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Acute Gastroenteritis in Children of the World: What Needs to be Done?

世界儿童急性胃肠炎: 需要做什么?

  • 影响因子:2.36
  • DOI:10.1097/MPG.0000000000002669
  • 作者列表:"Guarino A","Aguilar J","Berkley J","Broekaert I","Vazquez-Frias R","Holtz L","Vecchio AL","Meskini T","Moore S","Medina JFR","Sandhu B","Smarrazzo A","Szajewska H","Treepongkaruna S
  • 发表时间:2020-02-19
Abstract

The incidence of gastroenteritis has greatly reduced due to improved hygiene conditions in developing countries and the use of Rotavirus vaccine. However, still thousands of children die from gastroenteritis, most of them in poor countries. Yet gastroenteritis management is simple, inexpensive, and effective and is largely the same all over the world. Universal guidelines for gastroenteritis guide the management and include simple interventions put forward early in the course of the disease. Treatment includes rehydration, continuing oral feeding, and anti-infective drugs in selected clinical conditions related to the symptoms or to host-related risk, and possible additional drug treatment to reduce the duration and severity of symptoms. There may be minor geographical differences in the treatment applied due to health care organizations that do not substantially change the standard universal recommendations. Prevention is recommended with sanitation interventions and Rotavirus universal immunization. Implementation of those interventions through educational initiatives and local programs in target areas are needed. A series of recommendations for interventions, education, and research priorities are included here with the aim of reducing the burden of gastroenteritis, to be pursued by scientists, physicians, policy makers, and stakeholders involved. They include the need of recommendations for the management of gastroenteritis in malnourished children, in those with chronic conditions, in neonates, and in emergency settings. A reference system to score dehydration, the definition of optimal composition of rehydration solution and the indications for anti-infective therapy are also included. Rotavirus immunization should be actively promoted, and evidence-based guidelines should be universally implemented. Research priorities are also indicated.

摘要

由于发展中国家卫生条件的改善和轮状病毒疫苗的使用,胃肠炎的发病率大大降低。然而,仍有数千名儿童死于肠胃炎,其中大多数在贫穷国家。然而,胃肠炎的管理是简单、廉价和有效的,在世界各地基本相同。胃肠炎的通用指南指导管理,并包括在病程早期提出的简单干预措施。治疗包括补液,继续口服喂养,在选定的临床条件下抗感染药物与症状或宿主相关的风险, 和可能的额外的药物治疗,以减少症状的持续时间和严重程度。由于卫生保健组织没有实质性改变标准的普遍建议,所应用的治疗可能存在微小的地理差异。建议通过卫生干预和轮状病毒普遍免疫进行预防。需要通过目标地区的教育倡议和地方方案实施这些干预措施。这里包括了一系列关于干预、教育和研究重点的建议,目的是减轻胃肠炎的负担,供科学家、医生、决策者和相关利益相关者追求。它们包括需要对营养不良儿童、慢性病患者、新生儿和紧急情况下胃肠炎的管理提出建议。还包括脱水评分参考系统、补液最佳组成的定义和抗感染治疗的适应症。应积极推广轮状病毒免疫,并普遍实施循证指南。还指出了研究重点。

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影响因子:6.74700
发表时间:2020-01-21
来源期刊:mBio
DOI:10.1128/mBio.03105-19
作者列表:["Kuehl CJ","D'Gama JD","Warr AR","Waldor MK"]

METHODS:Shigella species cause diarrheal disease globally. Shigellosis is typically characterized by bloody stools and colitis with mucosal damage and is the leading bacterial cause of diarrheal death worldwide. After the pathogen is orally ingested, it invades and replicates within the colonic epithelium through mechanisms that rely on its type III secretion system (T3SS). Currently, oral infection-based small animal models to study the pathogenesis of shigellosis are lacking. Here, we found that orogastric inoculation of infant rabbits with Shigella flexneri resulted in diarrhea and colonic pathology resembling that found in human shigellosis. Fasting animals prior to S. flexneri inoculation increased the frequency of disease. The pathogen colonized the colon, where both luminal and intraepithelial foci were observed. The intraepithelial foci likely arise through S. flexneri spreading from cell to cell. Robust S. flexneri intestinal colonization, invasion of the colonic epithelium, and epithelial sloughing all required the T3SS as well as IcsA, a factor required for bacterial spreading and adhesion in vitro Expression of the proinflammatory chemokine interleukin 8 (IL-8), detected with in situ mRNA labeling, was higher in animals infected with wild-type S. flexneri versus mutant strains deficient in icsA or T3SS, suggesting that epithelial invasion promotes expression of this chemokine. Collectively, our findings suggest that oral infection of infant rabbits offers a useful experimental model for studies of the pathogenesis of shigellosis and for testing of new therapeutics.IMPORTANCEShigella species are the leading bacterial cause of diarrheal death globally. The pathogen causes bacillary dysentery, a bloody diarrheal disease characterized by damage to the colonic mucosa and is usually spread through the fecal-oral route. Small animal models of shigellosis that rely on the oral route of infection are lacking. Here, we found that orogastric inoculation of infant rabbits with S. flexneri led to a diarrheal disease and colonic pathology reminiscent of human shigellosis. Diarrhea, intestinal colonization, and pathology in this model were dependent on the S. flexneri type III secretion system and IcsA, canonical Shigella virulence factors. Thus, oral infection of infant rabbits offers a feasible model to study the pathogenesis of shigellosis and to develop and test new therapeutics.

影响因子:5.36
发表时间:2020-01-20
DOI:10.1007/s00259-020-04686-1
作者列表:["Willowson KP","Schembri GP","Bernard EJ","Chan DL","Bailey DL"]

METHODS:PURPOSE:To quantify the effects of absorbed radiation dose on healthy liver parenchyma following radioembolisation (RE) using [99mTc]TcMebrofenin to analyse both global and regional liver function. METHODS:Patients having RE to treat hepatic disease underwent a [99mTc]TcMebrofenin hepatobilliary scintigraphy (HBS) study at both baseline and 8 weeks following treatment. Changes in global liver uptake rate were compared with healthy liver absorbed dose measures derived from the post-treatment 90Y PET/CT, including average dose, minimum dose to 70% of the volume (D70) and volume receiving at least 50 Gy (V50). Changes in functional burden associated with treatment and spared liver volumes in patients receiving lobar RE were also assessed, as were changes experienced by regional volumes corresponding to various dose ranges. Standard liver function pathology tests (LFTs) (bilirubin, albumin, ALP, AST, ALT and GGT) were examined for changes between baseline and post-treatment. RESULTS:Thirty-five patients were included in the study, of which, 9 had lobar treatment. A significant linear correlation was found between both baseline global liver uptake rate (negative) and D70 with change in global liver uptake rate. Patients undergoing lobar treatments demonstrated a shift in functional burden, and a significant difference was seen between the mean dose corresponding to liver volumes that increased their functional burden (9 Gy) and those that decreased their functional burden (35 Gy). No baseline LFTs predicted a decrease in global liver function; however, D70 demonstrated a linear correlation with changes in bilirubin and GGT. CONCLUSIONS:Given the significant negative relationship between baseline and change in global liver uptake rate, baseline HBS studies should not be used alone to disqualify patients considered for RE. In terms of treatment planning and evaluation, D70 may be the most appropriate metric of dose, with values greater than 15 Gy indicative of a likely drop in global liver function. The evidence of increasing functional burden in spared liver volumes suggests that patients at risk of complications could benefit from a lobar approach to treatment.

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影响因子:3.32
发表时间:2020-01-09
DOI:10.1016/j.intimp.2019.106144
作者列表:["Fan M","Xiang G","Chen J","Gao J","Xue W","Wang Y","Li W","Zhou L","Jiao R","Shen Y","Xu Q"]

METHODS:NLRP3 inflammasome may serve as a potential target for the development of novel therapeutics for inflammatory bowel diseases. In this study, we found that Libertellenone M (Lib M), a secondary metabolite from the endophytic fungus Phomopsis sp. S12, has anti-inflammatory potential both in vitro and in vivo. Lib M selectively inhibited the expression of proinflammatory cytokine IL-1β and IL-18 in LPS-activated macrophages. The cleavage of pro-caspase 1 was remarkably reduced by Lib M in macrophages stimulated with three NLRP3 inflammasome activators. Administering Lib M attenuated dextran sulfate sodium-induced experimental acute colitis in mice and significantly reduced the production of these cytokines and cleaved caspase 1 in colon tissues. Apart from inhibition of NLRP3 inflammasome assembly, Lib M also suppressed NF-κB nuclear translocation in macrophages. Taken together, these findings suggest that Lib M-mediated inhibition of NLRP3 inflammasome activation could protect against colitis-like inflammatory diseases, and that this compound derived from a plant-associated fungus might inspire the exploration of novel immunosuppressive agents.

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