The prognosis of gastric cancer (GC) patients with peritoneal dissemination remains poor, and a better understanding of the underlying mechanisms is critical for the development of new treatments ...that will improve survival in these patients. This study aimed to clarify the clinical and biological role of two key metastasis-associated long non-coding RNAs (lncRNAs) in GC. We analyzed the expression levels of two lncRNAs-Metastasis-Associated Lung Adenocarcinoma Transcript 1 (MALAT1) and HOX-Antisense Intergenic RNA (HOTAIR)-by real-time reverse transcription PCR in 300 gastric tissues (150 GC and 150 adjacent normal mucosa), and in seven GC cell lines. Functional characterization for the role of HOTAIR in GC was performed by small interfering RNA (siRNA) knockdown, followed by series of in-vitro and in-vivo experiments. Expression of both lncRNAs was significantly higher in cancerous tissues than in corresponding normal mucosa, and higher expression of these lncRNAs significantly correlated with peritoneal metastasis in GC patients. In addition, elevated HOTAIR expression emerged both as an independent prognostic and risk factor for peritoneal dissemination. SiRNA knockdown of HOTAIR in GC cells significantly inhibited cell proliferation, migration and invasion, but concurrently enhanced the anoikis rate in transfected cells. In an in vivo assay, HOTAIR siRNA-transfected MKN45 cells injected into nude mice inhibited the growth of xenograft tumors and peritoneal metastasis compared with controls. Our data provide novel evidence for the biological and clinical significance of HOTAIR expression as a potential biomarker for identifying patients with peritoneal metastasis, and as a novel therapeutic target in patients with gastric neoplasia.
Background A fair system to identify alcoholic liver disease patients who are unlikely to recover hepatic function with sobriety and a low risk of alcohol relapse remains a challenge. Our study ...assesses the use of SIPAT in identifying suitable liver transpalnt candidates with limited sobriety. Methods A retrospective study of all LT recipients with ALD from 2015 to 2019. An official policy for limited (<6 months) sobriety was implemented in 2018, which included a SIPAT Assessment, psychiatric consultation and development of a post-LT relapse prevention plan (RPP). Results A total of 103 LTR were performed during the included period, mean age was 53.6 years, 75% male and 45% Caucasian; 16 LTRs had limited sobriety. Demographic variables and median SIPAT scores was similar in both groups; as were graft rejection, infection, and 1-year survival rates. Alcohol relapse occurred in 6 (7%) 33% has slips; 67% sustained relapse sustained sobriety patients, 1 (7%) patient with limited sobriety 100% sustained relapse. LT recipients with limited sobriety had excellent Conclusion LT for ALD with limited sobriety can achieve excellent outcomes in carefully selected patients. Our findings support current literature indicating that length of sobriety is not the only factor mediating success, but rather other factors are critically important (e.g., psychopathology, social support).
Summary
Background
The primary and secondary prevention of spontaneous bacterial peritonitis (SBP) is recommended in high‐risk patients with cirrhosis. Several studies evaluating the efficacy of ...rifaximin for SBP prophylaxis have yielded conflicting results. Rifaximin has the potential advantage of preventing bacterial overgrowth and translocation without the systemic side effects of broad‐spectrum antibiotics.
Aim
To evaluate the efficacy of rifaximin in the primary and secondary prevention of SBP.
Methods
A literature search using five databases was performed to identify studies on the association between rifaximin and SBP. We performed two meta‐analyses: (1) rifaximin compared to systemic antibiotics and (2) rifaximin compared to no antibiotics. Random‐effect modelling was conducted to determine overall pooled estimates and 95% confidence intervals (CIs).
Results
Five studies with 555 patients (295 rifaximin, 260 systemic antibiotics) compared rifaximin with systemic antibiotics. The pooled odds ratio (OR) for SBP was 0.45 (95% CI 0.16‐1.27; P = .13) in patients receiving rifaximin and strengthened on sensitivity analysis (OR 0.38, 95% CI 0.19‐0.76, P = .01). In the analysis comparing rifaximin with no antibiotics, there were five studies with 784 patients (186 rifaximin, 598 no antibiotics). The OR for SBP was 0.34 (95% CI 0.11‐0.99; P < .05) in patients receiving rifaximin. In subgroup analysis, rifaximin reduced the risk of SBP by 47% compared to no antibiotics for primary prophylaxis and by 74% compared to systemic antibiotics for secondary prophylaxis.
Conclusion
Rifaximin may be effective in preventing SBP in patients with cirrhosis and ascites compared to systemically absorbed antibiotics and compared to placebo.
Linked ContentThis article is linked to Goel and Nguyen, Woodhouse and Shawcross Zhao et al and Thévenot papers. To view these articles visit https://doi.org/10.1111/apt.14450, https://doi.org/10.1111/apt.14406, https://doi.org/10.1111/apt.14496 and https://doi.org/10.1111/apt.14544.
It is well established that sensory cortices of animals can be modified by sensory experience, especially during a brief early critical period in development. Theoretical analyses indicate that there ...are two synaptic plasticity mechanisms required: input-specific synaptic modifications and global homeostatic mechanisms to provide stability to neural networks. Experience-dependent homeostatic synaptic plasticity mechanisms have subsequently been demonstrated in the visual cortex of juvenile animals. Here, we report that experience-dependent homeostatic synaptic plasticity persists through adulthood in the superficial layers of the mouse visual cortex. We found that 2 d of visual deprivation in the form of dark rearing is necessary and sufficient to cause an increase in AMPA receptor-mediated miniature EPSC amplitude in layer 2/3 neurons. This increase was rapidly reversed by 1 d of light exposure. This reversible change in synaptic strength persisted in adult mice past the critical period for ocular dominance plasticity, which is reported to end at approximately 1 month of age in rodents. Interestingly, the mechanism of homeostatic synaptic modifications in 3-month-old mice differed from that in young mice (3 weeks old) in that the multiplicative nature of synaptic scaling is lost. Our results demonstrate that the superficial layers of adult mouse visual cortex retain the ability to undergo reversible experience-dependent homeostatic synaptic plasticity.
Linked Content
This article is linked to Goel et al and Woodhouse and Shawcross papers. To view these articles visit https://doi.org/10.1111/apt.14361 and https://doi.org/10.1111/apt.14406.
Accurate information about aerosol vertical distribution is needed to reduce uncertainties in aerosol radiative forcing and its effect on atmospheric dynamics. The present study deals with ...synergistic analyses of aerosol vertical distribution and aerosol optical depth (AOD) with meteorological variables using multisatellite and ground-based remote sensors over Kanpur in central Indo-Gangetic Plain (IGP). Micro-Pulse Lidar Network-derived aerosol vertical extinction (sigma) profiles are analyzed to quantify the interannual and daytime variations during monsoon onset period (May-June) for 2009-2011. The mean aerosol profile is broadly categorized into two layers viz., a surface layer (SL) extending up to 1.5 km (where sigma decreased exponentially with height) and an elevated aerosol layer (EAL) extending between 1.5 and 5.5 km. The increase in total columnar aerosol loading is associated with relatively higher increase in contribution from EAL loading than that from SL. The mean contributions of EALs are about 60%, 51%, and 50% to total columnar AOD during 2009, 2010, and 2011, respectively. We observe distinct parabolic EALs during early morning and late evening but uniformly mixed EALs during midday. The interannual and daytime variations of EALs are mainly influenced by long-range transport and convective capacity of the local emissions, respectively. Radiative flux analysis shows that clear-sky incoming solar radiation at surface is reduced with increase in AOD, which indicates significant cooling at surface. Collocated analysis of atmospheric temperature and aerosol loading reveals that increase in AOD not only resulted in surface dimming but also reduced the temperature (approximately 2-3 C) of lower troposphere (below 3 km altitude). Radiative transfer simulations indicate that the reduction of incoming solar radiation at surface is mainly due to increased absorption by EALs (with increase in total AOD). The observed cooling in lower troposphere in high aerosol loading scenario could be understood as a dynamical feedback of EAL-induced stratification of lower troposphere. Further, the observed radiative effect of EALs increases the stability of the lower troposphere, which could modulate the large-scale atmospheric dynamics during monsoon onset period. These findings encourage follow-up studies on the implication of EALs to the Indian summer monsoon dynamics using numerical models.
Abstract
Road Safety is a matter of great concern throughout the world. As number of casualties is increasing more than 4% annually in all age groups. It has been predicted that due to road accidents ...causality rate will grow around 8% till 2030. It’s entirely admissible and saddening to let citizens get killed in road accidents. As a result, to handle this sort of situation, an in-depth analysis is required. The Data of Road accidents are very heterogeneous in nature so analysis of such type of data is tricky. Segmentation is the main task for analyzing such data. So, K-means clustering method is mainly used for it as proposed in the research work. Second task of this model is to extract the data, images and hidden patterns by using Supervised Machine Learning algorithm that will help to form the policies for the prevention from road accidents. The combination of segmentation machine learning algorithm produces meaning full information.
•Plague, a classified re-emerging disease requires diagnosis at early stage for timely clinical management of patients and containment of infection.•PCR-LF assay being a molecular assay can rapidly ...detect Y. pestis obviating the requirement of agarose gel electrophoresis for end point detection of amplicons.•The described assay detected as low as 1 pg genomic DNA of Y. pestis and also detected Y. pestis in artificially spiked blood samples.•PCR-LF is a simple assay and may prove useful for plague diagnosis in peripheral laboratories with poor resources in endemic regions of plague.
Plague is a zoonotic disease caused by Yersinia pestis, a Gram-negative, rod shaped coccobacillus, which is primarily found in rodents and can be transmitted to humans through flea bite. The disease has three major clinical forms bubonic (by flea bite), pneumonic (by respiratory droplets) and septicemic plague. Y. pestis is classified as a category ‘A’ agent by NIAID, USA due to its high mortality and easy person to person dissemination. The conventional diagnostic methods available for Y. pestis show cross-reactivity with other enteropathogenic bacteria making its detection difficult. There is a need to develop sensitive and specific molecular assay for accurate detection of Y. pestis. PCR is well suited molecular biology tool for rapid diagnosis of plague but after completion of thermal cycling steps, it requires additional time to analyze amplified product using agarose gel electrophoresis. In the present study, PCR assay coupled with lateral flow strips has been developed for rapid detection of Y. pestis. Lateral flow strips give an alternative to gel electrophoresis and permit easy and rapid detection of PCR products. The PCR was performed with 5′ 6-FAM and biotin tagged primers specific for Y. pestis, targeting yihN gene located on chromosome. The PCR product was analyzed using lateral flow strips which yielded result within 2-3 minutes. The analytical sensitivity of PCR-lateral flow (PCR-LF) assay was 1 pg genomic DNA of Y. pestis and 500 copies of target DNA sequence harboured in a recombinant plasmid. The assay could detect Y. pestis DNA extracted from spiked human blood samples containing ≥104 CFU per mL of bacteria. The assay was found to be specific and did not cross react with other closely related bacterial species. The developed assay was highly specific, sensitive and also did not require agarose gel electrophoresis for post amplification analysis.
Yersinia pestis, the causative agent of plague mainly infects rodents, while humans are the accidental host. The conventional diagnostic methods available for Y. pestis exhibit cross-reactivity with ...other enteropathogenic bacteria which makes its detection difficult. Rapid and reliable point-of-care detection of Y. pestis is essential for timely initiation of medical treatment. In the present study, a pair of loop mediated isothermal amplification (LAMP) assays has been developed for rapid detection of Y. pestis. Two sets of LAMP primers, each containing 6 primers were specifically designed targeting caf1 and 3a genes located on pFra plasmid and chromosome of Y. pestis, respectively. Isothermal amplification was accomplished at 65 °C for 40 min for caf1 target, and at 63 °C for 50 min for 3a choromosomal target. The analytical sensitivity of the assay for the caf1 and 3a targets was found to be 500 fg and 100 fg genomic DNA of Y. pestis, respectively. The caf1 and 3a LAMP assays detected as few as 100 copies of caf1 and 10 copies of 3a gene targets harboured in the respective recombinant plasmids. The amplified products were detected visually under visible and UV light using SYBR Green 1 dye. The assay pair was found to be highly specific as it did not cross-react with closely related and other bacterial species.
•Plague necessitates an early stage diagnosis for timely medical management and to control spread of the disease.•Two LAMP assays in present study present simple and rapid tools for detection of Y. pestis without using a thermal cycler.•The assays are highly sensitive and specific and detected Y. pestis in artificially spiked blood samples.•The isothermal assays can be useful in detection of Y. pestis in plague endemic regions with limited laboratory resources.
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