Efficacy and safety of tigecycline for the treatment of severe infectious diseases: an updated meta-analysis of RCTs

Objectives: To assess the efficacy and safety of tigecycline in comparison with other antimicrobial treatments for infectious diseases. Design: Databases of PubMed, Embase and the Cochrane Library were searched through Feb. 2015. The reference lists of the initially identified articles and systemic review articles were manually searched. Randomized controlled trials assessing tigecycline and other antibiotics for infectious diseases in adult patients were included. Results: Fifteen RCTs including 7689 cases were identified. We found that tigecycline was not as effective as the comparator agents for clinical treatment success (for the clinically evaluable population, odds ratio [OR] = 0.83, 95% confidence interval [CI] = (0.73, 0.96), P=0.01; for the clinically modified intent-to-treat (mITT) population, OR = 0.81, 95% CI = (0.72, 0.92), P=0.001). There was no significant difference in microbiological treatment success with lower eradication rate in tigecycline versus comparators (for the microbiologically evaluable population, OR = 0.94, 95% CI = (0.77, 1.16), P=0.56; for the microbiological mITT populations, OR = 0.91, 95% CI = (0.74, 1.11), P=0.35). Adverse events and all-cause mortality were more common in the tigecycline group. Conclusions: Tigecycline is not as effective as other antibiotics with relatively more frequency of adverse events and higher mortality rate

The post-PAM interaction of RNA-guided spCas9 with DNA dictates its target binding and dissociation

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Impacts of Short-Term Grazing Intensity on the Plant Diversity and Ecosystem Function of Alpine Steppe on the Qinghai–Tibetan Plateau

Livestock grazing is the primary land use of grasslands worldwide. Grazing has been asserted to alter grassland ecosystem functions, such as productivity, nutrient cycling, and biodiversity conservation. However, few studies have focused on the impact of grazing intensity on the ecosystem multifunctionality (EMF) of alpine grasslands. We conducted a field experiment of manipulating sheep grazing intensity effects on alpine steppe by surveying plant community characteristics and ecosystem functions. Our results showed that plant community composition was altered with increasing grazing intensity, and the dominant species shifted from grasses and sedges to forbs. EMF was the highest under no grazing (CK) and the lowest under heavy grazing (HG), but there was insignificant difference between CK and HG. HG significantly decreased some indicators that reflected nutrient cycling functions, such as soil available nitrogen, plant leaf nitrogen (PN) and phosphorus content (PP). Furthermore, plant diversity had strong correlations with SOC, total nitrogen (TN), and PN. The results could provide scientific bases for biodiversity conservation and sustainable grazing management of alpine steppe

A neonatal mouse model of central nervous system infections caused by Coxsackievirus B5

Abstract As one of the key members of the coxsackievirus B group, coxsackievirus B5 (CV-B5) can cause many central nervous system diseases, such as viral encephalitis, aseptic meningitis, and acute flaccid paralysis. Notably, epidemiological data indicate that outbreaks of CV-B5-associated central nervous system (CNS) diseases have been reported worldwide throughout history. In this study, which was conducted to promote CV-B5 vaccine and anti-virus drug research, a 3-day-old BALB/c mouse model was established using a CV-B5 clinical isolate (CV-B5/JS417) as the challenge strain. Mice challenged with CV-B5/JS417 exhibited a series of neural clinical symptoms and death with necrosis of neuronal cells in the cerebral cortex and the entire spinal cord, hindlimb muscles, and cardiomyocytes. The viral load of each tissue at various post-challenge time points suggested that CV-B5 replicated in the small intestine and was subsequently transmitted to various organs via viremia; the virus potentially entered the brain through the spinal axons, causing neuronal cell necrosis. In addition, this mouse model was used to evaluate the protective effect of a CV-B5 vaccine. The results indicated that both the inactivated CV-B5 vaccine and anti-CVB5 serum significantly protected mice from a lethal infection of CV-B5/JS417 by producing neutralizing antibodies. In summary, the first CV-B5 neonatal mouse model has been established and can sustain CNS infections in a manner similar to that observed in humans. This model will be a useful tool for studies on pathogenesis, vaccines, and anti-viral drug evaluations

Short-term grazing changed temporal productivity stability of alpine grassland on Qinghai-Tibetan Plateau via response species richness and functional groups asynchrony

The stability of grassland is pivotal in maintaining the grassland functioning and services. However, the knowledge about the consequences of grazing on stability of grassland productivity is limited. Based on a 3-year manipulated experiment with two grazing regimes (i.e., continuous grazing and rotational grazing) along four levels of grazing-intensity (0, 4, 6, and 8 sheep per hectare) on the Qinghai-Tibetan Plateau, we researched the responses of temporal stability of plant community and functional groups of alpine grasslands to different grazing management regimes. We found that grazing regimes, intensity and their interaction affected the temporal stability of aboveground net primary productivity of alpine grassland (ANPP), and intermediate rotational grazing significantly reduced the temporal stability of ANPP, whereas increased the stability of productivity of functional group of forbs. The response species to continuous grazing and rotational grazing are different, for grasses and forbs respectively. Rotational grazing and intermediate continuous grazing increased the diversity of response species. Structural equation modeling further revealed that functional groups asynchrony stabilized the productivity of the alpine grassland ecosystem under grazing in the Qinghai-Tibetan Plateau. These results showed that the rotational grazing and intermediate continuous grazing can maintain the productivity stability, and highlighted importance of regulating the relationships among functional groups for promoting the stability of alpine grassland under grazing management

Hepatitis B virus infection and risk of non‐alcoholic fatty liver disease: A population‐based cohort study

Background & aimsAlthough non-alcoholic fatty liver disease (NAFLD) has been studied extensively, the potential risk factors for NAFLD among chronic hepatitis B (CHB) patients have not been fully known.MethodsA population-based cohort of adult CHB patients without a history of alcohol drinking or NAFLD were recruited and followed up from October 2012 to January 2015 in Jiangsu province, China. Using Cox proportional hazards regression model, potential risk factors including viral and metabolic factors for NAFLD were evaluated.ResultsTwo thousand three hundred and ninety-three adult CHB patients (mean age 50.7 ± 13.2 years) were included in the cohort. With 4429 person-years of follow-up, 283 individuals progressed to NAFLD with an incidence rate of 63.89/1000 person-years. Overweight and obese CHB patients had an increased risk of NAFLD (overweight adjusted hazard ratio [HR], 3.10; 95% CI, 2.29-4.18; obese HR, 8.52; 95%CI, 5.93-12.25) compared to normal weight carriers. The incidence of NAFLD was associated with concurrent type 2 diabetes mellitus (DM) (HR, 1.88; 95%CI, 1.15-3.08). However, no associations between viral factors with NAFLD incidence rate were identified. In a subgroup of participants with concurrent type 2 DM, detectable HBV DNA levels were negatively associated with the development of NAFLD (HR, 0.37; 95%CI, 0.14-0.98). There was super-multiplicative interaction between BMI and gender with respect to incidence of NAFLD, with an ROR of 2.08 (95%CI, 1.02-4.23).ConclusionMetabolic factors play an important role in the presence of NAFLD among Chinese CHB patients. However, viral replication factors are not related to NAFLD except among those with concurrent type 2 DM

Dynamics of Staphylococcus aureus

International audienceStaphylococcus aureus Cas9 (SaCas9) is an RNA-guided endonuclease that targets complementary DNA adjacent to a protospacer adjacent motif (PAM) for cleavage. Its small size facilitates in vivo delivery for genome editing in various organisms. Herein, using single-molecule and ensemble approaches, we systemically study the mechanism of SaCas9 underlying its interplay with DNA. We find that the DNA binding and cleavage of SaCas9 require complementarities of 6and 18-bp of PAM-proximal DNA with guide RNA, respectively. These activities are mediated by two steady interactions among the ternary complex, one of which is located approximately 6 bp from the PAM and beyond the apparent footprint of SaCas9 on DNA. Notably, the other interaction within the protospacer is significantly strong and thus poses DNA-bound SaCas9 a persistent block to DNA-tracking motors. Intriguingly, after cleavage, SaCas9 autonomously releases the PAM-distal DNA while retaining binding to the PAM. This partial DNA release immediately abolishes its strong interaction with the protospacer DNA and consequently promotes its subsequent dissociation from the PAM. Overall, these data provide a dynamic understanding of SaCas9 and instruct its effective applications

Additional file 1: Figure S1. of Microglia-derived IL-1β contributes to axon development disorders and synaptic deficit through p38-MAPK signal pathway in septic neonatal rats

The CCK-8 assay (cell counting kit 8) was performed to determine the IL-1β concentration. The viability of neuronal cells was significantly reduced when neurons were treated with IL-1β at a dose exceeding 40 ng/mL. (TIF 820 kb

Additional file 2: Figure S2. of Microglia-derived IL-1β contributes to axon development disorders and synaptic deficit through p38-MAPK signal pathway in septic neonatal rats

Apoptosis of neurons in the cortex. The incidence of apoptotic neurons co-labeled by caspase-3 (red) and NeuN (green) did not change markedly at 7 days (A–F), 14 days (G–L), and 28 days (M–R) in the cerebral cortex after LPS injection (D–F, J–L, P–R) when compared with controls (A–C, G–I, M–O). Scale bars: A–R 20μm. (TIF 6590 kb