Cigarette excise tax structure and cigarette prices in nine sub-Saharan African countries: evidence from the Global Adult Tobacco Survey.

BACKGROUND: Economic theory predicts that the excise tax structure influences the distribution of cigarette prices. Evidence shows that uniform specific excise tax structures exhibit the least price variability relative to other tax structures. The distribution of cigarette prices under different excise tax structures has never been examined for a group of African countries. OBJECTIVES: To examine the distribution of cigarette prices under different tax structures in nine African countries and to critically evaluate the effectiveness of African regional tax directives in promoting public health. METHODS: Data from the Global Adult Tobacco Survey, conducted in eight African countries during 2012-2018, and data from the 2017 Gambia Tobacco Survey were used to construct survey-derived cigarette prices. The coefficients of variation and skewness of the price distribution were compared in the context of each country's cigarette excise tax structure. RESULTS: The least price variability is found in countries with a uniform specific tax, or a mixed system with a minimum specific floor. Cigarette price variability is largest in countries with uniform ad valorem tax structures. Three of the four countries with ad valorem tax structures are in regional blocs, where the tax directives specify that they should implement an ad valorem structure. CONCLUSIONS: Regional tax directives that require the adoption of uniform specific excise taxes, or high minimum specific floors, could be an efficient way to get multiple African countries to adopt a tax structure that reduces substitution possibilities in response to excise tax increases.

A training program for improving the capacity of infection high-throughput sequencing and diagnosis in China.

BACKGROUND: Infectious diseases are a serious threat to human especially since the COVID-19 outbreak has proved the importance and urgency of their diagnosis and treatment again. Metagenomic next-generation sequencing (mNGS) has been widely used and recognized in clinical and carried out localized testing in hospitals. Increasing the training of mNGS detection technicians can enhance their professional quality and more effectively realize the application value of the hospital platform. METHODS: Based on the initial theoretical understanding and practice of the mNGS platform for localization construction, we have designed a training program to enhance the ability of technicians to detect pathogens by utilizing mNGS, and hence to conduct training practices nationwide. RESULTS: Until August 30, 2022, the page views of online classes have reached 51,500 times and 6 of offline small-scale training courses have been conducted. A total of 67 trainees from 67 hospitals have participated in the training with a qualified rate of 100%. After the training course, the localization platform of 1 participating hospital has been put into use, 2 have added the mNGS localization platform for admission, among which 3 have expressed strong intention of localization. CONCLUSIONS: This study focuses on the training procedures and practical experience of the project which is the first systematic standardized program of mNGS in the world. It solves the training difficulties in the current industry, and effectively promotes the localization construction and application of mNGS in hospitals. It has great development potential in the future and is worth further promotion.

Heterogeneity in Obesity Prevalence Among Asian American Adults.

BACKGROUND: Obesity increases the risk for metabolic and cardiovascular disease, and this risk occurs at lower body mass index (BMI) thresholds in Asian adults than in White adults. The degree to which obesity prevalence varies across heterogeneous Asian American subgroups is unclear because most obesity estimates combine all Asian Americans into a single group. OBJECTIVE: To quantify obesity prevalence in Asian American subgroups among U.S. adults using both standard BMI categorizations and categorizations tailored to Asian populations. DESIGN: Cross-sectional. SETTING: United States, 2013 to 2020. PARTICIPANTS: The analytic sample included 2 882 158 adults aged 18 years or older in the U.S. Behavioral Risk Factor Surveillance System surveys (2013 to 2020). Participants self-identified as non-Hispanic White ([NHW] n = 2 547 965); non-Hispanic Black ([NHB] n = 263 136); or non-Hispanic Asian ([NHA] n = 71 057), comprising Asian Indian (n = 13 916), Chinese (n = 11 686), Filipino (n = 11 815), Japanese (n = 12 473), Korean (n = 3634), and Vietnamese (n = 2618) Americans. MEASUREMENTS: Obesity prevalence adjusted for age and sex calculated using both standard BMI thresholds (≥30 kg/m2) and BMI thresholds modified for Asian adults (≥27.5 kg/m2), based on self-reported height and weight. RESULTS: Adjusted obesity prevalence (by standard categorization) was 11.7% (95% CI, 11.2% to 12.2%) in NHA, 39.7% (CI, 39.4% to 40.1%) in NHB, and 29.4% (CI, 29.3% to 29.5%) in NHW participants; the prevalence was 16.8% (CI, 15.2% to 18.5%) in Filipino, 15.3% (CI, 13.2% to 17.5%) in Japanese, 11.2% (CI, 10.2% to 12.2%) in Asian Indian, 8.5% (CI, 6.8% to 10.5%) in Korean, 6.5% (CI, 5.5% to 7.5%) in Chinese, and 6.3% (CI, 5.1% to 7.8%) in Vietnamese Americans. The prevalence using modified criteria (BMI ≥27.5 kg/m2) was 22.4% (CI, 21.8% to 23.1%) in NHA participants overall and 28.7% (CI, 26.8% to 30.7%) in Filipino, 26.7% (CI, 24.1% to 29.5%) in Japanese, 22.4% (CI, 21.1% to 23.7%) in Asian Indian, 17.4% (CI, 15.2% to 19.8%) in Korean, 13.6% (CI, 11.7% to 15.9%) in Vietnamese, and 13.2% (CI, 12.0% to 14.5%) in Chinese Americans. LIMITATION: Body mass index estimates rely on self-reported data. CONCLUSION: Substantial heterogeneity in obesity prevalence exists among Asian American subgroups in the United States. Future studies and public health efforts should consider this heterogeneity. PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute.

Changes in Tobacco Product Use Among Students Aged 13 to 15 Years in 34 Countries, Global Youth Tobacco Survey, 2012-2020.

INTRODUCTION: Most adults who currently use tobacco start before age 21. Comprehensive, cost-effective strategies and interventions to prevent initiation and encourage tobacco use cessation among youth are critical aspects of protecting youth from the harms of commercial tobacco. We describe changes in current tobacco product use among youth in 34 sites using data from the Global Youth Tobacco Survey (GYTS). METHODS: GYTS is a nationally representative school-based survey of students aged 13 to 15 years. The analysis included 34 sites that completed 2 survey waves during 2012-2020. Prevalence of current tobacco use was assessed for each country. Marginal effects in multivariable logistic regression models were used to estimate adjusted prevalence difference (aPD) between waves. RESULTS: The adjusted prevalence of current tobacco product use remained unchanged in more than 60% of the included sites. For any tobacco use, significant decreases were reported for Bhutan (aPD = -8.1; 95% CI, -12.9 to -3.4), Micronesia (aPD = -7.2; 95% CI, -9.7 to -4.7), San Marino (aPD = -7.0; 95% CI, -11.2 to -2.7), Togo (aPD = -2.7; 95% CI, -4.6 to -0.7), and Panama (aPD = -2.2; 95% CI, -4.1 to -0.4); significant increases were reported for Moldova, Albania, and Paraguay. Current e-cigarette use increased significantly in 7 of 10 sites. CONCLUSION: Data show that progress toward reducing tobacco use among youth stalled during 2012-2020, while e-cigarette use increased in a few sites with available data.

Reducing the water residence time is inadequate to limit the algal proliferation in eutrophic lakes.

The eutrophication problem now threatens many lakes and reservoirs. To avoid the occurrence of algal blooms, some cities try to increase the flow rate or directly choose lakes or reservoirs with a short water residence time (WRT) as drinking water sources. However, up to now, whether such a strategy can achieve its goal is still unclear. In this study, a newly restored lake with a WRT of approximately 3 days was chosen to investigate algal growth potential as well as its responses to external nitrogen (N) and phosphorus (P) inputs. The results suggested that although the water quality of the lake could generally meet the environmental quality standards for surface water, dissolved inorganic nitrogen reached a high level with an average value of 1.58 mg/L. Meanwhile, a considerable increase in Chl-a concentration was observed across the flow direction. Especially, in July, Chl-a concentration at the site near the outlet was 8.1 times higher than that at the inlet, and cyanobacteria became the dominant species accounting for 83% of the total cell density. Nutrient enrichment experiments showed that algae could grow rapidly within 3 days with average specific growth rates (µ) of 0.36-0.42 d-1. The addition of N and P furtherly promoted the algal growth, and µ values of the treatments with P addition were the highest at 0.67-0.83 d-1. These results indicated that even if the WRT was reduced to 3 days, the risk of the occurrence of algal blooms still exists, and this undesirable trend would be enhanced by the short-term external nutrient input. Our findings indicated that the hydrodynamic control measures may not be entirely successful in protecting the drinking water source from algal blooms, especially when its influent has already been under eutrophication.

Obese elderly patients with hip fractures may have better survival outcomes after surgery.

BACKGROUND: In recent years, there has been an increasing amount of research on the "obesity paradox". So our primary objective was to explore whether this phenomenon exists in our study, and secondary objective was to determine the effect of body mass index (BMI) on major complications, and the incidence of acute kidney injury (AKI) after hip fracture surgery after controlling for confounding factors. METHODS: We included patients over 70 years old with hip fracture who were admitted to the Department of Orthopedics, Peking University First Hospital between 2015 and 2021. Patients were classified as underweight (UW, < 18.5 kg/m2), normal weight (NW, 18.5-24.9 kg/m2), overweight (OW, 25.0-29.9 kg/m2) and obese (OB, ≥ 30.0 kg/m2). We analyzed demographic characteristics, operation information and postoperative outcomes. Using multivariate regression with normal-weight patients as the reference, we determined the odds of 1-year mortality, major complications, and AKI by BMI category. RESULTS: A total of 644 patients were included. Nine percent of patients died after 1 year, 18% had major postoperative complications, and 12% had AKI. There was a U-shaped relationship between BMI and the rates of major complications or AKI. However, there was a linear decreasing relationship between 1-year mortality and BMI. After controlling for confounding factors, multivariate regression analysis showed that the risk of 1-year mortality after surgery was 2.24 times higher in underweight patients than in normal-weight patients (P < 0.05, OR: 2.24, 95% CI 1.14-4.42). Compared with normal-weight patients, underweight patients had a 2.07 times increased risk of major complications (P < 0.05, OR 2.07, 95% CI 1.21-3.55), and the risk of major complications in obese patients was 2.57 times higher than that in normal-weight patients (P < 0.05, OR 2.57, 95% CI 1.09-6.09). Compared with normal-weight, underweight patients had a 2.18 times increased risk of AKI (P < 0.05, OR 2.18, 95% CI 1.17-4.05). CONCLUSIONS: The 1-year mortality risk of patients with higher BMI was significantly reduced. Besides, compared with normal-weight patients, underweight patients and obese patients have a higher risk of major complications; low-weight and obese patients are at higher risk for AKI.

Activatable Self-Dissociation of Watson-Crick Structures with Fluorescent Nucleotides for Sensing Multiple Human Glycosylases at Single-Cell Level.

Nucleobase oxidation and alkylation can destroy Watson-Crick base-pairing to challenge the genomic integrity. Human 8-oxoguanine glycosylase 1 (hOGG1) and alkyladenine glycosylase (hAAG) are evolved to counter these two cytotoxic lesions through base-excision repair, and their deregulations are implicated with multifactorial diseases and cancers. Herein, we demonstrate activatable self-dissociation of Watson-Crick structures with fluorescent nucleotides for sensing multiple human glycosylases at single-cell level. The presence of hOGG1 and hAAG catalyzes 8-oxoG and deoxyinosine removal in functional probe 1 to release two trigger probes (1 and 2). Then, trigger probes hybridize with functional probe 2 to activate the autocatalytic degradation of functional probes 2 (Cycle I) and 3 (Cycle II), replicating abundant trigger probes (1-4) and releasing two fluorophores (2-aminopurine (2-AP) and pyrrolo-dC (P-dC)). New trigger probes (1, 2) and (3, 4), in turn, hybridize with free functional probes 2 and 3, repeating Cycles I and II turnovers. Through multicycle self-dissociation of Watson-Crick structures, 2-AP and P-dC are exponentially accumulated for the simultaneous quantification of hOGG1 and hAAG. This nanodevice exhibits high sensitivity with a detection limit of 2.9 × 10-3 U/mL for hOOG1 and 1.5 × 10-3 U/mL for hAAG, and it can measure enzymatic kinetics, identify potential inhibitors, discriminate glycosylases between cancer and normal cell lines, and even quantify glycosylase activities in a single HeLa cell. Moreover, this assay may be rapidly and isothermally performed in one tube with only one tool enzyme in a quencher-free manner, promising a simple and powerful platform for multiple human glycosylase detection.

Alternations in neural oscillation related to attention network reveal influence of indoor toluene on cognition at low concentration.

Despite accumulative literature reporting negative impacts of high-concentration toluene, cognitive effects of toluene at low concentration are still unclear. Twenty-two healthy college students were exposed in a closed environmental chamber to investigate the influence of indoor toluene on cognitive performance and brain activity. During each toluene exposure condition (0 ppb, 17.5 ppb, 35 ppb, and 70 ppb), attention network test and electroencephalogram (EEG) recording were synchronously performed after 4-hour toluene exposure. Characteristic neural oscillation patterns in three attention networks were compared between four groups. The statistical analyses indicated that short-term exposure to toluene had no significant impact on behavioral performance of attention network. However, there was a significant increase in the power of theta and alpha band of executive network and orienting network in the whole brain, especially in frontal region when exposed to toluene. Besides, no significant difference was observed in alerting network. The alternations in neural oscillation demonstrated that more effort was required to accomplish the same tasks when exposed to toluene. The present study revealed that short-term exposure to toluene affected brain activity of attention network even at low concentration, which provided a theoretical basis for the development of safer evaluation methods and standards in the future.

Effects of Bedaquiline on Antimicrobial Activity and Cytokine Secretion of Macrophages Infected with Multidrug-Resistant Mycobacterium tuberculosis Strains.

Background: Bedaquiline (Bdq) exerts bactericidal effects against drug-susceptible and drug-resistant Mycobacterium tuberculosis strains, including multidrug-resistant M. tuberculosis strains (MDR-MTBs). However, few reported investigations exist regarding Bdq effects on MDR-MTBs-infected macrophages activities and cytokine secretion. Here, Bdq bactericidal activities against MDR-MTBs and related cellular immune mechanisms were explored. Methods: Macrophages infected with MDR-MTBs or H37Rv received Bdq treatments (4 h/8 h/24 h/48 h) at 1 × the minimum inhibitory concentration (1 × MIC), 10 × MIC and 20 × MIC. Intracellular colony-forming units (CFUs) and culture supernatant IL-12/23 p40, TNF-α, IL-6, and IL-10 were determined using the Luminex® 200TM system. Normally distributed continuous data (mean ± standard deviation) were analyzed using t-test or F-test (SPSS 25.0, P < 0.05 deemed statistically significant). Results: (1) 100% of Bdq-treated macrophages (all doses applied over 4-48 h) survived with 0% inhibition of proliferation observed. (2) Intracellular CFUs of Bdq-treated MDR-MTBs-infected macrophages decreased over 4-48 h of treatment, were lower than preadministration and control CFUs, decreased with increasing Bdq dose, and resembled H37Rv-infected group CFUs (48 h). (3) For MDR-MTBs-infected macrophages (various Bdq doses), IL-12/23 p40 levels resembled preadministration group levels and exceeded controls (4 h); TNF-α levels exceeded preadministration group levels (24 h/48 h) and controls (24 h); IL-12/23 p40 and TNF-α levels resembled H37Rv-infected group levels (4 h/8 h/24 h/48 h); IL-6 levels exceeded preadministration and H37Rv-infected group levels (24 h/48 h) and controls (24 h); IL-10 levels resembled preadministration and H37Rv-infected group levels (4 h/8 h/24 h/48 h) and were lower than controls (24 h/48 h); IL-12/23 p40 and IL-10 levels remained unchanged as intracellular CFUs changed, with IL-12/23 p40 levels exceeding controls (4 h) and IL-10 levels remaining lower than controls (24 h/48 h); TNF-α and IL-6 levels increased as intracellular CFUs decreased (24 h/48 h) and exceed controls (24 h). Conclusion: Bdq was strongly bactericidal against intracellular MDR-MTBs and H37Rv in a time-dependent, concentration-dependent manner. Bdq potentially exerted immunomodulatory effects by inducing high-level Th1 cytokine expression (IL-12/23 p40, TNF-α) and low-level Th2 cytokine expression (IL-10).

C-reactive protein (CRP)/albumin-to-globulin ratio (AGR) is a valuable test for diagnosing periprosthetic joint infection: a single-center retrospective study.

BACKGROUND: The diagnosis of periprosthetic joint infection (PJI) is challenging for clinicians, and the commonly used methods are too complicated and expensive for many clinical practices. The neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), the platelet-to-mean-platelet-volume ratio (PVR), globulin (GLB), the albumin-to-globulin ratio (AGR), and the C-reactive protein (CRP)/AGR ratio are simple biomarkers for infection and can be easily determined from routine blood tests. Due to their low cost and ready availability in clinical practice, many clinicians have considered the diagnostic value of these biomarkers for PJI. The aim of our study is to determine the value of NLR, PLR, PVR, GLB, AGR, and CRP/AGR for the diagnosis of PJI. MATERIALS AND METHODS: One hundred sixty-four patients who received revision surgery after total knee or total hip replacements were enrolled, 47 in a PJI group and 117 in an aseptic failure group. Receiver operating characteristic (ROC) analysis was used to evaluate the performance of NLR, PLR, PVR, GLB, AGR, and CRP/AGR for the diagnosis of PJI, and their performance levels were then compared with those of CRP and the erythrocyte sedimentation rate (ESR). RESULTS: The levels of all tested biomarkers were significantly higher in patients with PJI (all P < 0.05). ROC analysis showed that CRP/AGR performed best in diagnosing PJI, with an area under curve (AUC) value of 0.902, and the AUCs of NLR (0.740), PLR (0.721), PVR (0.668), GLB (0.719), and AGR (0.767) were all lower than those for CRP (0.896) and ESR (0.829). CONCLUSION: CRP/AGR was a valuable test for diagnosing PJI, but other novel biomarkers had only limited diagnostic value. LEVEL OF EVIDENCE: Level III.

Hsp16.3 of mycobacterium tuberculosis in exosomes as a biomarker of tuberculosis.

Exosomes are selectively packaged cell-derived vesicles that contain a rich cargo of nucleic acids and proteins. The small heat shock protein, Hsp16.3, is an important capsule protein produced by Mycobacterium tuberculosis (MTB). Exploring the distribution of Hsp16.3 in exosomes is valuable to tuberculosis biomarker development. Our results showed that Hsp16.3 protein overexpressed in cells can be efficiently packaged into exosomes. U937 cells infected with MTB secreted abnormally excessive amounts of Hsp16.3 protein in exosomes. Finally, a substantial number of Hsp16.3 proteins were detected in blood exosomes of tuberculosis patients. The research provides a potential exosome-based tuberculosis biomarker for MTB diagnosis.

Use of T-SPOT.TB for the diagnosis of unconventional pleural tuberculosis is superior to ADA in high prevalence areas: a prospective analysis of 601 cases.

BACKGROUND: Tuberculous pleural effusion (TPE) is the most common extrapulmonary manifestation and may have lasting effect on lung function. However conventional diagnostic tests for TPE register multiple limitations. This study estimates diagnostic efficacy of the interferon gamma release assay (IGRA: T-SPOT.TB) in TPE patients of different characteristics. METHODS: We performed a prospective, single-centre study including all suspected pleural effusion patients consecutively enrolled from June 2015 to October 2018. Through receiver operating characteristic (ROC) curves, technical cut-offs and the utility of T-SPOT on pleural fluid (PF) were determined and analysed. Logistic regression analysis was performed to obtain the independent risk factors for TPE, and evaluated the performance of the T-SPOT assay stratified by risk factors in comparison to ADA. RESULTS: A total of 601 individuals were consecutively recruited. The maximum spot-forming cells (SFCs) of early secretory antigenic target-6 (ESAT-6) and culture filtrate protein-10 (CFP-10) in the PF T-SPOT assay had the best diagnostic efficiency in our study, which was equal to ADA (0.885 vs 0.887, P = 0.957) and superior to peripheral blood (PB), with a sensitivity of 83.0% and a specificity of 83.1% (The cut-off value was 466 SFCs/106 mononuclear cells). Among the TPE patients with low ADA (< 40 IU/L), the sensitivity and specificity of PF T-SPOT were still 87.9 and 90.5%, respectively. The utility of ADA was negatively related to increasing age, but the PF T-SPOT test had a steady performance at all ages. Age (< 45 yrs.; odds ratio (OR) = 5.61, 95% confidence interval (CI) 3.59-8.78; P < 0.001), gender (male; OR = 2.68, 95% CI 1.75-2.88; P < 0.001) and body mass index (BMI) (< 22; OR = 1.93, 95% CI 1.30-2.88; P = 0.001) were independently associated with the risk of TB by multivariate logistic regression analysis. Notably, when stratified by risk factor, the sensitivity of PF T-SPOT was superior to the sensitivity for ADA (76.5% vs. 23.5%, P = 0.016) and had noninferior specificity (84.4% vs. 96.9%, P = 0.370). CONCLUSIONS: In conclusion, the PF T-SPOT assay can effectively discriminate TPE patients whose ADA is lower than 40 IU/L and is superior to ADA in unconventional TPE patients (age ≥ 45 yrs., female or BMI ≥ 22). The PF T-SPOT assay is an excellent choice to supplement ADA to diagnose TPE.

Alterations in neural oscillations related to working memory deficit in temporal lobe epilepsy.

OBJECTIVE: Working memory (WM) is critical for higher level cognition, but the underlying neural mechanisms are not fully understood. Impaired WM affects routine daily activities and is observed in patients with temporal lobe epilepsy (TLE). This study investigated neural oscillations associated with different WM phases, to determine the specific neural activity linked with the phases of WM impairment. METHODS: Patients with TLE (n = 52) and healthy volunteers (n = 35) completed a WM task, during which 34-channel electroencephalogram signals were recorded. Characteristic neural oscillation patterns during each WM phase were compared between the 2 groups. RESULTS: Patients with TLE showed decreased theta power during the encoding phase of WM, which was associated with reduced accuracy in the WM task. Altered theta power in the frontal region of the brain during the encoding phase was associated with a longer reaction time. CONCLUSIONS: Alterations in theta oscillation are related to WM impairment in patients with TLE and may serve as an early marker for evaluating WM deficits. SIGNIFICANCE: This study provides an early marker for evaluating WM deficits in TLE.

Functional brain network mechanism of executive control dysfunction in temporal lobe epilepsy.

BACKGROUND: Executive control dysfunction is observed in a sizable number of patients with temporal lobe epilepsy (TLE). Neural oscillations in the theta band are increasingly recognized as having a crucial role in executive control network. The purpose of this study was to investigate the alterations in the theta band in executive control network and explore the functional brain network mechanisms of executive control dysfunction in TLE patients. METHODS: A total of 20 TLE patients and 20 matched healthy controls (HCs) were recruited in the present study. All participants were trained to perform the executive control task by attention network test while the scalp electroencephalogram (EEG) data were recorded. The resting state signals were collected from the EEG in the subjects with quiet and closed eyes conditions. Functional connectivity among EEGs in the executive control network and resting state network were respectively calculated. RESULTS: We found the significant executive control impairment in the TLE group. Compared to the HCs, the TLE group showed significantly weaker functional connectivity among EEGs in the executive control network. Moreover, in the TLE group, we found that the functional connectivity was significantly positively correlated with accuracy and negatively correlated with EC_effect. In addition, the functional connectivity of the executive control network was significantly higher than that of the resting state network in the HCs. In the TLE group, however, there was no significant change in functional connectivity strengths between the executive control network and resting state network. CONCLUSION: Our results indicate that the decreased functional connectivity in theta band may provide a potential mechanism for executive control deficits in TLE patients.

Evaluation of digital PCR assay in detection of M.tuberculosis IS6110 and IS1081 in tuberculosis patients plasma.

BACKGROUND: Tuberculosis is still a significant diagnostic and therapeutic challenge with high proportion of smear- and culture- negative incidences worldwide. The conventional diagnostic tests are time-consuming and have a low sensitivity. Digital PCR is a novel technology which can detect target sequences with relatively low abundance and obtain the absolute copy numbers of the targets. METHODS: We assessed the accuracy of dPCR in TB diagnosis using more than 250 specimens, and for the first time, we selected M.tuberculosis-specific IS1081 in addition to widely used IS6110 as the amplification targets for dPCR. The quantification of target DNA was calculated using QuantaSoft Version 1.7.4.0917 (BioRad), and SPSS version 13.0 software (SPSS Inc., Chicago, IL, USA) was used for statistical analyses. RESULTS: IS6110-dPCR was more sensitive than IS1081, with the sensitivity and specificity accounting for 40.6 and 93.4% respectively. When we classified the TB patients by personal factors for high copy number of M.tuberculosis derived DNA in plasma: bilateral TB, extrapulmonary TB and disseminated TB, the sensitivity of both IS6110- and IS1081- dPCR was the highest in patients with disseminated TB (IS6110, 100%; IS1081, 68.8%), while their sensitivity was a bit higher in patients with extrapulmonary TB (IS6110, 50.0%; IS1081, 39.3%) than that in bilateral TB (IS6110, 43.3%; IS1081, 33.3%). Compared with traditional TB diagnostic tests, joint detection IS6110 & IS1081-dPCR was not as sensitive as smear microscope or mycobacterial culture, but it was higher than IS6110 qPCR (p < 0.05) and was able to detect 47.4% of smear-negative TB patients. CONCLUSION: Our study suggested that plasma IS6110-dPCR is a rapid, moderate accurate and less-invasive method to detect M.tuberculosis DNA in plasma of TB patients and IS6110 & IS1081-dPCR has a potential to aid diagnosis of smear-negative TB.

The endoplasmic reticulum stress induced by tunicamycin affects the viability and autophagy activity of chondrocytes.

Osteoarthritis (OA) is attributed to a reduction in chondrocytes within joint cartilage, and research has shown that endoplasmic reticulum (ER) stress and autophagy play important roles in the survival of chondrocytes. However, the relationship between ER stress and autophagy in chondrocytes remains unclear. In this study, we investigated the changes in apoptotic and autophagic activity in chondrocytes under ER stress. Following treatment with tunicamycin, the rate of apoptosis among chondrocytes increased. Western blot analysis showed the levels of unfolded protein response (UPR) related proteins increased, followed by elevated expression of light chain 3B-II (LC3B-II) and Beclin-1. An ultrastructural investigation showed that a large number of pre-autophagosomal structures or autophagosomes formed under tunicamycin treatment. However, the autophagy activity was significantly inhibited in chondrocytes after suppression of GRP78 by siRNA. The apoptosis ratio of chondrocytes pre-treated with 3-methyladenine was much higher than that of normal chondrocytes after exposure to tunicamycin. Our study revealed that the tunicamycin-induced persistent UPR expression led to apoptosis of chondrocytes and activation of autophagy incorporation with GRP78. Blocking autophagy accelerated the apoptosis induced by ER stress, which confirmed the protective function of autophagy in the homeostasis of chondrocytes. These findings advance our understanding of chondrocyte apoptosis and provide potential molecular targets for preventing apoptotic death of chondrocytes.

Sugar-Sweetened Beverage Intake Among Adults, by Residence in Metropolitan and Nonmetropolitan Counties in 12 States and the District of Columbia, 2017.

The objective of this study was to describe the prevalence of sugar-sweetened beverage (SSB) intake among US adults (n = 68,896) residing in metropolitan and nonmetropolitan counties, by state, using data from the Behavioral Risk Factor Surveillance System. We used multinomial logistic regression to calculate adjusted prevalence ratios for daily (≥1 time per day) SSB intake. Overall, 26.0% of respondents reported daily SSB intake, with significantly higher prevalence in nonmetropolitan counties (30.9%) than in metropolitan counties (24.8%) (adjusted prevalence ratio = 1.32, 95% confidence interval, 1.26-1.39). This same pattern was significant in 5 of 11 states with metropolitan and nonmetropolitan counties. These findings could inform efforts to reduce frequent SSB intake in nonmetropolitan areas.

Plasma Fibrinogen Performs Better Than Plasma d-Dimer and Fibrin Degradation Product in the Diagnosis of Periprosthetic Joint Infection and Determination of Reimplantation Timing.

BACKGROUND: The accurate and timely diagnosis of periprosthetic joint infection (PJI) is challenging, and no single biomarker can definitively confirm infection before revision arthroplasty. The coagulation cascade has been linked closely to infection. This study was performed to determine the value of plasma d-dimer, plasma fibrinogen, and plasma fibrin degradation product (FDP) for the diagnosis of PJI and timing of reimplantation. METHODS: We retrospectively enrolled 136 patients who underwent revision surgery from January 2008 to December 2019. They were assigned to 3 groups: aseptic failure (group A), PJI (group B), and reimplantation (group C). Receiver operating characteristic curves were constructed to estimate the value of plasma fibrinogen, plasma d-dimer, plasma FDP, erythrocyte sedimentation rate (ESR), and serum C-reactive protein (CRP) for PJI diagnosis and reimplantation timing. RESULTS: All biomarker levels were significantly higher in group B than in group A (P < .05), and plasma fibrinogen, CRP, and ESR values were significantly higher in group B than in group C (all P < .05). The receiver operating characteristic curves showed that the areas under the curve of plasma fibrinogen, plasma d-dimer, plasma FDP, CRP, and ESR were 0.848, 0.914, 0.728, 0.737, and 0.868, respectively, and the threshold values for plasma fibrinogen, plasma d-dimer, and plasma FDP were 3.61 g/L, 0.41 mg/L, and 3.55 mg/L, respectively. CONCLUSION: Plasma fibrinogen exhibits good value for the diagnosis of PJI and can be an indicator of residual infection before reimplantation in 2-stage arthroplasty. Plasma d-dimer and FDP are of limited value for PJI diagnosis and cannot be used to determine the timing of reimplantation.

Characterization of Fasiglifam-Related Liver Toxicity in Dogs.

Fasiglifam, a potent and highly selective agonist of G protein-coupled receptor 40, was developed for the treatment of type 2 diabetes mellitus. However, phase III clinical programs were terminated owing to liver safety concerns. Fasiglifam-related liver toxicity was also observed in repeat-dose dog toxicology studies, characterized by granulomatous inflammation with crystal formation in the liver and/or bile ducts. These histopathological changes were not observed in rat toxicology studies. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis of dog liver sections obtained from a repeat-dose toxicology study indicated that the crystalline material in the affected dog liver contained fasiglifam and fasiglifam glucuronide (fasiglifam-G). Nonclinical mechanistic studies indicated that after 14 days of repeated oral dosing with [14C]fasiglifam at 200 mg/kg per day to dogs, the concentrations of fasiglifam and fasiglifam-G in the bile exceeded the solubility limit of these compounds in the bile (approximately 3000 µg/ml). After single oral 2- and 200-mg/kg doses administered to rats and dogs, fasiglifam and fasiglifam-G concentrations in dog bile were 5- to 10-fold higher than those in rat bile for the same dose of fasiglifam, while the bile flow rate adjusted by body weight was 4- to 8-fold lower in dogs than in rats. High fasiglifam and fasiglifam-G concentrations in dog bile together with lower bile flow rate could cause crystal formation in dog bile, resulting in secondary granulomatous inflammation in the dog liver.

State-Specific Prevalence of Obesity Among Children Aged 2-4 Years Enrolled in the Special Supplemental Nutrition Program for Women, Infants, and Children - United States, 2010-2016.

Obesity negatively affects children's health because of its associations with cardiovascular disease risk factors, type 2 diabetes, asthma, fatty liver disease, victimization stemming from social stigma and bullying, and poor mental health (e.g., anxiety and depression) (1). Children who have overweight or obesity in early childhood are approximately four times as likely to have overweight or obesity in young adulthood as their normal weight peers (2). Obesity prevalence is especially high among children from low-income families (3). In 2010, the overall upward trend in obesity prevalence turned downward among children aged 2-4 years enrolled in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC), a program of the U.S. Department of Agriculture (USDA); prevalence decreased significantly in all racial/ethnic groups and in 34 of the 56 WIC state or territory agencies during 2010-2014 (4). A more recent study among young children enrolled in WIC reported that the overall obesity prevalence decreased from 15.9% in 2010 to 13.9% in 2016 and statistically significant decreases were observed in all age, sex, and racial/ethnic subgroups (3). However, this study did not provide obesity trends at the state level. In collaboration with USDA, CDC used data from the WIC Participant and Program Characteristics (WIC PC) to update state-specific trends through 2016. During 2010-2016, modest but statistically significant decreases in obesity prevalence among children aged 2-4 years enrolled in WIC occurred in 41 (73%) of 56 WIC state or territory agencies. Comprehensive approaches that create positive changes to promote healthy eating and physical activity for young children from all income levels,* strengthen nutrition education and breastfeeding support among young children enrolled in WIC, and encourage redemptions of healthy foods in WIC food packages could help maintain or accelerate these declining trends.