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Sample records for active tb disease

  1. Difference Between Latent TB Infection and Active TB Disease

    MedlinePlus

    ... ray, or positive sputum smear or culture • • Has active TB bacteria in his/her body • • Usually feels sick and may have symptoms such as coughing, fever, and weight loss • • May spread TB bacteria to others • • Needs treatment to treat ...

  2. Treatment: Latent TB Infection (LTBI) and TB Disease

    MedlinePlus

    ... Search The CDC Cancel Submit Search The CDC Tuberculosis (TB) Note: Javascript is disabled or is not ... message, please visit this page: About CDC.gov . Tuberculosis Basic TB Facts How TB Spreads Latent TB ...

  3. Combination of Cytokine Responses Indicative of Latent TB and Active TB in Malawian Adults

    PubMed Central

    Hur, Yun-Gyoung; Gorak-Stolinska, Patricia; Ben-Smith, Anne; Lalor, Maeve K.; Chaguluka, Steven; Dacombe, Russell; Doherty, T. Mark; Ottenhoff, Tom H.; Dockrell, Hazel M.; Crampin, Amelia C.

    2013-01-01

    Background An IFN-γ response to M. tuberculosis-specific antigens is an effective biomarker for M. tuberculosis infection but it cannot discriminate between latent TB infection and active TB disease. Combining a number of cytokine/chemokine responses to M. tuberculosis antigens may enable differentiation of latent TB from active disease. Methods Asymptomatic recently-exposed individuals (spouses of TB patients) were recruited and tuberculin skin tested, bled and followed-up for two years. Culture supernatants, from a six-day culture of diluted whole blood samples stimulated with M. tuberculosis-derived PPD or ESAT-6, were measured for IFN-γ, IL-10, IL-13, IL-17, TNF-α and CXCL10 using cytokine ELISAs. In addition, 15 patients with sputum smear-positive pulmonary TB were recruited and tested. Results Spouses with positive IFN-γ responses to M. tuberculosis ESAT-6 (>62.5 pg/mL) and TB patients showed high production of IL-17, CXCL10 and TNF-α. Higher production of IL-10 and IL-17 in response to ESAT-6 was observed in the spouses compared with TB patients while the ratios of IFN-γ/IL-10 and IFN-γ/IL-17 in response to M. tuberculosis-derived PPD were significantly higher in TB patients compared with the spouses. Tuberculin skin test results did not correlate with cytokine responses. Conclusions CXCL10 and TNF-α may be used as adjunct markers alongside an IFN-γ release assay to diagnose M. tuberculosis infection, and IL-17 and IL-10 production may differentiate individuals with LTBI from active TB. PMID:24260295

  4. Tuberculosis: Learn the Signs and Symptoms of TB Disease

    MedlinePlus

    ... What's this? Submit Button Past Emails CDC Features Tuberculosis (TB) Disease: Symptoms & Risk Factors Language: English Español (Spanish) Recommend on Facebook Tweet Share Compartir Tuberculosis (TB) is a disease caused by bacteria that ...

  5. Optimal Control for TB disease with vaccination assuming endogeneous reactivation and exogeneous reinfection

    NASA Astrophysics Data System (ADS)

    Anggriani, N.; Wicaksono, B. C.; Supriatna, A. K.

    2016-06-01

    Tuberculosis (TB) is one of the deadliest infectious disease in the world which caused by Mycobacterium tuberculosis. The disease is spread through the air via the droplets from the infectious persons when they are coughing. The World Health Organization (WHO) has paid a special attention to the TB by providing some solution, for example by providing BCG vaccine that prevent an infected person from becoming an active infectious TB. In this paper we develop a mathematical model of the spread of the TB which assumes endogeneous reactivation and exogeneous reinfection factors. We also assume that some of the susceptible population are vaccinated. Furthermore we investigate the optimal vaccination level for the disease.

  6. Evaluation of the Rapid Scale-up of Collaborative TB/HIV Activities in TB Facilities in Rwanda, 2005-2009

    PubMed Central

    2011-01-01

    Background In 2005, Rwanda drafted a national TB/HIV policy and began scaling-up collaborative TB/HIV activities. Prior to the scale-up, we evaluated existing TB/HIV practices, possible barriers to policy and programmatic implementation, and patient treatment outcomes. We then used our evaluation data as a baseline for evaluating the national scale-up of collaborative TB/HIV activities from 2005 through 2009. Methods Our baseline evaluation included a cross-sectional evaluation of 23/161 TB clinics. We conducted structured interviews with patients and clinic staff and reviewed TB registers and patient records to assess HIV testing practices, provision of HIV care and treatment for people with TB that tested positive for HIV, and patients' TB treatment outcomes. Following our baseline evaluation, we used nationally representative TB/HIV surveillance data to monitor the scale-up of collaborative TB/HIV activities Results Of 207 patients interviewed, 76% were offered HIV testing, 99% accepted, and 49% reported positive test results. Of 40 staff interviewed, 68% reported offering HIV testing to >50% of patients. From 2005-2009, scaled-up TB/HIV activities resulted in increased HIV testing of patients with TB (69% to 97%) and provision of cotrimoxazole (15% to 92%) and antiretroviral therapy (13% to 49%) for patients with TB disease and HIV infection (TB/HIV). The risk of death among patients with TB/HIV relative to patients with TB not infected with HIV declined from 2005 (RR = 6.1, 95%CI 2.6, 14.0) to 2007 (RR = 1.8, 95%CI 1.68, 1.94). Conclusions Our baseline evaluation highlighted that staff and patients were receptive to HIV testing. However, expanded access to testing, care, and treatment was needed based on the proportion of patients with TB having unknown HIV status and the high rate of HIV infection and poorer TB treatment outcomes for patients with TB/HIV. Following our evaluation, scale-up of TB/HIV services resulted in almost all patients with TB knowing

  7. Too Busy for TB: Managing a Case of Tuberculosis Disease in the School Setting.

    PubMed

    Galemore, Cynthia A

    2016-03-01

    School nurses actively monitor the school population for signs of communicable disease on a daily basis. State regulations outline reportable diseases and provide guidance to control disease outbreak, including management of disease outbreak in the school setting. The purpose of this article is to review strategies recently used in managing a tuberculosis (TB) outbreak at a large high school in Kansas. A timeline of events is presented along with a discussion of the differences between latent TB infection and TB disease. Partnering across agencies and departments enabled the timely testing of over 400 individuals and subsequent management of individuals testing positive for latent TB infection. Public information officers provided necessary guidance to communicate to audiences both internally and externally. PMID:26822133

  8. T-SPOT.TB in Detection of Active Tuberculosis During Pregnancy: A Retrospective Study in China

    PubMed Central

    Chen, Qiaopei; Guo, Xuxiao; Wang, Xinfeng; Wang, Maoshui

    2016-01-01

    Background Interferon-gamma release assays have not been validated in active TB among pregnant women. Therefore, the objective of this retrospective study was to estimate the diagnostic value of T-SPOT.TB in active TB among pregnant women. Material/Methods Between May 2012 and May 2015, 26 consecutive pregnant women with suspected TB were enrolled in our study. The clinicopathological characteristics and T-SPOT.TB results were reviewed and analyzed. Results Pregnant patients were divided into a TB group (n=21) and a Non-TB group (n=5). In the TB group, 5 patients had pulmonary TB, 5 had pulmonary TB+ extrapulmonary TB, and 11 had exclusively extrapulmonary TB. The most common site of extrapulmonary TB was pleural (n=11). Statistical analysis showed that the lymphocyte count in the TB group was lower than in the Non-TB group (P<0.05). For detection of active TB during pregnancy, T-SPOT.TB had a high sensitivity of 100.0% (84.5%–100.0%) and a specificity of 80.0% (37.6–96.4%). Conclusions T-SPOT.TB shows good performance in detection of active tuberculosis during pregnancy. Interferon gamma release assay for TB screening of pregnant women is recommended in clinical practice because it may be a more appropriate diagnostic tool than the tuberculin skin test. PMID:26732770

  9. The Use of Xpert MTB/Rif for Active Case Finding among TB Contacts in North West Province, South Africa.

    PubMed

    Lebina, Limakatso; Fuller, Nigel; Osoba, Tolu; Scott, Lesley; Motlhaoleng, Katlego; Rakgokong, Modiehi; Abraham, Pattamukkil; Variava, Ebrahim; Martinson, Neil Alexander

    2016-01-01

    Introduction. Tuberculosis is a major cause of morbidity and mortality especially in high HIV burden settings. Active case finding is one strategy to potentially reduce TB disease burden. Xpert MTB/Rif has recently been recommended for diagnosis of TB. Methods. Pragmatic randomized trial to compare diagnosis rate and turnaround time for laboratory testing for Xpert MTB/Rif with TB microscopy and culture in household contacts of patients recently diagnosed with TB. Results. 2464 household contacts enrolled into the study from 768 active TB index cases. 1068 (44%) were unable to give sputum, but 24 of these were already on TB treatment. 863 (53%) participants sputum samples were tested with smear and culture and 2.7% (23/863; CI: 1.62-3.78) were diagnosed with active TB. Xpert MTB/Rif was used in 515 (21%) participants; active TB was diagnosed in 1.6% (8/515; CI: 0.52-2.68). Discussion and Conclusions. Additional 31 cases were diagnosed with contact tracing of household members. When Xpert MTB/Rif is compared with culture, there is no significant difference in diagnostic yield. PMID:27493800

  10. The Use of Xpert MTB/Rif for Active Case Finding among TB Contacts in North West Province, South Africa

    PubMed Central

    Osoba, Tolu; Scott, Lesley; Motlhaoleng, Katlego; Rakgokong, Modiehi; Martinson, Neil Alexander

    2016-01-01

    Introduction. Tuberculosis is a major cause of morbidity and mortality especially in high HIV burden settings. Active case finding is one strategy to potentially reduce TB disease burden. Xpert MTB/Rif has recently been recommended for diagnosis of TB. Methods. Pragmatic randomized trial to compare diagnosis rate and turnaround time for laboratory testing for Xpert MTB/Rif with TB microscopy and culture in household contacts of patients recently diagnosed with TB. Results. 2464 household contacts enrolled into the study from 768 active TB index cases. 1068 (44%) were unable to give sputum, but 24 of these were already on TB treatment. 863 (53%) participants sputum samples were tested with smear and culture and 2.7% (23/863; CI: 1.62–3.78) were diagnosed with active TB. Xpert MTB/Rif was used in 515 (21%) participants; active TB was diagnosed in 1.6% (8/515; CI: 0.52–2.68). Discussion and Conclusions. Additional 31 cases were diagnosed with contact tracing of household members. When Xpert MTB/Rif is compared with culture, there is no significant difference in diagnostic yield. PMID:27493800

  11. CD4+ T cell polyfunctional profile in HIV-TB coinfection are similar between individuals with latent and active TB infection

    PubMed Central

    Canaday, David H.; Sridaran, Sankar; Van Epps, Puja; Aung, Htin; Burant, Christopher J.; Nsereko, Mary; Mayanja-Kizza, Harriet; Betts, Michael R.; Toossi, Zahra

    2015-01-01

    CD4+ T cell counts of HIV-infected individuals with pulmonary TB (PTB) are higher than with other opportunistic infections suggesting that progression to PTB is not merely due to T cell depletion but also dysfunction. There are limited data examining T cell functional signatures in human HIV-TB co-infection particularly in PTB which accounts for about 80% of active TB disease overall. We examined a cohort of HIV-infected anti-retroviral naïve individuals in Kampala, Uganda, a TB endemic area using multi-parametric flow cytometry analysis to determine IFN-γ, IL-2, IL-17, and TNF-α production in CD4+ memory T cell subsets. The cytokine frequency and polyfunctionality profile of Mycobacterium tuberculosis (MTB)-specific CD4+ T cells in HIV-infected persons with latent TB infection (LTBI) or PTB is comparable. This similarity suggests that LTBI may represent a smoldering state of persistent MTB replication rather than dormant infection. This may be a contributory mechanism to the significantly increased risk of progression to PTB in this population. PMID:25956974

  12. Tuberculosis Facts - Testing for TB

    MedlinePlus

    Tuberculosis (TB) Facts Testing for TB What is TB? “TB” is short for a disease called tuberculosis. TB is spread through the air from one ... Viral Hepatitis, STD, and TB Prevention Division of Tuberculosis Elimination

  13. Tuberculosis Facts - Exposure to TB

    MedlinePlus

    Tuberculosis (TB) Facts Exposure to TB What is TB? “TB” is short for a disease called tuberculosis. TB is spread through the air from one ... Viral Hepatitis, STD, and TB Prevention Division of Tuberculosis Elimination

  14. Differential Levels of Alpha-2-Macroglobulin, Haptoglobin and Sero-Transferrin as Adjunct Markers for TB Diagnosis and Disease Progression in the Malnourished Tribal Population of Melghat, India.

    PubMed

    Bapat, Prachi R; Satav, Ashish R; Husain, Aliabbas A; Shekhawat, Seema D; Kawle, Anuja P; Chu, Justin J; Purohit, Hemant J; Daginawala, Hatim F; Taori, Girdhar M; Kashyap, Rajpal S

    2015-01-01

    Lack of diagnostic capacity has been a crucial barrier preventing an effective response to the challenges of malnutrition and tuberculosis (TB). Point-of-care diagnostic tests for TB in immuno-incompetent, malnourished population are thus needed to ensure rapid and accurate detection. The aim of the study was to identify potential biomarkers specific for TB infection and progression to overt disease in the malnourished population of Melghat. A prospective cohort study was conducted in the year 2009 through 2011 in six villages of the Melghat region. 275 participants consisting of malnourished cases with a) active TB (n = 32), b) latent TB infection (n = 90), c) with no clinical or bacteriological signs of active or latent TB (n = 130) and healthy control subjects (n = 23) were recruited for the study. The proteome changes of the host serum in response to Mycobacterium tuberculosis (M.tb) infection were investigated using one dimensional electrophoresis in combination with matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Three most differentially expressed proteins; alpha-2-macroglobulin (A-2-M), sero-transferrin and haptoglobin were identified by MALDI-TOF MS analysis, which were up-regulated in the malnourished patients with active TB and down-regulated in the malnourished patients compared with the healthy controls. Additionally, follow-up studies indicated that the expression of these proteins increased to nearly two folds in patients who developed active disease from latent state. Our preliminary results suggest that A-2-M, sero-transferrin and haptoglobin may be clinically relevant host biomarkers for TB diagnosis and disease progression in the malnourished population. This study provides preliminary framework for an in-depth analysis of the biomarkers in larger well-characterized cohorts. Evaluation of these biomarkers in follow-up cases may further aid in improving TB diagnosis. PMID:26241963

  15. Differential Levels of Alpha-2-Macroglobulin, Haptoglobin and Sero-Transferrin as Adjunct Markers for TB Diagnosis and Disease Progression in the Malnourished Tribal Population of Melghat, India

    PubMed Central

    Bapat, Prachi R.; Satav, Ashish R.; Husain, Aliabbas A.; Shekhawat, Seema D.; Kawle, Anuja P.; Chu, Justin J.; Purohit, Hemant J.; Daginawala, Hatim F.; Taori, Girdhar M.; Kashyap, Rajpal S.

    2015-01-01

    Lack of diagnostic capacity has been a crucial barrier preventing an effective response to the challenges of malnutrition and tuberculosis (TB). Point-of-care diagnostic tests for TB in immuno-incompetent, malnourished population are thus needed to ensure rapid and accurate detection. The aim of the study was to identify potential biomarkers specific for TB infection and progression to overt disease in the malnourished population of Melghat. A prospective cohort study was conducted in the year 2009 through 2011 in six villages of the Melghat region. 275 participants consisting of malnourished cases with a) active TB (n = 32), b) latent TB infection (n = 90), c) with no clinical or bacteriological signs of active or latent TB (n = 130) and healthy control subjects (n = 23) were recruited for the study. The proteome changes of the host serum in response to Mycobacterium tuberculosis (M.tb) infection were investigated using one dimensional electrophoresis in combination with matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Three most differentially expressed proteins; alpha-2-macroglobulin (A-2-M), sero-transferrin and haptoglobin were identified by MALDI-TOF MS analysis, which were up-regulated in the malnourished patients with active TB and down-regulated in the malnourished patients compared with the healthy controls. Additionally, follow-up studies indicated that the expression of these proteins increased to nearly two folds in patients who developed active disease from latent state. Our preliminary results suggest that A-2-M, sero-transferrin and haptoglobin may be clinically relevant host biomarkers for TB diagnosis and disease progression in the malnourished population. This study provides preliminary framework for an in-depth analysis of the biomarkers in larger well-characterized cohorts. Evaluation of these biomarkers in follow-up cases may further aid in improving TB diagnosis. PMID:26241963

  16. Scaling up of HIV-TB collaborative activities: Achievements and challenges in India.

    PubMed

    Deshmukh, Rajesh; Shah, Amar; Sachdeva, K S; Sreenivas, A N; Gupta, R S; Khaparde, S D

    2016-01-01

    India has been implementing HIV/TB collaborative activities since 2001 with rapid scale-up of infrastructure across the country during past decade in National AIDS Control Programme and Revised National TB Control Programme. India has shown over 50% reduction in new infections and around 35% reduction in AIDS-related deaths, thereby being one of the success stories globally. Substantial progress in the implementation of collaborative TB/HIV activities has occurred in India and it is marching towards target set out in the Global Plan to Stop TB and endorsed by the UN General Assembly to halve HIV associated TB deaths by 2015. While the successful approaches have led to impressive gains in HIV/TB control in India, there are emerging challenges including newer pockets with rising HIV trends in North India, increasing drug resistance, high mortality among co-infected patients, low HIV testing rates among TB patients in northern and eastern states in India, treatment delays and drop-outs, stigma and discrimination, etc. In spite of these difficulties, established HIV/TB coordination mechanisms at different levels, rapid scale-up of facilities with decentralisation of treatment services, regular joint supervision and monitoring, newer initiatives like use of rapid diagnostics for early diagnosis of TB among people living with HIV, TB notification, etc. have led to success in combating the threat of HIV/TB in India. This article highlights the steps taken by India, one of the largest HIV/TB programmes in world, in scaling up of the joint HIV-TB collaborative activities, the achievements so far and discusses the emerging challenges which could provide important lessons for other countries in scaling up their programmes. PMID:27235937

  17. Diagnostic Utility of QuantiFERON-TB Gold (QFT-G) in Active Pulmonary Tuberculosis

    PubMed Central

    Anwar, Ahmed; Hamdan, AL-Jahdali; Salim, Baharoon; Yosra, Ali; Hani, Mohamed; Abdullah, AL-Harbi

    2015-01-01

    Background: The utility of QuantiFERON-TB Gold In-Tube (QFT-G) test in the diagnosis of tuberculosis disease has been validated in high and low tuberculosis-prevalent (TB) countries. Aim: The aim of this study is to assess the performance of the QFT-G test in the diagnosis of tuberculosis disease among tuberculosis patients in an intermediate prevalent country. Setting and Design: A retrospective study at the King Abdulaziz Medical City-Riyadh (KAMC-R) Materials and Methods: We retrospectively reviewed all the patients with a diagnosis of pneumonia, including tuberculosis, admitted to KAMC-R between 1 January 2009 and 31 December 2013. We included only patients with an available result of the QFT-G test. A total of 142 tuberculosis cases and 226 pneumonia cases were studied, to assess the utility of the QFT-G test in diagnosing tuberculosis cases. Results: Among the tuberculosis (n = 142) cases, the QFT-G tested positive in 68.3%, negative in 23.2%, and indeterminate in 12 cases (8.5%). Of the 226 pneumonia cases, the QFT-G tested positive in only 20.4%, while a majority of 66.4% tested negative, with 30 cases (13.3%) being indeterminate. When we excluded 42 patients with indeterminate results, the QFT-G test achieved a sensitivity of 74.6% [95% CI: 66.09 to 81.65%] and specificity of 76.53 % [95% CI: 69.85 to 82.15%] in the diagnosis of tuberculosis cases. Conclusions: This study concludes that the QFT-G test is a useful tool for detecting tuberculosis disease when used as an adjunct tool for the diagnosis of active TB cases. It certainly cannot be used solely and indiscriminately, separate from other clinical and radiological information, in the diagnosis of active tuberculosis cases. PMID:26392718

  18. Tuberculosis Facts - TB and HIV/AIDS

    MedlinePlus

    Tuberculosis (TB) Facts TB and HIV/AIDS What is TB? “TB” is short for a disease called tuberculosis. TB is spread through the air from one ... Viral Hepatitis, STD, and TB Prevention Division of Tuberculosis Elimination

  19. The effect of HIV coinfection, HAART and TB treatment on cytokine/chemokine responses to Mycobacterium tuberculosis (Mtb) antigens in active TB patients and latently Mtb infected individuals.

    PubMed

    Kassa, Desta; de Jager, Wilco; Gebremichael, Gebremedhin; Alemayehu, Yodit; Ran, Leonie; Fransen, Justin; Wolday, Dawit; Messele, Tsehaynesh; Tegbaru, Belete; Ottenhoff, Tom H M; van Baarle, Debbie

    2016-01-01

    Identification of Mtb specific induced cytokine/chemokine host biomarkers could assist in developing novel diagnostic, prognostic and therapeutic tools for TB. Levels of IFN-γ, IL-2, IL-17, IL-10, IP-10 and MIP-1α were measured in supernatants of whole blood stimulated with Mtb specific fusion protein ESAT-6/CFP-10 using xMAP technology. The study groups were HIV positive TB patients (HIV(+)TB(+)), HIV negative TB patients (HIV(-)TB(+)), HIV positive tuberculin skin test positive (TST+) (HIV(+)TST(+)), HIV negative TST+ (HIV(-)TST(+)), and HIV(-)TST(-) individuals. Compared to HIV(-)TST(-), latent TB infection led to increased levels of IP-10, IFN-γ and IL-17, while levels of IL-2 and IP-10 were increased with active TB. Levels of IFN-γ, IL-17, MIP-1α, and IL-10 were increased in HIV(-)TST(+) individuals compared to HIV(-)TB(+) patients. HIV coinfection decreased the level of IFN-γ, IL-17, IP-10 and IL-2. After six months (M6) of anti-TB treatment (ATT) in HIV(-)TB(+) patients, IFN-γ, IL-10, and MIP-1α levels normalized. After M6 and M18 of ATT plus HAART in HIV(+)TB(+) patients, levels of MIP-1α and IL-10 normalized, while this was not the case for IFN-γ, IL-2, IL-17, and IP-10 levels. In HIV(+)TST(+) patients on HAART, levels of IFN-γ, IL-17, IL-10 and MIP-1α normalized, while no change in the levels of IL-2 and IP-10 were observed. In conclusion, the simultaneous measurement of IFN-γ, IL-17 and IP-10 may assist in diagnosing LTBI; IL-2 and IP-10 may assist in diagnosing active TB; while IFN-γ, IL-17, MIP-1α, and IL-10 levels could help to discriminate LTBI and active TB. In addition, IL-10 and MIP-1α levels could help to monitor responses to TB treatment and HAART. PMID:26631832

  20. Microwave synthesis and photocatalytic activity of Tb(3+) doped BiVO4 microcrystals.

    PubMed

    Wang, Ying; Liu, Fuyang; Hua, Yingjie; Wang, Chongtai; Zhao, Xudong; Liu, Xiaoyang; Li, Hongdong

    2016-12-01

    Tb(3+) doped BiVO4 has been successfully synthesized by a simple microwave-assisted hydrothermal method at 140°C for 30min. The structure, morphology and optical property of the Tb(3+) doped BiVO4 products have been systematically investigated. This study indicates that the incorporation of Tb(3+) could induce the conversion of structure from monoclinic to tetragonal for BiVO4. Furthermore, the as-obtained Tb(3+) doped BiVO4 samples showed an obvious morphological change: the hollow square rod-like BiVO4 crystal gradually changed to spindle-like crystal. The Tb(3+) doped BiVO4 products exhibited extraordinary photocatalytic activity for Methylene Blue (MB) degradation under visible light irradiation. The doped BiVO4 at a molar ratio of 2at% (Tb and Bi) with a mixture of monoclinic and tetragonal phases showed and prominent photocatalytic degradation rate, which reached 99.9% in 120min. The results suggest that the differences in the photocatalytic activity of these BiVO4 crystals with different Tb(3+) doping concentrations can be attributed to the change of crystalline phases, and the coexistence of the monoclinic/tetragonal phases in BiVO4 products, which improve the efficient charge separation and transportation. PMID:27565962

  1. Old Disease, New Threat: TB Makes an Unwelcome Comeback.

    ERIC Educational Resources Information Center

    Pyszczynski, Dennis R.

    1992-01-01

    Tuberculosis is on the rise in the United States. The article discusses its background, factors contributing to its increase, the likelihood of children and teens developing tuberculosis, how to prevent the disease from spreading, and what schools and states can do. (SM)

  2. Tuberculosis Facts - You Can Prevent TB

    MedlinePlus

    Tuberculosis (TB) Facts You Can Prevent TB What is TB? “TB” is short for a disease called tuberculosis. TB is spread through the air from one ... Viral Hepatitis, STD, and TB Prevention Division of Tuberculosis Elimination TB Facts: You Can Prevent TB What ...

  3. Tuberculosis Facts - TB Can Be Treated

    MedlinePlus

    Tuberculosis (TB) Facts TB Can Be Treated What is TB? “TB” is short for a disease called tuberculosis. TB is spread through the air from one ... Viral Hepatitis, STD, and TB Prevention Division of Tuberculosis Elimination Page 1 of 2 TB Facts: TB ...

  4. Recent tuberculosis diagnosis toward the end TB strategy.

    PubMed

    Cheon, Seon Ah; Cho, Hyun Hee; Kim, Jeonghyo; Lee, Jaebeom; Kim, Hwa-Jung; Park, Tae Jung

    2016-04-01

    Tuberculosis (TB) is an infectious bacterial disease caused by Mycobacterium tuberculosis. Despite global TB eradication efforts, it is still a global public health concern, especially in low- and middle-income countries. Most of the active TB infections are curable with early diagnosis and appropriate treatment, but drug-resistant TB is difficult and expensive to treat in immunocompetent as well as immunocompromised individuals. Thus, rapid, economic, and accurate point-of care tools for TB diagnosis are required urgently. This review describes the history of M. tuberculosis detection methods up to date and the recent advances using nanotechnology for point-of-care testing of TB diagnosis. PMID:26853124

  5. Clinical features of active tuberculosis that developed during anti-tumor necrosis factor therapy in patients with inflammatory bowel disease

    PubMed Central

    Lee, Jang Wook; Park, Ji Hoon; Kim, Jeong Wook; Kang, Sang Bum; Koo, Ja Seol; Kim, Young-Ho; Kim, You Sun; Joo, Young Eun; Chang, Sae Kyung

    2016-01-01

    Background/Aims Anti-tumor necrosis factor (TNF) therapy for active ulcerative colitis (UC) and Crohn's disease (CD) is associated with increased risks of tuberculosis (TB) infection. We analyzed the incidence and clinical features of Korean patients with inflammatory bowel disease (IBD) who developed active TB during anti-TNF therapy. Methods Ten cases of active TB developed in patients treated with infliximab (n=592) or adalimumab (n=229) for UC (n=160) or CD (n=661) were reviewed. We analyzed demographics, interval between start of anti-TNF therapy and active TB development, tests for latent TB infection (LTBI), concomitant medications, and the details of diagnosis and treatments for TB. Results The incidence of active TB was 1.2% (10/821): 1.5% (9/592) and 0.4% (1/229) in patients receiving infliximab and adalimumab, respectively. The median time to the development of active TB after initiation of anti-TNF therapy was three months (range: 2–36). Three patients had past histories of treatment for TB. Positive findings in a TB skin test (TST) and/or interferon gamma releasing assay (IGRA) were observed in three patients, and two of them received anti-TB prophylaxis. Two patients were negative by both TST and IGRA. The most common site of active TB was the lungs, and the active TB was cured in all patients. Conclusions Active TB can develop during anti-TNF therapy in IBD patients without LTBI, and even in those with histories of TB treatment or LTBI prophylaxis. Physicians should be aware of the potential for TB development during anti-TNF therapy, especially in countries with a high prevalence of TB. PMID:27175115

  6. A Systematic Review of the Prevalence and Pattern of Imaging Defined Post-TB Lung Disease

    PubMed Central

    Meghji, Jamilah; Simpson, Hope; Squire, S. Bertel; Mortimer, Kevin

    2016-01-01

    Background Tuberculosis is an important risk factor for chronic respiratory disease in resource poor settings. The persistence of abnormal spirometry and symptoms after treatment are well described, but the structural abnormalities underlying these changes remain poorly defined, limiting our ability to phenotype post-TB lung disease in to meaningful categories for clinical management, prognostication, and ongoing research. The relationship between post-TB lung damage and patient-centred outcomes including functional impairment, respiratory symptoms, and health related quality of life also remains unclear. Methods We performed a systematic literature review to determine the prevalence and pattern of imaging-defined lung pathology in adults after medical treatment for pleural, miliary, or pulmonary TB disease. Data were collected on study characteristics, and the modality, timing, and findings of thoracic imaging. The proportion of studies relating imaging findings to spirometry results and patient morbidity was recorded. Study quality was assessed using a modified Newcastle-Ottowa score. (Prospero Registration number CRD42015027958) Results We identified 37 eligible studies. The principle features seen on CXR were cavitation (8.3–83.7%), bronchiectasis (4.3–11.2%), and fibrosis (25.0–70.4%), but prevalence was highly variable. CT imaging identified a wider range of residual abnormalities than CXR, including nodules (25.0–55.8%), consolidation (3.7–19.2%), and emphysema (15.0–45.0%). The prevalence of cavitation was generally lower (7.4–34.6%) and bronchiectasis higher (35.0–86.0%) on CT vs. CXR imaging. A paucity of prospective data, and data from HIV-infected adults and sub-Saharan Africa (sSA) was noted. Few studies related structural damage to physiological impairment, respiratory symptoms, or patient morbidity. Conclusions Post-TB structural lung pathology is common. Prospective data are required to determine the evolution of this lung damage and

  7. Infectious Diseases (ID) Learning Unit: How Rapidly to Evaluate for Active Tuberculosis Disease in Low-Prevalence Settings.

    PubMed

    Chida, Natasha; Shah, Maunank

    2016-03-01

    With declining tuberculosis (TB) incidence in low-prevalence settings, many clinicians are likely unaware that the approach to diagnosing active TB is evolving with newer technologies. Rapid molecular assays are commercially available, and more are likely to enter the market in the coming years. These tests, such as the Xpert MTB/RIF, which can detect TB and drug-resistance in 2 hours, are increasingly used in settings with higher TB prevalence; however, uptake has been slower in low-prevalence settings. Newer algorithms incorporating rapid TB diagnostics have the ability to alter current clinical and infection control practice patterns. In this learning unit, we review current and newly available tests for the detection of active TB disease and their usage in low-prevalence settings. PMID:27186583

  8. Infectious Diseases (ID) Learning Unit: How Rapidly to Evaluate for Active Tuberculosis Disease in Low-Prevalence Settings

    PubMed Central

    Chida, Natasha; Shah, Maunank

    2016-01-01

    With declining tuberculosis (TB) incidence in low-prevalence settings, many clinicians are likely unaware that the approach to diagnosing active TB is evolving with newer technologies. Rapid molecular assays are commercially available, and more are likely to enter the market in the coming years. These tests, such as the Xpert MTB/RIF, which can detect TB and drug-resistance in 2 hours, are increasingly used in settings with higher TB prevalence; however, uptake has been slower in low-prevalence settings. Newer algorithms incorporating rapid TB diagnostics have the ability to alter current clinical and infection control practice patterns. In this learning unit, we review current and newly available tests for the detection of active TB disease and their usage in low-prevalence settings. PMID:27186583

  9. Augmented photocatalytic activity and luminescence response of Tb³⁺ doped nanoscale titania systems

    SciTech Connect

    Paul, Nibedita; Deka, Amrita; Mohanta, Dambarudhar

    2014-10-14

    The present work reports on the effect of Tb³⁺ doping on the luminescence and photocatalytic performance of nano-structured titania derived through a sol-gel route. X-ray diffraction patterns have revealed the existence of anatase phase with and without Tb³⁺ doping and with an improved orientation factor along (004) and (200) planes. Transmission electron microscopy and selective area electron diffraction studies, while exhibiting ample poly-crystallinity feature, have predicted an average particle size of ~9 nm and ~6 nm for the un-doped and 5% Tb³⁺ doped nano-titania samples; respectively. Apart from emissions accompanied by different types of defects, Tb³⁺ related transitions, such as, ⁵D₃ → ⁷F₅, ⁵D₃ → ⁷F₄, and ⁵D₄ → ⁷F₆ were identified in the photoluminescence spectra. Brunauer-Emmett-Teller surface area analysis, as carried out on a Tb³⁺ doped nano-titania system, has demonstrated a more-open hysteretic loop owing to significant difference of N₂ adsorption/desorption rates. The photocatalytic activity of nano-titania, as evaluated from the nature of degradation of methyl orange under UV illumination, exhibited the highest efficiency for a Tb³⁺ doping level of 2.5%. The augmented photocatalytic degradation has also been discussed in the light of a model based on pseudo first-order kinetics.

  10. The Mycobacterium tuberculosis PPE protein Rv1168c induces stronger B cell response than Rv0256c in active TB patients.

    PubMed

    Abraham, Philip Raj; Udgata, Atul; Latha, Gaddam Suman; Mukhopadhyay, Sangita

    2016-06-01

    Tuberculosis (TB) caused by Mycobacterium tuberculosis is a serious global health problem and is responsible for millions of deaths every year. For effective control of this dreadful disease, it is necessary to diagnose TB cases at the initial stages of infection. The serodiagnosis of disease represents simple, rapid and inexpensive method that can be used at the primary health care levels. In this study we have compared sensitivity of two PPE proteins of M. tuberculosis, i.e., Rv0256c and Rv1168c for their use as serodiagnostic markers in active tuberculosis patients. Employing a standardized enzyme immunoassay with these PPE proteins as candidate antigens we were able to successfully discriminate the TB patients' sera from the BCG-vaccinated healthy controls. Further, we observed that Rv1168c displayed higher sensitivity in detecting extrapulmonary and smear negative pulmonary TB cases which are difficult to diagnose by available diagnostic methods. Overall the study highlights that Rv1168c can be used as a potential serodiagnostic marker for the diagnosis of active tuberculosis disease. PMID:26364913

  11. TB Terms

    MedlinePlus

    ... Search The CDC Cancel Submit Search The CDC Tuberculosis (TB) Note: Javascript is disabled or is not ... message, please visit this page: About CDC.gov . Tuberculosis Basic TB Facts How TB Spreads Latent TB ...

  12. A comparison between passive and active case finding in TB control in the Arkhangelsk region

    PubMed Central

    Kuznetsov, Vladimir N.; Grjibovski, Andrej M.; Mariandyshev, Andrey O.; Johansson, Eva; Bjune, Gunnar A.

    2014-01-01

    Background In Russia, active case finding (ACF) for certain population groups has been practiced uninterruptedly for many decades, but no studies comparing ACF and passive case finding (PCF) approaches in Russia have been published. Objective The aim of this study was to describe the main differences in symptoms and diagnostic delay between patients who come to TB services through PCF and ACF strategies. Methods A cross-sectional study was conducted among 453 new pulmonary tuberculosis (PTB) patients, who met criteria of TB diagnostic delay in Arkhangelsk. Results ACF patients used self-treatment more often than PCF patients (90.1% vs. 24.6%) and 36.3% of them were alcohol abusers (as opposed to only 26.2% of PCF patients). The median patient delay (PD) in PCF was 4 weeks, IQR (1–8 weeks), and less than 1 week in ACF. Twenty-three per cent of the PCF patients were seen by a medical provider within the first week of their illness onset. Conclusion Patients diagnosed through ACF tended to under-report their TB symptoms and showed low attention to their own health. However, ACF allowed for discovering TB patients earlier than PCF, and this was also the case for alcohol abusing patients. PCF systems should be supplemented with ACF strategies. PMID:24563859

  13. Toward an Evidence-Based Nonclinical Road Map for Evaluating the Efficacy of New Tuberculosis (TB) Drug Regimens: Proceedings of a Critical Path to TB Drug Regimens-National Institute of Allergy and Infectious Diseases In Vivo Pharmacology Workshop for TB Drug Development.

    PubMed

    Nuermberger, Eric; Sizemore, Christine; Romero, Klaus; Hanna, Debra

    2016-01-01

    Novel tuberculosis (TB) drug regimens are urgently needed, and their development will be enabled by improved preclinical approaches that more effectively inform and ensure safe selection of clinical candidates and drug combination/regimens. An evidence-based approach for the assessment of nonclinical models supporting TB drug development has been proposed by a joint partnership between the National Institute of Allergy and Infectious Diseases (NIAID) and the Critical Path to TB Drug Regimens (CPTR) Consortium. PMID:26824941

  14. The increased risk of active tuberculosis disease in patients with dermatomyositis – a nationwide retrospective cohort study

    PubMed Central

    Wu, Ping-Hsun; Lin, Yi-Ting; Yang, Yi-Hsin; Lin, Yu-Chih; Lin, Yi-Ching

    2015-01-01

    The risk of active tuberculosis (TB) in patients with dermatomyositis (DM) is poorly understood. The cohort study aimed to investigate the association between DM and the risk of active TB disease. We conducted a population based study on 4,958 patients with newly diagnosed DM and 19,832 matched controls according to age, sex, and index date between 1998 and 2008. The hazard ratios (HRs) and cumulative incidences of active TB disease between DM patients and controls were analyzed. During the study period, a total of 85 (1.7%) DM patients developed active TB disease, which was significantly higher than that of non-DM patients (0.64%). The incidence rate of active TB disease was higher among DM patients than controls (incidence rate ratio 2.95; 95% confidence interval [CI], 2.24 to 3.88). The Cox regression model demonstrated significantly higher active TB disease rate among DM patients compared with controls (adjusted HR, 2.64; 95% CI, 1.97 to 3.54; p < 0.001) after adjusting for age, sex, and underlying medical disorders. The most significant risk factors for developing active TB included male sex, diabetes mellitus comorbidity, and use of corticosteroids and azathioprine in DM patients. In conclusion, DM patients are at a greater risk for active TB disease. PMID:26573418

  15. Hepatitis C Virus Infection Is Associated With an Increased Risk of Active Tuberculosis Disease: A Nationwide Population-Based Study.

    PubMed

    Wu, Ping-Hsun; Lin, Yi-Ting; Hsieh, Kun-Pin; Chuang, Hung-Yi; Sheu, Chau-Chyun

    2015-08-01

    Tuberculosis (TB) and hepatitis C virus (HCV) infection contribute to major disease mortality and morbidity worldwide. However, the causal link between HCV infection and TB risk remains unclear. We conducted a population-based cohort study to elucidate the association between HCV infection and TB disease by analyzing Taiwan National Health Insurance Database. We enrolled 5454 persons with HCV infection and 54,274 age- and sex-matched non-HCV-infected persons between January 1998 and December 2007. Time-dependent Cox proportional hazards regression analysis was used to measure the association between HCV infection and active TB disease. Incidence rate of active TB disease was higher among HCV infection than in control (134.1 vs 89.1 per 100,000 person-years; incidence rate ratio 1.51; P = 0.014). HCV infection was significantly associated with active TB disease in multivariate Cox regression (adjusted hazard ratio [HR] 3.20; 95% confidence interval [CI], 1.85-5.53; P < 0.001) and competing death risk event analysis (adjusted HR 2.11; 95% CI, 1.39-3.20; P < 0.001). Multivariate stratified analysis further revealed that HCV infection was a risk of active TB disease in most strata. This nationwide cohort study suggests that HCV infection is associated with a higher risk of developing active TB disease. PMID:26287416

  16. Tuberculosis (TB)

    MedlinePlus

    ... Skip Content Marketing Share this: Main Content Area Tuberculosis (TB) Overview In developed countries, such as the ... thought to be infected with TB bacteria, Mycobacterium tuberculosis ( Mtb ). TB is a chronic bacterial infection. It ...

  17. Risk of Active Tuberculosis in HIV-Infected Patients in Taiwan with Free Access to HIV Care and a Positive T-Spot.TB Test

    PubMed Central

    Sun, Hsin-Yun; Hsueh, Po-Ren; Liu, Wen-Chun; Su, Yi-Ching; Chang, Sui-Yuan; Hung, Chien-Ching; Chang, Shan-Chwen

    2015-01-01

    Background Interferon-gamma release assays (IGRAs) have been used to identify individuals at risk for developing active tuberculosis (TB). However, data regarding the risk of TB development in HIV-infected patients testing positive for IGRAs remain sparse in the era of combination antiretroviral therapy. Methods Between 2011 and 2013, 608 HIV-infected patients without active TB undergoing T-Spot.TB testing were enrolled in this prospective observational study at a university hospital designated for HIV care in Taiwan with a declining TB incidence from 72 per 100,000 population in 2005 to 53 per 100,000 population in 2012. All of the subjects were followed until September 30, 2014. The national TB registry was accessed to identify any TB cases among those lost to follow-up. Results T-Spot.TB tested negative in 534 patients (87.8%), positive in 64 patients (10.5%), and indeterminate in 10 patients (1.6%). In multivariate analysis, positive T-Spot.TB was significantly associated with older age (adjusted odds ratio [AOR], 1.172 per 10-year increase; 95% confidence interval [CI], 1.022-1.344, P=0.023), past history of TB (AOR, 13.412; 95% CI, 6.106-29.460, P<0.001), and higher CD4 counts at enrollment (AOR, per 50-cell/μl increase, 1.062; 95% CI, 1.017-1.109, P=0.007). Of the 64 patients testing positive for T-Spot.TB, none received isoniazid preventive therapy and all but 5 received combination antiretroviral therapy at the end of follow-up with the latest CD4 count and plasma HIV RNA load being 592.8 cells/μL and 1.85 log10 copies/mL, respectively. One patient (1.6%) developed active TB after 167 person-years of follow-up (PYFU), resulting in an incidence rate of 0.599 per 100 PFYU. None of the 534 patients testing negative for T-Spot.TB developed TB after 1380 PYFU, nor did the 24 patients with old TB and positive T-Spot.TB tests develop TB after 62.33 PYFU. Conclusions The risk of developing active TB in HIV-infected patients with positive T-Spot.TB receiving

  18. Non-clinical factors associated with TB: important for DOTS impact evaluation and disease elimination.

    PubMed

    Hill, Philip C; Whalen, Christopher C

    2014-09-01

    Initial optimism that DOTS (Directly Observed Treatment, Short-course) would have a dramatic effect on TB incidence rates in developing countries has not been supported by the evidence accumulated so far. Indeed, where TB incidence rates have decreased, non-clinical socio-economic factors appear to have played at least as great a role. We postulate that in those settings with little or no decrease in TB incidence, there are likely to be common pathway blockages that interfere with the effectiveness of DOTS implementation as socio-economic factors evolve. Measuring socio-economic trends, as well as DOTS implementation, is important for understanding TB control and opens up the opportunity for broader public health engagement. PMID:25059524

  19. Disease Activity Measures in Paediatric Rheumatic Diseases

    PubMed Central

    Luca, Nadia J.; Feldman, Brian M.

    2013-01-01

    Disease activity refers to potentially reversible aspects of a disease. Measurement of disease activity in paediatric rheumatic diseases is a critical component of patient care and clinical research. Disease activity measures are developed systematically, often involving consensus methods. To be useful, a disease activity measure must be feasible, valid, and interpretable. There are several challenges in quantifying disease activity in paediatric rheumatology; namely, the conditions are multidimensional, the level of activity must be valuated in the context of treatment being received, there is no gold standard for disease activity, and it is often difficult to incorporate the patient's perspective of their disease activity. To date, core sets of response variables are defined for juvenile idiopathic arthritis, juvenile systemic lupus erythematosus, and juvenile dermatomyositis, as well as definitions for improvement in response to therapy. Several specific absolute disease activity measures also exist for each condition. Further work is required to determine the optimal disease activity measures in paediatric rheumatology. PMID:24089617

  20. Stereochemical Analysis of Leubethanol, an Anti-TB Active Serrulatane, from Leucophyllum frutescens

    PubMed Central

    Molina-Salinas, Gloria M.; Rivas-Galindo, Verónica M.; Said-Fernández, Salvador; Lankin, David C.; Muñoz, Marcelo A.; Joseph-Nathan, Pedro; Pauli, Guido F.; Waksman, Noemí

    2013-01-01

    Bioactivity-guided fractionation of the methanolic root bark extract of Leucophyllum frutescens (Berl.) I.M. Johnst. led to the identification of leubethanol (1), a new serrulatane-type diterpene with activity against both multi drug-resistant and drug-sensitive strains of virulent Mycobacterium tuberculosis. Leubethanol (1) was identified by 1D/2D NMR data, as a serrulatane closely related to erogorgiane (2), and exhibited anti-TB activity with minimum inhibitory concentrations in the range 6.25–12.50 µg/mL. Stereochemical evidence for 1 was gleaned from 1D and 2D NOE experiments, 1H-NMR full spin analysis, as well as by comparison of the experimental vibrational circular dichroism (VCD) spectrum to density functional theory calculated VCD spectra of two diastereomers. PMID:21859082

  1. Tuberculosis (TB)

    MedlinePlus

    ... Skip Content Marketing Share this: Main Content Area Tuberculosis Research The New Challenge for TB Research NIAID ... HIV/AIDS Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis Research Agenda (PDF) TB Research at NIAID Research ...

  2. Validation of the BrockTB Stat-Pak Assay for Detection of Tuberculosis in Eurasian Badgers (Meles meles) and Influence of Disease Severity on Diagnostic Accuracy▿

    PubMed Central

    Chambers, Mark A.; Crawshaw, Tim; Waterhouse, Sue; Delahay, Richard; Hewinson, R. Glyn; Lyashchenko, Konstantin P.

    2008-01-01

    A lateral-flow immunoassay (BrockTB Stat-Pak) for detecting tuberculosis in Eurasian badgers was 49% sensitive and 93% specific against culture for M. bovis (n = 1,464) at necropsy. However, the sensitivity was significantly higher (66 to 78%) in animals with more severe tuberculosis, indicating that the BrockTB Stat-Pak may be useful for the detection of badgers with the greatest risk of transmitting disease. PMID:18272706

  3. Photoluminescence of Tb 3+ and Mn 2+ activated Ca 8MgGd(PO 4) 7 under vacuum ultraviolet excitation

    NASA Astrophysics Data System (ADS)

    Zhang, Jia; Wang, Yuhua; Huang, Yan

    2011-06-01

    Novel Tb 3+ and Mn 2+ activated Ca 8MgGd(PO 4) 7 phosphors were synthesized by solid-state reaction and their photoluminescence properties in vacuum ultraviolet region were investigated for the first time. It can be observed from the excitation spectra that the host-related absorption band is located around 170 nm, and it overlaps the O 2- → Tb 3+ charge transfer band of Ca 8MgGd(PO 4) 7:Tb 3+ around 161 nm and the 3d 5 → 3d 44s transition band of Ca 8MgGd(PO 4) 7:Mn 2+ near 200 nm. The 4f-4f 5d spin-allowed and spin-forbidden transitions of Tb 3+ are verified to be located at 170-250 and 257-271 nm, respectively. Upon 147 nm excitation, the dominant emission peak intensity of the Ca 8MgGd 0.1(PO 4) 7:0.9Tb 3+ phosphor is about 2.7 times stronger than that of the commercial Zn 2SiO 4:Mn 2+ green phosphor, and the brightness of the former with a short decay time of 2.5 ms is about 98% of the latter's. The Ca 8MgGd(PO 4):Mn 2+ phosphor excited at 147 nm exhibits a deep red emission around 650 nm, which could be attributed to the 4T 1 → 6A 1 transition of Mn 2+, with the CIE index (0.679, 0.321). In a word, the results above indicate that both Tb 3+ and Mn 2+ activated Ca 8MgGd(PO 4) 7 phosphors could be promising for PDP or Hg-free lamp applications.

  4. Role of QuantiFERON-TB Gold antigen-specific IL-1β in diagnosis of active tuberculosis.

    PubMed

    Prabhavathi, Maddineni; Kabeer, Basirudeen Syed Ahamed; Deenadayalan, Anbarasu; Raja, Alamelu

    2015-10-01

    The main objective of the study was to evaluate whether in vitro QuantiFERON-TB Gold In-Tube (QFT-GIT) assay antigen-specific IL-1β, TNF-α, IL-2, IL-6, IL-8 and IL-12 (p40) production is associated with active TB. In a cohort of 77 pulmonary TB patients (PTB), 67 healthy household contacts (HHC) and 83 healthy control subjects (HCS), the antigen-specific cytokines levels were determined in supernatants generated from QFT-GIT tubes. Antigen-specific IL-1β levels were significantly higher in PTB than HHC and HCS. At a fixed cutoff point (1,108 pg/ml), IL-1β showed positivity of 62.33% in PTB, 22.38% in HHC and 22.89% in HCS. Moreover, antigen-specific IL-1β assay can differentiate PTB and HHC (believed to be latently infected) (p < 0.0001). Like IL-1β, significantly higher levels of antigen-specific TNF-α were associated with PTB and displayed 43.63% positivity in PTB. The antigen-specific IL-2 levels were associated both with PTB (54.54%) and HHC (48.14%). Other cytokines levels did not differ among the groups. Our results suggest that antigen-specific IL-1β can be used as a biomarker for active TB diagnosis as well as for differential diagnosis of PTB and LTBI. PMID:25504009

  5. Electrocatalysis of carbon black- or poly(diallyldimethylammonium chloride)-functionalized activated carbon nanotubes-supported Pd-Tb towards methanol oxidation in alkaline media

    NASA Astrophysics Data System (ADS)

    Wang, Li; Wang, Yi; Li, An; Yang, Yunshang; Tang, Qinghu; Cao, Hongbin; Qi, Tao; Li, Changming

    2014-07-01

    The Pd-Tb/C catalysts with different Pd/Tb ratios were synthesized by a simple simultaneous reduction reaction with sodium borohydride in aqueous solution. The structure and morphology of those catalysts had been characterized by X-ray diffraction (XRD) and transmission electron microscopy (TEM). The electrocatalytic performance of those catalysts for methanol oxidation in alkaline media was investigated using cyclic voltammetry (CV), linear sweep voltammetry (LSV) and CO stripping experiments. It is found that the 20%Pd-1%Tb/C catalyst has a higher catalytic activity than the 20%Pd/C catalyst, but the effect of Tb cannot be explained by a bi-functional mechanism. According to the X-Ray photoelectron spectroscopy (XPS) analyses, it is suggested that the higher content of metallic Pd caused by the addition of Tb contributes to the better catalytic activity of 20%Pd-1%Tb/C. Based on the good electrocatalytic performance of 20%Pd-1%Tb/C, the 20%Pd-1%Tb catalyst supported on poly(diallyldimethylammonium chloride) (PDDA)-functionalized activated carbon nanotubes was prepared, and it exhibits a better catalytic activity. The improvement mainly results from the further increase of metallic Pd due to the presence of PDDA.

  6. Luminescence properties of Ce3+ and Tb3+ co-activated ZnAl2O4 phosphor

    NASA Astrophysics Data System (ADS)

    Tshabalala, K. G.; Cho, S.-H.; Park, J.-K.; Pitale, Shreyas S.; Nagpure, I. M.; Kroon, R. E.; Swart, H. C.; Ntwaeaborwa, O. M.

    2012-05-01

    In this study, a solution combustion method was used to prepare green emitting Ce3+-Tb3+ co-activated ZnAl2O4 phosphor. The samples were annealed at 700 °C in air or hydrogen atmosphere to improve their crystallinity and optical properties. X-ray diffraction study confirmed that both as-prepared and post-preparation annealed samples crystallized in the well known cubic spinel structure of ZnAl2O4. An agglomeration of irregular platelet-like particles whose surfaces were encrusted with smaller spheroidal particles was confirmed by scanning electron microscopy (SEM). The fluorescence data collected from the annealed samples with different concentrations of Ce3+ and Tb3+ show the enhanced green emission at 543 nm associated with 5D4→7F5 transitions of Tb3+. The enhancement was attributed to energy transfer from Ce3+ to Tb3+. Possible mechanism of energy transfer via a down conversion process is discussed. Furthermore, cathodoluminescence (CL) intensity degradation of this phosphor was also investigated and the degradation data suggest that the material was chemically stable and the CL intensity was also stable after 10 h of irradiation by a beam of high energy electrons.

  7. Host Cytokine Responses Induced after Overnight Stimulation with Novel M. tuberculosis Infection Phase-Dependent Antigens Show Promise as Diagnostic Candidates for TB Disease

    PubMed Central

    Essone, Paulin N.; Chegou, Novel N.; Loxton, Andre G.; Stanley, Kim; Kriel, Magdalena; van der Spuy, Gian; Franken, Kees L.; Ottenhoff, Tom H.; Walzl, Gerhard

    2014-01-01

    Background We previously identified Mycobacterium tuberculosis (M.tb) antigen-induced host markers that showed promise as TB diagnostic candidates in 7-day whole blood culture supernatants. The aim of the present study was to evaluate the utility of these markers further, and cross-compare results with short-term antigen stimulated and unstimulated culture supernatants. Methods We recruited 15 culture confirmed TB cases and 15 non-TB cases from a high-TB endemic community in Cape Town, South Africa into a pilot case-control study from an on-going larger study. Blood samples collected from study participants were stimulated with 4 M.tb antigens that were previously identified as promising (ESAT6/CFP10 (early secreted), Rv2029c (latency), Rv2032 (latency) and Rv2389c (rpf)) in a 7-day or overnight culture assay. Supernatants were also collected form the standard QuantiFERON In Tube (QFT-IT) test. The levels of 26 host markers were evaluated in the three culture supernatants using the Luminex platform. Results The unstimulated levels of CRP, Serum amyloid P (SAP) and serum amyloid A (SAA) and ESAT-6/CFP-10 specific IP-10 and SAA were amongst the best discriminatory markers in all 3 assays, ascertaining TB with AUC of 72–84%. Four-marker models accurately classified up to 92%, 100% and 100% of study participants in the overnight, 7-day and Quantiferon culture supernatants, respectively, after leave-one-out cross validation. Conclusion Unstimulated and antigen-specific levels of CRP, SAA, IP-10, MMP-2 and sCD40L hold promise as diagnostic candidates for TB disease in short-term stimulation assays. Larger studies are required to validate these findings but the data suggest that antigen-specific cytokine production and in particular mutimarker biosignatures might contribute to future diagnostic strategies. PMID:25025278

  8. TB in Correctional Facilities Is a Public Health Concern

    MedlinePlus

    ... component to TB elimination in the United States. Tuberculosis (TB) is a disease caused by bacteria that ... is essential to these efforts. More Information Reported Tuberculosis in the United States, 2012 TB in Correctional ...

  9. Accuracy of QuantiFERON-TB Gold Test for Tuberculosis Diagnosis in Children

    PubMed Central

    Sali, Michela; Buonsenso, Danilo; Goletti, Delia; D’Alfonso, Pamela; Zumbo, Antonella; Fadda, Giovanni; Sanguinetti, Maurizio; Delogu, Giovanni; Valentini, Piero

    2015-01-01

    Objectives To evaluate the accuracy of the QuantiFERON-TB Gold assay (QFT-IT) in children with suspected active or latent TB infection (LTBI). Methods A retrospective study was conducted on 621 children (0–14 years old) evaluated for TB infection or disease. Following clinical assessment, children were tested with the QFT-IT assay. Results Among the 140 active TB suspects, we identified 19 cases of active disease. The overall sensitivity for active TB was 87.5%, ranging from 62.5% in children 25–36 months old to 100% in children older than 49 months. The overall specificity for active TB was 93.6%. Among the 481 children tested for LTBI screening, 38 scored positive and all but 2 had at least one risk factor for TB infection. Among the 26 children with indeterminate results, bacterial, viral or fungal pneumonia were later diagnosed in 11 (42.3%) cases and non-TB related extra-pulmonary infections in 12 (46.1%). Conclusions Our results indicate that the children's response to QFT-IT associates to active TB and risk factors for LTBI. Moreover, we show that mitogen response is also found in children of 1 year of age, providing support for QFT-IT use also in young children. PMID:26439935

  10. A model dynamic for effect latent population to co-epidemic of HIV-TB

    NASA Astrophysics Data System (ADS)

    Jafaruddin, Sutimin, Ariyanto

    2014-02-01

    Threat of co-epidemic HIV-TB is a major problem that must be faced by countries around the world. In 2011, approximately about one-third of the 34 million people living with HIV worldwide is infected with latent TB. Persons co-infected with TB and HIV are 21-34 times more likely to develop active TB disease than persons without HIV. In this paper, we develop a simple co-epidemic model of HIV-TB. We calculate the basic reproduction ratio at the disease-free equilibrium, and the quasi-disease-free equilibrium, which we define as the existence of one disease along with the complete eradication of the other disease, and the co-infection equilibrium for specific conditions. Using this model, we study co-epidemic HIV-TB in Indonesia based on demography data in 2009 to explore the effects of hypothetical prevention and treatment scenarios. Our simple model of co-epidemic HIV-TB describes the importance of including the effects of HIV on TB and vice versa on the transmission and progression of the HIV and TB epidemic.

  11. Bone marrow transplantation for T-B- severe combined immunodeficiency disease in Athabascan-speaking native Americans.

    PubMed

    O'Marcaigh, A S; DeSantes, K; Hu, D; Pabst, H; Horn, B; Li, L; Cowan, M J

    2001-04-01

    A distinct form of autosomal recessive T-B- severe combined immunodeficiency disease occurs with a high frequency among Athabascan-speaking Native Americans (SCIDA), including Navajo and Apache Indians from the southwestern US and Dene Indians from the Canadian Northwest Territories. The SCIDA gene has been linked to markers on chromosome 10p although its identity and role in the pathogenesis of this disease are unknown. We report our experience in treating 18 Navajo and Dene children with SCIDA between 1984 and 1999; 16 underwent bone marrow transplants (BMT). All children were symptomatic within 2 months of birth, had the T-B- NK(+)SCID phenotype and 67% presented with oral and/or genital ulcers. Three children had evidence of maternal engraftment prior to transplant. Two children died shortly after diagnosis. Three children required more than one BMT and 12 are alive with T cell reconstitution at a median follow-up of 7 years. Three children developed normal B cell immunity, two of whom received ablative conditioning therapy with either radiation or busulfan. Three of the four children who died received therapy with either radiation or busulfan and two of eight long-term survivors who were also recipients of cytotoxic chemotherapy have failed to develop secondary teeth. These results demonstrate the efficacy of BMT in treating infants with this distinct form of SCID, although B cell reconstitution remains a problem even with HLA-matched donors. Without conditioning, T cell engraftment is likely when closely HLA-matched donors are used. With T cell depletion of haplocompatible marrow, conditioning with immunosuppressive therapy may be necessary; however, children with SCIDA who were treated with intensive immunosuppressive and myeloablative therapy had a poor outcome. PMID:11360109

  12. TB in Children in the United States

    MedlinePlus

    ... Statistics Related Links TB in Children in the United States TB disease in children under 15 years ... BCG vaccine is not generally used in the United States, because of the low risk of infection ...

  13. Health system barriers to implementation of collaborative TB and HIV activities including prevention of mother to child transmission in South Africa.

    PubMed

    Uwimana, J; Jackson, D; Hausler, H; Zarowsky, C

    2012-05-01

    In South Africa, the control of TB and HIV co-infection remains a major challenge despite the availability of international and national guidelines for integration of TB and HIV services. This study was undertaken in KwaZulu-Natal, one of the provinces most affected by both TB and HIV, to identify and understand managers' and community care workers' (CCWs) perceptions of health systems barriers related to the implementation of collaborative TB/HIV activities, including prevention of mother to child transmission of HIV (PMTCT). We conducted 29 in-depth interviews with health managers at provincial, district and facility level and with managers of NGOs involved in TB and HIV care, as well as six focus group discussions with CCWs. Thematic analysis of transcripts revealed a convergence of perspectives on the process and the level of the implementation of policy directives on collaborative TB and HIV activities across all categories of respondents (i.e. province-, district-, facility- and community-based organizations). The majority of participants felt that the implementation of the policy was insufficiently consultative and that leadership and political will were lacking. The predominant themes related to health systems barriers include challenges related to structure and organisational culture; management, planning and power issues; unequal financing; and human resource capacity and regulatory problems notably relating to scope of practice of nurses and CCWs. Accelerated implementation of collaborative TB/HIV activities including PMTCT will require political will and leadership to address these health systems barriers. PMID:22394016

  14. Pechini synthesis of lanthanide (Eu3+/Tb3+or Dy3+) ions activated BaGd2O4 nanostructured phosphors: an approach for tunable emissions.

    PubMed

    Seeta Rama Raju, G; Pavitra, E; Yu, Jae Su

    2014-09-14

    Trivalent lanthanide (Eu(3+), Tb(3+) and Dy(3+)) ions activated tunable color emitting BaGd2O4 (BG) phosphors were synthesized by a facile Pechini-type sol-gel process. The X-ray diffraction pattern confirmed the orthorhombic phase after annealing at 1300 °C for 5 h. Morphological studies were performed based on the analysis of transmission electron microscopy images, which showed needle type nanorods. The BG phosphor exhibited good photoluminescence (PL) properties in the respective regions when doped with Eu(3+), Tb(3+) and Dy(3+) ions. The Eu(3+) co-activated BG:Tb(3+) phosphor yielded tunable emissions including tri-band established white light emission based on the co-activator concentration and excitation wavelength. The energy transfer from Tb(3+) to Eu(3+) ions was controlled by selecting a suitable excitation wavelength and the decay measurements were carried out for analyzing the energy transfer efficiency. The cathodoluminescence properties of these phosphors were almost similar to PL properties when doped with individual Eu(3+), Tb(3+), and Dy(3+) ions, but were different when co-doped with Eu(3+)/Tb(3+) or Eu(3+)/Dy(3+) ions. In the case of Eu(3+)/Tb(3+) doped samples, the energy transfer process occurred unlike the PL channel. The calculated Commission International de l'Eclairage chromaticity coordinates of individual ion doped BG phosphors confirmed red, green, and white emissions and for co-doped samples they showed tunable emission. PMID:25052006

  15. Comparison between Three Promising ß-emitting Radionuclides, 67Cu, 47Sc and 161Tb, with Emphasis on Doses Delivered to Minimal Residual Disease

    PubMed Central

    Champion, Christophe; Quinto, Michele A.; Morgat, Clément; Zanotti-Fregonara, Paolo; Hindié, Elif

    2016-01-01

    PURPOSE: Radionuclide therapy is increasingly seen as a promising option to target minimal residual disease. Copper-67, scandium-47 and terbium-161 have a medium-energy β- emission which is similar to that of lutetium-177, but offer the advantage of having diagnostic partner isotopes suitable for pretreatment imaging. The aim of this study was to compare the efficacy of 67Cu, 47Sc and 161Tb to irradiate small tumors. METHODS: The absorbed dose deriving from a homogeneous distribution of 67Cu, 47Sc or 161Tb in water-density spheres was calculated with the Monte Carlo code CELLDOSE. The diameters of the spheres ranged from 5 mm to 10 µm, thus simulating micrometastases or single tumor cells. All electron emissions, including β- spectra, Auger and conversion electrons were taken into account. Because these radionuclides differ in electron energy per decay, the simulations were run assuming that 1 MeV was released per µm3, which would result in a dose of 160 Gy if totally absorbed. RESULTS: The absorbed dose was similar for the three radionuclides in the 5-mm sphere (146-149 Gy), but decreased differently in smaller spheres. In particular, 161Tb delivered higher doses compared to the other radionuclides. For instance, in the 100-µm sphere, the absorbed dose was 24.1 Gy with 67Cu, 14.8 Gy with 47Sc and 44.5 Gy with 161Tb. Auger and conversion electrons accounted for 71% of 161Tb dose. The largest dose differences were found in cell-sized spheres. In the 10-µm sphere, the dose delivered by 161Tb was 4.1 times higher than that from 67Cu and 8.1 times that from 47Sc. CONCLUSION: 161Tb can effectively irradiate small tumors thanks to its decay spectrum that combines medium-energy β- emission and low-energy conversion and Auger electrons. Therefore 161Tb might be a better candidate than 67Cu and 47Sc for treating minimal residual disease in a clinical setting. PMID:27446495

  16. Transglutaminase activation in neurodegenerative diseases

    PubMed Central

    Jeitner, Thomas M; Muma, Nancy A; Battaile, Kevin P; Cooper, Arthur JL

    2009-01-01

    The following review examines the role of calcium in promoting the in vitro and in vivo activation of transglutaminases in neurodegenerative disorders. Diseases such as Alzheimer's disease, Parkinson's disease and Huntington's disease exhibit increased transglutaminase activity and rises in intracellular calcium concentrations, which may be related. The aberrant activation of transglutaminase by calcium is thought to give rise to a variety of pathological moieties in these diseases, and the inhibition has been shown to have therapeutic benefit in animal and cellular models of neurodegeneration. Given the potential clinical relevance of transglutaminase inhibitors, we have also reviewed the recent development of such compounds. PMID:20161049

  17. Testing for TB Infection

    MedlinePlus

    ... Search The CDC Cancel Submit Search The CDC Tuberculosis (TB) Note: Javascript is disabled or is not ... message, please visit this page: About CDC.gov . Tuberculosis Basic TB Facts How TB Spreads Latent TB ...

  18. HIV-Associated TB Syndemic: A Growing Clinical Challenge Worldwide.

    PubMed

    Montales, Maria Theresa; Chaudhury, Arun; Beebe, Alexandria; Patil, Sowmya; Patil, Naveen

    2015-01-01

    The association of tuberculosis (TB) with human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome over the past several years has become an emerging syndemic. Approximately 10% of people living with HIV (PLHIV) with latent TB infection will develop active TB disease each year. In this review, we highlight that this phenomenon is not limited to high endemic regions, such as Afro-Asian nations, but globalization/migration is causing increased case detection even in developed nations, such as the United States. Active screening should be performed for TB in PLHIV. A high degree of clinical suspicion for TB is warranted in PLHIV presenting with fever, cough, and unintentional weight loss. HIV-Mycobacterium tuberculosis (MTB) coinfection is often paucibacillary, precluding diagnosis by conventional diagnostics and/or smear microscopy/culture. Improved detection of pulmonary and extrapulmonary TB is now possible by incorporation of the GeneXPERT MTB/RIF assay (Cepheid Inc., Sunnyvale, CA, USA). The World Health Organization recommends instituting immediate therapy for MTB, in conjunction with ongoing or newly introduced anti-retroviral therapy. Vigilance is required to detect drug-induced organ injuries, and early-treatment-induced immune reconstitution inflammatory syndrome. Collaborating MTB and HIV activities in concentrated HIV epidemic settings should become a high public health priority. PMID:26779470

  19. HIV-Associated TB Syndemic: A Growing Clinical Challenge Worldwide

    PubMed Central

    Montales, Maria Theresa; Chaudhury, Arun; Beebe, Alexandria; Patil, Sowmya; Patil, Naveen

    2015-01-01

    The association of tuberculosis (TB) with human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome over the past several years has become an emerging syndemic. Approximately 10% of people living with HIV (PLHIV) with latent TB infection will develop active TB disease each year. In this review, we highlight that this phenomenon is not limited to high endemic regions, such as Afro-Asian nations, but globalization/migration is causing increased case detection even in developed nations, such as the United States. Active screening should be performed for TB in PLHIV. A high degree of clinical suspicion for TB is warranted in PLHIV presenting with fever, cough, and unintentional weight loss. HIV–Mycobacterium tuberculosis (MTB) coinfection is often paucibacillary, precluding diagnosis by conventional diagnostics and/or smear microscopy/culture. Improved detection of pulmonary and extrapulmonary TB is now possible by incorporation of the GeneXPERT MTB/RIF assay (Cepheid Inc., Sunnyvale, CA, USA). The World Health Organization recommends instituting immediate therapy for MTB, in conjunction with ongoing or newly introduced anti-retroviral therapy. Vigilance is required to detect drug-induced organ injuries, and early-treatment-induced immune reconstitution inflammatory syndrome. Collaborating MTB and HIV activities in concentrated HIV epidemic settings should become a high public health priority. PMID:26779470

  20. Towards new TB vaccines: What are the challenges?

    PubMed

    Dockrell, Hazel M

    2016-06-01

    New and effective tuberculosis (TB) vaccines are urgently needed to control pulmonary TB, and in particular to prevent the spread of drug-resistant strains of Mycobacterium tuberculosis. These drug-resistant strains can range from those resistant to first-line drugs to those that are almost impossible to treat. To develop new and effective vaccines for HIV and malaria has been difficult and it is proving to be just as challenging for TB. TB is a complicated disease with a spectrum from apparently controlled latent infection to active clinical disease and so different types of preventive or post-exposure vaccine may be needed. Identifying the most promising vaccine candidates to move into clinical trials is difficult, as we lack biomarker signatures that can predict protective efficacy. There is a risk that the failure of the MVA-85A vaccine to show efficacy when given to previously BCG-vaccinated South African infants will impact on the resources available for the development and trials of other candidate TB vaccines. Continued support for the development of new TB vaccines should remain a priority as an effective vaccine would bring huge public health benefits. PMID:26960944

  1. Review of policy and status of implementation of collaborative HIV-TB activities in 23 high-burden countries.

    PubMed

    Gupta, S; Granich, R; Date, A; Lepere, P; Hersh, B; Gouws, E; Samb, B

    2014-10-01

    Issuance of national policy guidance is a critical step to ensure quality HIV-TB (human immunodeficiency virus-tuberculosis) coordination and programme implementation. From the database of the Joint United Nations Programme on HIV/AIDS (UNAIDS), we reviewed 62 national HIV and TB guidelines from 23 high-burden countries for recommendations on HIV testing for TB patients, criteria for initiating antiretroviral therapy (ART) and the Three I's for HIV/TB (isoniazid preventive treatment [IPT], intensified TB case finding and TB infection control). We used UNAIDS country-level programme data to determine the status of implementation of existing guidance. Of the 23 countries representing 89% of the global HIV-TB burden, Brazil recommends ART irrespective of CD4 count for all people living with HIV, and four (17%) countries recommend ART at the World Health Organization (WHO) 2013 guidelines level of CD4 count ⩿500 cells/mm(3) for asymptomatic persons. Nineteen (83%) countries are consistent with WHO 2013 guidelines and recommend ART for HIV-positive TB patients irrespective of CD4 count. IPT is recommended by 16 (70%) countries, representing 67% of the HIV-TB burden; 12 recommend symptom-based screening alone for IPT initiation. Guidelines from 15 (65%) countries with 79% of the world's HIV-TB burden include recommendations on HIV testing and counselling for TB patients. Although uptake of ART, HIV testing for TB patients, TB screening for people living with HIV and IPT have increased significantly, progress is still limited in many countries. There is considerable variance in the timing and content of national policies compared with WHO guidelines. Missed opportunities to implement new scientific evidence and delayed adaptation of existing WHO guidance remains a key challenge for many countries. PMID:25216827

  2. Multicolored, Tb³⁺-Based Antibody-Free Detection of Multiple Tyrosine Kinase Activities.

    PubMed

    Lipchik, Andrew M; Perez, Minervo; Cui, Wei; Parker, Laurie L

    2015-08-01

    Kinase signaling is a major mechanism driving many cancers. While many inhibitors have been developed and are employed in the clinic, resistance due to crosstalk and pathway reprogramming is an emerging problem. High-throughput assays to detect multiple pathway kinases simultaneously could better model these complex relationships and enable drug development to combat this type of resistance. We developed a strategy to take advantage of time-resolved luminescence of Tb(3+)-chelated phosphotyrosine-containing peptides, which facilitated efficient energy transfer to small molecule fluorophores conjugated to the peptides to produce orthogonally colored biosensors for two different kinases. This enabled multiplexed detection with high signal-to-noise in a high-throughput-compatible format. This proof-of-concept study provides a platform that could be applied to other lanthanide metal and fluorophore combinations to achieve even greater multiplexing without the need for phosphospecific antibodies. PMID:26207839

  3. Systematic review on tuberculosis transmission on aircraft and update of the European Centre for Disease Prevention and Control risk assessment guidelines for tuberculosis transmitted on aircraft (RAGIDA-TB).

    PubMed

    Kotila, Saara M; Payne Hallström, Lara; Jansen, Niesje; Helbling, Peter; Abubakar, Ibrahim

    2016-01-01

    As a setting for potential tuberculosis (TB) transmission and contact tracing, aircraft pose specific challenges. Evidence-based guidelines are needed to support the related-risk assessment and contact-tracing efforts. In this study evidence of TB transmission on aircraft was identified to update the Risk Assessment Guidelines for TB Transmitted on Aircraft (RAGIDA-TB) of the European Centre for Disease Prevention and Control (ECDC). Electronic searches were undertaken from Medline (Pubmed), Embase and Cochrane Library until 19 July 2013. Eligible records were identified by a two-stage screening process and data on flight and index case characteristics as well as contact tracing strategies extracted. The systematic literature review retrieved 21 records. Ten of these records were available only after the previous version of the RAGIDA guidelines (2009) and World Health Organization guidelines on TB and air travel (2008) were published. Seven of the 21 records presented some evidence of possible in-flight transmission, but only one record provided substantial evidence of TB transmission on an aircraft. The data indicate that overall risk of TB transmission on aircraft is very low. The updated ECDC guidelines for TB transmission on aircraft have global implications due to inevitable need for international collaboration in contract tracing and risk assessment. PMID:26848520

  4. High Incidence of Tuberculosis Infection in Rheumatic Diseases and Impact for Chemoprophylactic Prevention of Tuberculosis Activation during Biologics Therapy

    PubMed Central

    Bai, Fengmin; Zhang, Shu; Jiang, Ting; Shen, Jie; Zhu, Qi; Yue, Tao; Shao, Lingyun; Gao, Yan; Feng, Yun; Weng, Xinhua; Zou, Hejian; Zhang, Ying

    2013-01-01

    We conducted a long-term follow-up study in patients with rheumatic diseases who were candidates for biologics treatment to evaluate the effects of biologic agents on the risk of tuberculosis infection and the effect of prophylactic treatment on tuberculosis activation. One hundred one patients with rheumatic diseases who were candidates for biologics treatment were recruited, and 57 healthy subjects were recruited as controls. Tuberculin skin test (TST) and the T-SPOT.TB test were performed for all subjects at baseline. Follow-up testing by the T-SPOT.TB assay was performed every 6 months in patients with rheumatic diseases and at 2 years of recruitment in the healthy controls. In patients with rheumatic diseases and healthy controls, the TST-positive (induration, ≥10 mm) rates were 37.6% (38/101) and 34.0% (18/53), respectively (P > 0.05), while the T-SPOT.TB-positive rates were 46.5% (47/101) and 21.1 (12/57), respectively (P = 0.0019). Fifty-two patients were followed up at month 6 with a T-SPOT.TB-positive rate of 40.4%, and 49 were followed up for ≥12 months with a T-SPOT.TB-positive rate of 36.7%, with no significant difference in the positive rate at different time points including baseline (P > 0.05). Long-term follow-up revealed that conversion to T-SPOT.TB positivity occurred only in the biologics treatment group, with a positive conversion rate of 11.2% (4/38). Most importantly, no latent tuberculosis developed into active tuberculosis during follow-up with T-SPOT.TB screening and preemptive treatment with isoniazid. Biologics treatment appears to increase the risk of tuberculosis infection. However, tuberculosis activation could be prevented by preemptive isoniazid treatment in patients with latent tuberculosis infection while receiving biologics therapy. PMID:23554465

  5. Tricks to translating TB transcriptomics.

    PubMed

    Deffur, Armin; Wilkinson, Robert J; Coussens, Anna K

    2015-05-01

    Transcriptomics and other high-throughput methods are increasingly applied to questions relating to tuberculosis (TB) pathogenesis. Whole blood transcriptomics has repeatedly been applied to define correlates of TB risk and has produced new insight into the late stage of disease pathogenesis. In a novel approach, authors of a recently published study in Science Translational Medicine applied complex data analysis of existing TB transcriptomic datasets, and in vitro models, in an attempt to identify correlates of protection in TB, which are crucially required for the development of novel TB diagnostics and therapeutics to halt this global epidemic. Utilizing latent TB infection (LTBI) as a surrogate of protection, they identified IL-32 as a mediator of interferon gamma (IFNγ)-vitamin D dependent antimicrobial immunity and a marker of LTBI. Here, we provide a review of all TB whole-blood transcriptomic studies to date in the context of identifying correlates of protection, discuss potential pitfalls of combining complex analyses originating from such studies, the importance of detailed metadata to interpret differential patient classification algorithms, the effect of differing circulating cell populations between patient groups on the interpretation of resulting biomarkers and we decipher weighted gene co-expression network analysis (WGCNA), a recently developed systems biology tool which holds promise of identifying novel pathway interactions in disease pathogenesis. In conclusion, we propose the development of an integrated OMICS platform and open access to detailed metadata, in order for the TB research community to leverage the vast array of OMICS data being generated with the aim of unraveling the holy grail of TB research: correlates of protection. PMID:26046091

  6. TB drug development: immunology at the table

    PubMed Central

    Nathan, Carl; Barry, Clifton E.

    2014-01-01

    Summary Our understanding of the host-pathogen relationship in tuberculosis can help guide tuberculosis (TB) drug discovery in at least two ways. First, the recognition that host immunopathology affects lesional TB drug distribution means that pharmacokinetic evaluation of drug candidates needs to move beyond measurements of drug levels in blood, whole lungs or alveolar epithelial lining fluid to include measurements in specific types of lesions. Second, by restricting the replication of M. tuberculosis (Mtb) subpopulations in latent TB infection and in active disease, the host immune response puts Mtb into a state associated with phenotypic tolerance to TB drugs selected for their activity against replicating Mtb. This has spurred a major effort to conduct high throughput screens in vitro for compounds that can kill Mtb when it is replicating slowly if at all. Each condition used in vitro to slow Mtb’s replication and thereby model the phenotypically drug-tolerant state has advantages and disadvantages. Lead candidates emerging from such in vitro studies face daunting challenges in the design of proof-of-concept studies in animal models. Moreover, some non-replicating subpopulations of Mtb fail to resume replication when plated on agar, although their viability is demonstrable by other means. There is as yet no widely replicated assay in which to screen compounds for their ability to kill this ‘viable but non-culturable’ subpopulation. Despite these hurdles, drugs that can kill slowly replicating or non-replicating Mtb may offer our best hope for treatment-shortening combination chemotherapy of TB. PMID:25703568

  7. TB vaccine development and the End TB Strategy: importance and current status

    PubMed Central

    Fletcher, Helen A.; Schrager, Lewis

    2016-01-01

    TB is now the leading, global cause of death due to a single infectious microbe. To achieve the End TB vision of reducing TB by 90% by 2035 we will need new interventions. The objectives of this manuscript are to summarize the status of the clinical TB vaccine pipeline; to assess the challenges facing the TB development field; and to discuss some of the key strategies being embraced by the field to overcome these challenges. Currently, 8 of the 13 vaccines in clinical development are subunit vaccines; 6 of these contain or express either Ag85A or Ag85B proteins. A major challenge to TB vaccine development is the lack of diversity in both the antigens included in TB vaccines, and the immune responses elicited by TB vaccine candidates. Both will need to be expanded to maximise the potential for developing a successful candidate by 2025. Current research efforts are focused on broadening both antigen selection and the range of vaccine-mediated immune responses. Previous and ongoing TB vaccine efficacy trials have built capacity, generated high quality data on TB incidence and prevalence, and provided insight into immune correlates of risk of TB disease. These gains will enable the design of better TB vaccines and, importantly, move these vaccines into efficacy trials more rapidly and at a lower cost than was possible for previous TB vaccine candidates. PMID:27076508

  8. TB vaccine development and the End TB Strategy: importance and current status.

    PubMed

    Fletcher, Helen A; Schrager, Lewis

    2016-04-01

    TB is now the leading, global cause of death due to a single infectious microbe. To achieve the End TB vision of reducing TB by 90% by 2035 we will need new interventions. The objectives of this manuscript are to summarize the status of the clinical TB vaccine pipeline; to assess the challenges facing the TB development field; and to discuss some of the key strategies being embraced by the field to overcome these challenges. Currently, 8 of the 13 vaccines in clinical development are subunit vaccines; 6 of these contain or express either Ag85A or Ag85B proteins. A major challenge to TB vaccine development is the lack of diversity in both the antigens included in TB vaccines, and the immune responses elicited by TB vaccine candidates. Both will need to be expanded to maximise the potential for developing a successful candidate by 2025. Current research efforts are focused on broadening both antigen selection and the range of vaccine-mediated immune responses. Previous and ongoing TB vaccine efficacy trials have built capacity, generated high quality data on TB incidence and prevalence, and provided insight into immune correlates of risk of TB disease. These gains will enable the design of better TB vaccines and, importantly, move these vaccines into efficacy trials more rapidly and at a lower cost than was possible for previous TB vaccine candidates. PMID:27076508

  9. TB-HIV co-infection: a catastrophic comradeship.

    PubMed

    Narendran, G; Swaminathan, S

    2016-04-01

    The symbiotic association of tuberculosis (TB) and HIV poses a challenge to human survival. HIV complicates every aspect of TB including presentation, diagnosis and treatment. HIV-TB patients encounter unique problems like drug-drug interactions, cumulative toxicity, immune reconstitution inflammatory syndrome (IRIS), lower plasma drug levels and emergence of drug resistance during treatment despite adherence. TB may also be overdiagnosed in HIV due to a number of diseases that closely resemble TB. Notable among them are non-tuberculous mycobacteria, Pneumocystis Jirovecii and Nocardia. Even though diagnostic procedures have improved over the years, patients in developing countries usually seek health care at later stage of the disease. Research data ascertains the duration of therapy for TB to be 6 months with rifampicin and isoniazid, reinforced with ethambutol and pyrazinamide in the first 2 months. The schedule of therapy is still debatable with daily regimens being preferred in the context of HIV. Many reasons exist for persistence of Mycobacterium Tuberculosis (M.TB) in sputum, or delayed-clearance of TB from sputum smears in HIV, apart from emergence of drug resistance and non-compliance. Acquired rifampicin resistance (ARR) is a unique phenomenon complicating HIV-associated TB when an intermittent regimen of antituberculosis therapy (ATT) is used without timely initiation of highly active antiretroviral therapy (HAART), especially in patients harbouring isoniazid-resistant strains Immune restoration is often incomplete ('swiss cheese' pattern) even with effective HAART if not started early. Immune reconstitution inflammatory syndrome (IRIS) is the paradoxical worsening of the patient's condition often with radiological deterioration, due to an enhanced immune response with HAART. IRIS occurs despite an effective virological suppression and a favourable response to ATT. The incidence of IRIS in HIV has reached up to 54%, requiring utilization of experts

  10. Bioassay-Guided Isolation and Structural Modification of the Anti-TB Resorcinols from Ardisia gigantifolia.

    PubMed

    Guan, Yi-Fu; Song, Xun; Qiu, Ming-Hua; Luo, Shi-Hong; Wang, Bao-Jie; Van Hung, Nguyen; Cuong, Nguyen M; Soejarto, Djaja Doel; Fong, Harry H S; Franzblau, Scott G; Li, Sheng-Hong; He, Zhen-Dan; Zhang, Hong-Jie

    2016-08-01

    Tuberculosis (TB) is a highly contagious disease mainly caused by Mycobacterium tuberculosis H37 RV . Antitubercular (anti-TB) bioassay-guided isolation of the CHCl3 extract of the leaves and stems of the medicinal plant Ardisia gigantifolia led to the isolation of two anti-TB 5-alkylresorcinols, 5-(8Z-heptadecenyl) resorcinol (1) and 5-(8Z-pentadecenyl) resorcinol (2). We further synthesized 15 derivatives based on these two natural products. These compounds (natural and synthetic) were evaluated for their anti-TB activity against Mycobacterium tuberculosis H37 RV . Resorcinols 1 and 2 exhibited anti-TB activity with MIC values at 34.4 and 79.2 μm in MABA assay, respectively, and 91.7 and 168.3 μm in LORA assay, respectively. Among these derivatives, compound 8 was found to show improved anti-TB activity than its synthetic precursor (2) with MIC values at 42.0 μm in MABA assay and 100.2 μm in LORA assay. The active compounds should be regarded as new hits for further study as a novel class of anti-TB agents. The distinct structure-activity correlations of the parent compound were elucidated based on these derivatives. PMID:26992112

  11. Hydrothermal fabrication of multi-functional Eu3+ and Tb3+ co-doped BiPO4: Photocatalytic activity and tunable luminescence properties

    NASA Astrophysics Data System (ADS)

    Wang, Yao; Huang, Hongwei; Quan, Chaoming; Tian, Na; Zhang, Yihe

    2016-01-01

    We demonstrated for first time the tunable photoluminescence (PL) properties and photocatalytic activity of the Tb3+ and Eu3+ co-doped BiPO4 assemblies. They are fabricated via a facile hydrothermal approach. Through co-doping of Eu3+ and Tb3+ ions and changing the doping ratio, the emission color of the co-doped BiPO4 phosphors can be tuned precisely from green to yellow and red. Meanwhile, a very efficient energy transfer from Tb3+ to Eu3+ can be observed. Fascinatingly, a warmwhite color has been realized in the co-doped sample by tuning the ratio of Tb3+/Eu3+ to a certain value as displayed in the CIE chromaticity diagram. The doped BiPO4 samples also exhibit significantly enhanced photocatalytic activity compared to the pristine BiPO4 pertaining to Rhodamine (RhB) degradation under UV light. This enhancement should be attributed to the trapping electron effect induced by ion doping that endows BiPO4 with high separation of photoinduced electron-hole pairs, thereby greatly promoting the photocatalytic reactivity. It was corroborated by the electrochemical impedance spectra (EIS). Moreover, the crystal structure, microstructure and optical properties of as-prepared samples were investigated in details.

  12. The Prevention and Control of HIV/AIDS, TB and Vector-borne Diseases in Informal Settlements: Challenges, Opportunities and Insights

    PubMed Central

    Mercado, Susan P.; Becker, Daniel; Edmundo, Katia; Mugisha, Frederick

    2007-01-01

    Today’s urban settings are redefining the field of public health. The complex dynamics of cities, with their concentration of the poorest and most vulnerable (even within the developed world) pose an urgent challenge to the health community. While retaining fidelity to the core principles of disease prevention and control, major adjustments are needed in the systems and approaches to effectively reach those with the greatest health risks (and the least resilience) within today’s urban environment. This is particularly relevant to infectious disease prevention and control. Controlling and preventing HIV/AIDS, tuberculosis and vector-borne diseases like malaria are among the key global health priorities, particularly in poor urban settings. The challenge in slums and informal settlements is not in identifying which interventions work, but rather in ensuring that informal settlers: (1) are captured in health statistics that define disease epidemiology and (2) are provided opportunities equal to the rest of the population to access proven interventions. Growing international attention to the plight of slum dwellers and informal settlers, embodied by Goal 7 Target 11 of the Millennium Development Goals, and the considerable resources being mobilized by the Global Fund to fight AIDS, TB and malaria, among others, provide an unprecedented potential opportunity for countries to seriously address the structural and intermediate determinants of poor health in these settings. Viewed within the framework of the “social determinants of disease” model, preventing and controlling HIV/AIDS, TB and vector-borne diseases requires broad and integrated interventions that address the underlying causes of inequity that result in poorer health and worse health outcomes for the urban poor. We examine insights into effective approaches to disease control and prevention within poor urban settings under a comprehensive social development agenda. PMID:17431796

  13. Enhanced visible light photocatalytic activity of ZnO doped with down-conversion NaSrBO3:Tb(3+) phosphors.

    PubMed

    Liu, Xinjuan; Wang, Xiaojun; Li, Huili; Li, Jinliang; Pan, Likun; Zhang, Jing; Min, Guoquan; Sun, Zhuo; Sun, Changqing

    2015-01-01

    ZnO-NaSrBO3:Tb(3+) (ZNT) composites were successfully synthesized via microwave-assisted reaction of the ZnO precursor with a NaSrBO3:Tb(3+) suspension using a microwave synthesis system. The morphology, structure and photocatalytic performance in the degradation of methylene blue (MB) were characterized by scanning electron microscopy, transmission electron microscopy, X-ray diffraction, UV-vis absorption spectroscopy, fluorescence spectrophotometry and electrochemical impedance spectroscopy, respectively. The results show that the ZNT composites exhibit enhanced photocatalytic activity in the degradation of MB with a maximum degradation rate of 97% under visible light irradiation compared with pure ZnO (12%), which is ascribed to the increased light absorption and the reduction of photoelectron-hole pair recombination in ZnO with the introduction of NaSrBO3:Tb(3+), as well as the light down-converting effect of NaSrBO3:Tb(3+), which facilitates the self-sensitized degradation of MB. PMID:25366251

  14. Drug Resistance Pattern of Mycobacterium tuberculosis Isolates From Patients Referred to TB Reference Laboratory in Ahvaz

    PubMed Central

    Badie, Fereshteh; Arshadi, Maniya; Mohsenpoor, Maryam; Gharibvand, Soodabeh S.

    2015-01-01

    Objectives Tuberculosis remains one of the top three infectious disease killers. The prevalence of multidrug-resistant tuberculosis (MDR-TB) has increased substantially in the past 20 years. When drug resistance is not detected, MDR-TB patients cannot access life-saving treatment; this puts their communities at risk of ongoing MDR-TB transmission. We aimed to determine the patterns of resistance to antituberculosis drugs among Mycobacterium tuberculosis isolates from Khuzestan province in Iran. Methods A total of 850 clinical specimens from patients suspected of active TB were cultured in 2015. Drug susceptibility testing to the first line antiTB drugs for culture positive MTB was performed on Lowenstein–Jensen medium using the proportion method. Results Of 850 cultured specimens, 272 (32%) were culture positive for mycobacteria. Of 64 MTB isolates that were analyzed by the proportion method, 62 (96.8%) were pan-susceptible and two (3.1%) were MDR. Conclusion An important way to prevent the emergence of MDR and XDR TB, and the principles of full implementation of the strategy is directly observed treatment, short-course (DOTS). The efficient diagnosis and timely treatment of MDR-TB patients can prevent disease transmission, reduce the risk of drug resistance developing, and avoid further lung damage. PMID:26981340

  15. The Role of Activator-Activator Interactions In Reducing in Low-Voltage-Cathodoluminescence Efficiency in Eu and Tb Doped Phosphors

    SciTech Connect

    SEAGER,CARLETON H.; TALLANT,DAVID R.

    1999-12-08

    High resolution measurements of spectrally resolved cathodoluminescence (CL) decay have been made in several commercial and experimental phosphors doped with Eu and Tb at beam energies ranging from 0.8 to 4 keV. CL emission from the lowest two excited states of both rare earth activators was compared to the decay of photoluminescence (PL) after pulsed laser excitation. We find that, at long times after the cessation of electron excitation, the CL decay rates are comparable to those measured in PL, at short times, the decay process is considerably faster and has a noticeable dependence on the energy of the electron beam. These beam energy effects are largest for the higher excited states and for phosphors with larger activator concentrations. Measurements of the experimental phosphors over a range of activator fractions from 0.1 to 0.002 show that the beam energy dependence of the steady-state CL efficiency is larger for higher excited states and weakens as the activator concentration is reduced. The latter effect is strongest for Y{sub 2}SiO{sub 5}:Tb, but also quite evident in Y{sub 2}O{sub 3}:Eu. We suggest that the electron beam dependence of both the decay lifetimes and the steady state CL efficiency may be due to interaction of nearby excited states which occurs as a result of the large energy deposition rate for low energy electrons. This picture-for non-radiative quenching of rare earth emission is an excited state analog of the well-known (ground state-excited state) concentration quenching mechanism.

  16. Estimating the cost of TB and its social impact on TB patients and their households

    PubMed Central

    Onazi, O.; Gidado, M.; Onazi, M.; Daniel, O.; Kuye, J.; Obasanya, O.; Odusote, T.; Gande, S.

    2015-01-01

    Illness often poses a significant financial burden on individuals and their households, and tuberculosis (TB) is no exception. Although TB treatment is free in Nigeria, patients are likely to incur costs due to multiple visits during treatment. The purpose of this study was 1) to examine the health-seeking behaviour of TB patients and the costs borne by TB patients in Nigeria, and 2) to assess the social impact of TB disease on TB patients and their families/households. Of 260 TB patients surveyed, the majority (74.7%) were aged between 20 and 49 years. TB patients expended an average of US$52.02 (N = 8323.58, at the rate of US$1 = N = 160) per person on all visits associated with diagnosis and receipt of diagnostic test results. Overall, households experienced a shortfall of about US$57.30 (N = 9174.72) or 24.9% of income loss due to TB illness. Further analysis revealed that 9.7% of TB patients relied on children of school age or below to finance the costs of TB illness. PMID:26400384

  17. Photoluminescence, energy transfer and tunable color of Ce(3+), Tb(3+) and Eu(2+) activated oxynitride phosphors with high brightness.

    PubMed

    Lü, Wei; Huo, Jiansheng; Feng, Yang; Zhao, Shuang; You, Hongpeng

    2016-06-21

    New tuneable light-emitting Ca3Al8Si4O17N4:Ce(3+)/Tb(3+)/Eu(2+) oxynitride phosphors with high brightness have been prepared. When doped with trivalent cerium or divalent europium they present blue luminescence under UV excitation. The energy transfer from Ce(3+) to Tb(3+) and Ce(3+) to Eu(2+) ions is deduced from the spectral overlap between Ce(3+) emission and Tb(3+)/Eu(2+) excitation spectra. The energy-transfer efficiencies and corresponding mechanisms are discussed in detail, and the mechanisms of energy transfer from the Ce(3+) to Tb(3+) and Ce(3+) to Eu(2+) ions are demonstrated to be a dipole-quadrupole and dipole-dipole mechanism, respectively, by the Inokuti-Hirayama model. The International Commission on Illumination value of color tuneable emission as well as luminescence quantum yield (23.8-80.6%) can be tuned by controlling the content of Ce(3+), Tb(3+) and Eu(2+). All results suggest that they are suitable for UV light-emitting diode excitation. PMID:27226201

  18. Is TB in Your Curriculum?

    ERIC Educational Resources Information Center

    Kerr, Joanne; Elwell, Jack

    2002-01-01

    Points out the importance of effective health education to fight against tuberculosis (TB) which is the number one fatal infectious disease around the world. Describes a science curriculum on tuberculosis that includes information on the facts about tuberculosis, a forum on tuberculosis, and evaluation. (Contains 17 references.) (YDS)

  19. Why healthcare workers are sick of TB.

    PubMed

    von Delft, Arne; Dramowski, Angela; Khosa, Celso; Kotze, Koot; Lederer, Philip; Mosidi, Thato; Peters, Jurgens A; Smith, Jonathan; van der Westhuizen, Helene-Mari; von Delft, Dalene; Willems, Bart; Bates, Matthew; Craig, Gill; Maeurer, Markus; Marais, Ben J; Mwaba, Peter; Nunes, Elizabete A; Nyirenda, Thomas; Oliver, Matt; Zumla, Alimuddin

    2015-03-01

    Dr Thato Mosidi never expected to be diagnosed with tuberculosis (TB), despite widely prevalent exposure and very limited infection control measures. The life-threatening diagnosis of primary extensively drug-resistant TB (XDR-TB) came as an even greater shock. The inconvenient truth is that, rather than being protected, Dr Mosidi and thousands of her healthcare colleagues are at an increased risk of TB and especially drug-resistant TB. In this viewpoint paper we debunk the widely held false belief that healthcare workers are somehow immune to TB disease (TB-proof) and explore some of the key factors contributing to the pervasive stigmatization and subsequent non-disclosure of occupational TB. Our front-line workers are some of the first to suffer the consequences of a progressively more resistant and fatal TB epidemic, and urgent interventions are needed to ensure the safety and continued availability of these precious healthcare resources. These include the rapid development and scale-up of improved diagnostic and treatment options, strengthened infection control measures, and focused interventions to tackle stigma and discrimination in all its forms. We call our colleagues to action to protect themselves and those they care for. PMID:25809771

  20. [Spanish Society for Pediatric Infectious Diseases guidelines on tuberculosis in pregnant women and neonates (i): Epidemiology and diagnosis. Congenital tuberculosis].

    PubMed

    Baquero-Artigao, F; Mellado Peña, M J; Del Rosal Rabes, T; Noguera Julián, A; Goncé Mellgren, A; de la Calle Fernández-Miranda, M; Navarro Gómez, M L

    2015-10-01

    Tuberculosis (TB) screening in pregnancy using tuberculin skin test (TST) is recommended in case of symptoms of TB disease, close contact with a patient with infectious TB, or high risk of developing active disease. The new interferon gamma release assay (IGRA) tests are recommended in BCG-vaccinated pregnant women with positive TST and no known risk factors for TB, and in those immunocompromised, with clinical suspicion of TB but negative TST. TB diagnosis is difficult due to the non-specific symptoms, the increased frequency of extrapulmonary disease, the delay in radiological examinations, and the high rate of tuberculin anergy. Neonatal TB can be acquired in utero (congenital TB), or through airborne transmission after delivery (postnatal TB). Congenital TB is extremely rare and does not cause fetal malformations. It may be evident at birth, although it usually presents after the second week of life. In newborns with no family history of TB, the disease should be considered in cases of miliary pneumonia, hepatosplenomegaly with focal lesions, or lymphocytic meningitis with hypoglycorrhachia, especially in those born to immigrants from high TB-burden countries. TST is usually negative, and IGRAs have lower sensitivity than in older children. However, the yield of acid-fast smear and culture is higher, mostly in congenital TB. Molecular diagnosis techniques enable early diagnosis and detection of drug resistance mutations. There is a substantial risk of disseminated disease and death. PMID:25754313

  1. Elevated serum 25-hydroxy (OH) vitamin D levels are associated with risk of TB progression in Gambian adults

    PubMed Central

    Owolabi, Olumuyiwa; Agbla, Schadrac; Owiafe, Patrick; Donkor, Simon; Togun, Toyin; Sillah, Abdou K.; Ota, Martin O.C.; Sutherland, Jayne S.

    2016-01-01

    Summary Background Vitamin D is essential in the host defence against tuberculosis (TB) as an immune modulator. The aim of this study was to determine the level of 25-hydroxyvitamin D (25 (OH) D) from adult TB index cases before and after treatment and their exposed household contacts (HHC) in The Gambia. Methods Serum from adult index TB cases and their TB-exposed household contacts (HHC) was analysed for 25(OH) D and Vitamin D binding protein (VDBP) concentrations. Tuberculin skin test (TST) status was used as a measure of Mycobacterium tuberculosis (Mtb) infectivity in the HHC. In addition, HHC who later progressed to active TB (incident cases) were assessed alongside non-progressors to determine the influence of 25 (OH) D levels on TB risk. Results Eighty-three TB cases, 46 TST+ and 52 TST− HHC were analysed. Generally levels of 25(OH) D were considered insufficient in all subjects. However, median levels of 25(OH) D and VDBP were significantly higher in TB cases compared to both TST+ and TST− HHC at recruitment and were significantly reduced after TB therapy (p < 0.0001 for all). In addition, levels of serum 25(OH) D at recruitment were significantly higher in TB progressors compared to non-progressors (median (IQR): 25.0(20.8–29.2) in progressors and 20.3 (16.3–24.6) ng/ml in non-progressors; p = 0.007). Conclusion In The Gambia, an equatorial country, 25(OH) D levels are higher in serum of TB progressors and those with active disease compared to latently infected and uninfected subjects. These results contrast to findings in non-equatorial countries. PMID:27156622

  2. A world of cities and the end of TB

    PubMed Central

    Prasad, Amit; Ross, Alex; Rosenberg, Paul; Dye, Christopher

    2016-01-01

    The WHO's End TB Strategy aims to reduce TB deaths by 95% and incidence by 90% between 2015 and 2035. As the world rapidly urbanizes, more people could have access to better infrastructure and services to help combat poverty and infectious diseases, including TB. And yet large numbers of people now live in overcrowded slums, with poor access to urban health services, amplifying the burden of TB. An alignment of the Sustainable Development Goals (SDGs) for health and for urban development provides an opportunity to accelerate the overall decline in infection and disease, and to create cities free of TB. PMID:26884491

  3. A world of cities and the end of TB.

    PubMed

    Prasad, Amit; Ross, Alex; Rosenberg, Paul; Dye, Christopher

    2016-03-01

    The WHO's End TB Strategy aims to reduce TB deaths by 95% and incidence by 90% between 2015 and 2035. As the world rapidly urbanizes, more people could have access to better infrastructure and services to help combat poverty and infectious diseases, including TB. And yet large numbers of people now live in overcrowded slums, with poor access to urban health services, amplifying the burden of TB. An alignment of the Sustainable Development Goals (SDGs) for health and for urban development provides an opportunity to accelerate the overall decline in infection and disease, and to create cities free of TB. PMID:26884491

  4. Questions and Answers about TB

    MedlinePlus

    ... Search The CDC Cancel Submit Search The CDC Tuberculosis (TB) Note: Javascript is disabled or is not ... message, please visit this page: About CDC.gov . Tuberculosis Basic TB Facts How TB Spreads Latent TB ...

  5. HIV/STD/TB PREVENTION NEWS DATABASE

    EPA Science Inventory

    The CDC National Prevention Information Network (NPIN) is the U.S. reference, referral, and distribution service for information on HIV/AIDS, sexually transmitted diseases (STDs), and tuberculosis (TB). NPIN produces, collects, catalogs, processes, stocks, and disseminates materi...

  6. Being active when you have heart disease

    MedlinePlus

    Heart disease - activity ... Getting regular exercise when you have heart disease is important. Exercise can make your heart muscle stronger. It may also help you be more active without chest pain or ...

  7. Latent tuberculosis screening tests and active tuberculosis infection rates in Turkish inflammatory bowel disease patients under anti-tumor necrosis factor therapy

    PubMed Central

    Çekiç, Cem; Aslan, Fatih; Vatansever, Sezgin; Topal, Firdevs; Yüksel, Elif Sarıtaş; Alper, Emrah; Dallı, Ayşe; Ünsal, Belkıs

    2015-01-01

    Background Tumor necrosis factor (TNF)-α inhibitors increase the risk of tuberculosis (TB). The objective of the present study was to determine the rate of active TB infection in inflammatory bowel disease (IBD) patients receiving anti-TNF therapy and to determine the results of their latent TB infection (LTBI) screening tests during the follow up. Methods This is a retrospective observational study of IBD patients receiving anti-TNF therapy. Tuberculin skin test (TST), interferon-γ release assay (IGRA), and chest radiography were used to determine LTBI. Active TB infection rate during anti-TNF treatment was determined. Results Seventy-six IBD patients (25 with ulcerative colitis, 51 with Crohn’s disease; 53 male; mean age 42.0±12.4 years) were included. Forty-four (57.9%) patients received infliximab and 32 (42.1%) adalimumab. Their median duration of anti-TNF therapy was 15 months. Forty-five (59.2%) patients had LTBI and received isoniazid (INH) prophylaxis. During the follow-up period, active TB was identified in 3 (4.7%) patients who were not receiving INH prophylaxis. There was a moderate concordance between the TST and the IGRA (kappa coefficient 0.44, 95% CI 0.24-0.76). Patients with or without immunosuppressive therapy did not differ significantly with respect to TST (P=0.318) and IGRA (P=0.157). Conclusion IBD patients receiving anti-TNF therapy and prophylactic INH have a decreased risk of developing active TB infection. However, despite LTBI screening, the risk of developing active TB infection persists. PMID:25831138

  8. A Mutation in IL4RA Is Associated with the Degree of Pathology in Human TB Patients

    PubMed Central

    Hölscher, Christoph; Heitmann, Lisa; Owusu-Dabo, Ellis; Horstmann, Rolf D.; Meyer, Christian G.; Ehlers, Stefan; Thye, Thorsten

    2016-01-01

    The contribution of interleukin- (IL-) 4 receptor-alpha- (Rα-) dependent events in the pathogenesis of tuberculosis (TB) is controversial. We have recently shown IL-13 overexpression in mice to cause recrudescent Mtb replication and centrally necrotizing granulomas strongly resembling pathology of human TB. A deletion of IL-4Rα completely abrogates TB tissue pathology in these mice. To validate our results in human TB patients, we here determined the association of distinct variants of the IL4, IL13, IL4RA, IL13RA1, and IL13RA2 genes with cavity formation in a large Ghanaian cohort of HIV-negative individuals with newly diagnosed pulmonary TB. In fact, the structural variant of the IL4RA I50V, previously shown to result in enhanced signal transduction, was significantly associated with greater cavity size, and a variant of IL13RA2 was associated with disease in females. To evaluate whether the human-like TB pathology in IL-13-overexpressing mice is specifically mediated through the IL-4Rα subunit, we analyzed IL-13 transgenic mice with a genetic ablation of the IL-4Rα. In these mice, the IL-13-mediated increased susceptibility, human-like pathology of collagen deposition around centrally necrotizing granulomas, and alternative macrophage activation were abolished. Together, our genetic association study in human TB patients further supports the assumption that IL-13/IL-4Rα-dependent mechanisms are involved in mediating tissue pathology of human TB. PMID:26977119

  9. Diagnostic 'omics' for active tuberculosis.

    PubMed

    Haas, Carolin T; Roe, Jennifer K; Pollara, Gabriele; Mehta, Meera; Noursadeghi, Mahdad

    2016-01-01

    The decision to treat active tuberculosis (TB) is dependent on microbiological tests for the organism or evidence of disease compatible with TB in people with a high demographic risk of exposure. The tuberculin skin test and peripheral blood interferon-γ release assays do not distinguish active TB from a cleared or latent infection. Microbiological culture of mycobacteria is slow. Moreover, the sensitivities of culture and microscopy for acid-fast bacilli and nucleic acid detection by PCR are often compromised by difficulty in obtaining samples from the site of disease. Consequently, we need sensitive and rapid tests for easily obtained clinical samples, which can be deployed to assess patients exposed to TB, discriminate TB from other infectious, inflammatory or autoimmune diseases, and to identify subclinical TB in HIV-1 infected patients prior to commencing antiretroviral therapy. We discuss the evaluation of peripheral blood transcriptomics, proteomics and metabolomics to develop the next generation of rapid diagnostics for active TB. We catalogue the studies published to date seeking to discriminate active TB from healthy volunteers, patients with latent infection and those with other diseases. We identify the limitations of these studies and the barriers to their adoption in clinical practice. In so doing, we aim to develop a framework to guide our approach to discovery and development of diagnostic biomarkers for active TB. PMID:27005907

  10. Differential expression of HLA-G and ILT-2 receptor in human tuberculosis: Localized versus disseminated disease.

    PubMed

    Saurabh, Abhinav; Thakral, Deepshi; Mourya, Manish K; Singh, Amar; Mohan, Anant; Bhatnagar, Anuj K; Mitra, Dipendra K; Kanga, Uma

    2016-09-01

    Human leukocyte antigen-G (HLA-G) is an anti-inflammatory and immunosuppressive molecule that can modulate immune cell activation. The role of HLA-G in tuberculosis, an immune-mediated and chronic bacterial disease remains to be elucidated. We investigated the expression profile of soluble and membrane bound HLA-G in pulmonary TB (PTB), TB pleural effusion (TB-PE, localized disease) and Miliary TB (disseminated form). The expression of HLA-G receptor, ILT-2 was also determined on the immune cells. We observed that the plasma sHLA-G levels were significantly increased in Miliary TB than in TB-PE patients. In contrast, immunophenotyping revealed that the percent frequency of CD3(+) T cells expressing HLA-G was significantly reduced in Miliary TB as compared to TB-PE, whereas frequency of CD14(+) monocytes expressing HLA-G was significantly higher in TB-PE patients. Strikingly in the TB-PE cases, comparison of disease site, i.e. pleural effusion with peripheral blood showed increased expression of both soluble and surface HLA-G, whereas ILT-2 expressing cells were reduced at the local disease site. Furthermore, we demonstrated that in TB-PE cases, HLA-G expression on CD3(+) T cells was influenced by broad spectrum MMP inhibitor. Thus, differential expression of HLA-G could potentially be a useful biomarker to distinguish different states of TB disease. PMID:26776460

  11. Cardiovascular Disease and Cancer: Student Awareness Activities.

    ERIC Educational Resources Information Center

    Meyer, James H., Comp.

    Awareness activities pertaining to cancer and cardiovascular disease are presented as a supplement for high school science classes. The exercises can be used to enrich units of study dealing with the circulatory system, the cell, or human diseases. Eight activities deal with the following topics: (1) cardiovascular disease risk factors; (2)…

  12. Measurement of the MACS of {sup 159}Tb(n, γ) at kT=30 keV by Activation

    SciTech Connect

    Praena, J.; Mastinu, P.F.; Pignatari, M.; Quesada, J.M.; Capote, R.; Morilla, Y.

    2014-06-15

    The measurement of the Maxwellian-Averaged Cross-Section (MACS) of the {sup 159}Tb(n, γ) reaction at kT=30 keV by the activation technique is presented. An innovative method for the generation of Maxwellian neutron spectra at kT=30 keV is used. An experimental value of 2166±181 mb agrees well with the MACS value derived from the ENDF/B-VII.1 evaluation, but is higher than KADoNiS recommended value of 1580±150 mb. Astrophysical implications are studied.

  13. Design, Syntheses, and Anti-TB Activity of 1,3-Benzothiazinone Azide and Click Chemistry Products Inspired by BTZ043.

    PubMed

    Tiwari, Rohit; Miller, Patricia A; Chiarelli, Laurent R; Mori, Giorgia; Šarkan, Michal; Centárová, Ivana; Cho, Sanghyun; Mikušová, Katarína; Franzblau, Scott G; Oliver, Allen G; Miller, Marvin J

    2016-03-10

    Electron deficient nitroaromatic compounds such as BTZ043 and its closest congener, PBTZ169, and related agents are a promising new class of anti-TB compounds. Herein we report the design and syntheses of 1,3-benzothiazinone azide (BTZ-N3) and related click chemistry products based on the molecular mode of activation of BTZ043. Our computational docking studies indicate that BTZ-N3 binds in the essentially same pocket as that of BTZ043. Detailed biochemical studies with cell envelope enzyme fractions of Mycobacterium smegmatis combined with our model biochemical reactivity studies with nucleophiles indicated that, in contrast to BTZ043, the azide analogue may have a different mode of activation for anti-TB activity. Subsequent enzymatic studies with recombinant DprE1 from Mtb followed by MIC determination in NTB1 strain of Mtb (harboring Cys387Ser mutation in DprE1 and is BTZ043 resistant) unequivocally indicated that BTZ-N3 is an effective reversible and noncovalent inhibitor of DprE1. PMID:26985313

  14. TB screening among people living with HIV/AIDS in resource-limited settings.

    PubMed

    Date, Anand; Modi, Surbhi

    2015-04-15

    Tuberculosis (TB) continues to be the leading cause of morbidity and mortality among people living with HIV (PLHIV), making improved prevention and treatment of HIV-associated TB critical to ensuring long-term survival of PLHIV. TB screening among PLHIV is central to implementation of the World Health Organization's 3 I's interventions for reducing the impact of the TB and HIV syndemics. Effective TB screening will result in the identification of PLHIV with presumptive TB disease (ie, those with a positive symptom screen who require appropriate evaluation, including the use of diagnostic tools such as the Xpert MTB/RIF assay) and those eligible for isoniazid preventive therapy (ie, those who have a negative clinical symptom screen or who have a positive screen but are found not to have TB disease). Identification of PLHIV with presumptive TB also facilitates implementation of basic administrative measures for TB infection control, including fast tracking of coughing patients and separation from noncoughing PLHIV to reduce TB transmission. By contributing to the early diagnosis of TB disease among PLHIV, TB screening is also critical to facilitate early initiation of antiretroviral treatment among PLHIV diagnosed with TB disease who might not otherwise be eligible for antiretroviral treatment based on CD4 count or clinical staging. TB screening thus serves as a gateway for multiple TB/HIV interventions and is an integral part of routine clinical services for PLHIV at each clinic visit. PMID:25768866

  15. Anti-Inflammatory and Antimicrobial Actions of Vitamin D in Combating TB/HIV

    PubMed Central

    Coussens, Anna K.; Martineau, Adrian R.; Wilkinson, Robert J.

    2014-01-01

    Tuberculosis (TB) disease activation is now believed to arise due to a lack of inflammatory homeostatic control at either end of the spectrum of inflammation: either due to immunosuppression (decreased antimicrobial activity) or due to immune activation (excess/aberrant inflammation). Vitamin D metabolites can increase antimicrobial activity in innate immune cells, which, in the context of HIV-1 coinfection, have insufficient T cell-mediated help to combat Mycobacterium tuberculosis (MTB) infection. Moreover, maintaining vitamin D sufficiency prior to MTB infection enhances the innate antimicrobial response to T cell-mediated interferon-γ. Conversely, vitamin D can act to inhibit expression and secretion of a broad range of inflammatory mediators and matrix degrading enzymes driving immunopathology during active TB and antiretroviral- (ARV-) mediated immune reconstitution inflammatory syndrome (IRIS). Adjunct vitamin D therapy during treatment of active TB may therefore reduce lung pathology and TB morbidity, accelerate resolution of cavitation and thereby decrease the chance of transmission, improve lung function following therapy, prevent relapse, and prevent IRIS in those initiating ARVs. Future clinical trials of vitamin D for TB prevention and treatment must be designed to detect the most appropriate primary endpoint, which in some cases should be anti-inflammatory and not antimicrobial. PMID:25101194

  16. Stimulus Response of Au-NPs@GMP-Tb Core-Shell Nanoparticles: Toward Colorimetric and Fluorescent Dual-Mode Sensing of Alkaline Phosphatase Activity in Algal Blooms of a Freshwater Lake.

    PubMed

    Zhang, Xiaolei; Deng, Jingjing; Xue, Yumeng; Shi, Guoyue; Zhou, Tianshu

    2016-01-19

    In this study, we demonstrate a colorimetric and fluorescent dual-mode method for alkaline phosphatase activity (APA) sensing in freshwater lake with stimuli-responsive gold nanoparticles@terbium-guanosine monophosphate (Au-NPs@GMP-Tb) core-shell nanoparticles. Initially, the core-shell nanoparticles were fabricated based on Au-NPs decorated with a fluorescent GMP-Tb shell. Upon being excited at 290 nm, the as-formed Au-NPs@GMP-Tb core-shell nanoparticles emit green fluorescence, and the decorated GMP-Tb shell causes the aggregation of Au-NPs. However, the addition of ALP destroys GMP-Tb shell, resulting in the release of Au-NPs from the shell into the solvent. As a consequence, the aggregated Au-NPs solubilizes with the changes in the UV-vis spectrum of the dispersion, and in the meantime, the fluorescence of GMP-Tb shell turns off, which constitutes a new mechanism for colorimetric and fluorescent dual-mode sensing of APA. With the method developed here, we could monitor the dynamic change of APA during an algal bloom of a freshwater lake, both by the naked eye and further confirmed by fluorometric determination. This study not only offers a new method for on-site visible detection of APA but also provides a strategy for dual-mode sensing mechanisms by the rational design of the excellent optical properties of Au-NPs and the adaptive inclusion properties of the luminescent infinite coordination polymers. PMID:26677868

  17. Drug-resistant TB: deadly, costly and in need of a vaccine

    PubMed Central

    Manjelievskaia, Janna; Erck, Dara; Piracha, Samina; Schrager, Lewis

    2016-01-01

    TB is an underappreciated public health threat in developed nations. In 2014, an estimated 9.6 million TB cases and 1.5 million deaths occurred worldwide; 3.3% of these cases resulted from multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) strains. These figures underestimate the economic burden associated with MDR-TB and XDR-TB, as the cost of treating disease caused by these strains can be 9–25 times higher than treating drug-susceptible TB. Developing new drugs, improved diagnostics and new TB vaccines are critical components of a strategy to combat TB in general, and drug-resistant TB in particular. Because Mycobacterium tuberculosis (MTB) has demonstrated a capacity to develop resistance to drugs developed to combat it, it is unlikely that drug-resistant MTB would be ‘resistant’ to vaccines capable of preventing disease or established infection with drug-sensitive MTB strains. Accordingly, the development of TB vaccines represents an important long-term investment in preventing the spread of drug-resistant TB and achieving WHO's goal of ending the global TB epidemic by 2035. Our current understanding of the epidemiology of drug-resistant TB and the interventions needed to limit its spread, reviewed in this article, illustrates the need for increased financial support for developing new TB drugs, diagnostics and vaccines to meet the WHO goal of TB elimination by 2035. PMID:26884499

  18. Inhibitory effect of Xenorhabdus nematophila TB on plant pathogens Phytophthora capsici and Botrytis cinerea in vitro and in planta

    PubMed Central

    Fang, Xiangling; Zhang, Manrang; Tang, Qian; Wang, Yonghong; Zhang, Xing

    2014-01-01

    Entomopathogenic bacteria Xenorhabdus spp. produce secondary metabolites with potential antimicrobial activity for use in agricultural productions. This study evaluated the inhibitory effect of X. nematophila TB culture on plant pathogens Botrytis cinerea and Phytophthora capsici. The cell-free filtrate of TB culture showed strong inhibitory effects (>90%) on mycelial growth of both pathogens. The methanol-extracted bioactive compounds (methanol extract) of TB culture also had strong inhibitory effects on mycelial growth and spore germinations of both pathogens. The methanol extract (1000 μg/mL) and cell-free filtrate both showed strong therapeutic and protective effects (>70%) on grey mold both in detached tomato fruits and plants, and leaf scorch in pepper plants. This study demonstrates X. nematophila TB produces antimicrobial metabolites of strong activity on plant pathogens, with great potential for controlling tomato grey mold and pepper leaf scorch and being used in integrated disease control to reduce chemical application. PMID:24599183

  19. Inhibitory effect of Xenorhabdus nematophila TB on plant pathogens Phytophthora capsici and Botrytis cinerea in vitro and in planta.

    PubMed

    Fang, Xiangling; Zhang, Manrang; Tang, Qian; Wang, Yonghong; Zhang, Xing

    2014-01-01

    Entomopathogenic bacteria Xenorhabdus spp. produce secondary metabolites with potential antimicrobial activity for use in agricultural productions. This study evaluated the inhibitory effect of X. nematophila TB culture on plant pathogens Botrytis cinerea and Phytophthora capsici. The cell-free filtrate of TB culture showed strong inhibitory effects (>90%) on mycelial growth of both pathogens. The methanol-extracted bioactive compounds (methanol extract) of TB culture also had strong inhibitory effects on mycelial growth and spore germinations of both pathogens. The methanol extract (1000 μg/mL) and cell-free filtrate both showed strong therapeutic and protective effects (>70%) on grey mold both in detached tomato fruits and plants, and leaf scorch in pepper plants. This study demonstrates X. nematophila TB produces antimicrobial metabolites of strong activity on plant pathogens, with great potential for controlling tomato grey mold and pepper leaf scorch and being used in integrated disease control to reduce chemical application. PMID:24599183

  20. On Modelling Minimal Disease Activity

    PubMed Central

    Jackson, Christopher H.; Su, Li; Gladman, Dafna D.

    2016-01-01

    Objective To explore methods for statistical modelling of minimal disease activity (MDA) based on data from intermittent clinic visits. Methods The analysis was based on a 2‐state model. Comparisons were made between analyses based on “complete case” data from visits at which MDA status was known, and the use of hidden model methodology that incorporated information from visits at which only some MDA defining criteria could be established. Analyses were based on an observational psoriatic arthritis cohort. Results With data from 856 patients and 7,024 clinic visits, analysis was based on virtually all visits, although only 62.6% provided enough information to determine MDA status. Estimated mean times for an episode of MDA varied from 4.18 years to 3.10 years, with smaller estimates derived from the hidden 2‐state model analysis. Over a 10‐year period, the estimated expected times spent in MDA episodes of longer than 1 year was 3.90 to 4.22, and the probability of having such an MDA episode was estimated to be 0.85 to 0.91, with longer times and greater probabilities seen with the hidden 2‐state model analysis. Conclusion A 2‐state model provides a useful framework for the analysis of MDA. Use of data from visits at which MDA status can not be determined provide more precision, and notable differences are seen in estimated quantities related to MDA episodes based on complete case and hidden 2‐state model analyses. The possibility of bias, as well as loss of precision, should be recognized when complete case analyses are used. PMID:26315478

  1. Influence of structural distortions upon photoluminescence properties of Eu{sup 3+} and Tb{sup 3+} activated Na{sub 3}Ln(BO{sub 3}){sub 2} (Ln=Y, Gd) borates

    SciTech Connect

    Asiri Naidu, S.; Boudin, S.; Varadaraju, U.V.; Raveau, B.

    2012-06-15

    The comparative study of the structure and photoluminescence (PL) properties of the Eu{sup 3+} and Tb{sup 3+} activated Na{sub 3}Ln(BO{sub 3}){sub 2}, with Ln=Y, Gd, showed the important role of the host lattice structure upon PL. Higher emission intensities of Eu{sup 3+} and Tb{sup 3+} are observed for Na{sub 3}Gd(BO{sub 3}){sub 2} than for Na{sub 3}Y(BO{sub 3}){sub 2}, through direct Eu{sup 3+} excitation at 395 nm for Eu{sup 3+} doped borates, and through Gd{sup 3+} excitation around 280 nm for Tb{sup 3+} doped borates. This higher performance for Na{sub 3}Gd(BO{sub 3}){sub 2} is due to the less regular environment of Eu{sup 3+} (Tb{sup 3+}) in the Gd sites than in the Y sites and to energy transfer from Gd{sup 3+} to Eu{sup 3+}(Tb{sup 3+}). The smaller critical concentration in Na{sub 3}Ln{sub 1-x}Tb{sub x}(BO{sub 3}){sub 2} observed for Ln=Gd, x=0.5, compared to x=0.6 for Ln=Y, is explained by shorter Ln-Ln distances (4.11 A for Gd-Gd vs. 4.59 A for Y-Y). Both Na{sub 3}Y{sub 0.4}Tb{sub 0.6}(BO{sub 3}){sub 2} and Na{sub 3}Gd{sub 0.5}Tb{sub 0.5}(BO{sub 3}){sub 2} show intense green emission under UV excitation. - Graphical abstract: The PL properties of Eu{sup 3+} and Tb{sup 3+} are studied in Na{sub 3}Ln(BO{sub 3}){sub 2} (Ln=Y, Gd) borates. Eu{sup 3+} and Tb{sup 3+}exhibits higher emission intensity in Na{sub 3}Gd(BO{sub 3}){sub 2} compared to Na{sub 3}Y(BO{sub 3}){sub 2} due to the less regular environment of the Gd{sup 3+} ion. Energy transfer from Gd{sup 3+} to Tb{sup 3+} is observed. Highlights: Black-Right-Pointing-Pointer Crystal structure of Na{sub 3}Gd(BO{sub 3}){sub 2} by X-ray powder diffraction. Black-Right-Pointing-Pointer Photoluminescence properties of Eu{sup 3+} and Tb{sup 3+} doped Na{sub 3}Ln(BO{sub 3}){sub 2} (Ln=Y, Gd). Black-Right-Pointing-Pointer Higher Eu{sup 3+} and Tb{sup 3+} emission for Na{sub 3}Gd(BO{sub 3}){sub 2} due to an irregular environment of Gd{sup 3+}. Black-Right-Pointing-Pointer Higher Eu{sup 3+} and Tb{sup 3+} emission

  2. TB Is Back.

    ERIC Educational Resources Information Center

    Natale, Jo Anna

    1992-01-01

    The reemergence of tuberculosis, particularly of new drug-resistant strains, points up the need for well-coordinated school health programs. Immigration effects, growing populations of HIV-infected persons, and relaxed screening procedures are partly responsible for TB's reemergence. Two sidebars offer advice on coping with TB at school and…

  3. [Spanish Society for Pediatric Infectious Diseases guidelines on tuberculosis in pregnant women and neonates (ii): Prophylaxis and treatment].

    PubMed

    Baquero-Artigao, F; Mellado Peña, M J; del Rosal Rabes, T; Noguera Julián, A; Goncé Mellgren, A; de la Calle Fernández-Miranda, M; Navarro Gómez, M L

    2015-10-01

    In pregnant women who have been exposed to tuberculosis (TB), primary isoniazid prophylaxis is only recommended in cases of immunosuppression, chronic medical conditions or obstetric risk factors, and close and sustained contact with a patient with infectious TB. Isoniazid prophylaxis for latent tuberculosis infection (LTBI) is recommended in women who have close contact with an infectious TB patient or have risk factors for progression to active disease. Otherwise, it should be delayed until at least three weeks after delivery. Treatment of TB disease during pregnancy is the same as for the general adult population. Infants born to mothers with disseminated or extrapulmonary TB in pregnancy, with active TB at delivery, or with postnatal exposure to TB, should undergo a complete diagnostic evaluation. Primary isoniazid prophylaxis for at least 12 weeks is recommended for those with negative diagnostic tests and no evidence of disease. Repeated negative diagnostic tests are mandatory before interrupting prophylaxis. Isoniazid for 9 months is recommended in LTBI. Treatment of neonatal TB disease is similar to that of older children, but should be maintained for at least 9 months. Respiratory isolation is recommended in congenital TB, and in postnatal TB with positive gastric or bronchial aspirate acid-fast smears. Separation of mother and infant is only necessary when the mother has received treatment for less than 2 weeks, is sputum smear-positive, or has drug-resistant TB. Breastfeeding is not contraindicated, and in case of mother-infant separation expressed breast milk feeding is recommended. PMID:25754314

  4. Disease activity in osteomyelitis: role of radiography

    SciTech Connect

    Tumeh, S.S.; Aliabadi, P.; Weissman, B.N.; McNeil, B.J.

    1987-12-01

    To determine the impact of radiographic findings on the interpretation of bone and gallium scans of patients with active osteomyelitis, the authors reviewed the medical records and radiologic examinations of 104 patients. The only diagnostic finding of active disease on radiographs was the presence of a sequestrum (three patients). Other findings--such as erosion, soft-tissue swelling, and periosteal reaction--proved nonspecific and did not differentiate active from inactive disease. Furthermore, these findings did not significantly change the sensitivity or specificity of the bone and gallium scans, either in detecting or in excluding the presence of active disease.

  5. Nitroimidazoles for the treatment of TB: past, present and future

    PubMed Central

    Mukherjee, Tathagata; Boshoff, Helena

    2011-01-01

    Tuberculosis remains a leading cause of death resulting from an infectious agent, and the spread of multi- and extensively drug-resistant strains of Mycobacterium tuberculosis poses a threat to management of global health. New drugs that effectively shorten the duration of treatment and are active against drug-resistant strains of this pathogen are urgently required to develop effective chemotherapies to combat this disease. Two nitroimidazoles, PA-824 and OPC-67683, are currently in Phase II clinical trials for the treatment of TB and the outcome of these may determine the future directions of drug development for anti-tubercular nitroimidazoles. In this review we summarize the development of these nitroimidazoles and alternative analogs in these series that may offer attractive alternatives to PA-824 and OPC-67683 for further development in the drug-discovery pipeline. Lastly, the potential pitfalls in the development of nitroimidazoles as drugs for TB are discussed. PMID:21879846

  6. Tuberculosis (TB): Treatment

    MedlinePlus

    ... Departments & Divisions Home Conditions Tuberculosis Treating Tuberculosis Treating Tuberculosis Make an Appointment Refer a Patient Ask a ... bones is treated longer. NEXT: Preventive Treatment Diagnosing Tuberculosis History of TB Our Specialists Charles L. Daley, ...

  7. TB Screening Tests

    MedlinePlus

    ... a risk that the first TST is a false-negative reaction, a second skin test is given ... species, for example Mycobacterium kansasii , will give a false-positive TST or IGRA result for TB. Positive ...

  8. An Imbalanced Learning based MDR-TB Early Warning System.

    PubMed

    Li, Sheng; Tang, Bo; He, Haibo

    2016-07-01

    As a man-made disease, multidrug-resistant tuberculosis (MDR-TB) is mainly caused by improper treatment programs and poor patient supervision, most of which could be prevented. According to the daily treatment and inspection records of tuberculosis (TB) cases, this study focuses on establishing a warning system which could early evaluate the risk of TB patients converting to MDR-TB using machine learning methods. Different imbalanced sampling strategies and classification methods were compared due to the disparity between the number of TB cases and MDR-TB cases in historical data. The final results show that the relative optimal predictions results can be obtained by adopting CART-USBagg classification model in the first 90 days of half of a standardized treatment process. PMID:27209184

  9. Successful Tuberculosis Treatment Outcomes among HIV/TB Coinfected Patients Down-Referred from a District Hospital to Primary Health Clinics in Rural South Africa

    PubMed Central

    Jacobson, Karen B.; Moll, Anthony P.; Friedland, Gerald H.; Shenoi, Sheela V.

    2015-01-01

    Background HIV and tuberculosis (TB) coinfection remains a major public health threat in sub-Saharan Africa. Integration and decentralization of HIV and TB treatment services are being implemented, but data on outcomes of this strategy are lacking in rural, resource-limited settings. We evaluated TB treatment outcomes in TB/HIV coinfected patients in an integrated and decentralized system in rural KwaZulu-Natal, South Africa. Methods We retrospectively studied a cohort of HIV/TB coinfected patients initiating treatment for drug-susceptible TB at a district hospital HIV clinic from January 2012-June 2013. Patients were eligible for down-referral to primary health clinics(PHCs) for TB treatment completion if they met specific clinical criteria. Records were reviewed for patients’ demographic, baseline clinical and laboratory information, past HIV and TB history, and TB treatment outcomes. Results Of 657(88.7%) patients, 322(49.0%) were female, 558(84.9%) were new TB cases, and 572(87.1%) had pulmonary TB. After TB treatment initiation, 280(42.6%) were down-referred from the district level HIV clinic to PHCs for treatment completion; 377(57.4%) remained at the district hospital. Retained patients possessed characteristics indicative of more severe disease. In total, 540(82.2%) patients experienced treatment success, 69(10.5%) died, and 46(7.0%) defaulted. Down-referred patients experienced higher treatment success, and lower mortality, but were more likely to default, primarily at the time of transfer to PHC. Conclusion Decentralization of TB treatment to the primary care level is feasible in rural South Africa. Treatment outcomes are favorable when patients are carefully chosen for down-referral. Higher mortality in retained patients reflects increased baseline disease severity while higher default among down-referred patients reflects failed linkage of care. Better linkage mechanisms are needed including improved identification of potential defaulters, increased

  10. Integrated Source Case Investigation for Tuberculosis (TB) and HIV in the Caregivers and Household Contacts of Hospitalised Young Children Diagnosed with TB in South Africa: An Observational Study

    PubMed Central

    Lala, Sanjay G.; Little, Kristen M.; Tshabangu, Nkeko; Moore, David P.; Msandiwa, Reginah; van der Watt, Martin; Chaisson, Richard E.; Martinson, Neil A.

    2015-01-01

    Background Contact tracing, to identify source cases with untreated tuberculosis (TB), is rarely performed in high disease burden settings when the index case is a young child with TB. As TB is strongly associated with HIV infection in these settings, we used source case investigation to determine the prevalence of undiagnosed TB and HIV in the caregivers and household contacts of hospitalised young children diagnosed with TB in South Africa. Methods Caregivers and household contacts of 576 young children (age ≤7 years) with TB diagnosed between May 2010 and August 2012 were screened for TB and HIV. The primary outcome was the detection of laboratory-confirmed, newly-diagnosed TB disease and/or HIV-infection in close contacts. Results Of 576 caregivers, 301 (52·3%) self-reported HIV-positivity. Newly-diagnosed HIV infection was detected in 63 (22·9%) of the remaining 275 caregivers who self-reported an unknown or negative HIV status. Screening identified 133 (23·1%) caregivers eligible for immediate anti-retroviral therapy (ART). Newly-diagnosed TB disease was detected in 23 (4·0%) caregivers. In non-caregiver household contacts (n = 1341), the prevalence of newly-diagnosed HIV infection and TB disease was 10·0% and 3·2% respectively. On average, screening contacts of every nine children with TB resulted in the identification of one case of newly-diagnosed TB disease, three cases of newly diagnosed HIV-infection, and three HIV-infected persons eligible for ART. Conclusion In high burden countries, source case investigation yields high rates of previously undiagnosed HIV and TB infection in the close contacts of hospitalised young children diagnosed with TB. Furthermore, integrated screening identifies many individuals who are eligible for immediate ART. Similar studies, with costing analyses, should be undertaken in other high burden settings–integrated source case investigation for TB and HIV should be routinely undertaken if our findings are confirmed

  11. Decrease of U(VI) immobilization capability of the facultative anaerobic strain Paenibacillus sp. JG-TB8 under anoxic conditions due to strongly reduced phosphatase activity.

    PubMed

    Reitz, Thomas; Rossberg, Andre; Barkleit, Astrid; Selenska-Pobell, Sonja; Merroun, Mohamed L

    2014-01-01

    Interactions of a facultative anaerobic bacterial isolate named Paenibacillus sp. JG-TB8 with U(VI) were studied under oxic and anoxic conditions in order to assess the influence of the oxygen-dependent cell metabolism on microbial uranium mobilization and immobilization. We demonstrated that aerobically and anaerobically grown cells of Paenibacillus sp. JG-TB8 accumulate uranium from aqueous solutions under acidic conditions (pH 2 to 6), under oxic and anoxic conditions. A combination of spectroscopic and microscopic methods revealed that the speciation of U(VI) associated with the cells of the strain depend on the pH as well as on the aeration conditions. At pH 2 and pH 3, uranium was exclusively bound by organic phosphate groups provided by cellular components, independently on the aeration conditions. At higher pH values, a part (pH 4.5) or the total amount (pH 6) of the dissolved uranium was precipitated under oxic conditions in a meta-autunite-like uranyl phosphate mineral phase without supplying an additional organic phosphate substrate. In contrast to that, under anoxic conditions no mineral formation was observed at pH 4.5 and pH 6, which was clearly assigned to decreased orthophosphate release by the cells. This in turn was caused by a suppression of the indigenous phosphatase activity of the strain. The results demonstrate that changes in the metabolism of facultative anaerobic microorganisms caused by the presence or absence of oxygen can decisively influence U(VI) biomineralization. PMID:25157416

  12. Decrease of U(VI) Immobilization Capability of the Facultative Anaerobic Strain Paenibacillus sp. JG-TB8 under Anoxic Conditions Due to Strongly Reduced Phosphatase Activity

    PubMed Central

    Reitz, Thomas; Rossberg, Andre; Barkleit, Astrid; Selenska-Pobell, Sonja; Merroun, Mohamed L.

    2014-01-01

    Interactions of a facultative anaerobic bacterial isolate named Paenibacillus sp. JG-TB8 with U(VI) were studied under oxic and anoxic conditions in order to assess the influence of the oxygen-dependent cell metabolism on microbial uranium mobilization and immobilization. We demonstrated that aerobically and anaerobically grown cells of Paenibacillus sp. JG-TB8 accumulate uranium from aqueous solutions under acidic conditions (pH 2 to 6), under oxic and anoxic conditions. A combination of spectroscopic and microscopic methods revealed that the speciation of U(VI) associated with the cells of the strain depend on the pH as well as on the aeration conditions. At pH 2 and pH 3, uranium was exclusively bound by organic phosphate groups provided by cellular components, independently on the aeration conditions. At higher pH values, a part (pH 4.5) or the total amount (pH 6) of the dissolved uranium was precipitated under oxic conditions in a meta-autunite-like uranyl phosphate mineral phase without supplying an additional organic phosphate substrate. In contrast to that, under anoxic conditions no mineral formation was observed at pH 4.5 and pH 6, which was clearly assigned to decreased orthophosphate release by the cells. This in turn was caused by a suppression of the indigenous phosphatase activity of the strain. The results demonstrate that changes in the metabolism of facultative anaerobic microorganisms caused by the presence or absence of oxygen can decisively influence U(VI) biomineralization. PMID:25157416

  13. TB/HIV pleurisy reduces Th17 lymphocyte proportion independent of the cytokine microenvironment.

    PubMed

    Korb, Vanessa C; Phulukdaree, Alisa; Lalloo, Umesh G; Chuturgoon, Anil A; Moodley, Devapregasan

    2016-07-01

    T-helper (Th) 17 cells are a pro-inflammatory subset of CD4(+) effector T-cells critical in mucosal immunity. Imbalances in Th17 cell proportion have been implicated in the pathogenesis of several diseases; however, this has not been adequately explored in tuberculosis (TB) and human immunodeficiency virus (HIV) co-infection. Since Th17 cells are predominantly mucosally associated, we assessed Th17 proportion and associated microenvironment in pleural effusions from patients co-infected with TB/HIV. Our results show that TB(+)HIV(+) pleurisy results in significantly reduced frequency of CD4(+)IL-17(+)RORC(+)STAT3(+) Th17 cells compared to TB(-)HIV(-)ex vivo (p = 0.0054) and was confirmed in conditioned media studies in vitro (p = 0.0001). This was not associated with alterations in Th17 polarising cytokines IL-6, IL-21 and IL-23 or changes in Th17 signature cytokines IL-17A and F. However, the mRNA expression of Th17 signalling molecules, IL-6 (p = 0.0022), IL-6R (p = 0.0247), IL-1β (p = 0.0022) and signal transducer and activator (STAT) 3 (p = 0.0022) were significantly upregulated. Notably, TB(+)HIV(+) pleural fluid contained significantly higher concentrations of IL-1β (p = 0.0008), IL-22 (p = 0.0115), IL-31 (p = 0.0210), TNF-α (p = 0.0251) and IFN-γ (p = 0.0026) than TB(-)HIV(-) pleural fluid ex vivo. Taken together, this suggests a reduced portion of Th17 lymphocytes in TB/HIV pleurisy is independent of locally mediated cytokine polarisation. PMID:27450010

  14. Physical Activity Fundamental to Preventing Disease.

    ERIC Educational Resources Information Center

    Office of the Assistant Secretary for Planning and Evaluation (DHHS), Washington, DC.

    Regular physical activity, fitness, and exercise are critically important for all people's health and wellbeing. It can reduce morbidity and mortality from many chronic diseases. Despite its well-known benefits, most U.S. adults, and many children, are not active enough to achieve these health benefits. Physical inactivity and related health…

  15. Biomarkers for Microglial Activation in Alzheimer's Disease

    PubMed Central

    Lautner, Ronald; Mattsson, Niklas; Schöll, Michael; Augutis, Kristin; Blennow, Kaj; Olsson, Bob; Zetterberg, Henrik

    2011-01-01

    Intensive research over the last decades has provided increasing evidence for neuroinflammation as an integral part in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease (AD). Inflammatory responses in the central nervous system (CNS) are initiated by activated microglia, representing the first line of the innate immune defence of the brain. Therefore, biochemical markers of microglial activation may help us understand the underlying mechanisms of neuroinflammation in AD as well as the double-sided qualities of microglia, namely, neuroprotection and neurotoxicity. In this paper we summarize candidate biomarkers of microglial activation in AD along with a survey of recent neuroimaging techniques. PMID:22114747

  16. Photoluminescence properties of rare earths (Eu{sup 3+}, Tb{sup 3+}, Dy{sup 3+} and Tm{sup 3+}) activated NaInW{sub 2}O{sub 8} wolframite host lattice

    SciTech Connect

    Asiri Naidu, S.; Boudin, S.; Varadaraju, U.V.; Raveau, B.

    2012-01-15

    The photoluminescence (PL) studies on NaIn{sub 1-x}RE{sub x}W{sub 2}O{sub 8}, with RE=Eu{sup 3+}, Tb{sup 3+}, Dy{sup 3+} and Tm{sup 3+} phases have shown that the relative contribution of the host lattice and of the intra-f-f emission of the activators to the PL varies with the nature of the rare earth cation. In the case of Dy{sup 3+} and Tm{sup 3+} activators, with yellow and blue emission, respectively, the energy transfer from host to the activator plays a major role. In contrast for Eu{sup 3+}, with intense red emission, the host absorption is less pronounced and the intra-f-f transitions of the Eu{sup 3+} ions play a major role, whereas for Tb{sup 3+} intra-f-f transitions are only observed, giving rise to green emission. - Graphical abstract: NaInW{sub 2}O{sub 8} double tungstate doped with Eu{sup 3+}, Dy{sup 3+}, Tb{sup 3+}and Tm{sup 3+} shows characteristic emission of intense red for Eu{sup 3+}, yellow for Dy{sup 3+}, green for Tb{sup 3+} and blue for Tm{sup 3+}. Highlights: Black-Right-Pointing-Pointer Characteristic emissions of rare earths (Eu{sup 3+}, Tb{sup 3+}, Dy{sup 3+} and Tm{sup 3+}) are observed NaInW{sub 2}O{sub 8} wolframite. Black-Right-Pointing-Pointer Energy transfer from host to the activators (Eu{sup 3+} Dy{sup 3+} Tm{sup 3+} is observed. Black-Right-Pointing-Pointer PL properties of rare earth ions depend on minor structural variations in the host lattice.

  17. Release and activity of histone in diseases.

    PubMed

    Chen, R; Kang, R; Fan, X-G; Tang, D

    2014-01-01

    Histones and their post-translational modifications have key roles in chromatin remodeling and gene transcription. Besides intranuclear functions, histones act as damage-associated molecular pattern molecules when they are released into the extracellular space. Administration of exogenous histones to animals leads to systemic inflammatory and toxic responses through activating Toll-like receptors and inflammasome pathways. Anti-histone treatment (e.g., neutralizing antibodies, activated protein C, recombinant thrombomodulin, and heparin) protect mice against lethal endotoxemia, sepsis, ischemia/reperfusion injury, trauma, pancreatitis, peritonitis, stroke, coagulation, and thrombosis. In addition, elevated serum histone and nucleosome levels have been implicated in multiple pathophysiological processes and progression of diseases including autoimmune diseases, inflammatory diseases, and cancer. Therefore, extracellular histones could serve as biomarkers and novel therapeutic targets in human diseases. PMID:25118930

  18. Physical activity, nutrition, and chronic disease.

    PubMed

    Blair, S N; Horton, E; Leon, A S; Lee, I M; Drinkwater, B L; Dishman, R K; Mackey, M; Kienholz, M L

    1996-03-01

    Epidemiologic, animal, clinical, and metabolic studies demonstrate the independent roles of physical activity and nutrition in the prevention and treatment of several chronic diseases. Fewer data are available to describe the synergistic effects of exercise and diet, and questions remain as to whether and how these two lifestyle factors work together to promote health and prevent disease. This paper briefly reviews many of the known effects of physical activity and nutrition on the prevention and treatment of coronary heart disease, non-insulin-dependent diabetes mellitus, obesity, and osteoporosis as well as how exercise and diet may work together. A discussion of how to increase physical activity levels and how to improve dietary intake also is included. Finally, current exercise and dietary recommendations are summarized, as are directions for future research. PMID:8776222

  19. Tracking and Treating Mobile Populations. The TB Net System. Migrant Clinicians Network Monograph Series. = El Sistema de Red para la TB.

    ERIC Educational Resources Information Center

    Migrant Clinicians Network, Inc., Austin, TX.

    A comprehensive tracking and referral network that helps provide continuity of care for mobile populations with active tuberculosis (TB) or TB infection is considered essential for effective treatment of TB. However, the interstate referral system that exists between state health departments has been highly inefficient for serving migrant…

  20. CCL2, CCL18 and sIL-4R in renal, meningeal and pulmonary TB; a 2 year study of patients and contacts.

    PubMed

    Mendez, Armando; Hernandez-Pando, Rogelio; Contreras, Salvador; Aguilar, Diana; Rook, Graham A W

    2011-03-01

    The role of Th2 cytokines and Th2-associated chemokines in tuberculosis (TB) remains controversial, though in Mexico a polymorphism causing increased production of CCL2 is a risk factor. We studied levels of the Th2-associated chemokines CCL2 and CCL18, circulating soluble IL-4 receptors (sIL-4R), IL-4 and the inhibitory splice variant of IL-4 (IL-4δ2) in a cohort of patients with pulmonary TB and their healthy contacts. These were followed for 2 years during which time 10 contacts developed pulmonary TB. Results were compared with measurements made in renal and meningeal TB, and in disease controls with bacterial pneumonias or Dengue fever that have large Th2 components. In these disease controls both chemokines were significantly raised. They were also very significantly raised in all forms of TB, irrespective of age or disease site. Levels of CCL18 were raised least in meningeal TB, and most in pulmonary patients with long histories, when levels were similar to those in disease controls. Levels of CCL2, although also raised in all three forms of TB, were negatively correlated with CCL18. We found that levels of sIL-4R were strikingly reduced in all forms of TB, particularly meningeal. Contacts who progressed could not be distinguished from contacts who remained healthy at 2 years in terms of IL-4, sIL-4R, CCL2 or CCL18. However contacts had raised expression of IL-4δ2 as previously found. These results indicate vigorous and previously unrecorded activity within the Th2 axis, and further investigation is warranted. PMID:21251883

  1. Cell Death and Autophagy in TB

    PubMed Central

    Moraco, Andrew H.; Kornfeld, Hardy

    2014-01-01

    Mycobacterium tuberculosis has succeeded in infecting one third of the human race though inhibition or evasion of innate and adaptive immunity. The pathogen is a facultative intracellular parasite that uses the niche provided by mononuclear phagocytes for its advantage. Complex interactions determine whether the bacillus will or will not be delivered to acidified lysosomes, whether the host phagocyte will survive infection or die, and whether the timing and mode of cell death works to the advantage of the host or the pathogen. Here we discuss cell death and autophagy in TB. These fundamental processes of cell biology feature in all aspects of TB pathogenesis and may be exploited to the treatment or prevention of TB disease. PMID:25453227

  2. Wavelength dependence of Verdet constant of Tb3+:Y2O3 ceramics

    NASA Astrophysics Data System (ADS)

    Snetkov, I. L.; Permin, D. A.; Balabanov, S. S.; Palashov, O. V.

    2016-04-01

    Samples of the magneto-active material—Tb3+:Y2O3 ceramics with Tb3+ ion concentrations of 10%, 20%, 30%, and 100% (Tb2O3)—were prepared and studied. The wavelength dependence of Verdet constant in the 380 nm-1750 nm range was approximated for all investigated ceramic samples and was predicted for a pure Tb2O3 material. Tb2O3 ceramics demonstrates a more than three times higher Verdet constant in comparison with terbium gallium garnet crystal or ceramics. The linear dependence of the Verdet constant on Tb3+ ion concentration in the Tb3+:Y2O3 ceramics was demonstrated. The obtained data will be useful for fabricating magneto-optical elements of Faraday devices based on Tb3+:Y2O3 with arbitrary Tb3+ ion concentration operating at room temperature in the wavelength range of 380 nm-1750 nm.

  3. Addressing diabetes mellitus as part of the strategy for ending TB.

    PubMed

    Harries, Anthony D; Kumar, Ajay M V; Satyanarayana, Srinath; Lin, Yan; Zachariah, Rony; Lönnroth, Knut; Kapur, Anil

    2016-03-01

    As we enter the new era of Sustainable Development Goals, the international community has committed to ending the TB epidemic by 2030 through implementation of an ambitious strategy to reduce TB-incidence and TB-related mortality and avoiding catastrophic costs for TB-affected families. Diabetes mellitus (DM) triples the risk of TB and increases the probability of adverse TB treatment outcomes such as failure, death and recurrent TB. The rapidly escalating global epidemic of DM means that DM needs to be addressed if TB-related milestones and targets are to be achieved. WHO and the International Union Against Tuberculosis and Lung Disease's Collaborative Framework for Care and Control of Tuberculosis and Diabetes, launched in 2011, provides a template to guide policy makers and implementers to combat the epidemics of both diseases. However, more evidence is required to answer important questions about bi-directional screening, optimal ways of delivering treatment, integration of DM and TB services, and infection control. This should in turn contribute to better and earlier TB case detection, and improved TB treatment outcomes and prevention. DM and TB collaborative care can also help guide the development of a more effective and integrated public health approach for managing non-communicable diseases. PMID:26884497

  4. Addressing diabetes mellitus as part of the strategy for ending TB

    PubMed Central

    Harries, Anthony D.; Kumar, Ajay M.V.; Satyanarayana, Srinath; Lin, Yan; Zachariah, Rony; Lönnroth, Knut; Kapur, Anil

    2016-01-01

    As we enter the new era of Sustainable Development Goals, the international community has committed to ending the TB epidemic by 2030 through implementation of an ambitious strategy to reduce TB-incidence and TB-related mortality and avoiding catastrophic costs for TB-affected families. Diabetes mellitus (DM) triples the risk of TB and increases the probability of adverse TB treatment outcomes such as failure, death and recurrent TB. The rapidly escalating global epidemic of DM means that DM needs to be addressed if TB-related milestones and targets are to be achieved. WHO and the International Union Against Tuberculosis and Lung Disease's Collaborative Framework for Care and Control of Tuberculosis and Diabetes, launched in 2011, provides a template to guide policy makers and implementers to combat the epidemics of both diseases. However, more evidence is required to answer important questions about bi-directional screening, optimal ways of delivering treatment, integration of DM and TB services, and infection control. This should in turn contribute to better and earlier TB case detection, and improved TB treatment outcomes and prevention. DM and TB collaborative care can also help guide the development of a more effective and integrated public health approach for managing non-communicable diseases. PMID:26884497

  5. Preparation and spectroscopic properties of rare-earth (RE) (RE = Sm, Eu, Tb, Dy, Tm)-activated K{sub 2}LnZr(PO{sub 4}){sub 3} (Ln = Y, La, Gd and Lu) phosphate in vacuum ultraviolet region

    SciTech Connect

    Zhang, Zhi-Jun; Lin, Xiao; Zhao, Jing-Tai; Zhang, Guo-Bin

    2013-02-15

    Graphical abstract: Display Omitted Highlights: ► We report the VUV spectroscopic properties of rare-earth ions in K{sub 2}LnZr(PO{sub 4}){sub 3}. ► The O{sup 2−}-Eu{sup 3+} charge transfer bands at about 220 nm have been observed. ► The 4f–5d spin-allowed and spin-forbidden transitions of Tb{sup 3+} have been observed. ► There is energy transfer between the host and rare-earth activators. -- Abstract: Rare earth (RE = Sm, Eu, Tb, Dy and Tm)-activated K{sub 2}LnZr(PO{sub 4}){sub 3} (Ln = Y, La, Gd and Lu) have been synthesized by solid-state reaction method, and their vacuum ultraviolet (VUV) excitation luminescent characteristics have been investigated. The band in the wavelength range of 130–157 nm and the other one range from 155 to 216 nm with the maximum at about 187 nm in the VUV excitation spectra of these compounds are attributed to the host lattice absorption and O–Zr charge transfer transition, respectively. The charge transfer bands (CTB) of O{sup 2−}-Sm{sup 3+}, O{sup 2−}-Dy{sup 3+} and O{sup 2−}-Tm{sup 3+}, in Sm{sup 3+}, Dy{sup 3+} and Tm{sup 3+}-activated samples, have not been obviously observed probably because the 2p electrons of oxygen are tightly bound to the zirconium ion in the host lattice. For Eu{sup 3+}-activated samples, the relatively weak O{sup 2−}-Eu{sup 3+} CTB at about 220 nm is observed. And for Tb{sup 3+}-activated samples, the bands at 223 and 258 nm are related to the 4f-5d spin-allowed and spin-forbidden transitions of Tb{sup 3+}, respectively. It is observed that there is energy transfer between the host lattice and the luminescent activators (e.g. Eu{sup 3+}, Tb{sup 3+}). From the standpoint of luminescent efficiency, color purity and chemical stability, K{sub 2}GdZr(PO{sub 4}){sub 3}:Sm{sup 3+}, Eu{sup 3+}, Tb{sup 3+} are attractive candidates for novel yellow, red, green-emitting PDP phosphors.

  6. Comparison of the Sensitivity of QuantiFERON-TB Gold In-Tube and T-SPOT.TB According to Patient Age.

    PubMed

    Bae, Won; Park, Kyoung Un; Song, Eun Young; Kim, Se Joong; Lee, Yeon Joo; Park, Jong Sun; Cho, Young-Jae; Yoon, Ho Il; Yim, Jae-Joon; Lee, Choon-Taek; Lee, Jae Ho

    2016-01-01

    Currently, there are two types of interferon-gamma release assays (IGRAs) in use for the detection of tuberculosis (TB) infection, the QuantiFERON-TB Gold In-Tube test (GFT-GIT) and T-SPOT.TB. Owing to contradictory reports regarding whether the results of these IGRAs are affected by the age of the patient, we aimed to determine if these two tests have age-related differences in sensitivity. We retrospectively reviewed the medical records of diagnosed TB patients who were tested using either QFT-GIT or T-SPOT.TB from February 2008 to December 2013. The positivity of the two tests was analyzed and compared with true TB infection, which was defined as active TB based on either a positive Mycobacterium culture or a positive TB polymerase chain reaction. The QFT-GIT group included 192 TB patients, and the T-SPOT.TB group included 212 TB patients. Of the patients with pulmonary TB, 76 (39.6%) were in the QFT-GIT group and 143 (67.5%) in the T-SPOT.TB group. The overall sensitivity was 80.2% for QFT-GIT and 91.0% for T.SPOT.TB. The sensitivities of QFT-GIT and T-SPOT.TB according to age group were as follows: <29 years, 93.3% and 96.7%; 30-49 years, 86.5% and 94.7%; 50-69 years, 76.8% and 87.5%; and >70 years, 68.3% and 85.7%, respectively. The trend of age-related changes in sensitivity was significant for both QFT-GIT (p = 0.004) and T.SPOT.TB (p = 0.039). However, only QFT-GIT was significantly related to age in the multivariate analysis. QFT-GIT, but not T-SPOT.TB, was significantly affected by patient age. PMID:27258377

  7. Comparison of the Sensitivity of QuantiFERON-TB Gold In-Tube and T-SPOT.TB According to Patient Age

    PubMed Central

    Bae, Won; Park, Kyoung Un; Song, Eun Young; Kim, Se Joong; Lee, Yeon Joo; Park, Jong Sun; Cho, Young-Jae; Yoon, Ho Il; Yim, Jae-Joon; Lee, Choon-Taek; Lee, Jae Ho

    2016-01-01

    Currently, there are two types of interferon-gamma release assays (IGRAs) in use for the detection of tuberculosis (TB) infection, the QuantiFERON-TB Gold In-Tube test (GFT-GIT) and T-SPOT.TB. Owing to contradictory reports regarding whether the results of these IGRAs are affected by the age of the patient, we aimed to determine if these two tests have age-related differences in sensitivity. We retrospectively reviewed the medical records of diagnosed TB patients who were tested using either QFT-GIT or T-SPOT.TB from February 2008 to December 2013. The positivity of the two tests was analyzed and compared with true TB infection, which was defined as active TB based on either a positive Mycobacterium culture or a positive TB polymerase chain reaction. The QFT-GIT group included 192 TB patients, and the T-SPOT.TB group included 212 TB patients. Of the patients with pulmonary TB, 76 (39.6%) were in the QFT-GIT group and 143 (67.5%) in the T-SPOT.TB group. The overall sensitivity was 80.2% for QFT-GIT and 91.0% for T.SPOT.TB. The sensitivities of QFT-GIT and T-SPOT.TB according to age group were as follows: <29 years, 93.3% and 96.7%; 30–49 years, 86.5% and 94.7%; 50–69 years, 76.8% and 87.5%; and >70 years, 68.3% and 85.7%, respectively. The trend of age-related changes in sensitivity was significant for both QFT-GIT (p = 0.004) and T.SPOT.TB (p = 0.039). However, only QFT-GIT was significantly related to age in the multivariate analysis. QFT-GIT, but not T-SPOT.TB, was significantly affected by patient age. PMID:27258377

  8. DFT calculations, spectroscopic, thermal analysis and biological activity of Sm(III) and Tb(III) complexes with 2-aminobenzoic and 2-amino-5-chloro-benzoic acids.

    PubMed

    Essawy, Amr A; Afifi, Manal A; Moustafa, H; El-Medani, S M

    2014-10-15

    The complexes of Sm(III) and Tb(III) with 2-aminobenzoic acid (anthranilic acid, AA) and 2-amino-5-chlorobenzoic acid (5-chloroanthranilic acid, AACl) were synthesized and characterized based on elemental analysis, IR and mass spectroscopy. The data are in accordance with 1:3 [Metal]:[Ligand] ratio. On the basis of the IR analysis, it was found that the metals were coordinated to bidentate anthranilic acid via the ionised oxygen of the carboxylate group and to the nitrogen of amino group. While in 5-chloroanthranilic acid, the metals were coordinated oxidatively to the bidentate carboxylate group without bonding to amino group; accordingly, a chlorine-affected coordination and reactivity-diversity was emphasized. Thermal analyses (TGA) and biological activity of the complexes were also investigated. Density Functional Theory (DFT) calculations at the B3LYP/6-311++G (d,p)_ level of theory have been carried out to investigate the equilibrium geometry of the ligand. The optimized geometry parameters of the complexes were evaluated using SDDALL basis set. Moreover, total energy, energy of HOMO and LUMO and Mullikan atomic charges were calculated. In addition, dipole moment and orientation have been performed and discussed. PMID:24835942

  9. Biofunctionalization of CeF3:Tb3+ nanoparticles

    NASA Astrophysics Data System (ADS)

    Kong, D. Y.; Wang, Z. L.; Lin, C. K.; Quan, Z. W.; Li, Y. Y.; Li, C. X.; Lin, J.

    2007-02-01

    CeF3:Tb3+ nanoparticles (short pillar-like morphology with an average length and width of 11 and 5 nm, respectively) were successfully prepared by a polyol process using diethyleneglycol (DEG) as solvent. After being functionalized with a SiO2-NH2 layer, these CeF3:Tb3+ nanoparticles can be conjugated with biotin molecules (activated by thionyl chloride) and further with avidin. The as-formed CeF3:Tb3+ nanoparticles, CeF3:Tb3+ nanoparticles functionalized with amino groups, biotin conjugated amino-functionalized CeF3:Tb3+ nanoparticles and biotinylated CeF3:Tb3+ nanoparticles bonded with avidin were characterized by x-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier transform infrared (FT-IR), UV/vis absorption spectra and luminescence spectra, respectively. The biofunctionalization of the CeF3:Tb3+ nanoparticles has less effect on their luminescence properties, i.e. they still show strong green emission (from Tb3+, with 5D4-7F5 at 543 nm as the most prominent group), indicative of the great potential for these CeF3:Tb3+ nanoparticles to be used as biological fluorescence probes.

  10. Biofunctionalization of CeF(3):Tb(3+) nanoparticles.

    PubMed

    Kong, D Y; Wang, Z L; Lin, C K; Quan, Z W; Li, Y Y; Li, C X; Lin, J

    2007-02-21

    CeF(3):Tb(3+) nanoparticles (short pillar-like morphology with an average length and width of 11 and 5 nm, respectively) were successfully prepared by a polyol process using diethyleneglycol (DEG) as solvent. After being functionalized with a SiO(2)-NH(2) layer, these CeF(3):Tb(3+) nanoparticles can be conjugated with biotin molecules (activated by thionyl chloride) and further with avidin. The as-formed CeF(3):Tb(3+) nanoparticles, CeF(3):Tb(3+) nanoparticles functionalized with amino groups, biotin conjugated amino-functionalized CeF(3):Tb(3+) nanoparticles and biotinylated CeF(3):Tb(3+) nanoparticles bonded with avidin were characterized by x-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier transform infrared (FT-IR), UV/vis absorption spectra and luminescence spectra, respectively. The biofunctionalization of the CeF(3):Tb(3+) nanoparticles has less effect on their luminescence properties, i.e. they still show strong green emission (from Tb(3+), with (5)D(4)-(7)F(5) at 543 nm as the most prominent group), indicative of the great potential for these CeF(3):Tb(3+) nanoparticles to be used as biological fluorescence probes. PMID:21730503

  11. Blood or Urine IP-10 Cannot Discriminate between Active Tuberculosis and Respiratory Diseases Different from Tuberculosis in Children

    PubMed Central

    Petrone, Linda; Cannas, Angela; Aloi, Francesco; Nsubuga, Martin; Sserumkuma, Joseph; Nazziwa, Ritah Angella; Jugheli, Levan; Lukindo, Tedson; Girardi, Enrico; Reither, Klaus; Goletti, Delia

    2015-01-01

    Objectives. Interferon-γ inducible protein 10 (IP-10), either in blood or in urine, has been proposed as a tuberculosis (TB) biomarker for adults. This study aims to evaluate the potential of IP-10 diagnostics in children from Uganda, a high TB-endemic country. Methods. IP-10 was measured in the blood and urine concomitantly taken from children who were prospectively enrolled with suspected active TB, with or without HIV infection. Clinical/microbiological parameters and commercially available TB-immune assays (tuberculin skin test (TST) and QuantiFERON TB-Gold In-Tube (QFT-IT)) were concomitantly evaluated. Results. One hundred twenty-eight children were prospectively enrolled. The analysis was performed on 111 children: 80 (72%) of them were HIV-uninfected and 31 (27.9%) were HIV-infected. Thirty-three healthy adult donors (HAD) were included as controls. The data showed that IP-10 is detectable in the urine and blood of children with active TB, independent of HIV status and age. However, although IP-10 levels were higher in active TB children compared to HAD, the accuracy of identifying “active TB” was low and similar to the TST and QFT-IT. Conclusion. IP-10 levels are higher in children with respiratory illness compared to controls, independent of “TB status” suggesting that the evaluation of this parameter can be used as an inflammatory marker more than a TB test. PMID:26346028

  12. Physical activity, obesity and cardiovascular diseases.

    PubMed

    Lakka, T A; Bouchard, C

    2005-01-01

    Sedentary lifestyle and overweight are major public health, clinical, and economical problems in modern societies. The worldwide epidemic of excess weight is due to imbalance between physical activity and dietary energy intake. Sedentary lifestyle, unhealthy diet, and consequent overweight and obesity markedly increase the risk of cardiovascular diseases. Regular physical activity 45-60 min per day prevents unhealthy weight gain and obesity, whereas sedentary behaviors such as watching television promote them. Regular exercise can markedly reduce body weight and fat mass without dietary caloric restriction in overweight individuals. An increase in total energy expenditure appears to be the most important determinant of successful exercise-induced weight loss. The best long-term results may be achieved when physical activity produces an energy expenditure of at least 2,500 kcal/week. Yet, the optimal approach in weight reduction programs appears to be a combination of regular physical activity and caloric restriction. A minimum of 60 min, but most likely 80-90 min of moderate-intensity physical activity per day may be needed to avoid or limit weight regain in formerly overweight or obese individuals. Regular moderate intensity physical activity, a healthy diet, and avoiding unhealthy weight gain are effective and safe ways to prevent and treat cardiovascular diseases and to reduce premature mortality in all population groups. Although the efforts to promote cardiovascular health concern the whole population, particular attention should be paid to individuals who are physically inactive, have unhealthy diets or are prone to weight gain. They have the highest risk for worsening of the cardiovascular risk factor profile and for cardiovascular disease. To combat the epidemic of overweight and to improve cardiovascular health at a population level, it is important to develop strategies to increase habitual physical activity and to prevent overweight and obesity in

  13. Physical activity, brain plasticity, and Alzheimer's disease.

    PubMed

    Erickson, Kirk I; Weinstein, Andrea M; Lopez, Oscar L

    2012-11-01

    In this review we summarize the epidemiological, cross-sectional, and interventional studies examining the association between physical activity and brain volume, function, and risk for Alzheimer's disease. The epidemiological literature provides compelling evidence that greater amounts of physical activity are associated with a reduced risk of dementia in late life. In addition, randomized interventions using neuroimaging tools have reported that participation in physical activity increases the size of prefrontal and hippocampal brain areas, which may lead to a reduction in memory impairments. Consistent with these findings, longitudinal studies using neuroimaging tools also find that the volume of prefrontal and hippocampal brain areas are larger in individuals who engaged in more physical activity earlier in life. We conclude from this review that there is convincing evidence that physical activity has a consistent and robust association with brain regions implicated in age-related cognitive decline and Alzheimer's disease. In addition to summarizing this literature we provide recommendations for future research on physical activity and brain health. PMID:23085449

  14. [Plasma cholinesterase activity in hepatic diseases].

    PubMed

    Araoud, Manel; Mhenni, Hamida; Hellara, Ilhem; Hellara, Olfa; Neffati, Fadoua; Douki, Wahiba; Mili, Marwa; Saffar, Hammouda; Najjar, Mohamed Fadhel

    2013-01-01

    Plasma cholinesterase activity (ChE) may vary in some pathological circumstances. We studied the changes in activity of this enzyme according to the type of liver injury, to assess the interest of this parameter in the diagnosis of liver diseases. Our study was performed on 102 patients with different liver diseases and 53 healthy controls. The ChE activity was lower in patients compared to control group (p < 0.0001), and more pronounced in cirrhotic patients compared to those suffering from hepatitis. Elevated activities of AST, ALT, GGT and ALP and bilirubinemia, and decreased albuminemia were noted in patients compared to controls (p < 0.001). Hypoalbuminemia was significantly important in cirrhotic patients compared to those suffering from cholestasis or hepatitis. A correlation between ChE and bilirubin, albumin and serum protein was found in patients with cirrhosis or those with chronic hepatitis. A significantly lower activity of ChE was found in patients with hepatic insufficiency (HI). In case of suspicion of HI, the prescription of ChE activity could guide or confirm the diagnosis of the impairment. PMID:23747666

  15. Bovine Tuberculosis Risk Factors for British Herds Before and After the 2001 Foot-and-Mouth Epidemic: What have we Learned from the TB99 and CCS2005 Studies?

    PubMed

    Vial, F; Miguel, E; Johnston, W T; Mitchell, A; Donnelly, C A

    2015-10-01

    Over the last couple of decades, the UK experienced a substantial increase in the incidence and geographical spread of bovine tuberculosis (TB), in particular since the epidemic of foot-and-mouth disease (FMD) in 2001. The initiation of the Randomized Badger Culling Trial (RBCT) in 1998 in south-west England provided an opportunity for an in-depth collection of questionnaire data (covering farming practices, herd management and husbandry, trading and wildlife activity) from herds having experienced a TB breakdown between 1998 and early 2006 and randomly selected control herds, both within and outside the RBCT (the so-called TB99 and CCS2005 case-control studies). The data collated were split into four separate and comparable substudies related to either the pre-FMD or post-FMD period, which are brought together and discussed here for the first time. The findings suggest that the risk factors associated with TB breakdowns may have changed. Higher Mycobacterium bovis prevalence in badgers following the FMD epidemic may have contributed to the identification of the presence of badgers on a farm as a prominent TB risk factor only post-FMD. The strong emergence of contact/trading TB risk factors post-FMD suggests that the purchasing and movement of cattle, which took place to restock FMD-affected areas after 2001, may have exacerbated the TB problem. Post-FMD analyses also highlighted the potential impact of environmental factors on TB risk. Although no unique and universal solution exists to reduce the transmission of TB to and among British cattle, there is an evidence to suggest that applying the broad principles of biosecurity on farms reduces the risk of infection. However, with trading remaining as an important route of local and long-distance TB transmission, improvements in the detection of infected animals during pre- and post-movement testing should further reduce the geographical spread of the disease. PMID:24330476

  16. Graves' disease: thyroid function and immunologic activity

    SciTech Connect

    Gossage, A.A.; Crawley, J.C.; Copping, S.; Hinge, D.; Himsworth, R.L.

    1982-11-01

    Patients with Graves' disease were studied for two years during and after a twelve-month course of treatment. Disease activity was determined by repeated measurements of thyroidal uptake of (/sup 99m/Tc)pertechnetate during tri-iodothyronine administration. These in-vivo measurements of thyroid stimulation were compared with the results of in-vitro assays of Graves, immunoglobulin (TSH binding inhibitory activity--TBIA). There was no correlation between the thyroid uptake and TBIA on diagnosis. Pertechnetate uptake and TBIA both declined during the twelve months of antithyroid therapy. TBIA was detectable in sera from 19 of the 27 patients at diagnosis; in 11 of these 19 patients there was a good correlation (p less than 0.05) throughout the course of their disease between the laboratory assay of the Graves, immunoglobulin and the thyroid uptake. Probability of recurrence can be assessed but sustained remission of Graves' disease after treatment cannot be predicted from either measurement alone or in combination.

  17. Graves' disease: thyroid function and immunologic activity

    SciTech Connect

    Gossage, A.A.R.; Crawley, J.C.W.; Copping, S.; Hinge, D.; Himsworth, R.L.

    1982-11-01

    Patients with Graves' disease were studied for two years during and after a twelve-month course of treatment. Disease activity was determined by repeated measurements of thyroidal uptake of (/sup 9/-9..mu..Tc)pertechnetate during tri-iodothyronine administration. These in-vivo measurements of thyroid stimulation were compared with the results of in-vitro assays of Graves, immunoglobulin (TSH binding inhibitory activity - TBIA). There was no correlation between the thyroid uptake and TBIA on diagnosis. Pertechnetate uptake and TBIA both declined during the twelve months of antithyroid therapy. TBIA was detectable in sera from 19 of the 27 patients at diagnosis; in 11 of these 19 patients there was a good correlation (p<0.05) throughout the course of their disease between the laboratory assay of the Graves, immunoglobulin and the thyroid uptake. Probability of recurrence can be assessed but sustained remission of Graves' disease after treatment cannot be predicted from either measurement alone or in combination.

  18. Macrophage activation syndrome in autoimmune disease.

    PubMed

    Deane, Sean; Selmi, Carlo; Teuber, Suzanne S; Gershwin, M Eric

    2010-01-01

    Macrophage activation syndrome (MAS) is a phenomenon characterized by cytopenia, organ dysfunction, and coagulopathy associated with an inappropriate activation of macrophages. Current diagnostic criteria are imprecise, but the syndrome is now recognized as a form of hemophagocytic lymphohistiocytosis that is characteristically associated with autoimmune diatheses. The diagnosis of incipient MAS in patients with autoimmune disease requires a high index of suspicion, as several characteristics of the disorder may be present in the underlying condition or infectious complications associated with the treatment thereof. Proposed treatment regimens include aggressive approaches that require validation in future controlled studies. This review discusses the major aspects of the pathophysiology, diagnosis, and management of MAS with a focus on the association with autoimmune disease. PMID:20407267

  19. Active music therapy and Parkinson's disease: methods.

    PubMed

    Pacchetti, C; Aglieri, R; Mancini, F; Martignoni, E; Nappi, G

    1998-01-01

    Music therapy (MT) is an unconventional, multisensorial therapy poorly assessed in medical care but widely used to different ends in a variety of settings. MT has two branches: active and passive. In active MT the utilisation of instruments is structured to correspond to all sensory organs so as to obtain suitable motor and emotional responses. We conducted a prospective study to evaluate the effects of MT in the neurorehabilitation of patients with Parkinson's Disease (PD), a common degenerative disorder involving movement and emotional impairment. Sixteen PD patients took part in 13 weekly sessions of MT each lasting 2 hours. At the beginning and at the end of the session, every 2 weeks, the patients were evaluated by a neurologist, who assessed PD severity with UPDRS, emotional functions with Happiness Measures (HM) and quality of life using the Parkinson's Disease Quality of Life Questionnaire (PDQL). After every session a significant improvement in motor function, particularly in relation to hypokinesia, was observed both in the overall and in the pre-post session evaluations. HM, UPDRS-ADL and PDQL changes confirmed an improving effect of MT on emotional functions, activities of daily living and quality of life. In conclusion, active MT, operating at a multisensorial level, stimulates motor, affective and behavioural functions. Finally, we propose active MT as new method to include in PD rehabilitation programmes. This article describes the methods adopted during MT sessions with PD patients. PMID:9584875

  20. Increased Complement C1q Level Marks Active Disease in Human Tuberculosis

    PubMed Central

    Zhang, Mingxia; Liu, Haiying; Zhang, Guoliang; Deng, Qunyi; Huang, Jian; Gao, Zhiliang; Zhou, Boping; Feng, Carl G.; Chen, Xinchun

    2014-01-01

    Background Complement functions as an important host defense system and complement C5 and C7 have been implicated in immunopathology of tuberculosis. However, little is known about the role of other complement components in tuberculosis. Methods Complement gene expression in peripheral blood mononuclear cells of tuberculosis patients and controls were determined using whole genome transcriptional microarray assays. The mRNA and protein levels of three C1q components, C1qA, C1qB, and C1qC, were further validated by qRT-PCR and enzyme-linked immunosorbent assay, respectively. The percentages of C1q expression in CD14 positive cells were determined by flow cytometry. Finally, C1qC protein level was quantified in the pleural fluid of tuberculosis and non-tuberculosis pleurisy. Results C1q expression increases significantly in the peripheral blood of patients with active tuberculosis compared to healthy controls and individuals with latent TB infection. The percentage of C1q-expressing CD14 positive cells is significantly increased in active TB patients. C1q expression in the peripheral blood correlates with sputum smear positivity in tuberculosis patients and is reduced after anti-tuberculosis chemotherapy. Notably, receiver operating characteristic analysis showed that C1qC mRNA levels in peripheral blood efficiently discriminate active from latent tuberculosis infection and healthy controls. Additionally, C1qC protein level in pleural effusion shows improved power in discriminating tuberculosis from non-tuberculosis pleurisy when compared to other inflammatory markers, such as IL-6 and TNF-α. Conclusions C1q expression correlates with active disease in human tuberculosis. C1q could be a potential diagnostic marker to discriminate active tuberculosis from latent tuberculosis infection as well as tuberculosis pleurisy from non-tuberculosis pleurisy. PMID:24647646

  1. TIME Impact - a new user-friendly tuberculosis (TB) model to inform TB policy decisions.

    PubMed

    Houben, R M G J; Lalli, M; Sumner, T; Hamilton, M; Pedrazzoli, D; Bonsu, F; Hippner, P; Pillay, Y; Kimerling, M; Ahmedov, S; Pretorius, C; White, R G

    2016-01-01

    Tuberculosis (TB) is the leading cause of death from infectious disease worldwide, predominantly affecting low- and middle-income countries (LMICs), where resources are limited. As such, countries need to be able to choose the most efficient interventions for their respective setting. Mathematical models can be valuable tools to inform rational policy decisions and improve resource allocation, but are often unavailable or inaccessible for LMICs, particularly in TB. We developed TIME Impact, a user-friendly TB model that enables local capacity building and strengthens country-specific policy discussions to inform support funding applications at the (sub-)national level (e.g. Ministry of Finance) or to international donors (e.g. the Global Fund to Fight AIDS, Tuberculosis and Malaria).TIME Impact is an epidemiological transmission model nested in TIME, a set of TB modelling tools available for free download within the widely-used Spectrum software. The TIME Impact model reflects key aspects of the natural history of TB, with additional structure for HIV/ART, drug resistance, treatment history and age. TIME Impact enables national TB programmes (NTPs) and other TB policymakers to better understand their own TB epidemic, plan their response, apply for funding and evaluate the implementation of the response.The explicit aim of TIME Impact's user-friendly interface is to enable training of local and international TB experts towards independent use. During application of TIME Impact, close involvement of the NTPs and other local partners also builds critical understanding of the modelling methods, assumptions and limitations inherent to modelling. This is essential to generate broad country-level ownership of the modelling data inputs and results. In turn, it stimulates discussions and a review of the current evidence and assumptions, strengthening the decision-making process in general.TIME Impact has been effectively applied in a variety of settings. In South Africa, it

  2. Concurrent loss of co-stimulatory molecules and functional cytokine secretion attributes leads to proliferative senescence of CD8(+) T cells in HIV/TB co-infection.

    PubMed

    Saeidi, Alireza; Chong, Yee K; Yong, Yean K; Tan, Hong Y; Barathan, Muttiah; Rajarajeswaran, Jayakumar; Sabet, Negar S; Sekaran, Shamala D; Ponnampalavanar, Sasheela; Che, Karlhans F; Velu, Vijayakumar; Kamarulzaman, Adeeba; Larsson, Marie; Shankar, Esaki M

    2015-09-01

    The role of T-cell immunosenescence and functional CD8(+) T-cell responses in HIV/TB co-infection is unclear. We examined and correlated surrogate markers of HIV disease progression with immune activation, immunosenescence and differentiation using T-cell pools of HIV/TB co-infected, HIV-infected and healthy controls. Our investigations showed increased plasma viremia and reduced CD4/CD8 T-cell ratio in HIV/TB co-infected subjects relative to HIV-infected, and also a closer association with changes in the expression of CD38, a cyclic ADP ribose hydrolase and CD57, which were consistently expressed on late-senescent CD8(+) T cells. Up-regulation of CD57 and CD38 were directly proportional to lack of co-stimulatory markers on CD8(+) T cells, besides diminished expression of CD127 (IL-7Rα) on CD57(+)CD4(+) T cells. Notably, intracellular IFN-γ, perforin and granzyme B levels in HIV-specific CD8(+) T cells of HIV/TB co-infected subjects were diminished. Intracellular CD57 levels in HIV gag p24-specific CD8(+) T cells were significantly increased in HIV/TB co-infection. We suggest that HIV-TB co-infection contributes to senescence associated with chronic immune activation, which could be due to functional insufficiency of CD8(+) T cells. PMID:26071876

  3. 1550 nm VCSEL-based 0.48 Tb/s transmission scheme employing PAM-4 and WDM for active optical cables

    NASA Astrophysics Data System (ADS)

    Markou, S.; Dris, S.; Kalavrouziotis, D.; Avramopoulos, H.; Pleros, N.; Tsiokos, Dimitris M.

    2014-05-01

    With this paper we investigate the system-level performance of VCSELs, parameterized with true experimental LI-VI data and dynamic characteristics of state-of-the-art VCSELs with 3 dB modulation bandwidth at 15 GHz, and propose their deployment as high-speed multi-level optical sources in a mid-range active optical cable (AOC) model for performance prediction of a rack-to-rack interconnection. The AOC architecture combines a 6-element 1550 nm VCSEL array, each directly modulated with 40 Gbaud PAM-4 data, with a wavelength division multiplexer (WDM), in order to implement a parallel link with aggregate traffic of 0.48 Tb/s. Transmission reach exceeded 300 m by deploying a two-tap feed forward equalizer filter at the electrical VCSEL driver. Bit Error Rate (BER) measurements and analysis were carried out in MATLAB. In practice, the thermal behavior and basic operational characteristics of the VCSELs fabricated by the Technische Universität München (TUM) were used to study the thermal performance and operational range of the complete AOC model. The VCSELs were initially operated at 20°C and BER measurements showed power penalties of 1.7 dB and 3.5 dB at 300 m and 500 m of transmission distance respectively for all 6 data channels. System performance was also investigated for elevated operating temperatures of the VCSEL module and the additional system degradation and BER penalties introduced by operation at 50°C and 65°C were also investigated for transmission distances of 300 m and 500 m.

  4. [Biologics and mycobacterial diseases].

    PubMed

    Tsuyuguchi, Kazunari; Matsumoto, Tomoshige

    2013-03-01

    Various biologics such as TNF-alpha inhibitor or IL-6 inhibitor are now widely used for treatment of rheumatoid arthritis. Many reports suggested that one of the major issues is high risk of developing tuberculosis (TB) associated with using these agents, which is especially important in Japan where tuberculosis still remains endemic. Another concern is the risk of development of nontuberculous mycobacterial (NTM) diseases and we have only scanty information about it. The purpose of this symposium is to elucidate the role of biologics in the development of mycobacterial diseases and to establish the strategy to control them. First, Dr. Tohma showed the epidemiologic data of TB risks associated with using biologics calculated from the clinical database on National Database of Rheumatic Diseases by iR-net in Japan. He estimated TB risks in rheumatoid arthritis (RA) patients to be about four times higher compared with general populations and to become even higher by using biologics. He also pointed out a low rate of implementation of QuantiFERON test (QFT) as screening test for TB infection. Next, Dr. Tokuda discussed the issue of NTM disease associated with using biologics. He suggested the airway disease in RA patients might play some role in the development of NTM disease, which may conversely lead to overdiagnosis of NTM disease in RA patients. He suggested that NTM disease should not be uniformly considered a contraindication to treatment with biologics, considering from the results of recent multicenter study showing relatively favorable outcome of NTM patients receiving biologics. Patients with latent tuberculosis infection (LTBI) should receive LTBI treatment before starting biologics. Dr. Kato, a chairperson of the Prevention Committee of the Japanese Society for Tuberculosis, proposed a new LTBI guideline including active implementation of LTBI treatment, introducing interferon gamma release assay, and appropriate selection of persons at high risk for

  5. Emergence in Western African Countries of MDR-TB, Focus on Côte d'Ivoire

    PubMed Central

    Ekaza, Euloge; N'Guessan, Raymond Kouassi; Kacou-N'Douba, Adèle; Aka, N'Guetta; Kouakou, Jacquemin; Le Vacon, Françoise; Altare, Fréderic; Potel, Gilles; de-La-Cochetiere, Marie-France

    2013-01-01

    Tuberculosis (TB) is responsible for a high mortality rate (2.5%) worldwide, mainly in developing countries with a high prevalence of human immunodeficiency virus (HIV). The emergence of multiresistant strains of TB poses an extreme risk for TB outbreaks and highlights the need for global TB control strategies. Among Western African countries, Côte d'Ivoire (CI) represents a specific example of a country with great potential to prevent TB. Specifically, CI has a promising healthcare system for monitoring diseases, including vaccination programs. However, military and political conflict in CI favors the spread of infectious diseases, TB being among the most devastating. Compilation of the studies identifying common causes of TB would be extremely beneficial for the development of treatment and prevention strategies. Therefore, the purpose of this comprehensive review is to evaluate the epidemiology of TB in CI, describe the factors involved in pathogenesis, and suggest simple and applicable prevention strategies. PMID:24093098

  6. Helping People with Alzheimer's Disease Stay Physically Active

    MedlinePlus

    ... Free Stuff Be a Partner Helping People with Alzheimer's Disease Stay Physically Active Regular physical activity has many benefits for people with Alzheimer’s disease. Exercise helps keep muscles, joints, and the ...

  7. Outbreak of Tuberculosis in a Colony of Rhesus Monkeys (Macaca mulatta) after Possible Indirect Contact with a Human TB Patient.

    PubMed

    Mätz-Rensing, K; Hartmann, T; Wendel, G M; Frick, J S; Homolka, S; Richter, E; Munk, M H; Kaup, F-J

    2015-01-01

    Simian tuberculosis is one of the most important bacterial diseases of non-human primates. Outbreaks of tuberculosis have been reported in primate colonies almost as long as these animals have been used experimentally or kept in zoological gardens. Significant progress has been made in reducing the incidence of tuberculosis in captive non-human primates, but despite reasonable precautions, outbreaks continue to occur. The most relevant reason is the high incidence of tuberculosis (TB) amongst the human population, in which tuberculosis is regarded as an important re-emerging disease. Furthermore, many non-human primate species originate from countries with a high burden of human TB. Therefore, Mycobacterium tuberculosis remains a significant threat in animals imported from countries with high rates of human infection. We report an outbreak of tuberculosis among a group of rhesus monkeys (Macaca mulatta) living in a closed, long-term colony. The outbreak coincided with reactivation of a TB infection in a co-worker who never had direct access to the animal house or laboratories. Eleven of 26 rhesus monkeys developed classical chronic active tuberculosis with typical caseous granulomata of varying size within different organs. The main organ system involved was the lung, suggesting an aerosol route of infection. Such an outbreak has significant economic consequences due to animal loss, disruption of research and costs related to disease control. Precautionary measures must be improved in order to avoid TB in non-human primate colonies. PMID:26166434

  8. Gamma interferon release assay for monitoring of treatment response for active tuberculosis: an explosion in the spaghetti factory.

    PubMed

    Denkinger, Claudia M; Pai, Madhukar; Patel, Meena; Menzies, Dick

    2013-02-01

    Few studies have correlated the results of interferon (gamma interferon) release assays (IGRAs) with known markers of tuberculosis (TB) treatment response. We report the results of serial QuantiFERON-TB gold in-tube assay (QFT) testing on 149 patients with active tuberculosis and correlate the results with smear and culture conversion. We show that QFT results do not offer much value for treatment monitoring of TB disease. PMID:23175268

  9. TB tracer teams in South Africa: knowledge, practices and challenges of tracing TB patients to improve adherence

    PubMed Central

    2013-01-01

    Background In 2008–2009 the South African National Tuberculosis (TB) Program (NTP) implemented a national pilot project, the TB Tracer Project, aiming to decrease default rates and improve patient outcomes. The current study aimed to inform the NTP by describing the knowledge, attitudes, and practices of TB program personnel involved with tracing activities. Methods A self-administered written questionnaire was sent to TB staff, managers and tracer team leaders to assess basic TB knowledge, attitudes and practices. Descriptive statistics were used to summarize results and the chi-squared statistic was used to compare responses of staff at facilities that participated in the TB Tracer Project (tracer) and those that followed standard NTP care (non-tracer). Results Of 560 total questionnaires distributed, 270 were completed and returned (response rate 48%). Total TB knowledge ranged from 70.8-86.3% correct across all response groups. However, just over half (range 50–59.3%) of each respondent group was able to correctly identify the four components of a DOT encounter. A patient no longer feeling sick was cited by 72.1% of respondents as the reason patients fail to adhere to treatment. Tracer teams were viewed as an effective means to get patients to return to treatment by 96.3% of health facility level respondents. Tracer team leaders reported concerns including lack of logistical support (41.7%), insufficient physical safety precautions (41.7%), and inadequate protection from contracting TB (39.1%). Upon patients returning to treatment at the clinic, facilities included in the TB Tracer Project were significantly more likely to discuss alternate DOTS arrangements than non-tracer facilities (79.2 vs. 66.4%, p = 0.03). Conclusions This study identified key components of knowledge, attitudes, and practices regarding TB patient tracing activities in South Africa. Educating patients on the essential need to complete treatment irrespective of clinical symptoms may

  10. [Recommendations for the diagnosis and treatment of latent and active tuberculosis in patients with inflammatory joint diseases treated with tumour necrosis factor alpha inhibitors].

    PubMed

    Fonseca, João Eurico; Lucas, Helena; Canhão, Helena; Duarte, Raquel; Santos, Maria José; Villar, Miguel; Faustino, Augusto; Raymundo, Elena

    2006-01-01

    The Portuguese Society of Rheumatology (SPR) and the Portuguese Society of Pulmonology (SPP) have developed guidelines for the diagnosis and treatment of latent tuberculosis infection (LTBI) and active tuberculosis (AT) in patients with inflammatory joint diseases (IJD), namely rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis, treated with tumour necrosis factor alpha (TNF-alpha) antagonists. Due to the high risk of tuberculosis (TB) in patients with IJD, LTBI and AT screening should be performed as soon as possible, ideally at the moment of IJD diagnosis. Even if TB screening was performed at the beginning of the disease, the evaluation should be repeated before starting anti-TNF-alpha therapy. When TB (LTBI orAT) treatment is indicated, it should be performed before the beginning of anti-TNF-alpha therapy. If the IJD activity requires urgent anti-TNF-alpha therapy, these drugs can be started after two months of antituberculosis therapy in AT cases, or after one month in LTBI cases. Chest X-ray is mandatory for all patients. If abnormal, e.g. Gohn complex, the patient should be treated as LTBI; residual lesions require the exclusion of AT and patients with history of untreated or incomplete TB treatment should be treated as LTBI. In cases of suspected active lesions, AT diagnosis should be confirmed and adequate therapy initiated. Tuberculin skin test (TST), with two units of RT23, should be performed in all patients. If induration is less than 5 mm, the test should be repeated after 1 to 2 weeks, on the opposite forearm, and should be considered negative if the result is again inferior to 5 mm. Positive TST implicates LTBI treatment. IfTST is performed in immunosupressed IJD patients, LTBI treatment should be offered to the patient before starting anti-TNFalpha therapy, even in the presence of a negative test. PMID:17094335

  11. HIV testing and disclosure: a qualitative analysis of TB patients in South Africa.

    PubMed

    Daftary, A; Padayatchi, N; Padilla, M

    2007-04-01

    In South Africa, more than 60% of TB patients have HIV co-infection. Voluntary counseling and testing (VCT) is critical to effective HIV prevention, and TB facilities are optimal venues for delivery of these services. This study employed qualitative research methods to explore the decision-making processes for HIV testing and serostatus disclosure by 21 patients hospitalized with multi/extensively-drug resistant TB (M/XDR-TB) in Durban, KwaZulu Natal. Data collected from in-depth interviews characterized 3 broad themes: HIV testing history, experiences and perceptions of stigma and disclosure, and the relationship between TB and HIV/AIDS. Fear of AIDS-related stigma, the singular stress of TB infection, the absence of partner's consent, asymptomatic or incurable disease, and uncertainty about subsequent eligibility for antiretroviral treatment while still receiving TB treatment were identified as potential barriers to the uptake of VCT. HIV serostatus disclosure was impeded by the felt stigma of a 'discreditable' infection, manifested by social rejection and discrimination. The public disclosure of TB illness helped relieve some co-infected patients' overall burden of stigma through a process of 'covering'. HIV prevention [corrected] measures such as VCTare likely to be more effective within TB facilities if greater sensitivity is paid to TB patients' specific social issues and perceptions. These patients are not only at greater risk for HIV co-infection but also for experiencing the double stigma of TB and HIV/AIDS. PMID:17453600

  12. Angiotensin-Converting Enzyme Inhibitors and Active Tuberculosis

    PubMed Central

    Wu, Jiunn-Yih; Lee, Meng-Tse Gabriel; Lee, Si-Huei; Lee, Shih-Hao; Tsai, Yi-Wen; Hsu, Shou-Chien; Chang, Shy-Shin; Lee, Chien-Chang

    2016-01-01

    Abstract Numerous epidemiological data suggest that the use of angiotensin-converting enzyme inhibitors (ACEis) can improve the clinical outcomes of pneumonia. Tuberculosis (TB) is an airborne bacteria like pneumonia, and we aimed to find out whether the use of ACEis can decrease the risk of active TB. We conducted a nested case–control analysis by using a 1 million longitudinally followed cohort, from Taiwan national health insurance research database. The rate ratios (RRs) for TB were estimated by conditional logistic regression, and adjusted using a TB-specific disease risk score (DRS) with 71 TB-related covariates. From January, 1997 to December, 2011, a total of 75,536 users of ACEis, and 7720 cases of new active TB were identified. Current use (DRS adjusted RR, 0.87 [95% CI, 0.78–0.97]), but not recent and past use of ACEis, was associated with a decrease in risk of active TB. Interestingly, it was found that chronic use (>90 days) of ACEis was associated with a further decrease in the risk of TB (aRR, 0.74, [95% CI, 0.66–0.83]). There was also a duration response effect, correlating decrease in TB risk with longer duration of ACEis use. The decrease in TB risk was also consistent across all patient subgroups (age, sex, heart failure, cerebrovascular diseases, myocardial infraction, renal diseases, and diabetes) and patients receiving other cardiovascular medicine. In this large population-based study, we found that subjects with recent and chronic use of ACEis were associated with decrease in TB risk. PMID:27175655

  13. TB control: challenges and opportunities for India.

    PubMed

    Pai, Madhukar; Daftary, Amrita; Satyanarayana, Srinath

    2016-03-01

    India's TB control programme has treated over 19 million patients, but the incidence of TB continues to be high. TB is a major killer and drug-resistant TB is a growing threat. There are several likely reasons, including social conditions and co-morbidities that fuel the TB epidemic: under-investment by the government, weak programme implementation and management, suboptimal quality of care in the private sector, and insufficient advocacy around TB. Fortunately, India possesses the technical know-how, competence and resources to address these challenges. The End TB Strategy by WHO offers India an excellent blueprint to advance the agenda of TB control. PMID:26884494

  14. Tracking early autoimmune disease by bioluminescent imaging of NF-kappaB activation reveals pathology in multiple organ systems.

    PubMed

    Zangani, Michael; Carlsen, Harald; Kielland, Anders; Os, Audun; Hauglin, Harald; Blomhoff, Rune; Munthe, Ludvig A; Bogen, Bjarne

    2009-04-01

    It is desirable to have an early and sensitive detection marker of autoimmune disease in intact animals. Nuclear factor (NF)-kappaB is a transcription factor that is associated with inflammatory responses and immune disorders. Previously, we demonstrated that so-called idiotypic-driven T-B cell collaboration in mice doubly transgenic for paired immunoglobulin and T cell receptor transgenes resulted in a systemic autoimmune disease with systemic lupus erythematosus-like features. Here, we investigated NF-kappaB activation by including an NF-kappaB-responsive luciferase reporter transgene in this animal model. Triply transgenic mice developed bioluminescence signals from diseased organs before onset of clinical symptoms and autoantibody production, and light emissions correlated with disease progression. Signals were obtained from secondary lymphoid organs, inflamed intestines, skin lesions, and arthritic joints. Moreover, bioluminescence imaging and immunohistochemistry demonstrated that a minority of mice suffered from an autoimmune disease of the small intestine, in which light emissions correlated with antibodies against tissue transglutaminase and gliadin. Detection of luciferase by immunohistochemistry revealed NF-kappaB activation in collaborating B and T cells, as well as in macrophages. These results demonstrate that bioluminescent in vivo imaging of NF-kappaB activation can be used for early and sensitive detection of autoimmune disease in an experimental mouse model, offering new possibilities for the evaluation of anti-inflammatory drugs. PMID:19286564

  15. Research Advances: New Weapon in War on TB

    ERIC Educational Resources Information Center

    King, Angela G.

    2005-01-01

    Tuberculosis (TB) is a disease caused by Mycobacterium tuberculosis, which usually attacks the lung and is spread through the air from one person to another. Researchers from Johnson & Johnson Pharmaceutical Research and Development, the Swedish Institute for Infectious Disease Control and The Pitie-Salpetriere School of Medicine began their…

  16. Granzyme A as a potential biomarker of Mycobacterium tuberculosis infection and disease.

    PubMed

    Guggino, Giuliana; Orlando, Valentina; Cutrera, Stella; La Manna, Marco P; Di Liberto, Diana; Vanini, Valentina; Petruccioli, Elisa; Dieli, Francesco; Goletti, Delia; Caccamo, Nadia

    2015-08-01

    Cytotoxic molecules such as granulysin, perforin and granzymes produced by cytolytic T cells directly contribute to immune defense against tuberculosis (TB). In search for novel TB biomarkers, we have evaluated the levels of granzyme A in plasma obtained from QuantiFERON-TB Gold In tube (QFT-IT) assays from patients with active TB disease and subjects with latent TB infection (LTBI). Granzyme A serum levels in TB patients were significantly lower than values found in LTBI subjects even after subtraction of the unstimulated levels from the antigen-stimulated responses. The receiver operator characteristics (ROC) curve analysis comparing TB patients and LTBI groups, showed that at a cut-off value of granzyme A of <3.425pg/ml, the sensitivity and the specificity of the assay were 29.41% and 94.74%, respectively. Our results suggest that granzyme A could be considered another biomarker of TB, that can be used, other than IFN-γ, to discriminate between patients with active TB and LTBI subjects in a well characterized cohort of confirmed Mycobacterium tuberculosis-infected individuals. PMID:26051682

  17. [Duties of TB patients or suspected patients and their close relations].

    PubMed

    Zielonka, Tadeusz M

    2015-01-01

    The effective laws impose the duty upon TB patients or persons suspected to have TB as well as their close relations to undergo compulsory sanitary and epidemiological examinations. Furthermore, treatment is also mandatory and in case of infective patients hospitalization and isolation. Duty does not however denote enforcement, which is required in certain particularly dangerous infectious diseases. Poland operates a system of mandatory TB vaccination applicable, today, only to infants. Persons suspected of TB have the obligation to provide necessary information helping in diagnosing the disease or helping to find the source of infection and transmission of the disease. TB patients are under obligation to discontinue performing their work to prevent the disease from spreading to other persons. PMID:26466461

  18. Use of a T cell interferon gamma release assay in the investigation for suspected active tuberculosis in a low prevalence area

    PubMed Central

    2009-01-01

    Background In settings with low background prevalence of tuberculosis (TB) infection, interferon-γ release assays (IGRA) could be useful for diagnosing active TB. This study aims to evaluate the performance of QuantiFERON®-TB Gold (QFT-G) in the investigation for suspected active TB, with particular attention to patients originating in high-incidence countries. Furthermore, factors associated with QFT-G results in patients with active TB were assessed. Methods From patients investigated for clinically suspected active TB, blood was obtained for QFT-G testing, in addition to routine investigations. Positive (PPV) and negative (NPV) predictive values for QFT-G were calculated, comparing patients with confirmed TB and those with other final diagnoses. QFT-G results in TB patients originating from countries with intermediate or high TB incidence were compared with QFT-G results from a control group of recently arrived asymptomatic immigrants from high-incidence countries. Factors associated with QFT-G outcome in patients with confirmed TB were assessed. Results Among 141 patients, 41/70 (58.6%) with confirmed TB had a positive QFT-G test, compared to 16/71 (22.6%) patients with other final diagnoses, resulting in overall PPV of 71.9% and NPV of 67.6%. For patients with pulmonary disease, PPV and NPV were 61.1% and 67.7%, respectively, and 90.5% and 66.7% for subjects with extrapulmonary manifestations. Comparing patients from high-incidence countries with controls yielded a PPV for active TB of 76.7%, and a NPV of 82.7%. Patients with confirmed TB and positive QFT-G results were characterized by a lower median peripheral white blood cell count (5.9 × 109/L vs. 8.8 × 109/L; P < 0.001) and a higher median body mass index (22.7 vs. 20.7; P = 0.043) as compared to QFT-G-negative TB patients. Conclusion The overall PPV and NPV of QFT-G for identifying active TB were unsatisfactory, especially for pulmonary disease. Thus, the usefulness of QFT-G for this purpose is

  19. Air Travel and TB: an airline perspective.

    PubMed

    Dowdall, Nigel P; Evans, Anthony D; Thibeault, Claude

    2010-03-01

    The commercial airline industry in the 21st century is a global business, able to transport large numbers of people to almost any part of the world within a few hours. There has long been concern in public health circles about the potential for transmission of communicable diseases, such as TB, on board aircraft. The recent threats from novel and emerging infectious diseases including SARS and pandemic flu has facilitated unprecedented levels of cooperation between international industry representatives, regulators and public health authorities in addressing the issues of air travel and communicable disease. This paper reviews the regulatory environment, ways in which the risks are mitigated through aspects of aircraft design, opportunities for prevention by identifying individuals who may be suffering from a communicable disease prior to flight and the approach used in managing suspected cases of communicable disease on board aircraft. PMID:20478517

  20. Coincident Helminth Infection Modulates Systemic Inflammation and Immune Activation in Active Pulmonary Tuberculosis

    PubMed Central

    George, Parakkal Jovvian; Kumar, Nathella Pavan; Sridhar, Rathinam; Hanna, Luke E.; Nair, Dina; Banurekha, Vaithilingam V.; Nutman, Thomas B.; Babu, Subash

    2014-01-01

    Background Helminth infections are known to modulate innate and adaptive immune responses in active and latent tuberculosis (TB). However, the role of helminth infections in modulating responses associated with inflammation and immune activation (reflecting disease activity and/or severity) in TB is not known. Methodology We measured markers of inflammation and immune activation in active pulmonary TB individuals (ATB) with co-incidental Strongyloides stercoralis (Ss) infection. These included systemic levels of acute phase proteins, matrix metalloproteinases and their endogenous inhibitors and immune activation markers. As a control, we measured the systemic levels of the same molecules in TB-uninfected individuals (NTB) with or without Ss infection. Principal Findings Our data confirm that ATB is associated with elevated levels of the various measured molecules when compared to those seen in NTB. Our data also reveal that co-incident Ss infection in ATB individuals is associated with significantly decreased circulating levels of acute phase proteins, matrix metalloproteinases, tissue inhibitors of matrix metalloproteinases as well as the systemic immune activation markers, sCD14 and sCD163. These changes are specific to ATB since they are absent in NTB individuals with Ss infection. Conclusions Our data therefore reveal a profound effect of Ss infection on the markers associated with TB disease activity and severity and indicate that co-incidental helminth infections might dampen the severity of TB disease. PMID:25375117

  1. Towards earlier inclusion of Children in Tuberculosis (TB) drugs trials: Consensus statements from an Expert Panel

    PubMed Central

    Nachman, Sharon; Ahmed, Amina; Amanullah, Farhana; Becerra, Mercedes C; Botgros, Radu; Brigden, Grania; Browning, Renee; Gardiner, Elizabeth; Hafner, Richard; Hesseling, Anneke; How, Cleotilde; Jean-Philippe, Patrick; Lessem, Erica; Makhene, Mamodikoe; Mbelle, Nontombi; Marais, Ben; McIlleron, Helen; Mc Neeley, David F; Mendel, Carl; Murray, Stephen; Navarro, Eileen; Oramasionwu, Gloria E; Porcalla, Ariel R; Powell, Clydette; Powell, Mair; Rigaud, Mona; Rouzier, Vanessa; Samson, Pearl; Schaaf, H. Simon; Shah, Seema; Starke, Jeff; Swaminathan, Soumya; Wobudeya, Eric; Worrell, Carol

    2015-01-01

    Children represent a significant proportion of the global tuberculosis (TB) burden, and may be disproportionately more affected by its most severe clinical manifestations. Currently available treatments for pediatric drug-susceptible (DS) and drug-resistant (DR) TB, albeit generally effective, are hampered by high pill burden, long duration of treatment, coexistent toxicities, and an overall lack of suitable, child-friendly formulations. The complex and burdensome nature of administering the existing regimens to treat DS TB also contributes to the rise of DR TB strains. Despite the availability and use of these therapies for decades, a dearth of dosing evidence in children underscores the importance of sustained efforts for TB drug development to better meet the treatment needs of children with TB. Several new TB drugs and regimens with promising activity against both DS and DR TB strains have recently entered clinical development and are in various phases of clinical evaluation in adults or have received marketing authorization for adults. However, initiation of clinical trials to evaluate these drugs in children is often deferred, pending the availability of complete safety and efficacy data in adults or after drug approval. This document summarizes consensus statements from an international panel of childhood TB opinion leaders which support the initiation of evaluation of new TB drugs and regimens in children at earlier phases of the TB Drug development cycle. PMID:25957923

  2. Risk Factors and Outcomes of Nontuberculous Mycobacterial Disease among Rheumatoid Arthritis Patients: A Case-Control study in a TB Endemic Area

    PubMed Central

    Liao, Tsai-Ling; Lin, Chin-Fu; Chen, Yi-Ming; Liu, Hung-Jen; Chen, Der-Yuan

    2016-01-01

    Increasing evidence indicates that the risk of nontuberculous mycobacteria (NTM) disease is elevated in patients with rheumatoid arthritis (RA). However, the risk factors and outcomes for NTM disease among RA patients remain unclear. We conducted a case-control study and estimated odds ratios (ORs) for RA patients with NTM disease according to comorbidities and anti-rheumatic medications by using conditional logistic regression. Prior tuberculosis history (adjusted OR (aOR) =5.58, p < 0.001), hypertension (aOR = 2.55, p = 0.013), diabetes mellitus (aOR = 3.31, p = 0.005), interstitial lung disease (aOR = 8.22, p < 0.001), chronic obstructive pulmonary disease (aOR = 8.59, p < 0.001) and exposure to oral corticosteroids in a dose-dependent manner (5− < 10 mg/day aOR = 2.51, Ptrend = 0.007) were associated with a significantly increased risk of NTM disease in RA patients. The predominant species causing NTM disease in RA patients was Mycobacterium intracellulare (46.0%). Most NTM isolates were resistant to the majority of the antibiotics that are currently available, which maybe caused treatment failure; hospitalization and mortality are increased. To prevent and treat NTM disease efficiently, we suggested that it is important to monitor the development of NTM disease in RA patients receiving therapy with corticosteroids, particularly in those with predisposing factors. PMID:27404002

  3. Risk Factors and Outcomes of Nontuberculous Mycobacterial Disease among Rheumatoid Arthritis Patients: A Case-Control study in a TB Endemic Area.

    PubMed

    Liao, Tsai-Ling; Lin, Chin-Fu; Chen, Yi-Ming; Liu, Hung-Jen; Chen, Der-Yuan

    2016-01-01

    Increasing evidence indicates that the risk of nontuberculous mycobacteria (NTM) disease is elevated in patients with rheumatoid arthritis (RA). However, the risk factors and outcomes for NTM disease among RA patients remain unclear. We conducted a case-control study and estimated odds ratios (ORs) for RA patients with NTM disease according to comorbidities and anti-rheumatic medications by using conditional logistic regression. Prior tuberculosis history (adjusted OR (aOR) =5.58, p < 0.001), hypertension (aOR = 2.55, p = 0.013), diabetes mellitus (aOR = 3.31, p = 0.005), interstitial lung disease (aOR = 8.22, p < 0.001), chronic obstructive pulmonary disease (aOR = 8.59, p < 0.001) and exposure to oral corticosteroids in a dose-dependent manner (5- < 10 mg/day aOR = 2.51, Ptrend = 0.007) were associated with a significantly increased risk of NTM disease in RA patients. The predominant species causing NTM disease in RA patients was Mycobacterium intracellulare (46.0%). Most NTM isolates were resistant to the majority of the antibiotics that are currently available, which maybe caused treatment failure; hospitalization and mortality are increased. To prevent and treat NTM disease efficiently, we suggested that it is important to monitor the development of NTM disease in RA patients receiving therapy with corticosteroids, particularly in those with predisposing factors. PMID:27404002

  4. Differential gene expression of activating Fcγ receptor classifies active tuberculosis regardless of human immunodeficiency virus status or ethnicity.

    PubMed

    Sutherland, J S; Loxton, A G; Haks, M C; Kassa, D; Ambrose, L; Lee, J-S; Ran, L; van Baarle, D; Maertzdorf, J; Howe, R; Mayanja-Kizza, H; Boom, W H; Thiel, B A; Crampin, A C; Hanekom, W; Ota, M O C; Dockrell, H; Walzl, G; Kaufmann, S H E; Ottenhoff, T H M

    2014-04-01

    New diagnostics and vaccines for tuberculosis (TB) are urgently needed, but require an understanding of the requirements for protection from/susceptibility to TB. Previous studies have used unbiased approaches to determine gene signatures in single-site populations. The present study utilized a targeted approach, reverse transcriptase multiplex ligation-dependent probe amplification (RT-MLPA), to validate these genes in a multisite study. We analysed ex vivo whole blood RNA from a total of 523 participants across four sub-Saharan countries (Ethiopia, Malawi, South Africa, and The Gambia) with differences in TB and human immunodeficiency virus (HIV) status. We found a number of genes that were expressed at significantly lower levels in participants with active disease than in those with latent TB infection (LTBI), with restoration following successful TB treatment. The most consistent classifier of active disease was FCGR1A (high-affinity IgG Fc receptor 1 (CD64)), which was the only marker expressed at significantly higher levels in participants with active TB than in those with LTBI before treatment regardless of HIV status or genetic background. This is the first study to identify a biomarker for TB that is not affected by HIV status or geo-genetic differences. These data provide valuable clues for understanding TB pathogenesis, and also provide a proof-of-concept for the use of RT-MLPA in rapid and inexpensive validation of unbiased gene expression findings. PMID:24205913

  5. Plasma metabolomics in human pulmonary tuberculosis disease: a pilot study.

    PubMed

    Frediani, Jennifer K; Jones, Dean P; Tukvadze, Nestan; Uppal, Karan; Sanikidze, Eka; Kipiani, Maia; Tran, ViLinh T; Hebbar, Gautam; Walker, Douglas I; Kempker, Russell R; Kurani, Shaheen S; Colas, Romain A; Dalli, Jesmond; Tangpricha, Vin; Serhan, Charles N; Blumberg, Henry M; Ziegler, Thomas R

    2014-01-01

    We aimed to characterize metabolites during tuberculosis (TB) disease and identify new pathophysiologic pathways involved in infection as well as biomarkers of TB onset, progression and resolution. Such data may inform development of new anti-tuberculosis drugs. Plasma samples from adults with newly diagnosed pulmonary TB disease and their matched, asymptomatic, sputum culture-negative household contacts were analyzed using liquid chromatography high-resolution mass spectrometry (LC-MS) to identify metabolites. Statistical and bioinformatics methods were used to select accurate mass/charge (m/z) ions that were significantly different between the two groups at a false discovery rate (FDR) of q<0.05. Two-way hierarchical cluster analysis (HCA) was used to identify clusters of ions contributing to separation of cases and controls, and metabolomics databases were used to match these ions to known metabolites. Identity of specific D-series resolvins, glutamate and Mycobacterium tuberculosis (Mtb)-derived trehalose-6-mycolate was confirmed using LC-MS/MS analysis. Over 23,000 metabolites were detected in untargeted metabolomic analysis and 61 metabolites were significantly different between the two groups. HCA revealed 8 metabolite clusters containing metabolites largely upregulated in patients with TB disease, including anti-TB drugs, glutamate, choline derivatives, Mycobacterium tuberculosis-derived cell wall glycolipids (trehalose-6-mycolate and phosphatidylinositol) and pro-resolving lipid mediators of inflammation, known to stimulate resolution, efferocytosis and microbial killing. The resolvins were confirmed to be RvD1, aspirin-triggered RvD1, and RvD2. This study shows that high-resolution metabolomic analysis can differentiate patients with active TB disease from their asymptomatic household contacts. Specific metabolites upregulated in the plasma of patients with active TB disease, including Mtb-derived glycolipids and resolvins, have potential as biomarkers

  6. An African woman with pulmonary cavities: TB or not TB?

    PubMed

    Delsing, C E; Ruesen, C; Boeree, M J; van Damme, P A; Kuipers, S; van Crevel, R

    2014-10-01

    Cavitary lung lesions in patients from developing countries are mostly caused by tuberculosis (TB). However, when TB cannot be confirmed, a primary lung abscess caused by anaerobic bacteria from the mouth should be considered, especially in patients with poor dentition. We present a case of a Sudanese woman with a cavitary lung lesion and severe gingivitis. Bulleidia extructa was isolated as a single pathogen from the pulmonary cavity. PMID:25387555

  7. Recommendations for the diagnosis and treatment of latent and active tuberculosis in inflammatory joint diseases candidates for therapy with tumor necrosis factor alpha inhibitors: March 2008 update.

    PubMed

    Fonseca, João Eurico; Lucas, Helena; Canhão, Helena; Duarte, Raquel; Santos, Maria José; Villar, Miguel; Faustino, Augusto; Raymundo, Elena

    2008-01-01

    The Portuguese Society of Rheumatology and the Portuguese Society of Pulmonology have updated the guidelines for the diagnosis and treatment of latent tuberculosis infection (LTBI) and active tuberculosis (ATB) in patients with inflammatory joint diseases (IJD) that are candidates to therapy with tumour necrosis factor alpha (TNFalpha) antagonists. In order to reduce the risk of tuberculosis (TB) reactivation and the incidence of new infections, TB screening is recommended to be done as soon as possible, ideally at the moment of IJD diagnosis, and patient assessment repeated before starting anti-TNFalpha therapy. Treatment for ATB and LTBI must be done under the care of a TB specialist. When TB treatment is indicated, it should be completed prior to starting anti-TNFalpha therapy. If the IJD activity justifies the need for immediate treatment, anti-TNFalpha therapy can be started two months after antituberculous therapy has been initiated, in the case of ATB, and one month after in the case of LTBI. Chest X-ray is mandatory for all patients. If Gohn s complex is present, the patient should be treated for LTBI; healed lesions require the exclusion of ATB. In cases of suspected active lesions ATB should be excluded/confirmed and adequate therapy initiated. Tuberculin skin test, with two units of RT23, should be performed in all patients. If the induration is <5 mm, the test should be repeated within 1 to 2 weeks, on the opposite forearm, and will be considered negative only if the result is again <5 mm. Positive TST implicates LTBI treatment, unless previous proper treatment was provided. If TST is performed in immunossuppressed IJD patients, LTBI treatment should be offered to the patient before starting anti-TNFalpha therapy, even in the presence of a negative test, after risk/benefit assessment. PMID:18344925

  8. Recommendations for the diagnosis and treatment of latent and active tuberculosis in inflammatory joint diseases candidates for therapy with tumor necrosis factor alpha inhibitors - March 2008 update.

    PubMed

    Fonseca, João Eurico; Lucas, Helena; Canhão, Helena; Duarte, Raquel; Santos, Maria José; Villar, Miguel; Faustino, Augusto; Raymundo, Elena

    2008-01-01

    The Portuguese Society of Rheumatology and the Portuguese Society of Pulmonology have updated the guidelines for the diagnosis and treatment of latent tuberculosis infection (LTBI) and active tuberculosis (ATB) in patients with inflammatory joint diseases (IJD) that are candidates to therapy with tumour necrosis factor alpha (TNFα) antagonists. In order to reduce the risk of tuberculosis (TB) reactivation and the incidence of new infections, TB screening is recommended to be done as soon as possible, ideally at the moment of IJD diagnosis, and patient assessment repeated before starting anti-TNFα therapy. Treatment for ATB and LTBI must be done under the care of a TB specialist. When TB treatment is indicated, it should be completed prior to starting anti-TNFα therapy. If the IJD activity justifies the need for immediate treatment, anti-TNFα therapy can be started two months after antituberculous therapy has been initiated, in the case of ATB, and one month after in the case of LTBI. Chest X-ray is mandatory for all patients. If Gohn's complex is present, the patient should be treated for LTBI; healed lesions require the exclusion of ATB. In cases of suspected active lesions, ATB should be excluded/confirmed and adequate therapy initiated. Tuberculin skin test, with two units of RT23, should be performed in all patients. If the induration is <5 mm, the test should be repeated within 1 to 2 weeks, on the opposite forearm, and will be considered negative only if the result is again <5 mm. Positive TST implicates LTBI treatment, unless previous proper treatment was provided. If TST is performed in immunossuppressed IJD patients, LTBI treatment should be offered to the patient before starting anti-TNF-α therapy, even in the presence of a negative test, after risk / benefit assessment. Rev Port Pneumol 2007; XIV (2): 271-283. PMID:25966834

  9. An investigation into the statistical properties of TB episodes in a South African community with high HIV prevalence.

    PubMed

    Pretorius, Carel; Dodd, Peter; Wood, Robin

    2011-02-01

    Continuous differential equations are often applied to small populations with little time spent on understanding uncertainty brought about by small-population effects. Despite large numbers of individuals being latently infected with Mycobacterium tuberculosis (TB), progression from latent infection to observable disease is a relatively rare event. For small communities, this means case counts are subject to stochasticity, and deterministic models may not be appropriate tools for interpreting transmission trends. Furthermore, the nonlinear nature of the underlying dynamics means that fluctuations are autocorrelated, which can invalidate standard statistical analyses which assume independent fluctuations. Here we extend recent work using a system of differential equations to study the HIV-TB epidemic in Masiphumelele, a community near Cape Town in South Africa [Bacaër, et al., J. Mol. Biol. 57(4), 557-593] by studying the statistical properties of active TB events. We apply van Kampen's system-size (or population-size) expansion technique to obtain an approximation to a master equation describing the dynamics. We use the resulting Fokker-Planck equation and point-process theory to derive two-time correlation functions for active TB events. This method can be used to gain insight into the temporal aspect of cluster identification, which currently relies on DNA classification only. PMID:21056044

  10. Risk factors for false-negative results of QuantiFERON-TB Gold In-Tube assay in non-HIV-infected patients with culture-confirmed tuberculosis.

    PubMed

    Kim, Eun Young; Park, Moo Suk; Kim, Young Sam; Kim, Se Kyu; Chang, Joon; Kang, Young Ae

    2011-07-01

    Limited information is available on the risk factors for false-negative results with the new generation of QuantiFERON-TB Gold In-Tube (QFT-GIT) tests in non-HIV-infected patients with tuberculosis (TB). We sought to identify risk factors for false-negative QFT-GIT results in culture-confirmed TB patients. We reviewed the microbiological, laboratory, radiographic, and clinical data of 362 patients with positive M. tuberculosis cultures who received QFT-GIT tests at a Korean tertiary hospital between September 2006 and March 2010. Of these, 311 (85.9%) had true-positive and 51 (14.1%) had false-negative results. The false-negative group was more likely to have immunosuppressant diseases and lower platelet, protein, and albumin levels than the true-positive group. An immunosuppressive condition was an independent risk factor for false-negative QFT-GIT results in non-HIV-infected patients with active TB (odds ratio, 2.98; 95% confidence interval, 1.38-6.47; P = .006). Careful interpretation of negative QFT-GIT results is thus necessary in immunocompromised patients suspected of having active TB. PMID:21546200

  11. Successfully treated but not fit for purpose: paying attention to chronic lung impairment after TB treatment.

    PubMed

    Harries, A D; Ade, S; Burney, P; Hoa, N B; Schluger, N W; Castro, J L

    2016-08-01

    In 2013, 86% of patients with newly diagnosed tuberculosis (TB) successfully completed treatment and were discharged from care. However, long-term studies in industrialised and resource-poor countries all point to a higher risk of death in TB survivors than in the general population. The likely explanation is chronic restrictive and obstructive lung disease consequent to TB. We call for better linkages between TB control programmes and respiratory medicine services, a better understanding of the burden of respiratory disability at the end of anti-tuberculosis treatment, and political, programmatic, clinical and research action to improve the quality of life of affected patients. PMID:27393532

  12. Designing and Construction of a DNA Vaccine Encoding Tb10.4 Gene of Mycobacterium tuberculosis

    PubMed Central

    Rashidian, Samira; Teimourpour, Roghayeh; Meshkat, Zahra

    2016-01-01

    Background: Tuberculosis (TB) remains as a major cause of death. Construction of a new vaccine against tuberculosis is an effective way to control it. Several vaccines against this disease have been developed. The aim of the present study was to cloning of tb10.4 gene in pcDNA3.1+ plasmid and evaluation of its expression in eukaryotic cells. Methods: Firstly, tb10.4 fragment was amplified by PCR and the PCR product was digested with restriction enzymes. Next, it was cloned into pcDNA3.1+ plasmid. Following that, pcDNA3.1+/tb10.4 recombinant plasmid was transfected into eukaryotic cells. Results: 5700 bp band for pcDNA3.1+/tb10.4 recombinant plasmid and 297 bp fragment for tb10.4 were observed. Cloning and transfection were successful. Conclusion: Successful cloning provides a basis for the development of new DNA vaccines against tuberculosis.

  13. Vaccines for TB: Lessons from the Past Translating into Future Potentials.

    PubMed

    Tye, Gee Jun; Lew, Min Han; Choong, Yee Siew; Lim, Theam Soon; Sarmiento, Maria Elena; Acosta, Armando; Norazmi, Mohd Nor

    2015-01-01

    Development of vaccines for infectious diseases has come a long way with recent advancements in adjuvant developments and discovery of new antigens that are capable of eliciting strong immunological responses for sterile eradication of disease. Tuberculosis (TB) that kills nearly 2 million of the population every year is also one of the highlights of the recent developments. The availability or not of diagnostic methods for infection has implications for the control of the disease by the health systems but is not related to the immune surveillance, a phenomenon derived from the interaction between the bacteria and their host. Here, we will review the immunology of TB and current vaccine candidates for TB. Current strategies of developing new vaccines against TB will also be reviewed in order to further discuss new insights into immunotherapeutic approaches involving adjuvant and antigens combinations that might be of potential for the control of TB. PMID:26146643

  14. Vaccines for TB: Lessons from the Past Translating into Future Potentials

    PubMed Central

    Tye, Gee Jun; Lew, Min Han; Choong, Yee Siew; Lim, Theam Soon; Sarmiento, Maria Elena; Acosta, Armando; Norazmi, Mohd Nor

    2015-01-01

    Development of vaccines for infectious diseases has come a long way with recent advancements in adjuvant developments and discovery of new antigens that are capable of eliciting strong immunological responses for sterile eradication of disease. Tuberculosis (TB) that kills nearly 2 million of the population every year is also one of the highlights of the recent developments. The availability or not of diagnostic methods for infection has implications for the control of the disease by the health systems but is not related to the immune surveillance, a phenomenon derived from the interaction between the bacteria and their host. Here, we will review the immunology of TB and current vaccine candidates for TB. Current strategies of developing new vaccines against TB will also be reviewed in order to further discuss new insights into immunotherapeutic approaches involving adjuvant and antigens combinations that might be of potential for the control of TB. PMID:26146643

  15. Innate and Adaptive Cytotoxic Lymphocytes and Prognostic Markers of Host Responses to Bovine TB

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cell mediated immunity (CMI) is essential for protection against TB in cattle, as in human disease. The cellular and molecular mechanisms of the bovine CMI responses to TB have been characterized during efforts to develop vaccines for cattle. These studies have identified similarities in mechanisms ...

  16. Clearing the smoke around the TB-HIV syndemic: smoking as a critical issue for TB and HIV treatment and care

    PubMed Central

    Jackson-Morris, A.; Fujiwara, P. I.; Pevzner, E.

    2016-01-01

    SUMMARY The collision of the tuberculosis (TB) and human immunodeficiency virus (HIV) epidemics has been described as a ‘syndemic’ due to the synergistic impact on the burden of both diseases. This paper explains the urgent need for practitioners and policy makers to address a third epidemic that exacerbates TB, HIV and TB-HIV. Tobacco use is the leading cause of preventable death worldwide. Smoking is more prevalent among persons diagnosed with TB or HIV. Smoking is associated with tuberculous infection, TB disease and poorer anti-tuberculosis treatment outcomes. It is also associated with an increased risk of smoking-related diseases among people living with HIV, and smoking may also inhibit the effectiveness of life-saving ART. In this paper, we propose integrating into TB and HIV programmes evidence-based strategies from the ‘MPO-WER’ package recommended by the World Health Organization’s Framework Convention on Tobacco Control. Specific actions that can be readily incorporated into current practice are recommended to improve TB and HIV outcomes and care, and reduce the unnecessary burden of death and disease due to smoking. PMID:26260816

  17. Clearing the smoke around the TB-HIV syndemic: smoking as a critical issue for TB and HIV treatment and care.

    PubMed

    Jackson-Morris, A; Fujiwara, P I; Pevzner, E

    2015-09-01

    The collision of the tuberculosis (TB) and human immunodeficiency virus (HIV) epidemics has been described as a 'syndemic' due to the synergistic impact on the burden of both diseases. This paper explains the urgent need for practitioners and policy makers to address a third epidemic that exacerbates TB, HIV and TB-HIV. Tobacco use is the leading cause of preventable death worldwide. Smoking is more prevalent among persons diagnosed with TB or HIV. Smoking is associated with tuberculous infection, TB disease and poorer anti-tuberculosis treatment outcomes. It is also associated with an increased risk of smoking-related diseases among people living with HIV, and smoking may also inhibit the effectiveness of life-saving ART. In this paper, we propose integrating into TB and HIV programmes evidence-based strategies from the 'MPOWER' package recommended by the World Health Organization's Framework Convention on Tobacco Control. Specific actions that can be readily incorporated into current practice are recommended to improve TB and HIV outcomes and care, and reduce the unnecessary burden of death and disease due to smoking. PMID:26260816

  18. Taking forward the World TB Day 2016 theme 'Unite to End Tuberculosis' for the WHO Africa Region.

    PubMed

    Ntoumi, Francine; Kaleebu, Pontiano; Macete, Eusebio; Mfinanga, Sayoki; Chakaya, Jeremiah; Yeboah-Manu, Dorothy; Bates, Matthew; Mwaba, Peter; Maeurer, Markus; Petersen, Eskild; Zumla, Alimuddin

    2016-05-01

    Tuberculosis (TB) remains a global emergency, with an estimated 9.6 million new TB cases worldwide reported in 2014. Twenty-eight percent of these cases were in the World Health Organization (WHO) Africa Region, where the annual case detection rate was 281 per 100000 population-more than double the global average of 133 per 100000. Of the 9.6 million people who developed TB, an estimated 1.2 million (12%) were HIV-positive, and the Africa Region accounted for 74% of these cases. Three million people with TB remain undiagnosed and untreated. Globally, an estimated 480000 had multidrug-resistant TB (MDR-TB). Whilst of the African countries, only South Africa has reported a high prevalence of MDR-TB, it is likely that all of Sub-Saharan Africa has an unreported high load of drug-resistant TB. Tragically, in 2014, only 48% of individuals diagnosed with MDR-TB had successful treatment and an estimated 190000 people died of MDR-TB. Of the global TB funding gap of US$ 0.8 billion, the largest funding gap was in the Africa Region, amounting to US$ 0.4 billion in 2015. The MDR-TB pandemic in particular now threatens to devastate entire regions and may fundamentally alter the life-expectancy and demographic profile of many countries in Sub-Saharan Africa. The theme designated for this year's World TB Day, March 24, 2016, is 'Unite to End TB'. From the Africa Region, there is an urgent need to seriously address the political, economic, and social factors that influence host-Mycobacterium tuberculosis interactions and result in disease. Recent political and funder initiatives that provide renewed hope for the alleviation of Africa's TB and TB/HIV problems are discussed. PMID:26969406

  19. The Risk of Tuberculosis Reinfection Soon after Cure of a First Disease Episode Is Extremely High in a Hyperendemic Community.

    PubMed

    Uys, Pieter; Brand, Hilmarie; Warren, Robin; van der Spuy, Gian; Hoal, Eileen G; van Helden, Paul D

    2015-01-01

    Elevated rates of reinfection tuberculosis in various hyperendemic regions have been reported and, in particular, it has been shown that in a high-incidence setting near Cape Town, South Africa, the rate of reinfection tuberculosis (TB) disease after cure of a previous TB disease episode is about four times greater than the rate of first-time TB disease. It is not known whether this elevated rate is caused by a high reinfection rate due, for instance, to living circumstances, or a high rate of progress to disease specific to the patients, or both. In order to address that question we analysed an extensive data set from clinics attended by TB patients in the high-incidence setting near Cape Town, South Africa and found that, in fact, the (average) rate of reinfection (as opposed to the rate of reinfection disease) after cure of a previous TB disease episode is initially about 0.85 per annum. This rate diminishes rapidly over time and after about ten years this rate is similar to the rate of infection in the general population. Also, the rate of progress to disease after reinfection is initially high but declines in subsequent years down to the figure typical for the general population. These findings suggest that the first few months after cure of a TB disease episode form a critical period for controlling reinfection disease in a hyperendemic setting and that monitoring such cured patients could pre-empt a reinfection progressing to active disease. PMID:26649422

  20. The Risk of Tuberculosis Reinfection Soon after Cure of a First Disease Episode Is Extremely High in a Hyperendemic Community

    PubMed Central

    Warren, Robin; van der Spuy, Gian; Hoal, Eileen G.; van Helden, Paul D

    2015-01-01

    Elevated rates of reinfection tuberculosis in various hyperendemic regions have been reported and, in particular, it has been shown that in a high-incidence setting near Cape Town, South Africa, the rate of reinfection tuberculosis (TB) disease after cure of a previous TB disease episode is about four times greater than the rate of first-time TB disease. It is not known whether this elevated rate is caused by a high reinfection rate due, for instance, to living circumstances, or a high rate of progress to disease specific to the patients, or both. In order to address that question we analysed an extensive data set from clinics attended by TB patients in the high-incidence setting near Cape Town, South Africa and found that, in fact, the (average) rate of reinfection (as opposed to the rate of reinfection disease) after cure of a previous TB disease episode is initially about 0.85 per annum. This rate diminishes rapidly over time and after about ten years this rate is similar to the rate of infection in the general population. Also, the rate of progress to disease after reinfection is initially high but declines in subsequent years down to the figure typical for the general population. These findings suggest that the first few months after cure of a TB disease episode form a critical period for controlling reinfection disease in a hyperendemic setting and that monitoring such cured patients could pre-empt a reinfection progressing to active disease. PMID:26649422

  1. Angiotensin-Converting Enzyme Inhibitors and Active Tuberculosis: A Population-Based Study.

    PubMed

    Wu, Jiunn-Yih; Lee, Meng-Tse Gabriel; Lee, Si-Huei; Lee, Shih-Hao; Tsai, Yi-Wen; Hsu, Shou-Chien; Chang, Shy-Shin; Lee, Chien-Chang

    2016-05-01

    Numerous epidemiological data suggest that the use of angiotensin-converting enzyme inhibitors (ACEis) can improve the clinical outcomes of pneumonia. Tuberculosis (TB) is an airborne bacteria like pneumonia, and we aimed to find out whether the use of ACEis can decrease the risk of active TB.We conducted a nested case-control analysis by using a 1 million longitudinally followed cohort, from Taiwan national health insurance research database. The rate ratios (RRs) for TB were estimated by conditional logistic regression, and adjusted using a TB-specific disease risk score (DRS) with 71 TB-related covariates.From January, 1997 to December, 2011, a total of 75,536 users of ACEis, and 7720 cases of new active TB were identified. Current use (DRS adjusted RR, 0.87 [95% CI, 0.78-0.97]), but not recent and past use of ACEis, was associated with a decrease in risk of active TB. Interestingly, it was found that chronic use (>90 days) of ACEis was associated with a further decrease in the risk of TB (aRR, 0.74, [95% CI, 0.66-0.83]). There was also a duration response effect, correlating decrease in TB risk with longer duration of ACEis use. The decrease in TB risk was also consistent across all patient subgroups (age, sex, heart failure, cerebrovascular diseases, myocardial infraction, renal diseases, and diabetes) and patients receiving other cardiovascular medicine.In this large population-based study, we found that subjects with recent and chronic use of ACEis were associated with decrease in TB risk. PMID:27175655

  2. Exercise Decreases Risk of Future Active Disease in Inflammatory Bowel Disease Patients in Remission

    PubMed Central

    Jones, Patricia D.; Kappelman, Michael D.; Martin, Christopher F.; Chen, Wenli; Sandler, Robert S.; Long, Millie D.

    2015-01-01

    Background Although exercise impacts quality of life in patients with inflammatory bowel disease (IBD), little is known about its role in disease activity. Among IBD patients in remission, we aimed to evaluate the association between exercise and subsequent active disease. Methods We performed a prospective study using the Crohn's and Colitis Foundation of America (CCFA) Partners Internet-based cohort of individuals with self-reported IBD. We identified participants in remission, defined as short Crohn's disease activity index (sCDAI) <150 or simple clinical colitis activity index (SCCAI) ≤2. The primary exposure was exercise status, measured using the validated Godin leisure time activity index. The primary study outcome, assessed after six months, was active disease defined using the above disease activity index thresholds. We used bivariate and multivariate analyses to describe the independent association between exercise and risk of active disease. Results We identified 1308 patients with Crohn's Disease (CD) and 549 with ulcerative or indeterminate colitis (UC/IC) in remission, of whom 227(17.4%) with CD and 135 (24.6%) with UC/IC developed active disease after 6 months. Higher exercise level was associated with decreased risk of active disease for CD (adjusted RR 0.72, 95% CI 0.55-0.94) and UC/IC (adjusted RR 0.78, 95% CI 0.54-1.13). Conclusions In patients with CD in remission, those with higher exercise levels were significantly less likely to develop active disease at six months. In patients with UC/IC in remission, patients with higher exercise levels were less likely to develop active disease at six months, however this was not statistically significant. PMID:25723616

  3. First-Line Treatment for Tuberculosis (TB), Drug Resistant TB -- A Visual Tour

    MedlinePlus

    ... Skip Content Marketing Share this: Main Content Area Tuberculosis Drugs First-Line Treatment of TB for Drug- ... ago. See how these drugs work . Multidrug-Resistant Tuberculosis (MDR TB) and Second-Line Treatments MDR TB ...

  4. The other side of surveillance: Monitoring, application, and integration of tuberculosis data to guide and evaluate programme activities in South Africa

    PubMed Central

    Podewils, L J; Murrison, L Bronner; Bristow, C; Bantubani, N; Mametja, L D

    2016-01-01

    Background The importance of using surveillance data to monitor and evaluate programme activities has been emphasised in international policies for tuberculosis (TB) control. Objectives A survey was conducted to assess the use of TB surveillance data to monitor and guide TB programme activities in South Africa (SA). Methods As part of an evaluation of the SA national TB surveillance system, semi-structured interviews were conducted among TB staff at health facilities and offices in three provinces. At each site, all persons involved with TB care, management and surveillance were invited to participate. Results At least one person (range 1 – 4) was interviewed at 47/54 health facilities (87.0%), 11/13 subdistrict and district TB offices (84.6%), 2/3 provincial TB offices (66.7%), and at the national level (1/1, 100.0%). Of 119 TB staff, 64.7% recognised the purpose of TB surveillance as guiding programme planning, implementation and evaluation. However, only 16.0% reported using data to measure disease burden, 8.4% to monitor trends, and 9.2% to inform resource allocation. The majority reported using TB management tools provided by the national programme, but 44.5% also described using additional tools. Personnel mentioned the need for dedicated surveillance staff, training on recording and reporting, improved computer access, and methods to apply information from surveillance data to the programme. Conclusions The majority of TB staff understood the purpose of surveillance but did not routinely use data to guide programme planning, implementation and evaluation. Training and supporting TB staff to utilise surveillance data will help improve the TB surveillance system. PMID:27032857

  5. Influence of annealing atmosphere and temperature on photoluminescence of Tb 3+ or Eu 3+-activated zinc silicate thin film phosphors via sol-gel method

    NASA Astrophysics Data System (ADS)

    Zhang, Q. Y.; Pita, K.; Ye, W.; Que, W. X.

    2002-01-01

    Thin films of Zn 2SiO 4:Tb 3+ or Eu 3+ were deposited on silicon wafers by a sol-gel method. The films exhibited prominent green or red photoluminescence, due to the sharp and strong intra-4f n-shell electronic transitions. The thermogravimetric analysis curve shows a remarkable weight loss in the temperature range 50-400 ° C, and a slow loss at higher temperature. The increases in fluorescence intensity and decay lifetimes of rare-earth ions sensitive to microstructure and chemical components are attributed to OH removal, nano-crystallite formation and the increased surface roughness by treatment of temperature. Strongly enhanced photoluminescence was observed in samples annealed at 950 °C in a nitrogen atmosphere.

  6. Changes of Tb Emission by Non-radiative Energy Transfer from Dy in Gd2O2S:Tb Phosphor

    NASA Astrophysics Data System (ADS)

    Saraee, Kh. Rezaee Ebrahim; Zadeh, M. Darvish; Mostajaboddavati, M.; Kharieky, A. Aghay

    2016-06-01

    In this study, the Gd2O2S:Tb1.5Dy x=0.3,0.6,0.9 nanophosphor were synthesized by the homogenous precipitation method followed with a sulfur reaction. The fluorescence of Gd2O2S:Tb1.5,Dy nanophosphors, and the energy transfer between dysprosium (Dy) and Tb have been studied. Although, the two weak emissions of Dy were observed, the terbium (Tb) emission was increased due to energy transfer from Dy ions to Tb ions. The results illustrated that the co-activator of Dy had a significant influence on the spectral properties of the Gd2O2S:Tb1.5 nanophosphor with an optimal amount of Dy (0.3 mol%). Moreover, Gd2O2S:Tb1.5 and Gd2O2S:Tb1.5,Dy nanophosphors screens were prepared with 10 mg/cm2 coating thickness. The scintillation properties of these screens have been investigated. We found a Gd2O2S:Tb1.5,Dy0.3 scintillator can be employed in x-ray imaging applications.

  7. Temperature-dependent structure of Tb-doped magnetite nanoparticles

    SciTech Connect

    Rice, Katherine P.; Russek, Stephen E. Shaw, Justin M.; Usselman, Robert J.; Evarts, Eric R.; Silva, Thomas J.; Nembach, Hans T.; Geiss, Roy H.; Arenholz, Elke; Idzerda, Yves U.

    2015-02-09

    High quality 5 nm cubic Tb-doped magnetite nanoparticles have been synthesized by a wet-chemical method to investigate tailoring of magnetic properties for imaging and biomedical applications. We show that the Tb is incorporated into the octahedral 3+ sites. High-angle annular dark-field microscopy shows that the dopant is well-distributed throughout the particle, and x-ray diffraction measurements show a small lattice parameter shift with the inclusion of a rare-earth dopant. Magnetization and x-ray magnetic circular dichroism data indicate that the Tb spins are unpolarized and weakly coupled to the iron spin lattice at room temperature, and begin to polarize and couple to the iron oxide lattice at temperatures below 50 K. Broadband ferromagnetic resonance measurements show no increase in magnetic damping at room temperature for Tb-doped nanoparticles relative to undoped nanoparticles, further confirming weak coupling between Fe and Tb spins at room temperature. The Gilbert damping constant, α, is remarkably low for the Tb-doped nanoparticles, with α = 0.024 ± 0.003. These nanoparticles, which have a large fixed moment, a large fluctuating moment and optically active rare-earth elements, are potential high-relaxivity T1 and T2 MRI agents with integrated optical signatures.

  8. Fast and intense green emission of Tb3+ in borosilicate glass modified by Cu+

    PubMed Central

    Xia, Fanshu; Liu, Siyuan; Wang, Yang; Mao, Jiayi; Li, Xinxi; Wang, Yiqun; Chen, Guorong

    2015-01-01

    We present photoluminescence properties of Tb3+ doped borosilicate glasses modified by Cu+. Around 5-time enhanced emission at 541 nm due to the superposed emission of Tb3+ and Cu+ is observed under the deep UV excitation. Excitation spectra demonstrate a greatly increased absorption of Tb3+ ions in the deep UV region towards the Cu+ excitation band, while the shortened Cu+ emission lifetime of glasses in association with presence of Tb3+ ions implies an energy transfer process from Cu+ to Tb3+ ions. Meanwhile, the Tb3+ emission lifetime is significantly shortened from the conventional millisecond level (~4 ms) to the microsecond regime up to around 90 μs. This most likely starts with the role of Cu+ as a co-activator by initiating the d-f orbital hybridization process via an interaction with Tb3+, thus relaxing the spin forbidden transition of Tb3+ ions to the partially allowed one. Moreover, combination of emissions from Cu+ and Tb3+ ions generates a composite green emission with adjustable CIE (Commission Internationale de L’Eclairage) chromaticity coordinates achievable by co-doping Cu+/Tb3+ in the different ratio and/or altering the excitation wavelength from deep UV to near UV region. PMID:26487264

  9. Fast and intense green emission of Tb3+ in borosilicate glass modified by Cu+

    NASA Astrophysics Data System (ADS)

    Xia, Fanshu; Liu, Siyuan; Wang, Yang; Mao, Jiayi; Li, Xinxi; Wang, Yiqun; Chen, Guorong

    2015-10-01

    We present photoluminescence properties of Tb3+ doped borosilicate glasses modified by Cu+. Around 5-time enhanced emission at 541 nm due to the superposed emission of Tb3+ and Cu+ is observed under the deep UV excitation. Excitation spectra demonstrate a greatly increased absorption of Tb3+ ions in the deep UV region towards the Cu+ excitation band, while the shortened Cu+ emission lifetime of glasses in association with presence of Tb3+ ions implies an energy transfer process from Cu+ to Tb3+ ions. Meanwhile, the Tb3+ emission lifetime is significantly shortened from the conventional millisecond level (~4 ms) to the microsecond regime up to around 90 μs. This most likely starts with the role of Cu+ as a co-activator by initiating the d-f orbital hybridization process via an interaction with Tb3+, thus relaxing the spin forbidden transition of Tb3+ ions to the partially allowed one. Moreover, combination of emissions from Cu+ and Tb3+ ions generates a composite green emission with adjustable CIE (Commission Internationale de L’Eclairage) chromaticity coordinates achievable by co-doping Cu+/Tb3+ in the different ratio and/or altering the excitation wavelength from deep UV to near UV region.

  10. Fast and intense green emission of Tb(3+) in borosilicate glass modified by Cu(.).

    PubMed

    Xia, Fanshu; Liu, Siyuan; Wang, Yang; Mao, Jiayi; Li, Xinxi; Wang, Yiqun; Chen, Guorong

    2015-01-01

    We present photoluminescence properties of Tb(3+) doped borosilicate glasses modified by Cu(+). Around 5-time enhanced emission at 541 nm due to the superposed emission of Tb(3+) and Cu(+) is observed under the deep UV excitation. Excitation spectra demonstrate a greatly increased absorption of Tb(3+) ions in the deep UV region towards the Cu(+) excitation band, while the shortened Cu(+) emission lifetime of glasses in association with presence of Tb(3+) ions implies an energy transfer process from Cu(+) to Tb(3+) ions. Meanwhile, the Tb(3+) emission lifetime is significantly shortened from the conventional millisecond level (~4 ms) to the microsecond regime up to around 90 μs. This most likely starts with the role of Cu(+) as a co-activator by initiating the d-f orbital hybridization process via an interaction with Tb(3+), thus relaxing the spin forbidden transition of Tb(3+) ions to the partially allowed one. Moreover, combination of emissions from Cu(+) and Tb(3+) ions generates a composite green emission with adjustable CIE (Commission Internationale de L'Eclairage) chromaticity coordinates achievable by co-doping Cu(+)/Tb(3+) in the different ratio and/or altering the excitation wavelength from deep UV to near UV region. PMID:26487264

  11. Mycobacterium tuberculosis infection as a zoonotic disease: transmission between humans and elephants.

    PubMed Central

    Michalak, K.; Austin, C.; Diesel, S.; Bacon, M. J.; Zimmerman, P.; Maslow, J. N.

    1998-01-01

    Between 1994 and 1996, three elephants from an exotic animal farm in Illinois died of pulmonary disease due to Mycobacterium tuberculosis. In October 1996, a fourth living elephant was culture-positive for M. tuberculosis. Twenty-two handlers at the farm were screened for tuberculosis (TB); eleven had positive reactions to intradermal injection with purified protein derivative. One had smear-negative, culture-positive active TB. DNA fingerprint comparison by IS6110 and TBN12 typing showed that the isolates from the four elephants and the handler with active TB were the same strain. This investigation indicates transmission of M. tuberculosis between humans and elephants. PMID:9621200

  12. TB deaths reach historic levels. International (global).

    PubMed

    More tuberculosis (TB)-related deaths occurred in 1995 than in any other year in history (almost 3 million, vs. 2.1 million for the TB epidemic around 1990). In the next 50 years, as many as 500 million people may develop TB if current rates continue. More and more of these people will develop multidrug resistant TB. TB affects all social groups. It is the leading fatal infection in youth and adults. HIV positive people are more likely to die from TB than any other condition. More women die from TB than all causes of maternal mortality combined. Almost 50% of the world's refugees may have TB. All people are at risk of TB since TB bacteria, which enter the air via coughing or sneezing, can be suspended in the air for hours. Increased air travel and migration have brought TB back to industrialized countries. Multi-drug resistant TB has emerged in New York City, London, Milan, Paris, Atlanta, Chicago, and cities in developing countries. Governments of industrialized and developing countries have been slow to understand the effects of multi-drug resistant TB for public health. During the 1970s and 1980s, TB was greatly neglected resulting in the current multi-drug resistant TB epidemic. Policy makers have not applied the tools discovered by scientists to help eliminate TB. The World Health Organization recommends directly observed treatment, short-course (DOTS) to fight TB. DOTS can increase the number of cured TB patients two-fold. It can cure almost 95% of TB patients with medicines costing less than $11 in some areas of the world. Yet DOTS is being used to cure only 10% of all TB patients in the world. If it were used in Bangladesh, Brazil, China, Ethiopia, India, Indonesia, Mexico, Nigeria, Pakistan, Russian Federation, South Africa, and Zaire, about 75% of all TB cases would be cured. In DOTS, health workers, not the TB patient, are responsible for curing the TB patient. Poor patient compliance is responsible for the current TB epidemic because TB patients remain

  13. Helminth-induced arginase-1 exacerbates lung inflammation and disease severity in tuberculosis

    PubMed Central

    Monin, Leticia; Griffiths, Kristin L.; Lam, Wing Y.; Gopal, Radha; Kang, Dongwan D.; Ahmed, Mushtaq; Rajamanickam, Anuradha; Cruz-Lagunas, Alfredo; Zúñiga, Joaquín; Babu, Subash; Kolls, Jay K.; Mitreva, Makedonka; Rosa, Bruce A.; Ramos-Payan, Rosalio; Morrison, Thomas E.; Murray, Peter J.; Rangel-Moreno, Javier; Pearce, Edward J.; Khader, Shabaana A.

    2015-01-01

    Parasitic helminth worms, such as Schistosoma mansoni, are endemic in regions with a high prevalence of tuberculosis (TB) among the population. Human studies suggest that helminth coinfections contribute to increased TB susceptibility and increased rates of TB reactivation. Prevailing models suggest that T helper type 2 (Th2) responses induced by helminth infection impair Th1 immune responses and thereby limit Mycobacterium tuberculosis (Mtb) control. Using a pulmonary mouse model of Mtb infection, we demonstrated that S. mansoni coinfection or immunization with S. mansoni egg antigens can reversibly impair Mtb-specific T cell responses without affecting macrophage-mediated Mtb control. Instead, S. mansoni infection resulted in accumulation of high arginase-1–expressing macrophages in the lung, which formed type 2 granulomas and exacerbated inflammation in Mtb-infected mice. Treatment of coinfected animals with an antihelminthic improved Mtb-specific Th1 responses and reduced disease severity. In a genetically diverse mouse population infected with Mtb, enhanced arginase-1 activity was associated with increased lung inflammation. Moreover, in patients with pulmonary TB, lung damage correlated with increased serum activity of arginase-1, which was elevated in TB patients coinfected with helminths. Together, our data indicate that helminth coinfection induces arginase-1–expressing type 2 granulomas, thereby increasing inflammation and TB disease severity. These results also provide insight into the mechanisms by which helminth coinfections drive increased susceptibility, disease progression, and severity in TB. PMID:26571397

  14. TbRGG2 facilitates kinetoplastid RNA editing initiation and progression past intrinsic pause sites.

    PubMed

    Ammerman, Michelle L; Presnyak, Vladimir; Fisk, John C; Foda, Bardees M; Read, Laurie K

    2010-11-01

    TbRGG2 is an essential kinetoplastid RNA editing accessory factor that acts specifically on pan-edited RNAs. To understand the mechanism of TbRGG2 action, we undertook an in-depth analysis of edited RNA populations in TbRGG2 knockdown cells and an in vitro examination of the biochemical activities of the protein. We demonstrate that TbRGG2 down-regulation more severely impacts editing at the 5' ends of pan-edited RNAs than at their 3' ends. The initiation of editing is reduced to some extent in TbRGG2 knockdown cells. In addition, TbRGG2 plays a post-initiation role as editing becomes stalled in TbRGG2-depleted cells, resulting in an overall decrease in the 3' to 5' progression of editing. Detailed analyses of edited RNAs from wild-type and TbRGG2-depleted cells reveal that TbRGG2 facilitates progression of editing past intrinsic pause sites that often correspond to the 3' ends of cognate guide RNAs (gRNAs). In addition, noncanonically edited junction regions are either absent or significantly shortened in TbRGG2-depleted cells, consistent with impaired gRNA transitions. Sequence analysis further suggests that TbRGG2 facilitates complete utilization of certain gRNAs. In vitro RNA annealing and in vivo RNA unwinding assays demonstrate that TbRGG2 can modulate RNA-RNA interactions. Collectively, these data are consistent with a model in which TbRGG2 facilitates initiation and 3' to 5' progression of editing through its ability to affect gRNA utilization, both during the transition between specific gRNAs and during usage of certain gRNAs. PMID:20855539

  15. TbRGG2 facilitates kinetoplastid RNA editing initiation and progression past intrinsic pause sites

    PubMed Central

    Ammerman, Michelle L.; Presnyak, Vladimir; Fisk, John C.; Foda, Bardees M.; Read, Laurie K.

    2010-01-01

    TbRGG2 is an essential kinetoplastid RNA editing accessory factor that acts specifically on pan-edited RNAs. To understand the mechanism of TbRGG2 action, we undertook an in-depth analysis of edited RNA populations in TbRGG2 knockdown cells and an in vitro examination of the biochemical activities of the protein. We demonstrate that TbRGG2 down-regulation more severely impacts editing at the 5′ ends of pan-edited RNAs than at their 3′ ends. The initiation of editing is reduced to some extent in TbRGG2 knockdown cells. In addition, TbRGG2 plays a post-initiation role as editing becomes stalled in TbRGG2-depleted cells, resulting in an overall decrease in the 3′ to 5′ progression of editing. Detailed analyses of edited RNAs from wild-type and TbRGG2-depleted cells reveal that TbRGG2 facilitates progression of editing past intrinsic pause sites that often correspond to the 3′ ends of cognate guide RNAs (gRNAs). In addition, noncanonically edited junction regions are either absent or significantly shortened in TbRGG2-depleted cells, consistent with impaired gRNA transitions. Sequence analysis further suggests that TbRGG2 facilitates complete utilization of certain gRNAs. In vitro RNA annealing and in vivo RNA unwinding assays demonstrate that TbRGG2 can modulate RNA–RNA interactions. Collectively, these data are consistent with a model in which TbRGG2 facilitates initiation and 3′ to 5′ progression of editing through its ability to affect gRNA utilization, both during the transition between specific gRNAs and during usage of certain gRNAs. PMID:20855539

  16. staffTRAK-TB: software for surveillance of tuberculosis infection in healthcare workers.

    PubMed

    Burwen, D R; Seawright, M F

    1999-11-01

    The Centers for Disease Control and Prevention (CDC) recommends periodic tuberculin skin testing of healthcare workers with potential exposure to Mycobacterium tuberculosis. However, many healthcare facilities have neither a system to identify workers due for their skin test nor a means of analyzing aggregate data. To illustrate some of the complexities involved in tuberculin skin test (TST) tracking and analysis, and how these might be addressed, this report describes a software package called staffTRAK-TB, developed by the CDC to facilitate surveillance of tuberculosis infection in healthcare workers. staffTRAK-TB records data for each healthcare worker, including demographic information, occupation, work location, multiple TST results, and results of evaluations to determine if clinically active tuberculosis is present. Programmed reports include lists of workers due and overdue for skin tests, and skin test conversion rates by occupation or worksite. Standardization of types of occupations and locations allows data from multiple facilities to be aggregated and compared. Data transfer to the CDC can be performed via floppy diskettes. staffTRAK-TB illustrates important issues in software structure, standardization of occupation and work-location information, relevant data items, and reports and analyses that would be useful in practice. Developing software that adequately addresses the epidemiological issues is complex, and the lessons learned may serve as a model for hospital epidemiologists, infection control personnel, occupational health personnel, and computer programmers considering software development in this area or trying to optimize their facility's TST surveillance. PMID:10580631

  17. Seasonal prevalence of MS disease activity(Podcast)

    PubMed Central

    Meier, D.S.; Balashov, K.E.; Healy, B.; Weiner, H.L.; Guttmann, C.R.G.

    2010-01-01

    Objective: This observational cohort study investigated the seasonal prevalence of multiple sclerosis (MS) disease activity (likelihood and intensity), as reflected by new lesions from serial T2-weighted MRI, a sensitive marker of subclinical disease activity. Methods: Disease activity was assessed from the appearance of new T2 lesions on 939 separate brain MRI examinations in 44 untreated patients with MS. Likelihood functions for MS disease activity were derived, accounting for the temporal uncertainty of new lesion occurrence, individual levels of disease activity, and uneven examination intervals. Both likelihood and intensity of disease activity were compared with the time of year (season) and regional climate data (temperature, solar radiation, precipitation) and among relapsing and progressive disease phenotypes. Contrast-enhancing lesions and attack counts were also compared for seasonal effects. Results: Unlike contrast enhancement or attacks, new T2 activity revealed a likelihood 2–3 times higher in March–August than during the rest of the year, and correlated strongly with regional climate data, in particular solar radiation. In addition to the likelihood or prevalence, disease intensity was also elevated during the summer season. The elevated risk season appears to lessen for progressive MS and occur about 2 months earlier. Conclusion: This study documents evidence of a strong seasonal pattern in subclinical MS activity based on noncontrast brain MRI. The observed seasonality in MS disease activity has implications for trial design and therapy assessment. The observed activity pattern is suggestive of a modulating role of seasonally changing environmental factors or season-dependent metabolic activity. GLOSSARY CEL = contrast-enhancing lesions; MS = multiple sclerosis. PMID:20805526

  18. Knowledge, attitudes, behaviour and prevalence of TB infection among dentists in the western Cape.

    PubMed

    Naidoo, S; Mahommed, A

    2002-12-01

    Tuberculosis (TB) remains the most important communicable disease in the world and in South Africa it accounts for 80% of all notifiable diseases. The impact of HIV on the TB epidemic is potentially catastrophic. HIV increases the susceptibility of the HIV-positive person to TB. The resurgence of TB as a public health problem has rekindled interest in this disease among oral health workers. The major concern is the risk of transmission in the dental setting. The aim of this study was to determine the prevalence of TB among dental practitioners and to assess their knowledge, attitudes and practices pertaining to TB. A cross-sectional survey was carried out. A structured questionnaire was used to obtain information on demography, infection control, TB status, behaviour, knowledge and perceived risk. In addition, Mantoux and multipuncture tests were performed to assess prevalence. The response rate was 78%. The sample consisted of 78 dentists, 80% male, with a mean age of 40 years. Ninety-two per cent reported always using gloves, 78% masks (68% surgical masks and 18% paper masks) and 50% glasses when treating patients. Two-thirds reported that they sterilise suction and three-in-one tips. Only 11% reported use of a rubber dam. No practitioner reported the use of high-volume externally vented aspirators or ultraviolet germicidal irradiation. Five per cent reported ever being diagnosed with TB, all after having qualified as a dentist. Half of the sample reported having being vaccinated against TB. The prevalence of those who developed a positive reaction was 33%. Thirty-one per cent reported having referred a patient suspected of having TB for further diagnosis and management. Dentists have a duty to take appropriate precautions to protect themselves, their staff and their patients from the risk of cross-infection. The implementation of infection control policies is critical to the provision of such protection. In addition, a dental health facility provides the

  19. Provision of antiretroviral therapy for HIV-positive TB patients--19 countries, sub-Saharan Africa, 2009-2013.

    PubMed

    Dokubo, E Kainne; Baddeley, Annabel; Pathmanathan, Ishani; Coggin, William; Firth, Jacqueline; Getahun, Haileyesus; Kaplan, Jonathan; Date, Anand

    2014-11-28

    Considerable progress has been made in the provision of life-saving antiretroviral therapy (ART) for persons with human immunodeficiency virus (HIV) infection worldwide, resulting in an overall decrease in HIV incidence and acquired immunodeficiency syndrome (AIDS)-related mortality. In the strategic scale-up of HIV care and treatment programs, persons with HIV and tuberculosis (TB) are a priority population for receiving ART. TB is the leading cause of death among persons living with HIV in sub-Saharan Africa and remains a potential risk to the estimated 35 million persons living with HIV globally. Of the 9 million new cases of TB disease globally in 2013, an estimated 1.1 million (13%) were among persons living with HIV; of the 1.5 million deaths attributed to TB in 2013, a total of 360,000 (24%) were among persons living with HIV. ART reduces the incidence of HIV-associated TB disease, and early initiation of ART after the start of TB treatment reduces progression of HIV infection and death among HIV-positive TB patients. To assess the progress in scaling up ART provision among HIV-positive TB patients in 19 countries in sub-Saharan Africa with high TB and HIV burdens, TB and HIV data collected by the World Health Organization (WHO) were reviewed. The results found that the percentage of HIV-positive TB patients receiving ART increased from 37% in 2010 to 69% in 2013. However, many TB cases among persons who are HIV-positive go unreported, and only 38% of the estimated number of HIV-positive new TB patients received ART in 2013. Although progress has been made, the combination of TB and HIV continues to pose a threat to global health, particularly in sub-Saharan Africa. PMID:25426652

  20. Remote Physical Activity Monitoring in Neurological Disease: A Systematic Review

    PubMed Central

    Block, Valerie A. J.; Pitsch, Erica; Tahir, Peggy; Cree, Bruce A. C.; Allen, Diane D.; Gelfand, Jeffrey M.

    2016-01-01

    Objective To perform a systematic review of studies using remote physical activity monitoring in neurological diseases, highlighting advances and determining gaps. Methods Studies were systematically identified in PubMed/MEDLINE, CINAHL and SCOPUS from January 2004 to December 2014 that monitored physical activity for ≥24 hours in adults with neurological diseases. Studies that measured only involuntary motor activity (tremor, seizures), energy expenditure or sleep were excluded. Feasibility, findings, and protocols were examined. Results 137 studies met inclusion criteria in multiple sclerosis (MS) (61 studies); stroke (41); Parkinson's Disease (PD) (20); dementia (11); traumatic brain injury (2) and ataxia (1). Physical activity levels measured by remote monitoring are consistently low in people with MS, stroke and dementia, and patterns of physical activity are altered in PD. In MS, decreased ambulatory activity assessed via remote monitoring is associated with greater disability and lower quality of life. In stroke, remote measures of upper limb function and ambulation are associated with functional recovery following rehabilitation and goal-directed interventions. In PD, remote monitoring may help to predict falls. In dementia, remote physical activity measures correlate with disease severity and can detect wandering. Conclusions These studies show that remote physical activity monitoring is feasible in neurological diseases, including in people with moderate to severe neurological disability. Remote monitoring can be a psychometrically sound and responsive way to assess physical activity in neurological disease. Further research is needed to ensure these tools provide meaningful information in the context of specific neurological disorders and patterns of neurological disability. PMID:27124611

  1. NALP3 inflammasome activation in protein misfolding diseases.

    PubMed

    Shi, Fushan; Kouadir, Mohammed; Yang, Yang

    2015-08-15

    Protein-misfolding diseases, such as Alzheimer's disease, type 2 diabetes, Prion diseases, and Parkinson's disease, are characterized by inflammatory reactions. In all these diseases, IL-1β (Interlukine-1β) has been shown to be an important regulator, and the misfolded proteins are proved to be triggers of the release of IL-1β. Recently, several reports demonstrated that the inflammasome activation is involved in the progress of the misfolded protein diseases, and that the inflammasome can recognize pathogenic proteins leading to the release of IL-1β. In this review, we discuss the role of inflammasome in the pathogenesis of misfolded protein diseases and the potential of inflammasome-targeting therapeutic interventions in the management of these diseases. PMID:26037399

  2. T-cell activation is an immune correlate of risk in BCG vaccinated infants

    PubMed Central

    Fletcher, Helen A.; Snowden, Margaret A.; Landry, Bernard; Rida, Wasima; Satti, Iman; Harris, Stephanie A.; Matsumiya, Magali; Tanner, Rachel; O'Shea, Matthew K.; Dheenadhayalan, Veerabadran; Bogardus, Leah; Stockdale, Lisa; Marsay, Leanne; Chomka, Agnieszka; Harrington-Kandt, Rachel; Manjaly-Thomas, Zita-Rose; Naranbhai, Vivek; Stylianou, Elena; Darboe, Fatoumatta; Penn-Nicholson, Adam; Nemes, Elisa; Hatherill, Mark; Hussey, Gregory; Mahomed, Hassan; Tameris, Michele; McClain, J Bruce; Evans, Thomas G.; Hanekom, Willem A.; Scriba, Thomas J.; McShane, Helen

    2016-01-01

    Vaccines to protect against tuberculosis (TB) are urgently needed. We performed a case–control analysis to identify immune correlates of TB disease risk in Bacille Calmette–Guerin (BCG) immunized infants from the MVA85A efficacy trial. Among 53 TB case infants and 205 matched controls, the frequency of activated HLA-DR+ CD4+ T cells associates with increased TB disease risk (OR=1.828, 95% CI=1.25–2.68, P=0.002, FDR=0.04, conditional logistic regression). In an independent study of Mycobacterium tuberculosis-infected adolescents, activated HLA-DR+ CD4+ T cells also associate with increased TB disease risk (OR=1.387, 95% CI=1.068–1.801, P=0.014, conditional logistic regression). In infants, BCG-specific T cells secreting IFN-γ associate with reduced risk of TB (OR=0.502, 95% CI=0.29–0.86, P=0.013, FDR=0.14). The causes and impact of T-cell activation on disease risk should be considered when designing and testing TB vaccine candidates for these populations. PMID:27068708

  3. T-cell activation is an immune correlate of risk in BCG vaccinated infants.

    PubMed

    Fletcher, Helen A; Snowden, Margaret A; Landry, Bernard; Rida, Wasima; Satti, Iman; Harris, Stephanie A; Matsumiya, Magali; Tanner, Rachel; O'Shea, Matthew K; Dheenadhayalan, Veerabadran; Bogardus, Leah; Stockdale, Lisa; Marsay, Leanne; Chomka, Agnieszka; Harrington-Kandt, Rachel; Manjaly-Thomas, Zita-Rose; Naranbhai, Vivek; Stylianou, Elena; Darboe, Fatoumatta; Penn-Nicholson, Adam; Nemes, Elisa; Hatheril, Mark; Hussey, Gregory; Mahomed, Hassan; Tameris, Michele; McClain, J Bruce; Evans, Thomas G; Hanekom, Willem A; Scriba, Thomas J; McShane, Helen

    2016-01-01

    Vaccines to protect against tuberculosis (TB) are urgently needed. We performed a case-control analysis to identify immune correlates of TB disease risk in Bacille Calmette-Guerin (BCG) immunized infants from the MVA85A efficacy trial. Among 53 TB case infants and 205 matched controls, the frequency of activated HLA-DR(+) CD4(+) T cells associates with increased TB disease risk (OR=1.828, 95% CI=1.25-2.68, P=0.002, FDR=0.04, conditional logistic regression). In an independent study of Mycobacterium tuberculosis-infected adolescents, activated HLA-DR(+) CD4(+) T cells also associate with increased TB disease risk (OR=1.387, 95% CI=1.068-1.801, P=0.014, conditional logistic regression). In infants, BCG-specific T cells secreting IFN-γ associate with reduced risk of TB (OR=0.502, 95% CI=0.29-0.86, P=0.013, FDR=0.14). The causes and impact of T-cell activation on disease risk should be considered when designing and testing TB vaccine candidates for these populations. PMID:27068708

  4. TB incidence and characteristics in the remote gulf province of Papua New Guinea: a prospective study

    PubMed Central

    2014-01-01

    Background The incidence and characteristics of tuberculosis (TB) in remote areas of Papua New Guinea (PNG) are largely unknown. The purpose of our study was to determine the incidence of TB in the Gulf Province of PNG and describe disease characteristics, co-morbidities and drug resistance profiles that could impact on disease outcomes and transmission. Methods Between March 2012 and June 2012, we prospectively collected data on 274 patients presenting to Kikori Hospital with a presumptive diagnosis of TB, and on hospital inpatients receiving TB treatment during the study period. Sputum was collected for microscopy, GeneXpert analysis, culture and genotyping of isolates. Results We estimate the incidence of TB in Kikori to be 1290 per 100,000 people (95% CI 1140 to 1460) in 2012. The proportion of TB patients co-infected with HIV was 1.9%. Three of 32 TB cases tested were rifampicin resistant. Typing of nine isolates demonstrated allelic diversity and most were related to Beijing strains. Conclusions The incidence of TB in Kikori is one of the highest in the world and it is not driven by HIV co-infection. The high incidence and the presence of rifampicin resistant warrant urgent attention to mitigate substantial morbidity in the region. PMID:24555577

  5. Extensively Drug-Resistant Tuberculosis (XDR TB)

    MedlinePlus

    ... other federal agencies and international partners to raise awareness and enhance strategies for TB prevention worldwide by: Strengthening TB services for people living with HIV/AIDS; Guiding preparedness and outbreak investigation responses; Improving ...

  6. Multiple plasma enzyme activities in liver disease

    PubMed Central

    Hargreaves, T.; Janota, I.; Smith, M. J. H.

    1961-01-01

    The measurement of the plasma activities of glutamic-oxaloacetic and glutamic-pyruvic transaminases, aldolase, cholinesterase, and isocitric, lactic, and phosphogluconic dehydrogenases in random samples of blood was found to be of no value in the differential diagnosis of hepatitis, obstructive jaundice, hepatic cirrhosis, and neoplastic conditions involving the liver. Serial determinations of the enzyme activities provided useful information about the course of certain hepatic disorders, particularly acute viral hepatitis. PMID:13711559

  7. Mast cells and their activation in lung disease.

    PubMed

    Virk, Harvinder; Arthur, Greer; Bradding, Peter

    2016-08-01

    Mast cells and their activation contribute to lung health via innate and adaptive immune responses to respiratory pathogens. They are also involved in the normal response to tissue injury. However, mast cells are involved in disease processes characterized by inflammation and remodeling of tissue structure. In these diseases mast cells are often inappropriately and chronically activated. There is evidence for activation of mast cells contributing to the pathophysiology of asthma, pulmonary fibrosis, and pulmonary hypertension. They may also play a role in chronic obstructive pulmonary disease, acute respiratory distress syndrome, and lung cancer. The diverse mechanisms through which mast cells sense and interact with the external and internal microenvironment account for their role in these diseases. Newly discovered mechanisms of redistribution and interaction between mast cells, airway structural cells, and other inflammatory cells may offer novel therapeutic targets in these disease processes. PMID:26845625

  8. Update in tuberculosis and nontuberculous mycobacterial disease 2012.

    PubMed

    Menzies, Dick; Nahid, Payam

    2013-10-15

    In 2012, new publications in the Journal described both the predictive value of the new IFN-γ release assays for diagnosis of latent tuberculosis (TB), but also provided evidence that these new tests cannot be interpreted simply as positive or negative, as initially hoped. Surgical masks can reduce transmission of TB infection, but other measures such as state-wide implementation of targeted testing and treatment of latent TB or active case finding require substantial and sustained effort to successfully reduce TB morbidity and mortality. A quasiexperimental study revealed that a package of social interventions could substantially reduce risk of TB disease in heavily exposed (and infected) children in the preantibiotic era. A study in a high-TB burden setting suggested that a new rapid drug-susceptibility test for TB may be more practical for implementation than traditional culture-based phenotypic tests. And two studies of TB vaccines revealed that currently used bacillus Calmette-Guérin strains vary in their ability to affect correlates of immunogenicity, whereas a new candidate vaccine, MVA85A, was safe and immunogenic in adults. Studies of nontuberculous mycobacteria (NTM) described a rapid rise in the prevalence and spatial clustering of NTM in the United States over the past decade. Although risk factors for pulmonary NTM such as advanced age and low BMI are known, the mechanisms underlying infection and disease remain mysterious. Four studies of therapy of NTM disease highlighted the pressing need for well-designed international randomized controlled trials to improve our management of NTM disease. PMID:24127799

  9. Noninvasive Molecular Imaging of Disease Activity in Atherosclerosis.

    PubMed

    Dweck, Marc R; Aikawa, Elena; Newby, David E; Tarkin, Jason M; Rudd, James H F; Narula, Jagat; Fayad, Zahi A

    2016-07-01

    Major focus has been placed on the identification of vulnerable plaques as a means of improving the prediction of myocardial infarction. However, this strategy has recently been questioned on the basis that the majority of these individual coronary lesions do not in fact go on to cause clinical events. Attention is, therefore, shifting to alternative imaging modalities that might provide a more complete pan-coronary assessment of the atherosclerotic disease process. These include markers of disease activity with the potential to discriminate between patients with stable burnt-out disease that is no longer metabolically active and those with active atheroma, faster disease progression, and increased risk of infarction. This review will examine how novel molecular imaging approaches can provide such assessments, focusing on inflammation and microcalcification activity, the importance of these processes to coronary atherosclerosis, and the advantages and challenges posed by these techniques. PMID:27390335

  10. Thermal and optical properties of Tb(III), Eu(III) and Tb(III)/Eu(III) co-complexed silicone fluorinated acrylate copolymer

    NASA Astrophysics Data System (ADS)

    Zhai, Yinfeng; Xie, Hongde; Cai, Haijun; Cai, Peiqing; Seo, Hyo Jin

    2015-07-01

    Tb(III), Eu(III) and Tb(III)/Eu(III) activated silicone fluorinated acrylate (SFA) have been successfully synthesized using the method of semi-continuous emulsion polymerization. The copolymers are characterized by flourier transform infrared (FT-IR), thermal gravity analysis (TGA), photoluminescence excitation (PLE) and emission (PL) spectroscopy. The copolymer containing Tb(III) and Eu(III) ions display green and red luminescent colors under UV light excitation, respectively. The TGA curves show the thermal decomposition temperatures of the copolymers are up to about 300 °C. The PL spectra show a strong green emission at 546 nm (5D4 → 7F5) of Tb(III) complexed copolymers, and show a prominent red emission at 615 nm (5D0 → 7F2) of Eu(III) complexed copolymers. Different concentrations of Eu(III) and Tb(III) ions are introduced into the copolymer and the energy transfer from Tb(III) to Eu(III) ions in the copolymer was found. Thus, based on the results it can be suggested that SFA:Eu(III), SFA:Tb(III) and SFA:Tb(III)/Eu(III) can be used potentially as luminescent materials.

  11. Patient Reported Delays in Seeking Treatment for Tuberculosis among Adult and Pediatric TB Patients and TB Patients Co-Infected with HIV in Lima, Peru: A Qualitative Study

    PubMed Central

    Paz-Soldan, Valerie A.; Alban, Rebecca E.; Dimos Jones, Christy; Powell, Amy R.; Oberhelman, Richard A.

    2014-01-01

    Introduction: Tuberculosis (TB) remains a significant public health challenge worldwide, and particularly in Peru with one of the highest incidence rates in Latin America. TB patient behavior has a direct influence on whether a patient will receive timely diagnosis and successful treatment of their illness. Objectives: The objective was to understand the complex factors that can impact TB patient health seeking behavior. Methods: In-depth interviews were conducted with adult and parents of pediatric patients receiving TB treatment (n = 43), within that group a sub-group was also co-infected with HIV (n = 11). Results: Almost all of the study participants recognized delays in seeking either their child’s or their own diagnosis of their TB symptoms. The principal reasons for treatment-seeking delays were lack of knowledge and confusion of TB symptoms, fear and embarrassment of receiving a TB diagnosis, and a patient tendency to self-medicate prior to seeking formal medical attention. Conclusion: Health promotion activities that target patient delays have the potential to improve individual patient outcomes and mitigate the spread of TB at a community level. PMID:25566523

  12. Effect of 2 Psychotherapies on Depression and Disease Activity in Pediatric Crohn's Disease

    PubMed Central

    Youk, Ada O.; Gonzalez-Heydrich, Joseph; Bujoreanu, Simona I.; Weisz, John; Fairclough, Diane; Ducharme, Peter; Jones, Neil; Lotrich, Francis; Keljo, David; Srinath, Arvind; Bousvaros, Athos; Kupfer, David; DeMaso, David R.

    2015-01-01

    Background: Crohn's disease (CD) is associated with depression. It is unclear if psychosocial interventions offer benefit for depressive symptoms during active CD. In this secondary analysis of a larger study of treating depression in pediatric inflammatory bowel disease, we assessed whether cognitive behavioral therapy (CBT) would differentiate from supportive nondirective therapy in treating depression and disease activity in youth with CD. We also explored whether somatic depressive symptoms showed a different pattern of response in the overall sample and the subset with active inflammatory bowel disease. Methods: Youth with depression and CD (n = 161) were randomized to 3 months of CBT (teaching coping skills) or supportive nondirective therapy (supportive listening). Depressive severity was measured using the Children's Depression Rating Scale-Revised (CDRS-R) with the somatic depressive subtype consisting of those CDRS-R items, which significantly correlated with CD activity. Disease activity was measured by the Pediatric Crohn's disease Activity Index. Given the potential confound of higher dose steroids, subanalyses excluded subjects on >20 mg/d prednisone equivalent (n = 34). Results: Total CDRS-R scores in the overall sample significantly decreased over time after both treatments (P < 0.0001). Treatment with CBT was associated with a significantly greater improvement in the Pediatric Crohn's disease Activity Index (P = 0.05) and somatic depressive subtype (P = 0.03) in those with active inflammatory bowel disease (n = 95) compared with supportive nondirective therapy. After excluding those on steroids (n = 34), there was a significant improvement in total CDRS-R (P = 0.03) and in Pediatric Crohn's disease Activity Index (P = 0.03) after CBT. Conclusions: Psychotherapy may be a useful adjunct to treat depression in the context of CD-related inflammation in youth who are not concurrently on higher dose steroids. PMID:25822010

  13. Fluctuating Behavior and Influential Factors in the Performance of the QuantiFERON-TB Gold In-Tube Assay in the Diagnosis of Tuberculosis

    PubMed Central

    Shen, Yaojie; Shao, Lingyun; Zhang, Ying; Lu, Shuihua; Zhang, Wenhong

    2015-01-01

    Background The QuantiFERON-TB Gold In-Tube (QFT-GIT) is a newly developed but widely used interferon-γ release assay for diagnosing tuberculosis (TB). However, research has not determined whether age or the use of an immune suppressive or anti-TB treatment influences this assay’s ability to detect TB. We assessed the QFT-GIT diagnostic performance for active tuberculosis (ATB) in children and adults in an endemic country and explored the effects of glucocorticoids and anti-TB therapy on the diagnostic value of the QFT-GIT. Methods A total of 60 children and 212 adults with suspected ATB were evaluated with the QFT-GIT. The association between the QFT-GIT diagnostic value and pretreatment factors was qualitatively and quantitatively assessed. Results The sensitivity of the QFT-GIT was 83.9% (95% CI 66.3%-94.6%) in children, and 73.7% (95% CI 57.8%-85.2%) in adults. Glucocorticoids affected the mitogen-stimulated response in both children and adults. In subjects undergoing glucocorticoid pretreatment, 25.0% of the children presented with false-negative QFT-GIT results, 28.6% of adults presented with indeterminate results. For subjects pre-treated with anti-TB drugs, 44.4% presented with false-negative QFT-GIT results. Conclusions The QFT-GIT has higher sensitivity and specificity in children than adults. Glucocorticoid treatment negatively impacts the diagnostic value of the QFT-GIT in all age groups. Anti-TB treatment decreases the sensitivity of the QFT-GIT. Therefore, we recommend that the QFT-GIT assay be performed before TB-specific treatment is initiated and the test should not be used on people undergoing immunosuppression treatment, regardless of their age. A quantitative analysis of the QFT-GIT could be useful for assessing and monitoring TB-specific and non-specific immunity during conversion of the disease. PMID:26287382

  14. Movement-related cortical activation in familial Parkinson disease.

    PubMed

    Delval, A; Defebvre, L; Labyt, E; Douay, X; Bourriez, J-L; Waucquiez, N; Derambure, P; Destée, A

    2006-09-26

    We sought to determine whether or not first-degree relatives of patients with familial Parkinson disease (FDRs) present impaired movement-related cortical activity. We studied 10 familial Parkinson disease subjects, 10 FDRs, and 10 controls and analyzed event-related mu desynchronization (ERD) and beta synchronization. Forty percent FDRs presented reduced premovement mu ERD latency, suggesting that premovement cortical activation is impaired in FDRs. PMID:17000986

  15. Host Protein Biomarkers Identify Active Tuberculosis in HIV Uninfected and Co-infected Individuals

    PubMed Central

    Achkar, Jacqueline M.; Cortes, Laetitia; Croteau, Pascal; Yanofsky, Corey; Mentinova, Marija; Rajotte, Isabelle; Schirm, Michael; Zhou, Yiyong; Junqueira-Kipnis, Ana Paula; Kasprowicz, Victoria O.; Larsen, Michelle; Allard, René; Hunter, Joanna; Paramithiotis, Eustache

    2015-01-01

    Biomarkers for active tuberculosis (TB) are urgently needed to improve rapid TB diagnosis. The objective of this study was to identify serum protein expression changes associated with TB but not latent Mycobacterium tuberculosis infection (LTBI), uninfected states, or respiratory diseases other than TB (ORD). Serum samples from 209 HIV uninfected (HIV−) and co-infected (HIV+) individuals were studied. In the discovery phase samples were analyzed via liquid chromatography and mass spectrometry, and in the verification phase biologically independent samples were analyzed via a multiplex multiple reaction monitoring mass spectrometry (MRM-MS) assay. Compared to LTBI and ORD, host proteins were significantly differentially expressed in TB, and involved in the immune response, tissue repair, and lipid metabolism. Biomarker panels whose composition differed according to HIV status, and consisted of 8 host proteins in HIV− individuals (CD14, SEPP1, SELL, TNXB, LUM, PEPD, QSOX1, COMP, APOC1), or 10 host proteins in HIV+ individuals (CD14, SEPP1, PGLYRP2, PFN1, VASN, CPN2, TAGLN2, IGFBP6), respectively, distinguished TB from ORD with excellent accuracy (AUC = 0.96 for HIV− TB, 0.95 for HIV+ TB). These results warrant validation in larger studies but provide promise that host protein biomarkers could be the basis for a rapid, blood-based test for TB. PMID:26501113

  16. Host Protein Biomarkers Identify Active Tuberculosis in HIV Uninfected and Co-infected Individuals.

    PubMed

    Achkar, Jacqueline M; Cortes, Laetitia; Croteau, Pascal; Yanofsky, Corey; Mentinova, Marija; Rajotte, Isabelle; Schirm, Michael; Zhou, Yiyong; Junqueira-Kipnis, Ana Paula; Kasprowicz, Victoria O; Larsen, Michelle; Allard, René; Hunter, Joanna; Paramithiotis, Eustache

    2015-09-01

    Biomarkers for active tuberculosis (TB) are urgently needed to improve rapid TB diagnosis. The objective of this study was to identify serum protein expression changes associated with TB but not latent Mycobacterium tuberculosis infection (LTBI), uninfected states, or respiratory diseases other than TB (ORD). Serum samples from 209 HIV uninfected (HIV(-)) and co-infected (HIV(+)) individuals were studied. In the discovery phase samples were analyzed via liquid chromatography and mass spectrometry, and in the verification phase biologically independent samples were analyzed via a multiplex multiple reaction monitoring mass spectrometry (MRM-MS) assay. Compared to LTBI and ORD, host proteins were significantly differentially expressed in TB, and involved in the immune response, tissue repair, and lipid metabolism. Biomarker panels whose composition differed according to HIV status, and consisted of 8 host proteins in HIV(-) individuals (CD14, SEPP1, SELL, TNXB, LUM, PEPD, QSOX1, COMP, APOC1), or 10 host proteins in HIV(+) individuals (CD14, SEPP1, PGLYRP2, PFN1, VASN, CPN2, TAGLN2, IGFBP6), respectively, distinguished TB from ORD with excellent accuracy (AUC = 0.96 for HIV(-) TB, 0.95 for HIV(+) TB). These results warrant validation in larger studies but provide promise that host protein biomarkers could be the basis for a rapid, blood-based test for TB. PMID:26501113

  17. [Medical economics in tuberculosis management: what will come after the TB ward?].

    PubMed

    Yotsumoto, Hideki

    2009-11-01

    Current unprofitability of medical services in tuberculosis (TB) ward in Japan has been induced by low medical fee and long-term hospital stays, aggravated by unoccupied beds due to the decrease in the number of patients. For the solution of this issue, the increase of medical fee, shortening of the length of hospital stay and drastic reduction of oversupplied beds are essential. An increment of medical fee by the change in the system would be appreciated, but even under the current system, the balance between revenue and expenditure could be obtained by reducing the length of hospital stay toward 4 weeks, and the elimination of deficit in TB ward could be accomplished by these efforts; shortening of length of hospital stay and reduction of TB beds. Although the latter might result in the difficulty of sustaining TB wards, these patients could be treated in the infectious disease ward. The integration of TB Control Law to Infectious Disease Control Law suggests that TB is not a special disease in Japan. If a true "short course therapy" era would be realized by novel anti-tuberculosis drugs, a dramatic change in TB management would occur in the near future. PMID:19999596

  18. The relationship between chitotriosidase activity and tuberculosis.

    PubMed

    Chen, M; Deng, J; Li, W; Su, C; Xia, Y; Wang, M; Li, X; Abuaku, B K; Tan, H; Wen, S W

    2015-11-01

    Chitotriosidase, secreted by activated macrophages, is a biomarker of activated macrophages. In this study, we explored whether chitotriosidase could be adopted as a biomarker to evaluate the curative effect on tuberculosis (TB). Five counties were randomly selected out of 122 counties/cities/districts in Hunan Province, China. Our cases were all TB patients who were newly diagnosed or had been receiving treatment at the Centers for Disease Control (CDCs) of these five counties between April and August in 2009. Healthy controls were selected from a community health facility in the Kaifu district of Changsha City after frequency-matching of gender and age with the cases. Chitotriosidase activity was evaluated by a fluorometric assay. Categorical variables were analysed with the χ 2 test. Measurement data in multiple groups were tested with analysis of variance and least significant difference (LSD). Correlation between chitotriosidase activity and the degree of radiological extent (DRE) was examined by Spearman's rank correlation test. The average chitotriosidase activity levels of new TB cases, TB cases with different periods of treatment (6 months) and the control group were 54·47, 34·77, 21·54, 12·73 and 10·53 nmol/h.ml, respectively. Chitotriosidase activity in TB patients declined along with the continuity of treatment. The chitotriosidase activity of both smear-positive and the smear-negative pulmonary TB patients decreased after 6 months' treatment to normal levels (P < 0·05). Moreover, chitotriosidase activity was positively correlated with DRE (r = 0·607, P < 0·001). Our results indicate that chitotriosidase might be a marker of TB treatment effects. However, further follow-up study of TB patients is needed in the future. PMID:26418349

  19. Downregulation of Sulfotransferase Expression and Activity in Diseased Human Livers

    PubMed Central

    Yalcin, Emine B.; More, Vijay; Neira, Karissa L.; Lu, Zhenqiang James; Cherrington, Nathan J.; Slitt, Angela L.

    2013-01-01

    Sulfotransferase (SULT) function has been well studied in healthy human subjects by quantifying mRNA and protein expression and determining enzyme activity with probe substrates. However, it is not well known if sulfotransferase activity changes in metabolic and liver disease, such as diabetes, steatosis, or cirrhosis. Sulfotransferases have significant roles in the regulation of hormones and excretion of xenobiotics. In the present study of normal subjects with nonfatty livers and patients with steatosis, diabetic cirrhosis, and alcoholic cirrhosis, we sought to determine SULT1A1, SULT2A1, SULT1E1, and SULT1A3 activity and mRNA and protein expression in human liver tissue. In general, sulfotransferase activity decreased significantly with severity of liver disease from steatosis to cirrhosis. Specifically, SULT1A1 and SULT1A3 activities were lower in disease states relative to nonfatty tissues. Alcoholic cirrhotic tissues further contained lower SULT1A1 and 1A3 activities than those affected by either of the two other disease states. SULT2A1, on the other hand, was only reduced in alcoholic cirrhotic tissues. SULT1E1 was reduced both in diabetic cirrhosis and in alcoholic cirrhosis tissues, relative to nonfatty liver tissues. In conclusion, the reduced levels of sulfotransferase expression and activity in diseased versus nondiseased liver tissue may alter the metabolism and disposition of xenobiotics and affect homeostasis of endobiotic sulfotransferase substrates. PMID:23775849

  20. Liposomes for Targeted Delivery of Active Agents against Neurodegenerative Diseases (Alzheimer's Disease and Parkinson's Disease)

    PubMed Central

    Spuch, Carlos; Navarro, Carmen

    2011-01-01

    Neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease represent a huge unmet medical need. The prevalence of both diseases is increasing, but the efficacy of treatment is still very limited due to various factors including the blood brain barrier (BBB). Drug delivery to the brain remains the major challenge for the treatment of all neurodegenerative diseases because of the numerous protective barriers surrounding the central nervous system. New therapeutic drugs that cross the BBB are critically needed for treatment of many brain diseases. One of the significant factors on neurotherapeutics is the constraint of the blood brain barrier and the drug release kinetics that cause peripheral serious side effects. Contrary to common belief, neurodegenerative and neurological diseases may be multisystemic in nature, and this presents numerous difficulties for their potential treatment. Overall, the aim of this paper is to summarize the last findings and news related to liposome technology in the treatment of neurodegenerative diseases and demonstrate the potential of this technology for the development of novel therapeutics and the possible applications of liposomes in the two most widespread neurodegenerative diseases, Alzheimer's disease and Parkinson's disease. PMID:22203906

  1. A Threshold Value for the Time Delay to TB Diagnosis

    PubMed Central

    Uys, Pieter W.; Warren, Robin M.; van Helden, Paul D.

    2007-01-01

    Background In many communities where TB occurs at high incidence, the major force driving the epidemic is transmission. It is plausible that the typical long delay from the onset of infectious disease to diagnosis and commencement of treatment is almost certainly the major factor contributing to the high rate of transmission. Methodology/Principal Findings This study is confined to communities which are epidemiologically relatively isolated and which have low HIV incidence. The consequences of delays to diagnosis are analyzed and the existence of a threshold delay value is demonstrated. It is shown that unless a sufficient number of cases are detected before this threshold, the epidemic will escalate. The method used for the analysis avoids the standard computer integration of systems of differential equations since the intention is to present a line of reasoning that reveals the essential dynamics of an epidemic in an intuitively clear way that is nevertheless quantitatively realistic. Conclusions/Significance The analysis presented here shows that typical delays to diagnosis present a major obstacle to the control of a TB epidemic. Control can be achieved by optimizing the rapid identification of TB cases together with measures to increase the threshold value. A calculated and aggressive program is therefore necessary in order to bring about a reduction in the prevalence of TB in a community by decreasing the time to diagnosis in all its ramifications. Intervention strategies to increase the threshold value relative to the time to diagnosis and which thereby decrease disease incidence are discussed. PMID:17712405

  2. Reductions in disease activity in the AMPLE trial: clinical response by baseline disease duration

    PubMed Central

    Schiff, Michael; Weinblatt, Michael E; Valente, Robert; Citera, Gustavo; Maldonado, Michael; Massarotti, Elena; Yazici, Yusuf; Fleischmann, Roy

    2016-01-01

    Objectives To evaluate clinical response by baseline disease duration using 2-year data from the AMPLE trial. Methods Patients were randomised to subcutaneous abatacept 125 mg weekly or adalimumab 40 mg bi-weekly, with background methotrexate. As part of a post hoc analysis, the achievement of validated definitions of remission (Clinical Disease Activity Index (CDAI) ≤2.8, Simplified Disease Activity Index (SDAI) ≤3.3, Routine Assessment of Patient Index Data 3 (RAPID3) ≤3.0, Boolean score ≤1), low disease activity (CDAI <10, SDAI <11, RAPID3 ≤6.0), Health Assessment Questionnaire-Disability Index response and American College of Rheumatology responses were evaluated by baseline disease duration (≤6 vs >6 months). Disease Activity Score 28 (C-reactive protein) <2.6 or ≤3.2 and radiographic non-progression in patients achieving remission were also evaluated. Results A total of 646 patients were randomised and treated (abatacept, n=318; adalimumab, n=328). In both treatment groups, comparable responses were achieved in patients with early rheumatoid arthritis (≤6 months) and in those with later disease (>6 months) across multiple clinical measures. Conclusions Abatacept or adalimumab with background methotrexate were associated with similar onset and sustainability of response over 2 years. Patients treated early or later in the disease course achieved comparable clinical responses. Trial registration number NCT00929864, Post-results. PMID:27110385

  3. [Guidelines for the diagnosis and treatment of latent tuberculosis infection and active tuberculosis in patients with inflammatory joint diseases proposed for treatment with tumour necrosis factor alpha antagonist drugs].

    PubMed

    Fonseca, João Eurico; Lucas, Helena; Canhão, Helena; Duarte, Raquel; Santos, Maria José; Villar, Miguel; Faustino, Augusto; Raymundo, Elena

    2006-01-01

    The Portuguese Society of Rheumatology (SPR) and the Portuguese Society of Pulmonology (SPP) have developed guidelines for the diagnosis and treatment of latent tuberculosis infection (LTBI) and active tuberculosis (AT) in patients with inflammatory joint diseases (IJD), namely rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis, treated with tumour necrosis factor alpha (TNF-a) antagonists. Due to the high risk of tuberculosis (TB) in patients with IJD, LTBI and AT screening should be performed as soon as possible, ideally at the moment of IJD diagnosis. Even if TB screening was performed at the beginning of the disease, the evaluation should be repeated before starting anti-TNF-a therapy. When TB (LTBI or AT) treatment is indicated, it should be performed before the beginning of anti-TNF-a therapy. If the IJD activity requires urgent anti-TNF-a therapy, these drugs can be started after two months of antituberculosis therapy in AT cases, or after one month in LTBI cases. Chest X-ray is mandatory for all patients. If abnormal, e.g. Gohn complex, the patient should be treated as LTBI; residual lesions require the exclusion of AT and patients with history of untreated or incomplete TB treatment should be treated as LTBI. In cases of suspected active lesions, AT diagnosis should be confirmed and adequate therapy initiated. Tuberculin skin test (TST), with two units of RT23, should be performed in all patients. If induration is less than 5 mm, the test should be repeated after 1 to 2 weeks, on the opposite forearm, and should be considered negative if the result is again inferior to 5 mm. Positive TST implicates LTBI treatment. If TST is performed in immunosuppressed IJD patients, LTBI treatment should be offered to the patient before starting anti-TNF-a therapy, even in the presence of a negative test. PMID:17117328

  4. Immunologic findings, thrombocytopenia and disease activity in lupus nephritis.

    PubMed Central

    Clark, W. F.; Linton, A. L.; Cordy, P. E.; Keown, P. E.; Lohmann, R. C.; Lindsay, R. M.

    1978-01-01

    Twenty patients with nephritis due to systemic lupus erythematosus were followed up for a mean of 34 months after renal biopsy with serial determinations of total serum complement and C3 and C4 concentrations, binding of deoxyribonucleic acid (DNA), antinuclear antibody pattern and platelet count. There were 25 episodes of nonhematologic observed disease activity in 16 of the 20 patients; elevated DNA binding and thrombocytopenia correlated well with these episodes. The mean platelet count during episodes of observed disease activity was 96 +/- 42 X 10(9)/L, which was significantly different from the mean count of 248 +/- 90 X 10(9)/L during disease quiescence. The proportion of false-positive results with the immunologic tests varied from 25% to 67% and with platelet counts it was 11%. It is suggested that thrombocytopenia may be a simple and accurate index of disease activity in lupus nephritis. PMID:350367

  5. Presumed latent ocular tuberculosis diagnosed with the positive quantiFERON-TB Gold In-Tube Test in a HLA-A29-positive patient.

    PubMed

    Rangel, Carlos Mario; Atencia, Cesar; Merayo-Lloves, Jesus; Fernandez-Vega Sanz, Alvaro

    2015-01-01

    A 59-year-old Hispanic woman presented with a 3-year history of floaters associated with bilateral reduced visual acuity. Her best-corrected visual acuity (BCVA) was 20/40. Both anterior segments were without inflammation, but fundoscopy showed mild vitreous inflammation and multiple inflammatory choroidal lesions. Tests for inflammatory and infectious diseases were negative except for human leucocyte antigen A29. The patient was diagnosed with birdshot choroidoretinopathy, and treatment was initiated with cyclosporine A 2.5 mg/kg/day. One year after treatment, the patient reported systemic symptoms with no improvement in visual acuity. Fundus findings remained with vitreal inflammation. QuantiFERON-TB Gold In-Tube Test was positive, and a diagnosis of presumed latent ocular tuberculosis (TB) was made. We initiated anti-TB treatment for 9 months. At 6 months of anti-TB therapy, there was no active inflammation. The patient was followed for 2 years with no medications and no active inflammation. Her final BCVA was 20/25. PMID:26045521

  6. Systematic Expression Profiling Analysis Identifies Specific MicroRNA-Gene Interactions that May Differentiate between Active and Latent Tuberculosis Infection

    PubMed Central

    Wu, Lawrence Shih-Hsin; Huang, Kai-Yao; Lee, Tzong-Yi; Hsu, Paul Wei-Che

    2014-01-01

    Tuberculosis (TB) is the second most common cause of death from infectious diseases. About 90% of those infected are asymptomatic—the so-called latent TB infections (LTBI), with a 10% lifetime chance of progressing to active TB. To further understand the molecular pathogenesis of TB, several molecular studies have attempted to compare the expression profiles between healthy controls and active TB or LTBI patients. However, the results vary due to diverse genetic backgrounds and study designs and the inherent complexity of the disease process. Thus, developing a sensitive and efficient method for the detection of LTBI is both crucial and challenging. For the present study, we performed a systematic analysis of the gene and microRNA profiles of healthy individuals versus those affected with TB or LTBI. Combined with a series of in silico analysis utilizing publicly available microRNA knowledge bases and published literature data, we have uncovered several microRNA-gene interactions that specifically target both the blood and lungs. Some of these molecular interactions are novel and may serve as potential biomarkers of TB and LTBI, facilitating the development for a more sensitive, efficient, and cost-effective diagnostic assay for TB and LTBI for the Taiwanese population. PMID:25276827

  7. Antiretroviral Treatment Scale-Up and Tuberculosis Mortality in High TB/HIV Burden Countries: An Econometric Analysis

    PubMed Central

    Yan, Isabel; Bendavid, Eran; Korenromp, Eline L.

    2016-01-01

    Introduction Antiretroviral therapy (ART) reduces mortality in patients with active tuberculosis (TB), but the population-level relationship between ART coverage and TB mortality is untested. We estimated the reduction in population-level TB mortality that can be attributed to increasing ART coverage across 41 high HIV-TB burden countries. Methods We compiled TB mortality trends between 1996 and 2011 from two sources: (1) national program-reported TB death notifications, adjusted for annual TB case detection rates, and (2) WHO TB mortality estimates. National coverage with ART, as proportion of HIV-infected people in need, was obtained from UNAIDS. We applied panel linear regressions controlling for HIV prevalence (5-year lagged), coverage of TB interventions (estimated by WHO and UNAIDS), gross domestic product per capita, health spending from domestic sources, urbanization, and country fixed effects. Results Models suggest that that increasing ART coverage was followed by reduced TB mortality, across multiple specifications. For death notifications at 2 to 5 years following a given ART scale-up, a 1% increase in ART coverage predicted 0.95% faster mortality rate decline (p = 0.002); resulting in 27% fewer TB deaths in 2011 alone than would have occurred without ART. Based on WHO death estimates, a 1% increase in ART predicted a 1.0% reduced TB death rate (p<0.001), and 31% fewer deaths in 2011. TB mortality was higher at higher HIV prevalence (p<0.001), but not related to coverage of isoniazid preventive therapy, cotrimoxazole preventive therapy, or other covariates. Conclusion This econometric analysis supports a substantial impact of ART on population-level TB mortality realized already within the first decade of ART scale-up, that is apparent despite variable-quality mortality data. PMID:27536864

  8. Understanding the gender aspects of tuberculosis: a narrative analysis of the lived experiences of women with TB in slums of Delhi, India.

    PubMed

    Khan, Koushambhi Basu

    2012-01-01

    There have been few ethnographic studies on gender aspects of tuberculosis (TB). In this article, drawing on a qualitative study on TB in Delhi slums and through an intersectional analysis of group interviews and personal narratives of women living with TB, I bring forth the "genderization" of TB and the associated sufferings for women. With my findings I demonstrate how gender, in conjunction with other social forces, influences the disease outcomes and stigmatizes women, how lives in slums are uniquely organized by multiple discourses that contribute to the gender makings of TB, and, finally, how women strategize to reduce their burden of illness. PMID:22150263

  9. [Macrophage activation syndrome associated with adult-onset Still's disease].

    PubMed

    Iwamoto, Masahiro

    2007-12-01

    Macrophage activation syndrome (MAS) is a rare and potentially lethal disease, resulting from uncontrolled activation and proliferation of T lymphocytes and macrophages. Adult-onset Still's disease (AOSD) is an inflammatory disease. AOSD resemble reactive MAS in its symptoms and laboratory data. Moreover, AOSD per se induces MAS. It is, therefore, quite difficult to differentiate these syndrome and disease. The immunodeficiency state induced by treatment in AOSD could reactivate latent viruses such as Epstein-Barr virus, which could potentially lead to MAS. The therapeutic agents for AOSD, such as sulfasalazine, also could provoke reactive MAS. Because multiple factors are involved in inducing MAS to a different degree, the main cause should be searched for and targeted for the therapy. PMID:18174671

  10. EULAR Sjogren's syndrome disease activity index: development of a consensus systemic disease activity index for primary Sjogren's syndrome

    PubMed Central

    Seror, Raphaèle; Ravaud, Philippe; Bowman, Simon; Baron, Gabriel; Tzioufas, Athanasios; Theander, Elke; Gottenberg, Jacques-Eric; Bootsma, Hendrika; Mariette, Xavier; Vitali, Claudio

    2010-01-01

    Objective To develop a disease activity index for patients with primary Sjögren’s syndrome (SS): the European League Against Rheumatism (EULAR) Sjögren’s Syndrome Disease Activity Index (ESSDAI). Methods Thirty-nine SS experts participated in an international collaboration, promoted by EULAR, to develop the ESSDAI. Experts identified 12 organ-specific “domains” contributing to disease activity. For each domain, features of disease activity were classified in 3 or 4 levels according to their severity. Data abstracted from 96 patients with systemic complications of primary SS were used to generate 702 realistic vignettes for which all possible systemic complications were represented. Using the 0–10 physician global assessment (PhGA) scale, each expert scored the disease activity of 5 patient profiles and 20 realistic vignettes. Multiple regression modelling, with PhGA used as the dependent variable, was used to estimate the weight of each domain. Results All 12 domains were significantly associated with disease activity in the multivariate model, domain weights ranged from 1 to 6. The ESSDAI scores varied from 2 to 47 and were significantly correlated with PhGA for both real patient profiles and realistic vignettes (r=0.61 and r=0.58, respectively, p<0.0001). Compared to 57 (59.4%) of the real patient profiles, 468 (66.7%) of the realistic vignettes were considered likely or very likely to be true. Conclusion The ESSDAI is a clinical index designed to measure disease activity in patients with primary SS. Once validated, such a standardized evaluation of primary SS should facilitate clinical research and should be helpful as an outcome measure in clinical trials. PMID:19561361

  11. Dramatic effect of redox pre-treatments on the CO oxidation activity of Au/Ce(0.50)Tb(0.12)Zr(0.38)O(2-x) catalysts prepared by deposition-precipitation with urea: a nano-analytical and nano-structural study.

    PubMed

    del Río, Eloy; López-Haro, Miguel; Cíes, José M; Delgado, Juan J; Calvino, José J; Trasobares, Susana; Blanco, Ginesa; Cauqui, Miguel A; Bernal, Serafín

    2013-08-01

    Nano-structural and nano-analytical studies show that the dramatic difference in CO oxidation activity observed between two Au/Ce0.50Tb0.12Zr0.38O2-x samples prepared by deposition-precipitation with urea and further activated under oxidising or reducing conditions is due to the poisoning effect of a very thin layer of carbon grown on the pre-reduced catalyst. PMID:23785711

  12. Inflammation, immune activation, and cardiovascular disease in HIV.

    PubMed

    Nou, Eric; Lo, Janet; Grinspoon, Steven K

    2016-06-19

    Cardiovascular disease is one of the leading causes of morbidity and mortality in people living with HIV. Several epidemiological studies have shown an increased risk of myocardial infarction and stroke compared to uninfected controls. Although traditional risk factors contribute to this increased risk of cardiovascular disease, HIV-specific mechanisms likely also play a role. Systemic inflammation has been linked to cardiovascular disease in several populations suffering from chronic inflammation, including people living with HIV. Although antiretroviral therapy reduces immune activation, levels of inflammatory markers remain elevated compared to uninfected controls. The causes of this sustained immune response are likely multifactorial and incompletely understood. In this review, we summarize the evidence describing the relationship between inflammation and cardiovascular disease and discuss potential anti-inflammatory treatment options for cardiometabolic disease in people living with HIV. PMID:27058351

  13. Antibacterial Activity of Hawaiian Corals: Possible Protection from Disease?

    NASA Astrophysics Data System (ADS)

    Gochfeld, D. J.; Aeby, G. S.; Miller, J. D.

    2006-12-01

    Reports of coral diseases in the Caribbean have appeared with increasing frequency over the past two decades; however, records of coral diseases in the Pacific have lagged far behind. Recent surveys of coral disease in the Hawaiian Islands indicate relatively low, but consistent, levels of disease throughout the inhabited Main and uninhabited Northwestern Hawaiian Islands, and demonstrate variation in levels of disease among the major genera of Hawaiian corals. Although little is known about immune defense to disease in corals, one potential mechanism of defense is the production of antimicrobial compounds that protect corals from pathogens. A preliminary survey of antibacterial chemical defenses among three dominant species of Hawaiian corals was undertaken. Crude aqueous extracts of Porites lobata, Pocillopora meandrina and Montipora capitata were tested against nine strains of bacteria in a growth inhibition assay. Inhibitory extracts were further tested to determine whether their effects were cytostatic or cytotoxic. The bacteria selected included known coral pathogens, potential marine pathogens found in human waste and strains previously identified from the surfaces of Hawaiian corals. Extracts from all three species of coral exhibited a high degree of antibacterial activity, but also a high degree of selectivity against different bacterial strains. In addition, some extracts were stimulatory to some bacteria. In addition to interspecific variability, extracts also exhibited intraspecific variability, both within and between sites. Hawaiian corals have significant antibacterial activity, which may explain the relatively low prevalence of disease in these corals; however, further characterization of pathogens specifically responsible for disease in Hawaiian corals is necessary before we can conclude that antibacterial activity protects Hawaiian corals from disease.

  14. The second Geneva Consensus: Recommendations for novel live TB vaccines.

    PubMed

    Walker, K B; Brennan, M J; Ho, M M; Eskola, J; Thiry, G; Sadoff, J; Dobbelaer, R; Grode, L; Liu, M A; Fruth, U; Lambert, P H

    2010-03-01

    Infection with Mycobacterium tuberculosis continues to be a major public health burden in most developing parts of the world and efforts to develop effective strategies for containing the disease remain a priority. It has long been evident that effective mass vaccination programmes are a cost effective and efficient approach to controlling communicable diseases in a public health setting and tuberculosis (TB) continues to be a major target. One approach with increasing acceptance is based upon on live mycobacterial vaccines, either as recombinant BCG or rationally attenuated M. tuberculosis, thus generating a new live TB vaccine. The Geneva Consensus published in March 2005 set out the opinion on priorities and requirements for developing live mycobacterial vaccines for Phase I trials. In the intervening period much progress has been made in both preclinical and clinical development of new TB vaccines and has provided the impetus for organising the second Geneva Consensus (held at WHO headquarters, April 2009) to discuss issues, including: i. Explore the regulatory requirements for live TB vaccines to enter Phase I trials, in particular those based on attenuated M. tuberculosis. Particular attention was paid to the characterisation and safety package likely to be required, including issues of attenuation, the presence of antibiotic resistance markers in live vaccines and the nature of any attenuated vaccine phenotype. ii. To identify the general criteria for further clinical development from Phase I through to Phase III. iii. Obtain a perspective of the regulatory landscape of developing countries where Phase II and III trials are to be held. iv. Review manufacturing considerations for live TB vaccines and relevance of the WHO and European Pharmacopeia guidelines and requirements for BCG vaccine. v. Consider requirements and associated issues related to the use of these new vaccines within an existing BCG vaccination programme. PMID:20074686

  15. Development of a POC Test for TB Based on Multiple Immunodominant Epitopes of M. tuberculosis Specific Cell-Wall Proteins

    PubMed Central

    Gonzalez, Jesus M.; Francis, Bryan; Burda, Sherri; Hess, Kaitlyn; Behera, Digamber; Gupta, Dheeraj; Agarwal, Ashutosh Nath; Verma, Indu; Verma, Ajoy; Myneedu, Vithal Prasad; Niedbala, Sam; Laal, Suman

    2014-01-01

    The need for an accurate, rapid, simple and affordable point-of-care (POC) test for Tuberculosis (TB) that can be implemented in microscopy centers and other peripheral health-care settings in the TB-endemic countries remains unmet. This manuscript describes preliminary results of a new prototype rapid lateral flow TB test based on detection of antibodies to immunodominant epitopes (peptides) derived from carefully selected, highly immunogenic M. tuberculosis cell-wall proteins. Peptide selection was initially based on recognition by antibodies in sera from TB patients but not in PPD-/PPD+/BCG-vaccinated individuals from TB-endemic settings. The peptides were conjugated to BSA; the purified peptide-BSA conjugates striped onto nitrocellulose membrane and adsorbed onto colloidal gold particles to devise the prototype test, and evaluated for reactivity with sera from 3 PPD-, 29 PPD+, 15 PPD-unknown healthy subjects, 10 patients with non-TB lung disease and 124 smear-positive TB patients. The assay parameters were adjusted to determine positive/negative status within 15 minutes via visual or instrumented assessment. There was minimal or no reactivity of sera from non-TB subjects with the striped BSA-peptides demonstrating the lack of anti-peptide antibodies in subjects with latent TB and/or BCG vaccination. Sera from most TB patients demonstrated reactivity with one or more peptides. The sensitivity of antibody detection ranged from 28–85% with the 9 BSA-peptides. Three peptides were further evaluated with sera from 400 subjects, including additional PPD-/PPD+/PPD-unknown healthy contacts, close hospital contacts and household contacts of untreated TB patients, patients with non-TB lung disease, and HIV+TB- patients. Combination of the 3 peptides provided sensitivity and specificity>90%. While the final fully optimized lateral flow POC test for TB is under development, these preliminary results demonstrate that an antibody-detection based rapid POC lateral flow test

  16. Natural Compounds Preventing Neurodegenerative Diseases Through Autophagic Activation.

    PubMed

    Huang, Zhe; Adachi, Hiroaki

    2016-06-01

    Neurodegenerative diseases (NDDs) are a group of intractable diseases that significantly affect human health. To date, the pathogenesis of NDDs is still poorly understood and effective disease-modifying therapies for NDDs have not been established. NDDs share the common morphological characteristic of the deposition of abnormal proteins in the nervous system, including neurons. Autophagy is one of the major processes by which damaged organelles and abnormal proteins are removed from cells. Impairment of autophagy has been found to be involved in the pathogenesis of NDDs, and the regulation of autophagy may become a therapeutic strategy for NDDs. In recent years, some active compounds from plants have been found to regulate autophagy and exert neuroprotection against NDDs, including Alzheimer's disease, Parkinson's disease, Huntington's disease, spinal and bulbar muscular atrophy, spinocerebellar ataxia 3, and amyotrophic lateral sclerosis, via activating autophagy. In this paper, we review recent advances in the use of active ingredients from plants for the regulation of autophagy and treatment of NDDs. PMID:27302727

  17. Inflammation activation and resolution in human tendon disease

    PubMed Central

    Dakin, Stephanie G; Martinez, Fernando O; Yapp, Clarence; Wells, Graham; Oppermann, Udo; Dean, Benjamin JF; Smith, Richard DJ; Wheway, Kim; Watkins, Bridget; Roche, Lucy; Carr, Andrew J

    2016-01-01

    Improved understanding of the role of inflammation in tendon disease is required to facilitate therapeutic target discovery. We studied supraspinatus tendons from patients experiencing pain before and after surgical subacromial decompression treatment. Tendons were classified as having early, intermediate or advanced disease and inflammation was characterized through activation of pathways mediated by Interferon, NF-κB, glucocorticoid receptor and STAT-6. Inflammation signatures revealed expression of genes and proteins induced by Interferon and NF-κB in early stage disease and genes and proteins induced by STAT-6 and glucocorticoid receptor activation in advanced stage disease. The pro-resolving proteins FPR2/ALX and ChemR23 were increased in early stage disease compared to intermediate-advanced stage disease. Patients who were pain-free post-treatment had tendons with increased expression of CD206 and ALOX15 mRNA compared to tendons from patients who continued to experience pain post-treatment, suggesting that these genes and their pathways may moderate tendon pain. Stromal cells from diseased tendons cultured in vitro showed increased expression of NF-κB and Interferon target genes after treatment with lipopolysaccharide or IFNγ compared to stromal cells derived from healthy tendons. We identified 15-epi Lipoxin A4, a stable lipoxin metabolite derived from aspirin treatment, as potentially beneficial in the resolution of tendon inflammation. PMID:26511510

  18. Can China achieve the WHO global targets for TB control by 2035?

    PubMed

    Huynh, Grace H

    2016-03-01

    To reach the ambitious WHO TB global targets by 2035, it is likely that China will need a comprehensive strategy that builds on its existing high-quality directly observed treatment, short-course program. This will require optimizing the use of existing tools within a changing health system landscape. In addition, new tools are needed to identify and treat TB in high-risk groups and in older people, who are a growing driver of disease incidence. Lastly, strategies are needed to address the proximate risk factors and social determinants that underlie trends in TB burden. PMID:26884495

  19. Data Needs for Evidence-Based Decisions: A TB Modeler’s “Wish List”

    PubMed Central

    Dowdy, David W.; Dye, Christopher; Cohen, Ted

    2014-01-01

    Summary Infectious disease models are important tools for understanding epidemiology and supporting policy decisions for disease control. In the case of tuberculosis (TB), such models have informed our understanding and control strategies for over 40 years, but the primary assumptions of these models – and their most urgent data needs – remain obscure to many TB researchers and control officers. The structure and parameter values of TB models are informed by observational studies and experiments, but the evidence base in support of these models remains incomplete. Speaking from the perspective of infectious disease modelers addressing the broader TB research and control communities, we describe the basic structure common to most TB models and present a “wish list” that would improve the evidence foundation upon which these models are built. As a comprehensive TB research agenda is formulated, we argue that the data needs of infectious disease models – our primary long-term decision-making tools – should figure prominently. PMID:23743307

  20. Linking estrogen receptor β expression with inflammatory bowel disease activity

    PubMed Central

    Pierdominici, Marina; Maselli, Angela; Varano, Barbara; Barbati, Cristiana; Cesaro, Paola; Spada, Cristiano; Zullo, Angelo; Lorenzetti, Roberto; Rosati, Marco; Rainaldi, Gabriella; Limiti, Maria Rosaria; Guidi, Luisa

    2015-01-01

    Crohn disease (CD) and ulcerative colitis (UC) are chronic forms of inflammatory bowel disease (IBD) whose pathogenesis is only poorly understood. Estrogens have a complex role in inflammation and growing evidence suggests that these hormones may impact IBD pathogenesis. Here, we demonstrated a significant reduction (p < 0.05) of estrogen receptor (ER)β expression in peripheral blood T lymphocytes from CD/UC patients with active disease (n = 27) as compared to those in remission (n = 21) and healthy controls (n = 29). Accordingly, in a subgroup of CD/UC patients undergoing to anti-TNF-α therapy and responsive to treatment, ERβ expression was higher (p < 0.01) than that observed in not responsive patients and comparable to that of control subjects. Notably, ERβ expression was markedly decreased in colonic mucosa of CD/UC patients with active disease, reflecting the alterations observed in peripheral blood T cells. ERβ expression inversely correlated with interleukin (IL)-6 serum levels and exogenous exposure of both T lymphocytes and intestinal epithelial cells to this cytokine resulted in ERβ downregulation. These results demonstrate that the ER profile is altered in active IBD patients at both mucosal and systemic levels, at least in part due to IL-6 dysregulation, and highlight the potential exploitation of T cell-associated ERβ as a biomarker of endoscopic disease activity. PMID:26497217

  1. Synchrotron and laser excitation of luminescence in PbWO4:Tb crystals at different temperatures

    NASA Astrophysics Data System (ADS)

    Novosad, S. S.; Kostyk, L. V.; Novosad, I. S.

    2011-09-01

    The effect of temperature on the spectral luminescence characteristics of PbWO4:Tb3+ crystals with synchrotron and laser excitation is studied. If PbWO4:Tb3+ is excited by synchrotron radiation with λ = 88 nm at 300 K, a faint recombination luminescence of the impurity terbium is observed against the matrix luminescence. When the temperature is reduced to 8 K, the luminescence intensity of PbWO4:Tb3+ increases by roughly an order of magnitude and the characteristic luminescence of the unactivated crystal is observed. Excitation of PbWO4:Tb3+ by a nitrogen laser at 300 K leads to the appearance of emission from Tb3+ ions. At 90 K, a faint matrix luminescence is observed in addition to the activator emission. The formation of the luminescence excitation spectra for wavelengths of 60-320 nm is analyzed and the nature of the emission bands is discussed.

  2. Inhibiting caspase-6 activation and catalytic activity for neurodegenerative diseases.

    PubMed

    Flygare, John A; Arkin, Michelle R

    2014-01-01

    Partnerships between industry and academia are becoming increasingly complex and relevant in the drive to discover innovative new medicines. We describe the structure of the collaboration between the University of California - San Francisco - Small Molecule Discovery Center (UCSF-SMDC) and Genentech to develop chemical matter that inhibits the activity of caspase-6. We focus on the scientific basis for the partnership and how the orientation- and transaction-related barriers were overcome. We describe the division of labor that allowed two groups to operate as a unified team to generate multiple chemical series with distinct mechanisms of action. The successful structure of the agreement serves as a model for future collaborations at both institutions. PMID:24283214

  3. Understanding Market Size and Reporting Gaps for Paediatric TB in Indonesia, Nigeria and Pakistan: Supporting Improved Treatment of Childhood TB in the Advent of New Medicines

    PubMed Central

    2015-01-01

    Objective of the Study We sought to understand gaps in reporting childhood TB cases among public and private sector health facilities (dubbed “non-NTP” facilities) outside the network of national TB control programmes, and the resulting impact of under-reporting on estimates of paediatric disease burden and market demand for new medicines. Methodology Exploratory assessments were carried out in Indonesia, Nigeria and Pakistan, reaching a range of facility types in two selected areas of each country. Record reviews and interviews of healthcare providers were carried out to assess numbers of unreported paediatric TB cases, diagnostic pathways followed and treatment regimens prescribed. Main Findings A total of 985 unreported diagnosed paediatric TB cases were identified over a three month period in 2013 in Indonesia from 64 facilities, 463 in Pakistan from 35 facilities and 24 in Nigeria from 20 facilities. These represent an absolute additional annualised yield to 2013 notifications reported to WHO of 15% for Indonesia, 2% for Nigeria and 7% for Pakistan. Only 12% of all facilities provided age and sex-disaggregated data. Findings highlight the challenges of confirming childhood TB. Diagnosis patterns in Nigeria highlight a very low suspicion for childhood TB. Providers note the need for paediatric medicines aligned to WHO recommendations. Conclusion: How Market Data Can Support Better Public Health Interventions This study emphasises the impact of incomplete reporting on the estimation of disease burden and potential market size of paediatric TB medicines. Further studies on “hubs” (facilities treating large numbers of childhood TB cases) will improve our understanding of the epidemic, support introduction efforts for new treatments and better measure markets for new paediatric medicines. PMID:26460607

  4. Perivascular fat, AMP-activated protein kinase and vascular diseases

    PubMed Central

    Almabrouk, T A M; Ewart, M A; Salt, I P; Kennedy, S

    2014-01-01

    Perivascular adipose tissue (PVAT) is an active endocrine and paracrine organ that modulates vascular function, with implications for the pathophysiology of cardiovascular disease (CVD). Adipocytes and stromal cells contained within PVAT produce mediators (adipokines, cytokines, reactive oxygen species and gaseous compounds) with a range of paracrine effects modulating vascular smooth muscle cell contraction, proliferation and migration. However, the modulatory effect of PVAT on the vascular system in diseases, such as obesity, hypertension and atherosclerosis, remains poorly characterized. AMP-activated protein kinase (AMPK) regulates adipocyte metabolism, adipose biology and vascular function, and hence may be a potential therapeutic target for metabolic disorders such as type 2 diabetes mellitus (T2DM) and the vascular complications associated with obesity and T2DM. The role of AMPK in PVAT or the actions of PVAT have yet to be established, however. Activation of AMPK by pharmacological agents, such as metformin and thiazolidinediones, may modulate the activity of PVAT surrounding blood vessels and thereby contribute to their beneficial effect in cardiometabolic diseases. This review will provide a current perspective on how PVAT may influence vascular function via AMPK. We will also attempt to demonstrate how modulating AMPK activity using pharmacological agents could be exploited therapeutically to treat cardiometabolic diseases. PMID:24490856

  5. A Bioassay for Lafora Disease and Laforin Glucan Phosphatase Activity

    PubMed Central

    Sherwood, Amanda R.; Johnson, Mary Beth; Delgado-Escueta, Antonio V.; Gentry, Matthew S.

    2013-01-01

    Objectives Lafora disease is a rare yet invariably fatal form of progressive neurodegenerative epilepsy resulting from mutations in the phosphatase laforin. Several therapeutic options for Lafora disease patients are currently being explored, and these therapies would benefit from a biochemical means of assessing functional laforin activity following treatment. To date, only clinical outcomes such as decreases in seizure frequency and severity have been used to indicate success of epilepsy treatment. However, these qualitative measures exhibit variability and must be assessed over long periods of time. In this work, we detail a simple and sensitive bioassay that can be used for the detection of functional endogenous laforin from human and mouse tissue. Design and methods We generated antibodies capable of detecting and immunoprecipitating endogenous laforin. Following laforin immunoprecipitation, laforin activity was assessed via phosphatase assays using para-nitrophenylphosphate (pNPP) and a malachite green-based assay specific for glucan phosphatase activity. Results We found that antibody binding to laforin does not impede laforin activity. Furthermore, the malachite green-based glucan phosphatase assay used in conjunction with a rabbit polyclonal laforin antibody was capable of detecting endogenous laforin activity from human and mouse tissue. Importantly, this assay discriminated between laforin activity and other phosphatases. Conclusions The bioassay that we have developed utilizing laforin antibodies and an assay specific for glucan phosphatase activity could prove valuable in the rapid detection of functional laforin in patients to which novel Lafora disease therapies have been administered. PMID:24012855

  6. Glucocerebrosidase enzyme activity in GBA mutation Parkinson's disease.

    PubMed

    Ortega, Roberto A; Torres, Paola A; Swan, Matthew; Nichols, William; Boschung, Sarah; Raymond, Deborah; Barrett, Matthew J; Johannes, Brooke A; Severt, Lawrence; Shanker, Vicki; Hunt, Ann L; Bressman, Susan; Pastores, Gregory M; Saunders-Pullman, Rachel

    2016-06-01

    Mutations in the glucocerebrosidase (GBA1) gene, the most common genetic contributor to Parkinson's disease (PD), are associated with an increased risk of PD in heterozygous and homozygous carriers. While glucocerebrosidase enzyme (GCase) activity is consistently low in Gaucher disease, there is a range of leukocyte GCase activity in healthy heterozygous GBA1 mutation carriers. To determine whether GCase activity may be a marker for PD with heterozygous GBA1 mutations (GBA1 mutation PD, GBA PD), GBA PD patients (n=15) were compared to PD patients without heterozygous GBA1 mutations (idiopathic PD; n=8), heterozygous GBA1 carriers without PD (asymptomatic carriers; n=4), and biallelic mutation carriers with PD (Gaucher disease with PD, GD1 PD; n=3) in a pilot study. GCase activity (nmol/mg protein/hour) in GD1 PD (median [interquartile range]; minimum-maximum: 6.4 [5.7]; 5.3-11) was lower than that of GBA PD (16.0 [7.0]; 11-40) (p=0.01), while GCase activity in GBA PD was lower than idiopathic PD (28.5 [15.0]; 16-56) (p=0.01) and asymptomatic carriers (25.5 [2.5]; 23-27) (p=0.04). Therefore, GCase activity appears to be a possible marker of heterozygous GBA1 mutation PD, and larger studies are warranted. Prospective studies are also necessary to determine whether lower GCase activity precedes development of PD. PMID:26857292

  7. Heme Oxygenase-1 Regulation of Matrix Metalloproteinase-1 Expression Underlies Distinct Disease Profiles in Tuberculosis.

    PubMed

    Andrade, Bruno B; Pavan Kumar, Nathella; Amaral, Eduardo P; Riteau, Nicolas; Mayer-Barber, Katrin D; Tosh, Kevin W; Maier, Nolan; Conceição, Elisabete L; Kubler, Andre; Sridhar, Rathinam; Banurekha, Vaithilingam V; Jawahar, Mohideen S; Barbosa, Theolis; Manganiello, Vincent C; Moss, Joel; Fontana, Joseph R; Marciano, Beatriz E; Sampaio, Elizabeth P; Olivier, Kenneth N; Holland, Steven M; Jackson, Sharon H; Moayeri, Mahtab; Leppla, Stephen; Sereti, Irini; Barber, Daniel L; Nutman, Thomas B; Babu, Subash; Sher, Alan

    2015-09-15

    Pulmonary tuberculosis (TB) is characterized by oxidative stress and lung tissue destruction by matrix metalloproteinases (MMPs). The interplay between these distinct pathological processes and the implications for TB diagnosis and disease staging are poorly understood. Heme oxygenase-1 (HO-1) levels were previously shown to distinguish active from latent TB, as well as successfully treated Mycobacterium tuberculosis infection. MMP-1 expression is also associated with active TB. In this study, we measured plasma levels of these two important biomarkers in distinct TB cohorts from India and Brazil. Patients with active TB expressed either very high levels of HO-1 and low levels of MMP-1 or the converse. Moreover, TB patients with either high HO-1 or MMP-1 levels displayed distinct clinical presentations, as well as plasma inflammatory marker profiles. In contrast, in an exploratory North American study, inversely correlated expression of HO-1 and MMP-1 was not observed in patients with other nontuberculous lung diseases. To assess possible regulatory interactions in the biosynthesis of these two enzymes at the cellular level, we studied the expression of HO-1 and MMP-1 in M. tuberculosis-infected human and murine macrophages. We found that infection of macrophages with live virulent M. tuberculosis is required for robust induction of high levels of HO-1 but not MMP-1. In addition, we observed that CO, a product of M. tuberculosis-induced HO-1 activity, inhibits MMP-1 expression by suppressing c-Jun/AP-1 activation. These findings reveal a mechanistic link between oxidative stress and tissue remodeling that may find applicability in the clinical staging of TB patients. PMID:26268658

  8. Cardiac parasympathetic activity in severe uncomplicated coronary artery disease.

    PubMed Central

    Nolan, J.; Flapan, A. D.; Reid, J.; Neilson, J. M.; Bloomfield, P.; Ewing, D. J.

    1994-01-01

    BACKGROUND--Previous studies have suggested that coronary artery disease is independently associated with reduced cardiac parasympathetic activity, and that this is important in its pathophysiology. These studies included many patients with complications that might be responsible for the reported autonomic abnormalities. OBJECTIVE--To measure cardiac parasympathetic activity in patients with uncomplicated coronary artery disease. PATIENTS AND METHODS--44 patients of mean (SD) age 56 (8) with severe uncomplicated coronary artery disease (symptoms uncontrolled on maximal medical treatment; > 70% coronary stenosis at angiography; normal ejection fraction; no evidence of previous infarction, diabetes, or hypertension). Heart rate variability was measured from 24 hour ambulatory electrocardiograms by counting the number of times successive RR intervals exceeded the preceding RR interval by > 50 ms, a previously validated sensitive and specific index of cardiac parasympathetic activity. RESULTS--Mean (range) of counts were: waking 112 (range 6-501)/h, sleeping 198 (0-812)/h, and total 3912 (151-14 454)/24 h. These mean results were unremarkable, and < 10% of patients fell below the lower 95% confidence interval for waking, sleeping, or total 24 hour counts in normal people. There was no relation between the severity of coronary artery disease or the use of concurrent antianginal drug treatment and cardiac parasympathetic activity. CONCLUSION--In contrast with previous reports no evidence of a specific independent association between coronary artery disease and reduced cardiac parasympathetic activity was found. The results of previous studies may reflect the inclusion of patients with complications and not the direct effect of coronary artery disease itself. PMID:7913823

  9. New advances on glial activation in health and disease

    PubMed Central

    Lee, Kim Mai; MacLean, Andrew G

    2015-01-01

    In addition to being the support cells of the central nervous system (CNS), astrocytes are now recognized as active players in the regulation of synaptic function, neural repair, and CNS immunity. Astrocytes are among the most structurally complex cells in the brain, and activation of these cells has been shown in a wide spectrum of CNS injuries and diseases. Over the past decade, research has begun to elucidate the role of astrocyte activation and changes in astrocyte morphology in the progression of neural pathologies, which has led to glial-specific interventions for drug development. Future therapies for CNS infection, injury, and neurodegenerative disease are now aimed at targeting astrocyte responses to such insults including astrocyte activation, astrogliosis and other morphological changes, and innate and adaptive immune responses. PMID:25964871

  10. A single-phase full-color phosphor based on Ba3MgSi2O8 co-activated with Eu2+, Tb3+, and Mn2+

    NASA Astrophysics Data System (ADS)

    Birkel, Alexander; DeCino, Nicholas A.; Cozzan, Clayton; Mikhailovsky, Alexander A.; Hong, Byung-Chul; Seshadri, Ram

    2015-10-01

    We present a rapid and energy-efficient microwave-assisted approach to prepare a single-phase full-color phosphor based on Ba3MgSi2O8. The samples were prepared using a citric acid based sol-gel preparation pathway with a microwave-assisted heating step, which reduces the time required for the final heat treatment to less than 30 min. Thermogravimetric analysis was utilized to optimize the solution-based preparation prior to microwave heating. The structural properties of the obtained luminescent materials have been thoroughly investigated by means of X-ray powder diffraction and Rietveld analyses. To study the optical behavior, the excitation and emission spectra were recorded. Full-color emission is achieved using Eu2+ (blue), Tb3+ (green), and Mn2+ (red) as the activator ions. The thermally robust emission was investigated using temperature-dependent luminescence spectroscopy. The energy-transfer processes within the samples were studied using time-dependent spectroscopy, and the quantum yield of this true color phosphor as a function of the composition was determined.

  11. Usefulness of Endoscopic Indices in Determination of Disease Activity in Patients with Crohn's Disease

    PubMed Central

    Kucharski, Marcin; Karczewski, Jacek; Mańkowska-Wierzbicka, Dorota; Karmelita-Katulska, Katarzyna; Kaczmarek, Elżbieta; Iwanik, Katarzyna; Rzymski, Piotr; Grzymisławski, Marian; Linke, Krzysztof; Dobrowolska, Agnieszka

    2016-01-01

    Background. Assessment of endoscopic activity of Crohn's disease (CD) is of growing importance both in clinical practice and in clinical trials. The study aimed to assess which of the endoscopic indices used for evaluation of mucosal changes correlates with the currently used clinical indices for determination of disease activity and with the results of histopathological examination. Study. A group of 71 patients with CD and 52 individuals without a diagnosis of GI tract disease as a control group were investigated, considering clinical and histological severity of the disease and the severity of inflammatory changes in the bowel. Evaluation was conducted with the use of clinical, endoscopic, and histopathological indices. Endoscopic indices were then correlated with different clinical and histopathological indices with the aim of finding the strongest correlations. Results and Conclusions. Correlation between the clinical disease activity and the severity of endoscopic lesions in CD was shown in this study to be poor. The results also indicate that the optimal endoscopic index used in the diagnostic stage and in the assessment of treatment effects in CD is Simple Endoscopic Score for Crohn's Disease (SES-CD). PMID:26997952

  12. Activities of the korean institute of tuberculosis.

    PubMed

    Ryoo, Sungweon; Kim, Hee Jin

    2014-12-01

    The Korean National Tuberculosis Association (KNTA) set up the Korean Institute of Tuberculosis (KIT) in 1970 to foster research and technical activities pertaining to tuberculosis (TB). The KNTA/KIT had successfully conducted a countrywide TB prevalence survey from 1965 to 1995 at 5-year intervals. The survey results (decline in TB rates) established Korea as a country that had successfully implemented national control programs for TB. The KIT developed the Korea Tuberculosis Surveillance System and the Laboratory Management Information System, both of which were transferred to the Korea Centers for Disease Control and Prevention after its establishment. The KIT functions as a central and supranational reference TB laboratory for microbiological and epidemiological research and provides training and education for health-care workers and medical practitioners. Recently, the KIT has expanded its activities to countries such as Ethiopia, Laos, and Timor-Leste to support TB control and prevention. The KIT will continue to support research activities and provide technical assistance in diagnosing the infection until it is completely eliminated in Korea. PMID:25861580

  13. Nutrition and Physical Activity in Nonalcoholic Fatty Liver Disease

    PubMed Central

    Oliveira, Claudia P.; de Lima Sanches, Priscila; de Abreu-Silva, Erlon Oliveira; Marcadenti, Aline

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and it is associated with other medical conditions such as diabetes mellitus, metabolic syndrome, and obesity. The mechanisms of the underlying disease development and progression are not completely established and there is no consensus concerning the pharmacological treatment. In the gold standard treatment for NAFLD weight loss, dietary therapy, and physical activity are included. However, little scientific evidence is available on diet and/or physical activity and NAFLD specifically. Many dietary approaches such as Mediterranean and DASH diet are used for treatment of other cardiometabolic risk factors such as insulin resistance and type-2 diabetes mellitus (T2DM), but on the basis of its components their role in NAFLD has been discussed. In this review, the implications of current dietary and exercise approaches, including Brazilian and other guidelines, are discussed, with a focus on determining the optimal nonpharmacological treatment to prescribe for NAFLD. PMID:26770987

  14. Nutrition and Physical Activity in Nonalcoholic Fatty Liver Disease.

    PubMed

    Oliveira, Claudia P; de Lima Sanches, Priscila; de Abreu-Silva, Erlon Oliveira; Marcadenti, Aline

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and it is associated with other medical conditions such as diabetes mellitus, metabolic syndrome, and obesity. The mechanisms of the underlying disease development and progression are not completely established and there is no consensus concerning the pharmacological treatment. In the gold standard treatment for NAFLD weight loss, dietary therapy, and physical activity are included. However, little scientific evidence is available on diet and/or physical activity and NAFLD specifically. Many dietary approaches such as Mediterranean and DASH diet are used for treatment of other cardiometabolic risk factors such as insulin resistance and type-2 diabetes mellitus (T2DM), but on the basis of its components their role in NAFLD has been discussed. In this review, the implications of current dietary and exercise approaches, including Brazilian and other guidelines, are discussed, with a focus on determining the optimal nonpharmacological treatment to prescribe for NAFLD. PMID:26770987

  15. Human ZMPSTE24 disease mutations: residual proteolytic activity correlates with disease severity

    PubMed Central

    Barrowman, Jemima; Wiley, Patricia A.; Hudon-Miller, Sarah E.; Hrycyna, Christine A.; Michaelis, Susan

    2012-01-01

    The zinc metalloprotease ZMPSTE24 plays a critical role in nuclear lamin biology by cleaving the prenylated and carboxylmethylated 15-amino acid tail from the C-terminus of prelamin A to yield mature lamin A. A defect in this proteolytic event, caused by a mutation in the lamin A gene (LMNA) that eliminates the ZMPSTE24 cleavage site, underlies the premature aging disease Hutchinson-Gilford Progeria Syndrome (HGPS). Likewise, mutations in the ZMPSTE24 gene that result in decreased enzyme function cause a spectrum of diseases that share certain features of premature aging. Twenty human ZMPSTE24 alleles have been identified that are associated with three disease categories of increasing severity: mandibuloacral dysplasia type B (MAD-B), severe progeria (atypical ‘HGPS’) and restrictive dermopathy (RD). To determine whether a correlation exists between decreasing ZMPSTE24 protease activity and increasing disease severity, we expressed mutant alleles of ZMPSTE24 in yeast and optimized in vivo yeast mating assays to directly compare the activity of alleles associated with each disease category. We also measured the activity of yeast crude membranes containing the ZMPSTE24 mutant proteins in vitro. We determined that, in general, the residual activity of ZMPSTE24 patient alleles correlates with disease severity. Complete loss-of-function alleles are associated with RD, whereas retention of partial, measureable activity results in MAD-B or severe progeria. Importantly, our assays can discriminate small differences in activity among the mutants, confirming that the methods presented here will be useful for characterizing any new ZMPSTE24 mutations that are discovered. PMID:22718200

  16. Active immunotherapy options for Alzheimer’s disease

    PubMed Central

    2014-01-01

    Alzheimer’s disease (AD) is the most common cause of dementia and a major contributor to disability and dependency among older people. AD pathogenesis is associated with the accumulation of amyloid-beta protein (Aβ) and/or hyperphosphorylated tau protein in the brain. At present, current therapies provide temporary symptomatic benefit, but do not treat the underlying disease. Recent research has thus focused on investigating the molecular and cellular pathways and processes involved in AD pathogenesis to support the development of effective disease-modifying agents. In accordance with the existing Aβ-cascade hypothesis for AD pathogenesis, immunotherapy has been the most extensively studied approach in Aβ-targeted therapy. Both passive and active immunotherapies have been shown to effectively reduce Aβ accumulation and prevent downstream pathology in preclinical models. Following AN1792, second-generation active immunotherapies have shown promising results in terms of antibody response and safety. Comparatively, tau immunotherapy is not as advanced, but preclinical data support its development into clinical trials. Results from active amyloid-based immunotherapy studies in preclinical models indicate that intervention appears to be more effective in early stages of amyloid accumulation, highlighting the importance of diagnosing AD as early as possible and undertaking clinical trials at this stage. This strategy, combined with improving our understanding of the complex AD pathogenesis, is imperative to the successful development of these disease-modifying agents. This paper will review the active immunotherapies currently in development, including the benefits and challenges associated with this approach. PMID:24476230

  17. TB an epidemic in Russia's prisons.

    PubMed

    1999-01-01

    Over 100,000 prisoners are infected with tuberculosis (TB) in Russia, which has the highest incarceration rate in the world. Drug-resistant TB is found in thousands of inmates, and approximately 20,000 have died from it within the past 2 years. Although the country now has 50 centers for TB-infected prisoners, many are not being cured because of medicine shortages and failure to complete treatment. Up to 25 percent of TB infections found in Russian jails are multi-drug resistant, as opposed to 4 percent in Russia's general population and under 2 percent in the United States. PMID:11367347

  18. Social, Economic, and Psychological Impacts of MDR-TB Treatment in Tijuana, Mexico: A Patient's Perspective

    PubMed Central

    Morris, Meghan D.; Quezada, Liliana; Bhat, Priya; Moser, Kathleen; Smith, Jennifer; Perez, Hector; Laniado-Laborin, Rafael; Estrada-Guzman, Julia; Rodwell, Timothy C.

    2013-01-01

    Setting The state of Baja California, Mexico had the highest prevalence of multidrug-resistant tuberculosis (MDR-TB) in Mexico in 2009. Objective To understand the socioeconomic burdens of MDR-TB disease and its treatment on patients in Tijuana and Mexicali, Mexico. Design From July to November 2009, qualitative interviews were conducted with 12 patients who were enrolled in a US-Mexico binational MDR-TB treatment program called “Puentes de Esperanza” (Bridges of Hope), which was designed to support MDR-TB patients. In-depth interviews were coded to identify major themes in patient experiences of MDR-TB diagnosis and care. Results While some patients were able to maintain their pre-MDR-TB lives to a limited extent, most patients reported losing their sense of identity due to their inability to work, social isolation, and stigmatization from family and friends. The majority of participants expressed appreciation for Puentes’ role in “saving their life.” Conclusion Being diagnosed with MDR-TB and undergoing treatment imposes significant psychological, social, and economic stress on patients. Strong social support elements within Puentes helped ameliorate these burdens. Improvements to the program might include peer-support groups for patients undergoing treatment and transitioning back into the community after treatment. PMID:23743315

  19. Management and treatment outcomes of patients enrolled in MDR-TB treatment in Viet Nam

    PubMed Central

    Nhung, N. V.; Hoa, N. B.; Thuy, H. T.; Takarinda, K. C.; Tayler-Smith, K.; Harries, A. D.

    2016-01-01

    Setting: The programmatic management of drug-resistant tuberculosis (TB) in Viet Nam has been rapidly scaled up since 2009. Objectives: To document the annual numbers of patients enrolled for multidrug-resistant tuberculosis (MDR-TB) treatment during 2010–2014 and to determine characteristics and treatment outcomes of patients initiating treatment during 2010–2012. Design: A retrospective cohort study using national reports and data from the national electronic data system for drug-resistant TB. Results: The number of patients enrolled annually for MDR-TB treatment increased from 97 in 2010 to 1522 in 2014. The majority of patients were middle-aged men who had pulmonary disease and had failed a retreatment regimen; 77% had received ⩾2 courses of TB treatment. Favourable outcomes (cured and treatment completed) were attained in 73% of patients. Unfavourable outcomes included loss to follow-up (12.5%), death (8%) and failure (6.3%). Having had ⩾2 previous treatment courses and being human immunodeficiency virus-positive were associated with unfavourable outcomes. Conclusion: Increasing numbers of patients are being treated for MDR-TB each year with good treatment outcomes under national programme management in Viet Nam. However, there is a need to increase case detection—currently at 30% of the estimated 5100 MDR-TB cases per year, reduce adverse outcomes and improve monitoring and evaluation. PMID:27051608

  20. Diet and Physical Activity for Cardiovascular Disease Prevention.

    PubMed

    Lanier, Jeffrey B; Bury, David C; Richardson, Sean W

    2016-06-01

    Cardiovascular disease (CVD) is the leading cause of death in the United States. One-third of these deaths may be preventable through healthy lifestyle choices including diet and physical activity. The Mediterranean diet is associated with reduced cardiovascular mortality, whereas the Dietary Approaches to Stop Hypertension (DASH) eating plan is associated with a reduced risk of coronary artery disease. Substituting dietary saturated fat with polyunsaturated fatty acids is associated with improved cardiovascular outcomes, although exogenous supplementation with omega-3 fatty acids does not improve cardiovascular outcomes. There is an association between increased sodium intake and cardiovascular risk, but reducing dietary sodium has not consistently shown a reduction in cardiovascular risk. Physical activity recommendations for adults are at least 150 minutes of moderate-intensity aerobic activity per week, 75 minutes of vigorous-intensity aerobic activity per week, or an equivalent combination. Increases in physical activity by any level are associated with reduced cardiovascular risk. Introducing muscle-strengthening activities at least twice per week in previously inactive adults is associated with improved cardiovascular outcomes. Inactive adults without known CVD can gradually increase activity to a moderate-intensity level without consulting a physician. The U.S. Preventive Services Task Force recommends behavioral counseling to promote healthy diet and physical activity in adults at high risk of CVD. Evidence of benefit for counseling patients at average risk is less established. PMID:27281836

  1. The transmission and control of XDR TB in South Africa: an operations research and mathematical modelling approach

    PubMed Central

    BASU, S.; GALVANI, A. P.

    2008-01-01

    SUMMARY Extensively drug-resistant tuberculosis (XDR TB) has emerged as a threat to TB control efforts in several high-burden areas, generating international concern. XDR TB is now found in every region of the world, but appears most worrisome in the context of HIV and in resource-limited settings with congregate hospital wards. Here, we examine the emergence and transmission dynamics of the disease, incorporating the mathematical modelling literature related to airborne infection and epidemiological studies related to the operations of TB control programmes in resource-limited settings. We find that while XDR TB may present many challenges in the setting of resource constraints, the central problems highlighted by the emergence of XDR TB are those that have plagued TB programmes for years. These include a slow rate of case detection that permits prolonged infectiousness, the threat of airborne infection in enclosed spaces, the problem of inadequate treatment delivery and treatment completion, and the need to develop health systems that can address the combination of TB and poverty. Mathematical models of TB transmission shed light on the idea that community-based therapy and rapid detection systems may be beneficial in resource-limited settings, while congregate hospital wards are sites for major structural reform. PMID:18606028

  2. Identifying locations of recent TB transmission in rural Uganda: a multidisciplinary approach

    PubMed Central

    Chamie, Gabriel; Wandera, Bonnie; Marquez, Carina; Kato-Maeda, Midori; Kamya, Moses R.; Havlir, Diane V.; Charlebois, Edwin D.

    2015-01-01

    Objectives Targeting high TB transmission sites may offer a novel approach to TB prevention in sub-Saharan Africa. We sought to characterize TB transmission sites in a rural Ugandan township. Methods We recruited adults starting TB treatment in Tororo, Uganda over one year. 54 TB cases provided names of frequent contacts, sites of residence, health care, work and social activities, and two sputum samples. Mycobacterium tuberculosis (MTB) culture-positive specimens underwent spoligotyping to identify strains with shared genotypes. We visualized TB case social networks, and obtained, mapped and geo-coded global positioning system measures for every location that cases reported frequenting one month before treatment. Locations of spatial overlap among genotype-clustered cases were considered potential transmission sites. Results Six distinct genotypic clusters were identified involving 21/33(64%) MTB culture-positive, genotyped cases; none shared a home. Although 18/54(33%) TB cases shared social network ties, none of the genotype-clustered cases shared social ties. Using spatial analysis, we identified potential sites of within-cluster TB transmission for five of six genotypic clusters. All sites but one were health care and social venues, including sites of drinking, worship and marketplaces. Cases reported spending the largest proportion of pre-treatment person-time (22.4%) at drinking venues. Conclusions Using molecular epidemiology, geospatial and social network data from adult TB cases identified at clinics, we quantified person-time spent at high-risk locations across a rural Ugandan community, and determined the most likely sites of recent TB transmission to be health care and social venues. These sites may not have been identified using contact investigation alone. PMID:25583212

  3. [Spectra characteristics of LiM (M = Ca, Sr, Ba) BO3 : Tb3+ phosphor].

    PubMed

    Wang, Zhi-Jun; Li, Pan-Lai; Yang, Zhi-Ping; Guo, Qing-Lin

    2009-11-01

    LiM (M = Ca, Sr, Ba) BO3 : Tb3+ phosphors were synthesized by solid state reaction. The starting materials CaCO3, SrCO3, BaCO3, H3 BO3, Li2 CO3, Na2 CO3, K2 CO3 and Tb4 O7 (99.99% in mass) in appropriate stoichiometric ratio were mixed in the alumina crucible, then the mixed powders were calcined at 700 degrees C for 2 h, and LiCaBO3 : Tb3+, LiSrBO3 : Tb3+ and LiB-aBO3 : Tb3+ phosphors were obtained. The emission and excitation spectra were measured by a Shimadzu RF-540 ultraviolet spectrophotometer. All the photoluminescence properties of these phosphors were measured at room temperature. The emission spectra of LiM (M = Ca, Sr, Ba) BO3 : Tb3+ phosphors show several bands, and the main emission peaks correspond to the 5D4 --> 7F6(486, 486, 488 nm), 5D4 --> F5 (544, 544, 544 nm), 5D4 --> 7F4 (590, 595, 593 nm) and 5D4 --> 7F3 (620, 620, 616 nm) typical transitions of Tb3+, and the typical transitions of Tb3+ happens to split because of the effects of LiM (M = Ca, Sr, Ba) BO3 crystals field. The excitation spectra for the 544 nm green emission of LiM (M = Ca, Sr, Ba)BO3 : Tb3+ phosphors illuminate that these kinds of phosphors can be effectively excited by ultraviolet (350-410 nm) light, and emit green light, therefore, they are promising phosphors for white light emitting diodes. Effects of activation and charge compensation on the luminescence intensities of LiM (M = Ca, Sr, Ba) BO3 : Tb3+ phosphors were studied, and the results show that the intensities were obviously effected. PMID:20101952

  4. Distinct features of circulating microparticles and their relationship with disease activity in inflammatory bowel disease

    PubMed Central

    Voudoukis, Evangelos; Vetsika, Eleni-Kyriaki; Giannakopoulou, Konstantina; Karmiris, Konstantinos; Theodoropoulou, Angeliki; Sfiridaki, Aekaterini; Georgoulias, Vassilis; Paspatis, Gregorios A.; Koutroubakis, Ioannis E.

    2016-01-01

    Background There is evidence that circulating microparticles (MPs) and annexin (+) platelet-derived MPs (PDMPs) are increased in inflammatory bowel disease (IBD). The aim of our study was to characterize the abundance, origin, and annexin V binding of MPs in patients with IBD and correlate them with the disease characteristics. Methods Case-control study of 46 IBD patients (23 Crohn’s disease, 23 ulcerative colitis) and 40 matched healthy controls (HC). MPs were divided according to annexin V binding, their origin was estimated based on specific cell membrane markers in plasma samples and their number was calculated via flow cytometry. Clinical and laboratory activity indices were also analyzed. Results Annexin (-) PDMPs (P=0.0004), total (P=0.04) and annexin (+) monocyte-derived MPs (P=0.02) were increased and annexin (-) total MPs (P=0.0007) were decreased in IBD patients compared to HC. The annexin (+)/(-) ratio of all MP types were significantly elevated in IBD patients compared to HC (P<0.003). IBD patients with active disease displayed elevated total and annexin (+) total MPs, total, annexin (+) and (-) PDMPs compared with those in remission (P<0.05). Annexin (-) PDMPs were considerably increased in IBD patients with active compared to those with inactive disease (P=0.0013). Total and annexin (-) PDMPs were significantly correlated with most of the disease activity indices (P<0.05). Conclusion The majority of circulating MPs, their counterparts and particularly annexin (-) PDMPs are increased in active IBD patients. Annexin (+)/(-) ratio proved to be the most reliable distinctive MP index between HC and IBD patients. PMID:27065731

  5. Mouse models of human TB pathology: roles in the analysis of necrosis and the development of host-directed therapies.

    PubMed

    Kramnik, Igor; Beamer, Gillian

    2016-03-01

    A key aspect of TB pathogenesis that maintains Mycobacterium tuberculosis in the human population is the ability to cause necrosis in pulmonary lesions. As co-evolution shaped M . tuberculosis (M.tb) and human responses, the complete TB disease profile and lesion manifestation are not fully reproduced by any animal model. However, animal models are absolutely critical to understand how infection with virulent M.tb generates outcomes necessary for the pathogen transmission and evolutionary success. In humans, a wide spectrum of TB outcomes has been recognized based on clinical and epidemiological data. In mice, there is clear genetic basis for susceptibility. Although the spectra of human and mouse TB do not completely overlap, comparison of human TB with mouse lesions across genetically diverse strains firmly establishes points of convergence. By embracing the genetic heterogeneity of the mouse population, we gain tremendous advantage in the quest for suitable in vivo models. Below, we review genetically defined mouse models that recapitulate a key element of M.tb pathogenesis-induction of necrotic TB lesions in the lungs-and discuss how these models may reflect TB stratification and pathogenesis in humans. The approach ensures that roles that mouse models play in basic and translational TB research will continue to increase allowing researchers to address fundamental questions of TB pathogenesis and bacterial physiology in vivo using this well-defined, reproducible, and cost-efficient system. Combination of the new generation mouse models with advanced imaging technologies will also allow rapid and inexpensive assessment of experimental vaccines and therapies prior to testing in larger animals and clinical trials. PMID:26542392

  6. Platelet activity in the pathophysiology of inflammatory bowel diseases.

    PubMed

    Chen, Chunqiu; Li, Yongyu; Yu, Zhen; Liu, Zhanju; Shi, Yanhong; Lewandowska, Urszula; Sobczak, Marta; Fichna, Jakub; Kreis, Martin

    2015-01-01

    Platelets play a crucial role in immune responses. Impaired platelet activation may cause persistent mucosal inflammation through P-selectin, CD40-CD40L and other systems influencing granulocytes, macrophages or endothelial cells. Pharmacological regulation of platelet activation may reduce thromboembolism and limit the interaction of platelets with endothelial and inflammatory cells, in turn weakening the inflammatory responses. In this review we focus on pathophysiological activities of platelets in inflammatory bowel diseases and discuss the studies on currently available anti-platelet therapies in the treatment of gastrointestinal inflammation. Finally, we provide a prospective view to new anti-platelet agents currently under development. PMID:25585124

  7. Active immunization therapies for Parkinson's disease and multiple system atrophy.

    PubMed

    Schneeberger, Achim; Tierney, Lanay; Mandler, Markus

    2016-02-01

    Vaccination is increasingly being investigated as a potential treatment for synucleinopathies, a group of neurodegenerative diseases including Parkinson's disease, multiple system atrophy, and dementia with Lewy bodies associated with α-synuclein pathology. All lack a causal therapy. Development of novel, disease-altering treatment strategies is urgently needed. Vaccination has positioned itself as a prime strategy for addressing these diseases because it is broadly applicable, requires infrequent administration, and maintains low production costs for treating a large population or as a preventive measure. Current evidence points to a causal role of misfolded α-synuclein in the development and progression of synucleinopathies. In the past decade, significant progress in active immunization against α-synuclein has been shown both in preclinical animal models and in early clinical development. In this review, we describe the state-of-the-art in active immunization approaches to synucleinopathies, with a focus on advances in Parkinson's disease (PD) and multiple-system atrophy (MSA). We first review preclinical animal models, highlighting their progress in translation to the clinical setting. We then discuss current clinical applications, stressing different approaches taken to address α-synuclein pathology. Finally, we address challenges, trends, and future perspectives of current vaccination programs. PMID:26260853

  8. Chronic lymphocytic leukemia: a disease of activated monoclonal B cells

    PubMed Central

    Damle, Rajendra N.; Calissano, Carlo; Chiorazzi, Nicholas

    2010-01-01

    B-cell type chronic lymphocytic leukemia (CLL) has long been considered a disease of resting lymphocytes. However cell surface and intracellular phenotypes suggest that most CLL cells are activated cells, although only a small subset progresses beyond the G1 stage of the cell cycle. In addition, traditional teaching says that CLL cells divide rarely, and therefore the buildup of leukemic cells is due to an inherent defect in cell death. However, in vivo labeling of CLL cells indicates a much more active rate of cell birth than originally estimated, suggesting that CLL is a dynamic disease. Here we review the observations that have led to these altered views of the activation state and proliferative capacities of CLL cells and also provide our interpretation of these observations in light of their potential impact on patients. PMID:20620969

  9. Diversity and Activity of Lysobacter Species from Disease Suppressive Soils

    PubMed Central

    Gómez Expósito, Ruth; Postma, Joeke; Raaijmakers, Jos M.; De Bruijn, Irene

    2015-01-01

    The genus Lysobacter includes several species that produce a range of extracellular enzymes and other metabolites with activity against bacteria, fungi, oomycetes, and nematodes. Lysobacter species were found to be more abundant in soil suppressive against the fungal root pathogen Rhizoctonia solani, but their actual role in disease suppression is still unclear. Here, the antifungal and plant growth-promoting activities of 18 Lysobacter strains, including 11 strains from Rhizoctonia-suppressive soils, were studied both in vitro and in vivo. Based on 16S rRNA sequencing, the Lysobacter strains from the Rhizoctonia-suppressive soil belonged to the four species Lysobacter antibioticus, Lysobacter capsici, Lysobacter enzymogenes, and Lysobacter gummosus. Most strains showed strong in vitro activity against R. solani and several other pathogens, including Pythium ultimum, Aspergillus niger, Fusarium oxysporum, and Xanthomonas campestris. When the Lysobacter strains were introduced into soil, however, no significant and consistent suppression of R. solani damping-off disease of sugar beet and cauliflower was observed. Subsequent bioassays further revealed that none of the Lysobacter strains was able to promote growth of sugar beet, cauliflower, onion, and Arabidopsis thaliana, either directly or via volatile compounds. The lack of in vivo activity is most likely attributed to poor colonization of the rhizosphere by the introduced Lysobacter strains. In conclusion, our results demonstrated that Lysobacter species have strong antagonistic activities against a range of pathogens, making them an important source for putative new enzymes and antimicrobial compounds. However, their potential role in R. solani disease suppressive soil could not be confirmed. In-depth omics'–based analyses will be needed to shed more light on the potential contribution of Lysobacter species to the collective activities of microbial consortia in disease suppressive soils. PMID:26635735

  10. Diversity and Activity of Lysobacter Species from Disease Suppressive Soils.

    PubMed

    Gómez Expósito, Ruth; Postma, Joeke; Raaijmakers, Jos M; De Bruijn, Irene

    2015-01-01

    The genus Lysobacter includes several species that produce a range of extracellular enzymes and other metabolites with activity against bacteria, fungi, oomycetes, and nematodes. Lysobacter species were found to be more abundant in soil suppressive against the fungal root pathogen Rhizoctonia solani, but their actual role in disease suppression is still unclear. Here, the antifungal and plant growth-promoting activities of 18 Lysobacter strains, including 11 strains from Rhizoctonia-suppressive soils, were studied both in vitro and in vivo. Based on 16S rRNA sequencing, the Lysobacter strains from the Rhizoctonia-suppressive soil belonged to the four species Lysobacter antibioticus, Lysobacter capsici, Lysobacter enzymogenes, and Lysobacter gummosus. Most strains showed strong in vitro activity against R. solani and several other pathogens, including Pythium ultimum, Aspergillus niger, Fusarium oxysporum, and Xanthomonas campestris. When the Lysobacter strains were introduced into soil, however, no significant and consistent suppression of R. solani damping-off disease of sugar beet and cauliflower was observed. Subsequent bioassays further revealed that none of the Lysobacter strains was able to promote growth of sugar beet, cauliflower, onion, and Arabidopsis thaliana, either directly or via volatile compounds. The lack of in vivo activity is most likely attributed to poor colonization of the rhizosphere by the introduced Lysobacter strains. In conclusion, our results demonstrated that Lysobacter species have strong antagonistic activities against a range of pathogens, making them an important source for putative new enzymes and antimicrobial compounds. However, their potential role in R. solani disease suppressive soil could not be confirmed. In-depth omics'-based analyses will be needed to shed more light on the potential contribution of Lysobacter species to the collective activities of microbial consortia in disease suppressive soils. PMID:26635735

  11. Measurement of Fractional Exhaled Nitric Oxide as a Marker of Disease Activity in Inflammatory Bowel Disease

    PubMed Central

    Ikonomi, Erkanda; Rothstein, Robin D.; Ehrlich, Adam C.; Friedenberg, Frank K.

    2016-01-01

    Background and Aims Definitive diagnosis of IBD requires endoscopic and pathologic confirmation. These tools are also used to classify disease activity. Our aim was to determine if the fractional exhaled nitric oxide (FeNO) could be utilized to screen for IBD and assess for disease activity. Methods We matched weighted IBD cases and controls from the 2009–2010 NHANES dataset. All subjects underwent measurement of FeNO using standardized techniques. We assessed for potential confounders for FeNO measurement including age, height, and asthma. For IBD subjects, we used the presence of diarrhea, fatigue, and weight loss as a proxy for IBD activity. Laboratory parameters examined to estimate disease activity included anemia (≤ 10 g/dl), iron deficiency (ferritin ≤ 20 ng/ml), hypoalbuminemia (≤ 3.2 g/dl), and CRP (≥ 1.1 mg/dl). Results The weighted sample represented 199,414,901 subjects. The weighted prevalence of IBD was 2,084,895 (1.0%). IBD subjects had nearly the same FeNO level as those without IBD (17.0 ± 16.2 vs. 16.7 ± 14.5 ppb). The odds of a FeNO > 25 ppb was half (OR=0.501; 95% CI 0.497–0.504) for subjects with IBD compared to those without IBD after controlling for confounders. The AUROC curve for FeNO was 0.47 (0.35–0.59). FeNO levels were not higher in patients with laboratory values suggestive of active disease. FeNO levels were higher in IBD patients with diarrhea, rectal urgency, and fatigue but were lower in those with unintentional weight loss. Conclusion Measurement of FeNO does not appear to be useful to screen for IBD or assess disease activity. PMID:27398403

  12. Elevation of Serum Acid Sphingomyelinase Activity in Acute Kawasaki Disease.

    PubMed

    Konno, Yuuki; Takahashi, Ikuko; Narita, Ayuko; Takeda, Osamu; Koizumi, Hiromi; Tamura, Masamichi; Kikuchi, Wataru; Komatsu, Akira; Tamura, Hiroaki; Tsuchida, Satoko; Noguchi, Atsuko; Takahashi, Tsutomu

    2015-01-01

    Kawasaki disease (KD) is an acute systemic vasculitis that affects both small and medium-sized vessels including the coronary arteries in infants and children. Acid sphingomyelinase (ASM) is a lysosomal glycoprotein that hydrolyzes sphingomyelin to ceramide, a lipid, that functions as a second messenger in the regulation of cell functions. ASM activation has been implicated in numerous cellular stress responses and is associated with cellular ASM secretion, either through alternative trafficking of the ASM precursor protein or by means of an unidentified mechanism. Elevation of serum ASM activity has been described in several human diseases, suggesting that patients with diseases involving vascular endothelial cells may exhibit a preferential elevation of serum ASM activity. As acute KD is characterized by systemic vasculitis that could affect vascular endothelial cells, the elevation of serum ASM activity should be considered in these patients. In the present study, serum ASM activity in the sera of 15 patients with acute KD was determined both before and after treatment with infusion of high-dose intravenous immunoglobulin (IVIG), a first-line treatment for acute KD. Serum ASM activity before IVIG was significantly elevated in KD patients when compared to the control group (3.85 ± 1.46 nmol/0.1 ml/6 h vs. 1.15 ± 0.10 nmol/0.1 ml/6 h, p < 0.001), suggesting that ASM activation may be involved in the pathophysiology of this condition. Serum ASM activity before IVIG was significantly correlated with levels of C-reactive protein (p < 0.05). These results suggest the involvement of sphingolipid metabolism in the pathophysiology of KD. PMID:26447086

  13. Sensitivity of C-Tb: a novel RD-1-specific skin test for the diagnosis of tuberculosis infection.

    PubMed

    Hoff, Soren T; Peter, Jonathan G; Theron, Grant; Pascoe, Mellissa; Tingskov, Pernille N; Aggerbeck, Henrik; Kolbus, Daniel; Ruhwald, Morten; Andersen, Peter; Dheda, Keertan

    2016-03-01

    C-Tb, a novel Mycobacterium tuberculosis and 6-kDa early secretory antigenic target/10-kDa culture filtrate protein (ESAT-6/CFP-10)-specific skin test, has high specificity in bacille Calmette-Guerin-vaccinated healthy controls. However, the sensitivity of C-Tb has hitherto not been determined. The objective was to determine the sensitivity of C-Tb in patients with active tuberculosis (TB) in comparison with the tuberculin skin test (TST) and QuantiFERON-TB Gold In-Tube (QFT-GIT).C-Tb and TST were randomly administered in a double-blinded fashion to one or the other forearm in 253 patients with active TB with or without HIV co-infection. QFT-GIT testing was performed prior to skin testing.Using a receiver operating characteristic curve-derived cut-point of 5 mm, C-Tb sensitivity was similar to QFT-GIT (73.9 (95% CI 67.8-79.3) versus 75.1 (95% CI 69.3-80.2)), and similar in HIV-infected and HIV-uninfected patients (76.7 (95% CI 69.0-83.3) versus 69.5 (95% CI 59.2-78.5)). However, sensitivity was significantly diminished in HIV-infected patients with CD4 counts <100 cells·mm(-3). C-Tb and QFT-GIT combined had significantly higher sensitivity than C-Tb alone (p<0.0001). C-Tb was safe with no significant adverse events. The 5 mm cut-point corresponded to that found in the previously published specificity study (TESEC-04).C-Tb has similar sensitivity compared with QFT-GIT for the diagnosis of M. tuberculosis infection. Sensitivity was reduced only in HIV-infected patients with severe immunosuppression. Further studies in different settings are required to validate the proposed 5 mm cut-point. PMID:26677940

  14. Plasma Levels of Neopterin and C-Reactive Protein (CRP) in Tuberculosis (TB) with and without HIV Coinfection in Relation to CD4 Cell Count

    PubMed Central

    Skogmar, Sten; Schön, Thomas; Balcha, Taye Tolera; Sturegård, Erik; Jansson, Marianne; Björkman, Per

    2015-01-01

    Background While the risk of TB is elevated in HIV-positive subjects with low CD4 cell counts, TB may in itself be associated with CD4 lymphocytopenia. We investigated markers of immune activation (neopterin) and inflammation (CRP) in TB patients with and without HIV coinfection and their association with CD4 cell levels, and determined their predictive capacity as alternative markers of advanced immunosuppression. Methods Participants selected from a cohort of adults with TB at Ethiopian health centers (195 HIV+/TB+, 170 HIV-/TB+) and 31 controls were tested for plasma levels of neopterin and CRP. Baseline levels of neopterin and CRP were correlated to CD4 cell count before and after anti-TB treatment (ATT). The performance to predict CD4 cell strata for both markers were investigated using receiver operating curves. Results Levels of both biomarkers were elevated in TB patients (neopterin: HIV+/TB+ 54 nmol/l, HIV-/TB+ 23 nmol/l, controls 3.8 nmol/l; CRP: HIV+/TB+ 36 μg/ml, HIV-/TB+ 33 μg/ml, controls 0.5 μg/ml). Neopterin levels were inversely correlated (-0.53, p<0.001) to CD4 cell count, whereas this correlation was weaker for CRP (-0.25, p<0.001). Neither of the markers had adequate predictive value for identification of subjects with CD4 cell count <100 cells/mm3 (area under the curve [AUC] 0.64 for neopterin, AUC 0.59 for CRP). Conclusion Neopterin levels were high in adults with TB, both with and without HIV coinfection, with inverse correlation to CD4 cell count. This suggests that immune activation may be involved in TB-related CD4 lymphocytopenia. However, neither neopterin nor CRP showed promise as alternative tests for immunosuppression in patients coinfected with HIV and TB. PMID:26630153

  15. Airborne antituberculosis activity of Eucalyptus citriodora essential oil.

    PubMed

    Ramos Alvarenga, René F; Wan, Baojie; Inui, Taichi; Franzblau, Scott G; Pauli, Guido F; Jaki, Birgit U

    2014-03-28

    The rapid emergence of multi- and extensively drug-resistant tuberculosis (MDR/XDR-TB) has created a pressing public health problem, which mostly affects regions with HIV/AIDS prevalence and represents a new constraint in the already challenging disease management of tuberculosis (TB). The present work responds to the need to reduce the number of contagious MDR/XRD-TB patients, protect their immediate environment, and interrupt the rapid spread by laying the groundwork for an inhalation therapy based on anti-TB-active constituents of the essential oil (EO) of Eucalyptus citriodora. In order to address the metabolomic complexity of EO constituents and active principles in botanicals, this study applied biochemometrics, a 3-D analytical approach that involves high-resolution CCC fractionation, GC-MS analysis, bioactivity measurements, and chemometric analysis. Thus, 32 airborne anti-TB-active compounds were identified in E. citriodora EO: the monoterpenes citronellol (1), linalool (3), isopulegol (5), and α-terpineol (7) and the sesquiterpenoids spathulenol (11), β-eudesmol (23), and τ-cadinol (25). The impact of the interaction of multiple components in EOs was studied using various artificial mixtures (AMxs) of the active monoterpenes 1, 2, and 5 and the inactive eucalyptol (33). Both neat 1 and the AMx containing 1, 2, and 33 showed airborne TB inhibition of >90%, while the major E. citriodora EO component, 2, was only weakly active, at 18% inhibition. PMID:24641242

  16. Synchronizing activity of basal ganglia and pathophysiology of Parkinson's disease.

    PubMed

    Heimer, G; Rivlin, M; Israel, Z; Bergman, H

    2006-01-01

    Early physiological studies emphasized changes in the discharge rate of basal ganglia in the pathophysiology of Parkinson's disease (PD), whereas recent studies stressed the role of the abnormal oscillatory activity and neuronal synchronization of pallidal cells. However, human observations cast doubt on the synchronization hypothesis since increased synchronization may be an epi-phenomenon of the tremor or of independent oscillators with similar frequency. Here, we show that modern actor/ critic models of the basal ganglia predict the emergence of synchronized activity in PD and that significant non-oscillatory and oscillatory correlations are found in MPTP primates. We conclude that the normal fluctuation of basal ganglia dopamine levels combined with local cortico-striatal learning rules lead to noncorrelated activity in the pallidum. Dopamine depletion, as in PD, results in correlated pallidal activity, and reduced information capacity. We therefore suggest that future deep brain stimulation (DBS) algorithms may be improved by desynchronizing pallidal activity. PMID:17017503

  17. P21-activated kinase in inflammatory and cardiovascular disease

    PubMed Central

    Taglieri, Domenico M.; Ushio-Fukai, Masuko; Monasky, Michelle M.

    2014-01-01

    P-21 activated kinases, or PAKs, are serine–threonine kinases that serve a role in diverse biological functions and organ system diseases. Although PAK signaling has been the focus of many investigations, still our understanding of the role of PAK in inflammation is incomplete. This review consolidates what is known about PAK1 across several cell types, highlighting the role of PAK1 and PAK2 in inflammation in relation to NADPH oxidase activation. This review explores the physiological functions of PAK during inflammation, the role of PAK in several organ diseases with an emphasis on cardiovascular disease, and the PAK signaling pathway, including activators and targets of PAK. Also, we discuss PAK1 as a pharmacological anti-inflammatory target, explore the potentials and the limitations of the current pharmacological tools to regulate PAK1 activity during inflammation, and provide indications for future research. We conclude that a vast amount of evidence supports the idea that PAK is a central molecule in inflammatory signaling, thus making PAK1 itself a promising prospective pharmacological target. PMID:24794532

  18. Glycosphingolipid synthesis inhibition limits osteoclast activation and myeloma bone disease

    PubMed Central

    Ersek, Adel; Xu, Ke; Antonopoulos, Aristotelis; Butters, Terry D.; Santo, Ana Espirito; Vattakuzhi, Youridies; Williams, Lynn M.; Goudevenou, Katerina; Danks, Lynett; Freidin, Andrew; Spanoudakis, Emmanouil; Parry, Simon; Papaioannou, Maria; Hatjiharissi, Evdoxia; Chaidos, Aristeidis; Alonzi, Dominic S.; Twigg, Gabriele; Hu, Ming; Dwek, Raymond A.; Haslam, Stuart M.; Roberts, Irene; Dell, Anne; Rahemtulla, Amin; Horwood, Nicole J.; Karadimitris, Anastasios

    2015-01-01

    Glycosphingolipids (GSLs) are essential constituents of cell membranes and lipid rafts and can modulate signal transduction events. The contribution of GSLs in osteoclast (OC) activation and osteolytic bone diseases in malignancies such as the plasma cell dyscrasia multiple myeloma (MM) is not known. Here, we tested the hypothesis that pathological activation of OCs in MM requires de novo GSL synthesis and is further enhanced by myeloma cell–derived GSLs. Glucosylceramide synthase (GCS) inhibitors, including the clinically approved agent N-butyl-deoxynojirimycin (NB-DNJ), prevented OC development and activation by disrupting RANKL-induced localization of TRAF6 and c-SRC into lipid rafts and preventing nuclear accumulation of transcriptional activator NFATc1. GM3 was the prevailing GSL produced by patient-derived myeloma cells and MM cell lines, and exogenous addition of GM3 synergistically enhanced the ability of the pro-osteoclastogenic factors RANKL and insulin-like growth factor 1 (IGF-1) to induce osteoclastogenesis in precursors. In WT mice, administration of GM3 increased OC numbers and activity, an effect that was reversed by treatment with NB-DNJ. In a murine MM model, treatment with NB-DNJ markedly improved osteolytic bone disease symptoms. Together, these data demonstrate that both tumor-derived and de novo synthesized GSLs influence osteoclastogenesis and suggest that NB-DNJ may reduce pathological OC activation and bone destruction associated with MM. PMID:25915583

  19. Major Challenges in Clinical Management of TB/HIV Coinfected Patients in Eastern Europe Compared with Western Europe and Latin America

    PubMed Central

    Efsen, Anne Marie W.; Schultze, Anna; Post, Frank A.; Panteleev, Alexander; Furrer, Hansjakob; Miller, Robert F.; Losso, Marcelo H.; Toibaro, Javier; Skrahin, Aliaksandr; Miro, Jose M.; Caylà, Joan A.; Girardi, Enrico; Bruyand, Mathias; Obel, Niels; Podlekareva, Daria N.; Lundgren, Jens D.; Mocroft, Amanda; Kirk, Ole

    2015-01-01

    Objectives Rates of TB/HIV coinfection and multi-drug resistant (MDR)-TB are increasing in Eastern Europe (EE). We aimed to study clinical characteristics, factors associated with MDR-TB and predicted activity of empiric anti-TB treatment at time of TB diagnosis among TB/HIV coinfected patients in EE, Western Europe (WE) and Latin America (LA). Design and Methods Between January 1, 2011, and December 31, 2013, 1413 TB/HIV patients (62 clinics in 19 countries in EE, WE, Southern Europe (SE), and LA) were enrolled. Results Significant differences were observed between EE (N = 844), WE (N = 152), SE (N = 164), and LA (N = 253) in the proportion of patients with a definite TB diagnosis (47%, 71%, 72% and 40%, p<0.0001), MDR-TB (40%, 5%, 3% and 15%, p<0.0001), and use of combination antiretroviral therapy (cART) (17%, 40%, 44% and 35%, p<0.0001). Injecting drug use (adjusted OR (aOR) = 2.03 (95% CI 1.00–4.09), prior anti-TB treatment (3.42 (1.88–6.22)), and living in EE (7.19 (3.28–15.78)) were associated with MDR-TB. Among 585 patients with drug susceptibility test (DST) results, the empiric (i.e. without knowledge of the DST results) anti-TB treatment included ≥3 active drugs in 66% of participants in EE compared with 90–96% in other regions (p<0.0001). Conclusions In EE, TB/HIV patients were less likely to receive a definite TB diagnosis, more likely to house MDR-TB and commonly received empiric anti-TB treatment with reduced activity. Improved management of TB/HIV patients in EE requires better access to TB diagnostics including DSTs, empiric anti-TB therapy directed at both susceptible and MDR-TB, and more widespread use of cART. PMID:26716686

  20. Magnetoresistance in nanostructured Tb/Ti and Tb/Si multilayers

    SciTech Connect

    Svalov, A. V.; Kurlyandskaya, G. V.; Vas'kovskiy, V. O.; Sorokin, A. N.; Diercks, D.

    2011-01-15

    Magnetic, magnetoresistive and structural properties were studied for [Tb/Ti]{sub n} and [Tb/Si]{sub n} multilayers which were prepared by rf-sputtering. The thickness of the Tb layers varied from 1.5 to 12 nm. The thickness of 2 nm nonmagnetic spacers of Ti or Si was kept constant. Both anisotropic and isotropic magnetoresistance was observed in [Tb/Ti]{sub n} and [Tb/Si]{sub n} multilayers. A decrease in the thickness of the terbium layers led to a decrease in the anisotropic contribution to the total magnetoresistance. The negative isotropic magnetoresistanse in [Tb/Ti]{sub n} and [Tb/Si]{sub n} multilayers can be attributed to the giant magnetoresistance (GMR) and/or high field isotropic magnetoresistance. The structure of the samples of both types enabled the existence of the GMR effect.

  1. Predictors and Timing of ATT Initiation among HIV-TB Patients at ART Centers of Karnataka, India: Two Year Follow-Up

    PubMed Central

    Shastri, Suresh; Nagaraja, Sharath Burugina; Tripathy, Jaya Prasad; Satyanarayana, Srinath; Rewari, Bharat Bhushan

    2015-01-01

    Background In India, TB and HIV co-infection remains as a serious public health problem. From 2006 onwards, the intensified TB-HIV collaborative activities are being jointly implemented by National AIDS Control Programme (NACP) and Revised National TB Control programme (RNTCP) at high HIV burden states. Objectives To determine (a) the predictors of outcome among a cohort of HIV-TB co-infected patients after two years after initiation of ART treatment. (b) prognostic significance of time difference between the initiation of ATT and ART in HIV-TB co-infected patients. Methods Patients registered at sixteen ART centres in Karnataka, from October through December 2009 formed the study cohort and were followed till December 2011. Results A total of 604 HIV-TB patients were registered. Follow-up (a) at the end of one year had shown 63.6% (377)patients with unfavorable TB treatment outcomes (b) at the end of second year, 55.6% (336)patients were alive on ART treatment. The variables male, smear negative TB, CD4 count less than 50cells per cumm and unfavorable TB outcome were significantly associated with unfavorable ART treatment outcome. Conclusions The programmes need to review the existing strategies and strengthen HIV-TB collaborative activities for timely treatment initiation with intensive monitoring of HIV-TB patients on treatment. PMID:26394397

  2. Urinary glucaric acid excretion in rheumatoid arthritis: influence of disease activity and disease modifying drugs.

    PubMed Central

    Addyman, R; Beyeler, C; Astbury, C; Bird, H A

    1996-01-01

    OBJECTIVE: To examine if a correlation exists between cytochrome P-450 enzyme induction and disease activity in patients with rheumatoid arthritis (RA), measuring urinary excretion of D-glucaric acid (GA) as an index of phase II drug metabolism. METHODS: Patients with RA were treated with sulphasalazine, sodium aurothiomalate, or D-penicillamine in standard dose regimens, for 24 weeks. Patients with ankylosing spondylitis (AS) or non-inflammatory arthritis (NIA) acted as controls. The urinary GA:creatinine ratio was measured at 0, 12, and 24 weeks of treatment. RESULTS: Patients with RA had a slightly greater urinary GA:creatinine ratio than patients with AS or NIA at baseline; this increased during treatment with disease modifying antirheumatic drugs (DMARDs). Sulphasalazine treatment had a greater effect on GA excretion than sodium aurothiomalate or D-penicillamine; this difference was statistically significant between weeks 0 and 12 (p = 0.01). Gamma glutamyltranspeptidase concentration showed a weak correlation with GA excretion between weeks 0 and 12 (p = 0.03), but all other measurements of changes in disease activity (plasma viscosity, C reactive protein, platelets, and articular index) were found not to correlate with GA excretion between weeks 0-12 or 0-24. CONCLUSION: The increased excretion of GA in patients with RA receiving DMARD treatment is probably the result of an indirect effect on hepatic metabolism bearing no relationship to disease activity. PMID:8774168

  3. In Vivo Molecular Dissection of the Effects of HIV-1 in Active Tuberculosis

    PubMed Central

    Bell, Lucy C. K.; Pollara, Gabriele; Pascoe, Mellissa; Tomlinson, Gillian S.; Lehloenya, Rannakoe J.; Roe, Jennifer; Meldau, Richard; Miller, Robert F.; Ramsay, Alan; Chain, Benjamin M.; Dheda, Keertan; Noursadeghi, Mahdad

    2016-01-01

    Increased risk of tuberculosis (TB) associated with HIV-1 infection is primarily attributed to deficient T helper (Th)1 immune responses, but most people with active TB have robust Th1 responses, indicating that these are not sufficient to protect against disease. Recent findings suggest that favourable outcomes following Mycobacterium tuberculosis infection arise from finely balanced inflammatory and regulatory pathways, achieving pathogen control without immunopathology. We hypothesised that HIV-1 and antiretroviral therapy (ART) exert widespread changes to cell mediated immunity, which may compromise the optimal host protective response to TB and provide novel insights into the correlates of immune protection and pathogenesis. We sought to define these effects in patients with active TB by transcriptional profiling of tuberculin skin tests (TST) to make comprehensive molecular level assessments of in vivo human immune responses at the site of a standardised mycobacterial challenge. We showed that the TST transcriptome accurately reflects the molecular pathology at the site of human pulmonary TB, and used this approach to investigate immune dysregulation in HIV-1/TB co-infected patients with distinct clinical phenotypes associated with TST reactivity or anergy and unmasking TB immune reconstitution inflammatory syndrome (IRIS) after initiation of ART. HIV-1 infected patients with positive TSTs exhibited preserved Th1 responses but deficient immunoregulatory IL10-inducible responses. Those with clinically negative TSTs revealed profound anergy of innate as well as adaptive immune responses, except for preservation of type 1 interferon activity, implicated in impaired anti-mycobacterial immunity. Patients with unmasking TB IRIS showed recovery of Th1 immunity to normal levels, but exaggerated Th2-associated responses specifically. These mechanisms of immune dysregulation were localised to the tissue microenvironment and not evident in peripheral blood. TST

  4. In Vivo Molecular Dissection of the Effects of HIV-1 in Active Tuberculosis.

    PubMed

    Bell, Lucy C K; Pollara, Gabriele; Pascoe, Mellissa; Tomlinson, Gillian S; Lehloenya, Rannakoe J; Roe, Jennifer; Meldau, Richard; Miller, Robert F; Ramsay, Alan; Chain, Benjamin M; Dheda, Keertan; Noursadeghi, Mahdad

    2016-03-01

    Increased risk of tuberculosis (TB) associated with HIV-1 infection is primarily attributed to deficient T helper (Th)1 immune responses, but most people with active TB have robust Th1 responses, indicating that these are not sufficient to protect against disease. Recent findings suggest that favourable outcomes following Mycobacterium tuberculosis infection arise from finely balanced inflammatory and regulatory pathways, achieving pathogen control without immunopathology. We hypothesised that HIV-1 and antiretroviral therapy (ART) exert widespread changes to cell mediated immunity, which may compromise the optimal host protective response to TB and provide novel insights into the correlates of immune protection and pathogenesis. We sought to define these effects in patients with active TB by transcriptional profiling of tuberculin skin tests (TST) to make comprehensive molecular level assessments of in vivo human immune responses at the site of a standardised mycobacterial challenge. We showed that the TST transcriptome accurately reflects the molecular pathology at the site of human pulmonary TB, and used this approach to investigate immune dysregulation in HIV-1/TB co-infected patients with distinct clinical phenotypes associated with TST reactivity or anergy and unmasking TB immune reconstitution inflammatory syndrome (IRIS) after initiation of ART. HIV-1 infected patients with positive TSTs exhibited preserved Th1 responses but deficient immunoregulatory IL10-inducible responses. Those with clinically negative TSTs revealed profound anergy of innate as well as adaptive immune responses, except for preservation of type 1 interferon activity, implicated in impaired anti-mycobacterial immunity. Patients with unmasking TB IRIS showed recovery of Th1 immunity to normal levels, but exaggerated Th2-associated responses specifically. These mechanisms of immune dysregulation were localised to the tissue microenvironment and not evident in peripheral blood. TST

  5. Drug−disease interaction: Crohn's disease elevates verapamil plasma concentrations but reduces response to the drug proportional to disease activity

    PubMed Central

    Sanaee, Forough; Clements, John D; Waugh, Alistair W G; Fedorak, Richard N; Lewanczuk, Richard; Jamali, Fakhreddin

    2011-01-01

    AIM Inflammation is involved in the pathogenesis of cardiovascular diseases that includes reduced response to pharmacotherapy due to altered pharmacokinetics and pharmacodynamics. It is not known if these effects exist in general in all inflammatory conditions. It also remains unknown whether in a given population the effect is a function of disease severity. We investigated whether pharmacokinetics and pharmacodynamics of a typical calcium channel inhibitor are influenced by Crohn's disease (CD), a disease for which the disease severity can be readily ranked. METHODS We administered 80 mg verapamil orally to (i) healthy control subjects (n = 9), (ii) patients with clinically quiescent CD (n = 22) and (iii) patients with clinically active CD (n = 14). Serial analysis of verapamil enantiomers (total and plasma unbound), blood pressure and electrocardiograms were recorded over 8 h post dose. The severity of CD was measured using the Harvey-Bradshaw Index. RESULTS CD substantially and significantly increased plasma verapamil concentration and in a stereoselective fashion (S, 9-fold; R, 2-fold). The elevated verapamil concentration, however, failed to result in an increased verapamil pharmacodynamic effect so that the patients with elevated verapamil concentration demonstrated no significant increase in response measured as PR interval and blood pressure. Instead, the greater the disease severity, the lower was the drug potency to prolong PR interval (r = 0.86, P < 0.0006), CONCLUSIONS CD patients with severe disease may not respond to cardiovascular therapy with calcium channel blockers. Reducing the severity increases response despite reduced drug concentration. This observation may have therapeutic implication beyond the disease and the drug studies herein. PMID:21592185

  6. Lateral flow urine lipoarabinomannan assay for detecting active tuberculosis in Hiv-positive adults

    PubMed Central

    Shah, Maunank; Hanrahan, Colleen; Wang, Zhuo Yu; Dendukuri, Nandini; Lawn, Stephen D; Denkinger, Claudia M; Steingart, Karen R

    2016-01-01

    Background Rapid detection of tuberculosis (TB) among people living with human immunodeficiency virus (HIV) is a global health priority. HIV-associated TB may have different clinical presentations and is challenging to diagnose. Conventional sputum tests have reduced sensitivity in HIV-positive individuals, who have higher rates of extrapulmonary TB compared with HIV-negative individuals. The lateral flow urine lipoarabinomannan assay (LF-LAM) is a new, commercially available point-of-care test that detects lipoarabinomannan (LAM), a lipopolysaccharide present in mycobacterial cell walls, in people with active TB disease. Objectives To assess the accuracy of LF-LAM for the diagnosis of active TB disease in HIV-positive adults who have signs and symptoms suggestive of TB (TB diagnosis).To assess the accuracy of LF-LAM as a screening test for active TB disease in HIV-positive adults irrespective of signs and symptoms suggestive of TB (TB screening). Search methods We searched the following databases without language restriction on 5 February 2015: the Cochrane Infectious Diseases Group Specialized Register; MEDLINE (PubMed,1966); EMBASE (OVID, from 1980); Science Citation Index Expanded (SCI-EXPANDED, from 1900), Conference Proceedings Citation Index-Science (CPCI-S, from 1900), and BIOSIS Previews (from 1926) (all three using the Web of Science platform; MEDION; LILACS (BIREME, from 1982); SCOPUS (from 1995); the metaRegister of Controlled Trials (mRCT); the search portal of the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP); and ProQuest Dissertations & Theses A&l (from 1861). Selection criteria Eligible study types included randomized controlled trials, cross-sectional studies, and cohort studies that determined LF-LAM accuracy for TB against a microbiological reference standard (culture or nucleic acid amplification test from any body site). A higher quality reference standard was one in which two or more specimen types were

  7. Comparison of QuantiFERON-TB gold in tube test versus tuberculin skin test for screening of latent tuberculosis infection in Saudi Arabia: A population-based study

    PubMed Central

    Balkhy, Hanan H.; El Beltagy, Kamel; El-Saed, Aiman; Aljasir, Badr; Althaqafi, Abdulhakeem; Alothman, Adel F.; Alshalaan, Mohammad; Al-Jahdali, Hamdan

    2016-01-01

    OBJECTIVES: To compare QuantiFERON-TB gold in tube (QFT-GIT) test with tuberculin skin test (TST) in detecting latent tuberculosis infection (LTBI) among a general population in Saudi Arabia. METHODS: A population-based cross-sectional study was conducted between July 2010 and March 2013 among individuals randomly selected from the list of those receiving care at primary healthcare centers in three provinces of Saudi Arabia; Central, Western, and Eastern provinces. Those younger than 5 years, immunocompromised, had a current or previous history of active TB, LTBI, or who were receiving anti-TB medications were excluded. Informed consent was obtained before the study questionnaire was completed. Participants were then evaluated for LTBI using QFT-GIT test followed immediately by TST. RESULTS: Of the 1369 subjects included in the final analysis, QFT-GIT was positive in 124 (9.1%) and TST was positive in 127 (9.3%). Positive concordance was observed in 49 (3.6%) subjects while negative concordance was observed in 1167 (85.2%) subjects. The overall agreement between the two tests was 88.8% with a significant kappa (κ) test (κ = 0.332, P < 0.001). Concordance was significantly higher in younger age, female gender, single status, students, primary education, living in middle-sized families, and never smoked. CONCLUSIONS: The overall agreement of TST and QFT-GIT for the detection of LTBI among a Saudi general population was 88.8%. QFT-GIT is probably comparable to TST for detecting LTBI in an intermediate TB burden country with high at birth bacille calmette guerin vaccination coverage. Further prospective studies are needed to compare the ability of both tests to predict TB disease. PMID:27512509

  8. Neural activities during affective processing in people with Alzheimer's disease.

    PubMed

    Lee, Tatia M C; Sun, Delin; Leung, Mei-Kei; Chu, Leung-Wing; Keysers, Christian

    2013-03-01

    This study examined brain activities in people with Alzheimer's disease when viewing happy, sad, and fearful facial expressions of others. A functional magnetic resonance imaging and a voxel-based morphometry methodology together with a passive viewing of emotional faces paradigm were employed to compare the affective processing in 12 people with mild Alzheimer's disease and 12 matched controls. The main finding was that the clinical participants showed reduced activations in regions associated with the motor simulation system (the ventral premotor cortex) and in regions associated with emotional simulation-empathy (the anterior insula and adjacent frontal operculum). This regional decline in blood oxygen level-dependent signals appeared to be lateralized in the left hemisphere and was not related to any structural degeneration in the clinical participants. Furthermore, the regions that showed changes in neural activity differed for the 3 emotional facial expressions studied. Findings of our study indicate that neural changes in regions associated with the motor and emotional simulation systems might play an important role in the development of Alzheimer's disease. PMID:22840336

  9. Guidance from WHO on the prevention and control of TB during air travel.

    PubMed

    Martinez, Lindsay; Thomas, Kathrin; Figueroa, José

    2010-03-01

    Although tuberculosis (TB) is not highly transmissible, there is a risk of transmission of infection when close contact occurs between a person with active pulmonary TB and other passengers for prolonged periods during air travel. The World Health Organization first published Tuberculosis and air travel: guidelines for prevention and control in 1998, in response to several incidents involving TB in air travellers, with a second edition in 2006. A further revision was undertaken to address issues arising from the emergence of extensively resistant TB (XDR-TB), the occurrence of several international incidents involving TB and air travel, and the entry into force of the revised International Health Regulations (IHR) in 2007. This article describes the process followed in preparing the third edition, the special issues considered and the conclusions reached, with recommendations for travellers, physicians, public health authorities, and airline companies. New material includes: (i) additional guidance on the assessment of infectiousness, and on procedures, roles and responsibilities involved in the prevention of transmission of infection on board and for dealing with incidents; (ii) information on basic provisions of the IHR and measures relevant to incidents involving TB among air travellers; and (iii) a proposed procedure for carrying out contact investigations. PMID:20478515

  10. Efflux pump inhibitors: targeting mycobacterial efflux systems to enhance TB therapy.

    PubMed

    Pule, Caroline M; Sampson, Samantha L; Warren, Robin M; Black, Philippa A; van Helden, Paul D; Victor, Tommie C; Louw, Gail E

    2016-01-01

    The emergence of drug resistance continues to plague TB control, with a global increase in the prevalence of MDR-TB. This acts as a gateway to XDR-TB and thus emphasizes the urgency for drug development and optimal treatment options. Bedaquiline is the first new anti-TB drug approved by the FDA in 40 years and has been shown to be an effective treatment option for MDR Mycobacterium tuberculosis infection. Bedaquiline has also recently been included in clinical trials for new regimens with the aim of improving and shortening treatment periods. Alarmingly, efflux-mediated bedaquiline resistance, as well as efflux-mediated cross-resistance to clofazimine, has been identified in treatment failures. This mechanism of resistance results in efflux of a variety of anti-TB drugs from the bacterial cell, thereby decreasing the intracellular drug concentration. In doing so, the bacillus is able to render the antibiotic treatment ineffective. Recent studies have explored strategies to reverse the resistance phenotype conferred by efflux pump activation. It was observed that the addition of efflux pump inhibitors partially restored drug susceptibility in vitro and in vivo. This has significant clinical implications, especially in MDR-TB management where treatment options are extremely limited. This review aims to highlight the current efflux pump inhibitors effective against M. tuberculosis, the effect of efflux pump inhibitors on mycobacterial growth and the clinical promise of treatment with efflux pump inhibitors and standard anti-TB therapy. PMID:26472768

  11. Soil Moisture Active Passive (SMAP) Project Algorithm Theoretical Basis Document SMAP L1B Radiometer Data Product: L1B_TB

    NASA Technical Reports Server (NTRS)

    Piepmeier, Jeffrey; Mohammed, Priscilla; De Amici, Giovanni; Kim, Edward; Peng, Jinzheng; Ruf, Christopher; Hanna, Maher; Yueh, Simon; Entekhabi, Dara

    2016-01-01

    The purpose of the Soil Moisture Active Passive (SMAP) radiometer calibration algorithm is to convert Level 0 (L0) radiometer digital counts data into calibrated estimates of brightness temperatures referenced to the Earth's surface within the main beam. The algorithm theory in most respects is similar to what has been developed and implemented for decades for other satellite radiometers; however, SMAP includes two key features heretofore absent from most satellite borne radiometers: radio frequency interference (RFI) detection and mitigation, and measurement of the third and fourth Stokes parameters using digital correlation. The purpose of this document is to describe the SMAP radiometer and forward model, explain the SMAP calibration algorithm, including approximations, errors, and biases, provide all necessary equations for implementing the calibration algorithm and detail the RFI detection and mitigation process. Section 2 provides a summary of algorithm objectives and driving requirements. Section 3 is a description of the instrument and Section 4 covers the forward models, upon which the algorithm is based. Section 5 gives the retrieval algorithm and theory. Section 6 describes the orbit simulator, which implements the forward model and is the key for deriving antenna pattern correction coefficients and testing the overall algorithm.

  12. Uptake of Isoniazid Preventive Therapy among Under-Five Children: TB Contact Investigation as an Entry Point.

    PubMed

    Tadesse, Yared; Gebre, Nigussie; Daba, Shallo; Gashu, Zewdu; Habte, Dereje; Hiruy, Nebiyu; Negash, Solomon; Melkieneh, Kassahun; Jerene, Degu; K Haile, Yared; Kassie, Yewulsew; Melese, Muluken; G Suarez, Pedro

    2016-01-01

    A child's risk of developing tuberculosis (TB) can be reduced by nearly 60% with administration of 6 months course of isoniazid preventive therapy (IPT). However, uptake of IPT by national TB programs is low, and IPT delivery is a challenge in many resource-limited high TB-burden settings. Routinely collected program data was analyzed to determine the coverage and outcome of implementation of IPT for eligible under-five year old children in 28 health facilities in two regions of Ethiopia. A total of 504 index smear-positive pulmonary TB (SS+) cases were reported between October 2013 and June 2014 in the 28 health facilities. There were 282 under-five children registered as household contacts of these SS+ TB index cases, accounting for 17.9% of all household contacts. Of these, 237 (84%) were screened for TB symptoms, and presumptive TB was identified in 16 (6.8%) children. TB was confirmed in 5 children, producing an overall yield of 2.11% (95% confidence interval, 0.76-4.08%). Of 221 children eligible for IPT, 64.3% (142) received IPT, 80.3% (114) of whom successfully completed six months of therapy. No child developed active TB while on IPT. Contact screening is a good entry point for delivery of IPT to at risk children and should be routine practice as recommended by the WHO despite the implementation challenges. PMID:27196627

  13. Uptake of Isoniazid Preventive Therapy among Under-Five Children: TB Contact Investigation as an Entry Point

    PubMed Central

    Gebre, Nigussie; Daba, Shallo; Gashu, Zewdu; Habte, Dereje; Hiruy, Nebiyu; Negash, Solomon; Melkieneh, Kassahun; Jerene, Degu; K. Haile, Yared; Kassie, Yewulsew; Melese, Muluken; G. Suarez, Pedro

    2016-01-01

    A child’s risk of developing tuberculosis (TB) can be reduced by nearly 60% with administration of 6 months course of isoniazid preventive therapy (IPT). However, uptake of IPT by national TB programs is low, and IPT delivery is a challenge in many resource-limited high TB-burden settings. Routinely collected program data was analyzed to determine the coverage and outcome of implementation of IPT for eligible under-five year old children in 28 health facilities in two regions of Ethiopia. A total of 504 index smear-positive pulmonary TB (SS+) cases were reported between October 2013 and June 2014 in the 28 health facilities. There were 282 under-five children registered as household contacts of these SS+ TB index cases, accounting for 17.9% of all household contacts. Of these, 237 (84%) were screened for TB symptoms, and presumptive TB was identified in 16 (6.8%) children. TB was confirmed in 5 children, producing an overall yield of 2.11% (95% confidence interval, 0.76–4.08%). Of 221 children eligible for IPT, 64.3% (142) received IPT, 80.3% (114) of whom successfully completed six months of therapy. No child developed active TB while on IPT. Contact screening is a good entry point for delivery of IPT to at risk children and should be routine practice as recommended by the WHO despite the implementation challenges. PMID:27196627

  14. Factors Associated with Prevalent Tuberculosis Among Patients Receiving Highly Active Antiretroviral Therapy in a Nigerian Tertiary Hospital

    PubMed Central

    Iroezindu, MO; Ofondu, EO; Mbata, GC; van Wyk, B; Hausler, HP; DH, Au; Lynen, L; Hopewell, PC

    2016-01-01

    Background: Tuberculosis (TB) causes significant morbidity/mortality among human immunodeficiency virus-infected individuals in Africa. Reducing TB burden in the era of highly active antiretroviral therapy (HAART) is a public health priority. Aim: We determined the factors associated with prevalent TB among patients receiving HAART. Subjects and Methods: We conducted a cross-sectional study of adult patients who had received HAART for ≥12 weeks in a Nigerian tertiary hospital. Patients whose TB diagnosis predated HAART were excluded from the study. Pre-HAART data were collected from the clinic records, whereas post-HAART data were obtained through medical history, physical examination, and laboratory investigations. Standard TB screening/diagnostic algorithms as applicable in Nigeria were used. Logistic regression analysis was used to determine factors independently associated with prevalent TB. Results: about 65.8% (222/339) were women. The mean age was 41.1 (10.0) years and 23.6% (73/339) had past history of TB. The prevalence of active TB was 7.7% (26/339). Among these patients, 42.3% (11/26) had pulmonary TB, 34.6% (9/26) had disseminated TB, whereas 23.1% (6/26) had only extra-pulmonary disease. Only 45% (9/20) of patients with pulmonary involvement had positive sputum smear. Factors independently associated with prevalent TB were lower social class (adjusted odds ratio [aOR]: 31.7; 95% confidence interval [CI]: 1.1–1417.3), HAART non-adherence (aOR125.5; 95% CI: 9.6–1636.3), baseline CD4 <200cells/μl (aOR31.0; 95%CI: 1.6–590.6), previous TB (aOR13.8; 95% CI: 2.0–94.1), and current hemoglobin <10 g/dl (aOR10.3; 95% CI: 1.1–99.2). Conclusion: Factors associated with prevalent TB were a lower social class, HAART non-adherence, severe immunosuppression before HAART initiation, previous TB, and anemia post-HAART. TB case finding should be intensified in these high-risk groups. PMID:27213096

  15. [Physical activity in basic and primary prevention of cardiovascular disease].

    PubMed

    Sobieszczańska, Małgorzata; Kałka, Dariusz; Pilecki, Witold; Adamus, Jerzy

    2009-06-01

    On account of the frequency of appearing and character of atherosclerosis cardiac vascular disease, one of the most crucial elements of effective fight against it is preparation of complex preventive programs including as vast number of population as possible. Consequently, Benjamin and Smitch suggested attaching the notion of basic prevention to the standard division into primary and secondary one. The basic prevention, carrying out in the general population, should concern genetic predisposition, psychosocial factors, keeping up proper body weight, healthy eating and physical activity. Especially high hopes are connected with high efficiency, simplicity and low money-consumption of preventive activities associated with physical activity modification, which has a crucial influence on reducing negative impact of atherosclerosis hazard. The results of numerous scientific research, carried out in many countries and on various, large groups, proved undoubtedly that at the healthy adult people of both sex the systematic physical activity of moderate intensification plays an essential part in preventing CVD and decreasing the death risk because of that reason as well. Moreover, systematic physical exercises show many other health-oriented actions, thanks to which they have an influence on decreasing premature and total death rate. The risk of incidence of civilization-related diseases such as diabetes type II, hypertension, obesity, osteoporosis, tumors (of large intestine, breast, prostatic gland) and depression has decreased significantly. Unequivocally positive influence has been proved at many observations dedicated to health recreational physical activity and physical activity connected with professional work based on aerobe effort. The positive effects have been also observed at children population and senior population which is more and more numerous and the most at risk. The beneficial action of physical activity is connected with direct effect on organism

  16. Physical activity, functional ability, and disease activity in children and adolescents with juvenile idiopathic arthritis.

    PubMed

    Gueddari, S; Amine, B; Rostom, S; Badri, D; Mawani, N; Ezzahri, M; Moussa, F; Shyen, S; Abouqal, R; Chkirat, B; Hajjaj-Hassouni, N

    2014-09-01

    Juvenile idiopathic arthritis (JIA) is a chronic condition known to cause pain-related complications in youth and affect children's physical functioning. There is no data in Arabic children with JIA about the impact of illness upon their physical activity. The objective of this study was to explore physical activity (PA) in children and adolescents with JIA compared with a healthy population and to examine associations between PA, functional ability, and disease activity. Our study included patients with JIA and group control aged between 8 and 17 years. The diagnosis was used according to the International League of Association of Rheumatology (ILAR) criteria 2001. Sociodemographic data and clinical features were collected. Physical activity level and energy expenditure were assessed with a 1-day activity diary and the metabolic equivalent (MET), respectively. Functional ability was assessed with the Moroccan version of the Childhood Health Assessment Questionnaire (CHAQ). Disease activity was measured using the Juvenile Arthritis Disease Activity Score (JADAS). Fifty patients and 50 controls were included (mean ± SD age 11.5 ± 3.3 and 10.5 ± 3.8 years, respectively; p = 0.49) with masculine predominance n = 30 (59.6 %) and n = 29 (58 %), respectively (p = 0.26). The median disease duration was 4.3 years (2-5). The median analog scale (VAS) pain was 20 (10-40). Fourteen patients (28 %) had an active disease. Patient population consisted in majority of oligoarticular arthritis (28 %), 14 patients. The mean of energy expenditure and physical activity were significantly higher in the JIA group. The JIA group spent more time in bed and less time on moderate to vigorous PA than the control group. There is no significant relationship between PA, functional ability, and disease activity. Our study suggests that children and adolescents with JIA have low PA levels and are at risk of losing the benefits of PA. Low PA is not related to

  17. Active case finding of tuberculosis: historical perspective and future prospects

    PubMed Central

    Golub, J. E.; Mohan, C. I.; Comstock, G. W.; Chaisson, R. E.

    2015-01-01

    SUMMARY Despite a history of remarkable scientific achievements in microbiology and therapeutics, tuberculosis (TB) continues to pose an extraordinary threat to human health. Case finding and treatment of TB disease are the principal means of controlling transmission and reducing incidence. This review presents a historical perspective of active case finding (ACF) of TB, detailing case detection strategies that have been used over the last century. This review is divided into the following sections: mass radiography, house-to-house surveys, out-patient case detection, enhanced case finding, high-risk populations and cost-effectiveness. The report concludes with a discussion and recommendations for future case finding strategies. Understanding the strengths and weaknesses of these methods will help inform and shape ACF as a TB control policy in the twenty-first century. PMID:16333924

  18. Medicinal plant activity on Helicobacter pylori related diseases

    PubMed Central

    Wang, Yuan-Chuen

    2014-01-01

    More than 50% of the world population is infected with Helicobacter pylori (H. pylori). The bacterium highly links to peptic ulcer diseases and duodenal ulcer, which was classified as a group I carcinogen in 1994 by the WHO. The pathogenesis of H. pylori is contributed by its virulence factors including urease, flagella, vacuolating cytotoxin A (VacA), cytotoxin-associated gene antigen (Cag A), and others. Of those virulence factors, VacA and CagA play the key roles. Infection with H. pylori vacA-positive strains can lead to vacuolation and apoptosis, whereas infection with cagA-positive strains might result in severe gastric inflammation and gastric cancer. Numerous medicinal plants have been reported for their anti-H. pylori activity, and the relevant active compounds including polyphenols, flavonoids, quinones, coumarins, terpenoids, and alkaloids have been studied. The anti-H. pylori action mechanisms, including inhibition of enzymatic (urease, DNA gyrase, dihydrofolate reductase, N-acetyltransferase, and myeloperoxidase) and adhesive activities, high redox potential, and hydrophilic/hydrophobic natures of compounds, have also been discussed in detail. H. pylori-induced gastric inflammation may progress to superficial gastritis, atrophic gastritis, and finally gastric cancer. Many natural products have anti-H. pylori-induced inflammation activity and the relevant mechanisms include suppression of nuclear factor-κB and mitogen-activated protein kinase pathway activation and inhibition of oxidative stress. Anti-H. pylori induced gastric inflammatory effects of plant products, including quercetin, apigenin, carotenoids-rich algae, tea product, garlic extract, apple peel polyphenol, and finger-root extract, have been documented. In conclusion, many medicinal plant products possess anti-H. pylori activity as well as an anti-H. pylori-induced gastric inflammatory effect. Those plant products have showed great potential as pharmaceutical candidates for H. pylori

  19. Memory activation reveals abnormal EEG in preclinical Huntington's disease.

    PubMed

    van der Hiele, Karin; Jurgens, Caroline K; Vein, Alla A; Reijntjes, Robert H A M; Witjes-Ané, Marie-Noëlle W; Roos, Raymund A C; van Dijk, Gert; Middelkoop, Huub A M

    2007-04-15

    The EEG is potentially useful as a marker of early Huntington's disease (HD). In dementia, the EEG during a memory activation challenge showed abnormalities where the resting EEG did not. We investigated whether memory activation also reveals EEG abnormalities in preclinical HD. Sixteen mutation carriers for HD and 13 nonmutation carriers underwent neurological, neuropsychological, MRI and EEG investigations. The EEG was registered during a rest condition, i.e. eyes closed, and a working memory task. In each condition we determined absolute power in the theta (4-8 Hz) and alpha (8-13 Hz) bands and subsequently calculated relative alpha power. The EEG during eyes closed did not differ between groups. The EEG during memory activation showed less relative alpha power in mutation carriers as compared to nonmutation carriers, even though memory performance was similar [F (1,27) = 10.87; P = 0.003]. Absolute powers also showed less alpha power [F (1,27) = 7.02; P = 0.013] but similar theta power. No correlations were found between absolute and relative alpha power on the one hand and neuropsychological scores, motor scores or number of CAG repeats on the other. In conclusion, memory activation reveals functional brain changes in Huntington's disease before clinical signs become overt. PMID:17266047

  20. Partners against tuberculosis: Ethiopia's "TB clubs".

    PubMed

    Getahun, H

    1998-11-01

    TB (tuberculosis) clubs were first introduced in the Estie district of South Gonder administrative zone, Amhara region of northwestern Ethiopia in January 1997, in an attempt to improve TB control in rural areas. Before the clubs were introduced, patients who were family members or close neighbors were given different treatment follow-up dates. Walking long distances alone to secure treatment, patients often grew discouraged from continuing treatment once their health began to improve. However, upon the introduction of the TB clubs, neighboring patients, or those in the same family, had their follow-up appointment dates rearranged in the same clinics. Local neighborhoods were also used to group nearby patients in the same follow-up clinic. The patients then formed their own groups (TB clubs) and elected leaders. 3-10 members usually comprise each club, with the club leaders monitoring drug intake and new developments, such as drug side effects and toxic skin reactions. The social ostracism and stigma otherwise experienced by patients have been largely overcome as a result of the TB information disseminated within the communities by the clubs, while patient attendance for treatment has increased from 68% to 98%, according to one study's findings. This intervention has taken place using the long-course treatment protocol (2STH/EH and 10TH/EH). TB clubs are improving patient adherence to treatment, passive case detection, defaulter tracing, TB reporting and recording, and community involvement in health care. PMID:12294916

  1. Functional activity of human hepatocytes under traumatic disease.

    PubMed

    Kudryavtseva, M V; Stein, G I; Shashkov, B V; Kudryavtsev, B N

    1998-03-01

    Absorption and fluorescent cytophotometry techniques were applied to studies of RNA as well as of total glycogen and its fractions as the parameters of functional activity of the hepatocytes in patients with severe mechanical trauma, both with and without autointoxication (AI). Slides were stained with gallocyanine-chromalums to determine the RNA content and were processed by the fluorescent PAS-reaction for the glycogen content. To trace the dynamics of RNA and glycogen contents in the liver punction biopsies were done in the same patients. A quick increase in the RNA content took place in both groups of patients at the first period (within the first 3 days) of traumatic disease. At the second period of disease the hepatocyte RNA content in patients without AI was found to decrease up to the initial level whereas that in patients with AI increased on the average by 36% of the initial values. The total glycogen content in hepatocytes of all the patients changed insignificantly in the course of disease but its labile fraction in patients with AI decreased to 70% of the total. The increase of hepatocyte synthetic activity and the maintenance of the high glycogen level are indicative of the large compensatory potential of the liver that enables it to carry an intensive functional load under AI conditions. PMID:9570502

  2. Subcortical evoked activity and motor enhancement in Parkinson's disease

    PubMed Central

    Anzak, Anam; Tan, Huiling; Pogosyan, Alek; Khan, Sadaquate; Javed, Shazia; Gill, Steven S.; Ashkan, Keyoumars; Akram, Harith; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Green, Alexander L.; Aziz, Tipu; Brown, Peter

    2016-01-01

    Enhancements in motor performance have been demonstrated in response to intense stimuli both in healthy subjects and in the form of ‘paradoxical kinesis’ in patients with Parkinson's disease. Here we identify a mid-latency evoked potential in local field potential recordings from the region of the subthalamic nucleus, which scales in amplitude with both the intensity of the stimulus delivered and corresponding enhancements in biomechanical measures of maximal handgrips, independent of the dopaminergic state of our subjects with Parkinson's disease. Recordings of a similar evoked potential in the related pedunculopontine nucleus – a key component of the reticular activating system – provide support for this neural signature in the subthalmic nucleus being a novel correlate of ascending arousal, propagated from the reticular activating system to exert an ‘energizing’ influence on motor circuitry. Future manipulation of this system linking arousal and motor performance may provide a novel approach for the non-dopaminergic enhancement of motor performance in patients with hypokinetic disorders such as Parkinson's disease. PMID:26687971

  3. Pharmacological treatment options for mast cell activation disease.

    PubMed

    Molderings, Gerhard J; Haenisch, Britta; Brettner, Stefan; Homann, Jürgen; Menzen, Markus; Dumoulin, Franz Ludwig; Panse, Jens; Butterfield, Joseph; Afrin, Lawrence B

    2016-07-01

    Mast cell activation disease (MCAD) is a term referring to a heterogeneous group of disorders characterized by aberrant release of variable subsets of mast cell (MC) mediators together with accumulation of either morphologically altered and immunohistochemically identifiable mutated MCs due to MC proliferation (systemic mastocytosis [SM] and MC leukemia [MCL]) or morphologically ordinary MCs due to decreased apoptosis (MC activation syndrome [MCAS] and well-differentiated SM). Clinical signs and symptoms in MCAD vary depending on disease subtype and result from excessive mediator release by MCs and, in aggressive forms, from organ failure related to MC infiltration. In most cases, treatment of MCAD is directed primarily at controlling the symptoms associated with MC mediator release. In advanced forms, such as aggressive SM and MCL, agents targeting MC proliferation such as kinase inhibitors may be provided. Targeted therapies aimed at blocking mutant protein variants and/or downstream signaling pathways are currently being developed. Other targets, such as specific surface antigens expressed on neoplastic MCs, might be considered for the development of future therapies. Since clinicians are often underprepared to evaluate, diagnose, and effectively treat this clinically heterogeneous disease, we seek to familiarize clinicians with MCAD and review current and future treatment approaches. PMID:27132234

  4. Subcortical evoked activity and motor enhancement in Parkinson's disease.

    PubMed

    Anzak, Anam; Tan, Huiling; Pogosyan, Alek; Khan, Sadaquate; Javed, Shazia; Gill, Steven S; Ashkan, Keyoumars; Akram, Harith; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Green, Alexander L; Aziz, Tipu; Brown, Peter

    2016-03-01

    Enhancements in motor performance have been demonstrated in response to intense stimuli both in healthy subjects and in the form of 'paradoxical kinesis' in patients with Parkinson's disease. Here we identify a mid-latency evoked potential in local field potential recordings from the region of the subthalamic nucleus, which scales in amplitude with both the intensity of the stimulus delivered and corresponding enhancements in biomechanical measures of maximal handgrips, independent of the dopaminergic state of our subjects with Parkinson's disease. Recordings of a similar evoked potential in the related pedunculopontine nucleus - a key component of the reticular activating system - provide support for this neural signature in the subthalmic nucleus being a novel correlate of ascending arousal, propagated from the reticular activating system to exert an 'energizing' influence on motor circuitry. Future manipulation of this system linking arousal and motor performance may provide a novel approach for the non-dopaminergic enhancement of motor performance in patients with hypokinetic disorders such as Parkinson's disease. PMID:26687971

  5. Metabolic correlates of pallidal neuronal activity in Parkinson's disease.

    PubMed

    Eidelberg, D; Moeller, J R; Kazumata, K; Antonini, A; Sterio, D; Dhawan, V; Spetsieris, P; Alterman, R; Kelly, P J; Dogali, M; Fazzini, E; Beric, A

    1997-08-01

    We have used [18F]fluorodeoxyglucose and PET to identify specific metabolic covariance patterns associated with Parkinson's disease and related disorders previously. Nonetheless, the physiological correlates of these abnormal patterns are unknown. In this study we used PET to measure resting state glucose metabolism in 42 awake unmedicated Parkinson's disease patients prior to unilateral stereotaxic pallidotomy for relief of symptoms. Spontaneous single unit activity of the internal segment of the globus pallidus (GPi) was recorded intraoperatively in the same patients under identical conditions. The first 24 patients (Group A) were scanned on an intermediate resolution tomograph (full width at half maximum, 8 mm); the subsequent 18 patients (Group B) were scanned on a higher resolution tomograph (full width half maximum, 4.2 mm). We found significant positive correlations between GPi firing rates and thalamic glucose metabolism in both patient groups (Group A: r = 0.41, P < 0.05; Group B: r = 0.69, P < 0.005). In Group B, pixel-based analysis disclosed a significant focus of physiological-metabolic correlation involving the ventral thalamus and the GPi (statistical parametric map: P < 0.05, corrected). Regional covariance analysis demonstrated that internal pallidal neuronal activity correlated significantly (r = 0.65, P < 0.005) with the expression of a unique network characterized by covarying pallidothalamic and brainstem metabolic activity. Our findings suggest that the variability in pallidal neuronal firing rates in Parkinson's disease patients is associated with individual differences in the metabolic activity of efferent projection systems. PMID:9278625

  6. Adverse Events among HIV/MDR-TB Co-Infected Patients Receiving Antiretroviral and Second Line Anti-TB Treatment in Mumbai, India

    PubMed Central

    Isaakidis, Petros; Varghese, Bhanumati; Mansoor, Homa; Cox, Helen S.; Ladomirska, Joanna; Saranchuk, Peter; Da Silva, Esdras; Khan, Samsuddin; Paryani, Roma; Udwadia, Zarir; Migliori, Giovanni Battista; Sotgiu, Giovanni; Reid, Tony

    2012-01-01

    Background Significant adverse events (AE) have been reported in patients receiving medications for multidrug- and extensively-drug-resistant tuberculosis (MDR-TB & XDR-TB). However, there is little prospective data on AE in MDR- or XDR-TB/HIV co-infected patients on antituberculosis and antiretroviral therapy (ART) in programmatic settings. Methods Médecins Sans Frontières (MSF) is supporting a community-based treatment program for drug-resistant tuberculosis in HIV-infected patients in a slum setting in Mumbai, India since 2007. Patients are being treated for both diseases and the management of AE is done on an outpatient basis whenever possible. Prospective data were analysed to determine the occurrence and nature of AE. Results Between May 2007 and September 2011, 67 HIV/MDR-TB co-infected patients were being treated with anti-TB treatment and ART; 43.3% were female, median age was 35.5 years (Interquartile Range: 30.5–42) and the median duration of anti-TB treatment was 10 months (range 0.5–30). Overall, AE were common in this cohort: 71%, 63% and 40% of patients experienced one or more mild, moderate or severe AE, respectively. However, they were rarely life-threatening or debilitating. AE occurring most frequently included gastrointestinal symptoms (45% of patients), peripheral neuropathy (38%), hypothyroidism (32%), psychiatric symptoms (29%) and hypokalaemia (23%). Eleven patients were hospitalized for AE and one or more suspect drugs had to be permanently discontinued in 27 (40%). No AE led to indefinite suspension of an entire MDR-TB or ART regimen. Conclusions AE occurred frequently in this Mumbai HIV/MDR-TB cohort but not more frequently than in non-HIV patients on similar anti-TB treatment. Most AE can be successfully managed on an outpatient basis through a community-based treatment program, even in a resource-limited setting. Concerns about severe AE in the management of co-infected patients are justified, however, they should not cause delays

  7. Calcium-Activated Potassium Channels: Potential Target for Cardiovascular Diseases.

    PubMed

    Dong, De-Li; Bai, Yun-Long; Cai, Ben-Zhi

    2016-01-01

    Ca(2+)-activated K(+) channels (KCa) are classified into three subtypes: big conductance (BKCa), intermediate conductance (IKCa), and small conductance (SKCa) KCa channels. The three types of KCa channels have distinct physiological or pathological functions in cardiovascular system. BKCa channels are mainly expressed in vascular smooth muscle cells (VSMCs) and inner mitochondrial membrane of cardiomyocytes, activation of BKCa channels in these locations results in vasodilation and cardioprotection against cardiac ischemia. IKCa channels are expressed in VSMCs, endothelial cells, and cardiac fibroblasts and involved in vascular smooth muscle proliferation, migration, vessel dilation, and cardiac fibrosis. SKCa channels are widely expressed in nervous and cardiovascular system, and activation of SKCa channels mainly contributes membrane hyperpolarization. In this chapter, we summarize the physiological and pathological roles of the three types of KCa channels in cardiovascular system and put forward the possibility of KCa channels as potential target for cardiovascular diseases. PMID:27038376

  8. Active Tuberculosis Is Associated with Worse Clinical Outcomes in HIV-Infected African Patients on Antiretroviral Therapy

    PubMed Central

    Siika, Abraham M.; Yiannoutsos, Constantin T.; Wools-Kaloustian, Kara K.; Musick, Beverly S.; Mwangi, Ann W.; Diero, Lameck O.; Kimaiyo, Sylvester N.; Tierney, William M.; Carter, Jane E.

    2013-01-01

    Objective This cohort study utilized data from a large HIV treatment program in western Kenya to describe the impact of active tuberculosis (TB) on clinical outcomes among African patients on antiretroviral therapy (ART). Design We included all patients initiating ART between March 2004 and November 2007. Clinical (signs and symptoms), radiological (chest radiographs) and laboratory (mycobacterial smears, culture and tissue histology) criteria were used to record the diagnosis of TB disease in the program’s electronic medical record system. Methods We assessed the impact of TB disease on mortality, loss to follow-up (LTFU) and incident AIDS-defining events (ADEs) through Cox models and CD4 cell and weight response to ART by non-linear mixed models. Results We studied 21,242 patients initiating ART–5,186 (24%) with TB; 62% female; median age 37 years. There were proportionately more men in the active TB (46%) than in the non-TB (35%) group. Adjusting for baseline HIV-disease severity, TB patients were more likely to die (hazard ratio – HR = 1.32, 95% CI 1.18–1.47) or have incident ADEs (HR = 1.31, 95% CI: 1.19–1.45). They had lower median CD4 cell counts (77 versus 109), weight (52.5 versus 55.0 kg) and higher ADE risk at baseline (CD4-adjusted odds ratio = 1.55, 95% CI: 1.31–1.85). ART adherence was similarly good in both groups. Adjusting for gender and baseline CD4 cell count, TB patients experienced virtually identical rise in CD4 counts after ART initiation as those without. However, the overall CD4 count at one year was lower among patients with TB (251 versus 269 cells/µl). Conclusions Clinically detected TB disease is associated with greater mortality and morbidity despite salutary response to ART. Data suggest that identifying HIV patients co-infected with TB earlier in the HIV-disease trajectory may not fully address TB-related morbidity and mortality. PMID:23301015

  9. Upper Airway Genioglossal Activity in Children with Sickle Cell Disease

    PubMed Central

    Huang, Jingtao; Pinto, Swaroop J.; Allen, Julian L.; Arens, Raanan; Bowdre, Cheryl Y.; Jawad, Abbas F.; Mason, Thornton B.A.; Ohene-Frempong, Kwaku; Smith-Whitley, Kim; Marcus, Carole L.

    2011-01-01

    Study Objectives: The prevalence of obstructive sleep apnea syndrome (OSAS) in sickle cell disease (SCD) has been reported to be higher than that in the general pediatric population. However, not all subjects with SCD develop OSAS. We hypothesized that SCD patients with OSAS have a blunted neuromuscular response to subatmospheric pressure loads during sleep, making them more likely to develop upper airway collapse. Design: Subjects with SCD with and without OSAS underwent pressure-flow measurements during sleep using intraoral surface electrodes to measure genioglossal EMG (EMGgg). Two techniques were applied to decrease the nasal pressure (PN) to subatmospheric levels, resulting in an activated and relatively hypotonic upper airway. The area under the curve of the inspiratory EMGgg moving time average was analyzed. EMGgg activity was expressed as a percentage of baseline. Changes in EMGgg in response to decrements in nasal pressure were expressed as the slope of the EMGgg vs. nasal pressure (slope of EMGgg-PN). Setting: Sleep laboratory. Participants: 4 children with SCD and OSAS and 18 children with SCD but without OSAS. Results: The major findings of this study were: (1) using the activated but not the hypotonic technique, the slope of EMGgg-PN was more negative in SCD controls than SCD OSAS; (2) the slope of EMGgg-PN was significantly lower using the activated technique compared to the hypotonic technique in SCD controls only; (3) similarly, the critical closing pressure, Pcrit, was more negative using the activated technique than the hypotonic technique in SCD controls but not in SCD OSAS. Conclusion: This preliminary study has shown that children with SCD but without OSAS have more prominent upper airway reflexes than children with SCD and OSAS. Citation: Huang J; Pinto SJ; Allen JL; Arens R; Bowdre CY; Jawad AF; Mason TBA; Ohene-Frempong K; Smith-Whitely K; Marcus CL. Upper airway genioglossal activity in children with sickle cell disease. SLEEP 2011

  10. Active learning based segmentation of Crohns disease from abdominal MRI.

    PubMed

    Mahapatra, Dwarikanath; Vos, Franciscus M; Buhmann, Joachim M

    2016-05-01

    This paper proposes a novel active learning (AL) framework, and combines it with semi supervised learning (SSL) for segmenting Crohns disease (CD) tissues from abdominal magnetic resonance (MR) images. Robust fully supervised learning (FSL) based classifiers require lots of labeled data of different disease severities. Obtaining such data is time consuming and requires considerable expertise. SSL methods use a few labeled samples, and leverage the information from many unlabeled samples to train an accurate classifier. AL queries labels of most informative samples and maximizes gain from the labeling effort. Our primary contribution is in designing a query strategy that combines novel context information with classification uncertainty and feature similarity. Combining SSL and AL gives a robust segmentation method that: (1) optimally uses few labeled samples and many unlabeled samples; and (2) requires lower training time. Experimental results show our method achieves higher segmentation accuracy than FSL methods with fewer samples and reduced training effort. PMID:27040833

  11. Performance of the Interferon Gamma Release Assays in Tuberculosis Disease in Children Five Years Old or Less

    PubMed Central

    Yin, Qing-qin; Xiao, Jing; Li, Jie-qiong; Guo, Ya-jie; Feng, Guo-shuang; Peng, Xiao-xia; Qi, Hui; Xu, Fang; Jiao, Wei-wei; Shen, Chen; Shen, A-dong

    2015-01-01

    Interferon Gamma Release Assays (IGRAs) were developed for the indirect or immunologic diagnosis of tuberculosis infection; however, they have also been used to assist in difficult to diagnose cases of tuberculosis disease in adults, and to a lesser extent, in children, especially in those under 5 years old. We evaluated the utility of using an IGRA in pediatric tuberculosis in younger children in a hospital setting. The diagnostic accuracy of T-SPOT.TB and TST was assessed in 117 children with active tuberculosis and 413 children with respiratory tract infection. Sensitivity and specificity were calculated for the tests used individually and together. Concordance was also calculated. Sensitivity of T-SPOT.TB (82.9%) was higher than TST (78.6% using a 5mm cut-off), especially in children confirmed to have TB. T-SPOT.TB was more specific than TST using a 5mm cut-off (96.1% vs. 70.9%). Combining T-SPOT.TB and TST results improved the sensitivity to 96.6%. In conclusion, the results of the current study indicate that T-SPOT.TB has good sensitivity and specificity, supporting its use among patients of this age. A combination of IGRA and TST would be useful additions to assist in the diagnosis of childhood TB. PMID:26640948

  12. Sulforaphane Protects against Cardiovascular Disease via Nrf2 Activation

    PubMed Central

    Bai, Yang; Wang, Xiaolu; Zhao, Song; Ma, Chunye; Cui, Jiuwei; Zheng, Yang

    2015-01-01

    Cardiovascular disease (CVD) causes an unparalleled proportion of the global burden of disease and will remain the main cause of mortality for the near future. Oxidative stress plays a major role in the pathophysiology of cardiac disorders. Several studies have highlighted the cardinal role played by the overproduction of reactive oxygen or nitrogen species in the pathogenesis of ischemic myocardial damage and consequent cardiac dysfunction. Isothiocyanates (ITC) are sulfur-containing compounds that are broadly distributed among cruciferous vegetables. Sulforaphane (SFN) is an ITC shown to possess anticancer activities by both in vivo and epidemiological studies. Recent data have indicated that the beneficial effects of SFN in CVD are due to its antioxidant and anti-inflammatory properties. SFN activates NF-E2-related factor 2 (Nrf2), a basic leucine zipper transcription factor that serves as a defense mechanism against oxidative stress and electrophilic toxicants by inducing more than a hundred cytoprotective proteins, including antioxidants and phase II detoxifying enzymes. This review will summarize the evidence from clinical studies and animal experiments relating to the potential mechanisms by which SFN modulates Nrf2 activation and protects against CVD. PMID:26583056

  13. Tuberculosis: a disease without boundaries.

    PubMed

    Fogel, Nicole

    2015-09-01

    Tuberculosis (TB) is an airborne disease caused by Mycobacterium tuberculosis (MTB) that usually affects the lungs leading to severe coughing, fever, and chest pains. Although current research in the past four years has provided valuable insight into TB transmission, diagnosis, and treatment, much remains to be discovered to effectively decrease the incidence of and eventually eradicate TB. The disease still puts a strain on public health, being only second to HIV/AIDS in causing high mortality rates. This review will highlight the history of TB as well as provide an overview of the current literature on epidemiology, pathogenesis and the immune response, treatment, and control of TB. In this race to combat a disease that knows no boundaries, it is necessary to have a conceptual and clear understanding of TB overall with the hope of providing better treatment through novel and collaborative research and public health efforts. PMID:26198113

  14. Effect of hydrogen passivation on the photoluminescence of Tb ions in silicon rich silicon oxide films

    NASA Astrophysics Data System (ADS)

    Zatryb, G.; Klak, M. M.; Wojcik, J.; Misiewicz, J.; Mascher, P.; Podhorodecki, A.

    2015-12-01

    In this work, silicon-rich silicon oxide films containing terbium were prepared by means of plasma enhanced chemical vapor deposition. The influence of hydrogen passivation on defects-mediated non-radiative recombination of excited Tb3+ ions was investigated by photoluminescence, photoluminescence excitation, and photoluminescence decay measurements. Passivation was found to have no effect on shape and spectral position of the excitation spectra. In contrast, a gradual increase in photoluminescence intensity and photoluminescence decay time was observed upon passivation for the main 5D4-7F5 transition of Tb3+ ions. This observation was attributed to passivation of non-radiative recombination defects centers with hydrogen. It was found that the number of emitted photons increases upon passivation as a result of two effects: (1) longer Tb3+ lifetime in the 5D4 excited state and (2) optical activation of new Tb3+ emitters. The obtained results were discussed and compared with other experimental reports.

  15. Analysis of 161Tb by radiochemical separation and liquid scintillation counting

    DOE PAGESBeta

    Jiang, J.; Davies, A.; Arrigo, L.; Friese, J.; Seiner, B. N.; Greenwood, L.; Finch, Z.

    2015-12-05

    The determination of 161Tb activity is problematic due to its very low fission yield, short half-life, and the complication of its gamma spectrum. At AWE, radiochemically purified 161Tb solution was measured on a PerkinElmer 1220 QuantulusTM Liquid Scintillation Spectrometer. Since there was no 161Tb certified standard solution available commercially, the counting efficiency was determined by the CIEMAT/NIST Efficiency Tracing method. The method was validated during a recent inter-laboratory comparison exercise involving the analysis of a uranium sample irradiated with thermal neutrons. Lastly, the measured 161Tb result was in excellent agreement with the result using gamma spectrometry and the result obtainedmore » by Pacific Northwest National Laboratory.« less

  16. Analysis of 161Tb by radiochemical separation and liquid scintillation counting

    SciTech Connect

    Jiang, J.; Davies, A.; Arrigo, L.; Friese, J.; Seiner, B. N.; Greenwood, L.; Finch, Z.

    2015-12-05

    The determination of 161Tb activity is problematic due to its very low fission yield, short half-life, and the complication of its gamma spectrum. At AWE, radiochemically purified 161Tb solution was measured on a PerkinElmer 1220 QuantulusTM Liquid Scintillation Spectrometer. Since there was no 161Tb certified standard solution available commercially, the counting efficiency was determined by the CIEMAT/NIST Efficiency Tracing method. The method was validated during a recent inter-laboratory comparison exercise involving the analysis of a uranium sample irradiated with thermal neutrons. Lastly, the measured 161Tb result was in excellent agreement with the result using gamma spectrometry and the result obtained by Pacific Northwest National Laboratory.

  17. Activity enhances dopaminergic long-duration response in Parkinson disease

    PubMed Central

    Auinger, Peggy; Fahn, Stanley; Oakes, David; Shoulson, Ira; Kieburtz, Karl; Rudolph, Alice; Marek, Kenneth; Seibyl, John; Lang, Anthony; Olanow, C. Warren; Tanner, Caroline; Schifitto, Giovanni; Zhao, Hongwei; Reyes, Lydia; Shinaman, Aileen; Comella, Cynthia L.; Goetz, Christopher; Blasucci, Lucia M.; Samanta, Johan; Stacy, Mark; Williamson, Kelli; Harrigan, Mary; Greene, Paul; Ford, Blair; Moskowitz, Carol; Truong, Daniel D.; Pathak, Mayank; Jankovic, Joseph; Ondo, William; Atassi, Farah; Hunter, Christine; Jacques, Carol; Friedman, Joseph H.; Lannon, Margaret; Russell, David S.; Jennings, Danna; Fussell, Barbara; Standaert, David; Schwarzschild, Michael A.; Growdon, John H.; Tennis, Marsha; Gauthier, Serge; Panisset, Michel; Hall, Jean; Gancher, Stephen; Hammerstad, John P.; Stone, Claudia; Alexander-Brown, Barbara; Factor, Stewart A.; Molho, Eric; Brown, Diane; Evans, Sharon; Clark, Jeffrey; Manyam, Bala; Simpson, Patricia; Wulbrecht, Brian; Whetteckey, Jacqueline; Martin, Wayne; Roberts, Ted; King, Pamela; Hauser, Robert; Zesiewicz, Theresa; Gauger, Lisa; Trugman, Joel; Wooten, G. Frederick; Rost-Ruffner, Elke; Perlmutter, Joel; Racette, Brad A.; Suchowersky, Oksana; Ranawaya, Ranjit; Wood, Susan; Pantella, Carol; Kurlan, Roger; Richard, Irene; Pearson, Nancy; Caviness, John N.; Adler, Charles; Lind, Marlene; Simuni, Tanya; Siderowf, Andrew; Colcher, Amy; Lloyd, Mary; Weiner, William; Shulman, Lisa; Koller, William; Lyons, Kelly; Feldman, Robert G.; Saint-Hilaire, Marie H.; Ellias, Samuel; Thomas, Cathi-Ann; Juncos, Jorge; Watts, Ray; Partlow, Anna; Tetrud, James; Togasaki, Daniel M.; Stewart, Tracy; Mark, Margery H.; Sage, Jacob I.; Caputo, Debbie; Gould, Harry; Rao, Jayaraman; McKendrick, Ann; Brin, Mitchell; Danisi, Fabio; Benabou, Reina; Hubble, Jean; Paulson, George W.; Reider, Carson; Birnbaum, Alex; Miyasaki, Janis; Johnston, Lisa; So, Julie; Pahwa, Rajesh; Dubinsky, Richard M.; Wszolek, Zbigniew; Uitti, Ryan; Turk, Margaret; Tuite, Paul; Rottenberg, David; Hansen, Joy; Ramos, Serrano; Waters, Cheryl; Lew, Mark; Welsh, Mickie; Kawai, Connie; O'Brien, Christopher; Kumar, Rajeev; Seeberger, Lauren; Judd, Deborah; Barclay, C. Lynn; Grimes, David A.; Sutherland, Laura; Dawson, Ted; Reich, Stephen; Dunlop, Rebecca; Albin, Roger; Frey, Kirk; Wernette, Kristine; Fahn, Stanley; Oakes, David; Shoulson, Ira; Kieburtz, Karl; Rudolph, Alice; Marek, Kenneth; Seibyl, John; Lang, Anthony; Olanow, C. Warren; Tanner, Caroline; Schifitto, Giovanni; Zhao, Hongwei; Reyes, Lydia; Shinaman, Aileen; Comella, Cynthia L.; Goetz, Christopher; Blasucci, Lucia M.; Samanta, Johan; Stacy, Mark; Williamson, Kelli; Harrigan, Mary; Greene, Paul; Ford, Blair; Moskowitz, Carol; Truong, Daniel D.; Pathak, Mayank; Jankovic, Joseph; Ondo, William; Atassi, Farah; Hunter, Christine; Jacques, Carol; Friedman, Joseph H.; Lannon, Margaret; Russell, David S.; Jennings, Danna; Fussell, Barbara; Standaert, David; Schwarzschild, Michael A.; Growdon, John H.; Tennis, Marsha; Gauthier, Serge; Panisset, Michel; Hall, Jean; Gancher, Stephen; Hammerstad, John P.; Stone, Claudia; Alexander-Brown, Barbara; Factor, Stewart A.; Molho, Eric; Brown, Diane; Evans, Sharon; Clark, Jeffrey; Manyam, Bala; Simpson, Patricia; Wulbrecht, Brian; Whetteckey, Jacqueline; Martin, Wayne; Roberts, Ted; King, Pamela; Hauser, Robert; Zesiewicz, Theresa; Gauger, Lisa; Trugman, Joel; Wooten, G. Frederick; Rost-Ruffner, Elke; Perlmutter, Joel; Racette, Brad A.; Suchowersky, Oksana; Ranawaya, Ranjit; Wood, Susan; Pantella, Carol; Kurlan, Roger; Richard, Irene; Pearson, Nancy; Caviness, John N.; Adler, Charles; Lind, Marlene; Simuni, Tanya; Siderowf, Andrew; Colcher, Amy; Lloyd, Mary; Weiner, William; Shulman, Lisa; Koller, William; Lyons, Kelly; Feldman, Robert G.; Saint-Hilaire, Marie H.; Ellias, Samuel; Thomas, Cathi-Ann; Juncos, Jorge; Watts, Ray; Partlow, Anna; Tetrud, James; Togasaki, Daniel M.; Stewart, Tracy; Mark, Margery H.; Sage, Jacob I.; Caputo, Debbie; Gould, Harry; Rao, Jayaraman; McKendrick, Ann; Brin, Mitchell; Danisi, Fabio; Benabou, Reina; Hubble, Jean; Paulson, George W.; Reider, Carson; Birnbaum, Alex; Miyasaki, Janis; Johnston, Lisa; So, Julie; Pahwa, Rajesh; Dubinsky, Richard M.; Wszolek, Zbigniew; Uitti, Ryan; Turk, Margaret; Tuite, Paul; Rottenberg, David; Hansen, Joy; Ramos, Serrano; Waters, Cheryl; Lew, Mark; Welsh, Mickie; Kawai, Connie; O'Brien, Christopher; Kumar, Rajeev; Seeberger, Lauren; Judd, Deborah; Barclay, C. Lynn; Grimes, David A.; Sutherland, Laura; Dawson, Ted; Reich, Stephen; Dunlop, Rebecca; Albin, Roger; Frey, Kirk; Wernette, Kristine; Mendis, Tilak

    2012-01-01

    Objective: We tested the hypothesis that dopamine-dependent motor learning mechanism underlies the long-duration response to levodopa in Parkinson disease (PD) based on our studies in a mouse model. By data-mining the motor task performance in dominant and nondominant hands of the subjects in a double-blind randomized trial of levodopa therapy, the effects of activity and dopamine therapy were examined. Methods: We data-mined the Earlier versus Later Levodopa Therapy in Parkinson's Disease (ELLDOPA) study published in 2005 and performed statistical analysis comparing the effects of levodopa and dominance of handedness over 42 weeks. Results: The mean change in finger-tapping counts from baseline before the initiation of therapy to predose at 9 weeks and 40 weeks increased more in the dominant compared to nondominant hand in levodopa-treated subjects in a dose-dependent fashion. There was no significant difference in dominant vs nondominant hands in the placebo group. The short-duration response assessed by the difference of postdose performance compared to predose performance at the same visit did not show any significant difference between dominant vs nondominant hands. Conclusions: Active use of the dominant hand and dopamine replacement therapy produces synergistic effect on long-lasting motor task performance during “off” medication state. Such effect was confined to dopamine-responsive symptoms and not seen in dopamine-resistant symptoms such as gait and balance. We propose that long-lasting motor learning facilitated by activity and dopamine is a form of disease modification that is often seen in trials of medications that have symptomatic effects. PMID:22459675

  18. Metabolic correlates of subthalamic nucleus activity in Parkinson's disease.

    PubMed

    Lin, Tanya P; Carbon, Maren; Tang, Chengke; Mogilner, Alon Y; Sterio, Djordje; Beric, Aleksandar; Dhawan, Vijay; Eidelberg, David

    2008-05-01

    Overactivity of subthalamic nucleus (STN) neurons is a consistent feature of Parkinson's disease (PD) and is a target of therapy for this disorder. However, the relationship of STN firing rate to regional brain function is not known. We scanned 17 PD patients with (18)F-fluorodeoxyglucose (FDG) PET to measure resting glucose metabolism before the implantation of STN deep brain stimulation electrodes. Spontaneous STN firing rates were recorded during surgery and correlated with preoperative regional glucose metabolism on a voxel-by-voxel basis. We also examined the relationship between firing rate and the activity of metabolic brain networks associated with the motor and cognitive manifestations of the disease. Mean firing rates were 47.2 +/- 6.1 and 48.7 +/- 8.5 Hz for the left and right hemispheres, respectively. These measures correlated (P < 0.007) with glucose metabolism in the putamen and globus pallidus, which receive projections from this structure. Significant correlations (P < 0.0005) were also evident in the primary motor (BA4) and dorsolateral prefrontal (BA46/10) cortical areas. The activity of both the motor (P < 0.0001) and the cognitive (P < 0.006) PD-related metabolic networks was elevated in these patients. STN firing rates correlated with the activity of the former (P < 0.007) but not the latter network (P = 0.39). The findings suggest that the functional pathways associated with motor disability in PD are linked to the STN firing rate. These pathways are likely to mediate the clinical benefit that is seen following targeted STN interventions for this disease. PMID:18400841

  19. Parkinson's disease and CYP1A2 activity

    PubMed Central

    Forsyth, J T; Grünewald, R A; Rostami-Hodjegan, A; Lennard, M S; Sagar, H J; Tucker, G T

    2000-01-01

    Aims MPTP, a neurotoxin which induces parkinsonism is partially metabolized by the enzyme CYP1A2. Smoking appears to protect against Parkinson's disease (PD) and cigarette smoke induces CYP1A2 activity. Thus, we investigated the hypothesis that idiopathic PD is associated with lower CYP1A2 activity using caffeine as a probe compound. Methods CYP1A2 activity was assessed using saliva paraxanthine (PX) to caffeine (CA) ratios. Caffeine half-life was also estimated from salivary concentrations of caffeine at 2 and 5 h post dose. 117 treated and 40 untreated patients with PD and 105 healthy control subjects were studied. Results PX/CA ratios were 0.57, 0.93 and 0.77 in treated patients, untreated patients and healthy control subjects, respectively, with no significant differences between study groups (95% CI: treated patients vs controls −0.24, 0.57; untreated patients vs controls −0.75, 0.35). However, patients with PD (treated or untreated) had caffeine half-lives shorter than that in controls (treated patients: 262 min, untreated patients: 244 min, controls: 345 min; 95% CI: controls vs treated patients 23, 143 (P = 0.003); controls vs untreated patients 19, 184 (P = 0.011)). Amongst the patients with PD, caffeine half-life was also inversely related to the age of onset of disease (P = 0.012); gender and concomitant drugs did not influence this significantly. Conclusions Based on PX/CA ratio, there was no evidence of decreased CYP1A2 activity in patients compared with control subjects. The observed decrease in the elimination half-life of caffeine in PD may be caused by increased CYP2E1 activity, an enzyme that also contributes to the metabolism of caffeine. The latter warrants further investigation. PMID:11012552

  20. Developing aerosol vaccines for Mycobacterium tuberculosis: Workshop proceedings: National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA, April 9, 2014.

    PubMed

    2015-06-12

    On April 9, 2014, Aeras and the National Institute of Allergy and Infectious Diseases convened a workshop entitled "Developing Aerosol Vaccines for Mycobacterium tuberculosis" in Bethesda, MD. The purpose of the meeting was to explore the potential for developing aerosol vaccines capable of preventing infection with M. tuberculosis (Mtb), preventing the development of active tuberculosis (TB) among those latently infected with Mtb, or as immunotherapy for persons with active TB. The workshop was organized around four key questions relevant to developing and assessing aerosol TB vaccines: (1) What is the current knowledge about lung immune responses and early pathogenesis resulting after Mtb infection and what are the implications for aerosol TB vaccine strategies? (2) What are the technical issues surrounding aerosol vaccine delivery? (3) What is the current experience in aerosol TB vaccine development? and (4) What are the regulatory implications of developing aerosol vaccines, including those for TB? Lessons learned from the WHO effort to develop an aerosol measles vaccine served as a case example for overall discussions at the meeting. Workshop participants agreed that aerosol delivery represents a potentially important strategy in advancing TB vaccine development efforts. As no major regulatory, manufacturing or clinical impediments were identified, members of the workshop emphasized the need for greater support to further explore the potential for this delivery methodology, either alone or as an adjunct to traditional parenteral methods of vaccine administration. PMID:25869894

  1. Synthesis, phase composition modification, and optical properties of Ce{sup 3+}/Tb{sup 3+} activated KGdF{sub 4} and GdF{sub 3} submicrocrystals

    SciTech Connect

    Cao Chunyan; Yang, Hyun Kyoung; Moon, Byung Kee; Choi, Byung Chun; Jeong, Jung Hyun; Kim, Kwang Ho

    2012-03-15

    Ce{sup 3+}/Tb{sup 3+} co-doped series of samples have been synthesized based on a citric acid assisted hydrothermal method. By controlling the hydrothermal treating time, the samples evolve from the Ce{sup 3+}/Tb{sup 3+} co-doped cubic phase KGdF{sub 4} with spherical morphology into the Ce{sup 3+}/Tb{sup 3+} co-doped orthorhombic phase GdF{sub 3} with rhombic shape finally. The X-ray diffraction data illustrate the phase composition modification process of the samples. The field emission scanning electron microscopy and the transmission electron microscopy images suggest the transformation in the morphology of final products. The spectra of the energy-dispersive spectroscopy reveal the constituents of the samples. And the selected area electronic diffraction patterns prove the crystalline phases of the samples. Based on previous studies and the experimental data, one possible phase composition modification process has been summarized. The photoluminescence excitation and emission spectra and the luminescent dynamic decay curves demonstrate the variations in optical properties of the Ce{sup 3+}/Tb{sup 3+} co-doped final products. - Graphical abstract: Schematic illustration for the phase composition modification from the Ce{sup 3+}/Tb{sup 3+} doped KGdF{sub 4} to the Ce{sup 3+}/Tb{sup 3+}doped GdF{sub 3} with multiform morphologies and different sizes. (C presents cubic phase, H presents hexagonal phase, and O presents orthorhombic phase.) Highlights: Black-Right-Pointing-Pointer The samples were synthesized by a hydrothermal method. Black-Right-Pointing-Pointer The samples evolved from the cubic phase KGdF{sub 4} into the orthorhombic phase GdF{sub 3}. Black-Right-Pointing-Pointer The morphology evolved from the spherical shape into the rhombic shape finally. Black-Right-Pointing-Pointer A possible phase composition modification process was summarized. Black-Right-Pointing-Pointer The optical properties of final products were compared and studied.

  2. A Selective Na(+) Aptamer Dissected by Sensitized Tb(3+) Luminescence.

    PubMed

    Zhou, Wenhu; Ding, Jinsong; Liu, Juewen

    2016-08-17

    A previous study of two RNA-cleaving DNAzymes, NaA43 and Ce13d, revealed the possibility of a common Na(+) aptamer motif. Because Na(+) binding to DNA is a fundamental biochemical problem, the interaction between Ce13d and Na(+) was studied in detail by using sensitized Tb(3+) luminescence spectroscopy. Na(+) displaces Tb(3+) from the DNAzyme, and thus quenches the emission from Tb(3+) . The overall requirement for Na(+) binding includes the hairpin and the highly conserved 16-nucleotide loop in the enzyme strand, along with a few unpaired nucleotides in the substrate. Mutation studies indicate good correlation between Na(+) binding and cleavage activity, thus suggesting a critical role of Na(+) binding for the enzyme activity. Ce13d displayed a Kd of ∼20 mm with Na(+) (other monovalent cations: 40-60 mm). The Kd values for other metal ions are mainly due to non-specific competition. With a single nucleotide mutation, the specific Na(+) binding was lost. Another mutant improved Kd to 8 mm with Na(+) . This study has demonstrated a Na(+) aptamer with important biological implications and analytical applications. It has also defined the structural requirements for Na(+) binding and produced an improved mutant. PMID:27238890

  3. Immunomodulation by vitamin D: implications for TB

    PubMed Central

    Chun, Rene F; Adams, John S; Hewison, Martin

    2011-01-01

    TB remains a major cause of mortality throughout the world. Low vitamin D status has been linked to increased risk of TB and other immune disorders. These observations suggest a role for vitamin D as a modulator of normal human immune function. This article will detail the cellular and molecular mechanisms by which vitamin D regulates the immune system and how vitamin D insufficiency may lead to immune dysregulation. The importance of vitamin D bioavailability as a mechanism for defining the immunomodulatory actions of vitamin D and its impact on TB will also be discussed. The overall aim will be to provide a fresh perspective on the potential benefits of vitamin D supplementation in the prevention and treatment of TB. PMID:22046197

  4. HIV-Associated TB: Facts 2013

    MedlinePlus

    ... Intensified case finding for TB, Isoniazid preventive therapy (IPT), and Infection control) will reduce the burden of ... the 42 countries that reported data for 2012, IPT was provided to 520,000 people living with ...

  5. Multidrug-Resistant Tuberculosis (MDR TB)

    MedlinePlus

    ... prisons, or homeless shelters. If you work in hospitals or health-care settings where TB patients are likely to be seen, you should consult infection control or occupational health experts. Ask about administrative and ...

  6. The association between the ratio of monocytes:lymphocytes at age 3 months and risk of tuberculosis (TB) in the first two years of life

    PubMed Central

    2014-01-01

    Background Recent transcriptomic studies revived a hypothesis suggested by historical studies in rabbits that the ratio of peripheral blood monocytes to lymphocytes (ML) is associated with risk of tuberculosis (TB) disease. Recent data confirmed the hypothesis in cattle and in adults infected with HIV. Methods We tested this hypothesis in 1,336 infants (540 HIV-infected, 796 HIV-exposed, uninfected (HEU)) prospectively followed in a randomized controlled trial of isoniazid prophylaxis in Southern Africa, the IMPAACT P1041 study. We modeled the relationship between ML ratio at enrollment (91 to 120 days after birth) and TB disease or death in HIV-infected children and latent Mycobacterium tuberculosis (MTB) infection, TB disease or death in HEU children within 96 weeks (with 12 week window) of randomization. Infants were followed-up prospectively and routinely assessed for MTB exposure and outcomes. Cox proportional hazards models allowing for non-linear associations were used; in all cases linear models were the most parsimonious. Results Increasing ML ratio at baseline was significantly associated with TB disease/death within two years (adjusted hazard ratio (HR) 1.17 per unit increase in ML ratio; 95% confidence interval (CI) 1.01 to 1.34; P = 0.03). Neither monocyte count nor lymphocyte counts alone were associated with TB disease. The association was not statistically dissimilar between HIV infected and HEU children. Baseline ML ratio was associated with composite endpoints of TB disease and death and/or TB infection. It was strongest when restricted to probable and definite TB disease (HR 1.50; 95% CI 1.19 to 1.89; P = 0.006). Therefore, per 0.1 unit increase in the ML ratio at three to four months of age, the hazard of probable or definite TB disease before two years was increased by roughly 4% (95% CI 1.7% to 6.6%). Conclusion Elevated ML ratio at three- to four-months old is associated with increased hazards of TB disease before two years among

  7. Potential Role of M. tuberculosis Specific IFN-γ and IL-2 ELISPOT Assays in Discriminating Children with Active or Latent Tuberculosis

    PubMed Central

    Chiappini, Elena; Della Bella, Chiara; Bonsignori, Francesca; Sollai, Sara; Amedei, Amedeo; Galli, Luisa; Niccolai, Elena; Singh, Mahavir; D'Elios, Mario M.; de Martino, Maurizio

    2012-01-01

    Background Although currently available IGRA have been reported to be promising markers for TB infection, they cannot distinguish active tuberculosis (TB) from latent infection (LTBI). Objective Children with LTBI, active TB disease or uninfected were prospectively evaluated by an in-house ELISPOT assay in order to investigate possible immunological markers for a differential diagnosis between LTBI and active TB. Methods Children at risk for TB infection prospectively enrolled in our infectious disease unit were evaluated by in-house IFN-γ and IL-2 based ELISPOT assays using a panel of Mycobacterium tuberculosis antigens. Results Twenty-nine children were classified as uninfected, 21 as LTBI and 25 as active TB cases (including 5 definite and 20 probable cases). Significantly higher IFN-γ ELISPOT responses were observed in infected vs. uninfected children for ESAT-6 (p<0.0001), CFP-10 (p<0.0001), TB 10.3 (p = 0.003), and AlaDH (p = 0.001), while differences were not significant considering Ag85B (p = 0.063), PstS1 (p = 0.512), and HspX (16 kDa) (p = 0.139). IL-2 ELISPOT assay responses were different for ESAT-6 (p<0.0001), CFP-10 (p<0.0001), TB 10.3 (p<0.0001), HspX (16 kDa) (p<0.0001), PstS1 (p<0.0001) and AlaDH (p = 0.001); but not for Ag85B (p = 0.063). Comparing results between children with LTBI and those with TB disease differences were significant for IFN-γ ELISPOT only for AlaDH antigen (p = 0.021) and for IL-2 ELISPOT assay for AlaDH (p<0.0001) and TB 10.3 antigen (p = 0.043). ROC analyses demonstrated sensitivity of 100% and specificity of 81% of AlaDH-IL-2 ELISPOT assay in discriminating between latent and active TB using a cut off of 12.5 SCF per million PBMCs. Conclusion Our data suggest that IL-2 based ELISPOT with AlaDH antigen may be of help in discriminating children with active from those with latent TB. PMID:23029377

  8. Predictive and prognostic properties of TB-LAM among HIV-positive patients initiating ART in Johannesburg, South Africa

    PubMed Central

    d'Elia, Alexander; Evans, Denise; McNamara, Lynne; Berhanu, Rebecca; Sanne, Ian; Lönnermark, Elisabet

    2015-01-01

    While the diagnostic properties of the TB LAM urine assay (LAM) have been well-described, little is known about its predictive and prognostic properties at ART initiation in a routine clinic setting. We describe the predictive and prognostic properties of LAM in HIV-positive patients initiating ART at an urban hospital in Johannesburg, South Africa. Retrospective study of HIV-positive adults (>18 years) who initiated standard first-line ART between February 2012 and April 2013 and had a LAM test at initiation. In HIV-positive patients with no known TB at ART initiation, we assessed the sensitivity, specificity and positive/negative likelihood ratios of LAM to predict incident TB within 6 months of ART initiation. In addition, in patients with a TB diagnosis and on TB treatment <3 months at ART initiation, we measured the CD4 response at 6 months on ART. Of the 274 patients without TB at ART initiation, 65% were female with median CD4 count of 213 cells/mm3. Among the 14 (5.1%) patients who developed active TB, none were urine LAM +ve at baseline. LAM had poor sensitivity (0.0% 95% CI 0.00-23.2) to predict incident TB within 6 months of initiation. We analyzed 22 patients with a confirmed TB diagnosis at initiation separately. Of these, LAM +ve patients (27%) showed lower CD4 gains compared to LAM negative patients (median increase 103 vs 199 cells/mm3; p = 0.08). LAM has limited value for accurately predicting incident TB in patients with higher CD4 counts after ART initiation. LAM may help identify TB/HIV co-infected patients at ART initiation who respond more slowly to treatment and require targeted interventions to improve treatment outcomes. Larger studies with longer patient follow-up are needed. PMID:26600904

  9. Imaging Microglial Activation with TSPO PET: Lighting Up Neurologic Diseases?

    PubMed

    Vivash, Lucy; O'Brien, Terence J

    2016-02-01

    Neuroinflammation is implicated in the pathogenesis of a wide range of neurologic and neuropsychiatric diseases. For over 20 years, (11)C-PK11195 PET, which aims to image expression of the translocator protein (TSPO) on activated microglia in the brain, has been used in preclinical and clinical research to investigate neuroinflammation in vivo in patients with brain diseases. However, (11)C-PK11195 suffers from two major limitations: its low brain permeability and high nonspecific and plasma binding results in a low signal-to-noise ratio, and the use of (11)C restricts its use to PET research centers and hospitals with an on-site cyclotron. In recent years, there has been a great deal of work into the development of new TSPO-specific PET radiotracers. This work has focused on fluorinated radiotracers, which would enable wider use and improved signal-to-noise ratios. These radiotracers have been utilized in preclinical and clinical studies of several neurologic diseases with varying degrees of success. Unfortunately, the application of these second-generation TSPO radiotracers has revealed additional problems, including a polymorphism that affects TSPO binding. In this review, the developments in TSPO imaging are discussed, and current limitations and suggestions for future directions are explored. PMID:26697963

  10. Phospholipase A2 activating protein and idiopathic inflammatory bowel disease.

    PubMed Central

    Peterson, J W; Dickey, W D; Saini, S S; Gourley, W; Klimpel, G R; Chopra, A K

    1996-01-01

    BACKGROUND: Crohn's disease and ulcerative colitis are idiopathic inflammatory bowel diseases (IBD) involving synthesis of eicosanoids from arachidonic acid (AA), which is released from membrane phospholipids by phospholipase A2 (PLA2). A potentially important regulator of the production of these mediators is a protein activator of PLA2, referred to as PLA2 activating protein (PLAP). AIMS: The purpose of this investigation was to discover if PLAP values might be increased in the inflamed intestinal tissue of patients with IBD and in intestinal tissue of mice with colitis. PATIENTS: Biopsy specimens were taken from patients with ulcerative colitis and Crohn's disease undergoing diagnostic colonoscopy, and normal colonic mucosa was obtained from patients without IBD after surgical resection. METHODS: Immunocytochemistry with affinity purified antibodies to PLAP synthetic peptides was used to locate PLAP antigen in sections of intestinal biopsy specimens from IBD patients compared with that of normal intestinal tissue. Northern blot analysis with a murine [32P] labelled plap cDNA probe was performed on RNA extracted from the colons of mice fed dextran sulphate sodium (DSS) and cultured HT-29 cells exposed to lipopolysaccharide (LPS). RESULTS: PLAP antigen was localised predominantly within monocytes and granulocytes in intestinal tissue sections from IBD patients, and additional deposition of extracellular PLAP antigen was associated with blood vessels and oedema fluid in the inflamed tissues. In contrast, tissue sections from normal human intestine were devoid of PLAP reactive antigen, except for some weak cytoplasmic reaction of luminal intestinal epithelial cells. Similarly, colonic tissue from DSS treated mice contained an increased amount of PLAP antigen compared with controls. The stroma of the lamina propria of the colonic mucosa from the DSS treated mice reacted intensely with antibodies to PLAP synthetic peptides, while no reaction was observed with control

  11. Contrasting behaviour of the co-activators in the luminescence spectra of Y2O2S:Tb3+,Er3+ nanometre sized particles under UV and red light excitation

    NASA Astrophysics Data System (ADS)

    Yan, Xiao; Fern, George R.; Withnall, Robert; Silver, Jack

    2013-01-01

    Nanometre sized particles of terbium and erbium co-doped yttrium oxysulfide up-converting phosphors were prepared by a urea homogeneous-precipitation method. Results from X-ray powder diffraction (XRPD), scanning electron microscopy (SEM) and photoluminescence spectroscopy studies on the microstructure and luminescent properties of the materials are reported. Upconversion emission was observed from the Er3+ cations when particles were excited with laser light of 632.8 nm wavelength. Under these conditions no interactions between the Er3+ cations and the Tb3+ cations were observed. In contrast there was evidence from the Stokes emission of the Er3+ cations under 254 nm excitation for an interaction between the Er3+ and Tb3+ cations reducing intensity of the latter's blue and green emission bands by cross relaxation processes.

  12. Contrasting behaviour of the co-activators in the luminescence spectra of Y2O2S:Tb3+,Er3+ nanometre sized particles under UV and red light excitation.

    PubMed

    Yan, Xiao; Fern, George R; Withnall, Robert; Silver, Jack

    2013-02-01

    Nanometre sized particles of terbium and erbium co-doped yttrium oxysulfide up-converting phosphors were prepared by a urea homogeneous-precipitation method. Results from X-ray powder diffraction (XRPD), scanning electron microscopy (SEM) and photoluminescence spectroscopy studies on the microstructure and luminescent properties of the materials are reported. Upconversion emission was observed from the Er(3+) cations when particles were excited with laser light of 632.8 nm wavelength. Under these conditions no interactions between the Er(3+) cations and the Tb(3+) cations were observed. In contrast there was evidence from the Stokes emission of the Er(3+) cations under 254 nm excitation for an interaction between the Er(3+) and Tb(3+) cations reducing intensity of the latter's blue and green emission bands by cross relaxation processes. PMID:23263157

  13. Peroxisome proliferator-activated receptors, metabolic syndrome and cardiovascular disease

    PubMed Central

    Azhar, Salman

    2011-01-01

    Metabolic syndrome (MetS) is a constellation of risk factors including insulin resistance, central obesity, dyslipidemia and hypertension that markedly increase the risk of Type 2 diabetes (T2DM) and cardiovascular disease (CVD). The peroxisome proliferators-activated receptor (PPAR) isotypes, PPARα, PPARδ/β and PPARγ are ligand-activated nuclear transcription factors, which modulate the expression of an array of genes that play a central role in regulating glucose, lipid and cholesterol metabolism, where imbalance can lead to obesity, T2DM and CVD. They are also drug targets, and currently, PPARα (fibrates) and PPARγ (thiazolodinediones) agonists are in clinical use for treating dyslipidemia and T2DM, respectively. These metabolic characteristics of the PPARs, coupled with their involvement in metabolic diseases, mean extensive efforts are underway worldwide to develop new and efficacious PPAR-based therapies for the treatment of additional maladies associated with the MetS. This article presents an overview of the functional characteristics of three PPAR isotypes, discusses recent advances in our understanding of the diverse biological actions of PPARs, particularly in the vascular system, and summarizes the developmental status of new single, dual, pan (multiple) and partial PPAR agonists for the clinical management of key components of MetS, T2DM and CVD. It also summarizes the clinical outcomes from various clinical trials aimed at evaluating the atheroprotective actions of currently used fibrates and thiazolodinediones. PMID:20932114

  14. Peroxisome proliferator-activated receptors, metabolic syndrome and cardiovascular disease.

    PubMed

    Azhar, Salman

    2010-09-01

    Metabolic syndrome (MetS) is a constellation of risk factors including insulin resistance, central obesity, dyslipidemia and hypertension that markedly increase the risk of Type 2 diabetes (T2DM) and cardiovascular disease (CVD). The peroxisome proliferators-activated receptor (PPAR) isotypes, PPARα, PPARδ/ß and PPARγ are ligand-activated nuclear transcription factors, which modulate the expression of an array of genes that play a central role in regulating glucose, lipid and cholesterol metabolism, where imbalance can lead to obesity, T2DM and CVD. They are also drug targets, and currently, PPARα (fibrates) and PPARγ (thiazolodinediones) agonists are in clinical use for treating dyslipidemia and T2DM, respectively. These metabolic characteristics of the PPARs, coupled with their involvement in metabolic diseases, mean extensive efforts are underway worldwide to develop new and efficacious PPAR-based therapies for the treatment of additional maladies associated with the MetS. This article presents an overview of the functional characteristics of three PPAR isotypes, discusses recent advances in our understanding of the diverse biological actions of PPARs, particularly in the vascular system, and summarizes the developmental status of new single, dual, pan (multiple) and partial PPAR agonists for the clinical management of key components of MetS, T2DM and CVD. It also summarizes the clinical outcomes from various clinical trials aimed at evaluating the atheroprotective actions of currently used fibrates and thiazolodinediones. PMID:20932114

  15. Predictors of tuberculosis (TB) and antiretroviral (ARV) medication non-adherence in public primary care patients in South Africa: a cross sectional study

    PubMed Central

    2013-01-01

    Background Despite the downward trend in the absolute number of tuberculosis (TB) cases since 2006 and the fall in the incidence rates since 2001, the burden of disease caused by TB remains a global health challenge. The co-infection between TB and HIV adds to this disease burden. TB is completely curable through the intake of a strict anti-TB drug treatment regimen which requires an extremely high and consistent level of adherence.The aim of this study was to investigate factors associated with adherence to anti-TB and HIV treatment drugs. Methods A cross-sectional survey method was used. Three study districts (14 primary health care facilities in each) were selected on the basis of the highest TB caseload per clinic. All new TB and new TB retreatment patients were consecutively screened within one month of anti-tuberculosis treatment. The sample comprised of 3107 TB patients who had been on treatment for at least three weeks and a sub-sample of the total sample were on both anti-TB treatment and anti-retro-viral therapy(ART) (N = 757). Data collection tools included: a Socio-Demographic Questionnaire; a Post-Traumatic-Stress-Disorder (PTSD) Screen; a Psychological Distress Scale; the Alcohol Use Disorder Identification Test (AUDIT); and self-report measures of tobacco use, perceived health status and adherence to anti-TB drugs and ART. Results The majority of the participants (N = 3107) were new TB cases with a 55.9% HIV co-infection rate in this adult male and female sample 18 years and older. Significant predictors of non-adherence common to both anti-TB drugs and to dual therapy (ART and anti-TB drugs) included poverty, having one or more co-morbid health condition, being a high risk for alcohol mis-use and a partner who is HIV positive. An additional predictor for non-adherence to anti-TB drugs was tobacco use. Conclusions A comprehensive treatment programme addressing poverty, alcohol mis-use, tobacco use and psycho-social counseling is indicated

  16. Role of MRP transporters in regulating antimicrobial drug inefficacy and oxidative stress-induced pathogenesis during HIV-1 and TB infections

    PubMed Central

    Roy, Upal; Barber, Paul; Tse-Dinh, Yuk-Ching; Batrakova, Elena V.; Mondal, Debasis; Nair, Madhavan

    2015-01-01

    Multi-Drug Resistance Proteins (MRPs) are members of the ATP binding cassette (ABC) drug-efflux transporter superfamily. MRPs are known to regulate the efficacy of a broad range of anti-retroviral drugs (ARV) used in highly active antiretroviral therapy (HAART) and antibacterial agents used in Tuberculus Bacilli (TB) therapy. Due to their role in efflux of glutathione (GSH) conjugated drugs, MRPs can also regulate cellular oxidative stress, which may contribute to both HIV and/or TB pathogenesis. This review focuses on the characteristics, functional expression, and modulation of known members of the MRP family in HIV infected cells exposed to ARV drugs and discusses their known role in drug-inefficacy in HIV/TB-induced dysfunctions. Currently, nine members of the MRP family (MRP1-MRP9) have been identified, with MRP1 and MRP2 being the most extensively studied. Details of the other members of this family have not been known until recently, but differential expression has been documented in inflammatory tissues. Researchers have found that the distribution, function, and reactivity of members of MRP family vary in different types of lymphocytes and macrophages, and are differentially expressed at the basal and apical surfaces of both endothelial and epithelial cells. Therefore, the prime objective of this review is to delineate the role of MRP transporters in HAART and TB therapy and their potential in precipitating cellular dysfunctions manifested in these chronic infectious diseases. We also provide an overview of different available options and novel experimental strategies that are being utilized to overcome the drug resistance and disease pathogenesis mediated by these membrane transporters. PMID:26441882

  17. The prevalence of human immunodeficiency virus infection among TB patients in Port Harcourt Nigeria

    PubMed Central

    Erhabor, O; Jeremiah, Z A; Adias, T C; Okere, CE

    2010-01-01

    The joint statement by the American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America recommends that all patients with tuberculosis (TB) undergo testing for human immunodeficiency virus (HIV) infection after counseling. In this study, we investigated the prevalence of HIV infection among 120 patients diagnosed with microbiologically proven TB aged 18 to 54 years with a mean age of 39.5 years (standard deviation 6.75). The subjects studied were 36 male (30%) and 84 females (70%). Enzyme-linked immunosorbent assay methods were used to screen for HIV infection among the subjects. Of the 120 TB patients tested 30 (25%) were positive for HIV infection. The prevalence of HIV was higher in females 24 (80%) compared to males 6 (20%) and among singles (66.7%) compared to married subjects (33.3%) (χ2 = 83.5 and χ2 = 126.2, respectively P = 0.001). HIV-1 was the predominant viral subtype. HIV prevalence was significantly higher in subjects in the 38–47 year and 28–37 year age groups (both 40%) followed by the 18–28 year age group (20%) (χ2 = 42.6, P = 0.05). The mean CD4 lymphocyte count of the HIV-infected TB subjects was significantly lower (195 ± 40.5 cells/μL) compared to the non-HIV infected (288 ± 35.25 cells/μL P = 0.01). This study has shown a high prevalence of HIV among TB patients. Reactivation of TB among people living with HIV can be reduced by TB preventive therapy and by universal access to antiretroviral therapy. PMID:22096379

  18. Synthesis and spectroscopic characterization of YPO{sub 4} activated with Tb{sup 3+} and effect of Bi{sup 3+} co-doping on the luminescence properties

    SciTech Connect

    Angiuli, Fabio; Cavalli, Enrico; Belletti, Alessandro

    2012-08-15

    Single crystals of YPO{sub 4}:Tb{sup 3+}(1%) have been grown from Pb{sub 2}P{sub 2}O{sub 7} flux and their emission dynamics have been characterized by steady state and time resolved optical spectroscopy. The investigation has then been extended to green emitting phosphors with composition Y{sub 0.95-x}Tb{sub 0.05}Bi{sub x}PO{sub 4} (x=0, 0.0025, 0.005, 0.01, 0.025), synthesized by the Pechini sol-gel method and by solid state reaction. The former procedure has yielded higher quality materials in terms of size and morphology of the particles and of emission performance. The effect of the Bi{sup 3+} co-doping on the emission properties has been related to the Bi{sup 3+}{yields}Tb{sup 3+} energy transfer process as well as to the influence of the bismuth ions on the optical properties of the host lattice. - Graphical abstract: The intensity of the 370 nm excited luminescence increases with the Bi{sup 3+} content. A possible mechanism accounting for this behavior is proposed and discussed. Highlights: Black-Right-Pointing-Pointer Green emitting YPO{sub 4}:Tb{sup 3+} phosphors were synthesized by different methods. Black-Right-Pointing-Pointer The emission dynamics have been investigated under different experimental conditions. Black-Right-Pointing-Pointer The co-doping with Bi{sup 3+} ions increases the emission performance of the phosphors.

  19. Activating transcription factor 6 derepression mediates neuroprotection in Huntington disease

    PubMed Central

    Naranjo, José R.; Zhang, Hongyu; Villar, Diego; González, Paz; Dopazo, Xose M.; Morón-Oset, Javier; Higueras, Elena; Oliveros, Juan C.; Arrabal, María D.; Prieto, Angela; Cercós, Pilar; González, Teresa; De la Cruz, Alicia; Casado-Vela, Juan; Rábano, Alberto; Valenzuela, Carmen; Gutierrez-Rodriguez, Marta; Li, Jia-Yi; Mellström, Britt

    2016-01-01

    Deregulated protein and Ca2+ homeostasis underlie synaptic dysfunction and neurodegeneration in Huntington disease (HD); however, the factors that disrupt homeostasis are not fully understood. Here, we determined that expression of downstream regulatory element antagonist modulator (DREAM), a multifunctional Ca2+-binding protein, is reduced in murine in vivo and in vitro HD models and in HD patients. DREAM downregulation was observed early after birth and was associated with endogenous neuroprotection. In the R6/2 mouse HD model, induced DREAM haplodeficiency or blockade of DREAM activity by chronic administration of the drug repaglinide delayed onset of motor dysfunction, reduced striatal atrophy, and prolonged life span. DREAM-related neuroprotection was linked to an interaction between DREAM and the unfolded protein response (UPR) sensor activating transcription factor 6 (ATF6). Repaglinide blocked this interaction and enhanced ATF6 processing and nuclear accumulation of transcriptionally active ATF6, improving prosurvival UPR function in striatal neurons. Together, our results identify a role for DREAM silencing in the activation of ATF6 signaling, which promotes early neuroprotection in HD. PMID:26752648

  20. Study on cholesteryl ester transfer activity in coronary heart disease.

    PubMed

    Fujinuma, Y; Tanaka, A; Maezawa, H

    1991-09-01

    The net cholesterol transfer activity from high density lipoprotein (HDL) to low density lipoprotein (LDL) was determined in the patients with coronary heart disease (CHD) to examine its effect on the pathogenesis of arteriosclerosis. Furthermore, in the CHD patients with high HDL cholesterolemia (more than 60 mg/dl), the HDL particle size was measured by high performance liquid chromatography. A significant cholesteryl ester transfer activity (P less than 0.02) was noted in the CHD patients with low HDL cholesterolemia (less than 60 mg/dl). The rate of cholesteryl ester transfer activity (cholesteryl ester transfer activity/hour) inversely correlated with the serum HDL cholesterol value (r = -0.483, P = 0.096) in the patients with CHD. These results suggest that an increase of CETA caused a low HDL cholesterol value in the CHD patients with low HDL cholesterolemia and it may have the risk of causing CHD. However, an increase of the CETA was not found in the CHD patients with high HDL cholesterolemia compared to the normal subjects, the HDL particle size being significantly greater than that in the normal subjects. In the CHD patients with high HDL cholesterolemia, the large size of HDL may have the risk of causing CHD. PMID:1934199

  1. Activating transcription factor 6 derepression mediates neuroprotection in Huntington disease.

    PubMed

    Naranjo, José R; Zhang, Hongyu; Villar, Diego; González, Paz; Dopazo, Xose M; Morón-Oset, Javier; Higueras, Elena; Oliveros, Juan C; Arrabal, María D; Prieto, Angela; Cercós, Pilar; González, Teresa; De la Cruz, Alicia; Casado-Vela, Juan; Rábano, Alberto; Valenzuela, Carmen; Gutierrez-Rodriguez, Marta; Li, Jia-Yi; Mellström, Britt

    2016-02-01

    Deregulated protein and Ca2+ homeostasis underlie synaptic dysfunction and neurodegeneration in Huntington disease (HD); however, the factors that disrupt homeostasis are not fully understood. Here, we determined that expression of downstream regulatory element antagonist modulator (DREAM), a multifunctional Ca2+-binding protein, is reduced in murine in vivo and in vitro HD models and in HD patients. DREAM downregulation was observed early after birth and was associated with endogenous neuroprotection. In the R6/2 mouse HD model, induced DREAM haplodeficiency or blockade of DREAM activity by chronic administration of the drug repaglinide delayed onset of motor dysfunction, reduced striatal atrophy, and prolonged life span. DREAM-related neuroprotection was linked to an interaction between DREAM and the unfolded protein response (UPR) sensor activating transcription factor 6 (ATF6). Repaglinide blocked this interaction and enhanced ATF6 processing and nuclear accumulation of transcriptionally active ATF6, improving prosurvival UPR function in striatal neurons. Together, our results identify a role for DREAM silencing in the activation of ATF6 signaling, which promotes early neuroprotection in HD. PMID:26752648

  2. [The biological activity of macrophages in health and disease].

    PubMed

    Nazimek, Katarzyna; Bryniarski, Krzysztof

    2012-01-01

    Macrophages are involved in immune response as phagocytes, antigen presenting cells and as effector cells of delayed-type hypersensitivity. Moreover, the activity of macrophages is associated with modulation of many biological processes during the whole life and depends on the actual macrophage phenotype induced under the influence of various microenvironmental stimuli. In pregnancy, placental macrophages induce the development of maternal tolerance to fetal antigens, while fetal macrophages are responsible for proper formation of tissues and organs. Residual macrophages play a very important role in tissue homeostasis, apoptotic cell clearance to prevent autoimmunization and first defense in infections. The inflammatory response of macrophages may be modulated by pathogens. Their suppressive activity is observed in immunologically privileged organs such as testes. In pathologies, macrophages are responsible for tissue damage in a case of nonspecific activation followed by overproduction of proinflammatory factors. Suppression of a specific immune response against tumors is mainly the effect of tumor associated macrophage (TAM) action. On the other hand, presentation of allergens or self-antigens by macrophages and their nonspecific activation by necrotic adipocytes leads to the induction of a chronic inflammatory response and impairment of immunity. Therefore, modulation of macrophage functions may be the key for improvement of therapy of cancer and allergic, autoimmune, metabolic, cardiovascular and Alzheimer's diseases. PMID:22922151

  3. Blood Transcriptional Biomarkers for Active Tuberculosis among Patients in the United States: a Case-Control Study with Systematic Cross-Classifier Evaluation

    PubMed Central

    Miller, Mikaela A.; Vasquez, Joshua; Weiner, Marc; Chapman, Adam; Engle, Melissa; Higgins, Michael; Quinones, Amy M.; Rosselli, Vanessa; Canono, Elizabeth; Yoon, Christina; Cattamanchi, Adithya; Davis, J. Lucian; Phang, Tzu; Stearman, Robert S.; Datta, Gargi; Garcia, Benjamin J.; Daley, Charles L.; Strong, Michael; Kechris, Katerina; Fingerlin, Tasha E.; Reves, Randall; Geraci, Mark W.

    2015-01-01

    Blood transcriptional signatures are promising for tuberculosis (TB) diagnosis but have not been evaluated among U.S. patients. To be used clinically, transcriptional classifiers need reproducible accuracy in diverse populations that vary in genetic composition, disease spectrum and severity, and comorbidities. In a prospective case-control study, we identified novel transcriptional classifiers for active TB among U.S. patients and systematically compared their accuracy to classifiers from published studies. Blood samples from HIV-uninfected U.S. adults with active TB, pneumonia, or latent TB infection underwent whole-transcriptome microarray. We used support vector machines to classify disease state based on transcriptional patterns. We externally validated our classifiers using data from sub-Saharan African cohorts and evaluated previously published transcriptional classifiers in our population. Our classifier distinguishing active TB from pneumonia had an area under the concentration-time curve (AUC) of 96.5% (95.4% to 97.6%) among U.S. patients, but the AUC was lower (90.6% [89.6% to 91.7%]) in HIV-uninfected Sub-Saharan Africans. Previously published comparable classifiers had AUC values of 90.0% (87.7% to 92.3%) and 82.9% (80.8% to 85.1%) when tested in U.S. patients. Our classifier distinguishing active TB from latent TB had AUC values of 95.9% (95.2% to 96.6%) among U.S. patients and 95.3% (94.7% to 96.0%) among Sub-Saharan Africans. Previously published comparable classifiers had AUC values of 98.0% (97.4% to 98.7%) and 94.8% (92.9% to 96.8%) when tested in U.S. patients. Blood transcriptional classifiers accurately detected active TB among U.S. adults. The accuracy of classifiers for active TB versus that of other diseases decreased when tested in new populations with different disease controls, suggesting additional studies are required to enhance generalizability. Classifiers that distinguish active TB from latent TB are accurate and generalizable

  4. Spectroscopic and energy transfer properties of Dy3+-doped, Tb3+/Dy3+-codoped dense oxyfluoride borogermanate scintillating glasses

    NASA Astrophysics Data System (ADS)

    Sun, Xin-Yuan; Yu, Xiao-Guang; Jiang, Da-Guo; Wang, Wen-Feng; Li, Yu-Nong; Chen, Zhi-Quan; Zhou, Yun-Zhi; Yang, Qing-Mei; Kang, Zhitao

    2016-06-01

    Dy3+-, Tb3+-activated, and Tb3+/Dy3+-coactivated oxyfluoride borogermanate scintillating glasses with the density of about 6.50 g/cm3 were successfully synthesized by a melt-quenching method. The structure and optical properties including transmittance, photoluminescence (excitation and emission spectra), photoluminescence decay, and X-ray excited luminescence (XEL) behaviors were studied in detail. Our results reveal that the energy transfer efficiency from Dy3+ to Tb3+ ions increases with an increase of Tb3+ concentration. The energy transfer mechanism is determined to be electric dipole-dipole interaction. However, the XEL intensity of Tb3+ decreases with the incorporation of sensitizer Dy3+ into borogermanate scintillating glass, which may result from the different mechanisms under ultraviolet light and X-ray excitation.

  5. Tunable luminescence properties and energy transfer in LaAl11 O18 :Eu,Tb phosphor.

    PubMed

    Mendhe, M S; Puppalwar, S P; Dhoble, S J

    2016-05-01

    Eu(2+) and Tb(3+) singly doped and co-doped LaAl11 O18 phosphors were prepared by a combustion method using urea as a fuel. The phase structure and photoluminescence (PL) properties of the prepared phosphors were characterized by powder X-ray diffraction (XRD), scanning electron microscopy (SEM), and photoluminescence excitation and emission spectra. When the content of Eu(2+) was fixed at 0.01, the emission chromaticity coordinates could be adjusted from blue to green region by tuning the contents of Tb(3+) ions from 0.01 to 0.03 through an energy transfer (ET) process. The fluorescence data collected from the samples with different contents of Tb(3+) into LaAl11 O18 : Eu, show the enhanced green emission at 545 nm associated with (5) D4 -(7) F5 transitions of Tb(3+) . The enhancement was attributed to ET from Eu(2+) to Tb(3+) , and therefore Eu(2+) ion acts as a sensitizer (an energy donor) while Tb(3+) ion as an activator. The ET from Eu(2+) to Tb(3+) is performed through dipole-dipole interaction. The ET efficiency and critical distance were also calculated. The present Eu(2+) -Tb(3+) co-doped LaAl11 O18 phosphor will have potential application for UV convertible white light-emitting diodes. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26592806

  6. A strategic approach to eradication of bovine TB from wildlife in New Zealand.

    PubMed

    Hutchings, S A; Hancox, N; Livingstone, P G

    2013-11-01

    A review and amendment of New Zealand's National Pest Management Strategy for bovine tuberculosis (TB) has led to adoption of new strategy objectives for localized eradication of disease from the principal wildlife maintenance host and infecting vector for farmed cattle and deer, the brushtail possum Trichosurus vulpecula. Historic programmes have been based on management of disease within herds and control of wildlife directed towards reducing infected herd prevalence. From July 2011, the TB strategy has been redirected towards eradication of TB from possums and other wildlife over a total area of at least 2.5 million hectares over a 15-year period. The amended strategy is intended to provide large-scale proof of concept, using two extensive bush areas, that TB can be eradicated from wildlife in New Zealand in the longer term, leading to eventual savings in control programmes needed to protect cattle and deer herds from infection. Achievement of strategy objectives will be supported by major research together with technical and managerial improvements in wildlife TB control and surveillance, and these are reviewed. PMID:24171853

  7. Activation of AMP-activated kinase as a strategy for managing autosomal dominant polycystic kidney disease.

    PubMed

    McCarty, Mark F; Barroso-Aranda, Jorge; Contreras, Francisco

    2009-12-01

    There is evidence that overactivity of both mammalian target of rapamycin (mTOR) and cystic fibrosis transmembrane conductance regulator (CFTR) contributes importantly to the progressive expansion of renal cysts in autosomal dominant polycystic kidney disease (ADPKD). Recent research has established that AMP-activated kinase (AMPK) can suppress the activity of each of these proteins. Clinical AMPK activators such as metformin and berberine may thus have potential in the clinical management of ADPKD. The traditional use of berberine in diarrhea associated with bacterial infections may reflect, in part, the inhibitory impact of AMPK on chloride extrusion by small intestinal enterocytes. PMID:19570618

  8. NIMA-related kinase TbNRKC is involved in basal body separation in Trypanosoma brucei.

    PubMed

    Pradel, Lydie C; Bonhivers, Mélanie; Landrein, Nicolas; Robinson, Derrick R

    2006-05-01

    The NIMA-related kinase 2 (NEK 2) has important cell cycle functions related to centriole integrity and splitting. Trypanosoma brucei does not possess centrioles, however, cytokinesis is coupled to basal body separation events. Here we report the first functional characterisation of a T. brucei basal body-cytoskeletal NIMA-related kinase (NRK) protein, TbNRKC. The TbNRKC kinase domain has high amino acid identity with the human NEK1 kinase domain (50%) but also shares 42% identity with human NEK2. TbNRKC is expressed in bloodstream and procyclic cells and functions as a bona fide kinase in vitro. Remarkably, RNAi knockdown of TbNRKC and overexpression of kinase-dead TbNRKC in procyclic forms induces the accumulation of cells with four basal bodies, whereas overexpression of active protein produces supernumary basal bodies and blocks cytokinesis. TbNRKC is located on mature and immature basal bodies and is the first T. brucei NRK to be found associated with the basal body cytokinesis pathway. PMID:16608878

  9. Generation and application of ssDNA aptamers against glycolipid antigen ManLAM of Mycobacterium tuberculosis for TB diagnosis.

    PubMed

    Tang, Xiao-Lei; Wu, Shi-Min; Xie, Yan; Song, Neng; Guan, Qing; Yuan, Chunhui; Zhou, Xiang; Zhang, Xiao-Lian

    2016-05-01

    The development of effective Mycobacterial antigen diagnostic reagents remains a high priority. Mannose-capped lipoarabinomannan (ManLAM) is a lipoglycan serving as a major cell wall component. ManLAM is also an early released antigen in the blood circulation system during Mycobacteria tuberculosis (M.tb) infection and is a perfect target antigen for TB diagnosis. In this study, ssDNA aptamers "antibodies" against ManLAM of the predominant clinical epidemic M.tb Beijing genotype strains were generated by the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) technique. The selected single aptamer T9 demonstrated the highest specificity and binding affinity, with an equilibrium dissociation constant (Kd) of 668 ± 159 nmol/L. We further detected ManLAM antigens in serum and sputum samples from active pulmonary tuberculosis (aPTB) patients, extrapulmonary TB (EPTB) patients and healthy donors by using a T9 based enzyme-linked oligonucleotide assay (ELONA). The results showed that the specificity and sensitivity were 95.31% and 83.00% (for 100 aPTB serum samples), 98.70% and 92.71% (for 96 aPTB sputum samples), and 94.44% and 88.71% (for 62 EPTB serum samples), respectively. A good correlation was observed between the T9 aptamer-based ELONA and the clinical T-SPOT.TB. Thus, T9 based ELONA has potentials for diagnosis of TB, including inactive TB, smear-negative TB, EPTB, and TB with immunodeficiency, and assist the diagnosis of LTBI albeit it could not distinguish LTBI and active TB. PMID:26850356

  10. Brain Na(+), K(+)-ATPase Activity In Aging and Disease.

    PubMed

    de Lores Arnaiz, Georgina Rodríguez; Ordieres, María Graciela López

    2014-06-01

    Na(+)/K(+) pump or sodium- and potassium-activated adenosine 5'-triphosphatase (Na(+), K(+)-ATPase), its enzymatic version, is a crucial protein responsible for the electrochemical gradient across the cell membranes. It is an ion transporter, which in addition to exchange cations, is the ligand for cardenolides. This enzyme regulates the entry of K(+) with the exit of Na(+) from cells, being the responsible for Na(+)/K(+) equilibrium maintenance through neuronal membranes. This transport system couples the hydrolysis of one molecule of ATP to exchange three sodium ions for two potassium ions, thus maintaining the normal gradient of these cations in animal cells. Oxidative metabolism is very active in brain, where large amounts of chemical energy as ATP molecules are consumed, mostly required for the maintenance of the ionic gradients that underlie resting and action potentials which are involved in nerve impulse propagation, neurotransmitter release and cation homeostasis. Protein phosphorylation is a key process in biological regulation. At nervous system level, protein phosphorylation is the major molecular mechanism through which the function of neural proteins is modulted in response to extracellular signals, including the response to neurotransmitter stimuli. It is the major mechanism of neural plasticity, including memory processing. The phosphorylation of Na(+), K(+)-ATPase catalytic subunit inhibits enzyme activity whereas the inhibition of protein kinase C restores the enzyme activity. The dephosphorylation of neuronal Na(+), K(+)-ATPase is mediated by calcineurin, a serine / threonine phosphatase. The latter enzyme is involved in a wide range of cellular responses to Ca(2+) mobilizing signals, in the regulation of neuronal excitability by controlling the activity of ion channels, in the release of neurotransmitters and hormones, as well as in synaptic plasticity and gene transcription. In the present article evidence showing Na(+), K(+)-ATPase involvement

  11. Brain Na+, K+-ATPase Activity In Aging and Disease

    PubMed Central

    de Lores Arnaiz, Georgina Rodríguez; Ordieres, María Graciela López

    2014-01-01

    Na+/K+ pump or sodium- and potassium-activated adenosine 5’-triphosphatase (Na+, K+-ATPase), its enzymatic version, is a crucial protein responsible for the electrochemical gradient across the cell membranes. It is an ion transporter, which in addition to exchange cations, is the ligand for cardenolides. This enzyme regulates the entry of K+ with the exit of Na+ from cells, being the responsible for Na+/K+ equilibrium maintenance through neuronal membranes. This transport system couples the hydrolysis of one molecule of ATP to exchange three sodium ions for two potassium ions, thus maintaining the normal gradient of these cations in animal cells. Oxidative metabolism is very active in brain, where large amounts of chemical energy as ATP molecules are consumed, mostly required for the maintenance of the ionic gradients that underlie resting and action potentials which are involved in nerve impulse propagation, neurotransmitter release and cation homeostasis. Protein phosphorylation is a key process in biological regulation. At nervous system level, protein phosphorylation is the major molecular mechanism through which the function of neural proteins is modulted in response to extracellular signals, including the response to neurotransmitter stimuli. It is the major mechanism of neural plasticity, including memory processing. The phosphorylation of Na+, K+-ATPase catalytic subunit inhibits enzyme activity whereas the inhibition of protein kinase C restores the enzyme activity. The dephosphorylation of neuronal Na+, K+-ATPase is mediated by calcineurin, a serine / threonine phosphatase. The latter enzyme is involved in a wide range of cellular responses to Ca2+ mobilizing signals, in the regulation of neuronal excitability by controlling the activity of ion channels, in the release of neurotransmitters and hormones, as well as in synaptic plasticity and gene transcription. In the present article evidence showing Na+, K+-ATPase involvement in signaling pathways

  12. Effect of tuberculosis on the survival of HIV-infected men in a country with low TB incidence

    PubMed Central

    López-Gatell, H; Cole, SR; Margolick, JB; Witt, MD; Martinson, J; Phair, JP; Jacobson, LP

    2010-01-01

    Evidence regarding the effect of tuberculosis disease (TB) on HIV disease progression at the population level remains inconclusive. We estimated the effect of incident TB on time to acquired immunodeficiency syndrome (AIDS)-related death, using a marginal structural Cox model. Between 1984 and 2005, 2,882 HIV-infected men in the Multicenter AIDS Cohort Study contributed 21,914 person-years while followed for a median of 5.4 years. At study entry, the median CD4 cell count and HIV-1 RNA viral load were 533 cells/mm3 (interquartile range [IQR], 365 – 737) and 12,953 copies/ml (IQR, 2,453 – 48,540), respectively. This study was performed in a setting with a modest exposure to HAART; 8,295 of 23,801 (35%) person-years were followed during the HAART era. Fifteen men incurred incident TB, yielding a TB incidence of 7 (95% confidence interval [CI]: 4, 14) per 10,000 person-years, and 1,072 died of AIDS-related causes. Accounting for potential confounders, including CD4 cell count and viral load, the hazard of AIDS-related death was 2.4 times larger for the person-time with TB, compared to the person-time without TB (95% CI: 1.2, 4.7). Results underscore the importance of avoiding TB by using preventive interventions, such as treatment of latent TB infection, particularly in populations with a large prevalence of HIV/TB co-infected individuals. PMID:18753866

  13. Physical Activity and Hemodynamic Reactivity in Chronic Kidney Disease

    PubMed Central

    Agarwal, Rajiv; Light, Robert P.

    2008-01-01

    Background and objectives: Patients with chronic kidney disease (CKD) have an elevated cardiovascular risk. This study was designed to understand better the presence and strength of the relationship between physical activity and BP and to explore determinants of hemodynamic reactivity. Design, setting, participants, & measurements: Twenty-four patients with CKD (mean age 69.5 yr; 3.1 antihypertensive drugs; estimated GFR 47 ml/min per 1.73 m2, albumin/creatinine ratio 403 mg/g) were studied on three occasions during a 6-wk period with 24-h ambulatory BP monitoring and simultaneous activity monitoring with wrist actigraphy. Results: Nondippers were found have a greater level of sleep activity compared with dippers, although the awake activity level was similar (7.06 versus 6.73) between groups (P = 0.042 for interaction). In 3587 BP activity pairs, hemodynamic reactivity was variable between individuals (systolic BP reactivity 1.06 [SD 10.50]; diastolic BP reactivity 0.89 [SD 7.80] heart rate reactivity 1.18 [SD 11.00]); those who were more sedentary had a greater increment in systolic BP compared with those who were less sedentary. Antihypertensive drugs blunted hemodynamic reactivity. Hemodynamic reactivity was greatest between 12 a.m. and 8 a.m., making this a vulnerable period for cardiovascular events. Conclusions: Greater hemodynamic reactivity in sedentary people with CKD offers a possible and thus far unrecognized mechanism of cardiovascular damage. Besides reducing BP, antihypertensive drugs reduce hemodynamic reactivity, which offers another plausible mechanism of cardiovascular protection with their use. PMID:18922983

  14. The Differential Gene Expression Pattern of Mycobacterium tuberculosis in Response to Capreomycin and PA-824 versus First-Line TB Drugs Reveals Stress- and PE/PPE-Related Drug Targets

    PubMed Central

    Fu, Li M.; Tai, Shu C.

    2009-01-01

    Tuberculosis is a leading infectious disease causing millions of deaths each year. How to eradicate mycobacterial persistence has become a central research focus for developing next-generation TB drugs. Yet, the knowledge in this area is fundamentally limited and only a few drugs, notably capreomycin and PA-824, have been shown to be active against non-replicating persistent TB bacilli. In this study, we performed a new bioinformatics analysis on microarray-based gene expression data obtained from the public domain to explore genes that were differentially induced by drugs between the group of capreomycin and PA-824 and the group of mainly the first-line TB drugs. Our study has identified 42 genes specifically induced by capreomycin and PA-824. Many of these genes are related to stress responses. In terms of the distribution of identified genes in a specific category relative to the whole genome, only the categories of PE/PPE and conserved hypotheticals have statistical significance. Six among the 42 genes identified in this study are on the list of the top 100 persistence targets selected by the TB Structural Genomics Consortium. Further biological elucidation of their roles in mycobacterial persistence is warranted. PMID:20016672

  15. TB/HIV Co-Infection Care in Conflict-Affected Settings: A Mapping of Health Facilities in the Goma Area, Democratic Republic of Congo

    PubMed Central

    Kaboru, Berthollet Bwira; Ogwang, Brenda. A.; Namegabe, Edmond Ntabe; Mbasa, Ndemo; Kabunga, Deka Kambale; Karafuli, Kambale

    2013-01-01

    Background: HIV/AIDS and Tuberculosis (TB) are major contributors to the burden of disease in sub-Saharan Africa. The two diseases have been described as a harmful synergy as they are biologically and epidemiologically linked. Control of TB/HIV co-infection is an integral and most challenging part of both national TB and national HIV control programmes, especially in contexts of instability where health systems are suffering from political and social strife. This study aimed at assessing the provision of HIV/TB co-infection services in health facilities in the conflict-ridden region of Goma in Democratic Republic of Congo. Methods: A cross-sectional survey of health facilities that provide either HIV or TB services or both was carried out. A semi-structured questionnaire was used to collect the data which was analysed using descriptive statistics. Results: Eighty facilities were identified, of which 64 facilities were publicly owned. TB care was more available than HIV care (in 61% vs. 9% of facilities). Twenty-three facilities (29%) offered services to co-infected patients. TB/HIV co-infection rates among patients were unknown in 82% of the facilities. Only 19 facilities (24%) reported some coordination with and support from concerned diseases’ control programmes. HIV and TB services are largely fragmented, indicating imbalances and poor coordination by disease control programmes. Conclusion: HIV and TB control appear not to be the focus of health interventions in this crisis affected region, despite the high risks of TB and HIV infection in the setting. Comprehensive public health response to this setting calls for reforms that promote joint TB/HIV co-infection control, including improved leadership by the HIV programmes that accuse weaknesses in this conflict-ridden region. PMID:24596866

  16. Safety of Adalimumab and Predictors of Adverse Events in 1693 Japanese Patients with Crohn’s Disease

    PubMed Central

    Watanabe, Mamoru; Matsui, Toshiyuki; Hase, Hidenori; Okayasu, Motohiro; Tsuchiya, Tsuyoshi; Shinmura, Yasuhiko; Hibi, Toshifumi

    2016-01-01

    Background and Aims: Data from an all-cases post-marketing study were used to evaluate the safety and effectiveness of adalimumab in Japanese patients with Crohn’s disease [CD]. Methods: Patients received adalimumab for 24 weeks. Data from all patients [n = 1693] were used for the safety assessment. Data from patients with CD activity index [CDAI] ≥ 150 at baseline were used for the effectiveness assessment. Results: The most frequent serious adverse drug reaction [ADR] was infection and infestations [6.6 events/100 patient-years]. The risk of serious infections increased in patients who had a history of malignancy and those with concomitant corticosteroid use. Of 415 patients who had switched from another anti-tumour necrosis factor alpha [TNFα] agent to adalimumab due to ADRs, 7.2% discontinued due to ADRs to adalimumab. Ten of 13 patients with a history of tuberculosis [TB] received prophylactic medication, and none developed TB. TB developed in one patient with no history of TB or anti-TB prophylaxis. Remission rates were 41.3% and 32.4% at 4 and 24 weeks, respectively. Remission rates did not differ between patients with and without concomitant use of immunomodulators. Predictive variables for increased effectiveness were CDAI ≤ 220 and disease duration of ≤ 2 years. Perianal lesions and loss of response to previous anti-TNFα agents affected effectiveness. Conclusions: The most frequent serious ADR was infection. Adalimumab significantly reduced disease activity, without any unexpected ADRs. Development of active TB during adalimumab therapy can be prevented through TB screening and prophylaxis. In patients who switched from another anti-TNFα agent to adalimumab due to ADRs, adalimumab was well tolerated. PMID:26961546

  17. Ubiquitin, Proteasomes and Proteolytic Mechanisms Activated by Kidney Disease

    PubMed Central

    Rajan, Vik; Mitch, William E.

    2008-01-01

    Summary The ubiquitin-proteasome system (UPS) includes 3 enzymes that conjugate ubiquitin to intracellular proteins that are then recognized and degraded in the proteasome. The process participates in the regulation of cell metabolism. In the kidney, the UPS regulates the turnover of transporters and signaling proteins and its activity is down regulated in acidosis-induced proximal tubular cell hypertrophy. In chronic kidney disease (CKD), muscle wasting occurs because complications of CKD including acidosis, insulin resistance, inflammation, and increased angiotensin II levels stimulate the UPS to degrade muscle proteins. This response also includes caspase-3 and calpains which act to cleave muscle proteins to provide substrates for the UPS. For example, caspase-3 degrades actomyosin, leaving a 14kD fragment of actin in muscle. The 14 kD actin fragment is increased in muscle of patient with kidney disease, burn injury and surgery. In addition, acidosis, insulin resistance, inflammation and angiotensin II stimulate glucocorticoid production. Glucocorticoids are also required for the muscle wasting that occurs in CKD. Thus, the UPS is involved in regulating kidney function and participates in highly organized responses that degrade muscle protein in response to loss of kidney function. PMID:18723090

  18. CENPA a Genomic Marker for Centromere Activity and Human Diseases

    PubMed Central

    M. Valdivia, Manuel; Hamdouch, Khaoula; Ortiz, Manuela; Astola, Antonio

    2009-01-01

    Inheritance of genetic material requires that chromosomes segregate faithfully during cell division. Failure in this process can drive to aneuploidy phenomenon. Kinetochores are unique centromere macromolecular protein structures that attach chromosomes to the spindle for a proper movement and segregation. A unique type of nucleosomes of centromeric chromatin provides the base for kinetochore formation. A specific histone H3 variant, CENPA, replaces conventional histone H3 and together with centromere-specific-DNA-binding factors directs the assembly of active kinetochores. Recent studies on CENPA nucleosomal structure, epigenetic inheritance of centromeric chromatin and transcription of pericentric heterochromatin provide new clues to our understanding of centromere structure and function. This review highlights the role and dynamics of CENPA assembly into centromeres and the potential contribution of this kinetochore protein to autoimmune and cancer diseases in humans. PMID:20119530

  19. The Correlation of Serum IL-12B Expression With Disease Activity in Patients With Inflammatory Bowel Disease

    PubMed Central

    Lee, Hye Won; Chung, Sook Hee; Moon, Chang Mo; Che, Xiumei; Kim, Seung Won; Park, Soo Jung; Hong, Sung Pil; Kim, Tae Il; Kim, Won Ho; Cheon, Jae Hee

    2016-01-01

    Abstract Genetic variants in IL12B, encoding the p40 subunit common in interleukin-12 (IL-12) and interleukin-23, were identified as the susceptibility loci for inflammatory bowel disease (IBD). This study aimed to identify the correlation of serum IL-12B expression with disease activity in patients with IBD and evaluate the possibility of IL-12B as a biomarker for assessing inflammatory status in IBD. A total of 102 patients with IBD, including 38, 32, and 32 patients with Crohn's disease (CD), ulcerative colitis (UC), and intestinal Behçet's disease (intestinal BD), respectively, were included. The clinical and laboratory data from the patients were collected at the time of serum IL-12B measurement. Serum IL-12B levels were measured using an enzyme-linked immunosorbent assay. The median IL-12B levels in patients with CD, UC, and intestinal BD were significantly higher than those in controls (1.87, 2.74, and 2.73 pg/mL, respectively, vs. 1.42 pg/mL, all P <0.05). IL-12B concentrations were associated with disease activity in patients with UC and intestinal BD but not in those with CD. IL-12B levels were increased with increasing disease activity in patients with UC (P <0.001). Likewise, patients with active intestinal BD had higher IL-12B levels than those without active disease (P = 0.008). IL-12B levels were correlated with the endoscopic disease activity of UC (P = 0.002) and intestinal BD (P = 0.001) but not that of CD. Serum IL-12B levels were significantly correlated with clinical and endoscopic disease activity in patients with UC and intestinal BD, suggesting its potential use as a biomarker for assessing disease activity in these patients. PMID:27281077

  20. Mind the gap: TB trends in the USA and the UK, 2000–2011

    PubMed Central

    Nnadi, Chimeremma D; Anderson, Laura F; Armstrong, Lori R; Stagg, Helen R; Pedrazzoli, Debora; Pratt, Robert; Heilig, Charles M; Abubakar, Ibrahim; Moonan, Patrick K

    2016-01-01

    Background TB remains a major public health concern, even in low-incidence countries like the USA and the UK. Over the last two decades, cases of TB reported in the USA have declined, while they have increased substantially in the UK. We examined factors associated with this divergence in TB trends between the two countries. Methods We analysed all cases of TB reported to the US and UK national TB surveillance systems from 1 January 2000 through 31 December 2011. Negative binominal regression was used to assess potential demographic, clinical and risk factor variables associated with differences in observed trends. Findings A total of 259 609 cases were reported. From 2000 to 2011, annual TB incidence rates declined from 5.8 to 3.4 cases per 100 000 in the USA, whereas in the UK, TB incidence increased from 11.4 to 14.4 cases per 100 000. The majority of cases in both the USA (56%) and the UK (64%) were among foreign-born persons. The number of foreign-born cases reported in the USA declined by 15% (7731 in 2000 to 6564 in 2011) while native-born cases fell by 54% (8442 in 2000 to 3883 in 2011). In contrast, the number of foreign-born cases reported in the UK increased by 80% (3380 in 2000 to 6088 in 2011), while the number of native-born cases remained largely unchanged (2158 in 2000 to 2137 in 2011). In an adjusted negative binomial regression model, significant differences in trend were associated with sex, age, race/ethnicity, site of disease, HIV status and previous history of TB (p<0.01). Among the foreign-born, significant differences in trend were also associated with time since UK or US entry (p<0.01). Interpretation To achieve TB elimination in the UK, a re-evaluation of current TB control policies and practices with a focus on foreign-born are needed. In the USA, maintaining and strengthening control practices are necessary to sustain the progress made over the last 20 years. PMID:26907187

  1. Serum ST2 in inflammatory bowel disease: a potential biomarker for disease activity.

    PubMed

    Boga, Salih; Alkim, Huseyin; Koksal, Ali Riza; Ozagari, Ayse Aysim; Bayram, Mehmet; Tekin Neijmann, Sebnem; Sen, Ilker; Alkim, Canan

    2016-06-01

    ST2, a specific ligand of interleukin 33, was described as a biomarker protein of inflammatory processes and overexpression of ST2 in ulcerative colitis (UC) was shown previously. We aimed to investigate the potential relationship of serum ST2 levels with the clinical, endoscopic and histopathological activity scores in UC and Crohn's disease (CD). Serum ST2 levels were determined in 143 patients with inflammatory bowel disease (IBD) (83 UC and 60 CD), in 50 healthy controls (HC), and in 32 patients with irritable bowel syndrome (IBS). Serum ST2 levels were elevated in IBD (56.8 (41.9-87.2) pg/mL) compared to HC and IBS (30.7 (20.2-54.3), p<0.001 and 39.9 (25.9-68.7) pg/mL, p=0.002, respectively). No significant difference was found between UC (54.2 (41.3-93.0) pg/mL) and CD (63.8 (42.7-88.4) pg/mL) and between IBS and HC. Serum ST2 levels were significantly increased in active UC compared to inactive UC (72.5 (44.1-99.5) vs 40.0 (34.7-51.6) pg/mL, p<0.001) and in active CD in comparison with inactive CD (63.8 (42.7-88.4) vs 48.4 (29.6-56.9) pg/mL, p=0.036). Patients with CD showing fistulizing behavior had significantly higher ST2 levels compared to patients with inflammatory and stricturing CD (p<0.001). Clinical activity scores of patients with UC and CD were correlated with serum ST2 levels (r=0.692, p<0.001 and r=0.242, p=0.043, respectively). Serum ST2 levels showed stepwise increases with the increasing histopathological scores of patients with UC and CD (p<0.001 for both). The present study highlights significant associations between ST2 and IBD presence and activity and demonstrates elevated serum ST2 levels in patients with active CD as a novel finding. PMID:27001944

  2. Spectroscopic investigation on tunable luminescence by energy transfer in Tb2-xSmx(MoO4)3 nanophosphors

    NASA Astrophysics Data System (ADS)

    Kamal, P. Mani; Vimal, G.; Biju, P. R.; Joseph, Cyriac; Unnikrishnan, N. V.; Ittyachen, M. A.

    2015-04-01

    New Sm3+ activated Tb2-xSmx(MoO4)3 nanophosphors were synthesized through sol-gel method. The structural and luminescence properties have been studied by XRD, TEM and photoluminescence measurements. The XRD pattern confirms that the Tb2-xSmx(MoO4)3 crystallizes in the same orthorhombic structure of Tb2(MoO4)3. The spectroscopic and laser parameters of Sm3+ ion in Tb2-x(MoO4)3 matrix were evaluated for the first time using Judd-Ofelt theoretical analysis. The higher value of stimulated emission cross-section of 4G5/2 → 6H7/2 transition of Sm3+ is favorable for low threshold and high gain to obtain continuous wave laser action. The photoluminescence excitation spectra suggest that this novel phosphor can be excited over a broad range from nUV to blue light (300-490 nm). Under the excitation of UV, Tb2-xSmx(MoO4)3 nanophosphor exhibits the characteristic emissions of Tb3+ and Sm3+. By varying the doping concentration of Sm3+, the emission color of the phosphors can be tuned and white emission in a single composition can be obtained under host excitation, in which an energy transfer from MoO42- → Sm3+/ Tb3+ and Tb3+ → Sm3+ was observed. The investigation of the luminescence decay curves and lifetime values implies the energy transfer between Tb3+ → Sm3+ and confirms the absence of Sm3+ → Tb3+ energy transfer. These phosphors might be a promising material for use in nUV LEDs and can exhibit tricolor luminescence under single excitation wavelength.

  3. Fecal Calprotectin and Clinical Disease Activity in Pediatric Ulcerative Colitis

    PubMed Central

    Kolho, Kaija-Leena; Turner, Dan

    2013-01-01

    Objective. To explore fecal calprotectin levels in pediatric ulcerative colitis (UC) in relation with the validated clinical activity index PUCAI. Methods. This study included all 37 children (median age 14 years) with UC who had calprotectin measured (PhiCal ELISA Test) by the time of PUCAI assessment at the Children's Hospital of Helsinki in a total of 62 visits. Calprotectin values <100 μg/g of stool were considered as normal. The best cut-off value of each measure to predict 3-month clinical outcome was derived by maximizing sensitivity and specificity. Results. In clinically active disease (PUCAI ≥ 10), calprotectin was elevated in 29/32 patients (91% sensitivity). When in clinical remission, 26% (8/30) of the children had normal calprotectin but 7 (23%) had an exceedingly high level (>1000 μg/g). The best cut-off value for calprotectin for predicting poor outcome was 800 μg/g (sensitivity 73%, specificity 72%; area under the ROC curve being 0.71 (95%CI 0.57–0.85)) and for the PUCAI best cut-off values >10 (sensitivity 62%, specificity 64%; area under the ROC curve 0.714 (95%CI 0.58–0.85)). Conclusion. The clinical relevance of somewhat elevated calprotectin during clinical remission in pediatric UC is not known and, until further evidence accumulates, does not indicate therapy escalation. PMID:23533791

  4. Steroid receptor RNA activator: Biologic function and role in disease.

    PubMed

    Liu, Chan; Wu, Hong-Tao; Zhu, Neng; Shi, Ya-Ning; Liu, Zheng; Ao, Bao-Xue; Liao, Duan-Fang; Zheng, Xi-Long; Qin, Li

    2016-08-01

    Steroid receptor RNA activator (SRA) is a type of long noncoding RNA (lncRNA) which coordinates the functions of various transcription factors, enhances steroid receptor-dependent gene expression, and also serves as a distinct scaffold. The novel, profound and expanded roles of SRA are emerging in critical aspects of coactivation of nuclear receptors (NRs). As a nuclear receptor coactivator, SRA can coactivate androgen receptor (AR), estrogen receptor α (ERα), ERβ, progesterone receptor (PR), glucocorticoid receptor (GR), thyroid hormone receptor and retinoic acid receptor (RAR). Although SRA is one of the least well-understood molecules, increasing studies have revealed that SRA plays a key role in both biological processes, such as myogenesis and steroidogenesis, and pathological changes, including obesity, cardiomyopathy, and tumorigenesis. Furthermore, the SRA-related signaling pathways, such as the mitogen-activated protein kinase (p38 MAPK), Notch and tumor necrosis factor α (TNFα) pathways, play critical roles in the pathogenesis of estrogen-dependent breast cancers. In addition, the most recent data demonstrates that SRA expression may serve as a new prognostic marker in patients with ER-positive breast cancer. Thus, elucidating the molecular mechanisms underlying SRA-mediated functions is important to develop proper novel strategies to target SRA in the diagnosis and treatment of human diseases. PMID:27282881

  5. Diaphragm activation during exercise in chronic obstructive pulmonary disease.

    PubMed

    Sinderby, C; Spahija, J; Beck, J; Kaminski, D; Yan, S; Comtois, N; Sliwinski, P

    2001-06-01

    Although it has been postulated that central inhibition of respiratory drive may prevent development of diaphragm fatigue in patients with chronic obstructive pulmonary disease (COPD) during exercise, this premise has not been validated. We evaluated diaphragm electrical activation (EAdi) relative to maximum in 10 patients with moderately severe COPD at rest and during incremental exhaustive bicycle exercise. Flow was measured with a pneumotachograph and volume by integration of flow. EAdi and transdiaphragmatic pressures (Pdi) were measured using an esophageal catheter. End-expiratory lung volume (EELV) was assessed by inspiratory capacity (IC) maneuvers, and maximal voluntary EAdi was obtained during these maneuvers. Minute ventilation (V E) was 12.2 +/- 1.9 L/min (mean +/- SD) at rest, and increased progressively (p < 0.001) to 31.0 +/- 7.8 L/min at end-exercise. EELV increased during exercise (p < 0.001) causing end-inspiratory lung volume to attain 97 +/- 3% of TLC at end-exercise. Pdi at rest was 9.4 +/- 3.2 cm H(2)O and increased during the first two thirds of exercise (p < 0.001) to plateau at about 13 cm H(2)O. EAdi was 24 +/- 6% of voluntary maximal at rest and increased progressively during exercise (p < 0.001) to reach 81 +/- 7% at end-exercise. In conclusion, dynamic hyperinflation during exhaustive exercise in patients with COPD reduces diaphragm pressure-generating capacity, promoting high levels of diaphragm activation. PMID:11401887

  6. Tackling tuberculosis: Insights from an international TB Summit in London

    PubMed Central

    Maitra, Arundhati; Danquah, Cynthia A; Scotti, Francesca; Howard, Tracey K; Kamil, Tengku K; Bhakta, Sanjib

    2015-01-01

    Tuberculosis (TB) poses a grave predicament to the world as it is not merely a scientific challenge but a socio-economic burden as well. A prime cause of mortality in human due to an infectious disease; the malady and its cause, Mycobacterium tuberculosis have remained an enigma with many questions that remain unanswered. The ability of the pathogen to survive and switch between varied physiological states necessitates a protracted therapeutic regimen that exerts an excessive strain on low-resource countries. To complicate things further, there has been a significant rise of antimicrobial resistance. Existing control measures, including treatment regimens have remained fairly uniform globally for at least half a century and require reinvention. Overcoming the societal and scientific challenges requires an increase in dialog to identify key regions that need attention and effective partners with whom successful collaborations can be fostered. In this report, we explore the discussions held at the International TB Summit 2015 hosted by EuroSciCon, which served as an excellent platform for researchers to share their recent findings. Ground-breaking results require outreach to affect policy design, governance and control of the disease. Hence, we feel it is important that meetings such as these reach a wider, global audience. PMID:26151309

  7. Tackling tuberculosis: Insights from an international TB Summit in London.

    PubMed

    Maitra, Arundhati; Danquah, Cynthia A; Scotti, Francesca; Howard, Tracey K; Kamil, Tengku K; Bhakta, Sanjib

    2015-01-01

    Tuberculosis (TB) poses a grave predicament to the world as it is not merely a scientific challenge but a socio-economic burden as well. A prime cause of mortality in human due to an infectious disease; the malady and its cause, Mycobacterium tuberculosis have remained an enigma with many questions that remain unanswered. The ability of the pathogen to survive and switch between varied physiological states necessitates a protracted therapeutic regimen that exerts an excessive strain on low-resource countries. To complicate things further, there has been a significant rise of antimicrobial resistance. Existing control measures, including treatment regimens have remained fairly uniform globally for at least half a century and require reinvention. Overcoming the societal and scientific challenges requires an increase in dialog to identify key regions that need attention and effective partners with whom successful collaborations can be fostered. In this report, we explore the discussions held at the International TB Summit 2015 hosted by EuroSciCon, which served as an excellent platform for researchers to share their recent findings. Ground-breaking results require outreach to affect policy design, governance and control of the disease. Hence, we feel it is important that meetings such as these reach a wider, global audience. PMID:26151309

  8. Influence of medical treatment, smoking and disease activity on pregnancy outcomes in Crohn's disease.

    PubMed

    Julsgaard, Mette; Nørgaard, Mette; Hvas, Christian Lodberg; Grosen, Anne; Hasseriis, Sara; Christensen, Lisbet Ambrosius

    2014-03-01

    OBJECTIVE. Little is known about predictors for adverse pregnancy outcomes among women with Crohn's disease (CD). In this population-based study, we examined pregnancy outcomes in CD stratified by medical treatment and smoking status while accounting for disease activity. METHODS. In two Danish regions with a population of 1.6 million, we identified 154 CD women who had given birth within a 6-year period. We combined questionnaire data, prescription data, data from medical records and population-based medical databases. We used logistic regression to estimate prevalence odds ratios (POR) for adverse pregnancy outcomes by different predictors. RESULTS. Among 105 (80%) respondents, 55 (52%) reported taking medication during pregnancy. The majority (95%) were in disease remission. The children's mean birth weight did not differ by maternal medical treatment. As expected, smoking was a predictor of low birth weight. Mean birth weight in children of smokers in medical treatment was significantly reduced by 274 g compared with children of non-smokers who received medical treatment. In children of women without medical treatment, this difference was 126 g between smokers and non-smokers. Women in medical treatment did not have an increased risk of preterm delivery (POR 0.71; 95% confidence interval (CI) 0.18-2.79), congenital malformations (POR 0.60; 0.10-3.76) or cesarean section (POR 1.40; 0.63-3.08). CONCLUSIon. In CD, smoking was negatively associated with child birth weight. This association was most pronounced among women who received medical treatment. Maternal medical treatment for CD did not seem to be a risk factor for adverse pregnancy outcomes. PMID:24417179

  9. Dopaminergic correlates of metabolic network activity in Parkinson's disease.

    PubMed

    Holtbernd, Florian; Ma, Yilong; Peng, Shichun; Schwartz, Frank; Timmermann, Lars; Kracht, Lutz; Fink, Gereon R; Tang, Chris C; Eidelberg, David; Eggers, Carsten

    2015-09-01

    Parkinson's disease (PD) is associated with distinct metabolic covariance patterns that relate to the motor and cognitive manifestations of the disorder. It is not known, however, how the expression of these patterns relates to measurements of nigrostriatal dopaminergic activity from the same individuals. To explore these associations, we studied 106 PD subjects who underwent cerebral PET with both (18) F-fluorodeoxyglucose (FDG) and (18) F-fluoro-L-dopa (FDOPA). Expression values for the PD motor- and cognition-related metabolic patterns (PDRP and PDCP, respectively) were computed for each subject; these measures were correlated with FDOPA uptake on a voxel-by-voxel basis. To explore the relationship between dopaminergic function and local metabolic activity, caudate and putamen FDOPA PET signal was correlated voxel-wise with FDG uptake over the entire brain. PDRP expression correlated with FDOPA uptake in caudate and putamen (P < 0.001), while PDCP expression correlated with uptake in the anterior striatum (P < 0.001). While statistically significant, the correlations were only of modest size, accounting for less than 20% of the overall variation in these measures. After controlling for PDCP expression, PDRP correlations were significant only in the posterior putamen. Of note, voxel-wise correlations between caudate/putamen FDOPA uptake and whole-brain FDG uptake were significant almost exclusively in PDRP regions. Overall, the data indicate that PDRP and PDCP expression correlates significantly with PET indices of presynaptic dopaminergic functioning obtained in the same individuals. Even so, the modest size of these correlations suggests that in PD patients, individual differences in network activity cannot be explained solely by nigrostriatal dopamine loss. PMID:26037537

  10. Targeted screening and treatment for latent tuberculosis infection using QuantiFERON®-TB Gold is cost-effective in Mexico

    PubMed Central

    Burgos, J. L.; Kahn, J. G.; Strathdee, S. A.; Valencia-Mendoza, A.; Bautista-Arredondo, S.; Laniado-Laborin, R.; Castañeda, R.; Deiss, R.; Garfein, R. S.

    2009-01-01

    SUMMARY OBJECTIVE To assess the cost-effectiveness of screening for latent tuberculosis infection (LTBI) using a commercially available detection test and treating individuals at high risk for human immunodeficiency virus (HIV) infection in a middle-income country. DESIGN We developed a Markov model to evaluate the cost per LTBI case detected, TB case averted and quality-adjusted life year (QALY) gained for a cohort of 1000 individuals at high risk for HIV infection over 20 years. Baseline model inputs for LTBI prevalence were obtained from published literature and cross-sectional data from tuberculosis (TB) screening using QuantiFERON®-TB Gold In-Tube (QFT-GIT) testing among sex workers and illicit drug users at high risk for HIV recruited through street outreach in Tijuana, Mexico. Costs are reported in 2007 US dollars. Future costs and QALYs were discounted at 3% per year. Sensitivity analyses were performed to evaluate model robustness. RESULTS Over 20 years, we estimate the program would prevent 78 cases of active TB and 55 TB-related deaths. The incremental cost per case of LTBI detected was US$730, cost per active TB averted was US$529 and cost per QALY gained was US$108. CONCLUSIONS In settings of endemic TB and escalating HIV incidence, targeting LTBI screening and treatment among high-risk groups may be highly cost-effective. PMID:19723375

  11. Magnetomechanical damping in cryogenic TbDy

    NASA Technical Reports Server (NTRS)

    Dooley, J.; Good, N.; White, C.; Leland, S.; Fultz, B.

    2002-01-01

    Vibration damping in polycrystalline TbDy alloys was studied at cryogenic temperatures. The material was prepared by cold-rolling to induce crystallographic texture, and was then heat-treated to relieve internal stress. Mechanical hysteretic losses were measured at various strains, frequencies, and loading configurations at 77 K. Some textured TbDy materials demonstrated 22.6% energy dissipation in mechanical measurements at low frequency (0.01 Hz) and a mean logarithmic decrement of 0.23 at a higher frequency (25 kHz). Ultrasonic velocities of longitudinal and shear elastic waves were measured on single and polycrystalline TbDy; little variation in ultrasonic velocities was found evenfor samples with large variation in crystallographic texture and magnetomechanical properties.

  12. Untreated Active Tuberculosis in Pregnancy with Intraocular Dissemination: A Case Report and Review of the Literature

    PubMed Central

    LoBue, Stephen; Adams, Daniel; Oladipo, Yewande; Posso, Ramses; Mapp, Tiffany; Santiago, Crystal; Jain, Manisha; Marino, William D.; Henderson, Cassandra E.

    2015-01-01

    Background. Tuberculosis (TB) is a disease that affects hundreds of millions of people across the world. However, the incidence in developed countries has decreased over the past decades causing physicians to become unfamiliar with its unspecific symptoms. Pregnant individuals are especially difficult because many symptoms of active TB can mimic normal physiological changes of pregnancy. We present a case report of a 26-year-old multiparous woman, G4P3003, at 38-week gestation with a history of positive PPD who emigrated from Ghana 6 years ago. She came to the hospital with an initial complaint of suprapubic pain, pressure, and possible leakage of amniotic fluid for the past week. Patient also complained of a productive cough for the past 3 to 4 months with a decrease in vision occurring with the start of pregnancy. Visual acuity was worse than 20/200 in both eyes. Definitive diagnosis of active TB was delayed due to patient refusal of chest X-ray. Fortunately, delay in diagnosis was minimized since patient delivered within 24 hours of admission. Active TB was confirmed with intraocular dissemination. Patient had optic atrophy OS (left eye) and papillitis, choroiditis, and uveitis OD (right eye) due to TB infiltration. Fetus was asymptomatic and anti-TB therapy was started for both patients. PMID:26693374

  13. Advanced development of the digital tuberculosis tester for MDR-TB screening

    NASA Astrophysics Data System (ADS)

    Smith, Jason E.; Simkulet, Michelle D.; Gutin, Alexander; Gutin, Alexy; Bardarov, Savco; Jacobs, William R., Jr.; Castracane, James; Tang, Oliver; Riska, Paul

    2001-05-01

    Tuberculosis (TB) remains the leading cause of death in the world from a single infectious disease, and the threat is becoming more critical with the spread of multi-drug resistant Tuberculosis (MDR-TB). TB detection, and susceptibility testing for drug resistant strain identification, is advancing with the development of Luciferase Reporter Mycobacteriophages (LRM). LRM will emit visible light at very low intensity when in the presence of live mycobacteria cells such as Tuberculosis strains. InterScience, Inc., together with its collaboration, is developing a highly sensitive, real-time digital detection system for the analysis of luminescent assays. Recent advances in system sensitivity, design, and implementation, as well as preliminary results of the development of individual test cartridges, will be presented. The ultimate goal of this work is to provide a versatile luminescence detection tool for widespread research and clinical applications.

  14. Mobile based gold nanoprobe TB diagnostics for point-of-need.

    PubMed

    Veigas, B; Fortunato, E; Baptista, P V

    2015-01-01

    Nanotechnology based diagnostics has provided improved tools for pathogen detection and sensitive and specific characterization of antibiotic resistance signatures. Tuberculosis (TB) is caused by members of the Mycobacterium tuberculosis Complex (MTBC) and, according to the World Health Organization, is one of the most serious infectious diseases in the world. Recent advances in molecular diagnostics of TB have improved both the detection time and sensitivity but they still require specialized technical personnel and cumbersome laboratory equipment. Diagnostics at point-of-need is crucial to TB control as it may provide rapid identification of pathogen together with the resistance profile of TB strains, originated from single nucleotide polymorphisms (SNPs) in different loci, allowing for a more accurate indication of the adequate therapy.Gold nanoparticles have been widely used in molecular diagnostics platforms. Here, we describe the use of gold nanoprobes (oligonucleotide functionalized gold nanoparticles) to be used in a non-cross-linking colorimetric method for the direct detection of specific DNA targets. Due to the remarkable optical properties of gold nanoparticles, this detection system provides colorimetric detection of the pathogen together with the potential of identification of several single nucleotide polymorphisms (SNPs) involved in TB resistance to antibiotics. For point-of-need use, we adapted this strategy to a low-cost mobile scheme using a paper based revelation platform and where the spectral signature is transposed to RGB data via a smartphone device. This way, identification of pathogen and characterization of resistance signatures is achieved at point-of-need. PMID:25626530

  15. The campaign against TB: governments must commit themselves. TB in Africa.

    PubMed

    Chaulet, P

    1996-01-01

    This article presents an interview with Pierre Chaulet on the campaign against tuberculosis (TB) in Africa. Chaulet noted during the 9th IUATLD Conference of the Africa Region that the national TB control programs have taken on a new commitment in Africa since the declaration of TB as a global emergency in the 1990s. The TB control program package consists of five principal components: 1) political will of the government and its commitment to support the program; 2) case detection; 3) initiation of short course chemotherapy among detected cases; 4) ensuring the regular supply of essential anti-TB drugs; and 5) establishing a registry and reporting system for program monitoring and evaluation. Of the 40 African countries participating in the conference, 30 have efficient programs. Comparing the management of National TB Control Programs in Francophone and Anglophone Africa, it is noted that both are complementary, although generally, public health issues are more easily integrated into the medical training in the Anglophone countries than they are in the Francophone. Anglophone uses a more comprehensive approach to public health while countries in the Francophone practiced a more traditional university centralization. Finally, Chaulet gives his comment on the role of WHO in addressing concerns over the financial issues involved in TB Control Programs, particularly in the mobilization of resources from nongovernmental organizations and international institutions. PMID:12179805

  16. Magnetic Order in TbCo2Zn20 and TbFe2Zn20

    SciTech Connect

    Tian, W.; Christianson, Andrew D; Zarestky, J. L.; Jia, S.; Bud'ko, S. L.; Canfield, P. C.; Piccoli, P. M. B.; Schultz, A. J.

    2010-01-01

    We report neutron di raction studies of TbCo2Zn20 and TbFe2Zn20, two isostructural compounds which exhibit dramatically di erent magnetic behavior. In the case of TbCo2Zn20, magnetic Bragg peaks corresponding to antiferromagnetic order are observed below TN 2.5 K with a propagation vector of (0.5 0.5 0.5). On the other hand, TbFe2Zn20 undergoes a ferromagnetic transition at temperatures as high as 66 K which shows a high sensitivity to sample-to-sample variations. Two samples of TbFe2Zn20 with the same nominal compositions but with substantially di erent mag- netic ordering temperatures (Tc 51 and 66 K) were measured by single crystal neutron di raction. Structural re nements of the neutron di raction data nd no direct signature of atomic site disorder between the two TbFe2Zn20 samples except for subtle di erences in the anisotropic thermal param- eters. The di erences in the anisotropic thermal parameters between the two samples is likely due to very small amounts of disorder. This provides further evidence for the extreme sensitivity of the magnetic properties of TbFe2Zn20 to small sample variations, even small amounts of disorder.

  17. An Innovative Method to Enhance the Modified DOTS for TB Patients

    PubMed Central

    Yekrang Sis, Hassan; Azabdaftari, Fariba; Mahdavi Poor, Behroz; Asgharzadeh, Mohammad; Jannati, Ali; Asghari Jafarabadi, Mohammad

    2015-01-01

    Background: Nowadays establishing communication and educating patients to enhance their knowledge regarding disease and treatment process at home is one of the most important principles in providing patient care. Materials and Methods: A semi-experimental study was done on 57 patients with active pulmonary tuberculosis in two care groups namely professional – family mix directly observed treatment short- course (PFM-DOTS) and family based-DOTS (FB-DOTS). The patients were referred to the tuberculosis and lung diseases research center for diagnosis and treatment of pulmonary tuberculosis. Both the patient and a family supervisor were evaluated regarding their level of knowledge of the disease and the treatment regimen. Results: A significant difference between the degree of knowledge of groups of patients and the groups of family relatives before and after the intervention was indicated, with a higher increase in PFM-DOTS group than in F-B-DOTS group (P< 0.001). In PFM- DOTS group 100% of the patients, and in the FB-DOTS group 86.8% of the patients followed the recommended drug regimen (P<0.001). Conclusion: According to the treatment recommendations by the World Health Organization (WHO) for appropriate implementation of DOTS project combating TB, it seems the PFM-DOTS implementation is a more suitable method with greater effects on correct care and treatment of tuberculosis patients. PMID:26858763

  18. A comparative study of magnetic behaviors in TbNi{sub 2}, TbMn{sub 2} and TbNi{sub 2}Mn

    SciTech Connect

    Wang, J. L.; Md Din, M. F.; Hong, F.; Cheng, Z. X.; Dou, S. X.; Kennedy, S. J.; Studer, A. J.; Campbell, S. J.; Wu, G. H.

    2014-05-07

    All TbNi{sub 2}, TbMn{sub 2}, and TbNi{sub 2}Mn compounds exhibit the cubic Laves phase with AB{sub 2}-type structure in spite of the fact that the ratio of the Tb to transition-metal components in TbNi{sub 2}Mn is 1:3. Rietveld refinement indicates that in TbNi{sub 2}Mn the Mn atoms are distributed on both the A (8a) and B (16d) sites. The values of the lattice constants were measured to be a = 14.348 Å (space group F-43 m), 7.618 Å, and 7.158 Å (space group Fd-3 m) for TbNi{sub 2}, TbMn{sub 2}, and TbNi{sub 2}Mn, respectively. The magnetic transition temperatures T{sub C} were found to be T{sub C} = 38 K and T{sub C} = 148 K for TbNi{sub 2} and TbNi{sub 2}Mn, respectively, while two magnetic phase transitions are detected for TbMn{sub 2} at T{sub 1} = 20 K and T{sub 2} = 49 K. Clear magnetic history effects in a low magnetic field are observed in TbMn{sub 2} and TbNi{sub 2}Mn. The magnetic entropy changes have been obtained.

  19. One health/veterinary links associated with TB vaccines

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objectives: participants will understand the current status of veterinary tuberculosis (TB) vaccine research for cattle and wildlife and their potential applications for development of human TB vaccines. Vaccines are lacking for many chronic intracellular pathogens requiring cell-mediated immunity ...

  20. Tuberculosis: The Connection between TB and HIV (the AIDS Virus)

    MedlinePlus

    ... Task Force Tuberculosis: The Connection between TB and HIV Recommend on Facebook Tweet Share Compartir Order this ... if I am infected with both TB and HIV? If you have HIV, it is important to ...

  1. HIV-1 and the immune response to TB

    PubMed Central

    Walker, Naomi F; Meintjes, Graeme; Wilkinson, Robert J

    2013-01-01

    TB causes 1.4 million deaths annually. HIV-1 infection is the strongest risk factor for TB. The characteristic immunological effect of HIV is on CD4 cell count. However, the risk of TB is elevated in HIV-1 infected individuals even in the first few years after HIV acquisition and also after CD4 cell counts are restored with antiretroviral therapy. In this review, we examine features of the immune response to TB and how this is affected by HIV-1 infection and vice versa. We discuss how the immunology of HIV–TB coinfection impacts on the clinical presentation and diagnosis of TB, and how antiretroviral therapy affects the immune response to TB, including the development of TB immune reconstitution inflammatory syndrome. We highlight important areas of uncertainty and future research needs. PMID:23653664

  2. Mathematical study of the thermoluminescence process in K2YF5:Tb(3+).

    PubMed

    Kadari, Ahmed; Mostefa, Rabah; Marcazzó, Julián; Kadri, Dahane

    2015-12-01

    This paper presents results of studying the simulated thermoluminescence (TL) glow curve in potassium-yttrium double fluoride doped with trivalent optically active Tb(3+) ions (K2YF5:Tb(3+)). Samples have been irradiated with different doses (0.24, 2.4 and 24 Gy) of beta particles. Four trapping states and one kind of recombination-centre model have been used in this simulation. The activation energy and order of kinetics are determined using the general-order kinetic model. The results obtained using the authors' proposed models were tested and compared with the experimental glow curve of K2YF5:Tb(3+). The comparison has shown that the proposed model can predict more accurately and easily the behaviour of the TL glow curve at three different doses. PMID:25543131

  3. Biomarkers of basic activities of daily living in Alzheimer's disease.

    PubMed

    Hall, James R; Johnson, Leigh A; Barber, Robert C; Vo, Hoa T; Winter, A Scott; O'Bryant, Sid E

    2012-01-01

    Functional impairment is common in Alzheimer's disease (AD) and related to increased caregiver burden and institutionalization. There is a dearth of research investigating the relationship between specific biomarkers and basic activities of daily living (BADLs) such as toileting, feeding, dressing, grooming, bathing, and ambulating. The present study examined the relationship between serum based biomarkers and specific ADLs in a sample of AD patients. Data were collected from 196 participants enrolled in the Texas Alzheimer's Research and Care Consortium Project and diagnosed with AD. BADLs were measured using the Lawton-Brody Physical Self-Maintenance Scale. A panel of 22 biomarkers previously found to be related to AD pathology was used for the analysis. Stepwise regression modeling was used to assess the link between the biomarkers and BADLs. Results were also examined by gender. Nine of the 22 biomarkers were significantly related to BADLs. When stratified by gender, the biomarkers accounted for 32% of the variance in the males and 27% in females. The pattern of significant biomarkers differed by gender with IL 7 and Tenascin C significantly related to BADLs for females and IL 15 significantly related to BADLs for males. The results of this study indicated that a small number of serum based biomarkers are related to BADLs, and these biomarkers differed by gender. PMID:22571981

  4. TB-HIV co-infection among pregnant women in Karnataka, South India: A case series.

    PubMed

    Suresh, Shastri; Sharath, Burugina N; Anita, Shet; Lalitha, Ravindra; Prasad, Tripathy J; Rewari, Bharat B

    2016-01-01

    Tuberculosis (TB) is a significant contributor to mortality in HIV-infected patients. Concurrent TB infection is also a significant contributing factor to maternal mortality in human immunodeficiency virus (HIV)-infected pregnant women. Studies addressing the outcomes of TB and HIV co-infection among pregnant women are generally infrequent. Although limited, the records maintained by the Revised National Tuberculosis Control Programme (RNTCP) and the National AIDS Control Programme (NACP) in Karnataka State, Southern India provide information about the numbers of pregnant women who are co-infected with TB and HIV and their pregnancy outcomes. We reviewed the data and conducted this study to understand how TB-HIV co-infection influences the outcomes of pregnancy in this setting. We sought to determine the incidence and treatment and delivery outcomes of TB-HIV co-infected pregnant women in programmatic settings in Karnataka State in southern India. The study participants were all the HIV-infected pregnant women who were screened for tuberculosis under the NACP from 2008 to 2012. For the purposes of this study, the program staff in the field gathered the data regarding on treatment and delivery outcomes of pregnant women. A total of seventeen pregnant women with TB-HIV co-infection were identified among 3,165,729 pregnant women (for an incidence of 5.4 per million pregnancies). The median age of these pregnant women was 24 years, and majority were primiparous women with WHO HIV stage III disease and were on a stavudine-based ART regimen. The maternal mortality rates were 18% before delivery and 24% after delivery. The abortion rate was 24%, and the neonatal mortality rate was 10%. The anti-tuberculosis treatment and anti-retroviral treatment outcome mortality rates were 30% and 53%, respectively. Although the incidence of TB among the HIV-infected pregnant women was marginally less than that among the non-HIV-infected women, the delivery outcomes were relatively

  5. The relationship between infliximab concentrations, antibodies to infliximab and disease activity in Crohn's disease

    PubMed Central

    Vande Casteele, Niels; Khanna, Reena; Levesque, Barrett G; Stitt, Larry; Zou, G Y; Singh, Sharat; Lockton, Steve; Hauenstein, Scott; Ohrmund, Linda; Greenberg, Gordon R; Rutgeerts, Paul J; Gils, Ann; Sandborn, William J; Vermeire, Séverine; Feagan, Brian G

    2015-01-01

    Objective Although low infliximab trough concentrations and antibodies to infliximab (ATI) are associated with poor outcomes in patients with Crohn's disease (CD), the clinical relevance of ATI in patients with adequate infliximab concentrations is uncertain. We evaluated this question using an assay sensitive for identification of ATI in the presence of infliximab. Design In an observational study, 1487 trough serum samples from 483 patients with CD who participated in four clinical studies of maintenance infliximab therapy were analysed using a fluid phase mobility shift assay. Infliximab and ATI concentrations most discriminant for remission, defined as a C-reactive protein concentration of ≤5 mg/L, were determined by receiver operating characteristic curves. A multivariable regression model evaluated these factors as independent predictors of remission. Results Based upon analysis of 1487 samples, 77.1% of patients had detectable and 22.9% had undetectable infliximab concentrations, of which 9.5% and 71.8%, respectively, were positive for ATI. An infliximab concentration of >2.79 μg/mL (area under the curve (AUC)=0.681; 95% CI 0.632 to 0.731) and ATI concentration of <3.15 U/mL (AUC=0.632; 95% CI 0.589 to 0.676) were associated with remission. Multivariable analysis showed that concentrations of both infliximab trough (OR 1.8; 95% CI 1.3 to 2.5; p<0.001) and ATI (OR 0.57; 95% CI 0.39 to 0.81; p=0.002) were independent predictors of remission. Conclusions The development of ATI increases the probability of active disease even at low concentrations and in the presence of a therapeutic concentration of drug during infliximab maintenance therapy. Evaluation of strategies to prevent ATI formation, including therapeutic drug monitoring with selective infliximab dose intensification, is needed. PMID:25336114

  6. Issues in design and interpretation of MDR-TB clinical trials: report of the first Global MDR-TB Clinical Trials Landscape Meeting

    PubMed Central

    2015-01-01

    Recognizing that the current MDR-TB regimen is suboptimal and based on low-quality evidence, the Global MDR-TB Clinical Trials Landscape Meeting was held in December, 2014 to strategize about coordination of research and development of new treatment regimens for this disease that affects millions of people worldwide every year. Sixty international experts on multidrug-resistant tuberculosis (MDR-TB) met in Washington D.C. and Cape Town, South Africa to consider key MDR-TB trial-related issues, including: standardization of definitions; clinical trial capacity building and; regimens optimized to foster compliance, avoid the emergence of resistance and have clinical relevance for special populations, including children and those co-infected with HIV. Underpinning all of this is the generation of a sufficient evidence base to facilitate regulatory approval and improved normative guidance. Participants discussed treatment combinations currently being studied in Phase 2B and Phase 3 trials as well as other promising new regimens and combinations that may be evaluated in the near future. These include regimens designed specifically to enable shorter duration and all-oral treatment as a means of maximizing treatment completion. It is hoped that clear definition of these challenges will facilitate the process of identifying solutions that accelerate progress towards effective, non-toxic treatments that can be programmatically implemented.

  7. Investigations on photoluminescence and cathodoluminescence properties of Ca3La6(SiO4)6:Tb3 +, Mn2 +

    NASA Astrophysics Data System (ADS)

    Zhang, Jia; Zhou, Beibei; Wang, Xichen

    2016-08-01

    Tb3 +/Mn2 + activated Ca3La6(SiO4)6 (CLS) phosphors were prepared by solid-state reaction method, and their photoluminescence and cathodoluminescence (CL) properties were investigated. The CLS:Tb3 + sample shows a yellowish green emission under 377 nm excitation, and the excitation spectrum reveals the excitation peaks between 340 and 390 nm can match with the near-ultraviolet LED chip. Excellent thermal stability has been obtained in the CLS:Tb3 + phosphor by studying the temperature dependence of the Tb3 + emission intensity. By introducing Mn2 + into CLS:Tb3 +, tunable emissions are generated due to the efficient energy transfer from Tb3 + to Mn2 +. The CL spectrum of CLS:Tb3 + displays that the characteristic 5D4-7FJ (J = 6 - 3) transitions of Tb3 + are found under electron beam excitation. The above investigation results imply that the CLS:Tb3 +, Mn2 + phosphors could have potential applications on LEDs and FEDs.

  8. Investigations on photoluminescence and cathodoluminescence properties of Ca3La6(SiO4)6:Tb(3+), Mn(2.).

    PubMed

    Zhang, Jia; Zhou, Beibei; Wang, Xichen

    2016-08-01

    Tb(3+)/Mn(2+) activated Ca3La6(SiO4)6 (CLS) phosphors were prepared by solid-state reaction method, and their photoluminescence and cathodoluminescence (CL) properties were investigated. The CLS:Tb(3+) sample shows a yellowish green emission under 377nm excitation, and the excitation spectrum reveals the excitation peaks between 340 and 390nm can match with the near-ultraviolet LED chip. Excellent thermal stability has been obtained in the CLS:Tb(3+) phosphor by studying the temperature dependence of the Tb(3+) emission intensity. By introducing Mn(2+) into CLS:Tb(3+), tunable emissions are generated due to the efficient energy transfer from Tb(3+) to Mn(2+). The CL spectrum of CLS:Tb(3+) displays that the characteristic (5)D4-(7)FJ (J=6-3) transitions of Tb(3+) are found under electron beam excitation. The above investigation results imply that the CLS:Tb(3+), Mn(2+) phosphors could have potential applications on LEDs and FEDs. PMID:27111156

  9. 'TB or not TB?' Problems of differential diagnosis of cutaneous mycobacteriosis and tuberculosis - A Case Study and interdisciplinary discussion.

    PubMed

    Szmygin-Milanowska, Katarzyna; Grzywa-Celińska, Anna; Zwolska, Zofia; Krawczyk, Paweł; Guz, Leszek; Milanowski, Janusz

    2016-03-01

    The diagnosis of cutaneous tuberculosis poses a serious challenge due to many skin diseases of different etiology resembling the lesions caused by the TB (tuberculosis) bacillus, and difficulties in confirming the disease. The presented case concerns skin lesions in a hobby aquarist stung in the finger of the left hand by a fish. The resulting inflammatory infiltration was to be cutaneous tuberculosis or mycobacteriosis caused by MOTT (Mycobacterium other than tuberculosis). Laboratory, pathomorphologic, genetic and microbiologic tests of samples obtained from the patient, fish and water in the aquarium gave ambiguous results. A multidisciplinary discussion is presented on the difficulties in the differential diagnosis, problems with a clear interpretation of the results of various conducted tests, and possible ways of transmission of the infection, relevant to the described example. PMID:27007525

  10. Community-based treatment of advanced HIV disease: introducing DOT-HAART (directly observed therapy with highly active antiretroviral therapy).

    PubMed Central

    Farmer, P.; Léandre, F.; Mukherjee, J.; Gupta, R.; Tarter, L.; Kim, J. Y.

    2001-01-01

    In 2000, acquired immunodeficiency syndrome (AIDS) overtook tuberculosis (TB) as the world's leading infectious cause of adult deaths. In affluent countries, however, AIDS mortality has dropped sharply, largely because of the use of highly active antiretroviral therapy (HAART). Antiretroviral agents are not yet considered essential medications by international public health experts and are not widely used in the poor countries where human immunodeficiency virus (HIV) takes its greatest toll. Arguments against the use of HAART have mainly been based on the high cost of medications and the lack of the infrastructure necessary for using them wisely. We re- examine these arguments in the setting of rising AIDS mortality in developing countries and falling drug prices, and describe a small community-based treatment programme based on lessons gained in TB control. With the collaboration of Haitian community health workers experienced in the delivery of home-based and directly observed treatment for TB, an AIDS-prevention project was expanded to deliver HAART to a subset of HIV patients deemed most likely to benefit. The inclusion criteria and preliminary results are presented. We conclude that directly observed therapy (DOT) with HAART, "DOT-HAART", can be delivered effectively in poor settings if there is an uninterrupted supply of high-quality drugs. PMID:11799447

  11. Boeing TB-29 Superfortress (B-29)

    NASA Technical Reports Server (NTRS)

    1945-01-01

    Boeing TB-29 Superfortress (B-29): Arriving for use with the NACA right at the end of World War II, this Boeing B-29 Superfortress was used for research into hydraulically boosting flight controls. After just over five years of study at Langley, the B-29 was returned to the Air Force.

  12. Differential cellular recognition pattern to M. tuberculosis targets defined by IFN-γ and IL-17 production in blood from TB + patients from Honduras as compared to health care workers: TB and immune responses in patients from Honduras

    PubMed Central

    2013-01-01

    Background A better understanding of the quality of cellular immune responses directed against molecularly defined targets will guide the development of TB diagnostics and identification of molecularly defined, clinically relevant M.tb vaccine candidates. Methods Recombinant proteins (n = 8) and peptide pools (n = 14) from M. tuberculosis (M.tb) targets were used to compare cellular immune responses defined by IFN-γ and IL-17 production using a Whole Blood Assay (WBA) in a cohort of 148 individuals, i.e. patients with TB + (n = 38), TB- individuals with other pulmonary diseases (n = 81) and individuals exposed to TB without evidence of clinical TB (health care workers, n = 29). Results M.tb antigens Rv2958c (glycosyltransferase), Rv2962c (mycolyltransferase), Rv1886c (Ag85B), Rv3804c (Ag85A), and the PPE family member Rv3347c were frequently recognized, defined by IFN-γ production, in blood from healthy individuals exposed to M.tb (health care workers). A different recognition pattern was found for IL-17 production in blood from M.tb exposed individuals responding to TB10.4 (Rv0288), Ag85B (Rv1886c) and the PPE family members Rv0978c and Rv1917c. Conclusions The pattern of immune target recognition is different in regard to IFN-γ and IL-17 production to defined molecular M.tb targets in PBMCs from individuals frequently exposed to M.tb. The data represent the first mapping of cellular immune responses against M.tb targets in TB patients from Honduras. PMID:23497342

  13. Women, men, and rheumatoid arthritis: analyses of disease activity, disease characteristics, and treatments in the QUEST-RA Study

    PubMed Central

    Sokka, Tuulikki; Toloza, Sergio; Cutolo, Maurizio; Kautiainen, Hannu; Makinen, Heidi; Gogus, Feride; Skakic, Vlado; Badsha, Humeira; Peets, Tõnu; Baranauskaite, Asta; Géher, Pál; Újfalussy, Ilona; Skopouli, Fotini N; Mavrommati, Maria; Alten, Rieke; Pohl, Christof; Sibilia, Jean; Stancati, Andrea; Salaffi, Fausto; Romanowski, Wojciech; Zarowny-Wierzbinska, Danuta; Henrohn, Dan; Bresnihan, Barry; Minnock, Patricia; Knudsen, Lene Surland; Jacobs, Johannes WG; Calvo-Alen, Jaime; Lazovskis, Juris; Pinheiro, Geraldo da Rocha Castelar; Karateev, Dmitry; Andersone, Daina; Rexhepi, Sylejman; Yazici, Yusuf; Pincus, Theodore

    2009-01-01

    Introduction Gender as a predictor of outcomes of rheumatoid arthritis (RA) has evoked considerable interest over the decades. Historically, there is no consensus whether RA is worse in females or males. Recent reports suggest that females are less likely than males to achieve remission. Therefore, we aimed to study possible associations of gender and disease activity, disease characteristics, and treatments of RA in a large multinational cross-sectional cohort of patients with RA called Quantitative Standard Monitoring of Patients with RA (QUEST-RA). Methods The cohort includes clinical and questionnaire data from patients who were seen in usual care, including 6,004 patients at 70 sites in 25 countries as of April 2008. Gender differences were analyzed for American College of Rheumatology Core Data Set measures of disease activity, DAS28 (disease activity score using 28 joint counts), fatigue, the presence of rheumatoid factor, nodules and erosions, and the current use of prednisone, methotrexate, and biologic agents. Results Women had poorer scores than men in all Core Data Set measures. The mean values for females and males were swollen joint count-28 (SJC28) of 4.5 versus 3.8, tender joint count-28 of 6.9 versus 5.4, erythrocyte sedimentation rate of 30 versus 26, Health Assessment Questionnaire of 1.1 versus 0.8, visual analog scales for physician global estimate of 3.0 versus 2.5, pain of 4.3 versus 3.6, patient global status of 4.2 versus 3.7, DAS28 of 4.3 versus 3.8, and fatigue of 4.6 versus 3.7 (P < 0.001). However, effect sizes were small-medium and smallest (0.13) for SJC28. Among patients who had no or minimal disease activity (0 to 1) on SJC28, women had statistically significantly higher mean values compared with men in all other disease activity measures (P < 0.001) and met DAS28 remission less often than men. Rheumatoid factor was equally prevalent among genders. Men had nodules more often than women. Women had erosions more often than men, but

  14. Rapid fecal calprotectin testing to assess for endoscopic disease activity in inflammatory bowel disease: A diagnostic cohort study

    PubMed Central

    Kwapisz, Lukasz; Mosli, Mahmoud; Chande, Nilesh; Yan, Brian; Beaton, Melanie; Micsko, Jessica; Mennill, Pauline W.; Barnett, William; Bax, Kevin; Ponich, Terry; Howard, John; Tirolese, Anthony; Lannigan, Robert; Gregor, James

    2015-01-01

    Background and Aim: With increasing numbers of patients diagnosed with inflammatory bowel disease (IBD), it is important to identify noninvasive methods of detecting disease activity. The aim of this study is to examine the diagnostic accuracy of fecal rapid calprotectin (FC) testing in the detection of endoscopically active IBD. Patients and Methods: All consecutive patients presenting to outpatient clinics with lower gastrointestinal symptoms were prospectively recruited. Patients provided FC samples. Sensitivity (Sn), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV) for FC were calculated. Receiver–operator characteristics (ROC) curve was used to identify the ideal FC cutoff that predicts endoscopic disease activity. Correlation between FC and endoscopic disease activity, disease location, and C-reactive protein (CRP) levels were measured. Results: One hundred and twenty-six patients, of whom 52% were females, were included in the final analysis with a mean age of 44.4 ± 16.7 years. Comparing FC to endoscopic findings, the following results were calculated: A cutoff point of 100 μg/g showed Sn = 83%, Sp = 67%, PPV = 65%, and NPV = 85%; and 200 μg/g showed Sn = 66%, Sp = 82%, PPV = 73%, and NPV = 77%. Based on ROC curve, the best FC cutoff point to predict endoscopic disease activity was 140 μg/g. Using this reference, FC levels strongly correlated with colorectal, ileocolonic, and ileal disease and predicted endoscopic activity. Conclusions: FC is an accurate test when used as an initial screening tool for patients suspected of having active IBD. Given its noninvasive nature, it may prove to reduce the need for colonoscopy and be an added tool in the management of IBD. PMID:26655130

  15. Timing of antiretroviral therapy and TB treatment outcomes in patients with TB-HIV in Myanmar

    PubMed Central

    Shewade, H. D.; Kyaw, N. T. T.; Oo, M. M.; Aung, T. K.; Aung, S. T.; Oo, H. N.; Win, T.; Harries, A. D.

    2016-01-01

    Setting: Integrated HIV Care programme, Mandalay, Myanmar. Objectives: To determine time to starting antiretroviral treatment (ART) in relation to anti-tuberculosis treatment (ATT) and its association with TB treatment outcomes in patients co-infected with tuberculosis (TB) and the human immunodeficiency virus (HIV) enrolled from 2011 to 2014. Design: Retrospective cohort study. Results: Of 1708 TB-HIV patients, 1565 (92%) started ATT first and 143 (8%) started ART first. Treatment outcomes were missing for 226 patients and were thus not included. In those starting ATT first, the median time to starting ART was 8.6 weeks. ART was initiated after 8 weeks in 830 (53%) patients. Unsuccessful outcome was found in 7%, with anaemia being an independent predictor. In patients starting ART first, the median time to starting ATT was 21.6 weeks. ATT was initiated within 3 months in 56 (39%) patients. Unsuccessful outcome was found in 12%, and in 20% of those starting ATT within 3 months. Patients with CD4 count <100/mm3 had a four times higher risk of an unsuccessful outcome. Conclusions: Timing of ART in relation to ATT was not an independent risk factor for unsuccessful outcome. Extensive screening for TB with rapid and sensitive diagnostic tests in HIV-infected persons and close monitoring of anaemia and immunosuppression are recommended to further improve TB treatment outcomes among patients with TB-HIV. PMID:27358804

  16. Evaluation of telomerase activity in non-genital Bowen's disease.

    PubMed

    Mitsuishi, T; Nakatake, M; Kaneko, T; Ohara, K; Kato, T; Iida, K; Iwabu, Y; Tokunaga, K; Sata, T; Kawana, S; Yamada, O

    2009-06-01

    We investigated the level of telomerase activity (TA) in 17 specimens of non-genital Bowen's disease (BD) and in 14 specimens of skin without sun exposure (non-exposed skin) using a non-isotopic PCR-based telomeric repeat amplification protocol (TRAP) assay. Expression of human telomerase reverse transcriptase (hTERT; the catalytic subunit of telomerase) was also evaluated by immunochemistry in the non-genital BD tissues. Moderate to high levels of TA were detected in 41.2% of 17 non-genital BD specimens (P = 0.001). In contrast, TA was not evident in non-exposed skin. Recently, nucleolin was reported to be associated with hTERT, so we used this antibody instead of hTERT antibody. Immunohistochemistry showed that nucleolin expression was associated with high TA levels in non-genital BD. Our results also revealed differences of TA levels among non-genital BD specimens. High levels of TA in those specimens were not age related. Five out of 7 specimens (71.4%) with moderate to high TA levels were from sun-exposed sites, while the remaining 10 specimens with low levels of TA were from non-exposed sites. These results suggested that cellular DNA damage caused by ultraviolet irradiation might be associated with an increase of TA in non-genital BD. Among non-genital BD specimens, 4 out of 17 (23.5%) showed high levels of TA (median relative TA value: 79.8%; P = 0.003), which might be associated with immortalization or transformation to invasive squamous cell carcinoma. PMID:19250332

  17. Disclosure of HIV status: Experiences of Patients Enrolled in an Integrated TB and HAART Pilot Programme in South Africa

    PubMed Central

    Gebrekristos, Hirut T; Lurie, Mark N; Mthethwa, Nkosinathi; Karim, Quarraisha Abdool

    2010-01-01

    The convergence between the tuberculosis (TB) and HIV epidemics has led to studies investigating strategies for integrated HIV and TB care. We present the experiences of a cohort of 17 patients enrolled in the first integrated TB and HIV treatment pilot programme, conducted in Durban, South Africa, as a precursor to a pivotal trial to answer the question of when to start antiretroviral treatment (ART) in patients co-infected with HIV and TB. Patients’ experiences with integrated TB and HIV care can provide insight about the problems or benefits of introducing HIV treatment into existing TB care in resource-constrained settings, where stigma and discrimination are often pervasive and determining factors influencing treatment uptake and coverage. Individual interviews, focus group discussions, and observations were used to understand patients’ experiences with integrated TB and HIV treatment. The patients described incorporating highly active antiretroviral therapy (HAART) into their daily routine as ‘easy’; however, the patients experienced difficulties with disclosing their HIV status. Non-disclosure to sexual partners may jeopardise safer-sex practices and enhance HIV transmission. Being on TB treatment created a safe space for all patients to conceal their HIV status from those to whom they did not wish to disclose. The data suggest that the context of directly observed therapy (DOT) for TB may have the added benefit of creating a safe space for introducing ART to patients who would benefit most from treatment initiation but who are not ready or prepared to disclose their HIV status to others. PMID:20411037

  18. Health-related quality of life in youth with Crohn's disease: The role of disease activity and parenting stress

    PubMed Central

    Gray, Wendy N.; Boyle, Shana L.; Graef, Danielle M.; Janicke, David M.; Jolley, Christopher D.; Denson, Lee A.; Baldassano, Robert N.; Hommel, Kevin A.

    2015-01-01

    Objectives Health-related quality of life (HRQOL) is an important, but understudied construct in pediatric IBD. Family-level predictors of HRQOL have been understudied as are the mechanisms through which disease activity impacts HRQOL. The current study examines the relationship between a family-level factor (parenting stress) and HRQOL in youth with Crohn's disease. Parenting stress is examined as a mechanism through with disease activity impacts HRQOL. Methods 99 adolescents with Crohn's disease and their parents were recruited across three sites. Adolescents completed the IMPACT-III (IBD-specific HRQOL). Parents completed the Pediatric Inventory for Parents, a measure of medically-related parenting stress that assesses: 1) stress due to the occurrence of medical stressors and 2) stress due to the perceived difficulty of stressors. Disease activity was obtained from medical records. Results Parenting stress due to the occurrence of medical stressors partially mediated the disease severity-HRQOL relationship, reducing the relationship between these variables from 49.67% to 31.58% (B = -.56, p <.0001). Boot strapping analysis confirmed that the indirect effect of disease severity on HQROL via parenting stress significantly differed from zero. Parenting stress due to the perceived difficulty of medical stressors partially mediated the disease severity-HRQOL relationship, reducing the relationship from 49.67% to 30.29% (B = -.55, p < .0001). The indirect effect was confirmed via bootstrapping procedures. Conclusions As disease severity increased, parenting stress also increased, and adolescent HRQOL decreased. Parenting stress should be considered and assessed for along with medical factors as part of a comprehensive approach to improving HRQOL in adolescents with Crohn's disease. PMID:25564807

  19. NF-κB Repressing Factor Inhibits Chemokine Synthesis by Peripheral Blood Mononuclear Cells and Alveolar Macrophages in Active Pulmonary Tuberculosis

    PubMed Central

    Huang, Kuo-Hsiung; Wang, Chun-Hua; Lee, Kang-Yun; Lin, Shu-Min

    2013-01-01

    NF-κB repressing factor (NRF) is a transcriptional silencer implicated in the basal silencing of specific NF-κB targeting genes, including iNOS, IFN-β and IL-8/CXCL8. IP-10/CXCL10 and IL-8/CXCL8 are involved in neutrophil and lymphocyte recruitment against M. tuberculosis (MTb) and disease progression of pulmonary tuberculosis (TB). Alveolar macrophages (AM) and peripheral blood mononuclear cells (PBMC) were used to study the regulatory role of NRF in pulmonary TB. AM and PBMC were purified from 19 TB patients and 15 normal subjects. To study the underlying mechanism, PBMC were exposed to heated TB bacilli. The regulation role of NRF in IP-10/CXCL10 and IL-8/CXCL8 was determined by NRF knock-down or over-expression. NRF binding capabilities in promoter sites were measured by chromatin immunoprecipitation (ChIP) assay. The levels of IP-10/CXCL10, IL-8/CXCL8 and NRF were significantly higher in AM and PBMC in patients with active TB. NRF played an inhibitory role in IP-10/CXCL10 and IL-8/CXCL8 inductions. We delineate the role of NRF in pulmonary TB, which inhibits the expressions of IP-10/CXCL10 and IL-8/CXCL8 in AM and PBMC of patients with high bacterial load. NRF may serve as an endogenous repressor to prevent robust increase in IP-10/CXCL10 and IL-8/CXCL8 when TB bacterial load is high. PMID:24223729

  20. Increased Risk of Active Tuberculosis following Acute Kidney Injury: A Nationwide, Population-Based Study

    PubMed Central

    Chang, Chia-Hsui; Huang, Hui-Yu; Huang, Tao-Min; Lai, Chun-Fu; Lin, Meng-Chun; Ko, Wen-Je; Wu, Kwan-Dun; Yu, Chong-Jen; Shu, Chin-Chung; Lee, Chih-Hsin; Wang, Jann-Yuan

    2013-01-01

    Background Profound alterations in immune responses associated with uremia and exacerbated by dialysis increase the risk of active tuberculosis (TB). Evidence of the long-term risk and outcome of active TB after acute kidney injury (AKI) is limited. Methods This population-based-cohort study used claim records retrieved from the Taiwan National Health Insurance database. We retrieved records of all hospitalized patients, more than 18 years, who underwent dialysis for acute kidney injury (AKI) during 1999–2008 and validated using the NSARF data. Time-dependent Cox proportional hazards model to adjust for the ongoing effect of end-stage renal disease (ESRD) was conducted to predict long-term de novo active TB after discharge from index hospitalization. Results Out of 2,909 AKI dialysis patients surviving 90 days after index discharge, 686 did not require dialysis after hospital discharge. The control group included 11,636 hospital patients without AKI, dialysis, or history of TB. The relative risk of active TB in AKI dialysis patients, relative to the general population, after a mean follow-up period of 3.6 years was 7.71. Patients who did (hazard ratio [HR], 3.84; p<0.001) and did not (HR, 6.39; p<0.001) recover from AKI requiring dialysis had significantly higher incidence of TB than patients without AKI. The external validated data also showed nonrecovery subgroup (HR = 4.37; p = 0.049) had high risk of developing active TB compared with non-AKI. Additionally, active TB was associated with long-term all-cause mortality after AKI requiring dialysis (HR, 1.34; p = 0.032). Conclusions AKI requiring dialysis seems to independently increase the long-term risk of active TB, even among those who weaned from dialysis at discharge. These results raise concerns that the increasing global burden of AKI will in turn increase the incidence of active TB. PMID:23936044

  1. A review of clinical models for the evaluation of human TB vaccines

    PubMed Central

    O'Shea, Matthew K.; McShane, Helen

    2016-01-01

    ABSTRACT While much progress has been made in the fight against the scourge of tuberculosis (TB), we are still some way from reaching the ambitious targets of eliminating it as a global public health problem by the mid twenty-first century. A new and effective vaccine that protects against pulmonary TB disease will be an essential element of any control strategy. Over a dozen vaccines are currently in development, but recent efficacy trial data from one of the most advanced candidates have been disappointing. Limitations of current preclinical animal models exist, together with a lack of a complete understanding of host immunity to TB or robust correlates of disease risk and protection. Therefore, in the context of such obstacles, we discuss the lessons identified from recent efficacy trials, current concepts of biomarkers and correlates of protection, the potential of innovative clinical models such as human challenge and conducting trials in high-incidence settings to evaluate TB vaccines in humans, and the use of systems vaccinology and novel technologies including transcriptomics and metabolomics, that may facilitate their utility. PMID:26810964

  2. A review of clinical models for the evaluation of human TB vaccines.

    PubMed

    O'Shea, Matthew K; McShane, Helen

    2016-05-01

    While much progress has been made in the fight against the scourge of tuberculosis (TB), we are still some way from reaching the ambitious targets of eliminating it as a global public health problem by the mid twenty-first century. A new and effective vaccine that protects against pulmonary TB disease will be an essential element of any control strategy. Over a dozen vaccines are currently in development, but recent efficacy trial data from one of the most advanced candidates have been disappointing. Limitations of current preclinical animal models exist, together with a lack of a complete understanding of host immunity to TB or robust correlates of disease risk and protection. Therefore, in the context of such obstacles, we discuss the lessons identified from recent efficacy trials, current concepts of biomarkers and correlates of protection, the potential of innovative clinical models such as human challenge and conducting trials in high-incidence settings to evaluate TB vaccines in humans, and the use of systems vaccinology and novel technologies including transcriptomics and metabolomics, that may facilitate their utility. PMID:26810964

  3. The Glycerol-3-Phosphate Acyltransferase TbGAT is Dispensable for Viability and the Synthesis of Glycerolipids in Trypanosoma brucei.

    PubMed

    Patel, Nipul; Pirani, Karim A; Zhu, Tongtong; Cheung-See-Kit, Melanie; Lee, Sungsu; Chen, Daniel G; Zufferey, Rachel

    2016-09-01

    Glycerolipids are the main constituents of biological membranes in Trypanosoma brucei, which causes sleeping sickness in humans. Importantly, they occur as a structural component of the glycosylphosphatidylinositol lipid anchor of the abundant cell surface glycoproteins procyclin in procyclic forms and variant surface glycoprotein in bloodstream form, that play crucial roles for the development of the parasite in the insect vector and the mammalian host, respectively. The present work reports the characterization of the glycerol-3-phosphate acyltransferase TbGAT that initiates the biosynthesis of ester glycerolipids. TbGAT restored glycerol-3-phosphate acyltransferase activity when expressed in a Leishmania major deletion strain lacking this activity and exhibited preference for medium length, unsaturated fatty acyl-CoAs. TbGAT localized to the endoplasmic reticulum membrane with its N-terminal domain facing the cytosol. Despite that a TbGAT null mutant in T. brucei procyclic forms lacked glycerol-3-phosphate acyltransferase activity, it remained viable and exhibited similar growth rate as the wild type. TbGAT was dispensable for the biosynthesis of phosphatidylcholine, phosphatidylinositol, phosphatidylserine, and GPI-anchored protein procyclin. However, the null mutant exhibited a slight decrease in phosphatidylethanolamine biosynthesis that was compensated with a modest increase in production of ether phosphatidylcholine. Our data suggest that an alternative initial acyltransferase takes over TbGAT's function in its absence. PMID:26909872

  4. Health-related quality of life in adolescents with inflammatory bowel disease depends on disease activity and psychiatric comorbidity.

    PubMed

    Engelmann, G; Erhard, D; Petersen, M; Parzer, P; Schlarb, A A; Resch, F; Brunner, R; Hoffmann, G F; Lenhartz, H; Richterich, A

    2015-04-01

    Adolescent patients with inflammatory bowel disease (IBD) show an increased risk for behavioral and emotional dysfunction. Health-related quality of life (HRQoL) is influenced by medical illnesses, as well as by psychiatric disorders, but for adolescents with IBD, the extent to which HRQoL is influenced by these two factors is unclear. For 47 adolescent IBD patients, we analyzed disease activity, HRQoL and whether or not a psychiatric disorder was present. Disease activity was estimated using pediatric Ulcerative Colitis Activity Index and pediatric Crohn's Disease Activity Index. The IMPACT-III and the EQ-5D were used to measure HRQoL and QoL, respectively. In addition, patient and parent diagnostic interviews were performed. 55.3 % patients fulfilled DSM-IV criteria for one or more psychiatric disorders. In all patients, psychiatric comorbidity together with disease activity contributed to a reduction in quality of life. Adolescents with IBD are at a high risk for clinically relevant emotional or behavioral problems resulting in significantly lower HRQoL. We conclude that accessible, optimally structured psychotherapeutic and/or psychiatric help is needed in adolescent patients with IBD. PMID:24838299

  5. Association Between Tuberculosis and Parkinson Disease

    PubMed Central

    Shen, Chih-Hao; Chou, Chung-Hsing; Liu, Feng-Cheng; Lin, Te-Yu; Huang, Wen-Yen; Wang, Yu-Chiao; Kao, Chia-Hung

    2016-01-01

    Abstract Few studies have investigated the association between tuberculosis (TB) and Parkinson disease (PD). This nationwide, population-based, retrospective cohort study investigated the risk of PD in patients with TB. We selected patients newly diagnosed with TB (International Classification of Diseases, Ninth Revision, Clinical Modification: 011) from 2000 to 2009 in the Taiwan National Health Insurance Database as the TB cohort. The comparison cohort (the non-TB cohort) was frequency matched to the TB cohort at a ratio of 4:1 by sex, age, and the index date. We analyzed the risks of PD by using Cox proportional hazard regression models. A total of 121,951 patients with TB and 487,800 non-TB controls were enrolled in this study. The TB cohort had a 1.38-fold risk of PD compared with the non-TB cohort after adjustment for age, sex, and comorbidities (aHR, 95% CI: 1.30–1.46). The adjusted risk of PD in the TB and non-TB cohorts increased in subgroups regardless of age, sex, and comorbidities. Combined effect of TB and comorbidities on the risk of PD were significant in patients with TB who had diabetes (aHR: 2.26, 95% CI: 2.02–2.52), hypertension (aHR: 2.23, 95% CI: 2.04–2.44), head injury (aHR: 2.32, 95% CI: 1.95–2.77), chronic kidney disease (aHR: 2.02, 95% CI: 1.49–2.72), chronic obstructive pulmonary disease (aHR: 1.84, 95% CI: 1.66–2.05), depression (aHR: 4.66, 95% CI: 3.59–6.05), dementia (aHR: 3.70, 95% CI: 2.99–4.59), and stroke (aHR: 2.56, 95% CI: 2.28–2.87). The risk of PD was higher in a follow-up within 1 year (aHR: 1.78, 95% CI: 1.58–2.00) and decreased with the follow-up period in the TB cohort. Patients with TB have an independently 1.38-fold risk of PD. The risk of PD decreased with the follow-up period in the TB cohort. Physicians should be aware of the risk of PD in patients with TB when treating such patients. PMID:26937925

  6. Neuron-specific enolase as a novel biomarker reflecting tuberculosis activity and treatment response

    PubMed Central

    Nam, Sung-Jin; Jeong, Jee-Yeong; Jang, Tae-Won; Jung, Mann-Hong; Chun, Bong-Kwon; Cha, Hee-Jae; Oak, Chul-Ho

    2016-01-01

    Background/Aims: It is not clear which tests are indicative of the activity and severity of tuberculosis (TB). This study aimed to investigate the predictive value of neuron-specific enolase (NSE) and to determine the origin of NSE in TB patients. Methods: A single-center retrospective analysis was conducted on newly diagnosed TB patients between January and December 2010. Patients were categorized into one of two disease groups (focal segmental or extensive) based on chest X-ray. Pre- and post-treatment NSE concentrations were evaluated. To determine the origin of serum NSE concentration, NSE staining was compared with macrophage-specific CD68 staining in lung tissues and with a tissue microarray using immunohistochemistry and immunofluorescence. Results: A total of 60 newly diagnosed TB patients were analyzed. In TB patients, NSE serum concentration was significantly increased and NSE level decreased after treatment (p < 0.001). In proportion to serum high-sensitivity C-reactive protein concentration, the mean serum concentration of NSE in the extensive group (25.12 ng/mL) was significantly higher than that in the focal segmental group (20.23 ng/mL, p = 0.04). Immunohistochemical staining revealed a large number of macrophages that stained positively for both NSE and CD68 in TB tissues. In addition, NSE signals mostly co-localized with CD68 signals in the tissue microarray of TB patients. Conclusions: Our results suggest that NSE may be a practical parameter that can be used to monitor TB activity and treatment response. Elevated serum NSE level originates, at least in part, from macrophages in granulomatous lesions. PMID:27271274

  7. Achieving high treatment success for multidrug-resistant TB in Africa: initiation and scale-up of MDR TB care in Ethiopia—an observational cohort study

    PubMed Central

    Meressa, Daniel; Hurtado, Rocío M; Andrews, Jason R; Diro, Ermias; Abato, Kassim; Daniel, Tewodros; Prasad, Paritosh; Prasad, Rebekah; Fekade, Bekele; Tedla, Yared; Yusuf, Hanan; Tadesse, Melaku; Tefera, Dawit; Ashenafi, Abraham; Desta, Girma; Aderaye, Getachew; Olson, Kristian; Thim, Sok; Goldfeld, Anne E

    2015-01-01

    Background In Africa, fewer than half of patients receiving therapy for multidrug-resistant TB (MDR TB) are successfully treated, with poor outcomes reported for HIV-coinfected patients. Methods A standardised second-line drug (SLD) regimen was used in a non-governmental organisation–Ministry of Health (NGO-MOH) collaborative community and hospital-based programme in Ethiopia that included intensive side effect monitoring, adherence strategies and nutritional supplementation. Clinical outcomes for patients with at least 24 months of follow-up were reviewed and predictors of treatment failure or death were evaluated by Cox proportional hazards models. Results From February 2009 to December 2014, 1044 patients were initiated on SLD. 612 patients with confirmed or presumed MDR TB had ≥24 months of follow-up, 551 (90.0%) were confirmed and 61 (10.0%) were suspected MDR TB cases. 603 (98.5%) had prior TB treatment, 133 (21.7%) were HIV coinfected and median body mass index (BMI) was 16.6. Composite treatment success was 78.6% with 396 (64.7%) cured, 85 (13.9%) who completed treatment, 10 (1.6%) who failed, 85 (13.9%) who died and 36 (5.9%) who were lost to follow-up. HIV coinfection (adjusted HR (AHR): 2.60, p<0.001), BMI (AHR 0.88/kg/m2, p=0.006) and cor pulmonale (AHR 3.61, p=0.003) and confirmed MDR TB (AHR 0.50, p=0.026) were predictive of treatment failure or death. Conclusions We report from Ethiopia the highest MDR TB treatment success outcomes so far achieved in Africa, in a setting with severe resource constraints and patients with advanced disease. Intensive treatment of adverse effects, nutritional supplementation, adherence interventions and NGO-MOH collaboration were key strategies contributing to success. We argue these approaches should be routinely incorporated into programmes. PMID:26506854

  8. Constitutive Activation of G Protein-Coupled Receptors and Diseases: Insights into Mechanisms of Activation and Therapeutics

    PubMed Central

    Tao, Ya-Xiong

    2008-01-01

    The existence of constitutive activity for G protein-coupled receptors (GPCRs) was first described in 1980s. In 1991, the first naturally occurring constitutively active mutations in GPCRs that cause diseases were reported in rhodopsin. Since then, numerous constitutively active mutations that cause human diseases were reported in several additional receptors. More recently, loss of constitutive activity was postulated to also cause diseases. Animal models expressing some of these mutants confirmed the roles of these mutations in the pathogenesis of the diseases. Detailed functional studies of these naturally occurring mutations, combined with homology modeling using rhodopsin crystal structure as the template, lead to important insights into the mechanism of activation in the absence of crystal structure of GPCRs in active state. Search for inverse agonists on these receptors will be critical for correcting the diseases cause by activating mutations in GPCRs. Theoretically, these inverse agonists are better therapeutics than neutral antagonists in treating genetic diseases caused by constitutively activating mutations in GPCRs. PMID:18768149

  9. PrimaTB STAT-PAK Assay, a Novel, Rapid Lateral-Flow Test for Tuberculosis in Nonhuman Primates▿

    PubMed Central

    Lyashchenko, Konstantin P.; Greenwald, Rena; Esfandiari, Javan; Greenwald, David; Nacy, Carol A.; Gibson, Susan; Didier, Peter J.; Washington, Marc; Szczerba, Peter; Motzel, Sherri; Handt, Larry; Pollock, John M.; McNair, James; Andersen, Peter; Langermans, Jan A. M.; Verreck, Frank; Ervin, Sean; Ervin, Frank; McCombs, Candace

    2007-01-01

    Tuberculosis (TB) is the most important zoonotic bacterial disease in nonhuman primates (NHP). The current diagnostic method, the intradermal palpebral tuberculin test, has serious shortcomings. We characterized antibody responses in NHP against Mycobacterium tuberculosis to identify immunodominant antigens and develop a rapid serodiagnostic test for TB. A total of 422 NHP were evaluated, including 243 rhesus (Macaca mulatta), 46 cynomolgus (Macaca fascicularis), and 133 African green (Cercopithecus aethiops sabaeus) monkeys at five collaborative centers. Of those, 50 monkeys of the three species were experimentally inoculated with M. tuberculosis. Antibody responses were monitored every 2 to 4 weeks for up to 8 months postinfection by MultiAntigen Print ImmunoAssay with a panel of 12 recombinant antigens. All of the infected monkeys produced antibodies at various levels and with different antigen recognition patterns. ESAT-6 and MPB83 were the most frequently recognized proteins during infection. A combination of selected antigens which detected antibodies in all of the infected monkeys was designed to develop the PrimaTB STAT-PAK assay by lateral-flow technology. Serological evaluation demonstrated high diagnostic sensitivity (90%) and specificity (99%). The highest rate of TB detection was achieved when the skin test was combined with the PrimaTB STAT-PAK kit. This novel immunoassay provides a simple, rapid, and accurate test for TB in NHP. PMID:17652522

  10. Elevated serum IL-35 and increased expression of IL-35-p35 or -EBI3 in CD4+CD25+ T cells in patients with active tuberculosis

    PubMed Central

    Kong, Bin; Liu, Gan-Bin; Zhang, Jun-Ai; Fu, Xiao-Xia; Xiang, Wen-Yu; Gao, Yu-Chi; Lu, Yuan-Bin; Wu, Xian-Jing; Qiu, Feng; Wang, Wan-Dang; Yi, Lai-Long; Zhong, Ji-Xin; Chen, Zheng W; Xu, Jun-Fa

    2016-01-01

    Despite the recent appreciation of interleukin 35 (IL-35) function in inflammatory diseases, little is known for IL-35 response in patients with active tuberculosis (ATB). In the current study, we demonstrated that ATB patients exhibited increases in serum IL-35 and in mRNA expression of both subunits of IL-35 (p35 and EBI3) in white blood cells and peripheral blood mononuclear cells. Consistently, anti-TB drug treatment led to reduction in serum IL-35 level and p35 or EBI3 expression. TB infection was associated with expression of p35 or EBI3 protein in CD4+ but not CD8+ T cells. Most p35+CD4+ T cells and EBI3+CD4+ T cells expressed Treg-associated marker CD25. Our findings may be important in understanding immune pathogenesis of TB. IL-35 in the blood may potentially serve as a biomarker for immune status and prognosis in TB. PMID:27158354

  11. Developing vaccines to prevent sustained infection with Mycobacterium tuberculosis: Conference proceedings: National Institute of Allergy and Infectious Diseases, Rockville, Maryland USA, November 7, 2014.

    PubMed

    2015-06-12

    On November 7, 2014, Aeras and the National Institute of Allergy and Infectious Diseases convened a conference entitled "Vaccine Prevention of Sustained Mycobacterium tuberculosis Infection." The purpose of this meeting was to explore the biologic plausibility, potential public health and economic impact, and regulatory feasibility in attempting to develop a vaccine to prevent sustained infection with Mycobacterium tuberculosis (Mtb). Currently there are two main goals for tuberculosis (TB) vaccine development, to develop a vaccine that could serve as a booster to Bacille Calmette-Guérin (BCG) vaccination and prevent active TB in adolescents and adults, and to develop an improved vaccine to replace BCG in infants. Although prevention of sustained Mtb infection is being used as a proof of biological activity for vaccines in mid-Phase 2 development, there currently are no plans for pursuing a prevention of Mtb infection licensure indication for TB vaccines. Ultimately, pursuing a prevention of sustained Mtb infection indication for TB vaccines, in parallel with ongoing efforts to develop vaccines to prevent active TB disease, was deemed a potentially important effort, but would require further resources, particularly to improve diagnostic assays, to increase the regulatory feasibility of this endeavor. PMID:25869889

  12. Ghrelin and adipokines as circulating markers of disease activity in patients with Takayasu arteritis

    PubMed Central

    2012-01-01

    Introduction The current markers of disease activity in Takayasu arteritis (TA) are insufficient for proper assessment. We investigated circulating levels of unacylated and acylated ghrelin, leptin and adiponectin and their relationships with disease activity in patients with TA. Methods This study included 31 patients with TA and 32 sex-, age- and body mass index-matched healthy controls. Disease activity was assessed in TA patients using various tools, including Kerr's criteria, disease extent index-Takayasu, physician's global assessment, radiological parameters, and laboratory markers. Plasma unacylated and acylated ghrelin, and serum leptin and adiponectin levels were measured using an enzyme-linked immunosorbent assay. Results Unacylated and acylated ghrelin levels were found to be significantly lower in TA patients than that in healthy controls. Patients with active disease had lower unacylated ghrelin levels than those with inactive disease and had lower acylated ghrelin levels than healthy controls. Ghrelin levels were negatively correlated with various parameters of disease activity. The leptin/ghrelin ratio was significantly higher in TA patients than controls. It was positively correlated with disease activity. There was a positive correlation between unacylated and acylated ghrelin and a negative correlation between leptin and ghrelin. There was no statistical difference in adiponectin levels between TA patients and controls. The radiological activity markers were positively correlated with other parameters of disease activity. Conclusions This study suggests that plasma unacylated and acylated ghrelin levels may be useful in monitoring disease activity and planning treatment strategies for patients with TA. The serum leptin level and leptin/ghrelin ratio may also be used to help assess the disease activity. PMID:23259466

  13. Development and assessment of a modified Pediatric Crohn Disease Activity Index.

    PubMed

    Leach, Steven T; Nahidi, Lily; Tilakaratne, Samantha; Day, Andrew S; Lemberg, Daniel A

    2010-08-01

    The Pediatric Crohn Disease Activity Index (PCDAI) is an established and validated measure of disease activity in children with Crohn disease. However, its use in the research setting can be limited because of ambiguity of the subjective and anthropometric components of the index. Here we propose and evaluate a modified PCDAI (Mod PCDAI) consisting of the laboratory measures of the PCDAI plus C-reactive protein. This Mod PCDAI can provide an indication of disease activity because it correlates with the PCDAI, physicians' global assessment, and fecal calprotectin, and therefore may provide a suitable alternative to the PCDAI when required. PMID:20479686

  14. Tuberculin skin test and ELISPOT/T. SPOT.TB in children and adolescents with juvenile idiopathic arthritis

    PubMed Central

    2014-01-01

    Background There are controversies regarding the accuracy of the tuberculin skin test (TST) and methods based on the production of interferon gamma by sensitized T cells for the diagnosis of latent tuberculosis infection (LTBI) in pediatrics and immunosuppressed patients. Our objectives are to study TST and ELISPOT/T. SPOT.TB in the diagnosis of LTBI in children and adolescents with JIA undergoing methotrexate, the correlation between both and the sensitivity and specificity of T. SPOT.TB. Methods This is an observational prospective longitudinal study in which children and adolescents with JIA undergoing methotrexate therapy were assessed for clinical and epidemiological data for LTBI, in addition to performing TST and T. SPOT.TB at baseline and after 3 and 12months. Results There were 24 patients. The prevalence of LTBI at inclusion was 20.8%, the incidence after initiation of immunosuppressions 26.3% and the prevalence at the end of the study 41.6%. Epidemiological history positive for TB showed a relative risk of 2.0 for the development of LTBI. Only 2 patients had positive T. SPOT.TB but only in one it was useful for detecting early LTBI. T. SPOT.TB presented a sensitivity of 10%, specificity of 92.8%, and low correlation with TST. No patient developed TB disease at a mean follow-up of 47months. Conclusions We found a high prevalence of ILTB that doubled with immunosuppression and that epidemiological history was an important relative risk. T. SPOT.TB showed low sensitivity and high specificity, and no superiority over TST. There was low agreement and little influence of immunosuppression on the results of both tests. PMID:24904240

  15. Leisure Time Physical Activity and Mortality in Chronic Kidney Disease: Preliminary findings from the MDRD study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chronic kidney disease (CKD) is an important risk factor for cardiovascular disease and all-cause mortality. In the general population, physical activity is associated with reduced mortality. We examined physical activity status in CKD patients and its relation to all-cause mortality. The Modified...

  16. Anti-biofilm properties of the antimicrobial peptide temporin 1Tb and its ability, in combination with EDTA, to eradicate Staphylococcus epidermidis biofilms on silicone catheters.

    PubMed

    Maisetta, Giuseppantonio; Grassi, Lucia; Di Luca, Mariagrazia; Bombardelli, Silvia; Medici, Chiara; Brancatisano, Franca Lisa; Esin, Semih; Batoni, Giovanna

    2016-08-01

    In search of new antimicrobials with anti-biofilm potential, in the present study activity of the frog-skin derived antimicrobial peptide temporin 1Tb (TB) against Staphylococcus epidermidis biofilms was investigated. A striking ability of TB to kill both forming and mature S. epidermidis biofilms was observed, especially when the peptide was combined with cysteine or EDTA, respectively. Kinetics studies demonstrated that the combination TB/EDTA was active against mature biofilms already after 2-4-h exposure. A double 4-h exposure of biofilms to TB/EDTA further increased the therapeutic potential of the same combination. Of note, TB/EDTA was able to eradicate S. epidermidis biofilms formed in vitro on silicone catheters. At eradicating concentrations, TB/EDTA did not cause hemolysis of human erythrocytes. The results shed light on the anti-biofilm properties of TB and suggest a possible application of the peptide in the lock therapy of catheters infected with S. epidermidis. PMID:27351824

  17. Peroxisome proliferator-activated receptor-delta agonist ameliorated inflammasome activation in nonalcoholic fatty liver disease

    PubMed Central

    Lee, Hyun Jung; Yeon, Jong Eun; Ko, Eun Jung; Yoon, Eileen L; Suh, Sang Jun; Kang, Keunhee; Kim, Hae Rim; Kang, Seoung Hee; Yoo, Yang Jae; Je, Jihye; Lee, Beom Jae; Kim, Ji Hoon; Seo, Yeon Seok; Yim, Hyung Joon; Byun, Kwan Soo

    2015-01-01

    AIM: To evaluate the inflammasome activation and the effect of peroxisome proliferator-activated receptors (PPAR)-δ agonist treatment in nonalcoholic fatty liver disease (NAFLD) models. METHODS: Male C57BL/6J mice were classified according to control or high fat diet (HFD) with or without PPAR-δ agonist (GW) over period of 12 wk [control, HFD, HFD + lipopolysaccharide (LPS), HFD + LPS + GW group]. HepG2 cells were exposed to palmitic acid (PA) and/or LPS in the absence or presence of GW. RESULTS: HFD caused glucose intolerance and hepatic steatosis. In mice fed an HFD with LPS, caspase-1 and interleukin (IL)-1β in the liver were significantly increased. Treatment with GW ameliorated the steatosis and inhibited overexpression of pro-inflammatory cytokines. In HepG2 cells, PA and LPS treatment markedly increased mRNA of several nucleotide-binding and oligomerization domain-like receptor family members (NLRP3, NLRP6, and NLRP10), caspase-1 and IL-1β. PA and LPS also exaggerated reactive oxygen species production. All of the above effects of PA and LPS were reduced by GW. GW also enhanced the phosphorylation of AMPK-α. CONCLUSION: PPAR-δ agonist reduces fatty acid-induced inflammation and steatosis by suppressing inflammasome activation. Targeting the inflammasome by the PPAR-δ agonist may have therapeutic implication for NAFLD. PMID:26668503

  18. Neuromyelitis Optica (NMO) with Abdominal Tuberculosis (TB).

    PubMed

    Bhatty, Shaheen A; Lal, Hari; Talib, Abu; Mahmood, Khalid; Naqvi, Iftekhar; Zaidi, Syeda Shaheera

    2015-10-01

    Neuromyelitis Optica (NMO), previously regarded as a form of multiple sclerosis, is defined by Gault and Devic, as a retrobulbar neuritis or papillitis accompanied by acute myelitis and occasionally other neurological symptom or signs not restricted to the spinal cord or optic nerves. With the diagnosis of specific antibodies, probable role of humoral immunity supports its pathogenesis. Only a few cases of NMO have been reported in association with pulmonary tuberculosis (TB). Here we report a case of young girl with acute onset paraplegia diagnosed to have NMO, who later on during hospital stay developed ascites which cultured positive for Mycobacterium tuberculosis. This association of abdominal TB with NMO is under-reported in literature. PMID:26522188

  19. Antiferromagnetic behaviour of Tb2Al alloy

    NASA Astrophysics Data System (ADS)

    Rojas, D. P.; André, G.; Rodríguez Fernández, J.; Sánchez Marcos, J.; Fernández Barquín, L.; Echevarria, C.

    2011-10-01

    The structural, thermal and magnetic properties ol the Tb2Al alloy have been investigated by AC/DC magnetic susceptibility, specific heat, X-ray and neutron diffraction measurements. DC and AC-magnetic susceptibility results are consistent with an AFM order at TN = 52 K. The specific heat data show a lambda anomaly associated to the magnetic transition with a peak at 52 K (cord = 99 J/molTbK). The analysis of thermodiffractograms of neutron diffraction patterns indicates that, below the ordering temperature, the magnetic reflections can be indexed with a commensurate lattice related to the crystallographic cell (Pmna) by a propagation vector k = (1/2, 1/2, 1/2). The results are compared with those reported for other magnetic rare earth alloys of R2Al-type (with R = Nd, Gd and Dy).

  20. Potential novel markers to discriminate between active and latent tuberculosis infection in Chinese individuals.

    PubMed

    Bai, Xue-juan; Liang, Yan; Yang, You-rong; Feng, Jin-dong; Luo, Zhan-peng; Zhang, Jun-Xian; Wu, Xue-qiong

    2016-02-01

    Latent tuberculosis infection (LTBI) constitutes the main reservoir for reactivation tuberculosis. The finding of potential biomarkers for differentiating between TB and LTBI is very necessary. In this study, the immunological characteristics and potential diagnostic utility of Rv2029c, Rv2628 and Rv1813c proteins were assessed. These three proteins stimulated PBMCs from ELISPOT-positive LTBI subjects produced higher levels of IFN-γ in comparison with TB patients and ELISPOT-negative healthy subjects (p<0.05). BCG vaccination and non-TB respiratory disease had little influence on the immunological responses of Rv2029c and Rv2628 proteins (p>0.05). The LTBI diagnostic performance of Rv2029c was higher than Rv2628 and Rv1813c by ROC evaluation. But Rv2628 had much higher specificity than Rv2029c in active TB patients and uninfected healthy subjects. The IgG level against Rv1813c was higher in the TB group than in LTBI and uninfected healthy subjects (p<0.05). These results suggest that T cell response to Rv2628 and antibody against Rv1813c might be applicable as biomarkers to distinguish TB from LTBI and uninfected individuals. PMID:26851588

  1. Markers of endothelial cell activation and immune activation are increased in patients with severe leptospirosis and associated with disease severity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objectives: Previous studies concluded that haemorrhage is one of the most accurate prognostic factors of mortality in leptospirosis. Therefore, endothelial cell activation was investigated in relation to disease severity in severe leptospirosis. Methods: Prospective cohort study of severe leptospi...

  2. Adverse neuro-immune-endocrine interactions in patients with active tuberculosis.

    PubMed

    Bottasso, Oscar; Bay, María Luisa; Besedovsky, Hugo; Del Rey, Adriana

    2013-03-01

    The nervous, endocrine and immune systems play a crucial role in maintaining homeostasis and interact with each other for a successful defensive strategy against injurious agents. However, the situation is different in long-term diseases with marked inflammation, in which defensive mechanisms become altered. In the case of tuberculosis (TB), this is highlighted by several facts: an imbalance of plasma immune and endocrine mediators, that results in an adverse environment for mounting an adequate response against mycobacteria and controlling inflammation; the demonstration that dehidroepiandrosterone (DHEA) secretion by a human adrenal cell line can be inhibited by culture supernatants from Mycobacterium tuberculosis-stimulated peripheral blood mononuclear cells - PBMC - of TB patients, with this effect being partly reverted when neutralizing transforming growth factor-β in such supernantants; the in vitro effects of adrenal steroids on the specific immune response of PBMC from TB patients, that is a cortisol inhibition of mycobacterial antigen-driven lymphoproliferation and interferon-γ production as well as a suppression of TGF-β production in DHEA-treated PBMC; and lastly the demonstration that immune and endocrine compounds participating in the regulation of energy sources and immune activity correlated with the consumption state of TB patients. Collectively, immune-endocrine disturbances of TB patients are involved in critical components of disease pathology with implications in the impaired clinical status and unfavorable disease outcome. This article is part of a Special Issue entitled 'Neuroinflammation in neurodegeneration and neurodysfunction'. PMID:23147110

  3. Predictive value of the tuberculin skin test and QuantiFERON-tuberculosis Gold In-Tube test for development of active tuberculosis in hemodialysis patients

    PubMed Central

    Seyhan, Ekrem Cengiz; Gunluoglu, Gulşah; Gunluoglu, Mehmet Zeki; Tural, Seda; Sökücü, Sinem

    2016-01-01

    BACKGROUND: Hemodialysis (HD) patients are at increased risk of reactivation of latent tuberculosis infection (LTBI) compared with the general population. QuantiFERON-TB Gold (QFT-G) for LTBI detection is more promising than tuberculin skin test (TST) in HD patients. AIM: In our study, we evaluated the value of the TST and QFT-G In-Tube (QFG-IT) test in the development of active tuberculosis (TB), in the HD patients, and in healthy controls. METHODS: The study enrolled 95 HD patients and ninety age-matched, healthy controls. The TST and QFG-IT were performed. All the subjects were followed up 5 years for active TB disease. RESULTS: Compared to the healthy controls, a high prevalence of LTBI was found in the HD patients by QFG-IT (41% vs. 25%). However, no significant difference was detected by TST (32% vs. 31%). Four HD patients and one healthy control progressed to active TB disease within the 5-year follow-up. For active TB discovered subjects, QFG-IT was positive in all, but TST was positive in two (one patient and one healthy control). In HD patients; sensitivity, specificity, positive and negative predictive values of QFG-IT, and TST for active TB was 100% and 25%, 62% and 67%, 10%, and 3%, and 100% and 95%, respectively. Receiver operating curve analysis revealed that the results are significantly different (P = 0.04). CONCLUSION: QFG-IT test is a more useful diagnostic method than TST for detecting those who will progress to active TB in HD patients. PMID:27168859

  4. Can directed activity improve mobility in Huntington's disease?

    PubMed

    Busse, M E; Rosser, A E

    2007-04-30

    Huntington's disease is an inherited disorder of the CNS that results in progressive deterioration of mobility and cognition and also affects behaviour. There are no disease-modifying interventions available to date, although there has been considerable progress in research directed at understanding the pathological basis of the disease with a view to identifying potential treatments. It is however important not to overlook currently available treatment strategies, including rehabilitation approaches. There has been little work to date to explore the potential of such approaches and here we highlight the need for more systematic studies in this area as well as the need for good objective assessment tools and the potential role that rehabilitation and training may have in the application of novel treatment options. PMID:17352942

  5. Human genes in TB infection: their role in immune response.

    PubMed

    Lykouras, D; Sampsonas, F; Kaparianos, A; Karkoulias, K; Tsoukalas, G; Spiropoulos, K

    2008-03-01

    Tuberculosis (TB) caused by the human pathogen Mycobacterium tuberculosis, is the leading cause of morbidity and mortality caused by infectious agents worldwide. Recently, there has been an ongoing concern about the clarification of the role of specific human genes and their polymorphisms involved in TB infection. In the vast majority of individuals, innate immune pathways and T-helper 1 (Th1) cell mediated immunity are activated resulting in the lysis of the bacterium. Firstly, PTPN22 R620W polymorphism is involved in the response to cases of infection. The Arg753Gln polymorphism in TLR-2 leads to a weaker response against the M. tuberculosis. The gene of the vitamin D receptor (VDR) has a few polymorphisms (BsmI, ApaI, Taq1, FokI) whose mixed genotypes alter the immune response. Solute carrier family 11 member (SLC11A1) is a proton/divalent cation antiporter that is more familiar by its former name NRAMP1 (natural resistance associated macrophage protein 1) and can affect M. tuberculosis growth. Polymorphisms of cytokines such as IL-10, IL-6, IFN-g, TNF-a, TGF-b1 can affect the immune response in various ways. Finally, a major role is played by M. tuberculosis antigens and the Ras-associated small GTP-ase 33A. As far as we know this is the first review that collates all these polymorphisms in order to give a comprehensive image of the field, which is currently evolving. PMID:18507196

  6. Discovery and antiparasitic activity of AZ960 as a Trypanosoma brucei ERK8 inhibitor.

    PubMed

    Valenciano, Ana L; Ramsey, Aaron C; Santos, Webster L; Mackey, Zachary B

    2016-10-01

    Human African trypanosomiasis (HAT) is a lethal, vector-borne disease caused by the parasite Trypanosoma brucei. Therapeutic strategies for this neglected tropical disease suffer from disadvantages such as toxicity, high cost, and emerging resistance. Therefore, new drugs with novel modes of action are needed. We screened cultured T. brucei against a focused kinase inhibitor library to identify promising bioactive compounds. Among the ten hits identified from the phenotypic screen, AZ960 emerged as the most promising compound with potent antiparasitic activity (IC50=120nM) and was shown to be a selective inhibitor of an essential gene product, T. brucei extracellular signal-regulated kinase 8 (TbERK8). We report that AZ960 has a Ki of 1.25μM for TbERK8 and demonstrate its utility in establishing TbERK8 as a potentially druggable target in T. brucei. PMID:27519462

  7. Mechanistic insights on immunosenescence and chronic immune activation in HIV-tuberculosis co-infection.

    PubMed

    Shankar, Esaki M; Velu, Vijayakumar; Kamarulzaman, Adeeba; Larsson, Marie

    2015-02-12

    Immunosenescence is marked by accelerated degradation of host immune responses leading to the onset of opportunistic infections, where senescent T cells show remarkably higher ontogenic defects as compared to healthy T cells. The mechanistic association between T-cell immunosenescence and human immunodeficiency virus (HIV) disease progression, and functional T-cell responses in HIV-tuberculosis (HIV-TB) co-infection remains to be elaborately discussed. Here, we discussed the association of immunosenescence and chronic immune activation in HIV-TB co-infection and reviewed the role played by mediators of immune deterioration in HIV-TB co-infection necessitating the importance of designing therapeutic strategies against HIV disease progression and pathogenesis. PMID:25674514

  8. Faecal alpha-1-antitrypsin and excretion of 111indium granulocytes in assessment of disease activity in chronic inflammatory bowel diseases.

    PubMed Central

    Fischbach, W; Becker, W; Mössner, J; Koch, W; Reiners, C

    1987-01-01

    Intestinal protein loss in chronic inflammatory bowel diseases may be easily determined by measurement of alpha-1-antitrypsin (alpha 1-AT) stool concentration and alpha 1-AT clearance. Both parameters were significantly raised in 36 and 34 patients respectively with chronic inflammatory bowel diseases, compared with eight patients with non-inflammatory bowel diseases, or 19 healthy volunteers. There was wide range of overlap between active and inactive inflammatory disease. Contrary to serum alpha 1-AT, faecal excretion and clearance of alpha 1-AT did not correlate with ESR, serum-albumin, orosomucoid, and two indices of disease activity. A comparison of alpha 1-AT faecal excretion and clearance with the faecal excretion of 111In labelled granulocytes in 27 patients with chronic inflammatory bowel diseases, showed no correlation between the intestinal protein loss and this highly specific marker of intestinal inflammation. Enteric protein loss expressed by faecal excretion and clearance of alpha 1-AT does not depend on mucosal inflammation only, but may be influenced by other factors. PMID:3495470

  9. Rheumatoid arthritis and pregnancy: evolution of disease activity and pathophysiological considerations for drug use

    PubMed Central

    Hazes, Johanna M.W.; Coulie, Pierre G.; Geenen, Vincent; Vermeire, Séverine; Carbonnel, Franck; Louis, Edouard; Masson, Pierre

    2011-01-01

    It has long been known that pregnancy and childbirth have a profound effect on the disease activity of rheumatic diseases. For clinicians, the management of patients with RA wishing to become pregnant involves the challenge of keeping disease activity under control and adequately adapting drug therapy during pregnancy and post-partum. This article aims to summarize the current evidence on the evolution of RA disease activity during and after pregnancy and the use of anti-rheumatic drugs around this period. Of recent interest is the potential use of anti-TNF compounds in the preconception period and during pregnancy. Accumulating experience with anti-TNF therapy in other immune-mediated inflammatory diseases, such as Crohn’s disease, provides useful insights for the use of TNF blockade in pregnant women with RA, or RA patients wishing to become pregnant. PMID:21890617

  10. Detection of Mycobacterium tuberculosis Peptides in the Exosomes of Patients with Active and Latent M. tuberculosis Infection Using MRM-MS

    PubMed Central

    Kruh-Garcia, Nicole A.; Wolfe, Lisa M.; Chaisson, Lelia H.; Worodria, William O.; Nahid, Payam; Schorey, Jeff S.; Davis, J. Lucian; Dobos, Karen M.

    2014-01-01

    The identification of easily measured, accurate diagnostic biomarkers for active tuberculosis (TB) will have a significant impact on global TB control efforts. Because of the host and pathogen complexities involved in TB pathogenesis, identifying a single biomarker that is adequately sensitive and specific continues to be a major hurdle. Our previous studies in models of TB demonstrated that exosomes, such as those released from infected macrophages, contain mycobacterial products, including many Mtb proteins. In this report, we describe the development of targeted proteomics assays employing multiplexed multiple reaction monitoring mass spectrometry (MRM-MS) in order to allow us to follow those proteins previously identified by western blot or shotgun mass spectrometry, and enhance biomarker discovery to include detection of Mtb proteins in human serum exosomes. Targeted MRM-MS assays were applied to exosomes isolated from human serum samples obtained from culture-confirmed active TB patients to detect 76 peptides representing 33 unique Mtb proteins. Our studies revealed the first identification of bacteria-derived biomarker candidates of active TB in exosomes from human serum. Twenty of the 33 proteins targeted for detection were found in the exosomes of TB patients, and included multiple peptides from 8 proteins (Antigen 85B, Antigen 85C, Apa, BfrB, GlcB, HspX, KatG, and Mpt64). Interestingly, all of these proteins are known mycobacterial adhesins and/or proteins that contribute to the intracellular survival of Mtb. These proteins will be included as target analytes in future validation studies as they may serve as markers for persistent active and latent Mtb infection. In summary, this work is the first step in identifying a unique and specific panel of Mtb peptide biomarkers encapsulated in exosomes and reveals complex biomarker patterns across a spectrum of TB disease states. PMID:25080351

  11. Withanolides: Biologically Active Constituents in the Treatment of Alzheimer's Disease.

    PubMed

    Khan, Shahid A; Khan, Sher B; Shah, Zarbad; Asiri, Abdullah M

    2016-01-01

    The use of natural products in drug discovery and development have an important history. Several therapeutic agents have been investigated during the biological screenings of natural compounds. It is well documented that plants are possibly the core of novel substances that led to the discovery of new, novel, and effective therapeutic agents. Therefore, in the last few decades, scientists were thoroughly attempting for the search of benevolent drugs to protect mankind from various diseases and discomforts. The diverse chemical structures of natural products are the key element of their success in modern drug discovery. Cholinesterase enzyme inhibitors (ChEI) are chemicals which inhibit the splitting of cholinesterase enzymes (acetylcholinesterase and butyrylcholinesterase). Acetyl cholinesterase (AChE) and butyrylcholinesterase (BChE) are two types of cholinesterase enzymes that have been identified in vertebrates that are responsible for Alzheimer's disease and related dementia. Withanolides are affective plant secondary metabolites which inhibit acetylcholinesterase and butyrylcholinesterase enzyme and thus possibly will be the future drug for Alzheimer's disease. By viewing the importance of natural products in drug discovery and development, we present here, the importance of withanolides in the treatment of Alzheimer's disease. In this article, we also describe the classification and structural characterization of withanolides. This review comprises of 114 compounds. PMID:26527154

  12. Photo- and cathodoluminescence of hydrothermally synthesized Y{sub 3}Al{sub 5}O{sub 12}:Tb and NaY(WO{sub 4}){sub 2}:Tb

    SciTech Connect

    Phillips, M.L.F.; Potter, B.G. Jr.

    1995-10-01

    Cathodoluminescent (CL) phosphors with improved low-voltage characteristics are needed for use in emissive flat panel displays. Conventional high-temperature methods for phosphor synthesis yield large polycrystalline grains that must be pulverized prior to screen deposition. Grinding has been implicated in reducing phosphor efficiency by causing surface contamination and defects. Hydrothermal synthesis has been used to improve the quality of ceramic powders by producing fine, well-formed crystallites without grinding. Two green-emitting phosphors, Y{sub 3}Al{sub 5}O{sub 12}:Tb (YAG:Tb) and NaY(WO{sub 4}){sub 2}:Tb, were used to test the effects of hydrothermal. synthesis on grain size and morphology, and on low-voltage CL properties. YAG:Th prepared hydrothermally consisted of submicron crystallites with a typical garnet habit. The CL efficiency of hydrothermally synthesized YAG:Tb (3 lm/W at 800 V) was comparable to that of equivalent YAG:Tb compositions prepared via high-temperature solid state reaction. In comparison, CL intensities of Gd{sub 3}Ga{sub 5}O{sub l2}:Tb were slightly better (3.5 lm/W at 800 V), while those of NaY(WO{sub 4}){sub 2}:Tb were approximately 1/100th that of YAG:Tb. Both CL and photoluminescence data show that the difference in the cathodoluminescence of YAG and NaY(WO{sub 4}){sub 2} can be understood in terms of differences in the mechanism of activation.

  13. Implementation of the Simple Endoscopic Activity Score in Crohn's Disease

    PubMed Central

    Koutroumpakis, Efstratios; Katsanos, Konstantinos H.

    2016-01-01

    Simple Endoscopic Score for Crohn's Disease (SES-CD) was developed as an attempt to simplify Crohn's Disease Endoscopic Index of Severity (CDEIS). Since it was constructed from CDEIS, SES-CD performs comparably but also carries similar limitations. Several studies have utilized SES-CD scoring to describe disease severity or response to therapy. Some of them used SES-CD score as a continuous variable while others utilized certain cutoff values to define severity grades. All SES-CD cutoff values reported in published clinical trials were empirically selected by experts. Although in most of the studies that used SEC-CD scoring to define disease severity, a score <3 reflected inactive disease, no study is using score 0 to predefine inactivity. Studies applying SES-CD to define response to treatment used score 0. There is no optimal SES-CD cut-off for endoscopic remission. The quantification of mucosal healing using SES-CD scoring has not been standardized yet. As the definition of mucosal healing by SES-CD is unset, the concept of deep remission is also still evolving. Serum and fecal biomarkers as well as new radiologic imaging techniques are complementary to SES-CD. Current practice as well as important changes in endoscopy should be taken into consideration when defining SES-CD cutoffs. The optimal timing of SES-CD scoring to assess mucosal healing is not defined yet. To conclude, SES-CD represents a valuable tool. However, a consensus agreement on its optimal use is required. PMID:27184635

  14. High IL-23 level is a marker of disease activity in rheumatoid arthritis.

    PubMed

    Abu Al Fadl, Esam M; Fattouh, Mona; Allam, Ahmed A

    2013-01-01

    Rheumatoid arthritis (RA) is a chronic autoimmune systemic disorder characterized by inflammatory responses mainly affecting the synovial joints. Interleukin-23 (IL-23) is a heterodimeric pro-inflammatory cytokine secreted by activated dendritic cells and activated macrophages. IL-23 is the key cytokine controlling inflammation in peripheral tissues leading to the development of autoimmune diseases. The objective of our study was to determine the relationship between the IL-23 level and disease activity in RA patients. Sixty RA patients were included in the study with mean age of 40 years; they included 44 (73.3 %) females and 16 males (26.7 %). The clinical parameters of disease activity were determined, including the 28-joint disease activity score (DAS28), serum levels of C-reactive protein (CRP), Anti-citrullinated peptide antibody (ACPA), rheumatoid factor (RF), and TNF-alpha and the degree of bony erosions based on X-rays. Patients were subdivided into active disease group (n = 30) with DAS28 score higher than 5.1 (Group I); and remission group (n = 30) with DAS28 score less than 2.6 (Group II). Thirty healthy individuals in the same age group of RA patients including 22 (73.3%) females and 8 males (26.7%) were randomly selected as the control group (Group III). The levels of IL-23 were determined by enzyme-linked immunosorbent assay (ELISA) and the correlations between the serum levels of IL-23 and disease activity parameters of patients with RA were determined. Serum levels of IL-23 were significantly higher in RA patients during active stage of the disease in comparison to the patients in remission and the control group. There was a significant positive correlation between serum IL-23 levels in RA patients and individual disease activity parameters. It is concluded that elevated serum IL-23 level may be a useful marker to detect active RA and disease progression in patients with RA. PMID:24617049

  15. Unemployment in TB Patients – Ten-Year Observation at Regional Center of Pulmonology in Bydgoszcz, Poland

    PubMed Central

    Przybylski, Grzegorz; Dąbrowska, Anita; Pilaczyńska-Cemel, Marta; Krawiecka, Dorota

    2014-01-01

    Background Tuberculosis (TB) affects the poorest of the poor and is an example of a disease that can contribute to the “disease-poverty trap”. The variable epidemiological situation is associated with social risk factors, such as unemployment, which may favor the occurrence of this disease. The aim of this study was to analyze unemployment as a factor that can influence the incidence and course of the disease. Material/Methods We analyzed TB patients with confirmed status of employment or unemployment admitted to the Regional Center of Pulmonology in Bydgoszcz in during the years 2001 to 2010. Out of 1130 patients, 604 were unemployed and the other confirmed their employment. Results The unemployed patients were mostly single men over age 40, with a low level of education, and living in a city. We observed that the proportions of smokers and alcohol abusers were significantly higher among the unemployed patients. The advanced radiological lesions, smear-positive pulmonary TB, and extra-pulmonary sites were diagnosed significantly more often in this group. The rate of death in the course of hospitalization was significantly higher in the group of unemployed patients. Conclusions Unemployment among TB patients is a serious problem. We found that more advanced radiological lesions were associated with more frequent treatment interruptions and a higher rate of death in the course of hospitalization. Increased efforts are needed to reduce and eliminate the problem of unemployment among patients with TB. This may, indirectly, contribute to a decrease in notifications of TB cases and improve treatment outcomes. PMID:25362504

  16. IL-27 and TGFβ mediated expansion of Th1 and adaptive regulatory T cells expressing IL-10 correlates with bacterial burden and disease severity in pulmonary tuberculosis.

    PubMed

    Kumar, Nathella P; Moideen, Kadar; Banurekha, Vaithilingam V; Nair, Dina; Sridhar, Rathinam; Nutman, Thomas B; Babu, Subash

    2015-09-01

    CD4(+) T cell expression of IL-10 is an important mechanism controlling immunity to tuberculosis (TB). To identify the CD4(+) T cell subsets producing IL-10 in human TB, we enumerated the frequencies of IL-10 expressing CD4(+) T cell subsets following TB-antigen stimulation of cells from individuals with pulmonary (PTB) and latent TB (LTB). We first demonstrate that TB antigens induce an expansion of IL-10 expressing Th1 (IL-10(+), IFNγ(+), T-bet(+)), Th2 (IL-10(+), IL-4(+), GATA-3(+)), Th9 (IL-10(+), IL-9(+), IL-4(-)), Th17 (IL-10(+), IL-17(+), IFNγ(-)), and natural and adaptive regulatory T cells [nTregs; IL-10(+), CD4(+), CD25(+), Foxp3(+) and aTregs; IL-10 single(+), CD4(+), CD25(-), Foxp3(-)] in PTB and LTB individuals, with frequencies being significantly higher in the former. However, only Th1 cells and adaptive Tregs expressing IL-10 exhibit a positive relationship with bacterial burdens and extent of disease in PTB. Finally, we show that IL-27 and TGFβ play an important role in the regulation of IL-10(+) Th cell subsets. Thus, active PTB is characterized by an IL-27 and TGFβ mediated expansion of IL-10 expressing CD4(+) T cell subsets, with IL-10(+) Th1 and IL-10(+) aTreg cells playing a potentially pivotal role in the pathogenesis of active disease. PMID:26417443

  17. Development and Retrospective Validation of the Juvenile Spondyloarthritis Disease Activity (JSpADA) Index

    PubMed Central

    Weiss, Pamela F.; Colbert, Robert A.; Xiao, Rui; Feudtner, Chris; Beukelman, Timothy; DeWitt, Esi Morgan; Pagnini, Ilaria; Wright, Tracey B.; Wallace, Carol A.

    2014-01-01

    Objectives To develop and validate a Juvenile Spondyloarthritis (JSpA) Disease Activity (JSpADA) index for use in clinical practice and research. Methods Using modified Delphi consensus techniques, ten items were selected by participants in the international pediatric rheumatology list-serve, the Childhood Arthritis and Rheumatology Research Alliance, and the list-serve for the Pediatric Section of the American College of Rheumatology. Validation was performed in a retrospective multicenter cohort of 243 children. Results 106 physicians representing 14 countries completed the initial questionnaire. Completion rates for the subsequent questionnaires were 84%, 75%, and 77% of the original respondents. Ten items reached 80% consensus: arthritis, enthesitis, patient pain assessment, inflammatory markers, morning stiffness, clinical sacroiliitis, uveitis, back mobility, and patient and physician assessments of disease activity. Two items were eliminated after item analysis (patient and physician assessments of disease activity). Factor analysis identified 3 primary domains that explain 58% of variance: peripheral disease, axial disease, and uveitis. Cronbach α coefficient was 0.66. The JSpADA had high or moderate correlations with the Juvenile Arthritis disease activity score (r=0.80), patient and physician assessments of disease activity (r=0.70 and 0.66), and the Childhood Health Assessment Questionnaire (r=0.56). The JSpADA discriminated well between subjects with active versus inactive disease (p<0.001) and was responsive to improvement or worsening in disease activity over time (p<0.001). Conclusion Using international input and consensus formation techniques, we developed and validated the first disease activity assessment for JSpA. Future studies should validate the JSpADA index in a prospective multi-center cohort. PMID:25047959

  18. Active ingredients of ginger as potential candidates in the prevention and treatment of diseases via modulation of biological activities

    PubMed Central

    Rahmani, Arshad H; shabrmi, Fahad M Al; Aly, Salah M

    2014-01-01

    The current mode of treatment based on synthetic drugs is expensive and also causes genetic and metabolic alterations. However, safe and sound mode of treatment is needed to control the diseases development and progression. In this regards, medicinal plant and its constituents play an important role in diseases management via modulation of biological activities. Ginger, the rhizome of the Zingiber officinale, has shown therapeutic role in the health management since ancient time and considered as potential chemopreventive agent. Numerous studies based on clinical trials and animal model has shown that ginger and its constituents shows significant role in the prevention of diseases via modulation of genetic and metabolic activities. In this review, we focused on the therapeutics effects of ginger and its constituents in the diseases management, and its impact on genetic and metabolic activities. PMID:25057339

  19. Indium 111-granulocyte scanning in the assessment of disease extent and disease activity in inflammatory bowel disease. A comparison with colonoscopy, histology, and fecal indium 111-granulocyte excretion

    SciTech Connect

    Saverymuttu, S.H.; Camilleri, M.; Rees, H.; Lavender, J.P.; Hodgson, H.J.; Chadwick, V.S.

    1986-05-01

    Indium 111-leukocyte scanning has recently been introduced as a new method for imaging inflammatory bowel disease. The technique has recently been made more specific for acute inflammation by labeling a pure granulocyte fraction rather than the conventional mixed leukocyte preparation. We now report a prospective study comparing 111In-granulocyte scanning with endoscopy, histology, and fecal 111In-granulocyte excretion for the assessment of disease extent and severity in colonic inflammatory bowel disease. In 52 patients with Crohn's disease or ulcerative colitis, disease extent and severity were assessed macroscopically, histologically, or by scanning using a numerical grading system. Excellent correlations were found between both endoscopy and histology and 111In scans (r = 0.90 (endoscopy) and r = 0.90 (histology) for extent; r = 0.86 and r = 0.91 for disease activity). Severity graded by scanning also showed a close correlation with fecal 111In-granulocyte excretion (r = 0.90). Indium 111-granulocyte scans are a rapid, accurate, noninvasive means of assessing both disease extent and severity of colonic involvement in inflammatory bowel disease.

  20. Design of novel camphane-based derivatives with antimycobacterial activity.

    PubMed

    Stavrakov, Georgi; Valcheva, Violeta; Philipova, Irena; Doytchinova, Irini

    2014-06-01

    Although tuberculosis (TB) continues to be one of the leading infectious disease killers globally, it is curable and preventable. Despite the existence of safe, well tolerated and effective drugs used in the TB treatment, the interest in new entities, combinations and regimens increases during the last 10 years. Recently, we reported for a new class of anti-TB agents - camphane-based derivatives with nanomolar activity against Mycobacterium tuberculosis strains. The quantitative structure-activity relationship (QSAR) study on 12 compounds revealed several structural requirements for antimycobacterial activity: two hydrogen bond donors, two or three rings and no large branched substituents. Here, we describe the design of a set of nine novel camphane-based derivatives following these requirements. The compounds were synthesized and tested against M. tuberculosis strain H37Rv. Four of them showed activities in the nanomolar range, significantly higher than the activities in the initial set. The QSAR study based on all 21 derivatives pointed to two main structural requirements for anti-TB activity: two hydrogen bond donors and a side chain with aromatic ring. PMID:24859319

  1. Temporal Effect of Depressive Symptoms on the Longitudinal Evolution of Rheumatoid Arthritis Disease Activity

    PubMed Central

    Rathbun, Alan M.; Harrold, Leslie R.; Reed, George W.

    2016-01-01

    Objective Depression is common in the rheumatoid arthritis (RA) population, yet little is known of its effect on the course of disease activity. The aim of our study was to determine if prevalent and incident depressive symptoms influenced longitudinal changes in RA disease activity. Methods RA patients with and without depressive symptoms were identified using single-item questions from an existing registry sample. Mixed-effects models were used to examine changes in disease activity over 2 years in those with and without prevalent and incident depressive symptoms. Outcome variables included composite disease activity, joint counts, global assessments, pain, function, and acute-phase reactants. Model-based outcome estimations at the index dates and corresponding 1- and 2-year changes were calculated. Results Rates of disease activity change were significantly different in patients with a lifetime prevalence of symptomology, but not incident depressive symptoms, when compared to controls. Prior symptoms were associated with slower rates of disease activity decline, evidenced by the estimated 1-year Clinical Disease Activity Index changes: −3.0 (−3.3, −2.6) and −4.0 (−4.3, −3.6) in patients with and without lifetime prevalence, respectively. Analogous results were obtained for most of the other disease activity outcomes; although, there was no temporal effect of prevalent symptoms of depression on swollen joints and acute-phase reactants. Conclusion Depressive symptoms temporally influence the evolution of RA disease activity, and the magnitude is dependent on the time of symptomatic onset. However, the effect is limited to patient-reported pain, global assessment, and function, as well as physician-reported global assessment and tender joints. PMID:25384985

  2. Carotid body chemoreceptors, sympathetic neural activation, and cardiometabolic disease.

    PubMed

    Iturriaga, Rodrigo; Del Rio, Rodrigo; Idiaquez, Juan; Somers, Virend K

    2016-01-01

    The carotid body (CB) is the main peripheral chemoreceptor that senses the arterial PO2, PCO2 and pH. In response to hypoxemia, hypercapnia and acidosis, carotid chemosensory discharge elicits reflex respiratory, autonomic and cardiovascular adjustments. The classical construct considers the CB as the main peripheral oxygen sensor, triggering reflex physiological responses to acute hypoxemia and facilitating the ventilatory acclimation to chronic hypoxemia at high altitude. However, a growing body of experimental evidence supports the novel concept that an abnormally enhanced CB chemosensory input to the brainstem contributes to overactivation of the sympathetic nervous system, and consequent pathology. Indeed, the CB has been implicated in several diseases associated with increases in central sympathetic outflow. These include hypertension, heart failure, sleep apnea, chronic obstructive pulmonary disease and metabolic syndrome. Indeed, ablation of the CB has been proposed for the treatment of severe and resistant hypertension in humans. In this review, we will analyze and discuss new evidence supporting an important role for the CB chemoreceptor in the progression of autonomic and cardiorespiratory alterations induced by heart failure, obstructive sleep apnea, chronic obstructive pulmonary disease and metabolic syndrome. PMID:26920146

  3. Cytomegalovirus Infection in Inflammatory Bowel Disease Is Not Associated with Worsening of Intestinal Inflammatory Activity

    PubMed Central

    do Carmo, Alexandre Medeiros; Santos, Fabiana Maria; Ortiz-Agostinho, Carmen Lucia; Nishitokukado, Iêda; Frota, Cintia S.; Gomes, Flavia Ubeda; de Arruda Leite, André Zonetti; Pannuti, Claudio Sérgio; Boas, Lucy Santos Vilas; Teixeira, Magaly Gemio; Sipahi, Aytan Miranda

    2014-01-01

    Background Cytomegalovirus is highly prevalent virus and usually occurs in immunocompromised patients. The pathophysiology and treatment of inflammatory bowel disease often induce a state of immunosuppression. Because this, there are still doubts and controversies about the relationship between inflammatory bowel disease and cytomegalovirus. Aim Evaluate the frequency of cytomegalovirus in patients with inflammatory bowel disease and identify correlations. Methods Patients with inflammatory bowel disease underwent an interview, review of records and collection of blood and fecal samples. The search for cytomegalovirus was performed by IgG and IgM blood serology, by real-time PCR in the blood and by qualitative PCR in feces. Results were correlated with red blood cell levels, C-reactive protein levels, erythrocyte sedimentation rates and fecal calprotectin levels for each patient. Results Among the 400 eligible patients, 249 had Crohn's disease, and 151 had ulcerative colitis. In the group of Crohn's disease, 67 of the patients had moderate or severe disease, but 126 patients presented with active disease, based on the evaluation of the fecal calprotectin. In patients with ulcerative colitis, only 21 patients had moderate disease, but 76 patients presented with active disease, based on the evaluation of the fecal calprotectin. A large majority of patients had positive CMV IgG. Overall, 10 patients had positive CMV IgM, and 9 patients had a positive qualitative detection of CMV DNA by PCR in the feces. All 400 patients returned negative results after the quantitative detection of CMV DNA in blood by real-time PCR. Analyzing the 19 patients with active infections, we only found that such an association occurred with the use of combined therapy (anti-TNF-alpha + azathioprine) Conclusion The findings show that latent cytomegalovirus infections are frequent and active cytomegalovirus infection is rare. We did not find any association between an active infection of CMV

  4. Dipstick urinalysis for diabetes screening in TB patients

    PubMed Central

    Restrepo, Blanca I.; Pino, Paula A.; Zarate, Izelda; Mora-Guzman, Francisco

    2013-01-01

    Introduction Diabetes knowledge among TB patients can contribute to improved TB treatment outcomes, but lack of diabetes diagnosis awareness is a limitation in developing countries. Given its low cost, the sensitivity of urine glucose dipsticks for diabetes screening in TB patients was assessed. Methods Glycosuria was assessed in 90 newly diagnosed TB patients (38 with diabetes) in south Texas, USA (n = 20) and northeast Mexico (n = 70) during January 2009–December 2010. Results Glycosuria was detected in 65% of the diabetic patients with chronic hyperglycemia (positive predictive value 91%, negative predictive value 84%). Conclusion We propose that TB clinics with limited budgets where portable glucometers may not be available conduct universal screening for diabetes with urine dipsticks. This could be followed by blood glucose or HbA1c testing in the subset of patients requiring confirmation or higher sensitivity assessment, to improve the comanagement of TB and diabetes. PMID:24030116

  5. Isoniazid toxicity and TB development during biological therapy of patients with psoriasis in Colombia.

    PubMed

    Cataño, Juan; Morales, Milena

    2016-10-01

    Background The use of biological therapy has been linked with an increased risk of tuberculosis (TB) reactivation. Objective The aim of this study was to present the follow-up results for Isoniazid (INH) chemoprophylaxis in patients with psoriasis receiving different biological therapies. Methods In this prospective observational study, patients with latent tuberculosis infection (LTBI) were given INH chemoprophylaxis between two and nine months prior to the beginning of biological therapy. All patients were followed up monthly for any signs or symptoms of active TB or INH toxicity. Results A total of 101 patients, 44.5% females, with a mean age of 46.9 ± 11.5 years (20-73) were enrolled. LTBI was identified in 100 patients (99%), of whom 81.2% completed nine months of chemoprophylaxis. Three patients (2.9%) developed active TB and 17 patients (16.8%) developed intolerance or toxicity related to INH. Conclusions Chemoprophylaxis with INH seems to be effective and safe for the prevention of most TB reactivations in individuals with LTBI receiving biological therapy, but toxicity must be monitored during follow-up. PMID:27003177

  6. [Measurement of physical activity in patients with chronic obstructive pulmonary disease].

    PubMed

    Magnussen, Helgo; Waschki, Benjamin; Watz, Henrik

    2009-04-15

    Physical activity is an important parameter related to morbidity and mortality in cardiovascular disease, metabolic syndrome/diabetes, mental disorders, cancer, and chronic obstructive pulmonary disease (COPD). In COPD, lower levels of physical activity as reported by the patients are associated with a faster annual lung function decline, increased number of hospitalizations, and higher risk of mortality. Self-reported physical activity, however, correlates only poorly with objectively quantified physical activity in patients with COPD. Recent data show that physical activity can reliably be measured in a substantial number of patients with COPD. Extrapulmonary effects of COPD are associated with reduced physical activity. Clinical characteristics commonly used to assess disease severity like the forced expiratory volume in 1 s or the 6-min walk distance only incompletely reflect the physical activity of patients with COPD. PMID:19399389

  7. Why and how should we measure disease activity and damage in lupus?

    PubMed

    Feld, Joy; Isenberg, David

    2014-06-01

    The assessment of disease activity and flare and differentiating them from permanent damage in patients with SLE is challenging. The SLEDAI, SLEDAI-2K and SELENA-SLEDAI measure global disease activity. The BILAG measures organ-specific activity. The BILAG better captures the change in the different organs at the expense of complexity. The SRI is a composite index incorporating both BILAG and SLEDAI indices and a physician's global assessment. It has been used in the most recent clinical trials. Damage correlates with prognosis; it is assessed by the SLICC/SDI index. This index scores damage whatever the cause, disease or treatment related, or the consequence of concomitant disease. The disease activity and damage indices do not correlate well with the patient's health related quality of life (HRQoL), the degree of disability or the impact of disease. The impact of the patients' joint disease on their HRQoL is assessed via the HAQ questionnaire and the global health status via the SF-36 index, or one of the more recently described lupus specific quality of life indices [Lupus QoL]. The global assessment instruments and the BILAG index can also be used in children and adolescents with SLE. However, a modified paediatric version of the SLICC/SDI damage index is advised. Many advances have been achieved in disease activity and damage measurement in the past 20 years but the problem of how best to capture flare accurately remains. PMID:24791651

  8. Quality of life among tuberculosis (TB), TB retreatment and/or TB-HIV co-infected primary public health care patients in three districts in South Africa

    PubMed Central

    2012-01-01

    Introduction TB and HIV co-morbidity amount to a massive burden on healthcare systems in many countries. This study investigates health related quality of life among tuberculosis (TB), TB retreatment and TB-HIV co-infected public primary health care patients in three districts in South Africa. Methods A cross sectional study was conducted among 4900 TB patients who were in the first month of anti-TB treatment in primary public health care clinics in three districts in South Africa. Quality of life was assessed using the social functioning (SF)-12 Health Survey through face to face interviews. Associations of physical health (Physical health Component Summary = PCS) and mental health (Mental health Component Summary = MCS) were identified using logistic regression analyses. Results The overall physical and mental health scores were 42.5 and 40.7, respectively. Emotional role, general health and bodily pain had the lowest sub-scale scores, while energy and fatigue and mental health had the highest domain scores. Independent Kruskal–Wallis tests found significant positive effects of being TB-HIV co-infected on the domains of mental health functioning, emotional role, energy and fatigue, social function and physical role, while significant negative effects were observed on general health, bodily pain and physical function. In multivariable analysis higher educational, lower psychological distress, having fewer chronic conditions and being HIV negative were significantly positively associated with PCS, and low poverty, low psychological distress and being HIV positive were positively significantly associated with MCS. Conclusion TB and HIV weaken patients’ physical functioning and impair their quality of life. It is imperative that TB control programmes at public health clinics design strategies to improve the quality of health of TB and HIV co-infected patients. PMID:22742511

  9. Can red cell distribution width be a marker of disease activity in ulcerative colitis?

    PubMed Central

    Ipek, Serkan; Cekic, Cem; Alper, Emrah; Coban, Eyup; Eliacik, Eylem; Arabul, Mahmut; Aslan, Fatih; Vatansever, Sezgin; Yalcin, Hulya; Unsal, Belkis

    2015-01-01

    Aim: The current study aimed to investigate the association between disease activity and red cell distribution width (RDW) levels in ulcerative colitis and to determine whether RDW can be used as a marker of disease activity in non-anemic ulcerative colitis. Methods: The RDW levels of 310 ulcerative colitis patients who underwent colonoscopy were analyzed retrospectively. The patients were divided into two groups (active disease and remission) according to the endoscopic activity index. In addition, the accuracy of RDW in determining disease activity in non-anemic patients was assessed. The efficacy of RDW in determining disease activity was compared to that of white blood cell count, platelet count, C-reactive protein, and erythrocyte sedimentation rate. Results: Two hundred and six (66.5%) patients had active disease, and 104 (33.5%) were in remission. The mean RDW levels in patients with active ulcerative colitis and in those in remission were 16.8±2.9 and 15.5±1.4, respectively (P<0.001). Ninety-six (46.6%) patients in the active disease group and 89 (85.6%) in the remission group were non-anemic, and their respective RDW levels were 15.4±1.2 and 15.3±1.1 (P=0.267). The sensitivity and specificity of RDW in determining inflammation were 41% and 91%, respectively (AUC 0.65, P<0.001). Conclusions: This study demonstrated that RDW can be used as a marker for disease activity in ulcerative colitis, but it did not have the same efficacy in the non-anemic group. PMID:26550336

  10. Invasive pneumococcal disease leads to activation and hyperreactivity of platelets.

    PubMed

    Tunjungputri, Rahajeng N; de Jonge, Marien I; de Greeff, Astrid; van Selm, Saskia; Buys, Herma; Harders-Westerveen, Jose F; Stockhofe-Zurwieden, Norbert; Urbanus, Rolf T; de Groot, Phillip G; Smith, Hilde E; van der Ven, Andre J; de Mast, Quirijn

    2016-08-01

    Using a novel porcine model of intravenous Streptococcus pneumoniae infection, we showed that invasive pneumococcal infections induce marked platelet activation and hyperreactivity. This may contribute to the vascular complications seen in pneumococcal infection. PMID:27322088

  11. Effect of dietary restrictions on disease activity in rheumatoid arthritis.

    PubMed Central

    Beri, D; Malaviya, A N; Shandilya, R; Singh, R R

    1988-01-01

    Additions in five steps were made, as a possible therapeutic measure, to the diet of 27 patients with rheumatoid arthritis (RA) after a period of two weeks of a basal isocaloric diet free from pulses, cereals, milk, and non-vegetarian protein foods. Fourteen patients finally took part in the trial, 10 (71%) of whom showed significant clinical improvement. Only three patients (11%) adhered to the diet for a period of 10 months. The others discontinued the diet and were then treated with conventional disease modifying drugs. The study indicates that dietary factors may influence inflammatory response in RA. PMID:3278696

  12. Magnetostriction of growth textured Tb-Zn alloys

    NASA Astrophysics Data System (ADS)

    Delaney, D. W.; Lograsso, T. A.

    1999-11-01

    The magnetostrictive performance of aligned microstructural composites of Tb-Zn alloys were experimentally tested at 77 K under compressive loads ranging from approximately 0-50 MPa and applied magnetic field up to 2000 Oe. Tb-8a/oZn, Tb-42a/oZn and the eutectic composition of Tb-27.8a/oZn were all directionally solidified to prepare aligned, textured microstructures. The eutectic sample grew with lamellar plates with the magnetically hard axes for each phase parallel with the rod axis and exhibited a strain of less than 100 ppm. The Tb-42a/oZn alloy solidified with TbZn dendrites in the magnetically hard [1 1 1] direction and exhibited a strain of 375 ppm. The Tb-8a/oZn alloy solidified pure Tb dendrites in the magnetically easy direction, the b-axis, yet it only displayed a 350-ppm magnetostriction at a maximum field of 2000 Oe due to the high anisotropy of the Tb dendrites.

  13. Influence of liver disease and environmental factors on hepatic monooxygenase activity in vitro.

    PubMed

    Brodie, M J; Boobis, A R; Bulpitt, C J; Davies, D S

    1981-01-01

    The effects of liver disease and environmental factors on hepatic microsomal cytochrome P-450 content, NADPH-cytochrome c reductase (reductase) activity and aryl hydrocarbon hydroxylase (AHH) activity have been simultaneously investigated in 70 patients undergoing diagnostic liver biopsy. The activity of reductase was not significantly affected by the presence of liver disease or any of the environmental factors studied. Cytochrome P-450 content decreased with increasing severity of liver disease whereas AHH activity was only significantly reduced in biopsies showing hepatocellular destruction. None of the parameters of monooxygenase activity varied significantly with the age or sex of the patients. Alcohol excess was associated with decreased cytochrome P-450 content and AHH activity and this effect was independent of the histological status of the biopsy. Both high caffeine intake and cigarette smoking increased AHH activity in the absence of any change in cytochrome P-450 content. There was a positive correlation between the number of meat meals eaten per week and cytochrome P-450 content. Chronic treatment with enzyme-inducing anticonvulsants appeared to increase both cytochrome P-450 content and AHH activity. Despite differential effects of liver disease and environmental influences on cytochrome P-450 content and AHH activity there was a highly significant correlation between the two parameters. The results of the present study correlate well with the known effects of disease and environment on drug metabolism in vivo. PMID:7308271

  14. Highly active antiretroviral therapy and tuberculosis control in Africa: synergies and potential.

    PubMed Central

    Harries, Anthony D.; Hargreaves, Nicola J.; Chimzizi, Rehab; Salaniponi, Felix M.

    2002-01-01

    HIV/AIDS (human immunodeficiency virus/acquired immunodeficiency syndrome) and TB (tuberculosis) are two of the world's major pandemics, the brunt of which falls on sub-Saharan Africa. Efforts aimed at controlling HIV/AIDS have largely focused on prevention, little attention having been paid to care. Work on TB control has concentrated on case detection and treatment. HIV infection has complicated the control of tuberculosis. There is unlikely to be a decline in the number of cases of TB unless additional strategies are developed to control both this disease and HIV simultaneously. Such strategies would include active case-finding in situations where TB transmission is high, the provision of a package of care for HIV-related illness, and the application of highly active antiretroviral therapy. The latter is likely to have the greatest impact, but for this therapy to become more accessible in Africa the drugs would have to be made available through international support and a programme structure would have to be developed for its administration. It could be delivered by means of a structure based on the five-point strategy called DOTS, which has been adopted for TB control. However, it may be unrealistic to give TB control programmes the responsibility for running such a programme. A better approach might be to deliver highly active antiretroviral therapy within a comprehensive HIV/AIDS management strategy complementing the preventive work already being undertaken by AIDS control programmes. TB programmes could contribute towards the development and implementation of this strategy. PMID:12132003

  15. Sarcoid-like lymphocytosis of the lower respiratory tract in patients with active Crohn's disease.

    PubMed

    Smiéjan, J M; Cosnes, J; Chollet-Martin, S; Soler, P; Basset, F M; Le Quintrec, Y; Hance, A J

    1986-01-01

    To re-evaluate the relationship between Crohn's disease and sarcoidosis, we compared the numbers and types of cells recovered by bronchoalveolar lavage from normal volunteers and patients with Crohn's disease, with other forms of inflammatory bowel disease, and with sarcoidosis. Patients with Crohn's disease, but not patients with other inflammatory bowel disorders, had an increase in the number of T lymphocytes on the surface of the lower respiratory tract similar to that seen in patients with sarcoidosis. As in sarcoidosis, this lymphocytosis results from an expansion of the T4+ T-lymphocyte subset, is characteristic of patients with active disease only, and is not associated with similar abnormalities in the peripheral blood. Thus, patients with apparently localized Crohn's disease have sarcoid-like lymphocytosis of the lower respiratory tract, a finding that emphasizes the systemic nature of Crohn's disease and the disorder's close relationship to sarcoidosis. PMID:3940500

  16. Gallic Acid, the Active Ingredient of Terminalia bellirica, Enhances Adipocyte Differentiation and Adiponectin Secretion.

    PubMed

    Makihara, Hiroko; Koike, Yuka; Ohta, Masatomi; Horiguchi-Babamoto, Emi; Tsubata, Masahito; Kinoshita, Kaoru; Akase, Tomoko; Goshima, Yoshio; Aburada, Masaki; Shimada, Tsutomu

    2016-01-01

    Visceral obesity induces the onset of metabolic disorders such as insulin resistance and diabetes mellitus. Adipose tissue is considered as a potential pharmacological target for treating metabolic disorders. The fruit of Terminalia bellirica is extensively used in Ayurvedic medicine to treat patients with diseases such as diabetes mellitus. We previously investigated the effects of a hot water extract of T. bellirica fruit (TB) on obesity and insulin resistance in spontaneously obese type 2 diabetic mice. To determine the active ingredients of TB and their molecular mechanisms, we focused on adipocyte differentiation using mouse 3T3-L1 cells, which are widely used to study adipocyte physiology. We show here that TB enhanced the differentiation of 3T3-L1 cells to mature adipocytes and that one of the active main components was identified as gallic acid. Gallic acid (10-30 µM) enhanced the expression and secretion of adiponectin via adipocyte differentiation and also that of fatty acid binding protein-4, which is the target of peroxisome proliferator-activated receptor gamma (PPARγ), although it does not alter the expression of the upstream genes PPARγ and CCAAT enhancer binding protein alpha. In the PPARγ ligand assay, the binding of gallic acid to PPARγ was undetectable. These findings indicate that gallic acid mediates the therapeutic effects of TB on metabolic disorders by regulating adipocyte differentiation. Therefore, TB shows promise as a candidate for preventing and treating patients with metabolic syndrome. PMID:27374289