Genetic interaction between two VNTRs in the MAOA gene is associated with the nicotine dependence

Nicotine dependence is an addiction to tobacco products and a global public health concern that in part would be influenced by our genetics. Smokers are reported to have reduced MAOA activity, but the results from genetic associations with this gene have been inconclusive. Two functionally relevant variable number tandem repeat (VNTR) domains, termed uVNTR and dVNTR, in the MAOA gene are well characterized transcriptional regulatory elements. In the present study, we analyzed uVNTR and dVNTR polymorphisms in the MAOA gene in the Vietnamese male population of smokers and non-smokers in order to assess the association of MAOA with the nicotine dependence measured by the Fagerström Test for Nicotine Dependence (FTND). Individual analysis of VNTRs separately identified uVNTR to be associated with the F6 question of the FTND indicating the stronger addiction to nicotine. No associations were found between the dVNTR and smoking behavior. The combination of dVNTR and uVNTR, that predicts low expression of MAOA (10–3 haplotypes), was significantly associated with the higher nicotine dependence (FTND score), longer smoking duration, and more persistent smoking behavior (fewer quit attempts). In conclusion, our study confirms that low MAOA expression is genetically predictive to the higher nicotine dependence

Inter-rater agreement in the assessment of abnormal chest X-ray findings for tuberculosis between two Asian countries

<p>Abstract</p> <p>Background</p> <p>Inter-rater agreement in the interpretation of chest X-ray (CXR) films is crucial for clinical and epidemiological studies of tuberculosis. We compared the readings of CXR films used for a survey of tuberculosis between raters from two Asian countries.</p> <p>Methods</p> <p>Of the 11,624 people enrolled in a prevalence survey in Hanoi, Viet Nam, in 2003, we studied 258 individuals whose CXR films did not exclude the possibility of active tuberculosis. Follow-up films obtained from accessible individuals in 2006 were also analyzed. Two Japanese and two Vietnamese raters read the CXR films based on a coding system proposed by Den Boon et al. and another system newly developed in this study. Inter-rater agreement was evaluated by kappa statistics. Marginal homogeneity was evaluated by the generalized estimating equation (GEE).</p> <p>Results</p> <p>CXR findings suspected of tuberculosis differed between the four raters. The frequencies of infiltrates and fibrosis/scarring detected on the films significantly differed between the raters from the two countries (<it>P </it>< 0.0001 and <it>P </it>= 0.0082, respectively, by GEE). The definition of findings such as primary cavity, used in the coding systems also affected the degree of agreement.</p> <p>Conclusions</p> <p>CXR findings were inconsistent between the raters with different backgrounds. High inter-rater agreement is a component necessary for an optimal CXR coding system, particularly in international studies. An analysis of reading results and a thorough discussion to achieve a consensus would be necessary to achieve further consistency and high quality of reading.</p

Expansion and Characterization of Human Melanoma Tumor-Infiltrating Lymphocytes (TILs)

Various immunotherapeutic strategies for cancer are aimed at augmenting the T cell response against tumor cells. Adoptive cell therapy (ACT), where T cells are manipulated ex vivo and subsequently re-infused in an autologous manner, has been performed using T cells from various sources. Some of the highest clinical response rates for metastatic melanoma have been reported in trials using tumor-infiltrating lymphocytes (TILs). These protocols still have room for improvement and furthermore are currently only performed at a limited number of institutions. The goal of this work was to develop TILs as a therapeutic product at our institution.TILs from 40 melanoma tissue specimens were expanded and characterized. Under optimized culture conditions, 72% of specimens yielded rapidly proliferating TILs as defined as at least one culture reaching ≥3×10(7) TILs within 4 weeks. Flow cytometric analyses showed that cultures were predominantly CD3+ T cells, with highly variable CD4+:CD8+ T cell ratios. In total, 148 independent bulk TIL cultures were assayed for tumor reactivity. Thirty-four percent (50/148) exhibited tumor reactivity based on IFN-γ production and/or cytotoxic activity. Thirteen percent (19/148) showed specific cytotoxic activity but not IFN-γ production and only 1% (2/148) showed specific IFN-γ production but not cytotoxic activity. Further expansion of TILs using a 14-day "rapid expansion protocol" (REP) is required to induce a 500- to 2000-fold expansion of TILs in order to generate sufficient numbers of cells for current ACT protocols. Thirty-eight consecutive test REPs were performed with an average 1865-fold expansion (+/- 1034-fold) after 14 days.TILs generally expanded efficiently and tumor reactivity could be detected in vitro. These preclinical data from melanoma TILs lay the groundwork for clinical trials of ACT

Decentralized care for multidrug-resistant tuberculosis: A systematic review and meta-analysis

© 2017, World Health Organization. All rights reserved. Objective To assess the effectiveness of decentralized treatment and care for patients with multidrug-resistant (MDR) tuberculosis, in comparison with centralized approaches. Methods We searched ClinicalTrials.gov, the Cochrane library, Embase®, Google Scholar, LILACS, PubMed®, Web of Science and the World Health Organization’s portal of clinical trials for studies reporting treatment outcomes for decentralized and centralized care of MDR tuberculosis. The primary outcome was treatment success. When possible, we also evaluated, death, loss to follow-up, treatment adherence and health-system costs. To obtain pooled relative risk (RR) estimates, we performed random-effects meta-analyses. Findings Eight studies met the eligibility criteria for review inclusion. Six cohort studies, with 4026 participants in total, reported on treatment outcomes. The pooled RR estimate for decentralized versus centralized care for treatment success was 1.13 (95% CI: 1.01–1.27). The corresponding estimate for loss to follow-up was RR: 0.66 (95% CI: 0.38–1.13), for death RR: 1.01 (95% CI: 0.67–1.52) and for treatment failure was RR: 1.07 (95% CI: 0.48–2.40). Two of three studies evaluating health-care costs reported lower costs for the decentralized models of care than for the centralized models. Conclusion Treatment success was more likely among patients with MDR tuberculosis treated using a decentralized approach. Further studies are required to explore the effectiveness of decentralized MDR tuberculosis care in a range of different settings

Adaptation to Land Degradation in Southeast Vietnam

A framework was developed to elucidate (1) the drivers of land degradation, (2) pressures, (3) local impacts and vulnerabilities and (4) adaptation strategies. The combination of participatory approaches, statistical data analysis, time series Landsat imagery and spatial data mining was tested in southeast Vietnam where the impacts of land degradation on the environment and economy are considerable. The major drivers of land degradation are climate, notably drought, and population density. The pressures include natural resource management and land use/cover change. A Landsat archive analysis showed an increase in agricultural land use from 31% to 50%, mostly at the expense of forests, from 1990 to 2019. Farmers adapted by investing in the irrigation of rice and dragon fruit, and by selecting their rainfed crops in line with the changing environment. The most vulnerable were the rural poor and farmers without access to land and water resources. The best protection against land degradation was prosperity, which is enhanced by the region’s location along Vietnam’s major national route, connecting major cities along a north–south axis. Our analysis shows that southeast Vietnam emerged as a region with an important human ecological resilience strengthened by increased prosperity. The current adaptation options and limitations warrant further research.status: publishe

Minimally Invasive Treatment of Chyle Leak After Thyroidectomy and Cervical Lymph Node Dissection in Patients with Thyroid Carcinoma: Results of a Study Involving 36 Patients

Nguyen Ngoc Cuong,1,&ast; Le Hoan,2,&ast; Thieu Thi Tra My,3 Doan Tien Luu,1 Le Tuan Linh,1 Pham Hong Canh,1 Trieu Quoc Tinh,1 Tran Nguyen Khanh Chi,1 Nguyen Quang Trung,1 Tran Quoc Hoa4 1Diagnostic Imaging and Interventional Center, Hanoi Medical University Hospital, Ha Noi, Viet Nam; 2Respiratory Department, Hanoi Medical University Hospital, Ha Noi, Viet Nam; 3Diagnostic Imaging and Nuclear Medicine Department, Vinmec Times City International Hospital, Ha Noi, Viet Nam; 4Urology Surgery department, Hanoi Medical university, Ha Noi, Viet Nam&ast;These authors contributed equally to this workCorrespondence: Nguyen Ngoc Cuong, Diagnostic Imaging and Interventional Center, Hanoi Medical University Hospital, No. 1, Ton That Tung, Dong Da, Ha Noi, Viet Nam, Email [email protected]: Chyle leak (CL) after head and neck surgery is a rare but well-known complication. In patients with high-output leakage, the treatment can be complicated. This study aims to report on a recent innovation in lymphatic intervention for treating such patients.Materials and Methods: A retrospective review of 36 patients with chyle leak after neck surgery for thyroid cancer was conducted to assess the efficacy of percutaneous lymphatic embolization and thoracic duct (TD) disruption.Results: Antegrade catheterization of the thoracic duct was achieved in 31 of 36 patients (86.1%). Therefore, embolization of the thoracic duct and thoracic duct branches was performed in 26 and 5 patients, respectively. In 5 cases of unsuccessful antegrade catheterization into the thoracic duct, transcervical access embolization was performed in 2 patients, and TD disruption (TDD) was performed in 3 patients. The pooled overall technical success rate of lymphatic embolization was 33/36 patients (91.7%). One patient who underwent thoracic duct embolization (TDE) with technical success (1/33 patients) but clinical failure had additional treatment directly sclerosing the TD under computed tomography scan. Cervical fluid collection sclerotherapy was done in 7 patients as an additional treatment. Resolution of the chyle leak after procedures was observed in all patients (100%). The mean time to resolution was 3 days (1– 7 days). There was no complication intra and after procedures.Conclusion: TDE, selective TD branches embolization and TDD are safe and effective minimally invasive treatments for CL post-surgery for thyroid carcinoma. Sclerosing cervical fluid collection contributes to clinical success.Keywords: thyroid cancer, thyroidectomy, chyle leak, thoracic duct embolization, thoracic duct disruption, sclerotherap

Immune response to intravenous immunoglobulin in patients with Kawasaki disease and MIS-C

BACKGROUNDMultisystem inflammatory syndrome in children (MIS-C) is a rare but potentially severe illness that follows exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Kawasaki disease (KD) shares several clinical features with MIS-C, which prompted the use of intravenous immunoglobulin (IVIG), a mainstay therapy for KD. Both diseases share a robust activation of the innate immune system, including the IL-1 signaling pathway, and IL-1 blockade has been used for the treatment of both MIS-C and KD. The mechanism of action of IVIG in these 2 diseases and the cellular source of IL-1β have not been defined.METHODSThe effects of IVIG on peripheral blood leukocyte populations from patients with MIS-C and KD were examined using flow cytometry and mass cytometry (CyTOF) and live-cell imaging.RESULTSCirculating neutrophils were highly activated in patients with KD and MIS-C and were a major source of IL-1β. Following IVIG treatment, activated IL-1β+ neutrophils were reduced in the circulation. In vitro, IVIG was a potent activator of neutrophil cell death via PI3K and NADPH oxidase, but independently of caspase activation.CONCLUSIONSActivated neutrophils expressing IL-1β can be targeted by IVIG, supporting its use in both KD and MIS-C to ameliorate inflammation.FUNDINGPatient Centered Outcomes Research Institute; NIH; American Asthma Foundation; American Heart Association; Novo Nordisk Foundation; NIGMS; American Academy of Allergy, Asthma and Immunology Foundation