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1.  Percutaneous nephrolithotomy versus open surgery for treatment of staghorn stones in pediatric patients 
Canadian Urological Association Journal  2014;8(11-12):E906-E909.
Introduction:
We compare percutaneous nephrolithotomy (PCNL) and open surgery in the treatment of staghorn stones in children.
Methods:
We retrospectively reviewed the electronic records of children who underwent treatment for staghorn stones between September 2000 and August 2013. They were divided between Group 1 (patients who underwent PCNL) and Group 2 (patients who underwent open surgery). We compared stone-free and complications rates, need for multiple procedures, and hospital stay.
Results:
The study included 41 patients (35 boys and 6 girls), with mean age 7.4 ± 3.1 years (range: 2–15). Of these 41 patients, 26 had unilateral renal stone and 15 had bilateral renal stones. The total number of treated renal units was 56: 28 underwent PCNL and 28 underwent open surgery. The complication rate was comparable for both groups (32% for open surgery vs. 28.6%, p = 0.771). Multiple procedures were more needed in PCNL group (60.7% vs. 32% in open surgery, p = 0.032). The stone-free rate was 71.4% after PCNL and 78.6% after open surgery (p = 0.537). A significant difference was observed in shorter hospital stay after PCNL (5 vs. 8.8 days, p < 0.001). Our study’s limitations include its retrospective design and relatively small sample size.
Conclusions:
For the treatment of staghorn stones in children, PCNL was comparable to open surgery in complication and stone-free rates. PCNL had the advantage of a shorter hospital stay and open surgery showed a decreased need for multiple procedures.
doi:10.5489/cuaj.1994
PMCID: PMC4277531  PMID: 25553164
2.  Insights into the possible role of IFNG and IFNGR1 in Kala-azar and Post Kala-azar Dermal Leishmaniasis in Sudanese patients 
BMC Infectious Diseases  2014;14(1):662.
Background
Little is known about the parasite/host factors that lead to Post Kala-azar Dermal Leishmaniasis (PKDL) in some visceral leishmaniasis (VL) patients after drug-cure. Studies in Sudan provide evidence for association between polymorphisms in the gene (IFNGR1) encoding the alpha chain of interferon-γ receptor type I and risk of PKDL. This study aimed to identify putative functional polymorphisms in the IFNGR1 gene, and to determine whether differences in expression of interferon-γ (IFNG) and IFNGR1 at the RNA level are associated with pathogenesis of VL and/or PKDL in Sudan.
Methods
Sanger sequencing was used to re-sequence 841 bp of upstream, exon1 and intron1 of the IFNGR1 gene in DNA from 30 PKDL patients. LAGAN and SYNPLOT bioinformatics tools were used to compare human, chimpanzee and dog sequences to identify conserved noncoding sequences carrying putative regulatory elements. The relative expression of IFNG and IFNGR1 in paired pre- and post-treatment RNA samples from the lymph nodes of 24 VL patients, and in RNA samples from skin biopsies of 19 PKDL patients, was measured using real time PCR. Pre- versus post-treatment expression was evaluated statistically using the nonparametric Wilcoxon matched pairs signed-rank test.
Results
Ten variants were identified in the 841 bp of sequence, four of which are novel polymorphisms at -77A/G, +10 C/T, +18C/T and +91G/T relative to the IFNGR1 initiation site. A cluster of conserved non-coding sequences with putative regulatory variants was identified in the distal promoter of IFNGR1. Variable expression of IFNG was detected in lymph node aspirates of VL patients before treatment, with a marked reduction (P = 0.006) in expression following treatment. IFNGR1 expression was also variable in lymph node aspirates from VL patients, with no significant reduction in expression with treatment. IFNG expression was undetectable in the skin biopsies of PKDL cases, while IFNGR1 expression was also uniformly low.
Conclusions
Uniformly low expression of IFN and IFNGR1 in PKDL skin biopsies could explain parasite persistence and is consistent with prior demonstration of genetic association with IFNGR1 polymorphisms. Identification of novel potentially functional rare variants at IFNGR1 makes an important general contribution to knowledge of rare variants of potential relevance in this Sudanese population.
doi:10.1186/s12879-014-0662-5
PMCID: PMC4265480  PMID: 25466928
PKDL; Visceral leishmaniasis; Polymorphisms; RNA expression; IFNG; IFNGR1; Rare variants; Sudan
3.  Whole Mitochondrial and Plastid Genome SNP Analysis of Nine Date Palm Cultivars Reveals Plastid Heteroplasmy and Close Phylogenetic Relationships among Cultivars 
PLoS ONE  2014;9(4):e94158.
Date palm is a very important crop in western Asia and northern Africa, and it is the oldest domesticated fruit tree with archaeological records dating back 5000 years. The huge economic value of this crop has generated considerable interest in breeding programs to enhance production of dates. One of the major limitations of these efforts is the uncertainty regarding the number of date palm cultivars, which are currently based on fruit shape, size, color, and taste. Whole mitochondrial and plastid genome sequences were utilized to examine single nucleotide polymorphisms (SNPs) of date palms to evaluate the efficacy of this approach for molecular characterization of cultivars. Mitochondrial and plastid genomes of nine Saudi Arabian cultivars were sequenced. For each species about 60 million 100 bp paired-end reads were generated from total genomic DNA using the Illumina HiSeq 2000 platform. For each cultivar, sequences were aligned separately to the published date palm plastid and mitochondrial reference genomes, and SNPs were identified. The results identified cultivar-specific SNPs for eight of the nine cultivars. Two previous SNP analyses of mitochondrial and plastid genomes identified substantial intra-cultivar ( = intra-varietal) polymorphisms in organellar genomes but these studies did not properly take into account the fact that nearly half of the plastid genome has been integrated into the mitochondrial genome. Filtering all sequencing reads that mapped to both organellar genomes nearly eliminated mitochondrial heteroplasmy but all plastid SNPs remained heteroplasmic. This investigation provides valuable insights into how to deal with interorganellar DNA transfer in performing SNP analyses from total genomic DNA. The results confirm recent suggestions that plastid heteroplasmy is much more common than previously thought. Finally, low levels of sequence variation in plastid and mitochondrial genomes argue for using nuclear SNPs for molecular characterization of date palm cultivars.
doi:10.1371/journal.pone.0094158
PMCID: PMC3981771  PMID: 24718264
4.  Safety and Efficacy of Single Dose versus Multiple Doses of AmBisome® for Treatment of Visceral Leishmaniasis in Eastern Africa: A Randomised Trial 
Background
Anti-leishmanial drug regimens that include a single dose AmBisome® could be suitable for eastern African patients with symptomatic visceral leishmaniasis (VL) but the appropriate single dose is unknown.
Methodology
A multi-centre, open-label, non-inferiority, randomized controlled trial with an adaptive design, was conducted to compare the efficacy and safety of a single dose and multiple doses of AmBisome® for the treatment of VL in eastern Africa. The primary efficacy endpoint was definitive cure (DC) at 6 months. Symptomatic patients with parasitologically-confirmed, non-severe VL, received a single dose of AmBisome® 7.5 mg/kg body weight or multiple doses, 7 times 3 mg/kg on days 1–5, 14, and 21. If interim analyses, evaluated 30 days after the start of treatment following 40 or 80 patients, showed the single dose gave significantly poorer parasite clearance than multiple doses at the 5% significance level, the single dose was increased by 2·5 mg/kg. In a sub-set of patients, parasite clearance was measured by quantitative reverse transcriptase (qRT) PCR.
Principal Findings
The trial was terminated after the third interim analysis because of low efficacy of both regimens. Based on the intention-to-treat population, DC was 85% (95%CI 73–93%), 40% (95%CI 19–64%), and 58% (95%CI 41–73%) in patients treated with multiple doses (n = 63), and single doses of 7·5 (n = 21) or 10 mg/kg (n = 40), respectively. qRT-PCR suggested superior parasite clearance with multiple doses as early as day 3. Safety data accorded with the drug label.
Conclusions
The tested AmBisome® regimens would not be suitable for VL treatment across eastern Africa. An optimal single dose regimen was not identified.
Trials Registration
www.clinicaltrials.gov NCT00832208
Author Summary
Visceral leishmaniasis is a potentially fatal disease which affects 0.2–0.4 million people every year, principally in South-East Asia, Latin America or Eastern Africa. Currently the safest drug in use is AmBisome®, which cures 90% of patients in India at 5 mg/kg, and is even more effective at higher doses (10 mg/kg) or in combination with miltefosine or paromomycin. These regimens have been shown to be equally cost-effective in India. However, the drug requires a cold chain for storage and reconstitution prior to injection. Although it is licensed for use in eastern Africa, in practice it is mainly used as a second-line treatment. A small study carried out in Kenya indicated that a higher dose is necessary in eastern Africa in contrast to Asia. This study aimed to determine the minimum single dose that is safe and effective for treatment of eastern African VL patients so as to be used in simplified treatment regimens. However, the tested regimens were found to be ineffective, and an optimal single dose that could potentially be used in simplified treatment regimens was not identified.
doi:10.1371/journal.pntd.0002613
PMCID: PMC3894173  PMID: 24454970
5.  Immunogenicity and immune modulatory effects of in silico predicted L. donovani candidate peptide vaccines 
Human Vaccines & Immunotherapeutics  2012;8(12):1769-1774.
Visceral leishmaniasis (VL) is a serious parasitic disease for which control measures are limited and drug resistance is increasing. First and second generation vaccine candidates have not been successful. The goal of the present study was to select possibly immunogenic L. donovani donovani GP63 peptides using immunoinformatics tools and to test their immunogenicity in vitro. The amino acid sequence of L. donovani donovani GP63 [GenBank accession: ACT31401] was screened using the EpiMatrix algorithm for putative T cell epitopes that would bind to the most common HLA class II alleles (DRB1*1101 and DRB1*0804) among at–risk populations. Four T cell epitopes were selected from nine potential candidates. Stimulation of whole blood from healthy volunteers using the peptides separately produced mean IFN-γ and IL-4 levels that were not significantly different from negative controls, while the pooled peptides produced a moderate IFN-γ increase in some volunteers. However, mean IL-10 levels were significantly reduced for all individuals compared with controls. The immunogenicity of these epitopes may be harnessed most effectively in a vaccine delivered in combination with immune-modulating adjuvants.
doi:10.4161/hv.21881
PMCID: PMC3656064  PMID: 22922767
visceral leishmaniasis; vaccine; T cell epitopes; EpiMatrix
6.  Ethyl 2-amino-4-(4-bromo­phen­yl)-6-meth­oxy-4H-benzo[h]chromene-3-carboxyl­ate 
In the title compound, C23H20BrNO4, the pyran ring has a flattened boat conformation with the O and methine C atoms lying to one side of the plane [0.160 (5) and 0.256 (6) Å, respectively] defined by the remaining atoms. Nevertheless, the 4H-benzo[h]chromene ring system approximates a plane (r.m.s. deviation = 0.116 Å) with the bromo­benzene ring almost perpendicular [dihedral angle = 83.27 (16)°] and the ester group coplanar [C—C—C—O = 3.4 (5)°]; the meth­oxy substituent is also coplanar [C—O—C—C = 174.5 (3)°]. In addition to an intra­molecular N—H⋯O(ester carbon­yl) hydrogen bond, the ester carbonyl O atom also forms an inter­molecular N—H⋯O hydrogen bond with the second amine H atom, generating a zigzag supra­molecular chain along the c axis in the crystal packing. The chains are linked into layers in the bc plane by N—H⋯Br hydrogen bonds, and these layers are consolidated into a three-dimensional architecture by C—H⋯π inter­actions.
doi:10.1107/S160053681300490X
PMCID: PMC3588478  PMID: 23476606
7.  Eichhornia crassipes (Mart) solms 
Plant Signaling & Behavior  2011;6(6):834-836.
Water hyacinth, Eichhornia crassipes (Mart) Solms, originating in the amazonian basin, is a warm water aquatic plant. Water hyacinth is considered one of the most productive plants on earth and, accordingly, is considered one of the top ten world's worst weeds. Water hyacinth spread to other tropical and subtropical regions by humans. It invaded about 62 countries in Africa, Asia and North America, and propagated extremely serious ecological, economical and social problems in the region between 40 degrees north and 45 degrees south. The dense weed of water hyacinth forms dense monocultures that can threaten local native species diversity and change the physical and chemical aquatic environment, thus altering ecosystem structure and function by disrupting food chains and nutrient cycling. We have separated and identified nine active fractions from water hyacinth and showed their promising therapeutic activities. Several compounds (alkaloid, phthalate derivatives, propanoid and phenyl derivatives) were identified in the extract of water hyacinth.
doi:10.4161/psb.6.6.15166
PMCID: PMC3218481  PMID: 21494097
water hyacinth; antimicrobial; anticancer; active compounds
8.  IFNG and IFNGR1 gene polymorphisms and susceptibility to post kala-azar dermal leishmaniasis in Sudan 
Genes and immunity  2006;8(1):75-78.
Post kala-azar dermal leishmanaisis (PKDL) in Sudan is associated with elevated interferon-γ. To study interferon-γ pathways in PKDL, we genotyped 80 trios from the Masalit ethnic group for polymorphisms at −470 ins/delTT, -270T/C, -56T/C and +95T/C in IFNGR1, and at −179G/A and +874T/A in IFNG. No associations occurred at IFNG. Global association with haplotypes comprising all 4 markers at IFNGR1 (χ210df = 21.97, P=0.015) was observed, associated with a significant (χ21df=4.54, P=0.033) bias in transmission of the haplotype insTT T T T, and less (χ21df=5.59, P=0.018) than expected transmission of insTT C C C. When compared with data on malaria associations from The Gambia, the results suggest a complex pattern of haplotypic variation at the IFNGR1 promoter locus associated with different infectious disease in African populations that reflect the complex roles of IFN-γ in parasite killing versus inflammation and pathogenesis.
doi:10.1038/sj.gene.6364353
PMCID: PMC2330095  PMID: 17136124
PKDL; leishmaniasis; association; IFNGR1
9.  Detecting hepatic steatosis using ultrasound-induced thermal strain imaging: an ex vivo animal study 
Physics in medicine and biology  2014;59(4):881-895.
Hepatic steatosis or fatty liver disease occurs when lipids accumulate within the liver and can lead to steatohepatitis, cirrhosis, liver cancer, and eventual liver failure requiring liver transplant. Conventional brightness mode (B-mode) ultrasound (US) is the most common noninvasive diagnostic imaging modality used to diagnose hepatic steatosis in clinics. However, it is mostly subjective or requires a reference organ such as the kidney or spleen with which to compare. This comparison can be problematic when the reference organ is diseased or absent. The current work presents an alternative approach to noninvasively detecting liver fat content using ultrasound-induced thermal strain imaging (US-TSI). This technique is based on the difference in the change in the speed of sound as a function of temperature between water- and lipid-based tissues. US-TSI was conducted using two system configurations including a mid-frequency scanner with a single linear array transducer (5-14 MHz) for both imaging and heating and a high-frequency (13-24 MHz) small animal imaging system combined with a separate custom-designed US heating transducer array. Fatty livers (n=10) with high fat content (45.6 ± 11.7%) from an obese mouse model and control livers (n=10) with low fat content (4.8± 2.9%) from wild-type mice were embedded in gelatin. Then, US imaging was performed before and after US induced heating. Heating time periods of ~3 s and ~9.2 s were used for the mid-frequency imaging and high-frequency imaging systems, respectively to induce temperature changes of approximately 1.5 °C. The apparent echo shifts that were induced as a result of sound speed change were estimated using 2D phase-sensitive speckle tracking. Following US-TSI, histology was performed to stain lipids and measure percentage fat in the mouse livers. Thermal strain measurements in fatty livers (−0.065±0.079%) were significantly (p<0.05) higher than those measured in control livers (−0.124±0.037%). Using histology as a gold standard to classify mouse livers, US-TSI had a sensitivity and specificity of 70% and 90%, respectively. The area under the receiver operating characteristic (ROC) curve (AUC) was 0.775. This ex vivo study demonstrates the feasibility of using US-TSI to detect fatty livers and warrants further investigation of US-TSI as a diagnostic tool for hepatic steatosis.
doi:10.1088/0031-9155/59/4/881
PMCID: PMC3971123  PMID: 24487698
Fatty liver disease; Obese mouse; Ultrasound thermal strain
10.  Economic considerations and health in all policies initiatives: evidence from interviews with key informants in Sweden, Quebec and South Australia 
BMC Public Health  2015;15:171.
Background
Health in All Policies (HiAP) is a form of intersectoral action that aims to include the promotion of health in government initiatives across sectors. To date, there has been little study of economic considerations within the implementation of HiAP.
Methods
As part of an ongoing program of research on the implementation of HiAP around the world, we examined how economic considerations influence the implementation of HiAP. By economic considerations we mean the cost and financial gain (or loss) of implementing a HiAP process or structure within government, or the cost and financial gain (or loss) of the policies that emerge from such a HiAP process or structure. We examined three jurisdictions: Sweden, Quebec and South Australia. Semi-structured telephone interviews were conducted with 12 to 14 key informants in each jurisdiction. Two investigators separately coded transcripts to identify relevant statements.
Results
Initial readings of transcripts led to the development of a coding framework for statements related to economic considerations. First, economic evaluations of HiAP are viewed as important for prompting HiAP and many forms of economic evaluation were considered. However, economic evaluations were often absent, informal, or incomplete. Second, funding for HiAP initiatives is important, but is less important than a high-level commitment to intersectoral collaboration. Furthermore, having multiple sources of funding of HiAP can be beneficial, if it increases participation across government, but can also be disadvantageous, if it exposes underlying tensions. Third, HiAP can also highlight the challenge of achieving both economic and social objectives.
Conclusions
Our results are useful for elaborating propositions for use in realist multiple explanatory case studies. First, we propose that economic considerations are currently used primarily as a method by health sectors to promote and legitimize HiAP to non-health sectors with the goal of securing resources for HiAP. Second, allocating resources and making funding decisions regarding HiAP are inherently political acts that reflect tensions within government sectors. This study contributes important insights into how intersectoral action works, how economic evaluations of HiAP might be structured, and how economic considerations can be used to both promote HiAP and to present barriers to implementation.
doi:10.1186/s12889-015-1350-0
PMCID: PMC4336489
Economic analysis; Healthy public policy; Health impact assessment; Public health; Policy and implementation; Health in all policies
11.  Neurochemical, structural and neurobehavioral evidence of neuronal protection by whey proteins in diabetic albino mice 
Background
Diabetes Mellitus (DM) is associated with pathological changes in the central nervous system (CNS) and alterations in oxidative stress. The aim of this study was to determine whether dietary supplement with whey protein (WP) could improve neurobehavior, oxidative stress and neuronal structure in the CNS.
Methods
Animals were distributed in three groups, a control group (N), a diabetic mellitus group (DM) and a DM group orally supplemented with WP (WP).
Results
The DM group of animals receiving WP had reduced blood glucose, significantly decreased free radical Diphenyl-picrylhydrazyl (DPPH) and lower lipid peroxidation in brain tissue. The WP group of animals showed improvement in balancing, coordination and fore-limb strength, oxidative stress and neuronal structure.
Conclusion
The results of this study show that dietary supplementation with WP reduced oxidative stress, protected CNS neurons and improved the neurobehavior of diabetic mice.
doi:10.1186/s12993-015-0053-0
PMCID: PMC4331294
Whey protein; Diabetes; Oxidative stress
12.  Synergistic effects of NOD1 or NOD2 and TLR4 activation on mouse sickness behavior in relation to immune and brain activity markers☆ 
Brain, Behavior, and Immunity  2015;44:106-120.
Toll-like receptors (TLRs) and nuclear-binding domain (NOD)-like receptors (NLRs) are sensors of bacterial cell wall components to trigger an immune response. The TLR4 agonist lipopolysaccharide (LPS) is a strong immune activator leading to sickness and depressed mood. NOD agonists are less active but can prime immune cells to augment LPS-induced cytokine production. Since the impact of NOD and TLR co-activation in vivo has been little studied, the effects of the NOD1 agonist FK565 and the NOD2 agonist muramyl dipeptide (MDP), alone and in combination with LPS, on immune activation, brain function and sickness behavior were investigated in male C57BL/6N mice.
Intraperitoneal injection of FK565 (0.001 or 0.003 mg/kg) or MDP (1 or 3 mg/kg) 4 h before LPS (0.1 or 0.83 mg/kg) significantly aggravated and prolonged the LPS-evoked sickness behavior as deduced from a decrease in locomotion, exploration, food intake and temperature. When given alone, FK565 and MDP had only minor effects. The exacerbation of sickness behavior induced by FK565 or MDP in combination with LPS was paralleled by enhanced plasma protein and cerebral mRNA levels of proinflammatory cytokines (IFN-γ, IL-1β, IL-6, TNF-α) as well as enhanced plasma levels of kynurenine. Immunohistochemical visualization of c-Fos in the brain revealed that NOD2 synergism with TLR4 resulted in increased activation of cerebral nuclei relevant to sickness.
These data show that NOD1 or NOD2 synergizes with TLR4 in exacerbating the immune, sickness and brain responses to peripheral immune stimulation.
Our findings demonstrate that the known interactions of NLRs and TLRs at the immune cell level extend to interactions affecting brain function and behavior.
doi:10.1016/j.bbi.2014.08.011
PMCID: PMC4295938  PMID: 25218901
Anxiety; c-Fos; Corticosterone; FK565; Food intake; Kynurenine; Lipopolysaccharide; Locomotion; Muramyl dipeptide; Proinflammatory cytokines
13.  Noninvasive Glaucoma Procedures: Current Options and Future Innovations 
Noninvasive glaucoma procedures (NIGPs) represent a new dawn in the management of glaucoma. They try to fill the gap between the shortcoming of invasive glaucoma surgeries and antiglaucoma medications. NIGPs were introduced as an adjunct or alternative treatments for glaucoma. Some of these procedures have shown good efficacy with few serious complications. Hence, they are now used as both primary and adjunctive therapy for glaucoma. The most common NIGPS involve laser and ultrasound technologies. Currently, the portfolio of NIGPs includes argon laser trabeculoplasty, selective laser trabeculoplasty, and micropulse diode laser trabeculoplasty. More recent innovations include therapeutic ultrasound for glaucoma, ultrasonic circular cyclocoagulation, and deep wave trabeculoplasty.
doi:10.4103/0974-9233.148342
PMCID: PMC4302472  PMID: 25624667
Deep Wave Trabeculoplasty; High-intensity Focused Ultrasound; Noninvasive Glaucoma Procedures; Laser Trabeculoplasty; Ultrasound Circular Coagulation
14.  Serodetection of Dengue virus and its antibodies among blood donors in the western region of Saudi Arabia: a preliminary study 
Blood Transfusion  2015;13(1):135-138.
doi:10.2450/2014.0134-14
PMCID: PMC4317098  PMID: 25369603
Dengue virus; Saudi Arabia; blood donors; seroprevalence
15.  Drinking water quality and public health in Southwestern Saudi Arabia: The need for a national monitoring program 
Aim of the Study:
The aim was to investigate the bacteriological quality of drinking water, and explore the factors involved in the knowledge of the public about the quality of drinking water in Najran region, Saudi Arabia.
Study Design:
A cross-sectional descriptive study.
Materials and Methods:
A total of 160 water samples were collected. Total coliforms, fecal coliform, and fecal streptococci were counted using Most Probable Number method. The bacterial genes lacZ and uidA specific to total coliforms and Escherichia coli, respectively, were detected using multiplex polymerase chain reaction. An interview was conducted with 1200 residents using a questionnaire.
Results:
Total coliforms were detected in 8 (20%) of 40 samples from wells, 13 (32.5%) of 40 samples from tankers, and 55 (68.8%) of 80 samples from roof tanks. Twenty (25%) and 8 (10%) samples from roof tanks were positive for E. coli and Streptococcus faecalis, respectively. Of the 1200 residents participating in the study, 10%, 45.5%, and 44.5% claimed that they depended on municipal water, bottled water, and well water, respectively. The majority (95.5%) reported the use of roof water tanks as a source of water supply in their homes. Most people (80%) believed that drinking water transmitted diseases. However, only 25% of them participated in educational programs on the effect of polluted water on health.
Conclusions:
Our results could help health authorities consider a proper regular monitoring program and a sustainable continuous assessment of the quality of well water. In addition, this study highlights the importance of the awareness and educational programs for residents on the effect of polluted water on public health.
doi:10.4103/2230-8229.149581
PMCID: PMC4317990  PMID: 25657607
Coliforms; drinking water; fecal streptococci; Pseudomonas aeruginosa; polymerase chain reaction; wells
16.  Factors associated with public awareness of the Crown Health Program in the Al-Jouf Region 
Objectives:
A community-based intervention, the Crown Health Project (CHP), was developed by the Ministry of Health. It was implemented on a small-scale in Al-Jouf Region in Northern Kingdom of Saudi Arabia to assess its feasibility and effectiveness so that it can be scaled up. This study primarily aimed at investigating factors associated with the awareness of CHP in order to improve subsequent campaigns for the program in Al-Jouf and other regions. A secondary aim was to assess possible changes of public awareness during intensification of the awareness campaign between October 2011 and May 2012.
Methods:
A pre- and post-questionnaire cross-sectional approach was undertaken, and the intervention was an awareness campaign. Variables collected included demographic characteristics (e.g., age, gender, education, occupation, urban/rural residence) and CHP awareness (its existence, sources of knowledge about CHP, its goals and objectives, its target diseases, location of activities, participation in such activities). Logistic regression was used to analyze the awareness of the program according to participant characteristics, with a time of the survey as a variable.
Results:
Awareness of the program was found to be 11 times higher among postsurvey respondents than presurvey respondents. Respondents of the second survey were better at correctly identifying “health education” as the main goal of the CHP (odds ratio [OR], 4.1; 95% confidence interval [CI], 3.1–5.5), “noncommunicable diseases” as the main diseases targeted (OR, 4.8; 95% CI, 3.6–6.4) and “attention to health” as the purpose (OR, 6.0; 95% CI, 4.0–8.9).
Conclusion:
The different activities of the CHP were successful in dramatically increasing awareness of the CHP program in Al-Jouf.
doi:10.4103/2230-8229.149586
PMCID: PMC4317992  PMID: 25657609
Community-based health education; noncommunicable diseases; Saudi Arabia
17.  The efficacy and safety of plasma exchange in patients with sepsis and septic shock: a systematic review and meta-analysis 
Critical Care  2014;18(6):699.
Introduction
Sepsis and septic shock are leading causes of intensive care unit (ICU) mortality. They are characterized by excessive inflammation, upregulation of procoagulant proteins and depletion of natural anticoagulants. Plasma exchange has the potential to improve survival in sepsis by removing inflammatory cytokines and restoring deficient plasma proteins. The objective of this study is to evaluate the efficacy and safety of plasma exchange in patients with sepsis.
Methods
We searched MEDLINE, EMBASE, CENTRAL, Scopus, reference lists of relevant articles, and grey literature for relevant citations. We included randomized controlled trials comparing plasma exchange or plasma filtration with usual care in critically ill patients with sepsis or septic shock. Two reviewers independently identified trials, extracted trial-level data and performed risk of bias assessments using the Cochrane Risk of Bias tool. The primary outcome was all-cause mortality reported at longest follow-up. Meta-analysis was performed using a random-effects model.
Results
Of 1,957 records identified, we included four unique trials enrolling a total of 194 patients (one enrolling adults only, two enrolling children only, one enrolling adults and children). The mean age of adult patients ranged from 38 to 53 years (n = 128) and the mean age of children ranged from 0.9 to 18 years (n = 66). All trials were at unclear to high risk of bias. The use of plasma exchange was not associated with a significant reduction in all-cause mortality (risk ratio (RR) 0.83, 95% confidence interval (CI) 0.45 to 1.52, I2 60%). In adults, plasma exchange was associated with reduced mortality (RR 0.63, 95% CI 0.42 to 0.96; I2 0%), but was not in children (RR 0.96, 95% CI 0.28 to 3.38; I2 60%). None of the trials reported ICU or hospital lengths of stay. Only one trial reported adverse events associated with plasma exchange including six episodes of hypotension and one allergic reaction to fresh frozen plasma.
Conclusions
Insufficient evidence exists to recommend plasma exchange as an adjunctive therapy for patients with sepsis or septic shock. Rigorous randomized controlled trials evaluating clinically relevant patient-centered outcomes are required to evaluate the impact of plasma exchange in this condition.
Electronic supplementary material
The online version of this article (doi:10.1186/s13054-014-0699-2) contains supplementary material, which is available to authorized users.
doi:10.1186/s13054-014-0699-2
PMCID: PMC4318234  PMID: 25527094
18.  Systematic Nucleo-Cytoplasmic Trafficking of Proteins Following Exposure of MCF7 Breast Cancer Cells to Estradiol 
Journal of proteome research  2014;13(2):1112-1127.
We have used a proteomics subcellular spatial razor approach to look at changes in total protein abundance and in protein distribution between the nucleus and cytoplasm following exposure of MCF7 breast cancer cells to estradiol. The dominant response of MCF7 cells to estrogen stimulation involves dynamic changes in protein subcellular spatial distribution rather than changes in total protein abundance. Of the 3604 quantitatively monitored proteins, only about 2% show substantial changes in total abundance (>2-fold), whereas about 20% of the proteins show substantial changes in local abundance and/or redistribution of their subcellular location, with up to 16-fold changes in their local concentration in the nucleus or the cytoplasm. We propose that dynamic redistribution of the subcellular location of multiple proteins in response to stimuli is a fundamental characteristic of cells and suggest that perturbation of cellular spatial control may be an important feature of cancer.
doi:10.1021/pr4012359
PMCID: PMC4261610  PMID: 24422525
Estrogen; MCF-7 cells; breast cancer; subcellular protein location; nucleus; cytoplasm; SILAC; quantitative proteomics; mass spectrometry; estrogen receptor; nuclear hormone receptors; protein trafficking
19.  Diagnostic accuracy of a screening electronic alert tool for severe sepsis and septic shock in the emergency department 
Background
Early recognition of severe sepsis and septic shock is challenging. The aim of this study was to determine the diagnostic accuracy of an electronic alert system in detecting severe sepsis or septic shock among emergency department (ED) patients.
Methods
An electronic sepsis alert system was developed as a part of a quality-improvement project for severe sepsis and septic shock. The system screened all adult ED patients for a combination of systemic inflammatory response syndrome and organ dysfunction criteria (hypotension, hypoxemia or lactic acidosis). This study included all patients older than 14 years who presented to the ED of a tertiary care academic medical center from Oct. 1, 2012 to Jan. 31, 2013. As a comparator, emergency medicine physicians or the critical care physician identified the patients with severe sepsis or septic shock.
In the ED, vital signs were manually entered into the hospital electronic heath record every hour in the critical care area and every two hours in other areas. We also calculated the time from the alert to the intensive care unit (ICU) referral.
Results
Of the 49,838 patients who presented to the ED, 222 (0.4%) were identified to have severe sepsis or septic shock. The electronic sepsis alert had a sensitivity of 93.18% (95% CI, 88.78% - 96.00%), specificity of 98.44 (95% CI, 98.33% – 98.55%), positive predictive value of 20.98% (95% CI, 18.50% – 23.70%) and negative predictive value of 99.97% (95% CI, 99.95% – 99.98%) for severe sepsis and septic shock. The alert preceded ICU referral by a median of 4.02 hours (Q1 - Q3: 1.25–8.55).
Conclusions
Our study shows that electronic sepsis alert tool has high sensitivity and specificity in recognizing severe sepsis and septic shock, which may improve early recognition and management.
doi:10.1186/s12911-014-0105-7
PMCID: PMC4261595  PMID: 25476738
Clinical decision support; Sepsis; Sensitivity and specificity; Septic shock; Emergency department; Electronic alert
20.  Cost-effectiveness of Newer Antiretroviral Drugs in Treatment-Experienced Patients with Multi-drug Resistant HIV Disease 
Objective
Newer antiretroviral drugs provide substantial benefits but are expensive. We determined the cost-effectiveness of using antiretroviral drugs in combination for patients with multi-drug resistant HIV disease.
Design
We built a cohort state-transition model representing treatment-experienced patients with low CD4 counts, high viral load levels, and multi-drug resistant virus. We estimated the effectiveness of newer drugs (those approved in 2005 or later) from published randomized trials. We estimated other parameters from a randomized trial and from the literature. The model had a lifetime time horizon and used the perspective of an ideal insurer in the United States. The interventions were combination antiretroviral therapy, consisting of two newer drugs and one conventional drug, compared to three conventional drugs. Outcome measures were life-years, quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness.
Results
Substituting newer antiretroviral drugs increased expected survival by 3.9 years in advanced HIV disease. The incremental cost-effectiveness ratio of newer, compared to conventional, antiretroviral drugs was $75,556/QALY gained. Sensitivity analyses showed that substituting only one newer antiretroviral drug cost $54,559 to $68,732/QALY, depending on assumptions about efficacy. Substituting three newer drugs cost $105,956 to $117,477/QALY. Cost-effectiveness ratios were higher if conventional drugs were not discontinued.
Conclusions
In treatment-experienced patients with advanced HIV disease, use of newer antiretroviral agents can be cost effective, given a cost-effectiveness threshold in the range of $50,000 to $75,000 per QALY gained. Newer antiretroviral agents should be used in carefully selected patients for whom less expensive options are clearly inferior.
doi:10.1097/QAI.0000000000000002
PMCID: PMC3932156  PMID: 24129369
Novel antiretroviral drugs; multi-drug resistant HIV infection; cost-effectiveness analysis; quality of life; health economics
21.  Quality of Antenatal Care in Primary Health Care Centers of Bangladesh 
Objective: To find out the quality of ANC in the Upazila Health Complexes (PHC centres) of Bangladesh.
Materials and methods: This cross sectional study was done in purposively selected three upazilas among the clients receiving antenatal care (ANC). Data were collected with questionnaire cum checklist in the context of two aspects of quality issues, namely assessment of physical arrangements for ANC (input) and services rendered by the providers (process).
Results: The mean age of respondents was 24.6±4.5 years. Majority of the respondents were with primary level education (60.3%). About half (52.8%) of the families had monthly income ranging from 3000-5000 taka (38-64 US$). Nearly half (48.9%) had no child, little more than one third (42.3%) were primigravida and 528 (57.7%) were multigravida. Out of 528 multigravid respondents 360 (68.2%) took ANC in their previous pregnancy whereas 168 (31.8%) did not take ANC Pregnancy outcome was found to be associated with receiving ANC (χ2=73.599; p=0.000). Respondents receiving ANC had more good pregnancy outcome. The mean waiting time for receiving ANC was 0.77±.49 hours. Out of the 13 centers, only 3 (23.1%) have sufficient instruments to render ANC services. Findings showed that where the modes of ANC service delivery in the ANC centers are fairly satisfactory. Though some of the points of standard operation procedures (SOPs) on ANC are not covered by some ANC centers, those were not considered necessary. But, regarding the physical facilities available for rendering ANC services, it is seen that facilities are not quite satisfactory. Number of doctors and nurses are not very satisfactory. One of the centers under this study has no doctor, where ANC services are given by nurses.
Conclusion: It can be concluded that the ANC services at the primary health care level is not adequate in Bangladesh. To ensure further improvement of the quality of ANC services, instruments used in logistics and supplies should be enhanced.
PMCID: PMC4266789  PMID: 25530770
Antenatal Care; Primigravida; Multigravida; Primary Health Care
22.  P-glycoprotein inhibitors of natural origin as potential tumor chemo-sensitizers: A review 
Journal of Advanced Research  2014;6(1):45-62.
Graphical abstract
Resistance of solid tumors to treatment is significantly attributed to pharmacokinetic reasons at both cellular and multi-cellular levels. Anticancer agent must be bio-available at the site of action in a cytotoxic concentration to exert its proposed activity. P-glycoprotein (P-gp) is a member of the ATP-dependent membrane transport proteins; it is known to pump substrates out of cells in ATP-dependent mechanism. The over-expression of P-gp in tumor cells reduces the intracellular drug concentrations, which decreases the cytotoxicity of a broad spectrum of antitumor drugs. Accordingly, P-gp inhibitors/blockers are potential enhancer for the cellular bioavailability of several clinically important anticancer drugs such as, anthracyclines, taxanes, vinca alkaloids, and podophyllotoxins. Besides several chemically synthesized P-gp inhibitors/blockers, some naturally occurring compounds and plant extracts were reported for their modulation of multidrug resistance; however, this review will focus only on major classes of naturally occurring inhibitors viz., flavonoids, coumarins, terpenoids, alkaloids and saponins.
doi:10.1016/j.jare.2014.11.008
PMCID: PMC4293676
Multidrug resistance (MDR); Multidrug resistance-associated protein 1 (MRP1); Natural products; P-gp (P-glycoprotein)
23.  Changes in Sexual Risk Behavior in the Mombasa Cohort: 1993–2007 
PLoS ONE  2014;9(11):e113543.
The Mombasa Cohort is an open cohort study following HIV-seronegative women reporting transactional sex. Established in 1993, the cohort provides regular HIV counseling and testing at monthly visits. Over time, HIV acquisition risk has declined steadily in this cohort. To evaluate whether this decline may reflect changes in sexual risk behavior, we investigated trends in condom use and partner numbers among women who participated in the Mombasa Cohort between 1993 and 2007. Multinomial logistic regression and generalized estimating equations were used to evaluate the association of calendar time and follow-up time with key risk behaviors, after adjustment for potential confounding factors. At enrollment visits by 1,844 women, the adjusted probability of never using condoms decreased over time, from 34.2% to 18.9%. Over 23,911 follow-up visits, the adjusted probabilities of reporting >2 partners decreased from 9.9% to 4.9% and inconsistent condom use decreased from 7.9% to 5.3% after ≥12 cohort visits. Important predictors of risk behavior were work venue, charging low fees for sex, and substance abuse. Women with a later sexual debut had less risky behavior. Although sexual risk has declined among women participating in the Mombasa Cohort, HIV acquisition continues to occur and interventions to promote and reinforce safer sex are clearly needed.
doi:10.1371/journal.pone.0113543
PMCID: PMC4240588  PMID: 25415287
24.  The Airport Gate Assignment Problem: A Survey 
The Scientific World Journal  2014;2014:923859.
The airport gate assignment problem (AGAP) is one of the most important problems operations managers face daily. Many researches have been done to solve this problem and tackle its complexity. The objective of the task is assigning each flight (aircraft) to an available gate while maximizing both conveniences to passengers and the operational efficiency of airport. This objective requires a solution that provides the ability to change and update the gate assignment data on a real time basis. In this paper, we survey the state of the art of these problems and the various methods to obtain the solution. Our survey covers both theoretical and real AGAP with the description of mathematical formulations and resolution methods such as exact algorithms, heuristic algorithms, and metaheuristic algorithms. We also provide a research trend that can inspire researchers about new problems in this area.
doi:10.1155/2014/923859
PMCID: PMC4258332  PMID: 25506074
25.  Vitreous Hemorrhage in Pediatric Age Group 
Journal of Ophthalmology  2014;2014:497083.
Purpose. To identify and study causes of vitreous hemorrhage (VH) in pediatric age group and to investigate factors predicting visual and anatomical outcomes. Procedure. A retrospective review of patients aged 16 years or less with the diagnosis of vitreous hemorrhage from January 2005 until December 2010. Results. A total number of 230 patients (240 eyes) were identified. Traumatic vitreous hemorrhage accounted for 82.5%. In cases of accidental trauma, final visual acuity of 20/200 was significantly associated with visual acuity of ≥20/200 at presentation and the absence of retinal detachment at last follow-up. Patients with nontraumatic vitreous hemorrhage were significantly younger with higher rates of enucleation/evisceration/exenteration and retinal detachment at last follow-up compared to traumatic cases. Conclusion. Trauma is the most common cause of VH in pediatric age group. In this group, initial visual acuity was the most important predictor for visual outcome, and the presence of retinal detachment is a negative predictor for final good visual outcome. The outcome is significantly worse in nontraumatic cases compared to traumatic cases.
doi:10.1155/2014/497083
PMCID: PMC4254071  PMID: 25505975

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