Seroprevalence of hepatitis B and hepatitis C among blood donors in Sierra Leone: A multi-year retrospective study.

OBJECTIVES: In Sierra Leone, very little data are available on hepatitis B virus (HBV) and hepatitis C virus (HCV) prevalence. Blood donor screening permits estimation of the prevalence of transfusion transmissible infections in a general open population. We analyzed blood donor data in Sierra Leone to estimate national viral hepatitis prevalence and identify risk factors for hepatitis infection among the donor population. METHODS: We conducted a retrospective data analysis in five government hospitals. We collected HBV and HCV screening results, donor demographics, and donation type (family replacement or voluntary donor; first-time or repeat). Univariate and multivariate analyses were performed to determine associations between infections and socio-demographic factors. RESULTS: The number of donors screened was 29,713. The overall prevalence was: 10.8% (3200) for HBV and 1.2% (357) for HCV. HBV infection was most strongly associated with male sex (p: <0.0001) and younger age (p: <0.0004 for the 22-27 age group). Both HBV and HCV infection were higher in certain locations. CONCLUSION: Our findings stress the presence of viral hepatitis infection throughout the country and the need to invest in safe blood services, vaccination and treatment of viral hepatitis at the national level.

Systemic Blockade of the CB1 Receptor Augments Hippocampal Gene Expression Involved in Synaptic Plasticity but Perturbs Hippocampus-Dependent Learning Task.

Chronic and acute agonism as well as acute antagonism of CB1 receptors reveal modulation of learning and memory during stable performance of a delayed-nonmatch-to-sample (DNMS) memory task. However, it remains unclear how chronic blockade of the CB1 receptor alters acquisition of the behavioral task. We examined the effects of chronic rimonabant exposure during DNMS task acquisition to determine if blockade of the CB1 receptor with the antagonist rimonabant enhanced acquisition of operant task. Long-Evans rats, trained in the DNMS task before imposition of the trial delay, were surgically implanted with osmotic mini pumps to administer rimonabant (1.0 mg/kg/day) or vehicle (dimethyl sulfoxide/Tween-80/Saline). Following surgical recovery, DNMS training was resumed with the imposition of gradually longer delays (1-30 sec). The number of days required to achieve stable performance with either increasing length of delay or reversal of task contingency was compared between vehicle and rimonabant-treated rats. Following the completion of DNMS training, animals were euthanized, and both hippocampi were harvested for gene expression assay analysis. Rimonabant treatment animals required more time to achieve stable DNMS performance than vehicle-treated controls. Quantitative real-time polymerase chain reaction analysis revealed that the expressions of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit, brain-derived neurotrophic factor, and synapsin 1 (Syn1) were significantly increased. These results are consistent with rimonabant increasing mRNAs for proteins associated with hippocampal synapse remodeling, but that those alterations did not necessarily accelerate the acquisition of an operant behavioral task that required learning new contingencies.

Bundling HIV and TB Care at a District-Level Center in Sierra Leone: A high-yield method for diagnosing co-infection with TB and antiretroviral treatment failure among people living with HIV.

BACKGROUND: Protocols for HIV care are widely accepted by all international organizations and are proven to reduce mortality and complications from living with HIV. Unfortunately, executing best practice recommendations in Sierra Leone is difficult due to shortages in staff, training, and medications. METHODS: From June 2016 to August 2016, we implemented both an HIV guideline-based clinical evaluation protocol and a patient-centered workflow for TB screening and CD4 testing in the HIV clinic at Koidu Government Hospital (KGH) in rural Sierra Leone. The primary outcome of interest was how often this service center resulted in a clinically significant change in the patients' HIV regimen. Reasons for changing regimen included diagnosis of co-infection with tuberculosis (TB), diagnosis of clinical or presumed immunologic treatment failure of antiretroviral (ART) medications and, need for adherence to weight-based dosing in pediatric patients. FINDINGS: A total of 188 patients with HIV were seen in the clinic; 49 (26%) of these patients had a clinically significant change in their HIV regimen. The most common reason for regimen change was TB co-infection diagnosis in 38 (20%) patients. The other reasons for HIV regimen changes included: eight children whose ART was adjusted to meet appropriate levels for weight-based guidelines, five patients diagnosed with presumed immunologic treatment failure (some also co-infected with tuberculosis), and two patients with a serious side effect to ART. INTERPRETATION: A comprehensive, patient-centric HIV clinic can result in high rates of case detection for tuberculosis and recognition of immunological ART failure.

Gαi/o-dependent Ca(2+) mobilization and Gαq-dependent PKCα regulation of Ca(2+)-sensing receptor-mediated responses in N18TG2 neuroblastoma cells.

A functional Ca(2+)-sensing receptor (CaS) is expressed endogenously in mouse N18TG2 neuroblastoma cells, and sequence analysis of the cDNA indicates high homology with both rat and human parathyroid CaS cDNAs. The CaS in N18TG2 cells appears as a single immunoreactive protein band at about 150 kDa on Western blots, consistent with native CaS from dorsal root ganglia. Both wild type (WT) and Gαq antisense knock-down (KD) cells responded to Ca(2+) and calindol, a positive allosteric modulator of the CaS, with a transient increase in intracellular Ca(2+) concentration ([Ca(2+)]i), which was larger in the Gαq KD cells. Stimulation with 1 mM extracellular Ca(2+) (Ca(2+)e) increased [Ca(2+)]i in N18TG2 Gαq KD compared to WT cells. Ca(2+) mobilization was dependent on pertussis toxin-sensitive Gαi/o proteins and reduced by 30 µM 2-amino-ethyldiphenyl borate and 50 µM nifedipine to the same plateau levels in both cell types. Membrane-associated PKCα and p-PKCα increased with increasing [Ca(2+)]e in WT cells, but decreased in Gαq KD cells. Treatment of cells with 1 µM GÓ§ 6976, a Ca(2+)-specific PKC inhibitor reduced Ca(2+) mobilization and membrane-associated PKCα and p-PKCα in both cell types. The results indicate that the CaS-mediated increase in [Ca(2+)]i in N18TG2 cells is dependent on Gαi/o proteins via inositol-1,4,5-triphosphate (IP3) channels and store-operated Ca(2+) entry channels, whereas modulation of CaS responses involving PKCα phosphorylation and translocation to the plasma membrane occurs via a Gαq mechanism.

Pharmacological elevation of anandamide impairs short-term memory by altering the neurophysiology in the hippocampus.

In rodents, many exogenous cannabinoid agonists including Δ(9)-THC and WIN55,212-2 (WIN-2) have been shown to impair short-term memory (STM) by inhibition of hippocampal neuronal assemblies. However, the mechanisms by which endocannabinoids such as anandamide and 2-arachidonyl glycerol (2-AG) modulate STM processes are not well understood. Here the effects of anandamide on performance of a Delayed-Non-Match-to-Sample (DNMS) task (i.e. STM task) and concomitant hippocampal ensemble activity were assessed following administration of either URB597 (0.3, 3.0 mg/kg), an inhibitor of the Fatty Acid Amide Hydrolase (FAAH), AM404 (1.5, 10.0 mg/kg), a putative anandamide uptake/FAAH inhibitor, or R-methanandamide (3.0, 10.0 mg/kg), a stable analog of anandamide. Principal cells from hippocampal CA3/CA1 were recorded extracellularly by multi-electrode arrays in Long-Evans rats during DNMS task (1-30 s delays) performance and tracked throughout drug administration and recovery. Both R-methanandamide and URB597 caused dose- and delay-dependent deficits in DNMS performance with suppression of hippocampal ensemble activity during the encoding (sample) phase. R-methanandamide-induced effects were not reversed by capsaicin excluding a contribution of TRPV-1 receptors. AM404 produced subtle deficits at longer delay intervals but did not alter hippocampal neuronal activity during task-specific events. Collectively, these data indicate that endocannabinoid levels affect performance in a STM task and their pharmacological elevation beyond normal concentrations is detrimental also for the underlying physiological responses. They also highlight a specific window of memory processing, i.e. encoding, which is sensitive to cannabinoid modulation.

Tracking the changes of hippocampal population nonlinear dynamics in rats learning a memory-dependent task.

Neurobiological processes associated with learning are known to be highly nonlinear, dynamical, and time-varying. Characterizing the time-varying functional input-output properties of neural systems is a critical step to understand the neurobiological basis of learning. In this paper, we present a study on tracking of the changes of neural dynamics in rat hippocampus during learning of a memory-dependent delayed nonmatch-to-sample (DNMS) task. The rats were first trained to perform the DNMS task without a delay between the sample and response events. After reaching a performance level, they were subjected to the DNMS task with variable delays with a 5s mean duration. Spike trains were recorded from hippocampal CA3 (input) and CA1 (output) regions during all training sessions and constitute the input-output data for modeling. We applied the time-varying Generalized Laguerre-Volterra Model to study the changes of the CA3-CA1 nonlinear dynamics using these data. Result showed significant changes in the Volterra kernels after the introduction of delays. This result suggests that the CA3-CA1 nonlinear dynamics established in the initial training sessions underwent a functional reorganization as animals were learning to perform the task that now requires delays.

Changes of hippocampal CA3-CA1 population nonlinear dynamics across different training sessions in rats performing a memory-dependent task.

Delayed-nonmatch-to-sample (DNMS) task is memory-dependent. Hippocampal CA3 and CA1 cells were shown to be encoding the required spatial and temporal information to complete this task. In order to identify possible changes in neural population nonlinear dynamics during learning of the DNMS task, we have first modeled the input-output transformation of spike trains across brain subregions from learning animals using a multiple-input, multiple-output (MIMO) nonlinear dynamic model. The feedforward and feedback kernels describing the relations between hippocampal CA3 and CA1 subregions have shown significant changes at different training sessions.