COVID-19 on the Nile: Review on the Management and Outcomes of the COVID-19 Pandemic in the Arab Republic of Egypt from February to August 2020.

As the world fights the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the World Health Organization (WHO) reports that over 17 million people globally were infected with SARS-CoV-2 as of 1 August 2020. Although infections are asymptomatic in 80% of cases, severe respiratory illness occurs in 20% of cases, requiring hospitalization and highly specialized intensive care. The WHO, under the International Health Regulations, declared this pandemic a public health emergency of international concern; it has affected nearly all health systems worldwide. The health system in Egypt, similar to many others, was severely challenged when confronted with the need for urgent and major expansion required to manage such a significant pandemic. This review uses publicly available data to provide an epidemiological summary of the COVID-19 pandemic behavior during the first wave of the outbreak in Egypt. The article covers mathematical modeling predictions, Egypt's healthcare system, economic and social impacts of COVID-19, as well as national responses that were crucial to the initial containment of the pandemic. We observed how the government managed the outbreak by enhancing testing capacity, contact tracing, announcing public health and social measures (PHSMs), as well as allocating extra funds and human resources to contain SARS-COV-2. Prospectively, economic losses from major sources of revenues-tourism, travel, and trade-may be reflected in future timelines, as Egypt continues to control cases and loss of life from COVID-19. Overall, trends indicate that the spread of COVID-19 in Egypt was initially contained. Revalidation of prediction models and follow-up studies may reveal the aftermath of the pandemic and how well it was managed in Egypt.

A multidimensional framework for rating health system performance and sustainability: A nine plus one ranking system.

BACKGROUND: Health Care provision in terms of prevention, detection and treatment is primarily dependent on the quality of the hosting Health System. In its health report 2000, the WHO's attempt to assess and rank health systems' quality Worldwide was heavily criticized. We propose a novel framework for health system performance and ranking using three indicators for three domains; general health system performance, clinical outcome of treatment applied to the main causes of death and health system sustainability domains. METHODS: Each domain was rated as "A - high", "B - intermediate" or "C - poor" according to the aggregate score values of its three indicators. Hence the highest rank a health system can achieve is "AAA" and the lowest is "CCC". If there is a need to define a "numerical rank" to further differentiate health systems with similar rating from one another, the total health expenditure per capita per year was used as an additional "number 10" indicator to achieve that level of differentiation. The framework was applied to Health Systems serving most of the World population including China, India, Brazil, USA, Russia, Germany, Japan, UK, France, Singapore and Switzerland. Data pertinent to each indicator was captured from published reports in peer-reviewed journals and/or from official websites. A Delphi survey was conducted for data not available online. RESULTS: Among the 11 health systems tested, no one scored AAA, Switzerland, France, Germany and Japan scored AAB, Singapore scored ABB, UK scored BBB, USA, Russia and China scored BBC, Brazil scored BCC while India scored CCC. Total health expenditure per capita per year lead to ranking Switzerland first followed by France, Germany, and Japan. CONCLUSION: This novel ranking system is a practical and an applicable tool that test health system performance and sustainability. It can be utilized to guide all organizations, people and actions whose primary intent is to promote, restore or maintain health to achieve their targets. An International Health System Ranking database that will be hosted by the Institute of Global, Health, Faculty of Medicine, University of Geneva, Switzerland.

Derivation and characterization of human fetal MSCs: an alternative cell source for large-scale production of cardioprotective microparticles.

The therapeutic effects of mesenchymal stem cells (MSCs) transplantation are increasingly thought to be mediated by MSC secretion. We have previously demonstrated that human ESC-derived MSCs (hESC-MSCs) produce cardioprotective microparticles in pig model of myocardial ischemia/reperfusion (MI/R) injury. As the safety and availability of clinical grade human ESCs remain a concern, MSCs from fetal tissue sources were evaluated as alternatives. Here we derived five MSC cultures from limb, kidney and liver tissues of three first trimester aborted fetuses and like our previously described hESC-derived MSCs; they were highly expandable and had similar telomerase activities. Each line has the potential to generate at least 10(16-19) cells or 10(7-10) doses of cardioprotective secretion for a pig model of MI/R injury. Unlike previously described fetal MSCs, they did not express pluripotency-associated markers such as Oct4, Nanog or Tra1-60. They displayed a typical MSC surface antigen profile and differentiated into adipocytes, osteocytes and chondrocytes in vitro. Global gene expression analysis by microarray and qRT-PCR revealed a typical MSC gene expression profile that was highly correlated among the five fetal MSC cultures and with that of hESC-MSCs (r(2)>0.90). Like hESC-MSCs, they produced secretion that was cardioprotective in a mouse model of MI/R injury. HPLC analysis of the secretion revealed the presence of a population of microparticles with a hydrodynamic radius of 50-65 nm. This purified population of microparticles was cardioprotective at approximately 1/10 dosage of the crude secretion.

Contractile and vasorelaxant effects of hydrogen sulfide and its biosynthesis in the human internal mammary artery.

This study aimed to test these hypotheses: cystathionine gamma-lyase (CSE) is expressed in a human artery, it generates hydrogen sulfide (H(2)S), and H(2)S relaxes a human artery. H(2)S is produced endogenously in rat arteries from cysteine by CSE. Endogenously produced H(2)S dilates rat resistance arteries. Although CSE is expressed in rat arteries, its presence in human blood vessels has not been described. In this study, we showed that both CSE mRNA, determined by reverse transcription-polymerase chain reaction, and CSE protein, determined by Western blotting, apparently occur in the human internal mammary artery (internal thoracic artery). Artery homogenates converted cysteine to H(2)S, and the H(2)S production was inhibited by dl-propargylglycine, an inhibitor of CSE. We also showed that H(2)S relaxes phenylephrine-precontracted human internal mammary artery at higher concentrations but produces contraction at low concentrations. The latter contractions are stronger in acetylcholine-prerelaxed arteries, suggesting inhibition of nitric oxide action. The relaxation is partially blocked by glibenclamide, an inhibitor of K(ATP) channels. The present results indicate that CSE protein is expressed in human arteries, that human arteries synthesize H(2)S, and that higher concentrations of H(2)S relax human arteries, in part by opening K(ATP) channels. Low concentrations of H(2)S contract the human internal mammary artery, possibly by reacting with nitric oxide to form an inactive nitrosothiol. The possibility that CSE, and the H(2)S it generates, together play a physiological role in regulating the diameter of arteries in humans, as has been demonstrated in rats, should be considered.

Late complex biventricular repair after bidirectional cavopulmonary shunt.

A child diagnosed with transposition of great arteries, multiple (Swiss cheese) ventricular septal defects, and a small right ventricle underwent pulmonary artery banding and patent ductus arteriosus ligation at the age of six months. At the age of three years bidirectional cavopulmonary shunt was performed as a first stage for univentricular repair. However, the patient was lost follow-up for four years, following which further evaluation showed that the right ventricle was reasonably adequate to support pulmonary circulation if the ventricular septal defects (VSDs) were closed using percutaneous techniques. Four VSDs were then closed using Amplatzer devices (AGA Medical Corporation, Plymouth, MN, USA). At the age of eight years she underwent complex biventricular repair in the form of arterial switch, closure of atrial septal defect, take down of Glenn shunt, and reanastomosis of the distal end of the superior vena cava to the distal superior vena cava stump on the right atrium. One year later the patient is alive and well. In conclusion; biventricular repair may be considered before completion of Fontan whenever cardiac anatomy allows.

Embryonic cell lines with endothelial potential: an in vitro system for studying endothelial differentiation.

OBJECTIVE: Endothelial differentiation is a fundamental process in angiogenesis and vasculogenesis with implications in development, normal physiology, and pathology. To better understand this process, an in vitro cellular system that recapitulates endothelial differentiation and is amenable to experimental manipulations is required. METHODS AND RESULTS: Embryonic cell lines that differentiate exclusively into endothelial cells were derived from early mouse embryos using empirical but reproducible culture techniques without viral or chemical transformation. The cells were not pluripotent and expressed reduced levels of Oct 4 and Rex-1. They were non-tumorigenic with a population doubling time of approximately 15 hours. When plated on matrigel, they readily differentiated to form patent tubular structures with diameters of 30 to 150 microm. The differentiated cells endocytosed acetylated low-density lipoprotein (LDL) and began to express endothelial-specific markers such as CD34, CD31, Flk-1, TIE2, P-selectin, Sca-1, and thy-1. They also expressed genes essential for differentiation and maintenance of endothelial lineages, eg, Flk-1, vascular endothelial growth factor (VEGF), and angiopoietin-1. When transplanted into animal models, these cells incorporated into host vasculature. CONCLUSIONS: These cell lines can undergo in vitro and in vivo endothelial differentiation that recapitulated known endothelial differentiation pathways. Therefore, they are ideal for establishing an in vitro cellular system to study endothelial differentiation.

Homocysteine is positively associated with cytokine IL-18 plasma levels in coronary artery bypass surgery patients.

Homocysteine, cytokines (IL-18, IL-6, IL-8) are involved in vascular inflammation and coronary artery disease. Homocysteine influences endothelial IL-6 and IL-8 cytokine expression and release, however, an association between homocysteine and IL-18 has not been previously investigated in endothelial/smooth muscle cells and or in coronary artery disease. We report in 9 coronary artery bypass surgery (CABG) patients a positive correlation r = 0.86 between homocysteine and IL-18 plasma levels (p < 0.05). Plasma IL-18 levels are significantly higher in those patients with elevated homocysteine compared to those with normal levels (p < 0.02; 153 +/- 19 pg/ml versus 116 +/- 14 pg/ml respectively). Our in vitro cell culture studies suggest that the source of IL-18 in CABG patients with elevated homocysteine is not from vascular smooth muscle or endothelial cells.

Hepatic expression of PPARalpha, a molecular target of fibrates, is regulated during inflammation in a gender-specific manner.

Dyslipidemia, inflammation and gender are major risk factors in cardiovascular disease. Here we show that hepatic expression of Peroxisome proliferator-activated receptor alpha (PPARalpha), a nuclear receptor that regulates lipid metabolism and inflammation, is regulated in a gender-specific manner during lipopolysaccharide (LPS)-induced systemic inflammation. Immediately following LPS-induced systemic inflammation, hepatic PPARalpha mRNA level decreased dramatically in mice. It was restored to baseline within 24 h in females but remained below baseline for >72 h in male mice. In gonadectomized mice of both sexes, PPARalpha mRNA level was restored to baseline within 48 h after the initial decrease.

Myocardial infarction in the C57BL/6J mouse: a quantifiable and highly reproducible experimental model.

INTRODUCTION: The laboratory mouse is a powerful tool in cardiovascular research. In this report, we describe a method for a reproducible mouse myocardial infarction model that would allow subsequent comparative and quantitative studies on molecular and pathophysiological variables. METHODS: (A) The distribution of the major coronary arteries including the septal artery in the left ventricle of the C57BL/6J mice (n=20) was mapped by perfusion of latex dye or fluorescent beads through the aorta. (B) The territory of myocardial infarction after the ligation of the most proximal aspect of the left anterior descending (LAD) coronary artery was quantified. (C) The consistency in the histological changes parallel to the infarction at different time points was analyzed. RESULTS: (A) The coronary artery tree of the mouse is different from human and, particularly, in regard to the blood supply of the septum. (B) Contrary to previous belief, the septal coronary artery in the mouse is variable in origin. (C) A constant ligation of the LAD immediately below the left auricular level ensures a statistically significant reproducible infarct size. (D) The ischemic changes can be monitored at a histological level in a way similar to what is described in the human. CONCLUSION: We illustrate a method for maximal reproducibility of experimental acute myocardial infarction in the mouse model, due to a consistent loss of perfusion in the lower half of the left ventricle. This will allow the study of molecular and physiological variables in a controlled and quantifiable experimental model environment.

Whole bone marrow transplantation induces angiogenesis following acute ischemia.

Several recent studies have shown that purified subsets of bone marrow (BM) cells can differentiate into endothelial, cardiac, and other cell types. During coronary artery bypass graft (CABG) surgery, sternal BM is routinely discarded. To determine if this BM can be used to induce angiogenesis and augment perfusion of the cardiac tissues after CABG, a simplified and more practical approach of using whole BM extract was tried to determine whether it would be adequate for the induction of BM-derived angiogenesis in experimental acute limb ischemia. BM was prepared from FVB/N-TgN(TIE2 lacZ)182 Sato (Tie2-lacZ) or B6.129S7-Gtrosa 26 (Rosa 26) mice that express beta-galactosidase (beta-gal) in endothelial cells and most adult tissues, respectively. Acute limb ischemia was induced in either C57BL6/J or FVB/N mice by double ligation of the left femoral artery just distal to the profunda femoral artery branch. Occlusion of the ligated artery was verified by angiography. The study group (n = 31) received an intramuscular injection of 50 micro l containing 1 x 10(6) BM cells, 5 mm proximal to the site of ligation. Experimental controls (n = 21) had an intramuscular injection of 50 micro l of saline. Angiogenesis in the mice was assessed by histological analysis. BM-derived beta-gal(+) cells were observed to aggregate in the vicinity of the ligated artery and not in the injected musculature BM-derived endothelial cells were incorporated within capillaries and small size blood vessels near the site of ligation. Generation of BM-derived blood vessels in experimental acute limb ischemia does not require purification of specific subset of cells. The elimination of cell purification will enhance the ease of using BM transplantation in generating blood vessels.

Generation of hybrid cell lines with endothelial potential from spontaneous fusion of adult bone marrow cells with embryonic fibroblast feeder.

We have previously isolated mouse embryonic cell lines with endothelial potential using a simple empirical approach. In an attempt to isolate similar cell lines from adult mouse bone marrow (BM), BM cells were cultured on mitotically inactive mouse embryonic fibroblast (MEF) feeder cells. Several cell lines with putative endothelial potential were generated. They expressed endothelial-specific genes and formed vascular-like structures when plated on matrigel. When transplanted into appropriate mouse models, they incorporated into the endothelium of the vasculature. Similar cell lines were also obtained using human or porcine BM. None of these lines induced tumor formation when transplanted into immunodeficient Rag1-/- mice. However, all the lines were aneuploid with genetic markers from BM samples and the MEF feeder, suggesting that they resulted from a non-species-specific fusion of a BM cell and mitotically inactive MEF. Together, these lines demonstrated for the first time that BM cells can also undergo fusion with commonly used mitotically inactive feeder cells. Although these fusion cell lines were culture artifacts, their derivation would be useful in understanding fusion of BM cells with other cell types, and their endothelial potential will also be useful in characterizing endothelial differentiation.

Coronary bypass surgery in patients on thyroxin replacement therapy.

The outcome of coronary bypass surgery was analyzed in 25 patients who were on thyroxin replacement therapy for chronic thyroid disorders at the time of operation. It was hypothesized that if such patients were given only their routine dose of thyroxin on the day of surgery, hemodynamic and cardiorespiratory recovery may be poor. All the patients on thyroxin replacement therapy were given their routine dose of thyroxin orally or via a nasogastric tube in the perioperative period. No supplemental dose was used. Based on preoperative levels of thyroid stimulating hormone, 68% of these patients were biochemically hypothyroid prior to surgery. Analysis of a large number of variables showed no difference in outcome against a control group who had no previous thyroid problems. We conclude that routine thyroxin administration is all that is required for a satisfactory outcome in patients undergoing coronary bypass surgery while on thyroxin replacement therapy.

Consultation on the Libyan health systems: towards patient-centred services.

The extra demand imposed upon the Libyan health services during and after the Libyan revolution in 2011 led the ailing health systems to collapse. To start the planning process to re-engineer the health sector, the Libyan Ministry of Health in collaboration with the World Health Organisation (WHO) and other international experts in the field sponsored the National Health Systems Conference in Tripoli, Libya, between the 26th and the 30th of August 2012. The aim of this conference was to study how health systems function at the international arena and to facilitate a consultative process between 500 Libyan health experts in order to identify the problems within the Libyan health system and propose potential solutions. The scientific programme adopted the WHO health care system framework and used its six system building blocks: i) Health Governance; ii) Health Care Finance; iii) Health Service Delivery; iv) Human Resources for Health; v) Pharmaceuticals and Health Technology; and vi) Health Information System. The experts used a structured approach starting with clarifying the concepts, evaluating the current status of that health system block in Libya, thereby identifying the strengths, weaknesses, and major deficiencies. This article summarises the 500 health expert recommendations that seized the opportunity to map a modern health systems to take the Libyan health sector into the 21st century.

Management-oriented classification of mitral valve regurgitation.

Mitral regurgitation (MR) has previously been classified into rheumatic, primary, and secondary MR according to the underlying disease process. Carpentier's/Duran functional classifications are apt in describing the mechanism(s) of MR. Modern management of MR, however, depends primarily on the severity of MR, status of the left ventricular function, and the presence or absence of symptoms, hence the need for a management-oriented classification of MR. In this paper we describe a classification of MR into 4 phases according to LV function: phase I = MR with normal left ventricle, phase II = MR with normal ejection fraction (EF) and indirect signs of LV dysfunction such as pulmonary hypertension and/or recent onset atrial fibrillation, phase III = EF ≥ 30%-< 50% and/or mild to moderate LV dilatation (ESID 40-54 mm), and phase IV = EF < 30% and/or severe LV dilatation (ESDID ≥ 55 mm). Each phase is further subdivided into three stages: stage "A" with an effective regurgitant orifice (ERO) < 20 mm, stage "B" with an ERO = 20-39 mm, and stage "C" with an ERO ≥ 40 mm. Evidence-based indications and outcome of intervention for MR will also be discussed.

Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury.

Human ESC-derived mesenchymal stem cell (MSC)-conditioned medium (CM) was previously shown to mediate cardioprotection during myocardial ischemia/reperfusion injury through large complexes of 50-100 nm. Here we show that these MSCs secreted 50- to 100-nm particles. These particles could be visualized by electron microscopy and were shown to be phospholipid vesicles consisting of cholesterol, sphingomyelin, and phosphatidylcholine. They contained coimmunoprecipitating exosome-associated proteins, e.g., CD81, CD9, and Alix. These particles were purified as a homogeneous population of particles with a hydrodynamic radius of 55-65 nm by size-exclusion fractionation on a HPLC. Together these observations indicated that these particles are exosomes. These purified exosomes reduced infarct size in a mouse model of myocardial ischemia/reperfusion injury. Therefore, MSC mediated its cardioprotective paracrine effect by secreting exosomes. This novel role of exosomes highlights a new perspective into intercellular mediation of tissue injury and repair, and engenders novel approaches to the development of biologics for tissue repair.