Al Faisal University

Riyadh, Saudi Arabia

Al Faisal University

Riyadh, Saudi Arabia
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Memish Z.A.,Global Center for Mass Gatherings Medicine | Memish Z.A.,Ministry of Health | Memish Z.A.,Al Faisal University | Zumla A.I.,Global Center for Mass Gatherings Medicine | And 7 more authors.
New England Journal of Medicine | Year: 2013

A human coronavirus, called the Middle East respiratory syndrome coronavirus (MERS-CoV), was first identified in September 2012 in samples obtained from a Saudi Arabian businessman who died from acute respiratory failure. Since then, 49 cases of infections caused by MERS-CoV (previously called a novel coronavirus) with 26 deaths have been reported to date. In this report, we describe a family case cluster of MERS-CoV infection, including the clinical presentation, treatment outcomes, and household relationships of three young men who became ill with MERS-CoV infection after the hospitalization of an elderly male relative, who died of the disease. Twenty-four other family members living in the same household and 124 attending staff members at the hospitals did not become ill. MERS-CoV infection may cause a spectrum of clinical illness. Although an animal reservoir is suspected, none has been discovered. Meanwhile, global concern rests on the ability of MERS-CoV to cause major illness in close contacts of patients. Copyright © 2013 Massachusetts Medical Society.

Assiri A.,Global Center for Mass Gatherings Medicine | McGeer A.,University of Toronto | Perl T.M.,Johns Hopkins University | Price C.S.,University of Colorado at Denver | And 17 more authors.
New England Journal of Medicine | Year: 2013

BACKGROUND: In September 2012, the World Health Organization reported the first cases of pneumonia caused by the novel Middle East respiratory syndrome coronavirus (MERSCoV). We describe a cluster of health care-acquired MERS-CoV infections. METHODS: Medical records were reviewed for clinical and demographic information and determination of potential contacts and exposures. Case patients and contacts were interviewed. The incubation period and serial interval (the time between the successive onset of symptoms in a chain of transmission) were estimated. Viral RNA was sequenced. RESULTS: Between April 1 and May 23, 2013, a total of 23 cases of MERS-CoV infection were reported in the eastern province of Saudi Arabia. Symptoms included fever in 20 patients (87%), cough in 20 (87%), shortness of breath in 11 (48%), and gastrointestinal symptoms in 8 (35%); 20 patients (87%) presented with abnormal chest radiographs. As of June 12, a total of 15 patients (65%) had died, 6 (26%) had recovered, and 2 (9%) remained hospitalized. The median incubation period was 5.2 days (95% confidence interval [CI], 1.9 to 14.7), and the serial interval was 7.6 days (95% CI, 2.5 to 23.1). A total of 21 of the 23 cases were acquired by person-to-person transmission in hemodialysis units, intensive care units, or in-patient units in three different health care facilities. Sequencing data from four isolates revealed a single monophyletic clade. Among 217 household contacts and more than 200 health care worker contacts whom we identified, MERS-CoV infection developed in 5 family members (3 with laboratory-confirmed cases) and in 2 health care workers (both with laboratory-confirmed cases). CONCLUSIONS: Person-to-person transmission of MERS-CoV can occur in health care settings and may be associated with considerable morbidity. Surveillance and infection-control measures are critical to a global public health response. Copyright © 2013 Massachusetts Medical Society.

Al-Tawfiq J.A.,Saudi Aramco | Al-Tawfiq J.A.,Indiana University | Zumla A.,University College London | Zumla A.,Global Center for Mass Gatherings Medicine | And 6 more authors.
The Lancet Infectious Diseases | Year: 2014

Several new viral respiratory tract infectious diseases with epidemic potential that threaten global health security have emerged in the past 15 years. In 2003, WHO issued a worldwide alert for an unknown emerging illness, later named severe acute respiratory syndrome (SARS). The disease caused by a novel coronavirus (SARS-CoV) rapidly spread worldwide, causing more than 8000 cases and 800 deaths in more than 30 countries with a substantial economic impact. Since then, we have witnessed the emergence of several other viral respiratory pathogens including influenza viruses (avian influenza H5N1, H7N9, and H10N8; variant influenza A H3N2 virus), human adenovirus-14, and Middle East respiratory syndrome coronavirus (MERS-CoV). In response, various surveillance systems have been developed to monitor the emergence of respiratory-tract infections. These include systems based on identification of syndromes, web-based systems, systems that gather health data from health facilities (such as emergency departments and family doctors), and systems that rely on self-reporting by patients. More effective national, regional, and international surveillance systems are required to enable rapid identification of emerging respiratory epidemics, diseases with epidemic potential, their specific microbial cause, origin, mode of acquisition, and transmission dynamics. © 2014 Elsevier Ltd.

DeNiro M.,King Faisal Specialist Hospital And Research Center | Al-Mohanna F.A.,King Faisal Specialist Hospital And Research Center | Al-Mohanna F.A.,Al Faisal University
PLoS ONE | Year: 2014

Retinal ischemia promotes the upregulation of VEGF expression and accounts for most pathological features of retinal neovascularization (NV). Paradoxically, VEGF remains the pivotal stimulator of ocular NV, despite the absence of ischemia. Therefore, the central question arises as to how the various molecular mechanisms interplay in ischemia-independent NV. It's been suggested that NFκB plays a crucial role in the pathogenesis of diabetic vasculopathies. Here, we dissected the molecular mechanism of ocular NV in the rho/VEGF transgenic mouse model, which develops subretinal NV in ischemiaindependent microenvironment. Furthermore, we examined whether intravitreal administration of YC-1, a HIF-1 inhibitor, can modulate the activation of NFκB and its downstream angiogenic signaling in the mouse retina. We demonstrated that YC-1 inhibited retinal NFκB/p65 DNA binding activity and downregulated NFκB/p65, FAK, α5β1, EPO, ET-1, and MMP-9 expression at the message and the protein levels. In addition, YC-1 significantly inhibited subretinal NV by reducing the number of neovascular lesions, the area of each lesion and the total area of NV per retina. We further investigated the influence of VEGF signaling pathway on HIF-1α transcriptional activity to substantiate that this mouse model develops subretinal NV in an ischemia-independent microenvironment. Our data demonstrated that VEGF overexpression didn't have any impact on HIF-1α transcriptional activity, whereas treatment with YC-1 significantly inhibited endogenous HIF-1 activity. Our study suggests that retinal NFκB transcriptional activity is pivotal to ischemia-independent mechanisms, which lead to the local activation of angiogenic cascades. Our data also indicate that the nexus between VEGF and NFκB is implicated in triggering the angiogenic cascade that promotes retinal NV. Hence, targeting the VEGF/NFκB axis may act in a negative feedback loop to suppress ocular NV. This study suggests that inhibition of NFκB activation may be a means of turning off a "master switch" responsible for initiating and perpetuating these ocular pathologies. © 2014 DeNiro, Al-Mohanna.

DeNiro M.,Johns Hopkins Hospital | DeNiro M.,King Faisal Specialist Hospital And Research Center | Al-Mohanna F.A.,King Faisal Specialist Hospital And Research Center | Al-Mohanna F.A.,Al Faisal University
PLoS ONE | Year: 2012

The zinc (Zn++) transporter ZnT8 plays a crucial role in zinc homeostasis. It's been reported that an acute decrease in ZnT8 levels impairs β cell function and Zn++ homeostasis, which contribute to the pathophysiology of diabetes mellitus (DM). Although ZnT8 expression has been detected in the retinal pigment epithelium (RPE), its expression profile in the retina has yet to be determined. Furthermore, the link between diabetes and ischemic retinopathy is well documented; nevertheless, the molecular mechanism(s) of such link has yet to be defined. Our aims were to; investigate the expression profile of ZnT8 in the retina; address the influence of ischemia on such expression; and evaluate the influence of YC-1; (3-(50-hydroxymethyl-20-furyl)-1-benzyl indazole), a hypoxia inducible factor-1 (HIF-1) inhibitor, on the status of ZnT8 expression. We used real-time RT-PCR, immunohistochemistry, and Western blot in the mouse model of oxygen-induced retinopathy (OIR) and Müller cells to evaluate the effects of ischemia/hypoxia and YC-1 on ZnT8 expression. Our data indicate that ZnT8 was strongly expressed in the outer nuclear layer (ONL), outer plexiform layer (OPL), ganglion cell layer (GCL), and nerve fiber layer (NFL), whereas the photoreceptor layer (PRL), inner nuclear layer (INL) and inner plexiform layer (IPL) showed moderate ZnT8 immunoreactivity. Furthermore, we demonstrate that retinal ischemic insult induces a significant downregulation of ZnT8 at the message and protein levels, YC-1 rescues the injured retina by restoring the ZnT8 to its basal homeostatic levels in the neovascular retinas. Our data indicate that ischemic retinopathy maybe mediated by aberrant Zn++ homeostasis caused by ZnT8 downregulation, whereas YC-1 plays a neuroprotective role against ischemic insult. Therefore, targeting ZnT8 provides a therapeutic strategy to combat neovascular eye diseases. © 2012 DeNiro, Al-Mohanna.

Gautret P.,Marseille University Hospital Center | Gautret P.,Aix - Marseille University | Gray G.C.,University of Florida | Charrel R.N.,Aix - Marseille University | And 4 more authors.
The Lancet Infectious Diseases | Year: 2014

The past decade has seen the emergence of several novel viruses that cause respiratory tract infections in human beings, including Middle East respiratory syndrome coronavirus (MERS-CoV) in Saudi Arabia, an H7N9 influenza A virus in eastern China, a swine-like influenza H3N2 variant virus in the USA, and a human adenovirus 14p1 also in the USA. MERS-CoV and H7N9 viruses are still a major worldwide public health concern. The pathogenesis and mode of transmission of MERS-CoV and H7N9 influenza A virus are poorly understood, making it more difficult to implement intervention and preventive measures. A united and coordinated global response is needed to tackle emerging viruses that can cause fatal respiratory tract infections and to fill major gaps in the understanding of the epidemiology and transmission dynamics of these viruses. © 2014 Elsevier Ltd.

Hui D.S.,Chinese University of Hong Kong | Memish Z.A.,Al Faisal University | Zumla A.,University College London
Current Opinion in Pulmonary Medicine | Year: 2014

PURPOSE OF REVIEW: This review compares the clinical features, laboratory aspects and treatment options of severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS). RECENT FINDINGS: Bats are the natural reservoirs of SARS-like coronaviruses (CoVs) and are likely the reservoir of MERS coronavirus (MERS-CoV). Although a small number of camels have been found to have positive nasal swabs by real-time polymerase chain reaction and to carry antibody against MERS-CoV, the transmission route and the intermediary animal source remain uncertain amongst the sporadic primary cases. Both SARS-CoV and MERS-CoV may cause severe respiratory failure and extrapulmonary features such as diarrhoea, whereas mild or asymptomatic cases also occur in both conditions. In comparison with SARS, patients with MERS are older with male predominance, more comorbid illness and relatively lower human-to-human transmission potential. Although the viral kinetics of MERS-CoV remain unknown, nosocomial infections of MERS occur early within the first week of illness of the index case, whereas those of SARS occurred mainly in the second week of illness when the patient's upper airway viral load peaks on day 10 of illness. In-vitro data suggest that interferon (IFN) with or without ribavirin and mycophenolic acid may inhibit MERS-CoV, whereas protease inhibitors and IFN have inhibitory activity against SARS-CoV. SUMMARY: Although there are some similarities in the clinical features, MERS progresses to respiratory failure much more rapidly than SARS. The higher case fatality rate of MERS is likely related to older age and comorbid illness. More studies are needed to understand MERS-CoV in order to guide public health infection control measures and treatment. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Al-Tawfiq J.A.,Aramco Services Company | Al-Tawfiq J.A.,Indiana University | Momattin H.,Aramco Services Company | Dib J.,Aramco Services Company | And 2 more authors.
International Journal of Infectious Diseases | Year: 2014

Background: The Middle East respiratory syndrome coronavirus (MERS-CoV) has been reported to have a high case-fatality rate. Currently, there is no specific therapy or vaccine with proven effectiveness for MERS-CoV infections. Methods: A combination of ribavirin and interferon therapy was used for the treatment of five MERS-CoV-positive patients. We reviewed the therapeutic schedule and the outcome of these patients. Results: All patients were critically ill with acute respiratory distress syndrome treated with adjunctive corticosteroids and were on mechanical ventilation at the time of initiation of therapy. The median time from admission to therapy with ribavirin and interferon was 19 (range 10-22) days. None of the patients responded to the supportive or therapeutic interventions and all died of their illness. Conclusions: While ribavirin and interferon may be effective in some patients, our practical experience suggests that critically ill patients with multiple comorbidities who are diagnosed late in the course of their illness may not benefit from combination antiviral therapy as preclinical data suggest. There is clearly an urgent need for a novel effective antiviral therapy for this emerging global threat. © 2014 The Authors.

Haverila M.,Al Faisal University
Telematics and Informatics | Year: 2013

The purpose of this study is to investigate the cell phone use and broad cell phone feature preferences among high school and undergraduate in Finland. Of particular interest is the issue of gender differences regarding the use of the cell phones and the broad phone feature preferences, and their conceptualization. In this research the female respondents seem to use the calendar, Internet, music, and E-mail significantly more than the male respondents. As far as the feature preferences are concerned the female respondents seem to appreciate more price, aesthetics, design, standard processes and parts used, local language capability, safety in terms of radiation, and ringing tones. Male respondents on the other hand appreciate significantly more the use of business services. Also the broad feature preferences were compared to the actual usage areas of the cell phone. With many of these (parts, process, water, solidity, safety, ease of use, and ringing tones) there were no significant relationship with the actual usage. Interestingly the game feature had a significant correlation with the usage of the games, but the correlation was quite low. Finally the conceptualization of the cell phone by different genders was analyzed, and differences in the conceptualization were discovered. © 2012 Elsevier Ltd. All rights reserved.

Haverila M.J.,Al Faisal University
Journal of High Technology Management Research | Year: 2012

We present an exploratory investigation of how managers conceptualize and perceive 'product-firm compatibility' variables in successful and unsuccessful new product development (NPD) projects, and explore the role that they play in differentiating between successful and unsuccessful NPD outcomes. The findings show that managers perceive two distinctive types of product-firm compatibility factors, technology and marketing. Furthermore an 'advertising-finance' factor in the unsuccessful NPD projects emerged. Consequently differences exist in metric equivalence across successful and unsuccessful NPD projects, and thus the comparison of the successful and unsuccessful NPD projects should be done with caution. All product-firm compatibility variables and factors are positively related to NPD success. The managers, however, put lower relative importance to marketing in comparison to technology variables and factors. © 2012 Elsevier Inc. All rights reserved.

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