The Ebola outbreak: effects on HIV reporting, testing and care in Bonthe district, rural Sierra Leone.

Setting: All public health facilities in Bonthe District, rural Sierra Leone. Objective: To compare, in the periods before and during the Ebola virus disease outbreak, 1) the submission and completeness of monthly human immunodeficiency virus (HIV) reports, and 2) the uptake of HIV testing and care for pregnant women and the general population. Design: A cross-sectional study using routine programme data. Results: Of the 627 HIV reports expected in each period, 406 (65%) were submitted in the pre-Ebola period and 376 (60%) during the Ebola outbreak (P = 0.08), of which respectively 318 (78%) and 335 (89%) had complete information (P < 0.001). In the pre-Ebola period, 5012 pregnant women underwent testing for HIV, of whom 25 were HIV-positive, compared to 4254 during the Ebola period, of whom 21 were HIV-positive (P < 0.001). Of those who were HIV-positive, respectively 14 (56%) and 21 (100%) received antiretroviral prophylaxis or antiretroviral therapy (ART) (P < 0.001). In the general population, 5770 persons underwent HIV testing pre-Ebola vs. 3095 in the Ebola period (P < 0.001); of those who tested positive for HIV, respectively 62% (33/53) and 81% (33/41) were started on ART (P = 0.06). Conclusion: There was suboptimal reporting on HIV/acquired immune-deficiency disease syndrome activities before and during the Ebola virus disease outbreak. HIV testing decreased during the Ebola outbreak, while the uptake of prevention of mother-to-child transmission and ART increased. Pre-emptive actions are needed to maintain the levels of HIV testing in any future outbreak

The Sleep Quality- and Myopia-Linked PDE11A-Y727C Variant Impacts Neural Physiology by Reducing Catalytic Activity and Altering Subcellular Compartmentalization of the Enzyme

Recently, a Y727C variant in the dual-specific 3′,5′-cyclic nucleotide phosphodiesterase 11A (PDE11A-Y727C) was linked to increased sleep quality and reduced myopia risk in humans. Given the well-established role that the PDE11 substrates cAMP and cGMP play in eye physiology and sleep, we determined if (1) PDE11A protein is expressed in the retina or other eye segments in mice, (2) PDE11A-Y7272C affects catalytic activity and/or subcellular compartmentalization more so than the nearby suicide-associated PDE11A-M878V variant, and (3) Pde11a deletion alters eye growth or sleep quality in male and female mice. Western blots show distinct protein expression of PDE11A4, but not PDE11A1-3, in eyes of Pde11a WT, but not KO mice, that vary by eye segment and age. In HT22 and COS-1 cells, PDE11A4-Y727C reduces PDE11A4 catalytic activity far more than PDE11A4-M878V, with both variants reducing PDE11A4-cAMP more so than PDE11A4-cGMP activity. Despite this, Pde11a deletion does not alter age-related changes in retinal or lens thickness or axial length, nor vitreous or anterior chamber depth. Further, Pde11a deletion only minimally changes refractive error and sleep quality. That said, both variants also dramatically alter the subcellular compartmentalization of human and mouse PDE11A4, an effect occurring independently of dephosphorylating PDE11A4-S117/S124 or phosphorylating PDE11A4-S162. Rather, re-compartmentalization of PDE11A4-Y727C is due to the loss of the tyrosine changing how PDE11A4 is packaged/repackaged via the trans-Golgi network. Therefore, the protective impact of the Y727C variant may reflect a gain-of-function (e.g., PDE11A4 displacing another PDE) that warrants further investigation in the context of reversing/preventing sleep disturbances or myopia.</p

Doubly nonlinear parabolic equations involving variable exponents

The Magazine Wharf area, Freetown, Sierra Leone was a focus of ongoing Ebola virus transmission from late June 2015. Viral genomes linked to this area contain a series of 13 T to C substitutions in a 150 base pair intergenic region downstream of viral protein 40 open reading frame, similar to the Ebolavirus/H.sapienswt/ SLE/2014/Makona-J0169 strain (J0169) detected in the same town in November 2014. This suggests that recently circulating viruses from Freetown descend from a J0169-like virus

Leaching as a pretreatment process to complement torrefaction in improving co-firing characteristics of Jatropha curcas seed cake

The presence of certain inorganic elements in biomass causes issues such as slagging, fouling and corrosion when co-firing with coal for power generation. In this work, the efficacy of leaching to remove these elements from Jatropha curcas seed cake was investigated. Leaching of both untorrefied and torrefied seed cakes was carried out in Milli-Q water at temperatures of 20, 35 and 50 °C. At 20 °C, the two critical elements, potassium and chlorine, decreased by as much as 85 and 97 %, respectively. Leaching at higher temperatures was only beneficial for the more intensely torrefied biomass, since they were more resistant to leaching. The electrical conductivity and ion content of the leachates were measured, as were the inorganic elemental content, dry ash content, volatile matter content and higher heating value (HHV) of the solid seed cake. A secondary benefit of the leaching was an increase in the HHV by up to 10 %

Mis-spliced transcripts generate de novo proteins in TDP-43–related ALS/FTD

Functional loss of TDP-43, an RNA binding protein genetically and pathologically linked to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), leads to the inclusion of cryptic exons in hundreds of transcripts during disease. Cryptic exons can promote the degradation of affected transcripts, deleteriously altering cellular function through loss-of-function mechanisms. Here, we show that mRNA transcripts harboring cryptic exons generated de novo proteins in TDP-43–depleted human iPSC–derived neurons in vitro, and de novo peptides were found in cerebrospinal fluid (CSF) samples from patients with ALS or FTD. Using coordinated transcriptomic and proteomic studies of TDP-43–depleted human iPSC–derived neurons, we identified 65 peptides that mapped to 12 cryptic exons. Cryptic exons identified in TDP-43–depleted human iPSC–derived neurons were predictive of cryptic exons expressed in postmortem brain tissue from patients with TDP-43 proteinopathy. These cryptic exons produced transcript variants that generated de novo proteins. We found that the inclusion of cryptic peptide sequences in proteins altered their interactions with other proteins, thereby likely altering their function. Last, we showed that 18 de novo peptides across 13 genes were present in CSF samples from patients with ALS/FTD spectrum disorders. The demonstration of cryptic exon translation suggests new mechanisms for ALS/FTD pathophysiology downstream of TDP-43 dysfunction and may provide a potential strategy to assay TDP-43 function in patient CSF

Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak

In its largest outbreak, Ebola virus disease is spreading through Guinea, Liberia, Sierra Leone, and Nigeria. We sequenced 99 Ebola virus genomes from 78 patients in Sierra Leone to ~2000× coverage. We observed a rapid accumulation of interhost and intrahost genetic variation, allowing us to characterize patterns of viral transmission over the initial weeks of the epidemic. This West African variant likely diverged from central African lineages around 2004, crossed from Guinea to Sierra Leone in May 2014, and has exhibited sustained human-to-human transmission subsequently, with no evidence of additional zoonotic sources. Because many of the mutations alter protein sequences and other biologically meaningful targets, they should be monitored for impact on diagnostics, vaccines, and therapies critical to outbreak response.Organismic and Evolutionary Biolog

Track E Implementation Science, Health Systems and Economics

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138412/1/jia218443.pd