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author:("jaffer, S")
1.  Deaths due to Intentional Explosions in Selected Governorates of Iraq from 2010 to 2013: Prospective Surveillance 
Prehospital and disaster medicine  2015;30(6):586-592.
The aim of this study was to describe the most recent trends and epidemiologic patterns of fatal injuries resulting from explosions in Iraq, one of the countries most affected by violence from explosive devices.
Iraqi Ministry of Health (MoH) routine prospective injury surveillance collects information on all fatal injuries recorded by coroners from physical examinations, police reports, and family members in eight governorates of Iraq: Baghdad, Al-Anbar, Basrah, Erbil, Kerbala, Maysan, Ninevah, and Al-Sulaimaniya. This study analyzed explosive-related fatal injuries that occurred from January 1, 2010 through December 31, 2013.
Analysis included 2,803 fatal injuries. The number of fatal injuries declined from 2010 through 2012, followed by an increase in 2013. One-thousand one-hundred and one explosion-related fatalities were documented in 2013, more than twice as many as in 2012 or in 2011. Most fatalities were among men aged 20–39 years. Of all causalities, 194 (6.9%) were among females and 302 (10.8%) were among children aged less than 18 years. The majority of fatalities were caused by improvised explosive devices (IEDs): car bombs (15.3%), suicide bombs (4.0%), and other IEDs (29.6%). The highest number of fatalities occurred in streets and roads. Of all deaths, 95.6% occurred in three governorates: Baghdad, Ninevah, and Al-Anbar.
Explosives continue to result in a high number of fatal injuries in Iraq. Following a period of declining violence from explosives, in 2013, fatalities increased. Most explosion-related injuries resulted from IEDs; males aged 20–39 years were at greatest risk.
PMCID: PMC4798834  PMID: 26517290
explosions; fatal outcome; Iraq; mortality; public health surveillance; wounds/injuries
2.  Middle East respiratory syndrome coronavirus (MERS-CoV): animal to human interaction 
Pathogens and Global Health  2015;109(8):354-362.
The Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel enzootic betacoronavirus that was first described in September 2012. The clinical spectrum of MERS-CoV infection in humans ranges from an asymptomatic or mild respiratory illness to severe pneumonia and multi-organ failure; overall mortality is around 35.7%. Bats harbour several betacoronaviruses that are closely related to MERS-CoV but more research is needed to establish the relationship between bats and MERS-CoV. The seroprevalence of MERS-CoV antibodies is very high in dromedary camels in Eastern Africa and the Arabian Peninsula. MERS-CoV RNA and viable virus have been isolated from dromedary camels, including some with respiratory symptoms. Furthermore, near-identical strains of MERS-CoV have been isolated from epidemiologically linked humans and camels, confirming inter-transmission, most probably from camels to humans. Though inter-human spread within health care settings is responsible for the majority of reported MERS-CoV cases, the virus is incapable at present of causing sustained human-to-human transmission. Clusters can be readily controlled with implementation of appropriate infection control procedures. Phylogenetic and sequencing data strongly suggest that MERS-CoV originated from bat ancestors after undergoing a recombination event in the spike protein, possibly in dromedary camels in Africa, before its exportation to the Arabian Peninsula along the camel trading routes. MERS-CoV serosurveys are needed to investigate possible unrecognized human infections in Africa. Amongst the important measures to control MERS-CoV spread are strict regulation of camel movement, regular herd screening and isolation of infected camels, use of personal protective equipment by camel handlers and enforcing rules banning all consumption of unpasteurized camel milk and urine.
PMCID: PMC4809235  PMID: 26924345
MERS-CoV; Coronavirus; Middle East; Animal; Dromedary; Camel; Bat; Zoonosis
3.  A Review of Computational Methods for Finding Non-Coding RNA Genes 
Genes  2016;7(12):113.
Finding non-coding RNA (ncRNA) genes has emerged over the past few years as a cutting-edge trend in bioinformatics. There are numerous computational intelligence (CI) challenges in the annotation and interpretation of ncRNAs because it requires a domain-related expert knowledge in CI techniques. Moreover, there are many classes predicted yet not experimentally verified by researchers. Recently, researchers have applied many CI methods to predict the classes of ncRNAs. However, the diverse CI approaches lack a definitive classification framework to take advantage of past studies. A few review papers have attempted to summarize CI approaches, but focused on the particular methodological viewpoints. Accordingly, in this article, we summarize in greater detail than previously available, the CI techniques for finding ncRNAs genes. We differentiate from the existing bodies of research and discuss concisely the technical merits of various techniques. Lastly, we review the limitations of ncRNA gene-finding CI methods with a point-of-view towards the development of new computational tools.
PMCID: PMC5192489  PMID: 27918472
gene; DNA; non-coding RNA; micro RNA; computational intelligence; support vector machine; Bayesian networks; genetic algorithm; neural network; deep learning
4.  Middle East respiratory syndrome coronavirus disease is rare in children: An update from Saudi Arabia 
To summarize the reported Middle East respiratory syndrome-coronavirus (MERS-CoV) cases, the associated clinical presentations and the outcomes.
We searched the Saudi Ministry of Health website, the World Health Organization website, and the Flutracker website. We also searched MEDLINE and PubMed for the keywords: Middle East respiratory syndrome-coronavirus, MERS-CoV in combination with pediatric, children, childhood, infancy and pregnancy from the initial discovery of the virus in 2012 to 2016. The retrieved articles were also read to further find other articles. Relevant data were placed into an excel sheet and analyzed accordingly. Descriptive analytic statistics were used in the final analysis as deemed necessary.
From June 2012 to April 19, 2016, there were a total of 31 pediatric MERS-CoV cases. Of these cases 13 (42%) were asymptomatic and the male to female ratio was 1.7:1. The mean age of patients was 9.8 ± 5.4 years. Twenty-five (80.6%) of the cases were reported from the Kingdom of Saudi Arabia. The most common source of infection was household contact (10 of 15 with reported source) and 5 patients acquired infection within a health care facility. Using real time reverse transcriptase polymerase chain reaction of pediatric patients revealed that 9 out of 552 (1.6%) was positive in the Kingdom of Saudi Arabia.
Utilizing serology for MERS-CoV infection in Jordan and Saudi Arabia did not reveal any positive patients. Thus, the number of the pediatric MERS-CoV is low; the exact reason for the low prevalence of the disease in children is not known.
PMCID: PMC5099592  PMID: 27872828
Pediatric; Middle East respiratory syndrome-coronavirus; Children; Respiratory tract infection
5.  Alterations in DNA methylation and airway hyperreactivity in response to in utero exposure to environmental tobacco smoke 
Inhalation toxicology  2015;27(13):724-730.
Growing evidence indicates that prenatal exposure to maternal smoking is a risk factor for the development of asthma in children. However, the effects of prenatal environmental tobacco smoke (ETS) exposure on the genome and lung immune cells are unclear. This study aims to determine whether in utero ETS exposure alters DNA methylation patterns and increases airway hyperreactivity (AHR) and inflammation. Pregnant C57BL/6 mice were exposed daily to a concentration of 1.0 mg/m3 ETS. AHR was determined in the 6-week-old offspring by measurement of airway resistance. Global and gene promoter methylation levels in lung DNA from offspring were analyzed by luminometric methylation and pyrosequencing assays, respectively. Offspring exposed to ETS showed a marked increase in the number of alveolar macrophages in the bronchoalveolar lavage fluid and level of IL-13 in the airways compared with offspring of filtered-air exposed dams (controls). ETS exposure significantly augmented AHR compared with controls. In the methylation analysis, ETS-exposed offspring had a significantly lower level of global DNA methylation than the controls. We observed a significant increase in IFN-γ, and significant decrease in IL-13 methylation levels in the ETS group compared with controls. Collectively, these data suggest that in utero ETS exposure increases the risk of pulmonary inflammation and AHR through altered DNA methylation, but additional studies are needed to fully determine the causal link between changes in methylation and cytokines levels, as well as AHR.
PMCID: PMC4760648  PMID: 26525176
Airway hyperreactivity; DNA promoter methylation; environmental tobacco smoke; genomic methylation; inflammation
6.  Effectiveness of Membrane Filtration to Improve Drinking Water: A Quasi-Experimental Study from Rural Southern India 
Since point-of-use methods of water filtration have shown limited acceptance in Vellore, southern India, this study evaluated the effectiveness of decentralized membrane filtration 1) with safe storage, 2) without safe storage, versus 3) no intervention, consisting of central chlorination as per government guidelines, in improving the microbiological quality of drinking water and preventing childhood diarrhea. Periodic testing of water sources, pre-/postfiltration samples, and household water, and a biweekly follow up of children less than 2 years of age was done for 1 year. The membrane filters achieved a log reduction of 0.86 (0.69–1.06), 1.14 (0.99–1.30), and 0.79 (0.67–0.94) for total coliforms, fecal coliforms, and Escherichia coli, respectively, in field conditions. A 24% (incidence rate ratio, IRR [95% confidence interval, CI] = 0.76 [0.51–1.13]; P = 0.178) reduction in diarrheal incidence in the intervention village with safe storage and a 14% (IRR [95% CI] = 1.14 [0.75–1.77]; P = 0.530) increase in incidence for the intervention village without safe storage versus no intervention village was observed, although not statistically significant. Microbiologically, the membrane filters decreased fecal contamination; however, provision of decentralized membrane-filtered water with or without safe storage was not protective against childhood diarrhea.
PMCID: PMC5094238  PMID: 27601525
7.  Major Neutrophilia Observed in Acute Phase of Human Leptospirosis Is Not Associated with Increased Expression of Granulocyte Cell Activation Markers 
PLoS ONE  2016;11(11):e0165716.
It has long been known that pathogenic Leptospira can mobilize the immune system but the specific contribution of neutrophils to control the infectious challenge remains to be clarified. We herein analyzed the phenotype of circulating neutrophils of patients with leptospirosis and healthy controls for the expression of toll-like receptor (TLR) type 2 (TLR2, to sense the leptospiral LPS) and several activation markers: interleukin 8 chemokine receptor CD182 (CXCR2), CD11b of the integrin/opsonin complement receptor type 3 (CR3) and CD15 (ligand of the selectin). The plasmatic level of the main CD182 ligand, interleukin 8 (CXCL8), was measured by ELISA. Hospitalized leptospirosis cases showed marked neutrophilia, particularly in the most severe cases. Interestingly, TLR2 was significantly increased in leptospirosis but identical levels of CD182 and CD11b were detected when compared to controls. CD15 was significantly decreased on neutrophils in leptospirosis but returned to normal within 1 month. Basal levels of IL-8 were measured in control subjects and were not increased in leptospirosis cases at the initial stage of the disease. In conclusion, we observed that neutrophils failed to regulate the expression of several of the receptors involved in cell activation and recruitment. This study further emphasizes the paradigm that neutrophils may be impaired in their overall capacity to thwart bacterial infection in leptospirosis patients.
PMCID: PMC5089758  PMID: 27802348
9.  Genetic and clinical characterization of Pakistani families with Bardet-Biedl syndrome extends the genetic and phenotypic spectrum 
Scientific Reports  2016;6:34764.
Bardet-Biedl syndrome (BBS) is an autosomal recessive disorder that is both genetically and clinically heterogeneous. To date 19 genes have been associated with BBS, which encode proteins active at the primary cilium, an antenna-like organelle that acts as the cell’s signaling hub. In the current study, a combination of mutation screening, targeted sequencing of ciliopathy genes associated with BBS, and whole-exome sequencing was used for the genetic characterization of five families including four with classic BBS symptoms and one BBS-like syndrome. This resulted in the identification of novel mutations in BBS genes ARL6 and BBS5, and recurrent mutations in BBS9 and CEP164. In the case of CEP164, this is the first report of two siblings with a BBS-like syndrome with mutations in this gene. Mutations in this gene were previously associated with nephronophthisis 15, thus the current results expand the CEP164-associated phenotypic spectrum. The clinical and genetic spectrum of BBS and BBS-like phenotypes is not fully defined in Pakistan. Therefore, genetic studies are needed to gain insights into genotype-phenotype correlations, which will in turn improve the clinician’s ability to make an early and accurate diagnosis, and facilitate genetic counseling, leading to directly benefiting families with affected individuals.
PMCID: PMC5052523  PMID: 27708425
10.  Etiology of Influenza-Like Illnesses from Sentinel Network Practitioners in Réunion Island, 2011-2012 
PLoS ONE  2016;11(9):e0163377.
In Réunion Island, despite an influenza surveillance established since 1996 by the sentinel general practitioner’s network, little is known about the etiology of Influenza like-illness (ILI) that differs from influenza viruses in a tropical area. We set up a retrospective study using nasal swabs collected by sentinel GPs from ILI patients in 2011 and 2012. A total of 250 swabs were randomly selected and analyzed by multiplex reverse transcriptase polymerase chain reaction (RT-PCR) including research of 18 viruses and 4 bacteria. We detected respiratory viruses in 169/222 (76.1%) samples, mostly rhinovirus (23.4%), influenza A virus (21.2%), influenza B virus (12.6%), coronavirus (4.9%) and Human metapneumovirus (3.6%). Nine swabs (5.3% of positive swabs) revealed co-infections with two viruses identified, among which six concerned co-infections with influenza viruses. We observed important seasonal differences, with circulation of Human Metapneumoviruses, RSV A and B and coronavirus only during summer; whereas parainfluenza viruses were identified only during winter. In conclusion, this study highlights a substantial circulation of multiple respiratory pathogens in Réunion Island throughout the year. It shows that ILI are not only attributable to influenza and underlines the need for biological surveillance. As the use of multiplex RT-PCR showed its efficacy, it is now used routinely in the surveillance of ILI.
PMCID: PMC5031398  PMID: 27654509
11.  Role of Gut Microbiota in the Aetiology of Obesity: Proposed Mechanisms and Review of the Literature 
Journal of Obesity  2016;2016:7353642.
The aetiology of obesity has been attributed to several factors (environmental, dietary, lifestyle, host, and genetic factors); however none of these fully explain the increase in the prevalence of obesity worldwide. Gut microbiota located at the interface of host and environment in the gut are a new area of research being explored to explain the excess accumulation of energy in obese individuals and may be a potential target for therapeutic manipulation to reduce host energy storage. Several mechanisms have been suggested to explain the role of gut microbiota in the aetiology of obesity such as short chain fatty acid production, stimulation of hormones, chronic low-grade inflammation, lipoprotein and bile acid metabolism, and increased endocannabinoid receptor system tone. However, evidence from animal and human studies clearly indicates controversies in determining the cause or effect relationship between the gut microbiota and obesity. Metagenomics based studies indicate that functionality rather than the composition of gut microbiota may be important. Further mechanistic studies controlling for environmental and epigenetic factors are therefore required to help unravel obesity pathogenesis.
PMCID: PMC5040794  PMID: 27703805
12.  Mature Biofilm Degradation by Potential Probiotics: Aggregatibacter actinomycetemcomitans versus Lactobacillus spp. 
PLoS ONE  2016;11(7):e0159466.
The biofilm degradation of Aggregatibacter actinomycetemcomitans is essential as a complete periodontal disease therapy, and here we show the effects of potential probiotic bacteria such as Lactobacillus spp. for the biofilm of several serotypes of A. actinomycetemcomitans strains. Eight of the 13 species showed the competent biofilm degradation of ≥ 90% reduction in biofilm values in A. actinomycetemcomitans Y4 (serotype b) as well as four of the seven species for the biofilm of A. actinomycetemcomitans OMZ 534 (serotype e). In contrast, the probiotic bacteria did not have a big impact for the degradation of A. actinomycetemcomitans SUNY 75 (serotype a) biofilm. The dispersed A. actinomycetemcomitans Y4 cells through the biofilm detachment were still viable and plausible factors for the biofilm degradation were not due to the lactic acid and low pH conditions. The three enzymes, protease, lipase, and amylase may be responsible for the biofilm degradation; in particular, lipase was the most effective enzyme for the biofilm degradation of A. actinomycetemcomitans Y4 along with the protease activity which should be also important for the other serotypes. Remarkable lipase enzyme activities were detected from some of the potential probiotics and a supporting result using a lipase inhibitor presented corroborating evidence that lipase activity is one of the contributing factors for biofilm degradation outside of the protease which is also another possible factor for the biofilm of the other serotype of A. actinomycetemcomitans strains. On the other hand, the biofilm of A. actinomycetemcomitans SUNY 75 (serotype a) was not powerfully degraded by the lipase enzyme because the lipase inhibitor was slightly functional for only two of potential probiotics.
PMCID: PMC4954673  PMID: 27438340
13.  The threatening but unpredictable Sarcoptes scabiei: first deadly outbreak in the Himalayan lynx, Lynx lynx isabellinus, from Pakistan 
Parasites & Vectors  2016;9:402.
Although neglected, the mite Sarcoptes scabiei is an unpredictable emerging parasite, threatening human and animal health globally. In this paper we report the first fatal outbreak of sarcoptic mange in the endangered Himalayan lynx (Lynx lynx isabellinus) from Pakistan. A 10-year-old male Himalayan lynx was found in a miserable condition with severe crusted lesions in Chitral District, and immediately died. Post-mortem examination determined high S. scabiei density (1309 mites/cm2 skin). It is most probably a genuine emergence, resulting from a new incidence due to the host-taxon derived or prey-to-predator cross-infestation hypotheses, and less probable to be apparent emergence resulting from increased infection in the Himalayan lynx population. This is an alarming situation for the conservation of this already threatened population, which demands surveillance for early detection and eventually rescue and treatment of the affected Himalayan lynx.
PMCID: PMC4950640  PMID: 27435176
Sarcoptes scabiei; Lynx lynx isabellinus; Human-lynx conflict; Chitral District; Pakistan; Neglected parasite; Emerging disease
14.  Prevention of pneumococcal infections during mass gathering 
The interest in mass gathering and its implications has been increasing due to globalization and international travel. The potential occurrence of infectious disease outbreaks during mass gathering is most feared. In this context, respiratory tract infections are of great concern due to crowding in a limited space which facilitates and magnifies the potential of disease spread among attendees. Pneumococcal disease is best described among pilgrims to Makkah and vaccination is one of the methods for the prevention of this disease. Pneumonia was described in a mass gathering with a prevalence of 4.8/100,000 pilgrims and contributes to 15–39% of hospitalizations. Various studies showed that 7–37% of pilgrims are 65 y of age or older. The uptake of pneumococcal vaccine among pilgrims is low at 5%. There is no available data to make strong recommendations for S. pneumoniae vaccination of all pilgrims, it is important that a high risk population receive the indicated vaccination. We reviewed the available literature on the burden of pneumococcal infections during mass gathering and evaluate the available literature on pneumococcal vaccinations for attendees of mass gathering.
PMCID: PMC5049738  PMID: 26176306
Mass gathering, Streptococcus pneumoniae, pneumococcus, Hajj, pilgrimage
15.  Mechanical perturbations trigger endothelial nitric oxide synthase activity in human red blood cells 
Scientific Reports  2016;6:26935.
Nitric oxide (NO), a vascular signaling molecule, is primarily produced by endothelial NO synthase. Recently, a functional endothelial NO synthase (eNOS) was described in red blood cells (RBC). The RBC-eNOS contributes to the intravascular NO pool and regulates physiological functions. However the regulatory mechanisms and clinical implications of RBC-eNOS are unknown. The present study investigated regulation and functions of RBC-eNOS under mechanical stimulation. This study shows that mechanical stimuli perturb RBC membrane, which triggers a signaling cascade to activate the eNOS. Extracellular NO level, estimated by the 4-Amino-5-Methylamino-2′, 7′-Difluorofluorescein Diacetate probe, was significantly increased under mechanical stimuli. Immunostaining and western blot studies confirmed that the mechanical stimuli phosphorylate the serine 1177 moiety of RBC-eNOS, and activates the enzyme. The NO produced by activation of RBC-eNOS in vortexed RBCs promoted important endothelial functions such as migration and vascular sprouting. We also show that mechanical perturbation facilitates nitrosylation of RBC proteins via eNOS activation. The results of the study confirm that mechanical perturbations sensitize RBC-eNOS to produce NO, which ultimately defines physiological boundaries of RBC structure and functions. Therefore, we propose that mild physical perturbations before, after, or during storage can improve viability of RBCs in blood banks.
PMCID: PMC4921846  PMID: 27345770
16.  Human Leptospirosis on Reunion Island, Indian Ocean: Are Rodents the (Only) Ones to Blame? 
PLoS Neglected Tropical Diseases  2016;10(6):e0004733.
Although leptospirosis is a zoonosis of major concern on tropical islands, the molecular epidemiology of the disease aiming at linking human cases to specific animal reservoirs has been rarely explored within these peculiar ecosystems.
Methodology/Principal Findings
Five species of wild small mammals (n = 995) as well as domestic animals (n = 101) were screened for Leptospira infection on Reunion Island; positive samples were subsequently genotyped and compared to Leptospira from clinical cases diagnosed in 2012–2013 (n = 66), using MLST analysis. We identified two pathogenic species in human cases, namely Leptospira interrogans and Leptospira borgpetersenii. Leptospira interrogans was by far dominant both in clinical samples (96.6%) and in infected animal samples (95.8%), with Rattus spp and dogs being its exclusive carriers. The genetic diversity within L. interrogans was apparently limited to two sequence types (STs): ST02, identified among most clinical samples and in all rats with complete MLST, and ST34, identified in six humans, but not in rats. Noteworthy, L. interrogans detected in two stray dogs partially matched with ST02 and ST34. Leptospira borgpetersenii was identified in two clinical samples only (3.4%), as well as in cows and mice; four haplotypes were identified, of which two seemingly identical in clinical and animal samples. Leptospira borgpetersenii haplotypes detected in human cases were clearly distinct from the lineage detected so far in the endemic bat species Mormopterus francoismoutoui, thus excluding a role for this volant mammal in the local human epidemiology of the disease.
Our data confirm rats as a major reservoir of Leptospira on Reunion Island, but also pinpoint a possible role of dogs, cows and mice in the local epidemiology of human leptospirosis. This study shows that a comprehensive molecular characterization of pathogenic Leptospira in both clinical and animal samples helps to gaining insight into leptospirosis epidemiology within a specific environmental setting.
Author Summary
Leptospirosis is a zoonosis caused by infection with pathogenic Leptospira species. A broad range of animals, including rodents, pets and livestock, are maintenance hosts for leptospires. However, assessing the relative importance of each host in the contamination of the environment and, in fine, in the infection of humans, has rarely been performed. In this study, we surveyed various wild and domestic animal species and their Leptospira carriage in Reunion Island, where human leptospirosis is endemic. We determined and compared the Leptospira genetic diversity at the species and infra-species levels in laboratory-confirmed human cases and in infected animals. The two Leptospira species infecting humans, Leptospira interrogans and Leptospira borgpetersenii, could be traced back to different animal species: rats and dogs for the former species, cows and mice for the latter. The Leptospira infecting the single bat species endemic to the island was not found to be involved in human leptospirosis. Aside from rats, which were expected to play a role in the local epidemiology of the disease, the putative role of dogs, cattle and mice in human epidemiology on Reunion Island, pinpointed by our data, deserves a specific investigation. These results have strong implications in terms of local control actions aimed at reducing the burden of human leptospirosis.
PMCID: PMC4905629  PMID: 27294677
17.  Middle East Respiratory Syndrome Coronavirus (MERS-CoV) origin and animal reservoir 
Virology Journal  2016;13:87.
Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) is a novel coronavirus discovered in 2012 and is responsible for acute respiratory syndrome in humans. Though not confirmed yet, multiple surveillance and phylogenetic studies suggest a bat origin. The disease is heavily endemic in dromedary camel populations of East Africa and the Middle East. It is unclear as to when the virus was introduced to dromedary camels, but data from studies that investigated stored dromedary camel sera and geographical distribution of involved dromedary camel populations suggested that the virus was present in dromedary camels several decades ago. Though bats and alpacas can serve as potential reservoirs for MERS-CoV, dromedary camels seem to be the only animal host responsible for the spill over human infections.
PMCID: PMC4891877  PMID: 27255185
MERS-CoV; Coronavirus; Middle East; Animal; Dromedary; Camels; Bats; Middle East Respiratory Syndrome
18.  Involvement of CmWRKY10 in Drought Tolerance of Chrysanthemum through the ABA-Signaling Pathway 
Drought is one of the important abiotic factors that adversely affects plant growth and production. The WRKY transcription factor plays a pivotal role in plant growth and development, as well as in the elevation of many abiotic stresses. Among three major groups of the WRKY family, the group IIe WRKY has been the least studied in floral crops. Here, we report functional aspects of group IIe WRKY member, i.e., CmWRKY10 in chrysanthemum involved in drought tolerance. The transactivation assay showed that CmWRKY10 had transcriptional activity in yeast cells and subcellular localization demonstrated that it was localized in nucleus. Our previous study showed that CmWRKY10 could be induced by drought in chrysanthemum. Moreover, the overexpression of CmWRKY10 in transgenic chrysanthemum plants improved tolerance to drought stress compared to wild-type (WT). High expression of DREB1A, DREB2A, CuZnSOD, NCED3A, and NCED3B transcripts in overexpressed plants provided strong evidence that drought tolerance mechanism was associated with abscisic acid (ABA) pathway. In addition, lower accumulation of reactive oxygen species (ROS) and higher enzymatic activity of peroxidase, superoxide dismutase and catalase in CmWRKY10 overexpressed lines than that of WT demonstrates its role in drought tolerance. Together, these findings reveal that CmWRKY10 works as a positive regulator in drought stress by regulating stress-related genes.
PMCID: PMC4881519  PMID: 27187353
chrysanthemum; drought; abscisic acid; WRKY
19.  Effect of angiotensin converting enzyme inhibitor on glomerular hyperfiltration in patients with type 1 diabetes 
To assess the effect of angiotensin converting enzyme inhibition on glomerular filtration rate (GFR) in normotensive patient with type 1 diabetes.
A two year non-placebo control prospective study was conducted after ethical approval at Diabetes Centre of Diabetic Association of Pakistan, a WHO collaborating centre in Karachi, Pakistan. All patients with type 1 diabetes visited the out-patients department from August 2009 till July 2011 and those who fulfilled the inclusion criteria were invited to participate. A total of 121 people aged ≥18 years and ≥ 5 years of diabetes were included. Pregnant and lactating woman and those aged <18 years were excluded. GFR was calculated by using CKD-EPI formula (eGFR) at baseline and after two year. On the basis of estimated GFR, patients at baseline were divided according to KDIGO classification of chronic kidney diseases into, hyperfiltration (eGFR ≥ 100 ml/min) and normal filtration group (eGFR < 100 ml/min). All subjects in hyperfiltration group received ACE inhibitor (treatment group) while patients with normal filtration did not receive ACE inhibitor (control group).
Fifty two patients (43%) were in the treatment and sixty nine (57%) were in the control group. At baseline eGFR, systolic and diastolic blood pressures between groups were non-significantly different. After two years, compared to baseline, eGFR of the treatment group declined and the control group increased significantly. No significant difference in systolic while diastolic blood pressure of the treatment group increased significantly after two years compared to baseline. In contrast both systolic and diastolic blood pressure of control group increased significantly after two years compared to their baseline values.
Present study demonstrated that initiation of ACEI in hyperfiltration stage declined GFR and keep blood pressure within normal range.
PMCID: PMC4928398  PMID: 27375689
Angiotensin converting enzyme inhibitor; Glomerular hyperfiltration; Type 1 diabetes
20.  Five years of experience with rituximab plus high-dose dexamethasone for relapsed/refractory chronic lymphocytic leukemia 
Archives of Medical Science : AMS  2015;12(2):421-427.
High-dose methylprednisolone (HDMP) in combination with rituximab is active in the treatment of relapsed/refractory chronic lymphocytic leukemia (CLL), but serious infections are frequent. Recently published data suggested that high-dose dexamethasone might be equally effective as HDMP despite a lower cumulative dose.
Material and methods
We performed retrospective analysis of 60 patients with relapsed/refractory CLL (median age: 66 years; range: 37–86) treated with rituximab plus dexamethasone (R-dex) at a single tertiary center between September 2008 and October 2012. The schedule of R-dex consisted of rituximab 500 mg/m2 i.v. day 1 (375 mg/m2 in cycle 1) and dexamethasone 40 mg orally on days 1-4 and 10-13 repeated every 3 weeks for a maximum of 8 cycles. Unfavorable prognostic features were frequent (Rai stages III/IV in 67%, unmutated IgVH 82%, del 11q 43%, TP53 mutation/deletion 23%, bulky lymphadenopathy 58% of patients).
Overall response (OR)/complete remission (CR) was achieved in 75/3%. At the median follow-up of 21 months, median progression-free survival (PFS) was 8 months, median time to next treatment 12.9 months and median overall survival 25.5 months. Refractoriness to fludarabine (p = 0.04) and age ≥ 65 years (p = 0.03) were significant predictors of shorter PFS. R-dex was successfully used for debulking before allogenic stem cell transplantation in 7 patients (12%). Serious (CTCAE grade III/IV) infections occurred in 27% of patients; 20% of patients developed steroid diabetes requiring temporary short-acting insulin.
Our results show that R-dex is an active and well-tolerated regimen for patients with relapsed/refractory CLL; however, major infections remain frequent despite combined antimicrobial prophylaxis.
PMCID: PMC4848354  PMID: 27186190
chronic lymphocytic leukemia; rituximab; dexamethasone; refractory disease; chemoimmunotherapy
21.  Infectious Middle East Respiratory Syndrome Coronavirus Excretion and Serotype Variability Based on Live Virus Isolates from Patients in Saudi Arabia 
Journal of Clinical Microbiology  2015;53(9):2951-2955.
The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) has infected at least 1,082 people, including 439 fatalities. So far, no empirical virus isolation study has been done to elucidate infectious virus secretion or serotype variability. Here, we used 51 respiratory samples from 32 patients with confirmed MERS-CoV infection for virus isolation in Vero B4 and Caco-2 cells. We found Caco-2 cells to significantly enhance isolation success over routinely used Vero cells. Isolation success correlated with viral RNA concentration and time after diagnosis as well as with the amount of IgA antibodies secreted in respiratory samples used for isolation. Results from plaque reduction neutralization assays using a representative range of serum samples and virus isolates suggested that all circulating human MERS-CoV strains represent one single serotype. The choice of prototype strain is not likely to influence the success of candidate MERS-CoV vaccines. However, vaccine formulations should be evaluated for their potential to induce IgA.
PMCID: PMC4540943  PMID: 26157150
22.  Road traffic fatalities in selected governorates of Iraq from 2010 to 2013: prospective surveillance 
Conflict and Health  2016;10:2.
The insurgency tactics that characterize modern warfare, such as suicide car bombs and roadside bombs, have the potential to significantly impact road traffic injuries in conflict affected-countries. As road traffic incidents are one of the top ten causes of death in Iraq, changes in incidence have important implications for the health system. We aimed to describe patterns of road traffic fatalities for all demographic groups and types of road users in Iraq during a period characterized by a resurgence in insurgency activity.
Iraqi Ministry of Health routine prospective injury surveillance collects information on all fatal injuries in eight governorates of Iraq: Baghdad, Al-Anbar, Basrah, Erbil, Kerbala, Maysan, Ninevah, and Al-Sulaimaniya. From all injury fatalities documented at the coroner office, we analyzed only those attributed to road traffic that occurred between 1 January 2010 and 31 December 2013. Coroners ascertain information from physical examinations, police reports and family members.
Analysis included 7,976 road traffic fatalities. Overall, 6,238 (78.2 %) fatalities were male and 2,272 (28.5 %) were children under 18 years of age. The highest numbers of road traffic fatalities were among males 15 to 34 years of age and children of both sexes under 5 years of age. 49.2 % of fatalities occurred among pedestrians. Among children and females, the majority of road traffic fatalities were pedestrians, 69.0 % and 56.6 %, respectively. Fatalities among motorcyclists (3.7 %) and bicyclists (0.4 %) were least common. Rates of road traffic fatalities ranged from 8.6 to 10.7 per 100,000 population.
The injury surveillance system provides the first data from a conflict-affected country on road traffic fatalities disaggregated by type of road user. The highest numbers of fatalities were among children and young men. Nearly half of fatalities were pedestrians, a proportion nearly double that of any neighboring country. As insurgency activity increased in 2013, the number of road traffic fatalities declined.
PMCID: PMC4765069  PMID: 26913063
Iraq; Injury; Conflict; Fatal; Road traffic; Surveillance
23.  An Observational, Laboratory-Based Study of Outbreaks of Middle East Respiratory Syndrome Coronavirus in Jeddah and Riyadh, Kingdom of Saudi Arabia, 2014 
In spring 2014, an outbreak of Middle East respiratory syndrome coronavirus in Jeddah caused conjectures about changes in viral transmissibility. Functional examination of viruses and analyses of diagnostic laboratory data suggest causation by nosocomial transmission of a biologically unchanged virus.
Background. In spring 2014, a sudden rise in the number of notified Middle East respiratory syndrome coronavirus (MERS-CoV) infections occurred across Saudi Arabia with a focus in Jeddah. Hypotheses to explain the outbreak pattern include increased surveillance, increased zoonotic transmission, nosocomial transmission, and changes in viral transmissibility, as well as diagnostic laboratory artifacts.
Methods. Diagnostic results from Jeddah Regional Laboratory were analyzed. Viruses from the Jeddah outbreak and viruses occurring during the same time in Riyadh, Al-Kharj, and Madinah were fully or partially sequenced. A set of 4 single-nucleotide polymorphisms distinctive to the Jeddah outbreak were determined from additional viruses. Viruses from Riyadh and Jeddah were isolated and studied in cell culture.
Results. Up to 481 samples were received per day for reverse transcription polymerase chain reaction (RT-PCR) testing. A laboratory proficiency assessment suggested positive and negative results to be reliable. Forty-nine percent of 168 positive-testing samples during the Jeddah outbreak stemmed from King Fahd Hospital. All viruses from Jeddah were monophyletic and similar, whereas viruses from Riyadh were paraphyletic and diverse. A hospital-associated transmission cluster, to which cases in Indiana (United States) and the Netherlands belonged, was discovered in Riyadh. One Jeddah-type virus was found in Riyadh, with matching travel history to Jeddah. Virus isolates representing outbreaks in Jeddah and Riyadh were not different from MERS-CoV EMC/2012 in replication, escape of interferon response, or serum neutralization.
Conclusions. Virus shedding and virus functions did not change significantly during the outbreak in Jeddah. These results suggest the outbreaks to have been caused by biologically unchanged viruses in connection with nosocomial transmission.
PMCID: PMC4303774  PMID: 25323704
MERS-coronavirus; outbreak; nosocomial transmission; virus isolation; transmission infection control
24.  Hypertension and diabetes in Africa: design and implementation of a large population-based study of burden and risk factors in rural and urban Malawi 
The emerging burden of cardiovascular disease and diabetes in sub-Saharan Africa threatens the gains made in health by the major international effort to combat infectious diseases. There are few data on distribution of risk factors and outcomes in the region to inform an effective public health response. A comprehensive research programme is being developed aimed at accurately documenting the burden and drivers of NCDs in urban and rural Malawi; to design and test intervention strategies. The programme includes population surveys of all people aged 18 years and above, linking individuals with newly diagnosed hypertension and diabetes to healthcare and supporting clinical services. The successes, challenges and lessons learnt from the programme to date are discussed.
Over 20,000 adults have been recruited in rural Karonga and urban Lilongwe. The urban population is significantly younger and wealthier than the rural population. Employed urban individuals, particularly males, give particular recruitment challenges; male participation rates were 80.3 % in the rural population and 43.6 % in urban, whilst female rates were 93.6 and 75.6 %, respectively. The study is generating high quality data on hypertension, diabetes, lipid abnormalities and risk factors.
It is feasible to develop large scale studies that can reliably inform the public health approach to diabetes, cardiovascular disease and other NCDs in Sub-Saharan Africa. It is essential for studies to capture both rural and urban populations to address disparities in risk factors, including age structure. Innovative approaches are needed to address the specific challenge of recruiting employed urban males.
PMCID: PMC4736489  PMID: 26839575
Non-communicable diseases; Hypertension; Diabetes; Methods; Epidemiology; Sub-Saharan Africa
25.  Chronic kidney disease hotspots in developing countries in South Asia 
Clinical Kidney Journal  2015;9(1):135-141.
In many developing countries in the South Asian region, screening for chronic diseases in the community has shown a widely varying prevalence. However, certain geographical regions have shown a high prevalence of chronic kidney disease (CKD) of unknown etiology. This predominantly affects the young and middle-aged population with a lower socioeconomic status. Here, we describe the hotspots of CKD of undiagnosed etiology in South Asian countries including the North, Central and Eastern provinces of Sri Lanka and the coastal region of the state of Andhra Pradesh in India. Screening of these populations has revealed cases of CKD in various stages. Race has also been shown to be a factor, with a much lower prevalence of CKD in whites compared to Asians, which could be related to the known influence of ethnicity on CKD development as well as environmental factors. The difference between developed and developing nations is most stark in the realm of healthcare, which translates into CKD hotspots in many regions of South Asian countries. Additionally, the burden of CKD stage G5 remains unknown due to the lack of registry reports, poor access to healthcare and lack of an organized chronic disease management program. The population receiving various forms of renal replacement therapy has dramatically increased in the last decade due to better access to point of care, despite the disproportionate increase in nephrology manpower. In this article we will discuss the nephrology care provided in various countries in South Asia, including India, Bangladesh, Pakistan, Nepal, Bhutan, Sri Lanka and Afghanistan.
PMCID: PMC4720189  PMID: 26798474
CKD; diabetes mellitus; glomerulonephritis; glomerulosclerosis; pediatrics

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