Background: Population allele frequencies of apolipoprotein E (APOE) vary by geographic region. The purpose of this study is to summarize and evaluate published estimates for the prevalence of APOE e4 carrier status among the population diagnosed with Alzheimer’s disease (AD) by geographic region and country. Methods: A systematic review of English-language publications from January 1, 1985, through May 31, 2010, was conducted. Studies reporting APOE e4 status for patients diagnosed with AD were included in the analysis; trials and autopsies were excluded. APOE e4 data were pooled, and prevalence and 95% confidence intervals (CIs) were calculated. Results: Pooled estimates for APOE e4 carrier prevalence data were derived from 142 independent samples: 48.7% (95% CI: 46.5–51.0), and from 73 samples for e4/4 (homozygotes): 9.6% (95% CI: 8.4–10.8). The highest estimates were in Northern Europe: 61.3% (95% CI: 55.9–66.7), e4/4 prevalence: 14.1% (95% CI: 12.2–16.0). The lowest estimates were in Asia and Southern Europe. Substantial heterogeneity of these prevalence estimates was observed. Conclusions: APOE e4 genotype prevalence varies among AD patients by region and within each country. Further exploration is warranted to better understand the substantial heterogeneity of these prevalence estimates.

Treatment of hepatitis C virus with potent, interferon-free, direct-acting antiviral regimens with no activity against hepatitis B virus (HBV) may increase the risk for HBV reactivation in coinfected patients. We present 2 cases of HBV reactivation during treatment with an all-oral regimen of simeprevir and sofosbuvir and discuss strategies to prevent HBV flare.

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Introduction Tuberculosis outbreaks emerge occasionally in long-term care facilities and various educational establishments. This study was designed to determine the five year overall prevalence and trend of tuberculosis and associated factors among students at Adama Science and Technology University and Addis Ababa University Sidist Kilo campus. Methods A five-year retrospective study was conducted on students medical records of tuberculosis Directly Observed Treatment Short Course clinics from September 2009 – July 2014. The overall prevalence and the trend of smear positive, smear negative and extra pulmonary tuberculosis cases was determined. Odds ratio with 95 percent confidence interval was calculated for categorical variables using a multivariate logistic regression model to assess the strength of association. Results A total of 112 and 263 tuberculos cases were recorded in Addis Ababa University Sidist Kilo campus and Adama Science and Technology University, respectively. The mean proportion of tuberculosis cases of all types among the total number of students enrolled at Adama Science and Technology University and Addis Ababa University Sidist Kilo campus was 1098.1 and 511.7 cases per 100,000 population, respectively. There was a statistically significant difference in prevalence of tuberculosis among students in Adama Science and Technology University compared to that in Addis Ababa University Sidist Kilo campus [adjusted odds ration: 2.881, 95% CI (1.76–4.71)]. The trend of tuberculosis prevalence showed a steady decline from the first to the last year of the study period. Conclusion The number of tuberculosis cases observed among university students in this study was high. Governmental and nongovernmental agencies involved in tuberculosis control must consider higher education institutions as focal points for prevention and elimination of tuberculosis in Ethiopia.

To investigate the neuroprotective effects of erythropoietin (EPO) in a rodent model of Parkinson disease, we inoculated a nonreplicating herpes simplex virus-based vector expressing EPO (vector DHEPO) into the striatum of mice 1 week prior to, or 2 weeks after, the start of continual administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (4 mg/kg intraperitoneally, 5 of 7 days) for 6 weeks. Inoculation with DHEPO prior to MPTP intoxication preserved behavioral function measured by pellet retrieval and the histological markers of tyrosine hydroxylase-immunoreactive (TH-IR) neuronal cell bodies in the substantia nigra (SN) and TH-IR and dopamine transporter-immunoreactive (DAT-IR) terminals in striatum. Inoculation of DHEPO 2 weeks into a 6-week course of MPTP resulted in improvement of behavioral function and restoration of TH-IR cells in SN and TH- and DAT-IR in the striatum. The effects of vector-produced EPO were similar in magnitude to the effects of vector-mediated expression of glial-derived neurotrophic factor in the same model. These results demonstrate that vector-mediated EPO production may be used to reverse dopaminergic neurodegeneration in the face of continued toxic insult.

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Background The ability of anti-tuberculosis drugs to cross the blood brain barrier and reach the central nervous system (CNS) is critical to their effectiveness in treating tuberculosis meningitis (TBM). We sought to fill a critical knowledge gap by providing data on the ability of new and repurposed anti-tuberculosis drugs to penetrate into the cerebrospinal fluid (CSF). Methods We conducted a clinical pharmacology study among patients treated for TBM in Tbilisi,Georgia from January 2019 until January 2020. Serial serum and CSF samples were collected while patients were hospitalized. CSF was collected from routine lumbar punctures with the timing of the lumbar puncture alternating between 2 and 6 hours to capture early and late CSF penetration. Results A total of seventeen patients treated for TBM (8 with confirmed diease) were included; all received linezolid, with a subset receiving cycloserine (5), clofazimine (5), delamanid (4) and bedaquiline (2). All CSF measurements of bedaquiline (12), clofazimine (24), and delaminid (19) were below the limit of detection. The median CSF concentrations of cycloserine at 2 and 6 hours were 15.90 and 15.10 µg/ml with adjusted CSF/serum ratios of 0.52 and 0.66. CSF concentrations of linezolid were 0.90 and 3.14 µg/ml at 2 and 6 hours, with adjusted CSF/serum ratios of 0.25 and 0.59, respectively. CSF serum linezolid concentrations were not impacted by rifampin coadministration. Conclusions Based on moderate to high CSF penetration, linezolid and cycloserine may be effective drugs for TBM treatment while the utility of bedaquiline, delaminid and clofazimine is uncertain given their low CSF penetration.

IntroductionPulmonary tuberculosis (TB) is a major worldwide health problem that lacks robust blood-based biomarkers for detection of active disease. High-resolution metabolomics (HRM) is an innovative method to discover low-abundance metabolites as putative blood biomarkers to detect TB disease, including those known to be produced by the causative organism, Mycobacterium tuberculosis (Mtb).MethodsWe used HRM profiling to measure the plasma metabolome for 17 adults with active pulmonary TB disease and 16 of their household contacts without active TB. We used a suspect screening approach to identify metabolites previously described in cell culture studies of Mtb based on retention time and accurate mass matches.ResultsThe association of relative metabolite abundance in active TB disease subjects compared to their household contacts predicted three Mtb-associated metabolites that were significantly increased in the active TB patients based on accurate mass matches: phosphatidylglycerol (PG) (16:0_18:1), lysophosphatidylinositol (Lyso-PI) (18:0) and acylphosphatidylinositol mannoside (Ac1PIM1) (56:1) (p<0.001 for all). These three metabolites provided excellent classification accuracy for active TB disease (AUC = 0.97). Ion dissociation spectra (tandem MS/MS) supported the identification of PG (16:0_18:1) and Lyso-PI (18:0) in the plasma of patients with active TB disease, though the identity of Ac1PIM1 could not be definitively confirmed.ConclusionsPresence of the Mtb-associated lipid metabolites PG (16:0_18:1) and Lyso-PI (18:0) in plasma accurately identified patients with active TB disease. Consistency of in vitro and in vivo data suggests suitability for exploring these in future studies for possible development as TB disease biomarkers.