44 research outputs found
serological markers of pulmonary tuberculosis and of response to anti tuberculosis treatment in a patient population in guinea
The aim of the study was to evaluate serological correlates of active tuberculosis and of response to antituberculosis treatment in a cohort of HIV-negative patients with pulmonary tuberculosis studied at diagnosis and during treatment at the Service de Pneumo-Phtisiologie, Centre Hospitalier-Universitaire Ignace Deen, Conakry, Republic of Guinea. Two similar cohorts of HIV-negative healthy households of patients and healthy community controls were included in the study. Plasma samples were obtained from 168 untreated tuberculosis patients, 167 healthy household controls, and 168 healthy community controls. Serial plasma samples were also obtained from the tuberculosis patients at 2 and 8 months after initiation of chemotherapy. IgG antibody levels were measured by an enzyme-linked immunosorbent assay (ELISA) using ten purified M. tuberculosis antigens. ELISA results were analysed by comparing geometric means of data. Of the ten antigens tested, five (14kDa Ag, 19kDa Ag, AlaDH, MS, and MPT83) elicited similar antibody responses in untreated TB patients and controls. In contrast, levels of three antibodies (ESAT-6, LAM, and 38kDa Ag) were higher in untreated TB patients than in household or community controls (p<0.0001). Levels were higher in untreated patients than in community controls also for the anti-Rv2626c antibody (p = 0.0001) and, at a lower significance level, for the anti-FdxA antibody (p<0.025). Antibody levels against ESAT-6 and Rv2626c decreased during therapy, while antibody levels to the 38 kDa antigen and LAM increased during therapy; FdxA antibody levels did not vary with treatment. Neither severity of presentation nor chest X-ray patterns affected levels of these antibodies before treatment. In contrast, after the 8-month therapeutic course, patients who presented with moderate/severe disease had higher levels of anti-ESAT-6, anti-FdxA, and anti-38kDa antibodies than those of patients with mild disease onset. Patients with bilateral lung lesions had significantly higher anti-38kDa and anti-LAM levels, both at diagnosis and after 8-month treatment, than patients with lesions involving only one lung. Antibodies to alanine dehydrogenase and malate synthetase measured at initiation of treatment were higher in tuberculosis patients who subsequently failed therapy than in those who were cured. The main conclusions of the study are: a) plasma levels of antibodies to a number of M. tuberculosis represent serological correlates of active disease; b) these correlates are affected in an antigen-specific fashion by anti-tuberculosis treatment; c) particular serological markers may be predictive of treatment outcome
Genome-wide discovery of small RNAs in Mycobacterium tuberculosis
Only few small RNAs (sRNAs) have been characterized in Mycobacterium tuberculosis and their role in regulatory networks is
still poorly understood. Here we report a genome-wide characterization of sRNAs in M. tuberculosis integrating experimental
and computational analyses. Global RNA-seq analysis of exponentially growing cultures of M. tuberculosis H37Rv had
previously identified 1373 sRNA species. In the present report we show that 258 (19%) of these were also identified by
microarray expression. This set included 22 intergenic sRNAs, 84 sRNAs mapping within 59/39 UTRs, and 152 antisense
sRNAs. Analysis of promoter and terminator consensus sequences identified sigma A promoter consensus sequences for
121 sRNAs (47%), terminator consensus motifs for 22 sRNAs (8.5%), and both motifs for 35 sRNAs (14%). Additionally, 20/23
candidates were visualized by Northern blot analysis and 59 end mapping by primer extension confirmed the RNA-seq data.
We also used a computational approach utilizing functional enrichment to identify the pathways targeted by sRNA
regulation. We found that antisense sRNAs preferentially regulated transcription of membrane-bound proteins. Genes
putatively regulated by novel cis-encoded sRNAs were enriched for two-component systems and for functional pathways
involved in hydrogen transport on the membrane
PPPC 4 DM ID: A Poor Particle Physicist Cookbook for Dark Matter Indirect Detection
We provide ingredients and recipes for computing signals of TeV-scale Dark
Matter annihilations and decays in the Galaxy and beyond. For each DM channel,
we present the energy spectra of electrons and positrons, antiprotons,
antideuterons, gamma rays, neutrinos and antineutrinos e, mu, tau at
production, computed by high-statistics simulations. We estimate the Monte
Carlo uncertainty by comparing the results yielded by the Pythia and Herwig
event generators. We then provide the propagation functions for charged
particles in the Galaxy, for several DM distribution profiles and sets of
propagation parameters. Propagation of electrons and positrons is performed
with an improved semi-analytic method that takes into account
position-dependent energy losses in the Milky Way. Using such propagation
functions, we compute the energy spectra of electrons and positrons,
antiprotons and antideuterons at the location of the Earth. We then present the
gamma ray fluxes, both from prompt emission and from Inverse Compton scattering
in the galactic halo. Finally, we provide the spectra of extragalactic gamma
rays. All results are available in numerical form and ready to be consumed.Comment: 57 pages with many figures and tables. v4: updated to include a 125
higgs boson, computation and discussion of extragalactic spectra corrected,
some other typos fixed; all these corrections and updates are reflected on
the numerical ingredients available at
http://www.marcocirelli.net/PPPC4DMID.html they correspond to Release 2.
Effects of sleep deprivation on neural functioning: an integrative review
Sleep deprivation has a broad variety of effects on human performance and neural functioning that manifest themselves at different levels of description. On a macroscopic level, sleep deprivation mainly affects executive functions, especially in novel tasks. Macroscopic and mesoscopic effects of sleep deprivation on brain activity include reduced cortical responsiveness to incoming stimuli, reflecting reduced attention. On a microscopic level, sleep deprivation is associated with increased levels of adenosine, a neuromodulator that has a general inhibitory effect on neural activity. The inhibition of cholinergic nuclei appears particularly relevant, as the associated decrease in cortical acetylcholine seems to cause effects of sleep deprivation on macroscopic brain activity. In general, however, the relationships between the neural effects of sleep deprivation across observation scales are poorly understood and uncovering these relationships should be a primary target in future research
Track E Implementation Science, Health Systems and Economics
Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138412/1/jia218443.pd
Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.
BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362