Discriminating active from latent tuberculosis in patients presenting to community clinics.

BACKGROUND: Because of the high global prevalence of latent TB infection (LTBI), a key challenge in endemic settings is distinguishing patients with active TB from patients with overlapping clinical symptoms without active TB but with co-existing LTBI. Current methods are insufficiently accurate. Plasma proteomic fingerprinting can resolve this difficulty by providing a molecular snapshot defining disease state that can be used to develop point-of-care diagnostics. METHODS: Plasma and clinical data were obtained prospectively from patients attending community TB clinics in Peru and from household contacts. Plasma was subjected to high-throughput proteomic profiling by mass spectrometry. Statistical pattern recognition methods were used to define mass spectral patterns that distinguished patients with active TB from symptomatic controls with or without LTBI. RESULTS: 156 patients with active TB and 110 symptomatic controls (patients with respiratory symptoms without active TB) were investigated. Active TB patients were distinguishable from undifferentiated symptomatic controls with accuracy of 87% (sensitivity 84%, specificity 90%), from symptomatic controls with LTBI (accuracy of 87%, sensitivity 89%, specificity 82%) and from symptomatic controls without LTBI (accuracy 90%, sensitivity 90%, specificity 92%). CONCLUSIONS: We show that active TB can be distinguished accurately from LTBI in symptomatic clinic attenders using a plasma proteomic fingerprint. Translation of biomarkers derived from this study into a robust and affordable point-of-care format will have significant implications for recognition and control of active TB in high prevalence settings

Interferon-β Pretreatment of Conventional and Plasmacytoid Human Dendritic Cells Enhances Their Activation by Influenza Virus

Influenza virus produces a protein, NS1, that inhibits infected cells from releasing type I interferon (IFN) and blocks maturation of conventional dendritic cells (DCs). As a result, influenza virus is a poor activator of both mouse and human DCs in vitro. However, in vivo a strong immune response to virus infection is generated in both species, suggesting that other factors may contribute to the maturation of DCs in vivo. It is likely that the environment in which a DC encounters a virus would contain multiple pro-inflammatory molecules, including type I IFN. Type I IFN is a critical component of the viral immune response that initiates an antiviral state in cells, primarily by triggering a broad transcriptional program that interferes with the ability of virus to establish infection in the cell. In this study, we have examined the activation profiles of both conventional and plasmacytoid dendritic cells (cDCs and pDCs) in response to an influenza virus infection in the context of a type I IFN-containing environment. We found that both cDCs and pDCs demonstrate a greater activation response to influenza virus when pre-exposed to IFN-β (IFN priming); although, the priming kinetics are different in these two cell types. This strongly suggests that type I IFN functions not only to reduce viral replication in these immune cells, but also to promote greater DC activation during influenza virus infections

Allozyme differentiation of two populations of the genus Neoplecostomus Eigenmann & Eigenmann, 1888 (Teleostei, Loricariidae) from the upper Paraná River basin, Brazil

Allozyme electrophoresis was used to examine 12 enzymatic systems in two populations of the genus Neoplecostomus from the Paraná River basin. Samples of Neoplecostomus sp. 1 were collected in Paraitinguinha stream of the Tietê River basin, in the municipality of Salesópolis, São Paulo State, and those of Neoplecostomus sp. 2 from São Domingos stream of the Rio Grande River basin, in the municipality of Muzambinho, Minas Gerais State. The genetic variability of the two populations was estimated by Nei’s expected heterozygosity and was considered lower than average for populations of freshwater fish. The proportion of polymorphic loci was low (only 5.26% for the locus Idh). The low frequency of heterozygosity for both populations revealed a high fixation of alleles for each locus. Homozygote excess was observed in both populations. The values of Nei’s genetic identity and the presence of loci with different allele frequencies in both populations may imply that the two populations belong to different species. The genetic variability between populations was compared to other data for loricariids

Increased incidence of traffic accidents in Toxoplasma-infected military drivers and protective effect RhD molecule revealed by a large-scale prospective cohort study

<p>Abstract</p> <p>Background</p> <p>Latent toxoplasmosis, protozoan parasitosis with prevalence rates from 20 to 60% in most populations, is known to impair reaction times in infected subjects, which results, for example, in a higher risk of traffic accidents in subjects with this life-long infection. Two recent studies have reported that RhD-positive subjects, especially RhD heterozygotes, are protected against latent toxoplasmosis-induced impairment of reaction times. In the present study we searched for increased incidence of traffic accidents and for protective effect of RhD positivity in 3890 military drivers.</p> <p>Methods</p> <p>Male draftees who attended the Central Military Hospital in Prague for regular entrance psychological examinations between 2000 and 2003 were tested for <it>Toxoplasma </it>infection and RhD phenotype at the beginning of their 1 to1.5-year compulsory military service. Subsequently, the data on <it>Toxoplasma </it>infection and RhD phenotype were matched with those on traffic accidents from military police records and the effects of RhD phenotype and <it>Toxoplasma </it>infection on probability of traffic accident was estimated with logistic regression.</p> <p>Results</p> <p>We confirmed, using for the first time a prospective cohort study design, increased risk of traffic accidents in <it>Toxoplasma</it>-infected subjects and demonstrated a strong protective effect of RhD positivity against the risk of traffic accidents posed by latent toxoplasmosis. Our results show that RhD-negative subjects with high titers of anti-<it>Toxoplasma </it>antibodies had a probability of a traffic accident of about 16.7%, i.e. a more than six times higher rate than <it>Toxoplasma</it>-free or RhD-positive subjects.</p> <p>Conclusion</p> <p>Our results showed that a common infection by <it>Toxoplasma gondii </it>could have strong impact on the probability of traffic accident in RhD negative subjects. The observed effects could provide not only a clue to the long-standing evolutionary enigma of the origin of RhD polymorphism in humans (the effect of balancing selection), but might also be the missing piece in the puzzle of the physiological function of the RhD molecule.</p

Water exercises and quality of life during pregnancy

<p>Abstract</p> <p>Background</p> <p>In Brazil, concern with the quality of life of pregnant women is one of the points emphasized in the Program for the Humanization of Prenatal Care and Childbirth launched in 2000. However, there are few references in the literature on the role of either land or water-based physical exercise on women's quality of life during pregnancy. The purpose of this study was to evaluate the effects of a physical exercise program of water aerobics on the quality of life (QOL) of sedentary pregnant women.</p> <p>Methods</p> <p>A comparative observational study involving sedentary low-risk pregnant women bearing a single fetus with gestational age less than 20 weeks at the time of admission to the study, who were receiving antenatal care at a public health service. One group of 35 women was given routine antenatal care, while another group of 31 women, in addition to receiving the same routine care as the first group, also participated in three classes of water aerobics per week. QOL was evaluated by applying the WHOQOL-BREF questionnaire in both groups at the 20^th, 28^thand 36^thweeks of pregnancy. In the same occasions, women also answered another questionnaire about their experience with pregnancy and antenatal care.</p> <p>Results</p> <p>The great majority of the participants considered that the practice of water aerobics had benefitted them in some way. QOL scores were found to be high in both groups during follow-up. There was no association between the practice of water aerobics and QOL.</p> <p>Conclusions</p> <p>Further studies involving larger sample sizes should be conducted in different sociocultural contexts and/or using other instruments to adequately evaluate the QOL of women during pregnancy.</p

Incidence of maternal Toxoplasma infections in pregnancy in Upper Austria, 2000-2007

Sagel U, Krämer A, Mikolajczyk RT. Incidence of maternal Toxoplasma infections in pregnancy in Upper Austria, 2000-2007. BMC Infectious Diseases. 2011;11(1): 348.UNLABELLED: ABSTRACT: BACKGROUND: Despite three decades of prenatal screening program for toxoplasmosis in Austria, population-based estimates for the incidence of maternal infections with Toxoplasma gondii during pregnancy are lacking. We studied the incidence of primary maternal infections during pregnancy in the Federal State of Upper Austria. METHODS: Screening tests for 63,416 women and over 90,000 pregnancies (more than 84.5% of pregnancies in the studied region) in the time period between 01.01.2000 and 31.12.2007 were analysed. The incidence of toxoplasmosis was estimated indirectly by binomial and directly by interval censored regression. RESULTS: During the studied period, 66 acute infections (risk of 0.07% per pregnancy) were detected, but only 29.8% of seronegative women were tested at least three times during their pregnancies. The seroprevalence of Toxoplasma antibodies among all tested women was 31%. Indirectly estimated incidence (from differences in prevalence by age) was 0.5% per pregnancy, while directly estimated incidence (interval censored regression) was 0.17% per pregnancy (95% confidence interval: 0.13-0.21%). CONCLUSIONS: Calculating incidence from observed infections results in severe underreporting due to many missed tests and potential diagnostic problems. Using statistical modelling, we estimated primary toxoplasmosis to occur in 0.17% (0.13-0.21%) of all pregnancies in Upper Austria

A systematic molecular and pharmacologic evaluation of AKT inhibitors reveals new insight into their biological activity.

Background AKT, a critical effector of the phosphoinositide 3-kinase (PI3K) signalling cascade, is an intensely pursued therapeutic target in oncology. Two distinct classes of AKT inhibitors have been in clinical development, ATP-competitive and allosteric. Class-specific differences in drug activity are likely the result of differential structural and conformational requirements governing efficient target binding, which ultimately determine isoform-specific potency, selectivity profiles and activity against clinically relevant AKT mutant variants.Methods We have carried out a systematic evaluation of clinical AKT inhibitors using in vitro pharmacology, molecular profiling and biochemical assays together with structural modelling to better understand the context of drug-specific and drug-class-specific cell-killing activity.Results Our data demonstrate clear differences between ATP-competitive and allosteric AKT inhibitors, including differential effects on non-catalytic activity as measured by a novel functional readout. Surprisingly, we found that some mutations can cause drug resistance in an isoform-selective manner despite high structural conservation across AKT isoforms. Finally, we have derived drug-class-specific phosphoproteomic signatures and used them to identify effective drug combinations.Conclusions These findings illustrate the utility of individual AKT inhibitors, both as drugs and as chemical probes, and the benefit of AKT inhibitor pharmacological diversity in providing a repertoire of context-specific therapeutic options

Search For Heavy Pointlike Dirac Monopoles

We have searched for central production of a pair of photons with high transverse energies in $p\bar p$ collisions at $\sqrt{s} = 1.8$ TeV using $70 pb^{-1}$ of data collected with the D\O detector at the Fermilab Tevatron in 1994--1996. If they exist, virtual heavy pointlike Dirac monopoles could rescatter pairs of nearly real photons into this final state via a box diagram. We observe no excess of events above background, and set lower 95% C.L. limits of $610, 870, or 1580 GeV/c^2$ on the mass of a spin 0, 1/2, or 1 Dirac monopole.Comment: 12 pages, 4 figure