Case 5 : The Precision of Aid: Remembering the Forgotten Disease in the Horn of Africa

The district of Burao, Somaliland is in its 16th epidemiologic week in the midst of a cholera outbreak. The Somaliland Ministry of Health, in need of emergency relief, has requested that humanitarian organizations come to its aid. Eve Tinuviel has been deployed to Burao as a member of the Canadian Red Cross, where she serves as a global health advisor responsible for emergency health services. Eve’s main responsibility is to analyze disease surveillance data, triangulating data from different sources. A Health Cluster Coordination meeting amongst different health and humanitarian organizations reveals gaps in the epidemic response. The scarcity of resources and volunteers, and more importantly the incompleteness and inadequacy of the passive surveillance data, threaten Eve’s ability to trace newly affected individuals, identify the origins of the disease and develop strategies to help the affected communities

Genotype and Haplotype Analysis of ABCB1 at 1236, 2677 and 3435 among Jordanian Population

Purpose: To determine the frequencies of important allelic variants and their haplotype frequencies of the gene among Jordanian population and to compare findings with those reported for other ethnic groups.Methods: Genotyping of ABCB1 (C1236T, G2677T/A and C3435T) was carried out on unrelated healthy Jordanian subjects. Different allelic variants were determined using polymerase chain reactionrestriction fragment length polymorphism (PCR-RFLP). The haplotype frequencies of these three SNPs were analyzed and compared them with those of other reported populations. Haplotype frequencies were calculated using Golden Helix Tree software and Linkage disequilibrium was represented by D”.Results: ABCB1 C3435T allele frequencies for C allele and T allele were 0.57 and 0.43, respectively. For ABCB1 G2677T/A the allele frequencies for G allele, T allele, and A allele were 0.65, 0.32 and 0.0, respectively. As for ABCB C1236T, its allele frequencies were 0.65 for C allele and 0.35 for T allele. C1236T, G2677T/A, and C3435T SNPs were expected to be structured in 8 different haplotypes with GC- C (37.6.0 %), T-T-T (18.6 %), G-C-T (14.3 %) and T-T-C (12 %) that were most prominent. The haplotype frequency distribution of our study group was found to be significantly different from those of Chinese, Indian, Japanese, African and Caucasian (p < 0.0001) and resemble Ashkenazi Jewish and Slovenian populations (p > 0.05).Conclusion: In addition to earlier studies, the findings of the current study provide evidence that suggest the use of genetic polymorphisms of ABCB1 SNPs as markers for ethnicity and ancestral origin. The analysis of haplotype and genotype can be useful in identifying the relation between ABCB1 polymorphism, disease susceptibility and drug disposition.Keywords: Genotype, Allele, MDR1, ABCB1, Polymorphism, Haplotype frequencie

Transfer of learning and patient outcome in simulated crisis resource management : a systematic review

PURPOSE: Simulation-based learning is increasingly used by healthcare professionals as a safe method to learn and practice non-technical skills, such as communication and leadership, required for effective crisis resource management (CRM). This systematic review was conducted to gain a better understanding of the impact of simulation-based CRM teaching on transfer of learning to the workplace and subsequent changes in patient outcomes. SOURCE: Studies on CRM, crisis management, crew resource management, teamwork, and simulation published up to September 2012 were searched in MEDLINE(®), EMBASE™, CINAHL, Cochrane Central Register of Controlled Trials, and ERIC. All studies that used simulation-based CRM teaching with outcomes measured at Kirkpatrick Level 3 (transfer of learning to the workplace) or 4 (patient outcome) were included. Studies measuring only learners' reactions or simple learning (Kirkpatrick Level 1 or 2, respectively) were excluded. Two authors independently reviewed all identified titles and abstracts for eligibility. PRINCIPAL FINDINGS: Nine articles were identified as meeting the inclusion criteria. Four studies measured transfer of simulation-based CRM learning into the clinical setting (Kirkpatrick Level 3). In three of these studies, simulation-enhanced CRM training was found significantly more effective than no intervention or didactic teaching. Five studies measured patient outcomes (Kirkpatrick Level 4). Only one of these studies found that simulation-based CRM training made a clearly significant impact on patient mortality. CONCLUSIONS: Based on a small number of studies, this systematic review found that CRM skills learned at the simulation centre are transferred to clinical settings, and the acquired CRM skills may translate to improved patient outcomes, including a decrease in mortality

Endothelial LRP1 transports amyloid-β1-42 across the blood-brain barrier

According to the neurovascular hypothesis, impairment of low-density lipoprotein receptor-related protein-1 (LRP1) in brain capillaries of the blood-brain barrier (BBB) contributes to neurotoxic amyloid-beta (A beta) brain accumulation and drives Alzheimer's disease (AD) pathology. However, due to conflicting reports on the involvement of LRP1 in A beta transport and the expression of LRP1 in brain endothelium, the role of LRP1 at the BBB is uncertain. As global Lrp1 deletion in mice is lethal, appropriate models to study the function of LRP1 are lacking. Moreover, the relevance of systemic A beta clearance to AD pathology remains unclear, as no BBB-specific knockout models have been available. Here, we developed transgenic mouse strains that allow for tamoxifen-inducible deletion of Lrp1 specifically within brain endothelial cells (Slo1c1-CreER(Tz) Lrp1(fl/fl) mice) and used these mice to accurately evaluate LRP1-mediated A beta BBB clearance in vivo. Selective deletion of Lrp1 in the brain endothelium of C57BL/6 mice strongly reduced brain efflux of injected [I-125] A beta(1-42). Additionally, in the 5xFAD mouse model of AD, brain endothelial-specific Lrp1 deletion reduced plasma A beta levels and elevated soluble brain A beta, leading to aggravated spatial learning and memory deficits, thus emphasizing the importance of systemic AD elimination via the BBB. Together, our results suggest that receptor-mediated A beta BBB clearance may be a potential target for treatment and prevention of A beta brain accumulation in AD

Emerging drug targets for Aβ and tau in Alzheimer's disease: a systematic review

Currently, treatment for Alzheimer's disease (AD) focuses on the cholinergic hypothesis and provides limited symptomatic effects. Research currently focuses on other factors that are thought to contribute to AD development such as tau proteins and Aβ deposits, and how modification of the associated pathology affects outcomes in patients. This systematic review summarizes and appraises the evidence for the emerging drugs affecting Aβ and tau pathology in AD. Methods A comprehensive, systematic online database search was conducted using the databases ScienceDirect and PubMed to include original research articles. A systematic review was conducted following a minimum set of standards, as outlined by The PRISMA Group 1. Specific inclusion and exclusion criteria were followed and studies fitting the criteria were selected. No human trials were included in this review. In vitro and in vivo AD models were used to assess efficacy to ensure studied agents were emerging targets without large bodies of evidence. Results The majority of studies showed statistically significant improvement (P < 0.05) of Aβ and/or tau pathology, or cognitive effects. Many studies conducted in AD animal models have shown a reduction in Aβ peptide burden and a reduction in tau phosphorylation post‐intervention. This has the potential to reduce plaque formation and neuronal degeneration. Conclusions There are many emerging targets showing promising results in the effort to modify the pathological effects associated with AD. Many of the trials also provided evidence of the clinical effects of such drugs reducing pathological outcomes, which was often demonstrated as an improvement of cognition

Mousebytes, an open-access high-throughput pipeline and database for rodent touchscreen-based cognitive assessment

© 2019, eLife Sciences Publications Ltd. All rights reserved. Open Science has changed research by making data accessible and shareable, contributing to replicability to accelerate and disseminate knowledge. However, for rodent cognitive studies the availability of tools to share and disseminate data is scarce. Automated touchscreen-based tests enable systematic cognitive assessment with easily standardised outputs that can facilitate data dissemination. Here we present an integration of touchscreen cognitive testing with an open-access database public repository (mousebytes.ca), as well as a Web platform for knowledge dissemination (https://touchscreencognition.org). We complement these resources with the largest dataset of age-dependent high-level cognitive assessment of mouse models of Alzheimer’s disease, expanding knowledge of affected cognitive domains from male and female mice of three strains. We envision that these new platforms will enhance sharing of protocols, data availability and transparency, allowing meta-analysis and reuse of mouse cognitive data to increase the replicability/reproducibility of datasets

Olive oil and prevention of chronic diseases: summary of an International conference

Abstract Olive oil is the foremost source of fat in the Mediterranean area and, among other features, sets the Mediterranean diet apart from other dietary regimens. In January 2018, the International Olive Council convened several worldwide experts at the Robert Mondavi Institute (Davis, CA), to discuss and summarize the available data on the effects of olive oil consumption on human health. In this paper, we critically provide a synthesis of the main reported findings, which underscore how and why consuming this oil as part of a balanced diet and healthful lifestyle improves prognosis and extends life- and health-spans

The restorative role of annexin A1 at the blood–brain barrier

Annexin A1 is a potent anti-inflammatory molecule that has been extensively studied in the peripheral immune system, but has not as yet been exploited as a therapeutic target/agent. In the last decade, we have undertaken the study of this molecule in the central nervous system (CNS), focusing particularly on the primary interface between the peripheral body and CNS: the blood–brain barrier. In this review, we provide an overview of the role of this molecule in the brain, with a particular emphasis on its functions in the endothelium of the blood–brain barrier, and the protective actions the molecule may exert in neuroinflammatory, neurovascular and metabolic disease. We focus on the possible new therapeutic avenues opened up by an increased understanding of the role of annexin A1 in the CNS vasculature, and its potential for repairing blood–brain barrier damage in disease and aging