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A One Health approach to fight antimicrobial resistance in Uganda: Implementation experience, results, and lessons learned

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Biosafety and Health 2024年第2期6卷 125-132页

作者： Reuben Kiggundu J.P.Waswa Niranjan Konduri Hassan Kasuja Marion Murungi Patrick Vudriko Harriet Akello Eric Lugada cecilia Muiva Esther Were Dinah Tjipura Henry Kajumbula kate Kikule Emmanuel Nfor Mohan P.Joshi USAID Medicines Technologiesand Pharmaceutical Services ProgramManagement Sciences for HealthKampala 256Uganda USAID Medicines Technologiesand Pharmaceutical Services ProgramManagement Sciences for HealthArlingtonVA 22203USA college of Veterinary Medicine Animal Resources and BiosecurityMakerere UniversityKampala 256Uganda Ministry of Health Uganda Kampala 256Uganda USAID Strengthening Supply chain Systems Activity Management Sciences for HealthKampala 256Uganda USAID Medicines Technologiesand Pharmaceutical Services ProgramManagement Sciences for HealthNairobi 254Kenya Department of Microbiology College of Health SciencesMakerere UniversityKampala 256Uganda

Uganda has been implementing the Global Health Security Agenda(GHSA)since 2015 to build its capacity according to World Health Organization(WHO)Benchmarks on International Health Regulations *** country remains prone to outbreaks,with more than 20 disease outbreaks reported in the past five years,including Ebola virus disease,crimean-congo haemorrhagic fever,Marburg haemorrhagic fever,measles,yellow fever,coronavirus disease 2019(cOVID-19),and *** resistance(AMR)is an ongoing *** scored capacity level 3 on infection prevention and control(IPc)and antimicrobial stewardship(AMS)in the 2017 Joint External Evaluation(JEE)*** gaps were being addressed after a self-assessment in *** paper describes the technical assistance approaches provided to Uganda by the Medicines,Technologies,and Pharmaceutical Services Program,funded by the United States(U.S.)Agency for International Development,and implemented by Management Sciences for *** program,through a One Health approach,supported systematic capacity strengthening based on the JEE's capacity advancement framework for global health security,specifically relating to *** program's interventions impacted 32 WHO benchmark actions(7 for AMR multisectoral coordination,16 for IPc,and 9 for AMS),contributing to Uganda's strengthened GHSA *** success built on the AMR platform,the program trained 745 health workers in IPc for the Ebola virus and provided support for simulation exercises by eight district IPc *** program also worked with the Ministry of Health to coordinate IPc for the cOVID-19 response in five health regions,covering 45 districts and reaching 5,452 health workers at 858 health facilities.

关键词： One health Antimicrobial resistance Antibiotic resistance Jointexternal evaluation Global health security Uganda Africa WHO Benchmarks for International Health Regulations capacities

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The Triple combination of Meropenem,Avibactam,and a Metallo-b-Lactamase Inhibitor Optimizes Antibacterial coverage Against Different b-Lactamase Producers

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Engineering 2024年第7期38卷 124-132页

作者： Zhuoren Ling Alistair James Macdonald Farley Aditya Lankapalli Yanfang Zhang Shonnette Premchand-Branker kate cook Andrei Baran charlotte Gray-Hammerton claudia Orbegozo Rubio Edgars Suna Jordan Mathias Jürgen Brem Kirsty Sands Maria Nieto-Rosado Maria Mykolaivna Trush Nadira Naznin Rakhi Willames Martins Yuqing Zhou christopher Joseph Schofield Timothy Walsh Department of Biology&Ineos Oxford Institute for Antimicrobial Research University of OxfordOxford OX13REUK chemistry Research Laboratory Department of Chemistry and the Ineos Oxford Institute for Antimicrobial ResearchUniversity of OxfordOxford OX13TAUK Latvian Institute of Organic Synthesis Riga LV-1006Latvia Department of Medical Microbiology Division of Infection and ImmunitySchool of MedicineCardiff UniversityCardiff CF144XNUK Enzymology and Applied Biocatalysis Research center Faculty of Chemistry and Chemical EngineeringBabes-Bolyai UniversityCluj-Napoca 400028Romania

This work explores the potential of a triple combination of meropenem(MEM),a novel metallo-blactamase(MBL)inhibitor(indole-2-carboxylate 58(Inc58)),and a serine-b-lactamase(SBL)inhibitor(avibactam(AVI))for broad-spectrum activity against carbapenemase-producing bacteria.A diverse panel comprising MBL-and SBL-producing strains was used for susceptibility testing of the triple combination using the agar dilution *** frequency of resistance(FoR)to MEM combined with Inc58 was *** were sequenced and tested for cross resistance,fitness,and the stability of the resistance *** with the double combinations of MEM plus an SBL or MBL inhibitor,the triple combination extended the spectrum of activity to most of the isolates bearing SBLs(oxacillinase-48(OXA-48)and Klebsiella pneumoniae carbapenemase-2(KPc-2))and MBLs(New Delhi metallo-blactamases(NDMs)),although it was not effective against Verona integron-encoded metallo-blactamase(VIM)-carrying Pseudomonas aeruginosa(***)and OXA-23-carrying Acinetobacter baumannii(***).The FoR to MEM plus Inc58 ranged from 2.22×10^(-7)to 1.13×10^(-6).The resistance correlated with mutations to ompc and comR,affecting porin c and copper permeability,*** mutants manifested a fitness cost,a decreased level of resistance during passage without antibiotic pressure,and cross resistance to another carbapenem(imipenem)and a b-lactamase inhibitor(taniborbactam).In conclusion,compared with the dual combinations,the triple combination of MEM with Inc58 and AVI showed a much wider spectrum of activity against different carbapenemaseproducing bacteria,revealing a new strategy to combat b-lactamase-mediated antimicrobial resistance.

关键词： carbapenemase Metallo/serine-b-lactamase inhibitor Avibactam Meropenem Antimicrobial resistance

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Sterile signals generate weaker and delayed macrophage NLRP3 inflammasome responses relative to microbial signals

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cellular & Molecular Immunology 2017年第1期14卷 118-126页

作者： Jelena S Bezbradica Rebecca c coll kate Schroder Institute for Molecular Bioscience (IMB) IMB Centre for Inflammation and Disease Research and Australian Infectious Diseases Research Centre The University of Queensland Brisbane St Lucia Queensland 4072 Australia

Inflammation is the host response to microbial infection or sterile injury that aims to eliminate the insult, repair the tissue and restore homeostasis. Macrophages and the NLRP3 inflammasome are key sentinels for both types of insult. Although it is well established that the NLRP3 inflammasome is activated by microbial products and molecules released during sterile injury, it is unclear whether the responses elicited by these different types of signals are distinct. In this study, we used lipopolysaccharide and tumor necrosis factor as prototypical microbial and sterile signal 1 stimuli, respectively, to prime the NLRP3 inflammasome. We then used the bacterial toxin nigericin and a common product released from necrotic cells, ATP, as prototypical microbial and sterile signal 2 stimuli, respectively, to trigger the assembly of the NLRP3 inflammasome complex in mouse and human macrophages. We found that NLRP3 inflammasome responses were weakest when both signal 1 and signal 2 were sterile, but responses were faster and stronger when at least one of the two signals was microbial. Ultimately, the most rapid and potent responses were elicited when both signals were microbial. Together, these data suggest that microbial versus sterile signals are distinct, both kinetically and in magnitude, in their ability to generate inflammasome-dependent responses. This hierarchy of NLRP3 responses to sterile versus microbial stimuli likely reflects the urgent need for the immune system to respond rapidly to the presence of infection to halt pathogen dissemination.

关键词： inflammasome NLRP3 sterile inflammation TNF

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Detection,management,and prevention of diabetes-related foot disease in the Australian context

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World Journal of Diabetes 2023年第7期14卷 942-957页

作者： Scott McNeil kate Waller Yves S Poy Lorenzo Olimpia c Mateevici Stacey Telianidis Sara Qi Irina churilov Richard J MacIsaac Anna Galligan High Risk Foot Service St Vincent’s Hospital MelbourneFitzroy 3065VictoriaAustralia Department of Endocrinology and Diabetes St Vincent’s Hospital MelbourneFitzroy 3065VictoriaAustralia Department of Podiatry St Vincent’s Hospital MelbourneFitzroy 3065VictoriaAustralia Infectious Diseases Unit Department of MedicineSt Vincent’s Hospital MelbourneFitzroy 3065VictoriaAustralia Department of Pharmacy St Vincent’s Hospital MelbourneFitzroy 3065Australia Department of Medicine St Vincent’s Hospital MelbourneUniversity of MelbourneFitzroy 3065VictoriaAustralia Department of Vascular Surgery St Vincent’s Hospital MelbourneFitzroy 3065VictoriaAustralia Department of Rehabilitation Medicine St Vincent’s Hospital MelbourneFitzroy 3065VictoriaAustralia the Australian centre for Accelerating Diabetes Innovations School of MedicineUniversity of MelbourneParkville 3010VictoriaAustralia

Diabetes-related foot disease(DFD)is a widely feared complication among people who live with *** Australia and globally,rates of disability,cardiovascular disease,lower extremity amputation,and mortality are significantly increased in patients with *** order to understand and prevent these outcomes,we analyse the common pathogenetic processes of neuropathy,arterial disease,and *** review then summarises important management considerations through the interdisciplinary *** Australian and international guidelines,we offer a stepwise,evidence-based practical approach to the care of patients with DFD.

关键词： Diabetes-related foot disease Foot ulceration Lower extremity amputation Neuropathy Peripheral arterial disease Infection

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Effects of moisture content and feed rate on milling characteristics of wild apricot pits (Prunus armeniaca L.)

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International Journal of Agricultural and Biological Engineering 2014年第1期7卷 103-110页

作者： A.E.kate U.c.Lohani N.c.Shahi J.P.Pandey A.Sarkar Khan chand Department of Post Harvest Process&Food Engineering College of TechnologyG.B.Pant University of Agriculture and TechnologyPantnagarU.S.Nagar(Uttarakhand)-263145India Department of agricultural and Biological Engineering South Dakota State UniversityBrookingsSD 57006USA

Milling with decortication of wild apricot pits was done in wild apricot pit decorticator working on the principle of“impact and compression”.The milling characteristics includes decortication efficiency,percentage of husk,percentage of broken kernels and output capacity was evaluated at the different levels of moisture content,i.e.,8%,10%,12%,14%and 16%(w.b.)and feed rates,i.e.,12 g/stroke,14 g/stroke,16 g/stroke,18 g/stroke and 20 g/*** moisture content as well as feed rate significantly(Pcted the decortication efficiency,percentage of husk as well as brokens and output *** efficiency was initially increased and then decreased and opposite nature was found for the percentage of *** percentage of broken kernels and output capacity decreases with the increase in moisture content,while output capacity increases with the increase in feed rate and brokens decreases with the increase in feed rate of wild apricot pits.

关键词： wild apricot pit milling characteristics decortication efficiency moisture content husk percentage broken percentage output capacity

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clumped Isotope Analysis of calcite and Dolomite Mixtures Using Selective Acid Extraction

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Journal of Earth Science 2023年第3期34卷 726-734页

作者： Sen Li Andrew Schauer Alexis Licht Jie Liang kate Huntington Kangning Peng Qingdao Institute of Marine Geology Qingdao 266237China Department of Earth and Space Sciences University of WashingtonSeattle 98195USA centre Européen de Recherche etd􀆳Enseignement des Géosciences del􀆳Environnement(cerege) UMR 7330Aix-Marseille UniversitéCNRSIRDINRAEAix-en-Provence 13545France Shandong Provincial Territorial Spatial Ecological Restoration center Jinan 250014China

Acid extraction methods have been used in the last half century to selectively extract the cO_(2)produced from different carbonate minerals in mixed ***,these methods are often time-consuming and labor *** application to clumped isotope(Δ47)analysis has not been *** propose here an acid extraction method with phosphoric acid for bulk stable and clumped isotope analysis that treats mixtures of calcite and dolomite the same regardless of the proportional ***_(2)evolved from calcite is extracted by allowing a reaction with phosphoric acid to proceed for 10 min at 50℃.We then extract cO_(2)evolved from dolomite by rapid ramping the acid temperature from 50 to 90℃and allowing the reaction to *** experimental results show that our method yields accurate calcite and dolomiteΔ_(47)values from mixed samples under different proportional *** method also displays equal or higher accuracy for calciteδ^(13)c and dolomiteδ^(13)c andδ^(18)O values from mixtures when compared to previous *** approach exhibits higher sample throughput than previous methods,is adequate for clumped isotopic analysis and simplifies the reaction progression from over 24 h to less than 2 h,while maintaining relatively high isotopic obtaining *** yet poorly resolves calciteδ18O values,as found with previous methods.

关键词： mixed carbonate samples selective acid extraction acid fractionation correction clumped isotope bulk isotope calcite dolomite

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凯特·丝蓓:将社会目标融入业务运营中

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家族企业 2024年第2期 154-156页

作者：泰伦·博德艾达·哈茨克凯特·罗尔朱迪斯·c.斯托尔赫凯特丝蓓公司牛津大学牛津大学赛德商学院

凯特·丝蓓践行“社会宗旨”的商业倡议,将赋予女性权利的社会承诺融入其核心业务运营。凯特·丝蓓(kateSpade)公司的故事始于1993年,当时凯特·布罗斯纳安·丝蓓(kate Brosnahan Spade)开始设计凯特·丝蓓公司的第一款手提包,其设计和... 详细信息

凯特·丝蓓践行“社会宗旨”的商业倡议,将赋予女性权利的社会承诺融入其核心业务运营。凯特·丝蓓(kateSpade)公司的故事始于1993年,当时凯特·布罗斯纳安·丝蓓(kate Brosnahan Spade)开始设计凯特·丝蓓公司的第一款手提包,其设计和色彩缤纷的图案受到客户和时尚编辑的热烈欢迎。同名品牌于1996年在纽约市开设其第一家商店。

关键词：色彩缤纷女性权利业务运营纽约市融入

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concentration–discharge patterns of weathering products from global rivers

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Acta Geochimica 2017年第3期36卷 405-409页

作者： Daniel E.Ibarra Seulgi Moon Jeremy K.caves c.Page chamberlain kate Maher Earth System Science Stanford University StanfordCA 94305-4216 USA Earth Planetary and Space Sciences University of California Los Angeles CA 90095-1567 USA Earth Science ETH Ziirich 8092 Zurich Switzerland Geological Sciences Stanford University StanfordCA 94305-2115 USA

Quantifying the functional relationships relating river discharge and weathering products places key constraints on the negative feedback between the silicate weathering and climate. In this study we analyze the concentration–discharge relationships of weathering products from global rivers using previously compiled time-series datasets for concentrations and discharge from global rivers. To analyze the nature of the covariation between specific discharge and concentrations, we use both a power law equation and a recently developed solute production equation. The solute production equation allows us to quantify weathering efficiency, or the resistance to dilution at high runoff, via the Damko¨hler coefficient. These results are also compared to those derived using average concentration–discharge *** the power law exponent and the Damk?hler coefficient increase and asymptote as catchments exhibit increasingly chemostatic behavior, resulting in an inverse relationship between the two parameters. We also show that using thedistribution of average concentration–discharge pairs from global rivers, rather than fitting concentration–discharge relationships for each individual river, underestimates global median weathering efficiency by up to a factor of ～10. This study demonstrates the utility of long time-series sampling of global rivers to elucidate controlling processes needed to quantify patterns in global silicate weathering rates.

关键词：风化产物河流排放平均浓度长时间序列幂律方程流量关系控制过程

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Putting things in place for fertilization： discovering roles for importin proteins in cell fate and spermatogenesis

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Asian Journal of Andrology 2015年第4期17卷 537-544页

作者： kate L Loveland Andrew T Major Romaly Butler Julia c Young David A Jan Yoichi Miyamoto Department of Biochemistry and Molecular Biology Monash University Clayton VIC Australia Department of Anatomy and Developmental Biology Monash UniversityClayton VlC Australia Hudson Institute of Medical Research Monash Medical Centre Clayton VlC Australia School of clinical Sciences Monash University ClaytonVlC Laboratory of Nuclear Transport Dynamics National Institutes of Biomedical Innovation Health and Nutrition Osaka Japan.

Importin proteins were originally characterized for their central role in protein transport through the nuclear pores, the only intracellular entry to the nucleus. This vital function must be tightly regulated to control access by transcription factors and other nuclear proteins to genomic DNA, to achieve appropriate modulation of cellular behaviors affecting cell fate. Importin-mediated nucleocytoplasmic transport relies on their specific recognition of cargoes, with each importin binding to distinct and overlapping protein subsets. Knowledge of importin function has expanded substantially in regard to three key developmental systems： embryonic stem cells, muscle cells and the germ line. In the decade since the potential for regulated nucleocytoplasmic transport to contribute to spermatogenesis was proposed, we and others have shown that the importins that ferry transcription factors into the nucleus perform additional roles, which control cell fate. This review presents key findings from studies of mammalian spermatogenesis that reveal potential new pathways by which male fertility and infertility arise. These studies of germline genesis illuminate new ways in which importin proteins govern cellular differentiation, includ ng v a d rect ng proteins to d st nct ntrace ular compartments and by determining cellular stress responses.

关键词： cell fate cell stress importin karyopherin nucleocytoplasmic transport spermatid spermatocyte spermatogenesis

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A tissue-engineered rostral migratory stream for directed neuronal replacement

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Neural Regeneration Research 2018年第8期13卷 1327-1331页

作者： John c.O'Donnell Kritika S.Katiyar kate V.Panzer D.Kacy cullen center for Brain Injury & Repair Department of Neurosurgery Perelman School of Medicine University of Pennsylvania center for Neurotrauma Neurodegeneration & Restoration Corporal Michael Crescenz Veterans Affairs Medical Center School of Biomedical Engineering Drexel University Department of Bioengineering School of Engineering and Applied Science University of Pennsylvania

New neurons are integrated into the circuitry of the olfactory bulb throughout the lifespan in the mamma- lian brain--including in humans. These new neurons are born in the subventricular zone and subsequently mature as they are guided over long distances via the rostral migratory stream through mechanisms we are only just beginning to understand. Regeneration after brain injury is very limited, and although some neuroblasts from the rostral migratory stream will leave the path and migrate toward cortical lesion sites, this neuronal replacement is generally not sustained and therefore does not provide enough new neurons to alleviate functional deficits. Using newly discovered microtissue engineering techniques, we have built the first self-contained, implantable constructs that mimic the architecture and function of the rostral migratory stream. This engineered microtissue emulates the dense cord-like bundles of astrocytic somata and processes that are the hallmark anatomical feature of the glial tube. As such, our living microtissue-en- gineered rostral migratory stream can serve as an in vitro test bed for unlocking the secrets of neuroblast migration and maturation, and may potentially serve as a living transplantable construct derived from a patient＇s own cells that can redirect their own neuroblasts into lesion sites for sustained neuronal replace- ment following brain injury or neurodegenerative disease. In this paper, we summarize the development of fabrication methods for this microtissue-engineered rostral migratory stream and provide proof-of-princi- ple evidence that it promotes and directs migration of immature neurons.

关键词： rostral migratory stream glial tube astrocyte neuroblast brain injury neural repair neural regeneration tissue engineering

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