- 作者列表："Lowenstein C","Vasco K","Sarzosa S","Salinas L","Mosco AT","Perry MJ","Simmens S","Trueba G","Eisenberg JNS","Graham JP
Domestic animals in the household environment have the potential to affect a child's carriage of zoonotic enteric pathogens and risk of diarrhea. This study examines the risk factors associated with pediatric diarrhea and carriage of zoonotic enteric pathogens among children living in communities where smallholder livestock production is prevalent. We conducted an observational study of children younger than 5 years that included the analysis of child (n = 306) and animal (n = 480) fecal samples for Campylobacter spp., atypical enteropathogenic Escherichia coli, Shiga toxin-producing E. coli, Salmonella spp., Yersinia spp., Cryptosporidium parvum, and Giardia lamblia. Among these seven pathogens, Giardia was the most commonly identified pathogen among children and animals in the same household, most of which was found in child-dog pairs. Campylobacter spp. was also relatively common within households, particularly among child-chicken and child-guinea pig pairs. We used multivariable Poisson regression models to assess risk factors associated with a child being positive for at least one zoonotic enteric pathogen or having diarrhea during the last week. Children who interacted with domestic animals-a behavior reported by nearly three-quarters of households owning animals-were at an increased risk of colonization with at least one zoonotic enteric pathogen (prevalence ratio [PR] = 1.56, 95% CI: 1.00-2.42). The risk of diarrhea in the last seven days was elevated but not statistically significant (PR = 2.27, CI: 0.91, 5.67). Interventions that aim to reduce pediatric exposures to enteric pathogens will likely need to be incorporated with approaches that remove animal fecal contamination from the domestic environment and encourage behavior change aimed at reducing children's contact with animal feces through diverse exposure pathways.
家庭环境中的家畜有可能影响儿童携带人畜共患的肠道病原体和腹泻的风险。本研究探讨了生活在小农畜牧生产流行的社区的儿童中与小儿腹泻和携带人畜共患肠道病原体相关的危险因素。我们对 5 岁以下儿童进行了一项观察性研究，包括分析儿童 (n = 306) 和动物 (n = 480) 粪便样本中的弯曲杆菌属。,非典型肠致病性大肠杆菌，产志贺毒素 E.大肠杆菌，沙门氏菌属,耶尔森菌属。微小隐孢子虫和蓝氏贾第鞭毛虫。在这 7 种病原体中，贾第鞭毛虫是同一家庭儿童和动物中最常见的病原体，其中大部分是在儿童-狗对中发现的。弯曲杆菌属。在家庭中也相对常见，特别是在儿童-鸡和儿童-豚鼠对中。我们使用多变量泊松回归模型评估与儿童至少一种人畜共患肠道病原体阳性或上周腹泻相关的危险因素。与家畜互动的儿童 -- 近四分之三拥有动物的家庭报告了这一行为 -- 至少感染一种人畜共患肠道病原体的风险增加 (患病率比 [PR] = 1.56, 95% CI: 1.00-2.42)。最近 7 天腹泻风险升高，但无统计学意义 (PR = 2.27，CI: 0.91，5.67)。旨在减少儿童肠道病原体暴露的干预措施可能需要纳入从家庭环境中去除动物粪便污染的方法，并鼓励旨在减少儿童接触动物粪便的行为改变。通过不同的暴露途径。
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.
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.
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.