid levels and the composition of intestinal flora through the TLR4/NF-κB pathway, suggesting that proteobacteria and christensenellaceae abundance changes may be biomarkers of potential diseases.

Analysis of Lung Microbiome in COVID-19 Patients during Time of Hospitalization.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the pathogenic agent of the rapidly spreading pneumonia called coronavirus disease 2019 (COVID-19), primarily infects the respiratory and digestive tract. Several studies have indicated the alterations of the bacterial microbiome in the lower respiratory tract during viral infection. However, both bacterial and fungal microbiota in the lung of COVID-19 patients remained to be explored. METHODS: In this study, we conducted nanopore sequencing analyses of the lower respiratory tract samples from 38 COVID-19 patients and 26 non-COVID-19 pneumonia controls. Both bacterial and fungal microbiome diversities and microbiota abundances in the lung were compared. RESULTS: Our results revealed significant differences in lung microbiome between COVID-19 patients and non-COVID-19 controls, which were strongly associated with SARS-CoV-2 infection and clinical status. COVID-19 patients exhibited a notably higher abundance of opportunistic pathogens, particularly Acinetobacter baumannii and Candida spp. Furthermore, the potential pathogens enriched in COVID-19 patients were positively correlated with inflammation indicators. CONCLUSIONS: Our study highlights the differences in lung microbiome diversity and composition between COVID-19 patients and non-COVID-19 patients. This may contribute to predicting co-pathogens and selecting optimal treatments for respiratory infections caused by SARS-CoV-2.

Macrophage metabolic reprogramming and atherosclerotic plaque microenvironment: Fostering each other?

Macrophages are the central immune cells in atherosclerosis (AS) and play a critical role in the initiation, progression and invasion of atherosclerotic plaques. Metabolic reprogramming is a crucial feature that determines macrophage function and is driven by a combination of intrinsic alterations in macrophages and extrinsic factors such as cytokines acting in the plaque microenvironment. Intrinsic macrophage mechanisms activate signal transduction pathways that change metabolic enzyme activity, and the expression of metabolic regulators. Extrinsic signalling mechanisms involve lipids and cytokines in the microenvironment, promoting and amplifying macrophage metabolic reprogramming. This review describes the intrinsic and extrinsic mechanisms driving macrophage metabolic reprogramming in the AS microenvironment and the interplay of these metabolic rewires in the microenvironment. Moreover, we discuss whether targeting these different pathways to treat macrophage microenvironmental changes can alter the fate of the vulnerable plaques.

[Advances in genomics of multi-drug resistant Stenotrophomonas].

Stenotrophomonas species are non-fermentative Gram-negative bacteria that are widely distributed in environment and are highly resistant to numerous antibiotics. Thus, Stenotrophomonas serves as a reservoir of genes encoding antimicrobial resistance (AMR). The detection rate of Stenotrophomonas is rapidly increasing alongside their strengthening intrinsic ability to tolerate a variety of clinical antibiotics. This review illustrated the current genomics advances of antibiotic resistant Stenotrophomonas, highlighting the importance of precise identification and sequence editing. In addition, AMR diversity and transferability have been assessed by the developed bioinformatics tools. However, the working models of AMR in Stenotrophomonas are cryptic and urgently required to be determined. Comparative genomics is envisioned to facilitate the prevention and control of AMR, as well as to gain insights into bacterial adaptability and drug development.

Posterior reversible encephalopathy syndrome triggered by FLOT (5-fluorouracil, oxaliplatin, docetaxel, and calcium levofolinate) chemotherapy and thrombocytopenia (docetaxel and cisplatin) chemotherapy.

INTRODUCTION: Posterior reversible encephalopathy syndrome is a clinical and imaging syndrome characterized by endothelial dysfunction, blood-brain barrier disruption, and vasogenic edema. The common clinical symptoms of posterior reversible encephalopathy syndrome include headache, altered consciousness, visual disturbances, and seizures, among which headache and seizures are the most common. The classic imaging patterns usually reveal vasogenic edema. CASE REPORT: We describe the case of a middle-aged woman with gastric cancer. She was under treatment by fluorouracil, leucovorin, oxaliplatin, and docetaxel regimen and thrombocytopenia regimen after tumor progression, but developed unconsciousness, irritability, and headache shortly after initiation of treatment. Her magnetic resonance imaging in our hospital shows abnormal signals in bilateral frontal parietal occipital lobes with hyperintensities on T2-weighted magnetic resonance imaging and fluid-attenuated inversion recovery imaging, accompanied by the increased value of apparent diffusion coefficient. And T1-weighted images illustrate hypointense foci, with increased diffusion-weighted imaging signals. MANAGEMENT AND OUTCOME: After admission, she was treated to control blood pressure, reduce brain edema, expand blood vessels, improve consciousness, and symptomatic support treatment. 3 days after the onset of the disease, her headache symptoms and state of consciousness gradually improved, and her blood pressure can be controlled at about 130/80 mmHg. DISCUSSION: This is the first report that posterior reversible encephalopathy syndrome is caused by a thrombocytopenia regimen, and our case highlights the pathogenic role of a thrombocytopenia regimen in posterior reversible encephalopathy syndrome. However, the association between the thrombocytopenia regimen and previous fluorouracil, leucovorin, oxaliplatin, and docetaxel regimens needs further study.

Analysis of Risky Riding Behavior Characteristics of the Related Road Traffic Injuries of Electric Bicycle Riders.

Electric bicycle (EB) riders, being vulnerable road users (VRUs), are increasingly becoming victims of road traffic injuries (RTIs). This study aimed to determine the current status and epidemiological characteristics of RTIs among EB riders through a questionnaire survey and roadside observations in Shantou to provide a scientific basis for the prevention and control of electric bicycle road traffic injuries (ERTIs). A total of 2412 EB riders were surveyed, and 34,554 cyclists were observed in the study. To analyze the relationship between riding habits and injuries among EB riders, chi-square tests and multi-factor logistic regression models were employed. The findings reveal that the prevalence of ERTIs in Shantou was 4.81%, and the most affected group was children under 16 years old, accounting for 9.84%. Risky behavior was widespread among EB riders, such as the infrequent wearing of safety helmets, carrying people on EBs, riding on sidewalks, and listening to music with headphones while bicycling. Notably, over 90% of those who wore headphones while bicycling engaged in this risky behavior. The logistic regression analysis showed that honking the horn (odds ratio (OR): 2.009, 95% CI: 1.245-3.240), riding in reverse (OR: 4.210, 95% CI: 2.631-6.737), and continuing to ride after a fault was detected (OR: 2.010, 95% CI: 1.188-3.402) all significantly increased the risk of ERTIs (all p < 0.05). Risky riding behavior was significantly less observed at traffic intersections with traffic officers than at those without (all p < 0.001).

Encapsulation of Paraffin Phase-Change Materials within Monolithic MTMS-Based Silica Aerogels.

To address the leakage issue of paraffin phase-change materials in thermal management, a monolithic MTMS-based silica aerogel (MSA) is employed to encapsulate paraffin through a facile impregnation process. We find that the paraffin and MSA form a physical combination, with little interaction occurring between them. The prepared no-leakage paraffin/MSA composites have a density of 0.70 g/cm3 and exhibit good mechanical properties and nice hydrophobicity, with a contact angle of 122°. Furthermore, the average latent heat of the paraffin/MSA composites is found to reach up to 209.3 J/g, about 85% of the pure paraffin's latent heat, which is significantly larger than other paraffin/silica aerogel phase-change composite materials. The thermal conductivity of the paraffin/MSA remains almost the same as that of the pure paraffin (~250 mW/m/K), without any heat transfer interference from the MSA skeletons. All these results indicate that MSA can effectively serve as a carrier material for encapsulating paraffin, which is beneficial for expanding the applications of MSAs in thermal management and energy storage.

A Cross-Sectional Survey of Different Types of School Bullying before and during COVID-19 in Shantou City, China.

BACKGROUND: Since the end of 2019, the COVID-19 pandemic has had serious wide-ranging effects on academic, occupational and other daily activities. Like other types of institutions, schools are facing unprecedented challenges. Students may face a variety of adverse consequences, including sleep disturbances and school bullying, if they are unable to adjust to the current learning and living environment. This study explored the effects of the COVID-19 pandemic on school bullying. METHODS: A total of 5782 middle school students were enrolled in this multi-stage, cross-sectional study (3071 before and 2711 during the pandemic). The pre-pandemic group had a mean age of 14.9 ± 1.73, the pandemic group of 14.75 ± 1.47. Three models were set up using binary logistic regression to adjust for confounding variables (gender, school type, alcohol consumption, smoking, playing violent video games). RESULTS: All types of bullying victimization and perpetration (physical, verbal, social and property bullying) were more common during the pandemic than before the pandemic. In terms of bullying victimization, property bullying victimization (crude odds ratio [OR]: 2.398, 95% CI: 2.014-2.854, p < 0.001; model 2 adjusted OR: 2.344, 95% CI: 1.966-2.795, p < 0.001; model 3 adjusted OR: 2.818, 95% CI: 2.292-3.464, p < 0.001) increased the most. In terms of bullying perpetration, verbal bullying perpetration (crude OR: 3.007, 95% CI: 2.448-3.693, p <0.001; model 2 adjusted OR: 2.954, 95% CI: 2.399-3.637, p < 0.001; model 3 adjusted OR:3.345, 95% CI: 2.703-4.139, p < 0.001) increased the most. CONCLUSION: This study corroborate the significance of the pandemic on traditional school bullying and suggests that we should further consider other types of bullying and establish and improve the response and prevention mechanisms during public health emergencies such as the COVID-19 pandemic.

Effect of Coal Mining on Soil Microorganisms from Stipa krylovii Rhizosphere in Typical Grassland.

The environmental changes caused by coal mining activities caused disturbances to the plant, soil, and microbial health in the mining area. Arbuscular mycorrhizal fungi (AMF) play an important role in the ecological restoration of mining areas. However, it is less understood how soil fungal communities with multiple functional groups respond to coal mining, and the quantitative impact and risk of mining disturbance. Therefore, in this study, the effect of coal mining on soil microorganisms' composition and diversity were analyzed near the edge of an opencast coal-mine dump in the Shengli mining area, Xilingol League, Inner Mongolia. The response strategy of soil fungi to coal mining and the stability of arbuscular mycorrhizal fungi (AMF) in the soil fungal community were determined. Our results showed that coal mining affected AMF and soil fungi in areas within 900 m from the coal mine. The abundance of endophytes increased with the distance between sampling sites and the mine dump, whereas the abundance of saprotroph decreased with the distance between sampling sites and the mine dump. Saprotroph was the dominant functional flora near the mining area. The nodes percentage of Septoglomus and Claroideoglomus and AMF phylogenetic diversity near the mining area were highest. AMF responded to the mining disturbance via the variety and evolution strategy of flora. Furthermore, AMF and soil fungal communities were significantly correlated with edaphic properties and parameters. Soil available phosphorus (AP) was the main influencer of soil AMF and fungal communities. These findings evaluated the risk range of coal mining on AMF and soil fungal communities and elucidated the microbial response strategy to mining disturbance.

Near-atomic, non-icosahedrally averaged structure of giant virus Paramecium bursaria chlorella virus 1.

Giant viruses are a large group of viruses that infect many eukaryotes. Although components that do not obey the overall icosahedral symmetry of their capsids have been observed and found to play critical roles in the viral life cycles, identities and high-resolution structures of these components remain unknown. Here, by determining a near-atomic-resolution, five-fold averaged structure of Paramecium bursaria chlorella virus 1, we unexpectedly found the viral capsid possesses up to five major capsid protein variants and a penton protein variant. These variants create varied capsid microenvironments for the associations of fibers, a vesicle, and previously unresolved minor capsid proteins. Our structure reveals the identities and atomic models of the capsid components that do not obey the overall icosahedral symmetry and leads to a model for how these components are assembled and initiate capsid assembly, and this model might be applicable to many other giant viruses.

Short-term Montreal Cognitive Assessment predicts functional outcome after endovascular therapy.

Background: The previous studies have shown that cognition in patients 4-8 weeks after stroke can predict early functional outcomes after stroke. The analyses of data from the REVASCAT trial proved that stent thrombectomy improves post-morbid wiring test outcomes in patients with AIS compared with drug therapy. However, few studies focus on the relationship between cognitive impairment and functional outcomes in patients undergoing endovascular treatment. Methods: A total of 647 participants registered from stroke centers. Stroke severity was evaluated by National Institutes of Health stroke scale (NIHSS). The functional status was estimated by modified Rankin scale (mRS). The cognitive impairment was assessed by trained neurologists at 14 (±4) and 90 (±7) days after stroke onset using the Montreal Cognitive Assessment (MoCA). A MoCA score of less than 26 was considered post-stroke cognitive impairment (PSCI). Results: A total of 120 Patients who underwent endovascular therapy were included. The PSCI group had higher levels of age, men, educational status, atrial fibrillation, smoking, alcoholism, Alberta Stroke Program Early CT (ASPECT) score of the anterior circulation, and OTP time than the non-PSCI group (p < 0.05). In contrast, the 14-day MoCA score, 14-day NIHSS score, 3-month MoCA score, 3-month NIHSS score, 3-month mRS score, and 3-month EQ5D score were lower in those PSCI patients. The risk predictors of PSCI were age, sex, educational level, atrial fibrillation, smoking, alcoholism, ASPECT Score (anterior circulation), 14-day MoCA score, and 14-day NIHSS score. There were strong relationships between 3-month NIHSS and MoCA (r = -0.483, p < 0.001). Receiver operating characteristic (ROC) curve indicated that 14-day MoCA score, memory, abstraction, visuospatial/executive functions, attention, and language, played a significant role to predict PSCI [area under the curve (AUC) > 0.7]. It had predictive value for the 14-day visuospatial/executive functions to predict 3-month functional outcomes. Conclusion: Early application of the MoCA in different cognitive regions could predict the PSCI and future functional outcomes, which is necessary to screen high-risk patients with poor prognosis and conduct an early intervention.

Research progress in the early diagnosis of Parkinson's disease.

Parkinson's disease is the second major neurodegenerative disease with increasing incidence and population in the world year by year. The pathogenesis of Parkinson's disease is still not completely clear, and the identification of Parkinson's disease prodromal manifestations and accurate diagnosis is still facing great challenges. This review summarizes the interaction of environmental toxicants, mitochondrial dysfunction, α-synuclein, gut microbiome dysbiosis, neuroinflammation, and other pathophysiological factors in Parkinson's disease. It also discusses the prodromal manifestations of Parkinson's disease, such as olfactory dysfunction, sleep dysfunction and other non-motor symptoms, the current diagnostic challenges, and the application status of emerging neuroimaging technologies such as magnetic resonance imaging (MRI), positron emission tomography (PET), and single-photon emission tomography (SPECT).

Evaluation of Patients with Vaccine Allergies Prior to mRNA-Based COVID-19 Vaccination.

During the initial rollout of coronavirus disease 2019 (COVID-19) vaccination in Singapore, the Ministry of Health (MOH) issued a recommendation that patients with a history of any previous vaccine allergy be referred to an allergist for further review of their suitability to proceed with mRNA-based COVID-19 vaccines. Patients fulfilling the above criterion were divided into three groups: immediate reaction (Group A), delayed reaction (Group B) and no/irrelevant reaction (Group C). They were subjected to either a skin prick test (SPT) and intradermal test (IDT) with polyethylene glycol (PEG) or polysorbate-containing products; direct injection with the Pfizer BNT162b2 vaccine in the allergy clinic; or injection at community vaccination centres, respectively. Groups A and B were also invited to complete a questionnaire survey on post-vaccination reactions, and blood sampling pre-vaccination and 1 h after the first dose of the BNT162b2 vaccine to measure immunoglobulin (Ig) G, IgM and IgE antibodies to the Pfizer BNT162b2 vaccine via ELISA assays immobilised with the BNT162b2 vaccine, as well as levels of allergic cytokines interleukin (IL)-4 and IL-33, complement C5a and the endothelial activation marker intercellular adhesion molecule-1 (ICAM-1). Groups A and B comprised 62 (20.5%) patients each. In Group A, two subjects (3.2%) with equivocal IDT results tolerated both doses of the BNT162b2 vaccine without major allergic reactions. The remaining 60 (96.8%) in Group A and 62 (100%) in Group B completed both doses of BNT162b2 vaccination without major adverse reactions. Among the 99 who completed the questionnaire survey, 13 (13%) patients reported mild allergic reactions after the first dose of the vaccine. Immunoglobulin (Ig) G and M antibodies, but not IgE antibodies to the Pfizer BNT162b2 vaccine were detected in 67 subjects prior to vaccination. The presence of anti-Pfizer BNT162b2 IgG and IgM prior to vaccination did not result in major allergic reactions nor increases in Th2-related cytokines (IL-4, IL-33), complement activation products (C5a) or endothelial activation (ICAM-1). The majority of those with suspected reactions to non-COVID-19 polysorbate-containing vaccines tolerated the BNT162b2 vaccine. Excipient skin tests for PEG and polysorbate prior to vaccination are unnecessary.