Enhanced terminal room disinfection and acquisition and infection caused by multidrug-resistant organisms and Clostridium diffcile(the Benefits of Enhanced Terminal Room Disinfection study):a cluster-randomised,multicentre,crossover study

中文:背景患者入院后可从不当消毒的环境表面获得多药耐药菌和艰难梭菌。本文确定了3种强化的终末消毒(入住同一病房的两名患者之间的消毒)策略,对感染耐甲氧西林金黄色葡萄球菌(MRSA)、耐万古霉素肠球菌(VRE)、艰难梭菌(CD)和多重耐药不动杆菌的影响。方法本文在美国东南部的9家医院开展了一项务实的、集群-随机、交叉研究。凡曾有感染或定植目标细菌感染患者居住过的病房,患者出院后随机采取4种消毒策略中的一种方法进行终末消毒:对照(季胺盐类消毒剂消毒,但凡遇到CD采用含氯消毒剂);UV(季胺盐类+UV-C消毒,但凡遇到CD采用含氯消毒剂+UV-C);含氯消毒剂;含氯消毒剂+UV-C。凡入住目标病房的患者被列为暴露人群。这4种终末消毒方法分别在每家医院连续实施7个月的周期。本文随机设计这几种消毒策略在每家医院内的实施顺序(1:1:1:1)。主要产出的结果是,观察暴露患者中目标细菌的感染的发生或定植情况,以及ITT人群中暴露患者CD感染发生率。本研究ClinicalTrials.gov注册编号:NCT01579370。结果共有31 226名患者暴露,其中21 395(69%)符合标准,包括4 916名对照组,5 178名UV组,5 438名含氯消毒剂组,以及5 863名含氯消毒剂+UV组。在对照组中,22 426个暴露日中有115名患者发生目标细菌的感染(51.3/10000暴露日)。在标准清洁策略的基础上增加UV消毒的暴露患者,其目标细菌感染的发生率明显较低(n=76;33.9/10 000暴露日;RR:0.70,95%CI:0.50～0.988;P=0.036)。含氯消毒剂组(n=101;41.6/10 000暴露日;RR:0.85,95%CI:0.69～1.04;P=0.116),或含氯消毒剂+UV组患者(n=131;45.6/10 000暴露日;RR:0.91,95%CI:0.76～1.09;P=0.303)的目标细菌的感染率,其差异无统计学意义。同样,在含氯消毒剂的基础上增加UV消毒,暴露患者中CD感染率也没有发生改变((n=38 vs 36;30.4 vs 31.6/10 000暴露日;RR:1.0,95%CI:0.57-1.75;P=0.997)。解释污染的医疗机构环境是获得病原微生物的重要来源;强化终末消毒可以降低这一风险。     

SimPEL: Simulation‐based power estimation for sequencing studies of low‐prevalence conditions

Power estimations are important for optimizing genotype‐phenotype association study designs. However, existing frameworks are designed for common disorders, and thus ill‐suited for the inherent challenges of studies for low‐prevalence conditions such as rare diseases and infrequent adverse drug reactions. These challenges include small sample sizes and the need to leverage genetic annotation resources in association analyses for the purpose of ranking potential causal genes. We present SimPEL, a simulation‐based program providing power estimations for the design of low‐prevalence condition studies. SimPEL integrates the usage of gene annotation resources for association analyses. Customizable parameters, including the penetrance of the putative causal allele and the employed pathogenic scoring system, allow SimPEL to realistically model a large range of study designs. To demonstrate the effects of various parameters on power, we estimated the power of several simulated designs using SimPEL and captured power trends in agreement with observations from current literature on low‐frequency condition studies. SimPEL, as a tool, provides researchers studying low‐frequency conditions with an intuitive and highly flexible avenue for statistical power estimation. The platform‐independent “batteries included” executable and default input files are available at https://github.com/precisionomics/SimPEL .     

Psychometric validation of the SF-36<Superscript>®</Superscript> Health Survey in ulcerative colitis: results from a systematic literature review

Purpose

To conduct a systematic literature review of the reliability, construct validity, and responsiveness of the SF-36^® Health Survey (SF-36) in patients with ulcerative colitis (UC).

Methods

We performed a systematic search of electronic medical databases to identify published peer-reviewed studies which reported scores from the eight scales and/or two summary measures of the SF-36 collected from adult patients with UC. Study findings relevant to reliability, construct validity, and responsiveness were reviewed.

Results

Data were extracted and summarized from 43 articles meeting inclusion criteria. Convergent validity was supported by findings that 83% (197/236) of correlations between SF-36 scales and measures of disease symptoms, disease activity, and functioning exceeded the prespecified threshold (r ≥ |0.40|). Known-groups validity was supported by findings of clinically meaningful differences in SF-36 scores between subgroups of patients when classified by disease activity (i.e., active versus inactive), symptom status, and comorbidity status. Responsiveness was supported by findings of clinically meaningful changes in SF-36 scores following treatment in non-comparative trials, and by meaningfully larger improvements in SF-36 scores in treatment arms relative to controls in randomized controlled trials. The sole study of SF-36 reliability found evidence supporting internal consistency (Cronbach’s α ≥ 0.70) for all SF-36 scales and test–retest reliability (intraclass correlation coefficient ≥0.70) for six of eight scales.

Conclusions

Evidence from this systematic literature review indicates that the SF-36 is reliable, valid, and responsive when used with UC patients, supporting the inclusion of the SF-36 as an endpoint in clinical trials for this patient population.

     

Pulmonary delivery of polyplexes for combined PAI-1 gene silencing and CXCR4 inhibition to treat lung fibrosis

This report describes the development of polyplexes based on CXCR4-inhibiting poly(ethylenimine) derivative (PEI-C) for pulmonary delivery of siRNA to silence plasminogen activator inhibitor-1 (siPAI-1) as a new combination treatment of pulmonary fibrosis (PF). Safety and delivery efficacy of the PEI-C/siPAI-1 polyplexes was investigated in vitro in primary lung fibroblasts isolated from mice with bleomycin-induced PF. Biodistribution analysis following intratracheal administration of fluorescently labeled polyplexes showed prolonged retention in the lungs. Treatment of mice with bleomycin-induced PF using the PEI-C/siPAI-1 polyplexes resulted in a significant down-regulation of the PAI-1 expression and decreased collagen deposition in the lung. The results of this study provide first evidence of the potential benefits of combined inhibition of CXCR4 and PAI-1 in the pulmonary treatment of PF.     

In vivo near infrared fluorescence imaging and dynamic quantification of pancreatic metastatic tumors using folic acid conjugated biodegradable mesoporous silica nanoparticles

Cancer metastasis is one of the biggest challenges in cancer treatments since it increases the likelihood that a patient will die from the disease. Therefore, the availability of techniques for the early detection and quantification of tumors is very important. We have prepared cyanine 7.5 NHS ester (Cy_7.5) and folic acid (FA) conjugated biodegradable mesoporous silica nanoparticles (bMSN@Cy_7.5-FA NPs) (~100 nm) for visualizing tumors in vivo. The fluorescence spectra revealed that the emission peak of bMSN@Cy_7.5-FA NPs had a red-shift of 1 nm. Confocal immunofluorescent images showed that bMSN@Cy_7.5-FA NPs had an excellent targeting ability for visualizing cancer cells. In vivo fluorescence imaging has been conducted using an orthotopic model for pancreatic cancer within 48 h, and the fluorescence intensity reached a maximum at a post injection time-point of 12 h, which demonstrated that the use of bMSN@Cy_7.5-FA NPs provides an excellent imaging platform for tumor precision therapy in mice.     

Neuroprotective effect of gold nanoparticles composites in Parkinson's disease model

Parkinson’s disease (PD) is second most common neurodegenerative disorder worldwide. Although drugs and surgery can relieve the symptoms of PD, these therapies are incapable of fundamentally treating the disease. For PD patients, over-expression of α-synuclein (SNCA) leads to the death of dopaminergic neurons. This process can be prevented by suppressing SNCA over-expression through RNA interference. Here, we successfully synthesized gold nanoparticles (GNP) composites (CTS@GNP-pDNA-NGF) via the combination of electrostatic adsorption and photochemical immobilization, which could load plasmid DNA (pDNA) and target specific cell types. GNP was transfected into cells via endocytosis to inhibiting the apoptosis of PC12 cells and dopaminergic neurons. Simultaneously, GNP composites are also used in PD models in vivo, and it can successfully cross the blood-brain barrier by contents of GNP in the mice brain. In general, all the works demonstrated that GNP composites have good therapeutic effects for PD models in vitro and in vivo.     

Nano in nano: Biosynthesized gold and iron nanoclusters cargo neoplastic exosomes for cancer status biomarking

Timely detection is crucial for successful treatment of cancer. The current study describes a new approach that involves utilization of the tumor cell environment for bioimaging with in-situ biosynthesized nanoscale gold and iron probes and subsequent dissemination of Au-Fe nanoclusters from cargo exosomes within the circulatory system. We have isolated the Au-Fe cargo exosomes from the blood of the treated murine models after in situ biosyntheses from their respective pre-ionic solutions (HAuCl₄, FeCl₂), whereas Na₂SeO₃ supplementation added into Au lethal effect. The microarray data of various differentially expressed genes revealed the up-regulated tumor ablation and metal binding genes in SGC-7901 cell lines after treatment with Au-Fe-Se triplet ionic solution. The isolation of Au-Fe nanoclusters cargo exosomes (nano in nano) after secretion from deeply seated tumors may help in early diagnosis and reveal the tumor ablation status during and after the relevant treatment like radio-chemo therapies et al.     

Clinical ultrasound stimulating angiogenesis following drug-release from polymersomes on the ischemic zone for peripheral arterial occlusive disease

Peripheral Arterial Occlusive Disease (PAOD) is an aging disease that affects the quality of life of many people by its intermittent claudication and critical limb ischemia presentations. Traditional treatment and management of PAOD are asking patients to make a life change and medication with antiplatelet, statins and cilostazol, which decrease the possibility of clot formation. Our strategy has employed a magnetic Fe₃O₄-PLGA polymersome to carry the cilostazol into the ischemic area by magnetic attraction following remote-control drug release through low-energy ultrasound exposure. In the animal studies, the cilostazol-loaded Fe₃O₄-PLGA polymersomes were injected and accumulated at ischemic leg through magnetic attraction. Then, using a clinical-use ultrasound machine the leg was irradiated to forward cilostazol release from the accumulated polymersomes. Dramatically, we found an observable result of bloody flux recovery in the leg after 7?days compared to the non-treated leg that showed no evidence of the blood recovery.