The Role of Butyric Acid in Treatment Response in Drug-Naive First Episode Schizophrenia

Background: Butyric acid, a major short-chain fatty acid (SCFA), has an important role in the microbiota-gut-brain axis and brain function. This study investigated the role of butyric acid in treatment response in drug-naive first episode schizophrenia. Methods: The study recruited 56 Chinese Han schizophrenia inpatients with normal body weight and 35 healthy controls. Serum levels of butyric acid were measured using Gas Chromatography-Mass Spectrometer (GC-MS) analysis at baseline (for all participants) and 24 weeks after risperidone treatment (for patients). Clinical symptoms were measured using the Positive and Negative Syndrome Scale (PANSS) for patients at both time points. Results: At baseline, there was no significant difference in serum levels of butyric acid between patients and healthy controls (p = 0.206). However, there was a significant increase in serum levels of butyric acid in schizophrenia patients after 24-week risperidone treatment (p = 0.030). The PANSS total and subscale scores were decreased significantly after 24-week risperidone treatment (p\u27s \u3c 0.001). There were positive associations between baseline serum levels of butyric acid and the reduction ratio of the PANSS total and subscale scores after controlling for age, sex, education, and duration of illness (p\u27s \u3c 0.05). Further, there was a positive association between the increase in serum levels of butyric acid and the reduction of the PANSS positive symptoms subscale scores (r = 0.38, p = 0.019) after controlling for potential confounding factors. Conclusions: Increased serum levels of butyric acid might be associated with a favorable treatment response in drug-naive, first episode schizophrenia. The clinical implications of our findings were discussed

Antioxidants and Antioxidant Capacity in Leafy, Stem, and Fruit Vegetables Including 50 Species

Epidemiological studies have confirmed that high intake of fruits and vegetables is associated with low incidence of many kinds of diseases, which are hypothesized to be owing to antioxidants in fruits and vegetables. In this study, three types (leafy, stem, fruit) vegetables including 50 species were systematically evaluated for their antioxidant capacity (AC) and antioxidants including total phenolic compound (TPC), total flavonoids (TF), and L-ascorbic acid (LAA). Results showed that vegetables types had no significant effects on antioxidants. Vegetables with vivid color like purple cabbage, purple dolichos lablab, purple cowpea, red pepper, yellow pepper, lotus root, and ginger ranked high in their antioxidants (TPC 32.76-117.63 mg gallic acid/g FW, TF 25.78-152.96 mg rutin/100g FW, LAA 69.11-165.44 mg/100g FW) and AC (FRAP 69.38-109.13 μmol Fe2+/100gFW, ABTS 2.19-3.75 μmol Trolox/gFW). Relatively, crown daisy, endive, celery stem, and cucumber had low antioxidants (TPC 2.66-6.29 mg gallic acid/g FW, TF 10.37-37.56 mg rutin/100g FW, LAA 14.64-39.44 mg/100g FW) and AC (FRAP 1.99-10.81 μmol Fe2+/100gFW, ABTS 0.39-0.68 μmol Trolox/gFW). TPC and LAA had strong positive correlations with AC regardless of vegetable types, while TF was positively related to AC only in leafy vegetables. The result would be valuable for both epidemiological research and dietary guidelines as these vegetables are affordable and widely available

Fat-mass and obesity-associated gene polymorphisms and weight gain after risperidone treatment in first episode schizophrenia

BACKGROUND: Obesity induced by antipsychotics severely increases the risk of many diseases and significantly reduces quality of life. Genome Wide Association Studies has identified fat-mass and obesity-associated (FTO) gene associated with obesity. The relationship between the FTO gene and drug-induced obesity is unclear. METHOD: Two hundred and fifty drug naive, Chinese Han patients with first-episode schizophrenia were enrolled in the study, and genotyped for four single nucleotide polymorphisms (SNPs rs9939609, rs8050136, rs1421085 and rs9930506) by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing. Body weight and body mass index (BMI) were measured at baseline and six months after risperidone treatment. RESULTS: At baseline, body weight and BMI of TT homozygotes were lower than those of A allele carriers in rs9939609; body weight of AA homozygotes was higher than those of G allele carriers in rs9930506 (p\u27s \u3c 0.05). After 6 months of risperidone treatment, body weight and BMI of TT homozygotes were lower than those of A allele carriers in rs9939609 (p\u27s \u3c 0.01); body weight and BMI of CC homozygotes were lower than those of A allele carriers in rs8050136 (p\u27s \u3c 0.05); body weight of AA homozygotes was higher than those of G allele carriers in rs9930506 (p\u27s \u3c 0.05). After controlling for age, gender, age of illness onset, disease duration, weight at baseline and education, weight gain of TT homozygotes at 6 months remained to be lower than those of A allele carriers in rs9939609 (p \u3c 0.01); weight gain of CC homozygotes at 6 months was lower than those of A allele carriers in rs8050136 (p = 0.01). Stepwise multiple regression analysis suggested that, among 4 SNPs, rs9939609 was the strongest predictor of weight gain after 6 months of risperidone treatment (p = 0.001). CONCLUSIONS: The FTO gene polymorphisms, especially rs9939609, seem to be related to weight gain after risperidone treatment in Chinese Han patients with first episode schizophrenia

Decreased Functional Connectivity of Insular Cortex in Drug Naive First Episode Schizophrenia: In Relation to Symptom Severity

BACKGROUND: This study was to examine the insular cortical functional connectivity in drug naive patients with first episode schizophrenia and to explore the relationship between the connectivity and the severity of clinical symptoms. METHODS: Thirty-seven drug naive patients with schizophrenia and 25 healthy controls were enrolled in this study. A seed-based approach was used to analyze the resting-state functional imaging data. Insular cortical connectivity maps were bilaterally extracted for group comparison and validated by voxel-based morphometry (VBM) analysis. Clinical symptoms were measured using the Positive and Negative Syndrome Scale (PANSS). RESULTS: There were significant reductions in the right insular cortical connectivity with the Heschl\u27s gyrus, anterior cingulate cortex (ACC), and caudate (p\u27s \u3c 0.001) in the patient group compared with the healthy control (HC) group. Reduced right insular cortical connectivity with the Heschl\u27s gyrus was further confirmed in the VBM analysis (FDR corrected p \u3c 0.05). Within the patient group, there was a significant positive relationship between the right insula-Heschl\u27s connectivity and PANSS general psychopathology scores (r = 0.384, p = 0.019). CONCLUSION: Reduced insula-Heschl\u27s functional connectivity is present in drug naive patients with first episode schizophrenia, which might be related to the manifestation of clinical symptoms

Gut microbial biomarkers for the treatment response in first-episode, drug-naive schizophrenia: a 24-week follow-up study

Preclinical studies have shown that the gut microbiota can play a role in schizophrenia (SCH) pathogenesis via the gut-brain axis. However, its role in the antipsychotic treatment response is unclear. Here, we present a 24-week follow-up study to identify gut microbial biomarkers for SCH diagnosis and treatment response, using a sample of 107 first-episode, drug-naive SCH patients, and 107 healthy controls (HCs). We collected biological samples at baseline (all participants) and follow-up time points after risperidone treatment (SCH patients). Treatment response was assessed using the Positive and Negative Symptoms Scale total (PANSS-T) score. False discovery rate was used to correct for multiple testing. We found that SCH patients showed lower alpha-diversity (the Shannon and Simpson\u27s indices) compared to HCs at baseline (p = 1.21 x 10(-9), 1.23 x 10(-8), respectively). We also found a significant difference in beta-diversity between SCH patients and HCs (p = 0.001). At baseline, using microbes that showed different abundance between patients and controls as predictors, a prediction model can distinguish patients from HCs with an area under the curve (AUC) of 0.867. In SCH patients, after 24 weeks of risperidone treatment, we observed an increase of alpha-diversity toward the basal level of HCs. At the genus level, we observed decreased abundance of Lachnoclostridium (p = 0.019) and increased abundance Romboutsia (p = 0.067). Moreover, the treatment response in SCH patients was significantly associated with the basal levels of Lachnoclostridium and Romboutsia (p = 0.005 and 0.006, respectively). Our results suggest that SCH patients may present characteristic microbiota, and certain microbiota biomarkers may predict treatment response in this patient population

Overexpression of Polo-like kinase1 (PLK1) in chondrosarcoma and its implications for cancer progression

Polo-like kinase1 (PLK1) is a new therapeutic target for osteosarcoma with good application prospects. Whether PLK1 is highly expressed in chondrosarcoma and whether PLK1 can be a potential therapeutic target for chondrosarcoma are worth exploring. However, PLK1 expression in chondrosarcoma is scarcely investigated. Therefore, we collected 11 cases of chondrosarcoma and 26 cases of osteochondroma with complete clinical pathological data and used immunohistochemical staining to detect the expression of PLK1 in chondrosarcoma and osteochondroma and then studied its significance and relationship with clinical pathological parameters. Our results showed that the positive expression rate of PLK1 in chondrosarcoma tissue (90.91%, 10/11) was significantly higher than the rate of osteochondroma tissues (53.85%, 14/26) (

A multimodal cell census and atlas of the mammalian primary motor cortex

ABSTRACT We report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex (MOp or M1) as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties, and cellular resolution input-output mapping, integrated through cross-modal computational analysis. Together, our results advance the collective knowledge and understanding of brain cell type organization: First, our study reveals a unified molecular genetic landscape of cortical cell types that congruently integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a unified taxonomy of transcriptomic types and their hierarchical organization that are conserved from mouse to marmoset and human. Third, cross-modal analysis provides compelling evidence for the epigenomic, transcriptomic, and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types and subtypes. Fourth, in situ single-cell transcriptomics provides a spatially-resolved cell type atlas of the motor cortex. Fifth, integrated transcriptomic, epigenomic and anatomical analyses reveal the correspondence between neural circuits and transcriptomic cell types. We further present an extensive genetic toolset for targeting and fate mapping glutamatergic projection neuron types toward linking their developmental trajectory to their circuit function. Together, our results establish a unified and mechanistic framework of neuronal cell type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake