Altered Functional and Causal Connectivity of Cerebello-Cortical Circuits between Multiple System Atrophy (Parkinsonian Type) and Parkinson’s Disease

Lesions of the cerebellum lead to motor and non-motor deficits by influencing cerebral cortex activity via cerebello-cortical circuits. It remains unknown whether the cerebello-cortical “disconnection” underlies motor and non-motor impairments both in the parkinsonian variant of multiple system atrophy (MSA-P) and Parkinson’s disease (PD). In this study, we investigated both the functional and effective connectivity of the cerebello-cortical circuits from resting-state functional magnetic resonance imaging (rs-fMRI) data of three groups (26 MSA-P patients, 31 PD patients, and 30 controls). Correlation analysis was performed between the causal connectivity and clinical scores. PD patients showed a weakened cerebellar dentate nucleus (DN) functional coupling in the posterior cingulate cortex (PCC) and inferior parietal lobe compared with MSA-P or controls. MSA-P patients exhibited significantly enhanced effective connectivity from the DN to PCC compared with PD patients or controls, as well as declined causal connectivity from the left precentral gyrus to right DN compared with the controls, and this value is significantly correlated with the motor symptom scores. Our findings demonstrated a crucial role for the cerebello-cortical networks in both MSA-P and PD patients in addition to striatal-thalamo-cortical (STC) networks and indicated that different patterns of cerebello-cortical loop degeneration are involved in the development of the diseases

Effects of nutrient loading on sediment bacterial and pathogen communities within seagrass meadows

Eutrophication can play a significant role in seagrass decline and habitat loss. Microorganisms in seagrass sediments are essential to many important ecosystem processes, including nutrient cycling and seagrass ecosystem health. However, current knowledge of the bacterial communities, both beneficial and detrimental, within seagrass meadows in response to nutrient loading is limited. We studied the response of sediment bacterial and pathogen communities to nutrient enrichment on a tropical seagrass meadow in Xincun Bay, South China Sea. The bacterial taxonomic groups across all sites were dominated by the Gammaproteobacteria and Firmicutes. Sites nearest to the nutrient source and with the highest NH4+ and PO43− content had approximately double the relative abundance of putative denitrifiers Vibrionales, Alteromonadales, and Pseudomonadales. Additionally, the relative abundance of potential pathogen groups, especially Vibrio spp. and Pseudoalteromonas spp., was approximately 2‐fold greater at the sites with the highest nutrient loads compared to sites further from the source. These results suggest that proximity to sources of nutrient pollution increases the occurrence of potential bacterial pathogens that could affect fishes, invertebrates and humans. This study shows that nutrient enrichment does elicit shifts in bacterial community diversity and likely their function in local biogeochemical cycling and as a potential source of infectious diseases within seagrass meadows

Sulforaphane Effects on Cognition and Symptoms in First and Early Episode Schizophrenia: A Randomized Double-Blind Trial.

OBJECTIVE: Cognitive symptoms are associated with significant dysfunction in schizophrenia. Oxidative stress and inflammation involving histone deacetylase (HDAC) have been implicated in the pathophysiology of schizophrenia. Sulforaphane has antioxidant properties and is an HDAC inhibitor. The objective of this study was to determine the efficacy of sulforaphane on cognition dysfunction for patients with schizophrenia. METHODS: This double-blind randomized 22-week trial of patients with first-episode schizophrenia was conducted in four psychiatric institutions in China. Patients were randomized to three groups (two doses of sulforaphane vs. placebo) and symptomatic and cognitive assessments were completed at multiple times. The primary outcome measure was change in the MATRICS Composite score. The secondary outcomes were change in MATRICS Domain scores, PANSS Total Scores and change in side-effects. RESULTS: A total of 172 patients were randomized and 151 patients had at least one follow up evaluation. There were no significant effects of sulforaphane, on the primary outcome, MATRICS overall composite score. However, on secondary outcomes, sulforaphane did significantly improve performance scores on MATRICS battery Domains of spatial working memory (F = 5.68, P = 0.004), reasoning-problem solving (F = 2.82, P = 0.063), and verbal learning (F = 3.56, P = 0.031). There were no effects on PANSS symptom scores. Sulforaphane was well tolerated. CONCLUSION: Although the primary outcome was not significant, improvement in three domains of the MATRICS battery, suggests a positive cognitive effect on some cognitive functions, which warrants further clinical trials to further assess whether sulforaphane may be a useful adjunct for treating some types of cognitive deficits in schizophrenia

Association between intraoperative dexmedetomidine and all-cause mortality and recurrence after laparoscopic resection of colorectal cancer: Follow-up analysis of a previous randomized controlled trial

BackgroundDexmedetomidine (DEX) has been widely applied in the anesthesia and sedation of patients with oncological diseases. However, the potential effect of DEX on tumor metastasis remains contradictory. This study follows up on patients who received intraoperative DEX during laparoscopic resection of colorectal cancer as part of a previous clinical trial, examining their outcomes 5 years later.MethodsBetween June 2015 and December 2015, 60 patients undergoing laparoscopic colorectal resection were randomly assigned to the DEX and control groups. The DEX group received an initial loading dose of 1μ/kg before surgery, followed by a continuous infusion of 0.3μg/kg/h during the operation and the Control group received an equivalent volume of saline. A 5-year follow-up analysis was conducted to evaluate the overall survival, disease-free survival, and tumor recurrence.ResultsThe follow-up analysis included 55 of the 60 patients. The DEX group included 28 patients, while the control group included 27 patients. Baseline characteristics were comparable between the two groups, except for vascular and/or neural invasion of the tumor in the DEX group (9/28 vs. 0/27, p = 0.002). We did not observe a statistically significant benefit but rather a trend toward an increase in overall survival and disease-free survival in the DEX group, 1-year overall survival (96.4% vs. 88.9%, p = 0.282), 2-year overall survival (89.3% vs. 74.1%, p = 0.144), 3-year overall survival (89.3% vs. 70.4%, p = 0.08), and 5-year overall survival (78.6% vs. 59.3%, p = 0.121). The total rates of mortality and recurrence between the two groups were comparable (8/28 vs. 11/27, p = 0.343).ConclusionAdministration of DEX during laparoscopic resection of colorectal cancer had a nonsignificant trend toward improved overall survival and disease-free survival.Clinical Trial Registrationhttp://www.chictr.org.cn/, identifier ChiCTRIOR-15006518

Early Non-Response as a Predictor of Later Non-Response to Antipsychotics in Schizophrenia: A Randomized Trial

BACKGROUND: It remains a challenge to predict the long-term response to antipsychotics in patients with schizophrenia who do not respond at an early stage. This study aimed to investigate the optimal predictive cut-off value for early non-response that would better predict later non-response to antipsychotics in patients with schizophrenia. METHODS: This multicenter, 8-week, open-label, randomized trial was conducted at 19 psychiatric centers throughout China. All enrolled participants were assigned to olanzapine, risperidone, amisulpride, or aripiprazole monotherapy for 8 weeks. The positive and negative syndrome scale (PANSS) was evaluated at baseline, week 2, week 4, and week 8. The main outcome was the prediction of nonresponse. Nonresponse is defined as a \u3c 20% reduction in the total scores of PANSS from baseline to endpoint. Severity ratings of mild, moderate, and severe illness corresponded to baseline PANSS total scores of 58, 75, and 95, respectively. RESULTS: At week 2, a reduction of \u3c 5% in the PANSS total score showed the highest total accuracy in the severe and mild schizophrenia patients (total accuracy, 75.0% and 80.8%, respectively), and patients who were treated with the risperidone and amisulpride groups (total accuracy, 82.4%, and 78.2%, respectively). A 10% decrease exhibited the best overall accuracy in the moderate schizophrenia patients (total accuracy, 84.0%), olanzapine (total accuracy, 79.2%), and aripiprazole group (total accuracy, 77.4%). At week 4, the best predictive cut-off value was \u3c 20%, regardless of the antipsychotic or severity of illness (total accuracy ranging from 89.8 to 92.1%). CONCLUSIONS: Symptom reduction at week 2 has acceptable discrimination in predicting later non-response to antipsychotics in schizophrenia, and a more accurate predictive cut-off value should be determined according to the medication regimen and baseline illness severity. The response to treatment during the next 2 weeks after week 2 could be further assessed to determine whether there is a need to change antipsychotic medication during the first four weeks. TRIAL REGISTRATION: This study was registered on Clinicaltrials.gov (NCT03451734)

Bacterial diversity and community structure of supragingival plaques in adults with dental health or caries revealed by 16S pyrosequencing

Dental caries has a polymicrobial etiology within the complex oral microbial ecosystem. However, the overall diversity and structure of supragingival plaque microbiota in adult dental health and caries are not well understood. Here, 160 supragingival plaque samples from patients with dental health and different severities of dental caries were collected for bacterial genomic DNA extraction, pyrosequencing by amplification of the 16S rDNA V1–V3 hypervariable regions, and bioinformatic analysis. High-quality sequences (2,261,700) clustered into 10,365 operational taxonomic units (OTUs; 97% identity), representing 453 independent species belonging to 122 genera, 66 families, 34 orders, 21 classes, and 12 phyla. All groups shared 7522 OTUs, indicating the presence of a core plaque microbiome. Smooth rarefaction curves were suggestive of plaque microbial diversity. α diversity analysis showed that healthy plaque microbial diversity exceeded that of dental caries, with the diversity decreasing gradually with the severity of caries. The dominant phyla of plaque microbiota included Bacteroidetes, Actinobacteria, Proteobacteria, Firmicutes, Fusobacteria, and TM7. The dominant genera included Capnocytophaga, Prevotella, Actinomyces, Corynebacterium, Neisseria, Streptococcus, Rothia, and Leptotrichia. β diversity analysis showed that the plaque microbial community structure was similar in all groups and that group members were relatively constant, only showing differences in abundance. Analysis of composition differences identified 10 health-related and 21 caries-related genera. Key genera (27) that potentially contributed to plaque microbiota distributions between groups were identified. Finally, co-occurrence network analysis and function prediction were performed. Treatment strategies directed toward modulating microbial interactions and their functional output should be further developed

Approximation of bivariate copulas by patched bivariate Fréchet copulas

Bivariate Fréchet (BF) copulas characterize dependence as a mixture of three simple structures: comonotonicity, independence and countermonotonicity. They are easily interpretable but have limitations when used as approximations to general dependence structures. To improve the approximation property of the BF copulas and keep the advantage of easy interpretation, we develop a new copula approximation scheme by using BF copulas locally and patching the local pieces together. Error bounds and a probabilistic interpretation of this approximation scheme are developed. The new approximation scheme is compared with several existing copula approximations, including shuffle of min, checkmin, checkerboard and Bernstein approximations and exhibits better performance, especially in characterizing the local dependence. The utility of the new approximation scheme in insurance and finance is illustrated in the computation of the rainbow option prices and stop-loss premiums.Bivariate Frechet copulas Patched bivariate Frechet copula Approximation of bivariate copulas Rainbow options

Moxibustion for Herpes Zoster and Postherpetic Neuralgia: A Meta-Analysis

Background. Herpes zoster (HZ) is a disease that mainly causes severe segmental neuralgia and vesicles after infection with herpes zoster virus (VZV). At the same time, more than 9 to 34 percent of patients have postherpetic neuralgia (PHN) present with chronic pain for months or even years. Moxibustion has been used to treat herpes zoster and postherpetic neuralgia for many years; however, there has been no comprehensive study to evaluate the efficacy and safety of moxibustion in the treatment of herpes zoster and postherpetic neuralgia. More studies evaluated the combined effects of acupuncture and moxibustion. Therefore, the purpose of this systematic review is to evaluate their efficacy and safety, so as to provide an evidence-based basis for the clinical application of moxibustion in the treatment of HZ and PHN. Method. The literature search was conducted in nine Chinese and English databases, and randomized controlled trials were pooled from their inceptions to June 2020. The included literature was screened, and data were extracted. RevMan 5.3 software and Stata software were used for statistical analysis. The primary outcome was the total effect. The secondary outcomes include VAS, NRS, and time of analgesia. Outcomes. From a total of 1957 identified studies, 31 were included in analysis (N = 2334 cases). 31 RCTs contained the experimental sample of 1185 cases and the control sample of 1149 cases reported efficiency of different moxibustions in the treatment of herpes zoster, statistical heterogeneity inspection without heterogeneity. So, we used the fixed-effects model, merge effect quantity OR = 3.89 (95% CI: 2.88∼5.25), Z = 8.86, and it suggested sample merger analysis was statistically significant. Also, the moxibustion, compared to other methods in the treatment of herpes zoster and herpes zoster neuralgia efficiency, increased significantly. The VAS scales, WMD = 1.69 (95% CI: 1.17∼2.22), and the time of analgesia, WMD = 2.41 (95% CI: 3.26∼1.73), indicated that moxibustion surpassed others in the relief of pain. NRS was just reported in one study. It was not statistically significant. There was no significant difference in adverse effects OR = 0.61 (95% CI: 0.33∼1.13), Z = 1.56 (P = 0.12). Conclusion. Moxibustion has obvious advantages over other therapies in the treatment of HZ and PHN. However, due to the obvious publication bias, the interpretation of the results should be cautious, and more rigorous randomized controlled clinical studies should be included to further confirm the results in the future

Ex situ Flora of China

The role of living collections-based research and discovery has been a prominent feature throughout the history of evolution and advance of botanical science: such research is the core and soul of the botanical gardens. Currently, there are c. 162 Chinese botanical gardens, harboring c. 20,000 species in China. As an example of initiatives to utilize the garden cultivated flora to address plant diversity conservation and germplasm discovery for sustainable agriculture and the bio-industries, the Ex situ Flora of China project aims to catalog and document this mega-diversity of plants that are cultivated in the Chinese botanical gardens. The concept of Ex situ Flora of China is a complete new formulation of species, based on garden cultivated individuals and populations, to obtain better morphological descriptions, provide multi-purpose applicability and a fundamental data service that will support national bio-strategies and bio-industries. It emphasises integrative information, accurately collected from living collections across different Chinese botanical gardens, on biology, phenology, cultivation requirements and uses of plant resources, which are normally not available from traditional Floras based on herbarium specimens. The ex situ flora should provide better information coverage for taxonomy, biological and introduction and collection data and color photos of stems, leaves, flowers, fruits and seed, as well as useful information of cultivation key points and main use of each plant. In general, the Ex situ Flora of China provides more useful information than the traditional Flora Reipublicae Popularis Sinicae. The project of Ex situ Flora of China is planned to be one of the most important initiatives of the plant diversity research platform for sustainable economic and social development in China. Keywords: Botanical garden, Living collections, Ex situ conservation, Botanical sciences, Cultivated flor