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Need for operational simplicity and timely disbursal of benefits—a qualitative exploration of the implementation of a direct benefit transfer scheme for persons with tuberculosis in India

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Infectious Diseases of Poverty 2024年第3期13卷 58-72页

作者： Malu Mohan Jeromie W.V.Thangaraj Sumit Pandey G.Sri Lakshmi Priya Sivavallinathan Arunachalam Rahul Sharma Hemant Deepak Shewade B.Aishwarya K.Afeeq Afsana Khatoon B.Gokulvijay Gude Sireesha Kavita Chandra S.Nandhakumar Prince Samuel C.Nanditha Viswanathan Devika Shanmugasundaram Raghuram Rao Manoj V.Murhekar Kathiresan Jeyashree Indian Council of Medical Research-National Institute of Epidemiology R-127TNHBAyapakkamChennaiTamil Nadu 600077India TB Support Network WHO Country Office for IndiaNew DelhiIndia central tuberculosis division Government of IndiaNew DelhiIndia

Background Ni-kshay Poshan Yojana(NPY)is a direct benefit transfer scheme of the Government of India introduced in 2018 to support the additional nutritional requirements of persons with TB(PwTB).Our recent nationwide evaluation of implementation and utilization of NPY using programmatic data of PwTB from nine randomly selected Indian states,reported a 70%coverage and high median delay in benefit *** undertook a qualitative study between January and July 2023,to understand the detailed implementation process of NPY and explore the enablers and barriers to effective implementation and utilization of the NPY *** We followed a grounded theory approach to inductively develop theoretical explanations for social phenomena through data generated from multiple *** conducted 36 in-depth interviews of national,district and field-level staff of the National tuberculosis Elimination Programme(NTEP)and NPY beneficiaries from 30 districts across nine states of India,selected using theoretical *** analytical framework developed through inductive coding of a set of six interviews,guided the coding of the subsequent *** and themes emerged through constant comparison and the data collection continued until theoretical *** Stakeholders perceived NPY as a beneficial *** political commitment from the state administration,mainstreaming of NTEP work with the district public healthcare delivery system,availability of good geographic and internet connectivity and state-specific grievance redressal mechanisms and innovations were identified as enablers of ***,the complex,multi-level benefit approval process,difficulties in accessing banking services,perceived inadequacy of benefits and overworked human resources in the NTEP were identified as barriers to implementation and *** The optimal utilization of NPY is enabled by strong political commitment and challenged by its length

关键词： National tuberculosis Elimination Programme Nutritional status Direct benefit transfer Implementation Cash transfer scheme Grounded theory India

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The virulence regulator AbsR in avian pathogenic Escherichia coli has pleiotropic effects on bacterial physiology

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Journal of Integrative Agriculture 2024年第2期23卷 649-668页

作者： Dongfang Zhao Haobo Zhang Xinyang Zhang Fengwei Jiang Yijing Li Wentong Cai Ganwu Li State Key Laboratory for Animal Disease Control and Prevention Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin 150069China College of Veterinary Medicine Northeast Agricultural UniversityHarbin 150038China National Animal tuberculosis Reference Laboratory Division of Zoonoses SurveillanceChina Animal Health and Epidemiology CenterQingdao 266032China Department of Veterinary Diagnostic and Production Animal Medicine College of Veterinary MedicineIowa State UniversityAmesIowa 50011-1134the United States

Avian pathogenic Escherichia coli(APEC)belonging to extraintestinal pathogenic ***(ExPEC)can cause severe infections in extraintestinal tissues in birds and humans,such as the lungs and ***(microcin production regulation,locus A,herein renamed AbsR,a blood survival regulator),a member of the MarR(multiple antibiotic resistance regulator)transcriptional regulator family,governs the expression of capsule biosynthetic genes in human ExPEC and represents a promising druggable target for ***,a deep understanding of the AbsR regulatory mechanism as well as its regulon is *** this study,we present a systems-level analysis of the APEC AbsR regulon using ChIP-Seq(chromatin immunoprecipitation sequencing)and RNA-Seq(RNA sequencing)*** found that AbsR directly regulates 99 genes and indirectly regulates 667 ***,we showed that:1)AbsR contributes to antiphagocytotic effects by macrophages and virulence in a mouse model for systemic infection by directly activating the capsular gene cluster;2)AbsR positively impacts biofilm formation via direct regulation of the T2SS(type II secretion system)but plays a marginal role in virulence;and 3)AbsR directly upregulates the acid tolerance signaling system EvgAS to withstand acid stress but is dispensable in ExPEC ***,our data indicate that the role of AbsR in virulence gene regulation is relatively conserved in ExPEC ***,this study provides a comprehensive analysis of the AbsR regulon and regulatory mechanism,and our data suggest that AbsR likely influences virulence primarily through the control of capsule ***,we found that AbsR severely represses the expression of the type I-F CRISPR(clustered regularly interspaced short palindromic repeats)-Cas(CRISPR associated)systems,which could have implications in CRISPR biology and application.

关键词： avian pathogenic Escherichia coli(APEC) extraintestinal pathogenic Escherichia coli(ExPEC) AbsR RNA-Seq ChIP-Seq gene regulation

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Design,synthesis,and biological evaluation of 1,2,4-triazole derivatives as potent antitubercular agents

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Chinese Chemical Letters 2024年第3期35卷 326-331页

作者： Yu Wen Shichun Lun Yuxue Jiao Wei Zhang Tianyu Hu Ting Liu Fan Yang Jie Tang Bing Zhang William R.Bishai Li-Fang Yu Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development School of Chemistry and Molecular EngineeringEast China Normal UniversityShanghai 200062China Center for tuberculosis Research Department of MedicineDivision of Infectious DiseaseJohns Hopkins School of MedicineBaltimoreMD21231-1044United States Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology ShanghaiTech UniversityShanghai 201210China Shanghai Key Laboratory of Green Chemistry and Chemical Process School of Chemistry and Molecular EngineeringEast China Normal UniversityShanghai 200062China

Inhibition of mycobacterial membrane protein large 3(MmpL3)thereby affecting the mycolic acid biosynthetic pathway has been proven to be an effective strategy for developing antitubercular *** on the X-ray crystal structure of MmpL3 inhibitor complexes,a series of novel 1,2,4-triazole derivatives were designed,synthesized and evaluated antitubercular activity against Mtb strain *** structure–activity relationship exploration resulted in the identification of compounds 21 and 28,which possess potent antitubercular activity against Mtb strain H37Rv[minimum inhibitory concentration(MIC)=0.03–0.13μg/mL]and the clinical isolates of multidrug resistance(MDR)and extensive drug resistance(XDR)tuberculosis(MIC=0.06–1.0μg/mL).Moreover,compounds 21 and 28 showed neglectable cytotoxicity(IC_(50)≥32μg/mL)to the mammalian Vero cells and favorable physicochemical and pharmacokinetic properties according to the in silico absorption,distribution,metabolism and excretion(ADME)***,the potential target of representative 1,2,4-triazole 28 was identified to be MmpL3 using a microscale thermophoresis(MST)assay.

关键词： tuberculosis MDR and XDR-TB MmpL3 inhibitor 1 2 4-Triazole Structure-based drug design

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Evaluation of IFIT3 and ORM1 as Biomarkers for Discriminating Active tuberculosis from Latent Infection

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Current Medical Science 2022年第6期42卷 1201-1212页

作者： Bing-fen YANG Fei ZHAI Shan YU Hong-juan AN Zhi-hong CAO Yan-hua LIU Ruo WANG Xiao-xing CHENG tuberculosis Prevention and Control Key Laboratory Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and TreatmentInstitute of Senior Department of Tuberculosisthe Eighth Medical Center of Chinese PLA General HospitalBeijing100091China Fourth division Senior Department of Tuberculosisthe Eighth Medical Center of PLA General HospitalBeijing100091China Department of tuberculosis Prevention and Control Senior Department of Tuberculosisthe Eighth Medical Center of PLA General HospitalBeijing100091China

Objective Current commercially available immunological tests cannot be used for discriminating active tuberculosis(TB)from latent TB *** evaluate the value of biomarker candidates in the diagnosis of active TB,this study aimed to identify differentially expressed genes in peripheral blood mononuclear cells(PBMCs)between patients with active TB and individuals with latent TB infection by transcriptome *** The differentially expressed genes in unstimulated PBMCs and in Mycobacterium tuberculosis(Mtb)antigen-stimulated PBMCs from patients with active TB and individuals with latent TB infection were identified by transcriptome *** candidate genes were evaluated in cohorts consisting of 110 patients with TB,30 individuals with latent TB infections,and 50 healthy controls by quantitative real-time *** operating characteristic(ROC)curve analysis was performed to calculate the diagnostic value of the biomarker *** Among the differentially expressed genes in PBMCs without Mtb antigen stimulation,interferon-induced protein with tetratricopeptide repeats 3(IFIT3)had the highest area under curve(AUC)value(0.918,95%CI:0.852-0.984,P<0.0001)in discriminating patients with active TB from individuals with latent TB infection,with a sensitivity of 91.86%and a specificity of 84.00%.In Mtb antigen-stimulated PBMCs,orosomucoid 1(ORM1)had a high AUC value(0.833,95%CI:0.752-0.915,P<0.0001),with a sensitivity of 81.94%and a specificity of 70.00%.Conclusion IFIT3 and ORM1 might be potential biomarkers for discriminating active TB from latent TB infection.

关键词： tuberculosis biomarker latent tuberculosis infection interferon-induced protein with tetratricopeptide repeats 3 orosomucoid 1

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FACTORS AFFECTING THE RESULTS OF AMBULATORY CHEMOTHERAPY IN PULMONARY tuberculosis

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中华医学杂志(英文版) 1964年第4期 201-210页

作者：李树森肖成志 Peking Municipal tuberculosis Dispensary and Epidemiologic division of the Peking tuberculosis Institute Peking

1. Studies were made on the effects of various factors that influence radiographic improvement or aggravation in 442 cases of pulmonary tuberculosis treated by ambulatory chemotherapy at the Peking Municipal tuberculosis Dispensary from 1953 to 1960.2. Analysis of the material was made after stratified randomization and the groups were rendered strictly comparable.3. With radiographic improvement, the effects of initial treatment or re-treatment, continuity of medication and the type of the initial lesion were found to be significant. However, the extent of the initial lesion, sex, age and drug regimen showed no significant effect. 4. With radiographic aggravation, the effects of the type and size of the residual lesion at the end of medication, and the duration of medication were significant. The other factors, namely, initial treatment or re-treatment, age, sex, initial lesion, degree of improvement, and drug regimen, showed no significant effect.5. The majority of previously untreated cases of pulmonary tuberculosis, where the lesion is reversible, can be rendered stable under uninterrupted chemotherapy. Further, continuous chemotherapy of any type of the initial lesion for 18 months or longer was satisfactory, provided that the post-treatment residual lesion reached a stable stage.

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Spatial-temporal Analysis of tuberculosis at the Community Level in the Baoshan District, Shanghai 2014–2019

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Biomedical and Environmental Sciences 2022年第5期35卷 458-462页

作者： MA Zhi Tao WANG Na HE Fan LIU Xiao Feng SHEN Xin Department of tuberculosis and HIV/AIDS Prevention Baoshan Centers for Disease Control and PreventionBaoshan 201901ShanghaiChina division of tuberculosis and HIV/AIDS Prevention Shanghai Municipal Center for Disease Control and PreventionShanghai 200336China Shanghai Institutes of Preventive Medicine Shanghai 200336China

Mycobacterium tuberculosis is the primary bacteria that leads to human tuberculosis(TB),which usually affects the pulmonary *** is one of the top 10 causes of death worldwide;however,China is one of eight countries th... 详细信息

关键词： organs tuberculosis death

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Design,synthesis and antimycobacterial activity of novel nitrobenzamide derivatives

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Chinese Chemical Letters 2019年第2期30卷 413-416页

作者： Hongjian Wang Kai Lv Xiaoning Li Bo Wang Apeng Wang Zeyu Tao Yunhe Geng Bin Wang Menghao Huang Mingliang Liu Huiyuan Guo Yu Lu Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences Peking Union Medical College Beijing Key Laboratory of Drug Resistance tuberculosis Research Department of Pharmacology Beijing Tuberculosis and Thoracic Tumor Research InstituteBeijing Chest Hospital Capital Medical University division of Gastroenterology and Hepatology Department of Medicine Indiana University School of Medicine

We report herein the design and synthesis of a series of novel nitrobenzamide derivatives. Results reveal that many of them display considerable in vitro antitubercular activity. Four N-benzyl or N- (pyridine-2-yl)methyl 3,5-dinitrobenzamides A6, All, Cl and C4 have not only the same excellent MIC values of 1500), opening a new direction for further development.

关键词： Nitrobenzamides Synthesis Antimycobacterial activity tuberculosis

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Systematic review and meta-analysis on the association of tuberculosis in Crohn's disease patients treated with tumor necrosis factor-α inhibitors(Anti-TNFα)

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World Journal of Gastroenterology 2018年第25期24卷 2764-2775页

作者： Brent L Cao Ahmad Qasem Robert C Sharp Latifa S Abdelli Saleh A Naser division of Molecular Microbiology Burnett School of Biomedical Sciences College of Medicine University of Central Florida

AIM To perform a meta-analysis on the risk of developing Mycobacterium tuberculosis(TB) infection in Crohn's disease(CD) patients treated with tumor necrosis factoralpha(TNFα) *** A meta-analysis of randomized, double-blind, placebocontrolled trials of TNFα inhibitors for treatment of CD in adults was conducted. Arcsine transformation of TB incidence was performed to estimate risk difference. A novel epidemiologically-based correction(EBC) enabling inclusions of studies reporting no TB infection cases in placebo and treatment groups was developed to estimate relative *** Twenty-three clinical trial studies were identified, including 5669 patients. Six TB infection cases were reported across 5 studies, all from patients receiving TNFα inhibitors. Eighteen studies reported no TB infection cases in placebo and TNFα inhibitor treatment arms. TB infection risk was significantly increased among patients receiving TNFα inhibitors, with a risk difference of 0.028(95%CI: 0.0011-0.055). The odds ratio was 4.85(95%CI: 1.02-22.99) with EBC and 5.85(95%CI: 1.13-30.38) without *** The risk of TB infection is higher among CD patients receiving TNFα inhibitors. Understanding the immunopathogenesis of CD is crucial, since using TNFα inhibitors in these patients could favor mycobacterial infections, particularly Mycobacterium avium subspecies paratuberculosis, which ultimately could worsen their clinical condition.

关键词： tuberculosis Tumor necrosis factor-alpha inhibitors Crohn’s Disease Meta-analysis Systematic review

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Mammalian cell cultures as models for Mycobacterium tuberculosis-human immunodeficiency virus(HIV) interaction studies:A review

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Asian Pacific Journal of Tropical Medicine 2016年第9期9卷 809-816页

作者： Walter Chingwaru Richard H.Glashoff Jerneja Vidmar Petrina Kapewangolo Samantha L.Sampson DST/NRF Centre of Excellence for Biomedical tuberculosis Research/SAMRC Centre for tuberculosis Research Division of Molecular Biology and Human GeneticsFaculty of Medicine and Health SciencesStellenbosch University Institute Ceres/Zavod Ceres Department of Biological Sciences Faculty of ScienceBindura University Science Education division of Medical Virology Faculty of Medicine and Health SciencesStellenbosch University Department of Plastic and Reconstructive Surgery University Medical Centre Maribor Department of Chemistry and Biochemistry Faculty of ScienceUniversity of Namibia

Mycobacterium tuberculosis(MTB) and human immunodeficiency virus(HIV) co-infections have remained a major public health concern worldwide,particularly in Southern *** our understanding of the molecular interactions between the pathogens has remained poor,primarily due to lack of suitable preclinical models for such *** reviewed the use,this far,of mammalian cell culture models in HIV-MTB interaction *** have described the use of primary human cell cultures,including monocyte-derived macrophage(MDM) fractions of peripheral blood mononuclear cell(PBMC),alveolar macrophages(AM),cell lines such as the monocyte-derived macrophage cell line(U937),T lymphocyte cell lines(CEMx174,ESAT-6-specific CD4+ T-cells) and an alveolar epithelial cell line(A549) and special models such as stem cells,three dimensional(3D) or organoid cell models [including a blood-brain barrier(BBB) cell model] in HIV-MTB interaction *** use of cell cultures from other mammals,including:mouse cell lines [macrophage cell lines RAW 264.7 and J774.2,fibroblast cell lines(NIH 3T3,C3 H clones),embryonic fibroblast cell lines and T-lymphoma cell lines(***,TIMI.4 and R1.1)]; rat(T cells:Rat2,RGE,XC and HH16,and alveolar cells:NR8383) and primary guinea pigs derived AMs,in HIV-MTB studies is also *** the spectrum of the models available,cell cultures offer great potential for host-HIV-MTB interactions studies.

关键词： HIV Mycobacterium tuberculosis Cell lines Primary cell models Co-infection

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THE RESULTS OF DIFFERENT METHODS OF CHEMOTHERAPY IN THE TREATMENT OF PULMONARY tuberculosis

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中华医学杂志(英文版) 1964年第3期 155-162页

作者：孙桐年邓伟吾虞积如 division of Pulmonary tuberculosis Shanghai Second Medical College Shanghai

1. The therapeutic results of 820 cases of pulmonary tuberculosis are analyzed. Exudative lesions showed rapid absorption in the first 6 months with a high percentage of marked improvement when the treatment was carried out up to 2 years. In some cases it was necessary to prolong the treatment to 2 years and a half or even longer.2. Combined treatment with INK and PAS or streptomycin is definitely superior to INH alone. The former showed more cases with marked improvement and less progression of the disease. 38.4% of cavity closure was obtained with the combined regimen as against 8% with INH alone. The relapse rate, too, was higher under single INH treatment (4.1%) than the combined regimen (1.3%).3. Under irregular medication, the therapeutic effect was only temporary, as evidenced by more frequent progression of the disease (10-45%), higher relapse rate (7.3%), and poor cavity closure.4. Under the combined regimen, 38.4% of the early cavities closed in the first year of chemotherapy, thereafter the chance of cavity closure diminished greatly. Cavities which fail to close in the first year of chemotherapy, should be resected if there is no contraindication. In view of the fact that the present routine combined regimen does not yield as high an incidence of cavity closure as has been expected, we feel it is necessary to increase the dosage of INH, preferably to 5-8 mg per kg combined with 1 gm streptomycin daily for 3-6 months at the beginning of treatment, followed by INH singly or INH combined with PAS.5. 37.4% of cavitary cases and 64.1% of noncavitary cases attained sputum conversion in the first year under the combined regimen. 15.8% of the positive sputum cases in the outpatient clinic attained sputum conversion at the end of 2 years under single INH treatment as compared to 53.3% under the combined regimen. In view of these differences, it is believed that INH alone is not an adequate form of chemotherapy.

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