665 research outputs found
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Tobacco smoke, indoor air pollution and tuberculosis: a systematic review and meta-analysis
Background: Tobacco smoking, passive smoking, and indoor air pollution from biomass fuels have been implicated as risk factors for tuberculosis (TB) infection, disease, and death. Tobacco smoking and indoor air pollution are persistent or growing exposures in regions where TB poses a major health risk. We undertook a systematic review and meta-analysis to quantitatively assess the association between these exposures and the risk of infection, disease, and death from TB. Methods and Findings: We conducted a systematic review and meta-analysis of observational studies reporting effect estimates and 95% confidence intervals on how tobacco smoking, passive smoke exposure, and indoor air pollution are associated with TB. We identified 33 papers on tobacco smoking and TB, five papers on passive smoking and TB, and five on indoor air pollution and TB. We found substantial evidence that tobacco smoking is positively associated with TB, regardless of the specific TB outcomes. Compared with people who do not smoke, smokers have an increased risk of having a positive tuberculin skin test, of having active TB, and of dying from TB. Although we also found evidence that passive smoking and indoor air pollution increased the risk of TB disease, these associations are less strongly supported by the available evidence. Conclusions: There is consistent evidence that tobacco smoking is associated with an increased risk of TB. The finding that passive smoking and biomass fuel combustion also increase TB risk should be substantiated with larger studies in future. TB control programs might benefit from a focus on interventions aimed at reducing tobacco and indoor air pollution exposures, especially among those at high risk for exposure to TB
High expression FUT1 and B3GALT5 is an independent predictor of postoperative recurrence and survival in hepatocellular carcinoma.
Cancer may arise from dedifferentiation of mature cells or maturation-arrested stem cells. Previously we reported that definitive endoderm from which liver was derived, expressed Globo H, SSEA-3 and SSEA-4. In this study, we examined the expression of their biosynthetic enzymes, FUT1, FUT2, B3GALT5 and ST3GAL2, in 135 hepatocellular carcinoma (HCC) tissues by qRT-PCR. High expression of either FUT1 or B3GALT5 was significantly associated with advanced stages and poor outcome. Kaplan Meier survival analysis showed significantly shorter relapse-free survival (RFS) for those with high expression of either FUT1 or B3GALT5 (P = 0.024 and 0.001, respectively) and shorter overall survival (OS) for those with high expression of B3GALT5 (P = 0.017). Combination of FUT1 and B3GALT5 revealed that high expression of both genes had poorer RFS and OS than the others (P < 0.001). Moreover, multivariable Cox regression analysis identified the combination of B3GALT5 and FUT1 as an independent predictor for RFS (HR: 2.370, 95% CI: 1.505-3.731, P < 0.001) and OS (HR: 2.153, 95% CI: 1.188-3.902, P = 0.012) in HCC. In addition, the presence of Globo H, SSEA-3 and SSEA-4 in some HCC tissues and their absence in normal liver was established by immunohistochemistry staining and mass spectrometric analysis
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Population Health Impact and Cost-Effectiveness of Tuberculosis Diagnosis with Xpert MTB/RIF: A Dynamic Simulation and Economic Evaluation
Background: The Xpert MTB/RIF test enables rapid detection of tuberculosis (TB) and rifampicin resistance. The World Health Organization recommends Xpert for initial diagnosis in individuals suspected of having multidrug-resistant TB (MDR-TB) or HIV-associated TB, and many countries are moving quickly toward adopting Xpert. As roll-out proceeds, it is essential to understand the potential health impact and cost-effectiveness of diagnostic strategies based on Xpert. Methods and findings: We evaluated potential health and economic consequences of implementing Xpert in five southern African countries—Botswana, Lesotho, Namibia, South Africa, and Swaziland—where drug resistance and TB-HIV coinfection are prevalent. Using a calibrated, dynamic mathematical model, we compared the status quo diagnostic algorithm, emphasizing sputum smear, against an algorithm incorporating Xpert for initial diagnosis. Results were projected over 10- and 20-y time periods starting from 2012. Compared to status quo, implementation of Xpert would avert 132,000 (95% CI: 55,000–284,000) TB cases and 182,000 (97,000–302,000) TB deaths in southern Africa over the 10 y following introduction, and would reduce prevalence by 28% (14%–40%) by 2022, with more modest reductions in incidence. Health system costs are projected to increase substantially with Xpert, by US959 (633–1,485) per disability-adjusted life-year averted over 10 y. Across countries, cost-effectiveness ratios ranged from US1,257 (767–2,276) in Botswana. Assessing outcomes over a 10-y period focuses on the near-term consequences of Xpert adoption, but the cost-effectiveness results are conservative, with cost-effectiveness ratios assessed over a 20-y time horizon approximately 20% lower than the 10-y values. Conclusions: Introduction of Xpert could substantially change TB morbidity and mortality through improved case-finding and treatment, with more limited impact on long-term transmission dynamics. Despite extant uncertainty about TB natural history and intervention impact in southern Africa, adoption of Xpert evidently offers reasonable value for its cost, based on conventional benchmarks for cost-effectiveness. However, the additional financial burden would be substantial, including significant increases in costs for treating HIV and MDR-TB. Given the fundamental influence of HIV on TB dynamics and intervention costs, care should be taken when interpreting the results of this analysis outside of settings with high HIV prevalence. Please see later in the article for the Editors' Summar
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Exposure to Secondhand Smoke and Risk of Tuberculosis: Prospective Cohort Study
Background: Prospective evidence on the association between secondhand-smoke exposure and tuberculosis is limited. Methods: We included 23,827 never smokers from two rounds (2001 and 2005) of Taiwan National Health Interview Survey. Information on exposure to secondhand smoke at home as well as other sociodemographic and behavioral factors was collected through in-person interview. The participants were prospectively followed for incidence of tuberculosis through cross-matching the survey database to the national tuberculosis registry of Taiwan. Results: A total of 85 cases of active tuberculosis were identified after a median follow-up of 7.0 years. The prevalence of exposure to secondhand smoke at home was 41.8% in the study population. In the multivariable Cox proportional hazards analysis, secondhand smoke was not associated with active tuberculosis (adjusted hazard ratio [HR], 1.03; 95% CI, 0.64 to 1.64). In the subgroup analysis, the association between secondhand smoke and tuberculosis decreased with increasing age; the adjusted HR for those = 18 and = 40 and = 60 years old was 8.48 (0.77 to 93.56), 2.29 (0.75 to 7.01), 1.33 (0.58 to 3.01), and 0.66 (0.35 to 1.23) respectively. Results from extensive sensitivity analyses suggested that potential misclassification of secondhand-smoke exposure would not substantially affect the observed associations. Conclusions: The results from this prospective cohort study did not support an overall association between secondhand smoke and tuberculosis. However, the finding that adolescents might be particularly susceptible to secondhand smoke's effect warrants further investigation
Assessment of the patient, health system, and population eff ects of Xpert MTB/RIF and alternative diagnostics for tuberculosis in Tanzania: an integrated modelling approach
Background Several promising new diagnostic methods and algorithms for tuberculosis have been endorsed by
WHO. National tuberculosis programmes now face the decision on which methods to implement and where to place
them in the diagnostic algorithm.
Methods We used an integrated model to assess the eff ects of diff erent algorithms of Xpert MTB/RIF and lightemitting
diode (LED) fl uorescence microscopy in Tanzania. To understand the eff ects of new diagnostics from the
patient, health system, and population perspective, the model incorporated and linked a detailed operational
component and a transmission component. The model was designed to represent the operational and epidemiological
context of Tanzania and was used to compare the eff ects and cost-eff ectiveness of diff erent diagnostic options.
Findings Among the diagnostic options considered, we identifi ed three strategies as cost eff ective in Tanzania. Full
scale-up of Xpert would have the greatest population-level eff ect with the highest incremental cost: 346 000
disability-adjusted life-years (DALYs) averted with an additional cost of US169 per DALY averted, 95% credible interval [CrI]
104–265) is below the willingness-to-pay threshold (45 (95% CrI 25–74), followed by LED fl uorescence microscopy
with an ICER of $29 (6–59). Compared with same-day LED fl uorescence microscopy and Xpert full rollout, targeted
use of Xpert in presumptive tuberculosis cases with HIV infection, either as an initial diagnostic test or as a followon
test to microscopy, would produce DALY gains at a higher incremental cost and therefore is dominated in the
context of Tanzania.
Interpretation For Tanzania, this integrated modelling approach predicts that full rollout of Xpert is a cost-eff ective
option for tuberculosis diagnosis and has the potential to substantially reduce the national tuberculosis burden. It also
estimates the substantial level of funding that will need to be mobilised to translate this into clinical practice. This
approach could be adapted and replicated in other developing countries to inform rational health policy formulation
Molecular Imaging, Pharmacokinetics, and Dosimetry of 111In-AMBA in Human Prostate Tumor-Bearing Mice
Molecular imaging with promise of personalized medicine can provide patient-specific information noninvasively, thus enabling treatment to be tailored to the specific biological attributes of both the disease and the patient. This study was to investigate the characterization of DO3A-CH2CO-G-4-aminobenzoyl-Q-W-A-V-G-H-L-M-NH2 (AMBA) in vitro, MicroSPECT/CT imaging, and biological activities of 111In-AMBA in PC-3 prostate tumor-bearing SCID mice. The uptake of 111In-AMBA reached highest with 3.87 ± 0.65% ID/g at 8 h. MicroSPECT/CT imaging studies suggested that the uptake of 111In-AMBA was clearly visualized between 8 and 48 h postinjection. The distribution half-life (t1/2α) and the elimination half-life (t1/2β) of 111In-AMBA in mice were 1.53 h and 30.7 h, respectively. The Cmax and AUC of 111In-AMBA were 7.57% ID/g and 66.39 h∗% ID/g, respectively. The effective dose appeared to be 0.11 mSv/MBq−1. We demonstrated a good uptake of 111In-AMBA in the GRPR-overexpressed PC-3 tumor-bearing SCID mice. 111In-AMBA is a safe, potential molecular image-guided diagnostic agent for human GRPR-positive tumors, ranging from simple and straightforward biodistribution studies to improve the efficacy of combined modality anticancer therapy
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On-Call Duty Effects on Sleep-State Physiological Stability in Male Medical Interns
Background: On-call duty among medical interns is characterized by sleep deprivation and stressful working conditions, both of which alter cardiac autonomic modulation. We hypothesized that sleep stability decreased in medical interns during on-call duty. We used cardiopulmonary-coupling (CPC) analysis to test our hypothesis. Methods: We used electrocardiogram (ECG)-based CPC analysis to quantify physiological parameters of sleep stability in 13 medical interns during on-call and on-call duty-free periods. There were ten 33.5-h on-call duty shifts per month for interns, each followed by 2 on-call duty-free days, over 3 months. Measurements during sleep were collected before, during, and after an on-call shift. Measurements were repeated 3 months later during an on-call duty-free period. Results: The medical interns had significantly reduced stable sleep, and displayed increased latency to the first epoch of stable sleep during the on-call night shift, compared to the pre-call and on-call duty-free nights. Interns also had significantly increased rapid-eye-movement (REM) sleep during the on-call night shift, compared to the pre-call and on-call duty-free nights. Conclusion: Medical interns suffer disrupted sleep stability and continuity during on-call night shifts. The ECG-based CPC analysis provides a straightforward means to quantify sleep quality and stability in medical staff performing shift work under stressful conditions
Myocardium-derived conditioned medium improves left ventricular function in rodent acute myocardial infarction
<p>Abstract</p> <p>Background</p> <p>We investigated whether myocardium-derived conditioned medium (MDCM) is effective in preserving left ventricular (LV) function in a rat acute myocardial infarction (AMI) model.</p> <p>Methods</p> <p>Adult male Sprague-Dawley (SD) rats (n = 36) randomized to receive either left coronary artery ligation (AMI induction) or thoracotomy only (sham procedure) were grouped as follows (n = 6 per group): Group I, II, and III were sham-controls treated by fresh medium, normal rat MDCM, and infarct-related MDCM, respectively. Group IV, V, and VI were AMI rats treated by fresh medium, normal MDCM, and infarct-related MDCM, respectively. Either 75 μL MDCM or fresh medium was administered into infarct myocardium, followed by intravenous injection (3 mL) at postoperative 1, 12, and 24 h.</p> <p>Results</p> <p>In vitro studies showed higher phosphorylated MMP-2 and MMP-9, but lower α-smooth muscle actin and collagen expressions in neonatal cardiac fibroblasts treated with MDCM compared with those in the cardiac fibroblasts treated with fresh medium (all p < 0.05). Sirius-red staining showed larger collagen deposition area in LV myocardium in Group IV than in other groups (all p < 0.05). Stromal cell-derived factor-1α and CXCR4 protein expressions were higher in Group VI than in other groups (all p < 0.05). The number of von Willebrand factor- and BrdU-positive cells and small vessels in LV myocardium as well as 90-day LV ejection fraction were higher, whereas oxidative stress was lower in Group VI than in Group IV and Group V (all p < 0.05).</p> <p>Conclusion</p> <p>MDCM therapy reduced cardiac fibrosis and oxidative stress, enhanced angiogenesis, and preserved 90-day LV function in a rat AMI model.</p
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