Unmasking histoplasmosis immune reconstitution inflammatory syndrome in a patient recently started on antiretroviral therapy

Histoplasmosis is the most common endemic mycoses among HIV-infected people. Patients with suppressed cell immunity mainly due to HIV are at increased risk of disseminated disease. Dermatological manifestations of immune reconstitution inflammatory syndrome (IRIS) and cutaneous manifestations of histoplasmosis similar to an IRIS event have been previously described. We report the case of a 43-year-old male who presented with cutaneous disseminated histoplasmosis due to Histoplasma capsulatum var. capsulatum 4 months after the onset of the antiretroviral therapy and some improvement in the immune reconstitution. After 2 weeks of amphotericin B and itraconazole therapy, the scheduled treatment involved fluconazole maintenance therapy, which resulted in an improvement of his skin lesion

Positron spectra from internal pair conversion observed in {238}U + {181}Ta collisions

We present new results from measurements and simulations of positron spectra, originating from 238U + 181Ta collisions at beam energies close to the Coulomb barrier. The measurements were performed using an improved experimental setup at the double-Orange spectrometer of GSI. Particular emphasis is put on the signature of positrons from Internal-Pair-Conversion (IPC) processes in the measured e+ energy spectra, following the de-excitation of electromagnetic transitions in the moving Ta-like nucleus. It is shown by Monte Carlo simulations that, for the chosen current sweeping procedure used in the present experiments, positron emission from discrete IPC transitions can lead to rather narrow line structures in the measured energy spectra. The measured positron spectra do not show evidence for line structures within the statistical accuracy achieved, although expected from the intensities of the observed $\gamma$ transitions (E$_{\gamma}~1250-1600$ keV) and theoretical conversion coefficients. This is due to the reduced detection efficiency for IPC positrons, caused by the limited spatial and momentum acceptance of the spectrometer. A comparison with previous results, in which lines have been observed, is presented and the implications are discussed.Comment: LaTeX, 20 pages including 5 EPS figures; Accepted by Eur. Phys.Jour.

Flow paths and variability of the North Atlantic Current: A comparison of observations and a high-resolution model

The North Atlantic Current (NAC) is subject to variability on multiannual to decadal time scales, influencing the transport of volume, heat, and freshwater from the subtropical to the eastern subpolar North Atlantic (NA). Current observational time series are either too short or too episodic to study the processes involved. Here we compare the observed continuous NAC transport time series at the western flank of the Mid-Atlantic Ridge (MAR) and repeat hydrographic measurements at the OVIDE line in the eastern Atlantic with the NAC transport and circulation in the high-resolution (1/20°) ocean model configuration VIKING20 (1960–2008). The modeled baroclinic NAC transport relative to 3400 m (24.5 ± 7.1 Sv) at the MAR is only slightly lower than the observed baroclinic mean of 27.4 ± 4.7 Sv from 1993 to 2008, and extends further north by about 0.5°. In the eastern Atlantic, the western NAC (WNAC) carries the bulk of the transport in the model, while transport estimates based on hydrographic measurements from five repeated sections point to a preference for the eastern NAC (ENAC). The model is able to simulate the main features of the subpolar NA, providing confidence to use the model output to analyze the influence of the North Atlantic Oscillation (NAO). Model based velocity composites reveal an enhanced NAC transport across the MAR of up to 6.7 Sv during positive NAO phases. Most of that signal (5.4 Sv) is added to the ENAC transport, while the transport of the WNAC was independent of the NAO

New Results on e+e- Line Emission in U+Ta Collisions

We present new results obtained from a series of follow-up e+e- coincidence measurements in heavy-ion collisions, utilizing an improved experimental set-up at the double-Orange beta-spectrometer of GSI. The collision system U+Ta was reinvestigated in three independent runs at beam energies in the range (6.0-6.4)xA MeV and different target thicknesses, with the objective to reproduce a narrow sum-energy e+e- line at ~635 keV observed previously in this collision system. At improved statistical accuracy, the line could not be found in these new data. For the ''fission'' scenario, an upper limit (1 sigma) on its production probability per collision of 1.3x10^{-8} can be set which has to be compared to the previously reported value of [4.9 +- 0.8 (stat.) +- 1.0 (syst)]x10^{-7}. In the light of the new results, a reanalysis of the old data shows that the continuous part of the spectrum at the line position is significantly higher than previously assumed, thus reducing the production probability of the line by a factor of two and its statistical significance to < 3.4sigma.Comment: 15 pages, standard LaTeX with 3 included PS figures; Submitted to Physics Letters

Exome sequencing helped the fine diagnosis of two siblings afflicted with atypical Timothy syndrome (TS2)

BACKGROUND: Long-QT syndrome (LQTS) causes a prolongation of the QT-interval in the ECG leading to life threatening tachyarrhythmia and ventricular fibrillation. One atypical form of LQTS, Timothy syndrome (TS), is associated with syndactyly, immune deficiency, cognitive and neurological abnormalities as well as distinct cranio-facial abnormalities. CASE PRESENTATION: On a family with both children diagnosed with clinical LQTS, we performed whole exome sequencing to comprehensively screen for causative mutations after a targeted candidate gene panel screen for Long-QT syndrome target genes failed to identify any underlying genetic defect. Using exome sequencing, we identified in both affected children, a p.402G > S mutation in exon 8 of the CACNA1C gene, a voltage-dependent Ca2+ channel. The mutation was inherited from their father, a mosaic mutation carrier. Based on this molecular finding and further more careful clinical examination, we refined the diagnosis to be Timothy syndrome (TS2) and thereby were able to present new therapeutic approaches. CONCLUSIONS: Our study highlights the difficulties in accurate diagnosis of patients with rare diseases, especially those with atypical clinical manifestation. Such challenge could be addressed with the help of comprehensive and unbiased mutation screening, such as exome sequencing

Observed and modeled meridional overturning circulation related flow into the Caribbean

A major pathway of the Atlantic meridional overturning circulation (MOC) is the warm inflow into the Caribbean Sea. The transport and the contribution of water from the South Atlantic is calculated from observations (ADCP data and hydrography) and compared to the results of the equation image° FLAME model. The model and the observations show high consistency in the strength of the mean total inflow and its range of variability as well as in the general distribution of water from South Atlantic origin. The measurements give an annual mean South Atlantic Water (SAW) transport into the Caribbean of 9.3 Sv with high variability. This estimate has to be regarded as a lower bound since the present method (using temperature and salinity data) cannot identify the SAW included in the North Equatorial Current (NEC), which recirculated and was transformed in the interior tropical Atlantic. The model transport reproduces the observational values rather closely, with an annual mean inflow of 8.6 Sv and similar high variability. Closer inspection of the SAW pathways in the model suggest that the additional contribution by the NEC‐pathway is only about 2 Sv. The model results confirm the relative importance of the MOC pathways suggested by observations: the Caribbean inflow seems to be the main pathway (63%) for the warm and central water (σθ < 27.1 kg m−3), whereas for the intermediate water a larger fraction (59%) is transported northward at the eastern side of the Lesser Antilles

Sensitivity of the Southern Ocean to enhanced regional Antarctic ice sheet meltwater input

Despite advances in our understanding of the processes driving contemporary sea level rise, the stability of the Antarctic ice sheets and their contribution to sea level under projected future warming remains uncertain due to the influence of strong ice-climate feedbacks. Disentangling these feedbacks is key to reducing uncertainty. Here we present a series of climate system model simulations that explore the potential effects of increased West Antarctic Ice Sheet (WAIS) meltwater flux on Southern Ocean dynamics. We project future changes driven by sectors of the WAIS, delivering spatially and temporally variable meltwater flux into the Amundsen, Ross and Weddell embayments over future centuries. Focusing on the Amundsen Sea sector of the WAIS over the next 200 years, we demonstrate that the enhanced meltwater flux rapidly stratifies surface waters, resulting in a significant decrease in the rate of Antarctic Bottom Water (AABW) formation. This triggers rapid pervasive ocean warming (>1°C) at depth due to advection from the original site(s) of meltwater input. The greatest warming predicted along sectors of the ice sheet that are highly sensitized to ocean forcing, creating a feedback loop that could enhance basal ice shelf melting and grounding line retreat. Given that we do not include the effects of rising CO2 - predicted to further reduce AABW formation - our experiments highlight the urgent need to develop a new generation of fully-coupled ice sheet climate models, that include feedback mechanisms such as this, to reduce uncertainty in climate and sea level projections

P11 promoter methylation predicts the antidepressant effect of electroconvulsive therapy

Although electroconvulsive therapy (ECT) is among the most effective treatment options for pharmacoresistant major depressive disorder (MDD), some patients still remain refractory to standard ECT practise. Thus, there is a need for markers reliably predicting ECT non/response. In our study, we have taken a novel translational approach for discovering potential biomarkers for the prediction of ECT response. Our hypothesis was that the promoter methylation of p11, a multifunctional protein involved in both depressive-like states and antidepressant treatment responses, is differently regulated in ECT responders vs. nonresponders and thus be a putative biomarker of ECT response. The chronic mild stress model of MDD was adapted with the aim to obtain rats that are resistant to conventional antidepressant drugs (citalopram). Subsequently, electroconvulsive stimulation (ECS) was used to select responders and nonresponders, and compare p11 expression and promoter methylation. In the rat experiments we found that the gene promoter methylation and expression of p11 significantly correlate with the antidepressant effect of ECS. Next, we investigated the predictive properties of p11 promoter methylation in two clinical cohorts of patients with pharmacoresistant MDD. In a proof-of-concept clinical trial in 11 patients with refractory MDD, higher p11 promoter methylation was found in responders to ECT. This finding was replicated in an independent sample of 65 patients with pharmacoresistant MDD. This translational study successfully validated the first biomarker reliably predicting the responsiveness to ECT. Prescreening of this biomarker could help to identify patients eligible for first-line ECT treatment and also help to develop novel antidepressant treatment procedures for depressed patients resistant to all currently approved antidepressant treatments.Peer reviewe

Gene network reconstruction from microarray data

<p>Abstract</p> <p>Background</p> <p>Often, software available for biological pathways reconstruction rely on literature search to find links between genes. The aim of this study is to reconstruct gene networks from microarray data, using Graphical Gaussian models.</p> <p>Results</p> <p>The <it>GeneNet </it>R package was applied to the Eadgene chicken infection data set. No significant edges were found for the list of differentially expressed genes between conditions MM8 and MA8. On the other hand, a large number of significant edges were found among 85 differentially expressed genes between conditions MM8 and MM24.</p> <p>Conclusion</p> <p>Many edges were inferred from the microarray data. Most of them could, however, not be validated using other pathway reconstruction software. This was partly due to the fact that a quite large proportion of the differentially expressed genes were not annotated. Further biological validation is therefore needed for these networks, using for example in vitro invalidation of genes.</p