Pulmonary histoplasmosis presenting as chronic productive cough, fever, and massive unilateral consolidation in a 15-year-old immune-competent boy: a case report

Severe histoplasmosis is known to be among the AIDS-defining opportunistic infections affecting patients with very low CD4 cell counts in histoplasmosis-endemic areas. Histoplasma capsulatum var. duboisii is common in West and Central Africa, where it occurs in both HIV/AIDS and non-HIV patients. Few cases of life-threatening histoplasmosis in immune-competent individuals have been reported worldwide. We describe a case of pulmonary histoplasmosis diagnosed on the basis of autopsy and histological investigations. A 15-year old East African immune-competent boy with a history of smear-positive tuberculosis and a two-year history of rock cutting presented to our hospital with chronic productive cough, fever, and massive unilateral consolidation. At the time of presentation to our hospital, this patient was empirically treated for recurrent tuberculosis without success, and he died on the seventh day after admission. The autopsy revealed a huge granulomatous lesion with caseation, but no acid-fast bacilli were detected on several Ziehl-Neelsen stains. However, periodic acid-Schiff staining was positive, and the histological examination revealed features suggestive of Histoplasma yeast cells. Severe pulmonary histoplasmosis should be considered in evaluating immune-competent patients with risk factors for the disease who present with pulmonary symptoms mimicking tuberculosis

Trends in Immunization Completion and Disparities in the Context of Health Reforms: The case study of Tanzania

\ud Of global concern is the decline in under five children mortality which has reversed in some countries in sub Saharan Africa (SSA) since the early 1990 s which could be due to disparities in access to preventive services including immunization. This paper is aimed at determining the trend in disparities in completion of immunization using Tanzania Demographic and Health Surveys (DHS). DHS studies randomly selected representative households from all regions in Tanzania since 1980 s, is repeated every five years in the same enumeration areas. The last three data sets (1990, 1996 and 2004) were downloaded and analyzed using STATA 9.0. The analysis included all children of between 12-23 months who would have completed all vaccinations required at 12 months. Across the time periods 1990, 1996 to 2004/05 the percentage of children completing vaccination was similar (71.0% in 1990, 72.7% in 1996 and 72.3% in 2005). There was no disparity in completion of immunization with wealth strata in 1990 and 1996 (p > 0.05) but not 2004. In 2004/05 there was marked disparity as most poor experienced significant decline in immunization completion while the least poor had significant increase (p < 0.001). All three periods children from households whose head had low education were less likely to complete immunization (p < 0.01). Equity that existed in 1990 and more pronounced in 1996 regressed to inequity in 2005, thus though at national level immunization coverage did not change, but at sub-group there was significant disparity associated with the changing contexts and reforms. To address sub-group disparities in immunization it is recommended to adopt strategies focused at governance and health system to reach all population groups and most poor.\u

Optimizing the diagnostic work-up of acute uncomplicated urinary tract infections

<p>Abstract</p> <p>Background</p> <p>Most diagnostic tests for acute uncomplicated urinary tract infections (UTIs) have been previously studied in so-called single-test evaluations. In practice, however, clinicians use more than one test in the diagnostic work-up. Since test results carry overlapping information, results from single-test studies may be confounded. The primary objective of the Amsterdam Cystitis/Urinary Tract Infection Study (ACUTIS) is to determine the (additional) diagnostic value of relevant tests from patient history and laboratory investigations, taking into account their mutual dependencies. Consequently, after suitable validation, an easy to use, multivariable diagnostic rule (clinical index) will be derived.</p> <p>Methods</p> <p>Women who contact their GP with painful and/or frequent micturition undergo a series of possibly relevant tests, consisting of patient history questions and laboratory investigations. Using urine culture as the reference standard, two multivariable models (diagnostic indices) will be generated: a model which assumes that patients attend the GP surgery and a model based on telephone contact only. Models will be made more robust using the bootstrap. Discrimination will be visualized in high resolution histograms of the posterior UTI probabilities and summarized as 5^th, 10^th, 25^th50^th, 75^th, 90^th, and 95^thcentiles of these, Brier score and the area under the receiver operating characteristics curve (ROC) with 95% confidence intervals. Using the regression coefficients of the independent diagnostic indicators, a diagnostic rule will be derived, consisting of an efficient set of tests and their diagnostic values.</p> <p>The course of the presenting complaints is studied using 7-day patient diaries. To learn more about the natural history of UTIs, patients will be offered the opportunity to postpone the use of antibiotics.</p> <p>Discussion</p> <p>We expect that our diagnostic rule will allow efficient diagnosis of UTIs, necessitating the collection of diagnostic indicators with proven added value. GPs may use the rule (preferably after suitable validation) to estimate UTI probabilities for women with different combinations of test results. Finally, in a subcohort, an attempt is made to identify which indicators (including antibiotic treatment) are useful to prognosticate recovery from painful and/or frequent micturition.</p

Human resources for health care delivery in Tanzania: a multifaceted problem

BACKGROUND: Recent years have seen an unprecedented increase in funds for procurement of health commodities in developing countries. A major challenge now is the efficient delivery of commodities and services to improve population health. With this in mind, we documented staffing levels and productivity in peripheral health facilities in southern Tanzania. METHOD: A health facility survey was conducted to collect data on staff employed, their main tasks, availability on the day of the survey, reasons for absenteeism, and experience of supervisory visits from District Health Teams. In-depth interview with health workers was done to explore their perception of work load. A time and motion study of nurses in the Reproductive and Child Health (RCH) clinics documented their time use by task. RESULTS: We found that only 14% (122/854) of the recommended number of nurses and 20% (90/441) of the clinical staff had been employed at the facilities. Furthermore, 44% of clinical staff was not available on the day of the survey. Various reasons were given for this. Amongst the clinical staff, 38% were absent because of attendance to seminar sessions, 8% because of long-training, 25% were on official travel and 20% were on leave. RCH clinic nurses were present for 7 hours a day, but only worked productively for 57% of time present at facility. Almost two-third of facilities had received less than 3 visits from district health teams during the 6 months preceding the survey. CONCLUSION: This study documented inadequate staffing of health facilities, a high degree of absenteeism, low productivity of the staff who were present and inadequate supervision in peripheral Tanzanian health facilities. The implications of these findings are discussed in the context of decentralized health care in Tanzania

DNA and histone deacetylases as targets for neuroblastoma treatment

Neuroblastoma, a tumor of the peripheral sympathetic nervous system, is the most frequent solid extra cranial tumor in children and is a major cause of death from neoplasia in infancy. Still little improvement in therapeutic options has been made, requiring a need for the development of new therapies. In our laboratory, we address still unsettled questions, which of mechanisms of action of DNA-damaging drugs both currently use for treatment of human neuroblastomas (doxorubicin, cis-platin, cyclophosphamide and etoposide) and another anticancer agent decreasing growth of neuroblastomas in vitro, ellipticine, are predominant mechanism(s) responsible for their antitumor action in neuroblastoma cell lines in vitro. Because hypoxia frequently occurs in tumors and strongly correlates with advanced disease and poor outcome caused by chemoresistance, the effects of hypoxia on efficiencies and mechanisms of actions of these drugs in neuroblastomas are also investigated. Since the epigenetic structure of DNA and its lesions play a role in the origin of human neuroblastomas, pharmaceutical manipulation of the epigenome may offer other treatment options also for neuroblastomas. Therefore, the effects of histone deacetylase inhibitors on growth of neuroblastoma and combination of these compounds with doxorubicin, cis-platin, etoposide and ellipticine as well as mechanisms of such effects in human neuroblastona cell lines in vitro are also investigated. Such a study will increase our knowledge to explain the proper function of these drugs on the molecular level, which should be utilized for the development of new therapies for neuroblastomas

Cholera- and Anthrax-Like Toxins Are among Several New ADP-Ribosyltransferases

Chelt, a cholera-like toxin from Vibrio cholerae, and Certhrax, an anthrax-like toxin from Bacillus cereus, are among six new bacterial protein toxins we identified and characterized using in silico and cell-based techniques. We also uncovered medically relevant toxins from Mycobacterium avium and Enterococcus faecalis. We found agriculturally relevant toxins in Photorhabdus luminescens and Vibrio splendidus. These toxins belong to the ADP-ribosyltransferase family that has conserved structure despite low sequence identity. Therefore, our search for new toxins combined fold recognition with rules for filtering sequences – including a primary sequence pattern – to reduce reliance on sequence identity and identify toxins using structure. We used computers to build models and analyzed each new toxin to understand features including: structure, secretion, cell entry, activation, NAD+ substrate binding, intracellular target binding and the reaction mechanism. We confirmed activity using a yeast growth test. In this era where an expanding protein structure library complements abundant protein sequence data – and we need high-throughput validation – our approach provides insight into the newest toxin ADP-ribosyltransferases

Authenticating the Presence of a Relativistic Massive Black Hole Binary in OJ 287 Using Its General Relativity Centenary Flare: Improved Orbital Parameters

Results from regular monitoring of relativistic compact binaries like PSR 1913+16 are consistent with the dominant (quadrupole) order emission of gravitational waves (GWs). We show that observations associated with the binary black hole (BBH) central engine of blazar OJ 287 demand the inclusion of gravitational radiation reaction effects beyond the quadrupolar order. It turns out that even the effects of certain hereditary contributions to GW emission are required to predict impact flare timings of OJ 287. We develop an approach that incorporates this effect into the BBH model for OJ 287. This allows us to demonstrate an excellent agreement between the observed impact flare timings and those predicted from ten orbital cycles of the BBH central engine model. The deduced rate of orbital period decay is nine orders of magnitude higher than the observed rate in PSR 1913+16, demonstrating again the relativistic nature of OJ 287's central engine. Finally, we argue that precise timing of the predicted 2019 impact flare should allow a test of the celebrated black hole "no-hair theorem" at the 10% level

Stochastic Modeling of Multiwavelength Variability of the Classical BL Lac Object OJ287 on Timescales Ranging from Decades to Hours

We present the results of our power spectral density analysis for the BL Lac object OJ 287, utilizing the Fermi-LAT survey at high-energy.-rays, Swift-XRT in X-rays, several ground-based telescopes and the Kepler satellite in the optical, and radio telescopes at GHz frequencies. The light curves are modeled in terms of continuous-time autoregressive moving average (CARMA) processes. Owing to the inclusion of the Kepler data, we were able to construct for the first time the optical variability power spectrum of a blazar without any gaps across similar to 6 dex in temporal frequencies. Our analysis reveals that the radio power spectra are of a colored-noise type on timescales ranging from tens of years down to months, with no evidence for breaks or other spectral features. The overall optical power spectrum is also consistent with a colored noise on the variability timescales ranging from 117 years down to hours, with no hints of any quasi-periodic oscillations. The X-ray power spectrum resembles the radio and optical power spectra on the analogous timescales ranging from tens of years down to months. Finally, the.-ray power spectrum is noticeably different from the radio, optical, and X-ray power spectra of the source: we have detected a characteristic relaxation timescale in the Fermi-LAT data, corresponding to similar to 150 days, such that on timescales longer than this, the power spectrum is consistent with uncorrelated (white) noise, while on shorter variability timescales there is correlated (colored) noise