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The Introduction of Bedaquiline Regimen for Drug-Resistant Tuberculosis in the Philippines: An Operational Study

Journal of Tuberculosis Research 2022年第4期10卷 205-219页

作者： Vincent M. Balanag Jr. Vivian S. Lofranco Mariquita J. Mantala Mary Rosary T. Santiago Patrice Jamie E. Cabasis Arnyl G. Araneta Anna Marie Celina G. Garfin Lung Center of the Philippines National Center for Pulmonary Research Quezon Philippines Department of Health National Tuberculosis Control Program Management Office Manila Philippines Philippine Business for Social Progress The Global Fund Project Manila Philippines Department of Health Disease Prevention and Control Bureau Manila Philippines

Objectives: Bedaquiline (BDQ) is the first new anti-tuberculosis (TB) drug introduced to the market after 45 years. Recent studies have shown the potential benefits of adding bedaquiline to regimens for drug-resistant TB (DR-TB). In search of more effective regimens for DR-TB, bedaquiline was introduced in the TB program in the Philippines under operational research to assess its effectiveness, safety, and tolerability when given with background regimens among patients with multi-or extensively DR-TB (MDR/XDR-TB). Design: A prospective cohort study of patients with MDR/XDR-TB was given with a bedaquiline-containing regimen from June 2016 to May 2017. Demographic data, presence of comorbidities, and microbiologic profile on entry were recorded. Bedaquiline was administered at the recommended dose of 400 mg once daily for 14 days, then 200 mg three times a week for 22 weeks together with World Health Organization (WHO)-compliant background regimen. The time to culture conversion, interim outcomes at the 6th month of treatment, end-of-treatment outcomes, and post-treatment follow-up outcomes after one year was determined. The frequency and severity of adverse events (SAE) were recorded as part of pharmacovigilance. Results: Seventy-five patients were given with bedaquiline-containing regimen during the study period. Forty-two (56.0%) had second-line injectable resistance, 23 (30.7%) had fluoroquinolone-resistance, 6 (8.0%) had MDR-TB, and 4 (5.3%) had XDR-TB. In the 6th month of post-enrolment, 79% were culture-negative. The treatment success rate was 65.3% (37 were cured and 12 completed treatment), 7 (9.3%) died, 17 (22.7%) lost to follow-up, and 2 (2.7%) were withdrawn from treatment. Adverse events included vomiting (80%), dizziness (69%), nausea (52%), cough (44%), and headache (36%). The post-treatment follow-up of 49 patients in the 12th month showed 92% were culture-negative while 8% of TBC were not done. Conclusion: Bedaquiline-containing regimens for patients

关键词： Bedaquiline Drug-Resistant TB XDR-TB

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Interim Outcomes and Adverse Events among Drug-Resistant Tuberculosis Patients Treated with Bedaquiline in the Philippines

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Journal of Tuberculosis Research 2022年第2期10卷 61-74页

作者： Vivian S. Lofranco Maria Rhoda A. Torres-Cervas Katherine A. Asence Khrizza Marianne A. Del Mundo Vincent M. Balanag Mary Rosary T. Santiago Anna Marie Celina G. Garfin National Center for Pulmonary Research Lung Center of the Philippines Quezon City Philippines The Global Fund Project Philippine Business for Social Progress Manila Philippine National Tuberculosis Control Program Management Office Department of Health Manila Philippines Disease Prevention and Control Bureau Department of Health Manila Philippines

Objectives: This study aimed to assess the interim outcomes for drug-resistant tuberculosis (DR-TB) patients treated with bedaquiline regimen under the operational research conditions compared to DR-TB patients treated without bedaquiline in their regimen, and to describe the adverse events that occurred among patients treated with bedaquiline in the Philippines. Design: Patients who were treated with a bedaquiline-containing regimen from June 2016 to May 2017 were included in this study as the intervention group, while patients who were treated without bedaquiline regimen from January 2013 to May 2016 were included as the comparison group. The interim treatment outcomes were compared using Chi-square test. The analysis of time to culture conversion within 6 months of treatment was conducted. A Cox proportional hazard model was constructed to identify the variables associated with a favorable interim treatment outcome. The R program was used for statistical analysis. Results: On the 6th month of treatment, the culture conversion for patients treated with a bedaquiline-containing regimen was significantly higher than with the comparison group [63/75 (84.0%) vs 84/117 (71.8%), p = 0.012)]. Nearly 15% of the patients treated with bedaquiline were lost to follow-up. Frequent adverse events included vomiting, dizziness, nausea, joint pain, and abdominal pain. Conclusion: The patients who were treated with bedaquiline-containing regimen have better interim treatment outcomes than those treated without bedaquiline, but the proportion of patients who were lost to follow-up remains substantial.

关键词： Operational Research New Anti-TB Drug Regimen Drug Interim Outcomes Adverse Events

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Associations between vaccination clinic factors and DTaP dropout in China: A cross-sectional study

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Human Vaccines & Immunotherapeutics 2025年第1期21卷 2510007页

作者： Jiakai Ye Lei Cao Yifan Song Wenzhou Yu Zhaonan Zhang Li Li Zundong Yin a National Immunization Program Chinese Center for Disease Control and Prevention Beijing Chinab National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases Chinese Center for Disease Control and Prevention Beijing China

ABSTRACTDiphtheria, tetanus, and acellular pertussis combined vaccine (DTaP) dropout reflects negatively on the ability of a vaccination clinic to ensure children are fully vaccinated with recommended vaccines. Our study examined associations between modifiable vaccination clinic factors and DTaP dropout in clinics in China. A cross-sectional study of 42,282 clinics used clinic-reported clinic-level factors and clinic-level vaccination data from the National Immunization Information Management System and the Coding Management System during calendar year 2021. We defined low dropout as < 5% and high dropout as ≥ 5%. Multivariable logistic regression analysis showed clinics having 18%-25% of their area devoted to vaccination were more likely to have low dropout rates than clinics with ≤ 17% (OR = 1.09 [95% CI, 1.03–1.16]. Clinics with 2, 3, 4, and ≥ 5 vaccination tables were more likely to have low dropout rates compared with single-table clinics (OR = 1.21 [1.13–1.30]; OR = 1.29 [1.20–1.38]; OR = 1.28 [1.17–1.39]; OR = 1.32 [1.20–1.45]). Clinics with 4–5, 6–8, and ≥ 9 staff were more likely to have low dropout rates compared with clinics with ≤ 3 staff (OR = 1.13 [1.07–1.20]; OR = 1.18 [1.10–1.25]; OR = 1.15 [1.08–1.23]). Compared to clinics with travel-based service radii of ≤ 5 km, clinics with 6–10 km radii were more likely to have low dropout rates (OR = 1.06 [95% CI,1.00–1.12]), and clinics with service radii of ≥ 21 km (OR = 0.90 [95% CI, 0.83–0.98]) were less likely. These four factors were independently associated with DTaP dropout. While considering environmental factors such as population size and level of economic development, these factors can be adjusted to help minimize dropout.

关键词： Vaccination clinic Factors DTaP dropout Utilization China

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Pilot Study of a Cognitive Behavioral Intervention for Pelvic Exam Anxiety Among Survivors of Endometrial and Cervical Cancer

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Women's Reproductive Health 2024年第1期12卷 221-245页

作者： Coleman, J.N. Lachman, S.E. Arthur, S.S. Stalls, J.M. Choi, Y. Zerubavel, N. Davidson, B. Reese, J.B. Shelby, R.A. Department of Psychology and Neuroscience Duke University Durham NC United States Department of Psychiatry and Behavioral Sciences Duke University Durham NC United States Center of Innovation to Accelerate Discovery and Practice Transformation Durham Veterans Affairs Health Care System Durham NC United States Department of Population Health Sciences Duke University Durham NC United States Arise Psychological Wellness and Consulting North Carolina United States Division of Gynecologic Oncology Duke University Durham NC United States Cancer Prevention and Control Program Fox Chase Cancer Center Philadelphia PA United States

No evidence-based interventions exist for anxiety related to pelvic exams after cancer treatment. A 3-session cognitive behavioral intervention, Pelvic Examination and Anxiety Coping Skills for Empowerment (PEACE), was developed. We conducted a proof-of concept pilot study (N=16) to evaluate intervention acceptability and feasibility and changes in anxiety and pain symptoms. Participants completed 3 assessments (baseline, post-intervention, post-pelvic exam) and post-exam interviews. Exploratory outcomes included exam-related distress and pain, and intervention mechanisms of change. The mixed methods findings indicated preliminary acceptability (e.g., 71% endorsed PEACE “made things a lot better”) and feasibility (e.g., 87.5% completed the protocol). PEACE shows promise for reducing procedural distress, which may ultimately improve care engagement. © 2024 Society for Menstrual Cycle Research.

关键词： anxiety cognitive behavioral therapy pain pelvic exam women’s health

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Polλ promotes microhomology-mediated end-joining (vol 30, pg 107, 2023)

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NATURE STRUCTURAL & MOLECULAR BIOLOGY 2023年第7期30卷 1048-1048页

作者： Chandramouly, Gurushankar Jamsen, Joonas Borisonnik, Nikita Tyagi, Mrityunjay Calbert, Marissa L. Tredinnick, Taylor Ozdemir, Ahmet Y. Kent, Tatiana Demidova, Elena V. Arora, Sanjeevani Wilson, Samuel H. Pomerantz, Richard T. Department of Biochemistry and Molecular Biology Sidney Kimmel Cancer Center Thomas Jefferson University Philadelphia PA USA Department of Biochemistry and Molecular Biology University of Arkansas for Medical Sciences Little Rock AR USA Spark Therapeutics Philadelphia PA USA Cancer Prevention and Control Program Fox Chase Cancer Center Philadelphia PA USA Kazan Federal University Kazan Russian Federation Department of Radiation Oncology Fox Chase Cancer Center Philadelphia PA USA Genome Integrity and Structural Biology Laboratory National Institute of Environmental Health Sciences National Institutes of Health Research Triangle Park NC USA

The double-strand break (DSB) repair pathway called microhomology-mediated end-joining (MMEJ) is thought to be dependent on DNA polymerase theta (Polθ) and occur independently of nonhomologous end-joining (NHEJ) factors. An unresolved question is whether MMEJ is facilitated by a single Polθ-mediated end-joining pathway or consists of additional undiscovered pathways. We find that human X-family Polλ, which functions in NHEJ, additionally exhibits robust MMEJ activity like Polθ. Polλ promotes MMEJ in mammalian cells independently of essential NHEJ factors LIG4/XRCC4 and Polθ, which reveals a distinct Polλ-dependent MMEJ mechanism. X-ray crystallography employing in situ photo-induced DSB formation captured Polλ in the act of stabilizing a microhomology-mediated DNA synapse with incoming nucleotide at 2.0 Å resolution and reveals how Polλ performs replication across a DNA synapse joined by minimal base-pairing. Last, we find that Polλ is semisynthetic lethal with BRCA1 and BRCA2. Together, these studies indicate Polλ MMEJ as a distinct DSB repair mechanism.

关键词： DNA DNA damage and repair Nanocrystallography Non-homologous-end joining X-ray crystallography

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Possible processes and origin-tracing methods of“human-to-item”contamination and“item-to-human”infection with SARS-CoV-2

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Biosafety and Health 2022年第4期4卷 209-212页

作者： Ji Wang Wenbo Xua Xuejun Ma Chinese Field Epidemiology Training Program(CFETP) Beijing 100050China NHC Key Laboratory of Medical Virology and Viral Diseases National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China Joint Center for Biosafety Mega-Science Wuhan 430071China

*** The first wave of coronavirus disease 2019(COVID-19)outbreak in China's Mainland was declared controlled after April *** then,the origins of all local outbreaks were imported cases of COVID-19 infection or imported articles contaminated with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)[1],[2],[3].The volume of import and export trade in China is enormous,and the entry of SARS-CoV-2-contaminated articles into China is ***,SARS-CoV-2 can survive on the surface of noncold-chain products for prolonged periods in cold environments during fall and winter[4],[5],[6].

关键词： origin mainland winter

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Construction and validation of a mouse model for studying severe human adenovirus infections

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Virologica Sinica 2024年第6期39卷 963-973页

作者： Dingbin Chen Yuqian Yan Ting Mei Peipei Yang Siqi Deng Yiqiang Li Tie Zhao Ning Xin Biyan Duan Weifeng Liang Yuemei Yang Wei Zhao Donald Seto Junxian Ou Qiwei Zhang Institute of Medical Microbiology Department of Immunology and MicrobiologyCollege of Life Science and TechnologyJinan UniversityGuangzhou510632China BSL-3 Laboratory(Guangdong) Guangdong Provincial Key Laboratory of Tropical Disease ResearchSchool of Public HealthSouthern Medical UniversityGuangzhou510515China Department of Clinical Laboratory Guangzhou Women and Children's Medical CenterGuangzhou Medical UniversityGuangzhou510620China South Yunnan Central Hospital(Honghe First People's Hospital) MengziYunnan661100China Bioinformatics and Computational Biology Program School of Systems BiologyGeorge Mason UniversityManassasVA20110USA The Affiliated Guangdong Second Provincial General Hospital of Jinan University Guangzhou510310China Key Laboratory of Viral Pathogenesis&Infection Prevention and Control(Jinan University) Ministry of EducationGuangzhou510632China

Human adenoviruses(HAdVs)are highly contagious pathogens with various genotypes implicated in acute respiratory disease(ARD)and linked to fatality,especially in immunosuppressed patients,young children,and military ***,no vaccines or specific drugs are approved for clinical *** hosts of adenoviruses are strictly species-specific,which strongly limits the development of vaccines and drugs against *** this study,immunocompetent BALB/c mice were challenged with different doses of human adenovirus type 5(HAdV-5)via tail intravenous injection(i.v.).All mice challenged with a high dose of HAdV-5(3.21010 TCID50/kg)died within 3–5 days,while those receiving a low dose of HAdV-5(8109 or 4109 TCID50/kg)***,among the mice receiving a medium dose of HAdV-5(1.61010 TCID50/kg),60%(n¼3/5)of male mice died,while all female mice *** suggests that male mice may be more susceptible to HAdV-5 infection than female mice,consistent with clinical findings in ***-5 DNA was mainly distributed in the liver,followed by the spleen and *** changes were observed in the lung,liver,and spleen,with severity increasing in correlation with the virus challenge *** and qPCR analyses of the liver indicated that the down-regulated expression of the H2-Aa,H2-Ea-ps,CD74,and H2-Eb1 genes in male mice,as well as the AHR gene in female mice,may contribute to the observed higher mortality rates in male ***,this effective,feasible,and costefficient mouse model could serve as a candidate for evaluating HAdV vaccines and anti-adenovirus therapeutics.

关键词： Human adenovirus type 5(HAdV-5) Animal model BALB/c mice Severe human adenovirus infections

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Cercarial dermatitis outbreak caused by ruminant parasite with intermediate snail host: schistosome in Chana, South Thailand

Evolutionary Systematics

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Evolutionary Systematics 2022年第2期6卷 151-173页

作者： Krailas, Duangduen Namchote, Suluck Komsuwan, Jirayus Wongpim, Thanaporn Apiraksena, Kitja Glaubrecht, Matthias Sonthiporn, Pichaya Sansawang, Choopong Suwanrit, Sirirat Parasitology and Medical Malacology Research Unit Department of Biology Faculty of Science Silpakorn University Nakhon Pathom 73000 Thailand Demonstration School of Slipakorn University Faculty of Education Silpakorn University Nakhon Pathom 73000 Thailand Department of Biodiversity of Animals Universität Hamburg Leibniz Institute for the Analysis of Biodiversity Change (LIB) Zoological Museum Martin-Luther-King-Platz 3 Hamburg 20146 Germany Field Epidemiology Training Program (FETP) Division of Epidemiology Department of Disease Control Ministry of Public Health Nonthaburi 11000 Thailand Office of Disease Prevention and Control Region 12 Songkhla Department of Disease Control Ministry of Public Health Songkhla 90000 Thailand Rajprachasamasai Institute Department of Disease Control Ministry of Public Health Samuthprakarn 10270 Thailand

A cercarial dermatitis outbreak occurred in Chana district, Songkhla Province, South Thailand, between August and October 2020. A total of 359 cases with cercarial dermatitis were confirmed with three cases of skin biopsy. The species of potential trematodes from infected snails were investigated, and the prevalence of infestation with schistosomes was described. As part of our ongoing studies of trematode diversity in freshwater systems, using morphological traits and sequence data to differentiate species, this study aimed to provide insights into the parasite species that cause cercarial dermatitis in the outbreak area and improve our understanding of parasite species distribution. Snail samples were collected in December 2020 and September and October 2021. Five main areas of outbreaks were investigated, and snails were collected by scooping and examined for infection with cercariae. The cercariae were characterized on the basis of morphological features. We found two species of snails to be infected, viz. Indoplanorbis exustus and Bithynia siamensis siamensis, with infection rates of 2.05% (12/586) and 7.93% (23/290), respectively. Three species of trematodes were found in B. s. siamensis, viz. Gastrothylax crumenifer, Astiotrema monticellii, and Loxogenes liberum. Moreover, three species of trematodes were found in Indoplanorbis exustus, viz. Clinostomum giganticum, Echinostoma spiniferum, and Schistosoma indicum. The latter is a ruminant schistosome, which causes the outbreak of cercarial dermatitis in the area. They were genetically analyzed using the internal transcribed spacer subunit II region to confirm the species identity at generic and infrageneric levels. Copyright Duangduen Krailas et al.

关键词： Schistosoma indicum snail-borne diseases trematode infection

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Quantile Differences in the Age-Related Decline in Cardiorespiratory Fitness Between Sexes in Adults Without Type 2 Diabetes Mellitus in the United States

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Mayo Clinic Proceedings: Innovations, Quality and Outcomes 2022年第4期6卷 302-310页

作者： Ortaglia, Andrew Stansbury, Melissa L. Wirth, Michael D. Sui, Xuemei Bottai, Matteo Department of Epidemiology and Biostatistics Arnold School of Public Health University of South Carolina Columbia SC Department of Exercise Science Arnold School of Public Health University of South Carolina Columbia SC College of Nursing and Department of Epidemiology and Biostatistics Cancer Prevention and Control Program Arnold School of Public Health University of South Carolina Columbia SC Division of Biostatistics Institute of Environmental Medicine Karolinska Institutet Stockholm Sweden

Objective: To comprehensively assess the extent to which the decline in cardiorespiratory fitness (CRF) with age differs between sexes. Participants and Methods: This study used data from the Aerobics Center Longitudinal Study, conducted between September 1974 and August 2006, consisting primarily of White adults from middle-to-upper socioeconomic strata restricted to adults without type 2 diabetes mellitus (33,742 men and 9,415 women). Quantile regression models were used to estimate the differences in age-associated changes in CRF between the sexes, estimated using a maximal treadmill test. Results: For adults aged up to 45 years, significant differences in slopes relating to age and CRF between men and women were observed for all adjusted percentiles of CRF other than the 90th percentile;women reported significantly greater declines in CRF per year. For those aged 45-60 years and those older than 60 years, no significant differences in age-related declines in CRF were observed between the sexes. Conclusion: This study found that compared with men, the onset of decline in CRF was found to occur earlier and at lower CRF percentiles in women. This is of particular concern, given that compared with men, women already tend to have lower CRF levels. These findings suggest that maintaining the levels of physical activity sufficient to maintain moderate-to-high levels of fitness is particularly important for women earlier during adulthood. © 2022 The Authors

关键词： CRF cardiorespiratory fitness NCD noncommunicable disease T2DM type 2 diabetes mellitus VO 2max maximal oxygen consumption

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Depression,suicidality and associated risk factors among police officers in urban Tanzania:a cross-sectional study

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General Psychiatry 2021年第3期34卷 135-142页

作者： Belinda Jackson Njiro Harrieth Peter Ndumwa Charles Joseph Msenga Thomas Kawala Ezekiel Matola Juhudi Mhonda Hillary Corbin Omary Ubuguyu Samuel Likindikoki School of Medicine Muhimbili University of Health and Allied SciencesDar es SalaamTanzaniaUnited Republic of Medical Unit Tanzania Police ForceDar es SalaamTanzaniaUnited Republic of National NCD Prevention and Control Program Ministry of HealthCommunityDevelopmentGenderElderly and ChildrenDodomaTanzaniaUnited Republic of

Background The WHO has classified depression as a disease of public *** officers are a particular subpopulation group that is at an increased risk for mental health *** study examined the prevalence of depression,suicidality and associated risk factors among police officers in urban *** The aim of this study was to examine the prevalence of depression,suicidality and associated risk factors among police officers in *** A cross-sectional study was conducted between April 2019 and October 2020 among 550 participants in Dar es Salaam recruited using a multistage cluster sampling *** Patient Health Questionnaire-9 was used to screen for depression and *** Interpersonal Support Evaluation List-12 tool was used to measure perceived social *** statistics were summarised using frequencies and *** and multivariate analyses were used to establish associations between predictors of interest,depression and *** There were 497 participants in the *** these,76.6%(376 of 491)were men,and the median(IQR)age was 37.0(17)*** 19.8%(96 of 486)of the police officers screened positive for depression and 15.4%(75 of 413)for suicidality.A significant proportion was either moderately(29 of 96,30.2%)or severely depressed(8 of 75,10.7%).Of those who experienced suicidal thoughts,10.7%(8 of 75)reported having daily suicidal *** low social support was associated with an increased risk of reporting depression(adjusted OR(aOR):28.04,95%CI:8.42 to 93.37,p<0.001)and suicidality(aOR:10.85,95%CI:3.56 to 33.08,p<0.001)as compared with those with high perceived social *** The magnitude of depression and suicidality among police officers in urban Tanzania is alarmingly *** study findings indicate the need for routine screening for depression and suicidality among police officers and design appropriate mental health responsive services in thi

关键词： routine sectional urban

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