A Typical Case of Multisystem Inflammatory Syndrome in a 10-yearold Girl with COVID-19: A Case Report from Ethiopia

BACKGROUND: Severe acute respiratory syndrome-Corona Virus-2 (SARS-CoV2) has infected more than 500 million and has claimed the lives of more than 6.1 million people worldwide.CASE: We are presenting a 10-year-old girl who fulfilled the criteria of Multisystem inflammatory disease associated with COVID-19(MIS-C). She had fever of > 3 days, muco-cutaneous lesions, hypotension/shock, myocardial dysfunction, acute gastrointestinal symptoms, elevated markers of inflammation, coagulopathy without other microbial causes and positive COVID RT-PCR test.CONCLUSIONS: When pediatric patients present with the above symptoms and signs we should have a high index of suspicion of MIS-C for timely action and better outcome

Urban Open space Use in Addis Ababa: The case of Meskel Square

Urban planning and design has proven to be an important element in shaping life styles, solving problems and giving new ways of living in the urban arena. The quality of urban life is one of the big goals that the field tries to reach. Urban open spaces are known to enhance the quality of urban life. So, every city needs these spaces. The planning and design of urban open spaces have been practiced in different parts of the world in different ways. The practice and use of these spaces differed from place to place as well as from time to time. A good approach in the planning and designing of these spaces is to first study the past and current trends of urban open space usage in a place. The existing local culture acts as a guiding element to design a space suitable for the need of the locals. This paper is a study on a local culture of using urban open space. The study is about the user trend of urban open spaces in the city of Addis Ababa. The paper covers a general history and development of urban open space usage in the city. It focuses on a case area which is found in the center of the city and has a significant historical perspective as well. The development and current use of this space will indicate the direction of urban open space trends in the city. This will in turn help the future approaches in planning and design of such spaces. So, the paper includes the case area study, its data analysis, findings and finally suggestion of problems found on the case area stu

The University of Gondar, Queen’s University and Mastercard Foundation Scholars Program: A partnership for disability-inclusive higher education in Ethiopia

This article describes the development and implementation process of an innovative 10-year partnership that draws on the strengths of existing community-based rehabilitation programs to support new education and leadership development activities in Ethiopia. Current global estimates indicate that over 17 million people may be affected by disability in Ethiopia. The national population projection for 2017 indicates that approximately 80 per cent of the population resides in underserved rural areas, with limited to no access to necessary health, rehabilitation, or social services. The University of Gondar (UoG) in Ethiopia has been serving people with disabilities in and around the North Gondar Zone since its inception in the mid-1950s. Over the years, its various units have designed and implemented numerous projects, employing alternative institutional and community-based models to promote the wellbeing of people with disabilities. Lessons drawn from these initiatives and shifts in health and social work practice informed UoG’s decision to establish its Community-Based Rehabilitation (CBR) program in 2005. Given a shared commitment to the principles and practice of CBR, the UoG is presently collaborating with the International Centre for the Advancement of Community Based Rehabilitation (ICACBR) at Queen’s University in Canada to create new disability-related education and mentorship opportunities. These include community-based research and internship opportunities for undergraduate and graduate scholars through a shared Mastercard Foundation Scholars Program. The two institutions, in collaboration with the Mastercard Foundation, have an overall goal of creating a disability-inclusive campus and regional rehabilitation hub at UoG. In this article, the authors discuss the unique collaborative structure of project management and implementation, and the embeddedness of university-community engagement to meet project objectives informed by the North–South/South–North partnership models. They also provide critical insights to, and reflections on, the challenges inherent in international, interdisciplinary university-community collaboration and the benefits from enhancing higher education in both Ethiopia and Canada. In contrast to shorter term or smaller projects that rely heavily on individual champions, this article focuses on larger scale, process-oriented institutional learning

Health-related quality of life of adults with cutaneous leishmaniasis at ALERT Hospital, Addis Ababa, Ethiopia

BACKGROUND: Cutaneous leishmaniasis (CL) is a growing public health threat in Ethiopia. Leishmania aethiopica is the predominant causative organism. Affected individuals develop chronic skin lesions on exposed parts of the body, mostly on the face, which are disfiguring and cause scarring. The effects of CL on the health-related quality of life (HRQoL) of affected individuals has not been assessed in Ethiopia. OBJECTIVE: To assess HRQoL in adults with active CL at ALERT Hospital, Addis Ababa, Ethiopia. METHODS: A cross-sectional study was done using the Amharic version of the Dermatology Life Quality Index (DLQI). Trained health staff administered the DLQI. RESULTS: Three hundred and two adults with active CL participated and all of them exhibited a reduced HRQoL. The median DLQI score was 10 (IQR 8). Almost half of the participants reported very poor HRQoL, 36.4% and 11.3% fell within the very large and extremely large effect categories respectively. DLQI scores were higher (median 18) in patients diagnosed with diffuse cutaneous leishmaniasis (DCL) compared to those with localized cutaneous leishmaniasis (LCL). The DLQI domain of 'work and school' was the most affected, scoring 73.3% and 66.6% of total possible score for female and male respectively, followed by that of 'symptom and feeling' (at 50.0% and 56.6% for female and male respectively). Men were more affected than women in the domains of 'leisure' (P = 0.002) and 'personal relationships' (P = 0.001). In the multivariate ordinal logistic regression site of lesion, clinical phenotype and age of participant remained associated with significantly poor HRQoL. CONCLUSION: The HRQoL impairment associated with CL is significant. Thus, patient-reported outcome measure should be used to assess the efficacy of treatments along with clinical outcome measures

Novel CCL21-Vault Nanocapsule Intratumoral Delivery Inhibits Lung Cancer Growth

Based on our preclinical findings, we are assessing the efficacy of intratumoral injection of dendritic cells (DC) transduced with an adenoviral vector expressing the secondary lymphoid chemokine (CCL21) gene (Ad-CCL21-DC) in a phase I trial in advanced non-small cell lung cancer (NSCLC). While this approach shows immune enhancement, the preparation of autologous DC for CCL21 genetic modification is cumbersome, expensive and time consuming. We are evaluating a non-DC based approach which utilizes vault nanoparticles for intratumoral CCL21 delivery to mediate antitumor activity in lung cancer.Here we describe that vault nanocapsule platform for CCL21 delivery elicits antitumor activity with inhibition of lung cancer growth. Vault nanocapsule packaged CCL21 (CCL21-vaults) demonstrated functional activity in chemotactic and antigen presenting activity assays. Recombinant vaults impacted chemotactic migration of T cells and this effect was predominantly CCL21 dependent as CCL21 neutralization abrogated the CCL21 mediated enhancement in chemotaxis. Intratumoral administration of CCL21-vaults in mice bearing lung cancer enhanced leukocytic infiltrates (CXCR3(+)T, CCR7(+)T, IFNγ(+)T lymphocytes, DEC205(+) DC), inhibited lung cancer tumor growth and reduced the frequencies of immune suppressive cells [myeloid derived suppressor cells (MDSC), T regulatory cells (Treg), IL-10 T cells]. CCL21-vaults induced systemic antitumor responses by augmenting splenic T cell lytic activity against parental tumor cells.This study demonstrates that the vault nanocapsule can efficiently deliver CCL21 to sustain antitumor activity and inhibit lung cancer growth. The vault nanocapsule can serve as an "off the shelf" approach to deliver antitumor cytokines to treat a broad range of malignancies

Recruitment of the Major Vault Protein by InlK: A Listeria monocytogenes Strategy to Avoid Autophagy

L. monocytogenes is a facultative intracellular bacterium responsible for listeriosis. It is able to invade, survive and replicate in phagocytic and non-phagocytic cells. The infectious process at the cellular level has been extensively studied and many virulence factors have been identified. Yet, the role of InlK, a member of the internalin family specific to L. monocytogenes, remains unknown. Here, we first show using deletion analysis and in vivo infection, that InlK is a bona fide virulence factor, poorly expressed in vitro and well expressed in vivo, and that it is anchored to the bacterial surface by sortase A. We then demonstrate by a yeast two hybrid screen using InlK as a bait, validated by pulldown experiments and immunofluorescence analysis that intracytosolic bacteria via an interaction with the protein InlK interact with the Major Vault Protein (MVP), the main component of cytoplasmic ribonucleoproteic particules named vaults. Although vaults have been implicated in several cellular processes, their role has remained elusive. Our analysis demonstrates that MVP recruitment disguises intracytosolic bacteria from autophagic recognition, leading to an increased survival rate of InlK over-expressing bacteria compared to InlK− bacteria. Together these results reveal that MVP is hijacked by L. monocytogenes in order to counteract the autophagy process, a finding that could have major implications in deciphering the cellular role of vault particles

Corrigendum: A systematic review and economic evaluation of bisphosphonates for the prevention of fragility fractures

Abstract Background Fragility fractures are fractures that result from mechanical forces that would not ordinarily result in fracture. Objectives To evaluate the clinical effectiveness and safety of bisphosphonates [alendronic acid (Fosamax® and Fosamax® Once Weekly, Merck Sharp & Dohme Ltd), risedronic acid (Actonel® and Actonel Once a Week®, Warner Chilcott UK Ltd), ibandronic acid (Bonviva®, Roche Products Ltd) and zoledronic acid (Aclasta®, Novartis Pharmaceuticals UK Ltd)] for the prevention of fragility fracture and to assess their cost-effectiveness at varying levels of fracture risk. Data sources For the clinical effectiveness review, six electronic databases and two trial registries were searched: MEDLINE, EMBASE, The Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, Web of Science and BIOSIS Previews, Clinicaltrials.gov and World Health Organization International Clinical Trials Registry Platform. Searches were limited by date from 2008 until September 2014. Review methods A systematic review and network meta-analysis (NMA) of effectiveness studies were conducted. A review of published economic analyses was undertaken and a de novo health economic model was constructed. Discrete event simulation was used to estimate lifetime costs and quality-adjusted life-years (QALYs) for each bisphosphonate treatment strategy and a strategy of no treatment for a simulated cohort of patients with heterogeneous characteristics. The model was populated with effectiveness evidence from the systematic review and NMA. All other parameters were estimated from published sources. A NHS and Personal Social Services perspective was taken, and costs and benefits were discounted at 3.5% per annum. Fracture risk was estimated from patient characteristics using the QFracture® (QFracture-2012 open source revision 38, Clinrisk Ltd, Leeds, UK) and FRAX® (web version 3.9, University of Sheffield, Sheffield, UK) tools. The relationship between fracture risk and incremental net benefit (INB) was estimated using non-parametric regression. Probabilistic sensitivity analysis (PSA) and scenario analyses were used to assess uncertainty. Results Forty-six randomised controlled trials (RCTs) were included in the clinical effectiveness systematic review, with 27 RCTs providing data for the fracture NMA and 35 RCTs providing data for the femoral neck bone mineral density (BMD) NMA. All treatments had beneficial effects on fractures versus placebo, with hazard ratios varying from 0.41 to 0.92 depending on treatment and fracture type. The effects on vertebral fractures and percentage change in BMD were statistically significant for all treatments. There was no evidence of a difference in effect on fractures between bisphosphonates. A statistically significant difference in the incidence of influenza-like symptoms was identified from the RCTs for zoledronic acid compared with placebo. Reviews of observational studies suggest that upper gastrointestinal symptoms are frequently reported in the first month of oral bisphosphonate treatment, but pooled analyses of placebo-controlled trials found no statistically significant difference. A strategy of no treatment was estimated to have the maximum INB for patients with a 10-year QFracture risk under 1.5%, whereas oral bisphosphonates provided maximum INB at higher levels of risk. However, the PSA suggested that there is considerable uncertainty regarding whether or not no treatment is the optimal strategy until the QFracture score is around 5.5%. In the model using FRAX, the mean INBs were positive for all oral bisphosphonate treatments across all risk categories. Intravenous bisphosphonates were estimated to have lower INBs than oral bisphosphonates across all levels of fracture risk when estimated using either QFracture or FRAX. Limitations We assumed that all treatment strategies are viable alternatives across the whole population. Conclusions Bisphosphonates are effective in preventing fragility fractures. However, the benefit-to-risk ratio in the lowest-risk patients may be debatable given the low absolute QALY gains and the potential for adverse events. We plan to extend the analysis to include non-bisphosphonate therapies. Study registration This study is registered as PROSPERO CRD42013006883. Funding The National Institute for Health Research Health Technology Assessment programme

Changes in T Cell and Dendritic Cell Phenotype from Mid to Late Pregnancy Are Indicative of a Shift from Immune Tolerance to Immune Activation.

During pregnancy, the mother allows the immunologically distinct fetoplacental unit to develop and grow. Opinions are divided as to whether this represents a state of fetal-specific tolerance or of a generalized suppression of the maternal immune system. We hypothesized that antigen-specific T cell responses are modulated by an inhibitory T cell phenotype and modified dendritic cell (DC) phenotype in a gestation-dependent manner. We analyzed changes in surface markers of peripheral blood T cells, ex vivo antigen-specific T cell responses, indoleamine 2,3-dioxygenase (IDO) activity (kynurenine/tryptophan ratio, KTR), plasma neopterin concentration, and the in vitro expression of progesterone-induced blocking factor (PIBF) in response to peripheral blood mononuclear cell culture with progesterone. We found that mid gestation is characterized by reduced antigen-specific T cell responses associated with (1) predominance of effector memory over other T cell subsets; (2) upregulation of inhibitory markers (programmed death ligand 1); (3) heightened response to progesterone (PIBF); and (4) reduced proportions of myeloid DC and concurrent IDO activity (KTR). Conversely, antigen-specific T cell responses normalized in late pregnancy and were associated with increased markers of T cell activation (CD38, neopterin). However, these changes occur with a simultaneous upregulation of immune suppressive mechanisms including apoptosis (CD95), coinhibition (TIM-3), and immune regulation (IL-10) through the course of pregnancy. Together, our data suggest that immune tolerance dominates in the second trimester and that it is gradually reversed in the third trimester in association with immune activation as the end of pregnancy approaches