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ObjectivesVulvar cancer is a rare gynecological malignancy. However, the incidence of human papillomavirus (HPV)-associated vulvar disease is increasing, particularly in low- and middle-income countries. HIV infection is associated with an increased risk of HPV-associated vulvar cancer. We evaluated treatment patterns and survival outcomes in a cohort of vulvar cancer patients in Botswana. The primary objective of this study was to determine overall survival and the impact of treatment modality, stage, and HIV status on overall survival.MethodsWomen with vulvar cancer who presented to oncology care in Botswana from January 2015 through August 2019 were prospectively enrolled in this observational cohort study. Demographics, clinical characteristics, treatment, and survival data were collected. Factors associated with survival including age, HIV status, stage, and treatment were evaluated.ResultsOur cohort included 120 women with vulvar cancer. Median age was 42 (IQR 38–47) years. The majority of patients were living with HIV (89%, n=107) that was well-controlled on antiretroviral treatment. Among women with HIV, 54.2% (n=58) were early stage (FIGO stage I/II). In those without HIV, 46.2% (n=6) were early stage (stage I/II). Of the 95 (79%) patients who received treatment, 20.8% (n=25) received surgery, 67.5% (n=81) received radiation therapy, and 24.2% (n=29) received chemotherapy, either alone or in combination. Median follow-up time of all patients was 24.7 (IQR 14.2–39.1) months and 2- year overall survival for all patients was 74%. Multivariate analysis demonstrated improved survival for those who received surgery (HR 0.26; 95% CI 0.08 to 0.86) and poor survival was associated with advanced stage (HR 2.56; 95% CI 1.30 to 5.02). Survival was not associated with HIV status.ConclusionsThe majority of women with vulvar cancer in Botswana are young and living with HIV infection. Just under half of patients present with advanced stage, which was associated with worse survival. Improved survival was seen for those who received surgery.

Brain inflammation is one of hypotheses explaining complex pathomechanisms of depression. Angiotensin II (ANGII), which is associated with hypertension, also induces brain inflammation. However, there is no animal study showing the direct relationship between ANGII and depression. To address this issue, ANGII-containing osmotic pumps were implanted into adult male C57BL/6 mice subcutaneously for subacute (7 days) and chronic (at least 21 days) periods and behavioral and molecular analyses were conducted. Chronic infusion of ANGII into mice induced depressive-like behaviors, including the tail suspension test and forced swimming test, which were reversed by imipramine. Chronic infusion of ANGII also induced microglial activation in the hippocampus with increase of Il-1β mRNA and decrease of Arg1 mRNA. In addition, chronic ANGII infusion activated the hypothalamic–pituitary–adrenal axis (HPA axis) and resulted in decreased hippocampal glucocorticoid receptor level. However, subacute ANGII infusion did not induce significant molecular and behavioral changes in mice compared to that of control. The molecular and behavioral changes by chronic ANGII infusion were reversed by co-treatment of minocycline or telmisartan. In addition, ANGII treatment also induced the pro-inflammatory changes in BV-2 microglial cells. Our results indicate that ANGII can induce depressive-like behaviors via microglial activation in the hippocampus and HPA axis hyperactivation in mice. These might suggest possible mechanism on depressive symptom in chronic hypertensive state.

Summary Background Evidence for the associations between mental illness and the likelihood of a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test result and the clinical outcomes of COVID-19 is scarce. We aimed to investigate these associations with data from a national register in South Korea. Methods A nationwide cohort study with propensity score matching was done in South Korea using data collected from the Health Insurance Review and Assessment Service of Korea. We defined mental illness as present if one of the relevant ICD-10 codes was recorded at least twice within 1 year for an outpatient or inpatient. Severe mental illness was considered as non-affective or affective disorders with psychotic features. We included all patients aged older than 20 years who were tested for SARS-CoV-2 through services facilitated by the Korea Centers for Disease Control and Prevention, the Health Insurance Review and Assessment Service of Korea, and the Ministry of Health and Welfare, South Korea. We investigated the primary outcome (SARS-CoV-2 test positivity) in the entire cohort and the secondary outcomes (severe clinical outcomes of COVID-19: death, admission to the intensive care unit, or invasive ventilation) among those who tested positive. Findings Between Jan 1 and May 15, 2020, 216 418 people were tested for SARS-CoV-2, of whom 7160 (3·3%) tested positive. In the entire cohort with propensity score matching, 1391 (3·0%) of 47 058 patients without a mental illness tested positive for SARS-CoV-2, compared with 1383 (2·9%) of 48 058 with a mental illness (adjusted odds ratio [OR] 1·00, 95% CI 0·93–1·08). Among the patients who tested positive for SARS-CoV-2, after propensity score matching, 109 (8·3%) of 1320 patients without a mental illness had severe clinical outcomes of COVID-19 compared with 128 (9·7%) of 1320 with a mental illness (adjusted OR 1·27, 95% CI 1·01–1·66). Interpretation Diagnosis of a mental illness was not associated with increased likelihood of testing positive for SARS-CoV-2. Patients with a severe mental illness had a slightly higher risk for severe clinical outcomes of COVID-19 than patients without a history of mental illness. Clinicians treating patients with COVID-19 should be aware of the risk associated with pre-existing mental illness. Funding National Research Foundation of Korea.

Comorbidity of tuberculosis (TB) and depression may lead to delayed TB treatment initiation. A cross sectional study was conducted between January and December 2019 to examine the association between depression and delayed TB treatment initiation among newly diagnosed TB patients in Botswana. We used the Patient Health Questionnaire-9 and the ZUNG self-rating anxiety scale to assess depressive and anxiety symptoms, respectively. Delayed TB treatment was defined as experiencing common TB symptoms for more than 2 months before treatment initiation. We used Poisson regression models with robust variance to assess the association between covariates and delayed treatment initiation. Majority of the enrolled 180 study participants were males (n =116, 64.4%). Overall, 99 (55%) were co-infected with HIV; depression and anxiety symptoms were reported by 47.2% and 38.5% of the participants respectively. The prevalence of delayed TB treatment was 42.6% and 18.8% among participants who indicated symptoms of depression and among participants without depression respectively. After adjusting for age, HIV status, gender and anxiety symptoms, depression was still associated with delayed TB treatment (adjusted prevalence ratio [aPR] = 2.09; 95% CI = 1.23–3.57). Integrating management of depressive symptoms during TB treatment may help in improving overall TB treatment outcomes.

Homeless persons have disproportionate rates of latent tuberculosis infection (LTBI). LTBI treatment can prevent and reduce active tuberculosis spread. We examined associations between mental health, social support, and perceptions of general health in 50 LTBI-positive, homeless adults enrolled in LTBI treatment. Depression and anxiety prevalence were 40% and 48%, respectively. Depression was negatively associated with general health, positive social interaction, and tangible, emotional/informational, and total social support, and positively associated with severe substance use ( ps

Background Treatment of human lung squamous cell carcinoma (LUSC) using current targeted therapies is limited because of their diverse somatic mutations without any specific dominant driver mutations. These mutational diversities preventing the use of common targeted therapies or the combination of available therapeutic modalities would require a preclinical animal model of this tumor to acquire improved clinical responses. Patient-derived xenograft (PDX) models have been recognized as a potentially useful preclinical model for personalized precision medicine. However, whether the use of LUSC PDX models would be appropriate enough for clinical application is still controversial. Methods In the process of developing PDX models from Korean patients with LUSC, the authors investigated the factors influencing the successful initial engraftment of tumors in NOD scid gamma mice and the retainability of the pathological and genomic characteristics of the parental patient tumors in PDX tumors. Conclusions The authors have developed 62 LUSC PDX models that retained the pathological and genomic features of parental patient tumors, which could be used in preclinical and co-clinical studies. Trial registration Tumor samples were obtained from 139 patients with LUSC between November 2014 and January 2019. All the patients provided signed informed consents. This study was approved by the institutional review board (IRB) of Samsung Medical Center (2018-03-110)

Objective Early trauma (ET) is widely recognized as a contributing factor to the development of panic disorder (PD) in patients. However, there is a dearth of research on the specific volumes of hippocampal subregions and their laterality with respect to ET and PD. Methods A total of 30 subjects with PD and 30 age- and sex-matched healthy controls (HCs) were included in this study. All the subjects were evaluated by 3T-magnetic resonance imaging. FreeSurfer version 6.0 was used for volumetric analysis of the hippocampal subregions and their laterality. A shortened version of the Early Trauma Inventory Self Report (ETISR) as well as Anxiety Sensitivity Inventory-Revised (ASI-R), and Panic Disorder Severity Scale were utilized for analysis. Results Multivariate analysis of variance showed that the volume of the right hippocampal tail and laterality indices (LIs) of the hippocampal body and tail were significantly larger in subjects with PD relative to HCs. The significance of the observations remained unchanged after multivariate analysis of covariance, controlling for age, sex, years of education, medication, depressive symptoms, and intracranial volume as covariates. The LIs of the hippocampal tails that showed a significant correlation to ETISR emotional and physical subscales were also associated with ASI-R for cardiovascular symptoms in PD. Conclusion Our study displayed an increased rightward lateralization of the hippocampal tails in subjects with PD compared with HCs. This alteration in the brain, which was associated with early emotional and physical trauma, would negatively affect anxiety sensitivity to cardiovascular symptoms in subjects with PD.

Background and Purpose— In unilateral moyamoya disease, altered endothelial shear stress on the intact-side terminal internal carotid artery might trigger the progression to bilateral disease. We analyzed the endothelial shear stress parameters of the normally appearing terminal internal carotid artery in unilateral moyamoya disease and its association with the progression to bilateral disease. Methods— This retrospective cohort study included patients diagnosed with unilateral moyamoya disease by cerebral angiography and followed-up with regular magnetic resonance imaging/magnetic resonance angiography evaluations for >1 year. Endothelial shear stress parameters acquired were mean and maximum signal intensity gradients (SIG) and SIG SD at the vessel boundary in time-of-flight sequences in initial brain magnetic resonance imaging/magnetic resonance angiography. Contralateral disease progression defined as the detection of newly developed vessel steno-occlusion with an magnetic resonance angiography steno-occlusive stage of ≥2, in the previously intact side of the brain on follow-up magnetic resonance imaging/magnetic resonance angiography evaluation. Results— Among 146 patients (66 males [45.2%] and 80 females [54.8%]; 76 pediatric [52.1%]), contralateral disease progression was detected in 43 patients (29.5%) after a mean follow-up of 4.3±2.4 years. Multivariate analysis showed that SIG SD was significantly associated with this progression (odds ratio, 13.001 [95% CI, 1.764−95.794], P =0.012). In receiver operating characteristic curve analysis, SIG SD predicted the contralateral progression with area under the curve values of 0.803 (95% CI, 0.726−0.880, P Conclusions— Increased spatial variability of the endothelial shear stress around the normally appearing terminal internal carotid artery, as measured by SIG SD in time-of-flight sequences, may predict the contralateral progression of unilateral moyamoya disease.

OBJECTIVES: The first confirmed case of coronavirus disease 2019 (COVID-19) in South Korea was reported in January 2020, with 28 confirmed cases reported as of February 14th, 2020. The epidemiological and clinical characteristics of all 28 cases were analyzed in response to this disease. METHODS: The epidemiological characteristics and early clinical features of the 28 patients from Korea with confirmed COVID-19 were analyzed using COVID-19 reporting and surveillance data and the epidemiological investigation reports prepared by the rapid response team. RESULTS: There were 16 patients that entered Korea from foreign countries: Wuhan, China (11 patients), Zhuhai, China, (1 patient), Singapore (2 patients), Japan (1 patient), and Thailand (1 patient). The early symptoms were fever, sore throat, cough or sputum production, chills, and muscle ache. Three patients were asymptomatic, however, 18 developed pneumonia. Of the 28 cases, 16 were index cases imported from abroad, with 10 cases of secondary infection originating in Korea, and the route of transmission still under investigation for 2 patients. The 10 patients with secondary infection were infected from contact with family members or acquaintances of primary patients, and the suspected sites of transmission were mostly at home. CONCLUSION: COVID-19 in Korea was spread by 16 infected individuals traveling from other countries, leading to second-generation cases. The initial symptoms were mostly minor, but the disease was infectious at this stage, resulting from close contact, particularly at home. Establishing an early detection strategy for COVID-19 is crucial for managing the transmission of the disease.

Objective:Tuberculosis (TB) remains one of the leading causes of mortality and morbidity among people living with HIV. We sought to estimate the incidence of TB in a national database of HIV-infected patients receiving antiretroviral therapy (ART) in Botswana.Design:A retrospective analysis of HIV-i

Although the majority of patients with schizophrenia are not actually violent, an increased tendency toward violent behaviors is known to be associated with schizophrenia. There are several factors to consider when identifying the subgroup of patients with schizophrenia who may commit violent or aggressive acts. Comorbidity with substance abuse is the most important clinical indicator of increased aggressive behaviors and crime rates in patients with schizophrenia. Genetic studies have proposed that polymorphisms in the promoter region of the serotonin transporter gene and in the catechol-O-methyltransferase gene are related to aggression. Neuroimaging studies have suggested that fronto-limbic dysfunction may be related to aggression or violence. By identifying specific risk factors, a more efficient treatment plan to prevent violent behavior in schizophrenia will be possible. Management of comorbid substance use disorder may help prevent violent events and overall aggression. Currently, clozapine may be the only effective antipsychotic medication to repress aggressive behavior. With the current medical field moving toward tailored medicine, it is important to identify vulnerable schizophrenia populations and provide efficient treatment.

BackgroundResearchers have increasingly recognized the adverse effects of smoking on tuberculosis (TB) outcomes. Smoking may be a maladaptive coping mechanism for depression and anxiety among TB patients; however, this association has not yet been investigated.Design/MethodsWe conducted a cross-sectional study among newly diagnosed TB patients between January and December 2019 in Gaborone, Botswana, and evaluated factors associated with cigarette smoking. Using the Patient Health Questionnaire-9 and the Zung Self-Rating Anxiety scale, we collected depression and anxiety scores, respectively; scores of ≥10 indicate depression and scores of ≥36 indicate anxiety. We performed Poisson regression analyses with robust variance to examine whether depression and anxiety were associated with smoking.ResultsOne hundred and eighty participants with TB were enrolled from primary health clinics. Among all enrollees, depression was reported in 46 (27.1%) participants, while anxiety was reported in 60 (44.4%) participants. Overall, 45 (25.0%) participants reported current smoking, and the median number of cigarettes per day was 10. Depressive symptoms were associated with a higher prevalence of smoking (aPR: 1.82; 95% CI = 1.11, 3.01) after adjusting for sex, HIV status, food insecurity, anxiety, and income. The association between anxiety symptoms and cigarette smoking did not reach statistical significance (aPR 1.26; 95% CI: 0.78-2.05).ConclusionsWe found the association between depressive symptoms and smoking among TB patients in Botswana to be significant and the association between anxiety symptoms and cigarette smoking insignificant. Future studies should further investigate these associations when addressing TB care.

BACKGROUND Tuberculosis (TB) disproportionately affects marginalized and impoverished homeless adults. Although active TB can be prevented by treating latent TB infection (LTBI), individual factors, such as high prevalence of depression and anxiety, drug and alcohol use, and unstable housing, lead to poor LTBI treatment adherence and completion among homeless adults. OBJECTIVES We hypothesized that the delivery of a tailored nurse-led, community health worker (RN/CHW) program across the LTBI continuum of care (e.g., screening, diagnosis, and treatment) that delivers 3HP treatment (3HP: rifapentine plus isoniazid) for homeless adults (e.g., sheltered and unsheltered) and is tailored to their health and social service needs will overcome existing treatment completion barriers. We also hypothesized that mental health symptoms (e.g., depression and anxiety), drug use score, and problematic alcohol use will decline over time among clients receiving this treatment. METHODS We assessed the effect of delivering a theoretically guided, RN/CHW-based, single-arm study among eligible LTBI-positive homeless adults (N = 50) on completion of a weekly, directly observed, 12-dose 3HP LTBI treatment in Central City East (Skid Row). Completing 3HP treatment was compared to the only known historical, clinic-based control that obtained 65% completion among homeless adults. Secondary outcomes included drug and alcohol use, depression, and anxiety. RESULTS The RN/CHW program achieved a 91.8% 3HP treatment completion rate among homeless adults. Younger homeless adults (

This study evaluated the time trends in mobile phone subscriber number by mobile network generation (G) and brain cancer incidence by type in Korea. We obtained data from the Information Technology Statistics of Korea (1984-2017) and Korea Central Cancer Registry (1999-2017). The average annual percent change was estimated using Joinpoint regression analysis. We evaluated 29,721 brain cancer cases with an age-standardized incidence rate (ASR) of 2.89/100,000 persons. The glioma and glioblastoma annual ASR significantly increased in 2.6% and 3.9% of males and 3.0% and 3.8% of females, respectively. The ASR for frontal lobe involvement was the highest. The ASR of gliomas of unspecified grade annually increased by 7.8%; those for unspecified topology and histology decreased. The incidence of glioma, glioblastoma, frontal, temporal, and high-grade glioma increased among those aged ≥60 years. No association was observed between the mobile phone subscriber number and brain cancer incidence in Korea. Furthermore, long-term research is warranted because of the latency period of brain cancer. © 2021 Bioelectromagnetics Society.

In 2017, the Korean government launched an unprecedentedly large-scaled latent tuberculosis infection (LTBI) screening project which covered more than a million individuals in congregate settings. A total of 1,047,689 participants of source population (n = 2,336,157) underwent LTBI testing from 2017 to 2018. The overall LTBI test uptake rate during this project was 44.8%. Workers in daycare centers (83.5%) and kindergartens (78.9%) showed high participation rate. A total of 1,012,206 individuals with valid results of interferon-gamma release assay (IGRA) were selected to constitute the IGRA cohort. Most of the enrolled participants in the IGRA cohort were in their working age. Approximately, three-quarters of total enrolled population were female. Investigating the LTBI prevalence, stages of LTBI care cascade, natural history of LTBI, efficacy of LTBI treatment and cost-effectiveness of LTBI screening are feasible within this IGRA cohort., Graphical Abstract

Cervical cancer is a leading cause of death among women in low- and middle-income countries, and women living with HIV are at high risk for cervical cancer. The objective of this study was to estimate the prevalence and correlates of cervical cancer and pre-cancer lesions and to examine cervical cancer knowledge among women living with HIV receiving antiretroviral therapy in rural Andhra Pradesh, India. We conducted cytology-based screening and administered a standardized questionnaire among 598 HIV-infected women. We found 5 (0.8%), 39 (6.5%), 29 (4.9%), and 4 (0.7%) had atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), and squamous cervical carcinoma (SCC), respectively. In multivariable logistic regression analysis, ASCUS/LSIL was independently associated with age >16 years old at first sexual encounter and smokeless tobacco use. We found no factors associated with HSIL/SCC. In total, 101 women (16.9%) had heard of cervical cancer and 28 (27.7%) of them correctly identified HIV infection as a risk factor. In light of the high prevalence of pre-cancer lesions and low level of cervical cancer knowledge in our study population, focused interventions are needed to improve cervical cancer literacy and prevention among rural women living with HIV.

Background Cervical cancer is the leading cause of cancer death in Sub-Saharan Africa. The risk of developing cancer is increased for women living with human immunodeficiency virus (HIV) infection. It is unknown which factors predict the initiation of curative chemoradiotherapy (CRT) in resource-limited settings and whether HIV is associated with initiating curative CRT in settings with a high HIV burden. Methods All women living with and without HIV infection who were initiating curative and noncurative CRT for locally advanced cervical cancer in Botswana were prospectively enrolled in an observational study. The factors associated with receiving CRT were evaluated in all patients and the subgroup of women living with HIV. Results Of 519 enrolled women, 284 (55%) initiated CRT with curative intent. The curative cohort included 200 women (70.4%) who were living with HIV and had a median CD4 count of 484.0 cells/μL (interquartile range, 342.0-611.0 cells/μL). In the noncurative cohort, 157 of 235 women (66.8%) were living with HIV and had a median CD4 count of 476.5 cells/μL (interquartile range, 308.0-649.5 cells/μL). HIV status was not associated with initiating curative CRT (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.58-1.56). The factors associated with receiving curative CRT treatment on multivariable analysis in all patients included baseline hemoglobin levels ≥10 g/dL (OR, 1.80; 95% CI, 1.18-2.74) and stage I or II versus stage III or IV disease (OR, 3.16; 95% CI, 2.10-4.75). Women aged >61 years were less likely to receive curative treatment (OR, 0.43; 95% CI, 0.24-0.75). Among women who were living with HIV, higher CD4 cell counts were associated with higher rates of CRT initiation. Conclusions The initiation of CRT with curative intent does not depend on HIV status. Significant predictors of CRT initiation include baseline hemoglobin level, disease stage, and age.

PURPOSE Though regular surveillance of hepatocellular carcinoma (HCC) for high-risk patients is widely recommended, its rate and effectiveness are not clear. The aim of this study is to investigate the actual rate of HCC surveillance and its related factors and to clarify its impact on survival in a Korean HCC cohort. Materials and Methods From 2012 to 2015, 319 newly diagnosed HCC patients were prospectively enrolled at a tertiary hospital. Patient interviews based on a structured questionnaire survey were conducted. Surveillance was defined as liver imaging test ≥ 2 times with at least 3-month interval within 2 years prior to HCC diagnosis. RESULTS Surveillance rate was 39.8%. Of the HCC patients with high-risk factors, only 182 (57.1%) had knowledge for the need for regular surveillance, and 141 (44.2%) had the accurate information about the method (ultrasound-based study). Surveillance group showed a higher proportion of early HCC (p < 0.001) and a longer overall survival (p < 0.001) compared to non-surveillance group. The multivariable Cox regression analysis indicated Child-Pugh class A, history of anti-viral therapy, low serum α-fetoprotein level, non-advanced Barcelona Clinic Liver Cancer stage as independent predictors of overall survival, while regular surveillance was not (p=0.436). CONCLUSION Less than half of the newly diagnosed Korean HCC patients were under surveillance and the accurate perception for the need of HCC surveillance was insufficient. Of those under surveillance, most patients were diagnosed with early stage HCC, which led to the improved survival. Comprehensive efforts to optimize the surveillance program for the target population are warranted.

One of the primary goals of epidemiology is to quantify various aspects of a population’s health, illness, and death status and the determinants (or risk factors) thereof by calculating health indicators that measure the magnitudes of various conditions. There has been some confusion regarding health indicators, with discrepancies in usage among organizations such as the World Health Organization the, Centers for Disease Control and Prevention (CDC), and the CDC of other countries, and the usage of the relevant terminology may vary across papers. Therefore, in this review, we would like to propose appropriate terminological definitions for health indicators based on the most commonly used meanings and/or the terms used by official agencies, in order to bring clarity to this area of confusion. We have used appropriate examples to make each health indicator easy for the reader to understand. We have included practical exercises for some health indicators to help readers understand the underlying concepts.

PURPOSE/OBJECTIVE(S) To present the stage and outcomes of patients with invasive cervical cancer with all stages in Botswana with or without HIV, and to prospectively evaluate factors associated with survival in this population. MATERIALS/METHODS Between April 2013 and November 2020, women with locally advanced cervical cancer (Stages IA-IVB) living with or without HIV infection were prospectively enrolled in an observational cohort study. Overall survival (OS) was evaluated using the Kaplan-Meier method. Associations with survival were analyzed using Cox proportional hazards modeling. RESULTS Among the 1,034 patients, 69% were women living with HIV (WLWH), 8% (n = 59) had surgery, 84% (n = 603) received radiation (RT), and 55% (n = 391) received chemoradiation (CRT). Median CD4 count at the time of cancer diagnosis in the cohort was 431.5 (245.3-613.8) and 13% had detectable viral load. 94% of patients were on anti-retroviral treatment at the time of cancer diagnosis. Median age of the WLWH was 44 years compared to 61 years in patients living without HIV infection (P < 0.001). Stage distribution in the cohort was as follows: Stage I was 16% (n = 170), Stage II was 37% (n = 384), Stage III was 35% (n = 364), and Stage IV was 8% (n = 86). Median follow up time was 1.95 years. OS at 2 years for Stage I was 95%, Stage II was 89%, Stage III was 54%, and Stage IV was 39%. Combined OS at 2 years was 67%. OS at 5 years for Stage I was 88%, Stage II was 63%, Stage III was 40%, and Stage IV was 32%. Combined OS at 5 years was 56%. WLWH did not show significant differences in OS as compared to those without HIV infection: OS at 2 years was 67% vs. 71% in women WLWH vs. without HIV infection and OS at 5 years was 49% in vs. 60% in women WLWH vs. without HIV infection (P = 0.105). In multivariable cox regression analysis including all patients, OS was associated with baseline hemoglobin (Hb) (HR 0.88, P < 0.001), baseline performance status (HR 1.42, P = 0.004), and disease stage: Stage II (HR 2.71, P = 0.001), Stage III (HR 4.96, P < 0.001), and Stage IV (HR 6.91, P < 0.001). CONCLUSION Among women in Botswana with cervical cancer, HIV status had no effect on OS. Survival was largely associated with patients' disease stage, Hb, and performance status at the time of treatment. Patients with early stage cervical cancer had adequate outcomes regardless of their HIV status. Therefore, for all women it is imperative to optimize their primary care to improve early detection of disease. AUTHOR DISCLOSURE J. George: Independent Contractor; AbbVie. S. Tuli: None. B. Monare: None. K. Lichter: None. D. Ramogola-Masire: None. T. Ralefala: None. A. Seiphetlheng: None. N. Zetola: None. S. Shin: None. L. Bazzett-Matabele: None. S. Grover: None.

The effectiveness of household contact investigations is limited by low referral uptake for clinic-based TB testing by symptomatic household contacts. We qualitatively investigated the acceptability and perceived benefits of home-based TB testing using a portable GeneXpert-I instrument (GX-I) in an urban South African township.In-depth interviews were conducted with household contacts tested and those that observed testing. Semi-structured interviews explored household contact's understanding of TB, perceptions of the GX-I device and testing procedures, confidentiality, willingness to refer others, and views on home- vs. clinic-based testing. Focus group discussions with home-based TB testing implementing staff assessed operational considerations for scale-up. Data were analysed using a constant comparison approach to qualitatively evaluate the acceptability and feasibility of home-based TB testing.Thirty in-depth interviews and two focus group discussions were conducted. Observing one's own sputum being tested resulted in an emergent trust in home-based TB testing, the GX-I device and one's test results. Home-based TB testing was considered convenient, helped to overcome apathy towards testing and mitigated barriers to clinic-based testing. Perceptions that home-based TB testing contributes to improved household and community health resulted in an emergent theme of alleviation of health insecurities. Operational concerns regarding inadvertent disclosure of one's diagnosis to household members and time spent in people's homes were identified.Home-based TB testing was acceptable and feasible. Individuals expressed belief in the machine by being able to witness the testing process. Though most themes mirrored qualitative studies of home-based HIV testing, the alleviation of health insecurities theme is unique to home-based TB testing. Future research must evaluate the impact of home-based TB testing on case finding yield, time-to-treatment initiation and household outcomes.L'efficacité des enquêtes sur les contacts familiaux est limitée par le faible taux de respect de l’orientation pour le dépistage de la tuberculose (TB) en clinique par les contacts familiaux symptomatiques. Nous avons investigué qualitativement l'acceptabilité et les avantages perçus du dépistage de la TB à domicile à l'aide d'un dispositif portable GeneXpert-I (GX-I) dans une ville urbaine sud-africaine. MÉTHODES: Des entretiens approfondis ont été menés avec des contacts familiaux testés et ceux qui ont observé la pratique des tests. Des entretiens semi-structurés ont permis d'explorer la compréhension de la TB par les contacts familiaux, les perceptions sur le dispositif GX-I et les procédures de test, la confidentialité, la volonté de référer d'autres personnes et les opinions sur le dépistage à domicile ou en clinique. Des discussions de groupe focalisées avec le personnel chargé de la mise en œuvre du dépistage de la TB à domicile ont évalué les considérations opérationnelles pour le déploiement. Les données ont été analysées en utilisant une approche de comparaison constante pour évaluer qualitativement l'acceptabilité et la faisabilité du dépistage de la TB à domicile. RÉSULTATS: Trente entretiens approfondis et deux discussions de groupe ont été menés. L'observation de ses propres expectorations testées a conduit à une émergente de confiance dans le dépistage de la TB à domicile, le dispositif GX-I et les résultats des tests. Le dépistage de la TB à domicile était considéré comme pratique, aidait à surmonter l'apathie envers le dépistage et atténuait les obstacles au dépistage en clinique. La perception selon laquelle le dépistage de la TB à domicile contribue à l'amélioration de la santé des ménages et de la communauté a donné lieu à l’émergence du thème de la réduction des insécurités sanitaires. Des préoccupations opérationnelles concernant la divulgation par inadvertance de son diagnostic aux membres du ménage et le temps passé au domicile des personnes ont été identifiées.Le dépistage de la TB à domicile était acceptable et faisable. Les individus ont exprimé leur croyance en la machine en étant en mesure d'assister au processus de test. Bien que la plupart des thèmes reflètent des études qualitatives sur le dépistage du VIH à domicile, le thème de l'atténuation des insécurités sanitaires est unique au dépistage de la TB à domicile. Les recherches futures doivent évaluer l'impact du dépistage de la TB à domicile sur le rendement de la recherche des cas, le délai de mise en route du traitement et les résultats au sein des ménages.

Homeless adults are at increased risk of latent tuberculosis infection (LTBI), which can lead to active tuberculosis (TB) disease. The purpose of this study was to assess acceptability and feasibility of a six-month, nurse-led, community health worker-partnered short-course treatment (3HP) LTBI adherence model for a high risk, LTBI positive, homeless population. Informed by our community advisory board (CAB) and community-based participatory research principles (CBPR), a qualitative study was undertaken and used focus group discussions to identify perspectives of homeless men and women who had undergone LTBI treatment (N = 11, Mage = 51.2, SD 8.60, range 35&ndash, 60). Three themes formed, which were engaging and recruiting LTBI intervention participants, delivering an LTBI intervention, and retaining LTBI intervention participants. Within those themes, barriers (e.g., lack of LTBI treatment readiness, substance use, etc.), and facilitators (e.g., LTBI and TB health education, familiarity with homeless population, etc.) were discussed to facilitate program recruitment, program delivery and program retention. These findings provide a greater understanding of how to effectively utilize a nurse-led, Community Health Worker (CHW) intervention delivery method to not only improve 3HP LTBI medication adherence, but also decrease substance use, improve mental health, and decrease unstable housing among this vulnerable population at high risk for active tuberculosis.

Objective To evaluate the diagnostic performance of the antimullerian hormone (AMH) level determined using the Access AMH assay for predicting poor ovarian response (POR) defined as ≤4 oocytes retrieved, including the validation of the predefined AMH cutoff of 0.93 ng/mL in both serum and plasma. Design Prospective cohort study. Setting Fifteen private and academic fertility centers (14 in the United States and 1 in Canada). Patient(s) Women aged 21–45 years planning controlled ovarian stimulation for in vitro fertilization. Intervention(s) None. Main Outcome Measure(s) Number of oocytes retrieved, categorized as POR and normal-to-high ovarian response (non-POR). The correlation of AMH level and antral follicle count. Result(s) Data were available for 472 participants who completed the study (74 with POR and 398 non-POR). The mean AMH serum level among those with POR was 0.99 ng/mL (median 0.76 ng/mL) compared with 2.83 ng/mL (median 2.36 ng/mL) among the normal-to-high responders. For confirmation of the 0.93 ng/mL AMH level cutoff as a predictor of POR, a receiver operating characteristic analysis gave an area under the curve of 0.852, with corresponding sensitivity and specificity of 63.5% and 89.2%, respectively. The associated positive predictive value was 52.2% and the negative predictive value was 92.9%. The AMH plasma values demonstrated a strong correlation with AMH serum values with an r value = 0.9980. The previously established AMH cutoff of 1.77 ng/mL for antral follicle count >15 resulted in a sensitivity of 83.8% (95% confidence interval [CI] 77.7–88.5) and a specificity of 59.9% (95% CI 54.2–65.4). Conclusion(s) This study validated the previously established AMH cut-point for the prediction of POR. Because this cut-point may vary depending on the assay used, the specific AMH assay should be reported in the literature whenever possible.

Background: Common carotid artery (CCA) and internal carotid artery (ICA) are aligned linearly, but their hemodynamic role in ischemic stroke has not been studied in depth. Objectives: We aimed to investigate whether CCA and ICA endothelial shear stress (ESS) could be associated with the ischemic stroke of large artery atherosclerosis (LAA). Methods: We enrolled consecutive patients with unilateral ischemic stroke of LAA and healthy controls aged >60 years in the stroke center of Jeonbuk National University Hospital. All patients and controls were examined with carotid artery time-of-flight magnetic resonance angiography, and their endothelial signal intensity gradients (SIGs) were determined, as a measure of ESS. The effect of right or left unilateral stroke on the association between carotid artery endothelial SIG and ischemic stroke of LAA was assessed. Results: In total, the results from 132 patients with ischemic stroke of LAA and 121 controls were analyzed. ICA endothelial SIG showed significant and independent associations with the same-sided unilateral ischemic stroke of LAA, even after adjusting for the potential confounders including carotid stenosis, whereas CCA endothelial SIG showed a significant association with the presence of the ischemic stroke of LAA. Conclusion: Although CCA and ICA are located with continuity, the hemodynamics and their roles in large artery ischemic stroke should be considered separately. Further studies are needed to delineate the pathophysiologic roles of ESS in CCA and ICA for large artery ischemic stroke.

Background Accurately diagnosing schizophrenia is still challenging due to the lack of validated biomarkers. Here, we aimed to investigate whether radiomic features in bilateral hippocampal subfields from magnetic resonance images (MRIs) can differentiate patients with schizophrenia from healthy controls (HCs). Methods A total of 152 participants with MRI (86 schizophrenia and 66 HCs) were allocated to training (n = 106) and test (n = 46) sets. Radiomic features (n = 642) from the bilateral hippocampal subfields processed with automatic segmentation techniques were extracted from T1-weighted MRIs. After feature selection, various combinations of classifiers (logistic regression, extra-trees, AdaBoost, XGBoost, or support vector machine) and subsampling were trained. The performance of the classifier was validated in the test set by determining the area under the curve (AUC). Furthermore, the association between selected radiomic features and clinical symptoms in schizophrenia was assessed. Results Thirty radiomic features were identified to differentiate participants with schizophrenia from HCs. In the training set, the AUC exhibited poor to good performance (range: 0.683–0.861). The best performing radiomics model in the test set was achieved by the mutual information feature selection and logistic regression with an AUC, accuracy, sensitivity, and specificity of 0.821 (95% confidence interval 0.681–0.961), 82.1%, 76.9%, and 70%, respectively. Greater maximum values in the left cornu ammonis 1–3 subfield were associated with a higher severity of positive symptoms and general psychopathology in participants with schizophrenia. Conclusion Radiomic features from hippocampal subfields may be useful biomarkers for identifying schizophrenia.

Cervical cancer remains a significant cause of morbidity and mortality in women worldwide and is the leading cause of cancer-related death in Botswana. It is well established that women with HIV have a higher risk of persistent HPV infection leading to cervical cancer. We assessed HPV prevalence and genotype distribution in 126 tissue specimens from confirmed invasive cervical cancer cases using Abbott real-time PCR assay. Overall, 88 (69.8%) women were HIV-infected. Fifty-seven (64.8%) of the HIV-infected women had a baseline CD4+ count ≥350 cells/μl, and 82 (93.2%) were on antiretroviral therapy at the time of cervical cancer diagnosis. The median age of HIV-infected patients was significantly younger than that of HIV-uninfected patients (p

Background Early trauma exposure is suggested to confer a greater risk for the development of panic disorder (PD) by altering neurodevelopmental processes. A body of studies have shown that white matter microstructures, particularly in the fronto-limbic and callosal regions, could be affected by a history of early trauma in patients with PD. The tapetum, the extended posterior part of the corpus callosum connecting the bilateral temporal lobes, has not yet been studied regarding its relationship with early trauma, especially sexual one. Methods Seventy participants with PD, sixty age- and sex-matched healthy controls were enrolled. The Early Trauma Inventory Self Report-Short Form (ETISR-SF), Neuroticism Scale, and Panic Disorder Severity Scale (PDSS) were administered. Voxel-wise statistical analysis of diffusion tensor imaging data was performed within the bilateral tapetum regions using Tract-Based Spatial Statistics (TBSS). Results In participants with PD, higher levels of sexual trauma were significantly associated with the increased fractional anisotropies (FAs) in a cluster of the right tapetum. Exploratory correlation analysis revealed that FAs in this cluster were significantly correlated with higher neuroticism and poorer treatment response after one year of pharmacotherapy. No significant correlation was found between FAs of the right tapetum cluster and the PDSS scores. Limitations The possibility of retrospective recall bias for early trauma cannot be completely ruled out. Conclusions The findings of this study suggest that the right tapetum may serve as a potential neural marker of early sexual trauma in patients with PD and contribute to personal vulnerability and poorer treatment outcome after pharmacotherapy.

Background In February 2020, a coronavirus disease 2019 (COVID-19) outbreak was reported in fitness centers in Cheonan, Korea. Methods From February 24 to March 13, an epidemiological investigation was conducted on the fitness center outbreak. All those who were screened were tested for severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) using real-time reverse transcriptase polymerase chain reaction. Contacts were traced and self-isolated for 14 days. We determined the epidemiological characteristics of confirmed cases of SARS-CoV-2 infection, and estimated the time-dependent reproduction number to assess the transmission dynamics of the infection. Results A total of 116 cases were confirmed, and 1,687 contacts were traced. The source cases were 8 Zumba instructors who led aerobics classes in 10 fitness centers, and had the largest average number of contacts. A total of 57 Zumba class participants, 37 of their family members, and 14 other contacts were confirmed as cases. The attack rate was 7.3%. The contacts at Zumba classes and homes had a higher attack rate than other contacts. The mean serial interval (± standard deviation) were estimated to be 5.2 (± 3.8) days. The time-dependent reproduction number was estimated to be 6.1 at the beginning of the outbreak, but it dropped to less than 1, 2 days after the epidemiological investigation was launched. Conclusion The results suggest that the COVID-19 outbreak was effectively contained with rigorous contact tracing, isolating, and testing in combination with social distancing without a lock-down., Graphical Abstract

It is well accepted that panic disorder (PD) is associated with early trauma, and that the limbic systems are one of the main structures involved in PD pathophysiology. However, previous studies have not addressed the relationship between early trauma and major limbic white-matter (WM) structures in PD.Participants enrolled in the study consisted of 53 right-handed patients with PD and 21 healthy controls (HC). The Early Trauma Inventory Self Report-Short Form (ETISR-SF), Anxiety Sensitivity Inventory-Revised (ASI-R), and the Albany Panic and Phobia Questionnaire (APPQ) were applied in the study. Tract-based spatial statistics were used for diffusion tensor magnetic resonance imaging analysis.Among the patients with PD, the fractional anisotropy (FA) values of the fornix body in major limbic WM regions showed significant negative correlation with the ETISR-SF total score, while the scores of mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) in the same region of fornix had significant positive correlation with those scores (p0.05; FWE corrected). Further significant correlation was observed between these four scores and the measures of symptom severity in PD, such as that in ASI-R and APPQ in the same region.Recall bias is possible in evaluating early trauma in the participants.The current study suggests a significant association of early trauma with the fornix body possibly through axons and myelin disruptions within major limbic structures in PD. A multi-centered large sample will be needed to confirm these findings.

Background Health care workers (HCWs) are at high risk for occupational blood exposures (OBEs) and transmission of bloodborne pathogens. This study elucidated the incidence rate and epidemiological characteristics of OBEs among HCWs and investigated the pathogen transmission rate for hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV). Methods Self-reported OBEs from January 1, 2011 to December 31, 2015 were obtained from the electronic recording system. OBE incidence densities per 100 person-years and per 100 bed-years were calculated with a 5-year trend analysis. OBE characteristics and pathogen transmission rates were evaluated. Results Among 10,452 HCWs and 1072 average yearly beds, 1076 OBEs were reported. OBE incidence rate was 5.6 cases per 100 person (full-time equivalent)-years and 20.3 per 100 bed-years. Incidence rate decreased and was significantly associated with a decrease of beds served per HCW. Housekeeping showed the highest OBE rate (14.8%) followed by doctors (8.5%) and nurses (6.2%). OBEs occurred in wards, emergency rooms, and operating rooms (38.1%, 13.3% and 12.2%, respectively) via percutaneous (86.7%) and mucocutaneous exposures (13.2%). Of OBEs associated with HBV (n = 133), HCV (n = 126), and HIV (n = 25), only one led to an infection (HCV; transmission rate of 0.8%). Neither HBV nor HIV infection occurred. Conclusions OBE incidence rate in a Korean university hospital was 5.6 cases per 100 person-years and 20.3 per 100 bed-years and was related to HCW workload and work proficiency. Though the actual bloodborne pathogen transmission rate was low, efforts to prevent OBE should be made for hospital safety.

To analyze the treatment outcomes and the effects of adjuvant radiotherapy (RT) in patients with synovial sarcoma (SS). The medical records of 103 patients treated with definitive surgery for SS, with/without RT, from August 1982 to July 2013 were reviewed retrospectively. The median age of the patients was 33 years (range, 5 to 72 y). The most frequent tumor location was the extremities (79 patients, 77%). Seventy-five patients (73%) received adjuvant RT and 26 (25%) did not. The median dose of adjuvant RT was 61.2 Gy (range, 45 to 66.6 Gy). The median follow-up period was 5.4 years (range, 0.2 to 31.0 y). The 5- and 10-year overall survival rates were 77 % and 65%, respectively. The progression-free survival (PFS) rates at 5 and 10 years were 52% and 43%, respectively. The most common site of initial failure was the lung (24 patients), followed by local recurrence (14 patients). The 5-year local-recurrence-free survival (LRFS) and distant-metastasis-free survival (DMFS) rates were 80% and 63%, respectively. On multivariate analysis, a mitosis count of

Bisphenol A (BPA) has been reported to be associated with adverse health effects, including high blood pressure (BP). BPA is also suspected to cross placenta in pregnancy and might affect children’s health. The present study was aimed to evaluate the effect of prenatal exposure to BPA on the BP of the child at the age of 4. We followed up 645 children at the age of 4 who were born from women who participated midterm during their pregnancy in a birth cohort study from August 2008 to July 2011. Because BPA and BP showed nonlinear association, we constructed a piecewise regression model to examine the association between urinary BPA concentration of mother at around 20 weeks of gestation and BP of the child at age 4 and to determine threshold level of BPA for the association. Diastolic BP of the children was positively associated with maternal urinary concentration of BPA above the threshold level measured at around 20 weeks of gestation. For 1 log unit increment of prenatal urinary BPA concentration, diastolic BP was increased by 7.9 mm Hg (SE=2.072; P =0.0001) after adjusting potential confounders. Pulse pressure was decreased by −8.0 mm Hg (SE=2.528; P =0.0015). However, systolic BP was not significantly associated with prenatal BPA concentration. The present study suggests that exposure to BPA during pregnancy is associated with higher diastolic BP of the children above a certain threshold (4.5 μg/g creatinine).

Background Blood pressure rises with a drop in external temperature, but the role of DNA methylation in such blood pressure modulation has not been studied in detail. We evaluated blood pressure and DNA methylation of vascular disease-related genes in association with low temperature. Methods To examine changes in blood pressure and DNA methylation associated with low temperature, we conducted repeated measures analysis among 50 participants over 3 repeated visits, and validated the association among another 52 participants. In addition, the mean of methylation changes in the identified CpG sites was evaluated with changes in blood pressure. Mediation analyses were also conducted to model the indirect association between low ambient temperature and blood pressure through changes in DNA methylation. Results With a 1 °C decrease in temperature, increases of 0.6 mmHg (standard error (SE), 0.2) in SBP and 0.3 mmHg (SE, 0.1) in DBP occurred (P ZNF ) genes were significantly associated with temperature after Bonferroni's correction in discovery and replication data. A 10% increase in methylation expression in 2 CpG sites in ZNF genes was associated with a 4-mmHg elevation in DBP (SE, 1.8; P=0.0236). The hypermethylation was attributable to the association of ambient temperature with DBP (proportion of mediation=11.8–20.4%). Conclusions Methylation changes in ZNF genes might be involved in the elevation of blood pressure when the body is exposed to cold temperature.

ObjectiveTo examine the use of the Prostate Health Index (PHI) as a continuous variable in multivariable risk assessment for aggressive prostate cancer in a large multicentre US study.Materials and methodsThe study population included 728 men, with prostate-specific antigen (PSA) levels of 2-10 ng/mL and a negative digital rectal examination, enrolled in a prospective, multi-site early detection trial. The primary endpoint was aggressive prostate cancer, defined as biopsy Gleason score ≥7. First, we evaluated whether the addition of PHI improves the performance of currently available risk calculators (the Prostate Cancer Prevention Trial [PCPT] and European Randomised Study of Screening for Prostate Cancer [ERSPC] risk calculators). We also designed and internally validated a new PHI-based multivariable predictive model, and created a nomogram.ResultsOf 728 men undergoing biopsy, 118 (16.2%) had aggressive prostate cancer. The PHI predicted the risk of aggressive prostate cancer across the spectrum of values. Adding PHI significantly improved the predictive accuracy of the PCPT and ERSPC risk calculators for aggressive disease. A new model was created using age, previous biopsy, prostate volume, PSA and PHI, with an area under the curve of 0.746. The bootstrap-corrected model showed good calibration with observed risk for aggressive prostate cancer and had net benefit on decision-curve analysis.ConclusionUsing PHI as part of multivariable risk assessment leads to a significant improvement in the detection of aggressive prostate cancer, potentially reducing harms from unnecessary prostate biopsy and overdiagnosis.

Anxiety sensitivity (AS) refers to a fear of anxiety-related sensations and is a dispositional variable especially elevated in patients with panic disorder (PD). Although several functional imaging studies of AS in patients with PD have suggested the presence of altered neural activity in paralimbic areas such as the insula, no study has investigated white matter (WM) alterations in patients with PD in relation to AS. The objective of this study was to investigate the WM correlates of AS in patients with PD.One-hundred and twelve right-handed patients with PD and 48 healthy control (HC) subjects were enrolled in this study. The Anxiety Sensitivity Inventory-Revised (ASI-R), the Panic Disorder Severity Scale (PDSS), the Albany Panic and Phobia Questionnaire (APPQ), the Beck Anxiety Inventory (BAI), and the Beck Depression Inventory (BDI) were administered. Tract-based spatial statistics were used for diffusion tensor magnetic resonance imaging analysis.Among the patients with PD, the ASI-R total scores were significantly correlated with the fractional anisotropy values of the WM regions near the insula, the splenium of the corpus callosum, the tapetum, the fornix/stria terminalis, the posterior limb of the internal capsule, the retrolenticular part of the internal capsule, the posterior thalamic radiation, the sagittal striatum, and the posterior corona radiata located in temporo-parieto-limbic regions and are involved in interoceptive processing (p0.01; threshold-free cluster enhancement [TFCE]-corrected). These WM regions were also significantly correlated with the APPQ interoceptive avoidance subscale and BDI scores in patients with PD (p0.01, TFCE-corrected). Correlation analysis among the HC subjects revealed no significant findings.There has been no comparative study on the structural neural correlates of AS in PD.The current study suggests that the WM correlates of AS in patients with PD may be associated with the insula and the adjacent temporo-parieto-limbic WM regions, which may play important roles in interoceptive processing in the brain and in depression in PD.

BackgroundDolutegravir (DTG) has recently been recommended as a preferred first-line regimen for the treatment of new and treatment-experienced HIV-infected patients. However, potential drug interactions between DTG and rifampicin remain a clinical and public health concern.MethodsWe analyzed HIV and Tuberculosis (TB) treatment outcomes of HIV-infected patients concomitantly receiving rifampicin- and DTG-based regimens under programmatic conditions in Botswana. The outcomes of interest were successful TB treatment and viral load suppression. We used multivariable logistic models to determine predictors for each outcome of interest.ResultsA total of 1225 patients were included in the analysis to evaluate predictors of successful TB outcome. Among patients on DTG and non-DTG regimens, 90.9% and 88.3% achieved favorable TB treatment outcomes, respectively. Of those who received DTG-based regimen; 44% received once-daily dosing and 53% twice-daily dosing. We found that DTG was associated with favorable TB treatment outcome (adjusted odds ratio = 1.56; 95% confidence interval = 1.06 to 2.31), after adjusting for age, gender, and CD4 cell counts. High rates of viral load suppression were found across all antiretroviral therapy (ART) regimen categories (>92% for all). We did not find an independent association between DTG and viral suppression after adjustment of other covariates.ConclusionsThe use of DTG-based ART regimens in patients coinfected with TB and HIV lead to favorable TB and HIV treatment outcomes, comparable to those achieved with alternative ART regimens. Our results provide reassurance to TB and HIV programs about the overall programmatic concomitant use of these first-line treatment regimens for the management of HIV and TB coinfected patients.

Background Panic disorder (PD) is a prevalent and highly disabling mental condition. However, less is known about relationships between biomarkers that may together predict a better response to pharmacological treatment. The objective of the present study was to compare the brain white matter (WM) connectivity between treatment-responsive patients with panic disorder (RPD) and non-responsive patients with panic disorder (NRPD) after 12 weeks of pharmacotherapy. Methods Sixty-four patients with PD were enrolled in this study (RPD, n = 37; NRPD, n = 27). All patients were examined by using magnetic resonance imaging at 3 Tesla. The Panic Disorder Severity Scale (PDSS), Albany Panic and Phobia Questionnaire (APPQ), Anxiety Sensitivity Inventory-Revised (ASI-R), Beck Anxiety Inventory (BAI), and Beck Depression Inventory (BDI) were administered at baseline of the study. Fractional anisotropy (FA) data were compared using tract-based spatial statistics (TBSS). Results TBSS results showed that the FA values of the patients with NRPD were significantly higher than of those with RPD in the WM regions such as the precentral gyrus, parahippocampal gyrus, posterior corona radiata, posterior thalamic radiation, posterior parts of the corpus callosum, and precuneus. Symptom severity scales, such as ASI-R scores, showed significant positive correlations of the FA values with the fronto-temporal WM regions in NRPD. Conclusions These results suggest that structural changes to areas such as the fronto-limbic regions and the posterior part of default mode network, could influence medication response in PD. Further studies with a larger number of patients should be performed to confirm our findings.

Cancer patients are at higher risk of tuberculosis (TB) infection, especially in hospital settings with high TB/HIV burden. The study was implemented among adult patients admitted to the largest tertiary-level referral hospital in Botswana. We estimated the TB prevalence at admission and the rate of newly diagnosed TB after hospitalization in the medical and oncology wards, separately. Presumptive TB cases were identified at admission through symptom screening and underwent the diagnostic evaluation through GeneXpert. Patients with no evidence of TB were followed-up until TB diagnosis or the end of the study. In the medical and oncology wards, four of 867 admitted patients and two of 240 had laboratory-confirmed TB at admission (prevalence = 461.4 and 833.3 per 100,000, respectively.) The post-admission TB rate from the medical wards was 28.3 cases per 1,000 person-year during 424.5 follow-up years (post-admission TB rate among HIV-positive versus. -negative = 54.1 and 9.8 per 1,000 person-year, respectively [Rate Ratio = 5.5]). No post-admission TB case was detected from the oncology ward. High rates of undetected TB at admission at both medical and oncology wards, and high rate of newly diagnosed TB after admission at medical wards suggest that TB screening and diagnostic evaluation should target all patients admitted to a hospital in high-burden settings.

The purpose of this pilot randomized controlled trial (RCT) was to compare the 6-month outcomes of a Dialectical Behavioral Therapy–Corrections Modified (DBT-CM) program versus a Health Promotion (HP) program on mitigating recidivism among 130 female parolees/probationers between baseline and 6-month follow-up. The effect of DBT-CM on reducing recidivism was greater among those who expressed a desire for help (risk ratio [RR] = 0.40; 95% confidence interval [CI] = [0.16, 1.00]; p = .050) and among homeless female ex-offenders (HFOs) who were younger ( 35 (Model 3; RR = 0.40; 95% CI = [0.16, 1.00]; p = .050). Findings from this pilot study suggest that the DBT-CM intervention may be effective in reducing reincarceration rates among some HFOs during reentry. Larger RCTs are needed to validate our findings.

BACKGROUND: Heteroresistant Mycobacterium tuberculosis infections (defined as concomitant infection with drug-resistant and drug-susceptible strains) may explain the higher risk of poor tuberculosis treatment outcomes observed among patients with mixed-strain M. tuberculosis infections. We investigated the clinical effect of mixed-strain infections while controlling for pretreatment heteroresistance in a population-based sample of patients with tuberculosis starting first-line tuberculosis therapy in Botswana. METHODS: We performed 24-locus mycobacterial interspersed repetitive unit–variable number tandem-repeat analysis and targeted deep sequencing on baseline primary cultured isolates to detect mixed infections and heteroresistance, respectively. Drug-sensitive, micro-heteroresistant, macro-heteroresistant, and fixed-resistant infections were defined as infections in which the frequency of resistance was

Desert dust is considered to be potentially toxic and its toxicity may change during long-range transportation. In Asian countries, the health effects of desert dust in different locations are not well understood. We therefore evaluated the city-combined and city-specific effects of Asian dust events on all-cause and cause-specific mortality in five populous cities in South Korea (Seoul) and Japan (Nagasaki, Matsue, Osaka and Tokyo). We obtained daily mean concentrations of Asian dust using light detection and ranging (lidar) between 2005 and 2011. We then evaluated city-specific and pooled associations of Asian dust with daily mortality for elderly residents (≥65 years old) using time-series analyses. Each 10 μg/m3 increase in the concentration of same-day (lag 0) or previous-day (lag 1) Asian dust was significantly associated with an elevated pooled risk of all-cause mortality (relative risk (RR): 1.003 [95% CI: 1.001–1.005] at lag 0 and 1.001 [95% CI: 1.000–1.003] at lag 1) and cerebrovascular disease (RR: 1.006 [95% CI: 1.000–1.011] at lag 1). This association was especially apparent in Seoul and western Japan (Nagasaki and Matsue). Conversely, no significant associations were observed in Tokyo, which is situated further from the origin of Asian dust and experiences low mean concentrations of Asian dust. Adverse health effects on all-cause and cerebrovascular disease mortality were observed in South Korea and Japan. However, the effects of Asian dust differed across the cities and adverse effects were more apparent in cities closer to Asian dust sources.

The objective of this study was to examine whether white-matter (WM) connectivity of patients with schizophrenia at early stage of treatment is related to treatment response after paliperidone extended-release (ER) treatment. Forty-one patients with schizophrenia and 17 age- and sex-matched healthy control subjects were included in this study. Brain magnetic resonance scans at 3 Tesla were conducted at early stage of treatment. Voxel-wise statistical analysis of the fractional anisotropy (FA) data was performed using Tract-Based Spatial Statistics. At baseline and eight weeks after paliperidone treatment, patients were assessed using the Positive and Negative Syndrome Scale, the Scale for the Assessment of Positive Symptoms and the Scale for the Assessment of Negative Symptoms. Among the patients with schizophrenia, the FA values of the corpus callosum, corona radiata, internal capsule, external capsule, superior longitudinal fasciculus and fronto-temporal WM regions showed significant negative correlations with scores of the treatment response. The current study suggests that the treatment response after paliperidone ER treatment may be associated with the fronto-temporo-limbic WM connectivity at early stage of treatment in patients with schizophrenia, and it could be used as a predictor of treatment response to paliperidone ER treatment after studies with large samples verify these results.

Background The possible involvement of microRNAs (miRNA) in psychiatric disorders has been recently recognized. Several miRNA polymorphisms have been found to be associated with panic disorder (PD) in European populations. However, the association of miRNA polymorphisms on PD has not been reported in Asian populations. We evaluated the effect of miR-22 and miR-491 polymorphisms on susceptibility to PD in a Korean population. Methods Genotyping for four polymorphic variants of the primary miRNA (pri-miRNA) regions of miR-22 (rs8076112 and rs6502892) and miR-491 (rs4977831 and rs2039391) was performed using blood samples of 341 Korean patients with PD and 229 healthy control subjects. To evaluate PD phenotypes, the Panic Disorder Severity Scale (PDSS) and Anxiety Sensitivity Inventory-Revised (ASI-R) were administered. Results Three single-nucleotide polymorphisms (SNPs) were found to be associated with PD: rs8076112 miR-22 and rs4977831 and miR-491 rs2039391. The rs8076112C/rs6502892C haplotypes of miR-22 and rs4977831G/rs2039391G and rs4977831A/rs2039391A haplotypes of miR-491 were significantly overrepresented in patients with PD than in healthy control subjects. In combination analysis, miR-22 rs8076112AC/rs6502892CC and rs8076112CC/rs6502892CC and miR-491 rs4977831AG/rs2039391AA were more frequent in patients with PD. Among the phenotype assessments, ASI-R scores were significantly associated with miR-22 rs6502892 in the subgroup with the agoraphobic phenotype. Limitations The results should be considered preliminary due to the relatively small sample size and the selection of only four SNPs. Conclusions This is the first report to show possible associations of miR-22 and miR-491 with genetic susceptibility to PD in a Korean population.

Dysfunctional social-emotional perception in patients with schizophrenia can result in adverse clinical symptoms and poorer long-term outcomes. The white matter tracts that interact among a number of brain regions have an important role to play. However, few neuroimaging studies focus on the effects of white matter connectivity on social-emotional perception in schizophrenia and its impact on patients’ clinical symptoms and long-term outcomes. Forty-one patients with schizophrenia spectrum psychosis and 42 healthy controls underwent structural magnetic resonance imaging. The white matter fractional anisotropy values of the emotion recognition areas, the bilateral anterior thalamic radiation, inferior longitudinal fasciculus, cingulum bundle, superior longitudinal fasciculus, and uncinate fasciculus were compared between patients with schizophrenia spectrum psychosis and healthy controls. Social-emotional perception levels and symptom severity at baseline and after 1 year were examined. A group analysis showed that white matter connectivity was significantly lower in the bilateral anterior thalamic radiation, cingulum bundle, right inferior longitudinal fasciculus, and uncinate fasciculus of patients with schizophrenia spectrum psychosis compared to the healthy controls. Contrastingly, a correlation analysis revealed that larger right uncinate fasciculus fractional anisotropy values were associated with lower social-emotional perception levels in patients with schizophrenia spectrum psychosis. Additionally, the white matter fractional anisotropy values of the right uncinate fasciculus showed a significant positive correlation with the severity of positive symptoms at baseline and with poor outcomes after 1 year. The findings of the present study suggest that impaired social-emotional perception in patients with schizophrenia spectrum psychosis is associated with larger white matter connectivity of the uncinate fasciculus, which is also associated with more severe symptoms at baseline and after 1-year. These results suggest that the uncinate fasciculus could affect the pathophysiology of schizophrenia.

Introduction: It is controversial whether RF (radiofrequency) exposure during pregnancy is hazardous to fetus. The aim of the present study is to elucidate the association between maternal RF expos...