A multi-faceted Case Area Targeted Intervention (CATI) approach emphasizing the integration of Water, Sanitation and Hygiene (WASH) interventions and Oral Cholera Vaccine (OCV) campaign was employed to respond to the ...A multi-faceted Case Area Targeted Intervention (CATI) approach emphasizing the integration of Water, Sanitation and Hygiene (WASH) interventions and Oral Cholera Vaccine (OCV) campaign was employed to respond to the outbreak of cholera in Garissa County. Drinking water sources in areas heavily impacted by cholera were systematically mapped and tested for microbiological quality. The quality assessment was carried out in April 2023 during an ongoing cholera outbreak in the county. A total of 109 samples were collected and tested for thermotolerant coliforms and other in situ parameters. The finding revealed that more than 87% of the samples did not meet the World Health Organization (WHO) standard for thermotolerant coliforms;and 30% had turbidity values above the recommended threshold values. None of the 109 samples had any traceable residual chlorine. Following these findings, the county government implemented the targeted interventions which resulted in a positive impact in the fight against cholera. The WHO supported key interventions which included capacity building in water quality monitoring and prepositioning of critical WASH commodities to the cholera affected areas.展开更多
At the beginning of the initial cholera outbreak in China,Wang Qingren(王清任),after years of clinical trials,became an early representative who discovered the infectious characteristics and observed the course of cho...At the beginning of the initial cholera outbreak in China,Wang Qingren(王清任),after years of clinical trials,became an early representative who discovered the infectious characteristics and observed the course of cholera in the field of traditional Chinesse medicine(TCM).Kou Langao(寇兰皋)and Xu Zimo(徐子默),both medical practitioners,constructed a diagnosis and treatment system for cholera with cold patterns under the theory of typhoid.They represented“School of Cholera with Cold Patterns”(SCCP).In the 1860s,with the influence of Wang Shixiong’s(王士雄)studies on the nature of cholera under the theory of epidemic febrile disease,the“School of Cholera with Heated Patterns”(SCHP)prevailed thereafter.The two schools complemented each other in theories and contributed to the integrity of TCM in cholera diagnosis and treatment.By reviewing previous literature,books,clinical cases,and historical materials in medical field,this article aims 1)to summarise the influence of TCM on the cognitive development towards cholera in the late Qing dynasty;2)to explore the origin of the controversy between SCCP and SCHP from historical evidence;3)to summarize the historical lessons from the debate over cholera in TCM based on the principle of treatment based on pattern identification,and offer suggestions for the current prevention and treatment of new diseases using TCM.展开更多
Cholera remains a public health threat in most developing countries in Asia and Africa including Malawi with seasonal recurrent outbreaks. Malawi’s recent Cholera outbreak in 2022 and 2023, exhibited higher morbidity...Cholera remains a public health threat in most developing countries in Asia and Africa including Malawi with seasonal recurrent outbreaks. Malawi’s recent Cholera outbreak in 2022 and 2023, exhibited higher morbidity and mortality rates than the past two decades. Lack of spatiotemporal-based technology and variability assessment tools in Malawi’s Cholera monitoring and management, limit our understanding of the disease’s epidemiology. The present work developed a spatiotemporal variability model for Cholera disease at district level and its relationship to socioeconomic and climatic factors based on cumulative confirmed Cholera cases in Malawi from March 2022 to July 2023 using Z-score statistic and multiscale geographically weighted regression (MGWR) in a Geographical Information System (GIS). We found out that socioeconomic factors such as access to safe drinking water, population density and poverty level, and climatic factors including temperature and rainfall strongly influenced Cholera prevalence in a complex and multifaceted manner. The model shows that Lilongwe, Mangochi, Blantyre and Balaka districts were highly vulnerable to Cholera disease followed by lakeshore districts of Salima, Nkhotakota, Nkhata-Bay and Karonga than other districts. We recommend strategic measures such as Water, Sanitation, and Hygiene (WASH) interventions, community awareness on proper water storage, Cholera case management, vaccination campaigns and spatial-based surveillance systems in the most affected districts. This research has shown that MGWR, as a surveillance system, has the potential of providing insights on the disease’s spatial patterns for public health authorities to identify high-risk districts and implement early response interventions to reduce the spread of the disease.展开更多
BACKGROUND Enterotoxins produce diarrhea through direct epithelial action and indirectly by activating the enteric nervous system.Calcium-sensing receptor(CaSR)inhibits both actions.The latter has been well documented...BACKGROUND Enterotoxins produce diarrhea through direct epithelial action and indirectly by activating the enteric nervous system.Calcium-sensing receptor(CaSR)inhibits both actions.The latter has been well documented in vitro but not in vivo.The hypothesis to be tested was that activating CaSR inhibits diarrhea in vivo.AIM To determine whether CaSR agonists ameliorate secretory diarrhea evoked by cholera toxin(CTX)in mice.METHODS CTX was given orally to C57BL/6 mice to induce diarrhea.Calcium and calci-mimetic R568 were used to activate CaSR.To maximize their local intestinal actions,calcium was administered luminally via oral rehydration solution(ORS),whereas R568 was applied serosally using an intraperitoneal route.To verify that their actions resulted from the intestine,effects were also examined on Cre-lox intestine-specific CaSR knockouts.Diarrhea outcome was measured biochemically by monitoring changes in fecal Cl-or clinically by assessing stool consistency and weight loss.RESULTS CTX induced secretory diarrhea,as evidenced by increases in fecal Cl-,stool consistency,and weight loss following CTX exposure,but did not alter CaSR,neither in content nor in function.Accordingly,calcium and R568 were each able to ameliorate diarrhea when applied to diseased intestines.Intestinal CaSR involvement is suggested by gene knockout experiments where the anti-diarrheal actions of R568 were lost in intestinal epithelial CaSR knockouts(villinCre/Casrflox/flox)and neuronal CaSR knockouts(nestinCre/Casrflox/flox).CONCLUSION Treatment of acute secretory diarrheas remains a global challenge.Despite advances in diarrhea research,few have been made in the realm of diarrhea therapeutics.ORS therapy has remained the standard of care,although it does not halt the losses of intestinal fluid and ions caused by pathogens.There is no cost-effective therapeutic for diarrhea.This and other studies suggest that adding calcium to ORS or using calcimimetics to activate intestinal CaSR might represent a novel approach for treating secretory diarrheal diseases.展开更多
目的:探讨罗汉果皂苷V(MV)对铁死亡诱导剂RAS选择性致死分子3(RSL3)诱导的人神经母细胞瘤SH-SY5Y细胞铁死亡的抑制作用及可能机制。方法:用RSL3诱导SH-SY5Y细胞建立铁死亡模型。MTT法检测细胞活力;倒置显微镜观察细胞形态;亚铁离子荧光...目的:探讨罗汉果皂苷V(MV)对铁死亡诱导剂RAS选择性致死分子3(RSL3)诱导的人神经母细胞瘤SH-SY5Y细胞铁死亡的抑制作用及可能机制。方法:用RSL3诱导SH-SY5Y细胞建立铁死亡模型。MTT法检测细胞活力;倒置显微镜观察细胞形态;亚铁离子荧光探针FerroFarRed检测细胞内亚铁离子含量;线粒体红色荧光探针MitoTracker Red CMXRos检测线粒体膜电位(MMP);超氧化物阴离子荧光探针二氢乙啶和线粒体超氧化物红色荧光探针MitoSoX Red分别检测细胞内和线粒体内活性氧(ROS)。微板法检测细胞谷胱甘肽(GSH)和丙二醛(MDA)水平。Western blot检测脂酰辅酶A合成酶长链家族成员4(ACSL4)、环加氧酶2(COX-2、)谷胱甘肽过氧化物酶4(GPX4)和溶质载体家族7成员11(SLC7A11)蛋白表达水平。分子对接技术预测MV与ACSL4、COX-2、GPX4和SLC7A11的靶向关系。结果:与control组相比,RSL3组SH-SY5Y细胞活力显著降低(P<0.01),细胞内亚铁离子含量、细胞内和线粒体内ROS水平及MDA水平显著升高(P<0.05或P<0.01),MMP和GSH水平显著降低(P<0.01),ACSL4和COX-2蛋白表达水平显著升高,而GPX4和SLC7A11蛋白表达水平显著降低(P<0.01),提示成功建立了细胞铁死亡模型。MV处理使细胞活力显著升高(P<0.05),细胞内亚铁离子含量、细胞内和线粒体内ROS水平及MDA水平显著降低(P<0.01),MMP和GSH水平显著升高(P<0.05或P<0.01);ACSL4和COX-2蛋白水平显著降低,而GPX4和SLC7A11蛋白水平显著升高(P<0.05或P<0.01)。分子对接结果显示,MV与铁死亡核心蛋白ACSL4、COX-2、GPX4和SLC7A11存在结合位点。结论:MV可抑制RSL3诱导的SH-SY5Y细胞铁死亡的发生,其机制可能与激活SLC7A11/GPX4和抑制ACSL4/COX-2有关。展开更多
文摘A multi-faceted Case Area Targeted Intervention (CATI) approach emphasizing the integration of Water, Sanitation and Hygiene (WASH) interventions and Oral Cholera Vaccine (OCV) campaign was employed to respond to the outbreak of cholera in Garissa County. Drinking water sources in areas heavily impacted by cholera were systematically mapped and tested for microbiological quality. The quality assessment was carried out in April 2023 during an ongoing cholera outbreak in the county. A total of 109 samples were collected and tested for thermotolerant coliforms and other in situ parameters. The finding revealed that more than 87% of the samples did not meet the World Health Organization (WHO) standard for thermotolerant coliforms;and 30% had turbidity values above the recommended threshold values. None of the 109 samples had any traceable residual chlorine. Following these findings, the county government implemented the targeted interventions which resulted in a positive impact in the fight against cholera. The WHO supported key interventions which included capacity building in water quality monitoring and prepositioning of critical WASH commodities to the cholera affected areas.
基金This study is financed by the grants from the Fundamental Research Funds for the Central Universities(No.23JNQMX48 and No.23JNSYS04)Major Project of the Key Research Bases of Humanities and Social Sciences of Ministry of Education(No.22JJD770054).
文摘At the beginning of the initial cholera outbreak in China,Wang Qingren(王清任),after years of clinical trials,became an early representative who discovered the infectious characteristics and observed the course of cholera in the field of traditional Chinesse medicine(TCM).Kou Langao(寇兰皋)and Xu Zimo(徐子默),both medical practitioners,constructed a diagnosis and treatment system for cholera with cold patterns under the theory of typhoid.They represented“School of Cholera with Cold Patterns”(SCCP).In the 1860s,with the influence of Wang Shixiong’s(王士雄)studies on the nature of cholera under the theory of epidemic febrile disease,the“School of Cholera with Heated Patterns”(SCHP)prevailed thereafter.The two schools complemented each other in theories and contributed to the integrity of TCM in cholera diagnosis and treatment.By reviewing previous literature,books,clinical cases,and historical materials in medical field,this article aims 1)to summarise the influence of TCM on the cognitive development towards cholera in the late Qing dynasty;2)to explore the origin of the controversy between SCCP and SCHP from historical evidence;3)to summarize the historical lessons from the debate over cholera in TCM based on the principle of treatment based on pattern identification,and offer suggestions for the current prevention and treatment of new diseases using TCM.
文摘Cholera remains a public health threat in most developing countries in Asia and Africa including Malawi with seasonal recurrent outbreaks. Malawi’s recent Cholera outbreak in 2022 and 2023, exhibited higher morbidity and mortality rates than the past two decades. Lack of spatiotemporal-based technology and variability assessment tools in Malawi’s Cholera monitoring and management, limit our understanding of the disease’s epidemiology. The present work developed a spatiotemporal variability model for Cholera disease at district level and its relationship to socioeconomic and climatic factors based on cumulative confirmed Cholera cases in Malawi from March 2022 to July 2023 using Z-score statistic and multiscale geographically weighted regression (MGWR) in a Geographical Information System (GIS). We found out that socioeconomic factors such as access to safe drinking water, population density and poverty level, and climatic factors including temperature and rainfall strongly influenced Cholera prevalence in a complex and multifaceted manner. The model shows that Lilongwe, Mangochi, Blantyre and Balaka districts were highly vulnerable to Cholera disease followed by lakeshore districts of Salima, Nkhotakota, Nkhata-Bay and Karonga than other districts. We recommend strategic measures such as Water, Sanitation, and Hygiene (WASH) interventions, community awareness on proper water storage, Cholera case management, vaccination campaigns and spatial-based surveillance systems in the most affected districts. This research has shown that MGWR, as a surveillance system, has the potential of providing insights on the disease’s spatial patterns for public health authorities to identify high-risk districts and implement early response interventions to reduce the spread of the disease.
基金Supported by Eunice Kennedy Shriver National Institute of Child Health&Human Development of the National Institutes of Health,No.1K08HD079674-01 and 1R41HD092133-01National Institute of Allergy and Infectious Diseases,No.1A21AI169282and VA Research Career Scientist Award,No.1IK6BX004835.
文摘BACKGROUND Enterotoxins produce diarrhea through direct epithelial action and indirectly by activating the enteric nervous system.Calcium-sensing receptor(CaSR)inhibits both actions.The latter has been well documented in vitro but not in vivo.The hypothesis to be tested was that activating CaSR inhibits diarrhea in vivo.AIM To determine whether CaSR agonists ameliorate secretory diarrhea evoked by cholera toxin(CTX)in mice.METHODS CTX was given orally to C57BL/6 mice to induce diarrhea.Calcium and calci-mimetic R568 were used to activate CaSR.To maximize their local intestinal actions,calcium was administered luminally via oral rehydration solution(ORS),whereas R568 was applied serosally using an intraperitoneal route.To verify that their actions resulted from the intestine,effects were also examined on Cre-lox intestine-specific CaSR knockouts.Diarrhea outcome was measured biochemically by monitoring changes in fecal Cl-or clinically by assessing stool consistency and weight loss.RESULTS CTX induced secretory diarrhea,as evidenced by increases in fecal Cl-,stool consistency,and weight loss following CTX exposure,but did not alter CaSR,neither in content nor in function.Accordingly,calcium and R568 were each able to ameliorate diarrhea when applied to diseased intestines.Intestinal CaSR involvement is suggested by gene knockout experiments where the anti-diarrheal actions of R568 were lost in intestinal epithelial CaSR knockouts(villinCre/Casrflox/flox)and neuronal CaSR knockouts(nestinCre/Casrflox/flox).CONCLUSION Treatment of acute secretory diarrheas remains a global challenge.Despite advances in diarrhea research,few have been made in the realm of diarrhea therapeutics.ORS therapy has remained the standard of care,although it does not halt the losses of intestinal fluid and ions caused by pathogens.There is no cost-effective therapeutic for diarrhea.This and other studies suggest that adding calcium to ORS or using calcimimetics to activate intestinal CaSR might represent a novel approach for treating secretory diarrheal diseases.
文摘目的:探讨罗汉果皂苷V(MV)对铁死亡诱导剂RAS选择性致死分子3(RSL3)诱导的人神经母细胞瘤SH-SY5Y细胞铁死亡的抑制作用及可能机制。方法:用RSL3诱导SH-SY5Y细胞建立铁死亡模型。MTT法检测细胞活力;倒置显微镜观察细胞形态;亚铁离子荧光探针FerroFarRed检测细胞内亚铁离子含量;线粒体红色荧光探针MitoTracker Red CMXRos检测线粒体膜电位(MMP);超氧化物阴离子荧光探针二氢乙啶和线粒体超氧化物红色荧光探针MitoSoX Red分别检测细胞内和线粒体内活性氧(ROS)。微板法检测细胞谷胱甘肽(GSH)和丙二醛(MDA)水平。Western blot检测脂酰辅酶A合成酶长链家族成员4(ACSL4)、环加氧酶2(COX-2、)谷胱甘肽过氧化物酶4(GPX4)和溶质载体家族7成员11(SLC7A11)蛋白表达水平。分子对接技术预测MV与ACSL4、COX-2、GPX4和SLC7A11的靶向关系。结果:与control组相比,RSL3组SH-SY5Y细胞活力显著降低(P<0.01),细胞内亚铁离子含量、细胞内和线粒体内ROS水平及MDA水平显著升高(P<0.05或P<0.01),MMP和GSH水平显著降低(P<0.01),ACSL4和COX-2蛋白表达水平显著升高,而GPX4和SLC7A11蛋白表达水平显著降低(P<0.01),提示成功建立了细胞铁死亡模型。MV处理使细胞活力显著升高(P<0.05),细胞内亚铁离子含量、细胞内和线粒体内ROS水平及MDA水平显著降低(P<0.01),MMP和GSH水平显著升高(P<0.05或P<0.01);ACSL4和COX-2蛋白水平显著降低,而GPX4和SLC7A11蛋白水平显著升高(P<0.05或P<0.01)。分子对接结果显示,MV与铁死亡核心蛋白ACSL4、COX-2、GPX4和SLC7A11存在结合位点。结论:MV可抑制RSL3诱导的SH-SY5Y细胞铁死亡的发生,其机制可能与激活SLC7A11/GPX4和抑制ACSL4/COX-2有关。
