274 research outputs found
A prospective multi-center observational study of children hospitalized with diarrhea in Ho Chi Minh City, Vietnam.
We performed a prospective multicenter study to address the lack of data on the etiology, clinical and demographic features of hospitalized pediatric diarrhea in Ho Chi Minh City (HCMC), Vietnam. Over 2,000 (1,419 symptomatic and 609 non-diarrheal control) children were enrolled in three hospitals over a 1-year period in 2009-2010. Aiming to detect a panel of pathogens, we identified a known diarrheal pathogen in stool samples from 1,067/1,419 (75.2%) children with diarrhea and from 81/609 (13.3%) children without diarrhea. Rotavirus predominated in the symptomatic children (664/1,419; 46.8%), followed by norovirus (293/1,419; 20.6%). The bacterial pathogens Salmonella, Campylobacter, and Shigella were cumulatively isolated from 204/1,419 (14.4%) diarrheal children and exhibited extensive antimicrobial resistance, most notably to fluoroquinolones and third-generation cephalosporins. We suggest renewed efforts in generation and implementation of policies to control the sale and prescription of antimicrobials to curb bacterial resistance and advise consideration of a subsidized rotavirus vaccination policy to limit the morbidity due to diarrheal disease in Vietnam
The unfolded protein response in immunity and inflammation.
The unfolded protein response (UPR) is a highly conserved pathway that allows the cell to manage endoplasmic reticulum (ER) stress that is imposed by the secretory demands associated with environmental forces. In this role, the UPR has increasingly been shown to have crucial functions in immunity and inflammation. In this Review, we discuss the importance of the UPR in the development, differentiation, function and survival of immune cells in meeting the needs of an immune response. In addition, we review current insights into how the UPR is involved in complex chronic inflammatory diseases and, through its role in immune regulation, antitumour responses.This work was supported by the Netherlands Organization for Scientific Research Rubicon grant 825.13.012 (J.G.); US National Institutes of Health (NIH) grants DK044319, DK051362, DK053056 and DK088199, and the Harvard Digestive Diseases Center (HDDC) grant DK034854 (R.S.B.); National Institutes of Health grants DK042394, DK088227, DK103183 and CA128814 (R.J.K.); and European Research Council (ERC) Starting Grant 260961, ERC Consolidator Grant 648889, and the Wellcome Trust Investigator award 106260/Z/14/Z (A.K.).This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/nri.2016.6
Recent Development of Algal Biochar for Contaminant Remediation and Energy Application: A State-of-the Art Review
Algae, as a low-impact aquatic feedstock, is regarded as a promising biomass for producing valuable biofuel, syngas, and biochar. Algae, on the other hand, are mostly composed of lipids, proteins, and carbohydrates, as opposed to lignocellulosic biomass. Algal species have a faster growth rate and higher photosynthetic efficiency than terrestrial plants, making them an excellent alternative for a sustainable environment. Algal biomass has shown great promise as a raw material for biochar production in recent years. Algae biochar has a high potential for use as a material for contamination remediation and energy application. This review paper summarizes the applicability of algal biochar, algal biochar modification strategies, fabrication methods, and algal biochar properties. Carbon sequestration, sediment and water treatment, and energy applications are all thoroughly discussed. More emphasis should be placed on practical applications, and more research should be conducted to address existing problems
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Recent Advances in the Diagnosis of Talaromycosis
Talaromycosis is an invasive fungal disease endemic to Southeast Asia. While culture is essential in identification, susceptibility testing, and typing, the low sensitivity and long turnaround times limit its clinical utility. Several promising monoclonal antibody–based (MAb) antigen-detection assays have been evaluated in large patient cohorts. This includes the MAb-Mp1p and MAb-4D1 enzyme immunoassays and their point-of-care platforms. Quantitative polymerase chain reaction (qPCR) assays targeting the 5.8S or 18S region of ribosomal RNA have been developed. These antigen and qPCR assays are highly specific and more sensitive than blood culture, making them excellent rapid rule-in tests for talaromycosis in people with a compatible clinical syndrome. Metagenomic next-generation sequencing is emerging as a promising tool for non-bias detection of talaromycosis. Host-based diagnostics targeting antibodies, interferon-gamma release, and transcriptomics are being actively developed. This review summarizes recent advances in the diagnosis of talaromycosis and provides expert recommendations on the application of these novel tests to improve the diagnostic algorithm and management of talaromycosis
Intelligent Insect–Computer Hybrid Robot: Installing Innate Obstacle Negotiation and Onboard Human Detection onto Cyborg Insect
Developing small mobile robots for Urban Search and Rescue (USAR) is a major challenge due to constraints in size and power required to perform vital functions such as obstacle navigation, victim detection, and wireless communication. Drawing upon the idea that insects’ locomotion can be controlled, what if we further utilize the insects’ intrinsic ability to avoid obstacles? Herein, a cockroach hybrid robot (≈ 1.5 cm height, 5.7 cm length) that implements the abovementioned functions is developed. It is tested in an arena with randomly placed obstacles, and a motion capture system is used to track the insect's position among the untracked obstacles. A navigation algorithm that uses an inertial measurement unit (IMU) is developed to heuristically predict the insect's situation and stimulate the insect to escape nearby obstacles. The utilization of insect's intrinsic locomotor ability and low-powered IMU reduces the onboard power load, allowing the addition of a human-detecting function. An image classification model enables the use of an onboard low-resolution infrared camera for human detection. Consequently, a single hybrid robot is established that includes locomotion control, autonomous navigation in obstructed areas, onboard human detection, and wireless communication, representing a significant step toward real USAR application
Comprehensive Analysis of MGMT Promoter Methylation: Correlation with MGMT Expression and Clinical Response in GBM
O6-methylguanine DNA-methyltransferase (MGMT) promoter methylation has been identified as a potential prognostic marker for glioblastoma patients. The relationship between the exact site of promoter methylation and its effect on gene silencing, and the patient's subsequent response to therapy, is still being defined. The aim of this study was to comprehensively characterize cytosine-guanine (CpG) dinucleotide methylation across the entire MGMT promoter and to correlate individual CpG site methylation patterns to mRNA expression, protein expression, and progression-free survival. To best identify the specific MGMT promoter region most predictive of gene silencing and response to therapy, we determined the methylation status of all 97 CpG sites in the MGMT promoter in tumor samples from 70 GBM patients using quantitative bisulfite sequencing. We next identified the CpG site specific and regional methylation patterns most predictive of gene silencing and improved progression-free survival. Using this data, we propose a new classification scheme utilizing methylation data from across the entire promoter and show that an analysis based on this approach, which we call 3R classification, is predictive of progression-free survival (HR = 5.23, 95% CI [2.089–13.097], p<0.0001). To adapt this approach to the clinical setting, we used a methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) test based on the 3R classification and show that this test is both feasible in the clinical setting and predictive of progression free survival (HR = 3.076, 95% CI [1.301–7.27], p = 0.007). We discuss the potential advantages of a test based on this promoter-wide analysis and compare it to the commonly used methylation-specific PCR test. Further prospective validation of these two methods in a large independent patient cohort will be needed to confirm the added value of promoter wide analysis of MGMT methylation in the clinical setting
Palmitoleate Induces Hepatic Steatosis but Suppresses Liver Inflammatory Response in Mice
The interaction between fat deposition and inflammation during obesity contributes to the development of non-alcoholic fatty liver disease (NAFLD). The present study examined the effects of palmitoleate, a monounsaturated fatty acid (16∶1n7), on liver metabolic and inflammatory responses, and investigated the mechanisms by which palmitoleate increases hepatocyte fatty acid synthase (FAS) expression. Male wild-type C57BL/6J mice were supplemented with palmitoleate and subjected to the assays to analyze hepatic steatosis and liver inflammatory response. Additionally, mouse primary hepatocytes were treated with palmitoleate and used to analyze fat deposition, the inflammatory response, and sterol regulatory element-binding protein 1c (SREBP1c) activation. Compared with controls, palmitoleate supplementation increased the circulating levels of palmitoleate and improved systemic insulin sensitivity. Locally, hepatic fat deposition and SREBP1c and FAS expression were significantly increased in palmitoleate-supplemented mice. These pro-lipogenic events were accompanied by improvement of liver insulin signaling. In addition, palmitoleate supplementation reduced the numbers of macrophages/Kupffer cells in livers of the treated mice. Consistently, supplementation of palmitoleate decreased the phosphorylation of nuclear factor kappa B (NF-κB, p65) and the expression of proinflammatory cytokines. These results were recapitulated in primary mouse hepatocytes. In terms of regulating FAS expression, treatment of palmitoleate increased the transcription activity of SREBP1c and enhanced the binding of SREBP1c to FAS promoter. Palmitoleate also decreased the phosphorylation of NF-κB p65 and the expression of proinflammatory cytokines in cultured macrophages. Together, these results suggest that palmitoleate acts through dissociating liver inflammatory response from hepatic steatosis to play a unique role in NAFLD
Genetic Biomarkers for ALS Disease in Transgenic SOD1G93A Mice
The pathophysiological mechanisms of both familial and sporadic Amyotrophic Lateral Sclerosis (ALS) are unknown, although growing evidence suggests that skeletal muscle tissue is a primary target of ALS toxicity. Skeletal muscle biopsies were performed on transgenic SOD1G93A mice, a mouse model of ALS, to determine genetic biomarkers of disease longevity. Mice were anesthetized with isoflurane, and three biopsy samples were obtained per animal at the three main stages of the disease. Transcriptional expression levels of seventeen genes, Ankrd1, Calm1, Col19a1, Fbxo32, Gsr, Impa1, Mef2c, Mt2, Myf5, Myod1, Myog, Nnt, Nogo A, Pax7, Rrad, Sln and Snx10, were tested in each muscle biopsy sample. Total RNA was extracted using TRIzol Reagent according to the manufacturer's protocol, and variations in gene expression were assayed by real-time PCR for all of the samples. The Pearson correlation coefficient was used to determine the linear correlation between transcriptional expression levels throughout disease progression and longevity. Consistent with the results obtained from total skeletal muscle of transgenic SOD1G93A mice and 74-day-old denervated mice, five genes (Mef2c, Gsr, Col19a1, Calm1 and Snx10) could be considered potential genetic biomarkers of longevity in transgenic SOD1G93A mice. These results are important because they may lead to the exploration of previously unexamined tissues in the search for new disease biomarkers and even to the application of these findings in human studies
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