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1.  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.
PMCID: PMC3981771  PMID: 24718264
2.  Safety and Efficacy of Single Dose versus Multiple Doses of AmBisome® for Treatment of Visceral Leishmaniasis in Eastern Africa: A Randomised Trial 
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.
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.
The tested AmBisome® regimens would not be suitable for VL treatment across eastern Africa. An optimal single dose regimen was not identified.
Trials Registration 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.
PMCID: PMC3894173  PMID: 24454970
3.  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.
PMCID: PMC3656064  PMID: 22922767
visceral leishmaniasis; vaccine; T cell epitopes; EpiMatrix
4.  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.
PMCID: PMC3588478  PMID: 23476606
5.  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.
PMCID: PMC2330095  PMID: 17136124
PKDL; leishmaniasis; association; IFNGR1
6.  Antibiotic resistance in lactic acid bacteria isolated from some pharmaceutical and dairy products 
A total of 244 lactic acid bacteria (LAB) strains were isolated from 180 dairy and pharmaceutical products that were collected from different areas in Minia governorate, Egypt. LAB were identified phenotypically on basis of morphological, physiological and biochemical characteristics. Lactobacillus isolates were further confirmed using PCR-based assay. By combination of phenotypic with molecular identification Lactobacillus spp. were found to be the dominant genus (138, 76.7%) followed by Streptococcus spp. (65, 36.1%) and Lactococcus spp. (27, 15%). Some contaminant organisms such as (Staphylococcus spp., Escherichia coli, Salmonella spp., mould and yeast) were isolated from the collected dairy samples but pharmaceutical products were free of such contaminants. Susceptibility of LAB isolates to antibiotics representing all major classes was tested by agar dilution method. Generally, LAB were highly susceptible to Beta-lactams except penicillin. Lactobacilli were resistant to vancomycin, however lactococci and streptococci proved to be very susceptible. Most strains were susceptible to tetracycline and showed a wide range of streptomycin MICs. The MICs of erythromycin and clindamycin for most of the LAB were within the normal range of susceptibility. Sixteen Lactobacillus, 8 Lactococcus and 8 Streptococcus isolates including all tetracycline and/or erythromycin resistant strains were tested for the presence of tetracycline and/or erythromycin resistant genes [tet(M) and/or erm(B)]. PCR assays shows that some resistant strains harbor tet(M) and/or erm(B) resistance genes.
PMCID: PMC4059307  PMID: 24948910
lactic acid bacteria; phenotypic and molecular identification; PCR assay; antibiotic resistance genes
7.  Seroprevalence of hepatitis B and C virus infections among health students and health care workers in the Najran region, southwestern Saudi Arabia: The need for national guidelines for health students 
BMC Public Health  2014;14:577.
The objectives of the study were to study the seroprevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections among health college students (HS) and health care workers (HCWs) in the Najran Region of south-western Saudi Arabia and to study the students’ knowledge of occupational exposure to blood-borne viral infections.
A cross-sectional study of a representative sample of 300 HS and 300 HCWs was conducted.
An overall seroprevalence of HBV of 1.7% and 8.7% was found among HS and HCWs, respectively. Two-thirds of HS (66.7%, 200) and 23.3% (70) of HCWs lack anti-HBs and are susceptible to HBV infection. An overall seroprevalence of HCV of 0% and 0.3% was found among the HS and HCWs, respectively. The present study indicates poor knowledge among HS and moderate knowledge among HCWs regarding occupationally transmitted blood-borne diseases, safe injection practices, and standard precautions to prevent occupationally transmitted blood-borne infections.
It is mandatory to develop a structured program to raise awareness among HS, and current health colleges’ curricula should be upgraded to address these issues early. The HS should be considered new recruits to health services in terms of their initial screening for blood-borne infections and vaccination against HBV. The development of a novel continuing medical education and pre-employment awareness program for HCWs is recommended to address the following: blood-borne diseases transmitted occupationally, standard precautions to prevent occupationally transmitted blood borne infections, and safe injection practices.
PMCID: PMC4059075  PMID: 24912684
HBV; HCV; HCW; Health Students; Saudi Arabia
8.  Isolation of Antiosteoporotic Compounds from Seeds of Sophora japonica 
PLoS ONE  2014;9(6):e98559.
Chemical investigation of Sophora japonica seeds resulted in the isolation of seven metabolites identified as: genistin (1), sophoricoside (2), sophorabioside (3), sophoraflavonoloside (4), genistein 7,4’-di-O-β-D-glucopyransoide (5), kaempferol 3-O-α–L-rhamnopyranosyl(1→6)β-D-glucopyranosyl(1→2)β-D-glucopyranoside (6) and rutin (7). Compounds 1, 2 and 5 showed significant estrogenic proliferative effect in MCF-7 cell in sub-cytotoxic concentration range. Compounds 1 and 2 showed minimal cell membrane damaging effect using LDH leakage assay. Accordingly, compound 2 (sophoricoside, (SPH)) was selected for further in-vivo studies as a potential anti-osteoporosis agent. The anti-osteoporotic effect of SPH was assessed in ovarectomized (OVX) rats after oral administration (15 mg/kg and 30 mg/kg) for 45 days compared to estradiol (10 µg/kg) as a positive control. Only in a dose of 30 mg/kg, SPH regained the original mechanical bone hardness compared to normal non-osteoporotic group. However, SPH (15 mg/kg) significantly increased the level of alkaline phosphatase (ALP) to normal level. Treatment with SPH (30 mg/kg) increased the level of ALP to be higher than normal group. SPH (15 mg/kg) did not significantly increase the serum level of osteocalcin (OC) compared to OVX group. On the other hand, treatment with SPH (30 mg/kg) significantly increased the level of OC to 78% higher than normal non-ovarectomized animals group. In addition, SPH (15 mg/kg) decreased the bone resorption marker, acid phosphatase (ACP) to normal level and SPH (30 mg/kg) further diminished the level of serum ACP. Histopathologically, sophoricoside ameliorated the ovarectomy induced osteoporosis in a dose dependent manner. The drug showed thicker bony trabeculae, more osteoid, and more osteoblastic rimming compared to OVX group.
PMCID: PMC4043785  PMID: 24892557
9.  Fetal Hemoglobin in Sickle Cell Anemia: Genetic Studies of the Arab-Indian Haplotype 
Sickle cell anemia is common in the Middle East and India where the HbS gene is sometimes associated with the Arab-Indian (AI) β-globin gene (HBB) cluster haplotype. In this haplotype of sickle cell anemia, fetal hemoglobin (HbF) levels are 3-4 fold higher than those found in patients with HbS haplotypes of African origin. Little is known about the genetic elements that modulate HbF in AI haplotype patients. We therefor studied Saudi HbS homozygotes with the AI haplotype (mean HbF 19.2±7.0%, range 3.6 to 39.6%) and known genotyped cis- and trans-acting elements associated with HbF expression. All cases, regardless of HbF concentration, were homozygous for AI haplotype-specific elements cis to HBB. SNPs in BCL11A and HBS1L-MYB that were associated with HbF in other populations explained only 8.8% of the variation of HbF. KLF1 polymorphisms associated previously with high HbF were not present In the 44 patients tested. The SNPs and genetic loci we have chosen for this study do not explain the high HbF in sickle cell patients with AI haplotype or its variation among patients with this haplotype. The dispersion of HbF levels among AI haplotype patients suggests that other genetic elements modulate the effects of the known cis- and trans-acting regulators. These regulatory elements, which remain to be discovered, might be specific in the Saudi and some other populations where HbF levels are especially high.
PMCID: PMC3647015  PMID: 23465615
10.  Dominant gain-of-function STAT1 mutations in FOXP3WT IPEX-like Syndrome 
Mutations in STAT1 cause a broad spectrum of disease, ranging from severe viral and bacterial infections (amorphic alleles), to mild disseminated mycobacterial disease (hypomorphic alleles), to chronic mucocutaneous candidiasis (hypermorphic alleles). The hypermorphic mutations are also associated with arterial aneurysms, autoimmunity and squamous cell cancers.
To investigate the role of STAT1 gain of function mutations in phenotypes other than CMC.
We initially screened patients with chronic mucocutaneous candidiasis and autoimmunity for STAT1 mutations. We functionally characterized mutations in vitro and studied immune profiles and regulatory T cells. After our initial case identifications we explored two large cohorts of FOXP3WT IPEX-like patients for STAT1 mutations.
We identified 5 children with polyendocrinopathy, enteropathy, and dermatitis, reminiscent of IPEX syndrome, all but one had a variety of mucosal and disseminated fungal infections. All patients lacked FOXP3 mutations but had uniallelic STAT1 mutations [c.629 G>T, p.R210I; c.1073 T>G, p.L358W, c.796G>A; p.V266I; c.1154C>T, T385M (2 patients)]. STAT1 phosphorylation in response to IFN-γ, IL-6 and IL-21 was increased and prolonged. CD4+ IL-17 producing T cells were diminished. All patients had a normal percentage of regulatory T cells in the CD4+ T cell compartment and their function was intact in the two patients tested. Patients with cells available for study had normal levels of IL-2-induced STAT5 phosphorylation..
Gain-of-function mutations in STAT1 can cause an IPEX-like syndrome with normal frequency and function of regulatory T cells.
PMCID: PMC3672257  PMID: 23534974
STAT1; IPEX; FOXP3; Treg; CMC; aneurysms
11.  Ethyl 5-methyl-7-phenyl-1,2,4-triazolo[4,3-a]pyrimidine-6-carboxyl­ate 
In the title compound, C15H14N4O2, the triazolo­pyrimidine ring system is almost planar (r.m.s. deviation = 0.02 Å) and the phenyl ring is inclined to its mean plane by 42.45 (9)°. The carboxyl group is inclined to the triazolo­pyrimidine ring mean plane by 57.8 (3)°. In the mol­ecule, there is a short C—H⋯O contact involving the carbonyl O atom and an H atom of the adjacent methyl substituent. In the crystal, neighbouring mol­ecules are linked by C—H⋯O hydrogen bonds, forming chains propagating along [010]. There are also weak π–π inter­actions present involving the pyridine and phenyl rings of neighbouring chains [inter­centroid distance = 3.8580 (16) Å].
PMCID: PMC4051068  PMID: 24940253
12.  Parity and Aortic Dimensions in Healthy Women 
International journal of cardiology  2012;165(2):383-384.
PMCID: PMC3532567  PMID: 22999343
Pregnancy; parity; aorta; magnetic resonance; aging
13.  Motion Artifact Reduction in Ultrasound Based Thermal Strain Imaging of Atherosclerotic Plaques Using Time Series Analysis 
Large lipid pools in vulnerable plaques, in principle, can be detected using US based thermal strain imaging (US-TSI). One practical challenge for in vivo cardiovascular application of US-TSI is that the thermal strain is masked by the mechanical strain caused by cardiac pulsation. ECG gating is a widely adopted method for cardiac motion compensation, but it is often susceptible to electrical and physiological noise. In this paper, we present an alternative time series analysis approach to separate thermal strain from the mechanical strain without using ECG. The performance and feasibility of the time-series analysis technique was tested via numerical simulation as well as in vitro water tank experiments using a vessel mimicking phantom and an excised human atherosclerotic artery where the cardiac pulsation is simulated by a pulsatile pump.
PMCID: PMC4010158  PMID: 24808628
14.  Safety and efficacy of Hansenula-derived PEGylated-interferon alpha-2a and ribavirin combination in chronic hepatitis C Egyptian children 
AIM: To investigate the safety and efficacy of a Hansenula-derived PEGylated (polyethylene glycol) interferon (IFN)-alpha-2a (Reiferon Retard) plus ribavirin customized regimen in treatment-naïve and previously treated (non-responders and relapsers) Egyptian children with chronic hepatitis C infection.
METHODS: Forty-six children with chronic hepatitis C virus (HCV) infection were selected from three tertiary pediatric hepatology centers. Clinical and laboratory evaluations were undertaken. Quantitative polymerase chain reaction (PCR) for HCV-RNA was performed before starting treatment, and again at 4, 12, 24, 48, 72 wk during treatment and 6 mo after treatment cessation. All patients were assigned to receive a weekly subcutaneous injection of PEG-IFN-alpha-2a plus daily oral ribavirin for 12 wk. Thirty-four patients were treatment-naïve and 12 had a previous treatment trial. Patients were then divided according to PCR results into two groups. Group I included patients who continued treatment on a weekly basis (7-d schedule), while group II included patients who continued treatment on a 5-d schedule. Patients from either group who were PCR-negative at week 48, but had at least one PCR-positive test during therapy, were assigned to have an extended treatment course up to 72 wk. The occurrence of adverse effects was assessed during treatment and follow up. The study was registered at (NCT02027493).
RESULTS: Only 11 out of 46 (23.9%) patients showed a sustained virological response (SVR), two patients were responders at the end of treatment; however, they were lost to follow up at 6 mo post treatment. Breakthrough was seen in 18 (39.1%) patients, one patient (2.17%) showed relapse and 14 (30.4%) were non-responders. Male gender, short duration of infection, low viral load, mild activity, and mild fibrosis were the factors related to a better response. On the other hand, patients with high viral load and absence of fibrosis failed to respond to treatment. Before treatment, liver transaminases were elevated. After commencing treatment, they were normalized in all patients at week 4 and were maintained normal in responders till the end of treatment, while they increased again significantly in non-responders (P = 0.007 and 0.003 at week 24 and 72 respectively). The 5-d schedule did not affect the response rate (1/17 had SVR). Treatment duration (whether 48 wk or extended course to 72 wk) gave similar response rates (9/36 vs 2/8 respectively; P = 0.49). Type of previous treatment (short acting IFN vs PEG-IFN) did not affect the response to retreatment. On the other hand, SVR was significantly higher in previous relapsers than in previous non-responders (P = 0.039). Only mild reversible adverse effects were observed and children tolerated the treatment well.
CONCLUSION: Reiferon Retard plus ribavirin combined therapy was safe. Our customized regimen did not influence SVR rates. Further trials on larger numbers of patients are warranted.
PMCID: PMC4000504  PMID: 24782620
Children; Chronic hepatitis C; Hansenula polymorpha; PEGylated interferon; Response rate; Ribavirin; Treatment
15.  The Potential Protective Effect of Physalis peruviana L. against Carbon Tetrachloride-Induced Hepatotoxicity in Rats Is Mediated by Suppression of Oxidative Stress and Downregulation of MMP-9 Expression 
The active constituent profile in Cape gooseberry (Physalis peruviana L.) juice was determined by GC-MS. Quercetin and kaempferol were active components in the juice. In this study we have evaluated its potential protective effect on hepatic injury and fibrosis induced by carbon tetrachloride (CCl4). Twenty-eight rats divided into 4 groups: Group I served as control group, and Group II received weekly i.p. injection of 2 mL CCl4/kg bwt for 12 weeks. Group III were supplemented with Physalis juice via the drinking water. The animals of Group IV received Physalis juice as Group III and also were intraperitoneally injected weekly with 2 mL CCl4/kg bwt for 12 weeks. Hepatoprotective effect was evaluated by improvement in liver enzymes serum levels, reduction in collagen areas, downregulation in expression of the fibrotic marker MMP-9, reduction in the peroxidative marker malonaldehyde and the inflammatory marker nitric oxide, and restoration of the activity of antioxidant enzymatic and nonenzymatic systems, namely, glutathione content, superoxide dismutase, catalase, glutathione-S-transferase, glutathione peroxidase, and glutathione reductase activities. The results show that the potential hepatoprotective effects of Physalis peruviana may be due to physalis acts by promotion of processes that restore hepatolobular architecture and through the inhibition of oxidative stress pathway.
PMCID: PMC4020166  PMID: 24876910
16.  The genus Micatagla Argaman, 1994 in Egypt, with three new species and a new record (Hymenoptera, Bradynobaenidae, Apterogyninae) 
ZooKeys  2014;71-81.
The genus Micatagla Argaman (Bradynobaenidae: Apterogyninae) is reviewed from Egypt, based on specimens collected from Wadi Allaqi (Aswan, Southern Egypt) and Kom Osheim (Fayoum) and those deposited in Egyptian insect collections as well as recorded data from the literature. A single species, Micatagla klugi (André), was previously recorded from Egypt. Micatagla allaqiensis sp. n., Micatagla ezzati sp. n. and Micatagla pseudorainerii sp. n. are described here. Micatagla antropovi Pagliano is also newly recorded from the Egyptian fauna. An illustrated key and a faunistic list comprising all Micatagla species recorded from Egypt are given.
PMCID: PMC3978232  PMID: 24715798
Apterogyninae; Micatagla; new species; new record; faunistic list
17.  Effects of Propranolol and Exercise Training in Children with Severe Burns 
The Journal of pediatrics  2012;162(4):799-803.e1.
To investigate whether propranolol administration blocks the benefits induced by exercise training in severely burned children.
Study design
Children aged 7–18 years (n=58) with burns covering ≥30% of the total body surface area (TBSA) were enrolled in this randomized trial during their acute hospital admission. Twenty-seven patients were randomized to receive propranolol, whilst 31 served as untreated controls. Both groups participated in 12 weeks of in-hospital resistance and aerobic exercise training. Muscle strength, lean body mass, and peak aerobic capacity (VO2 peak) were measured before and after exercise training. Paired and unpaired Student T-tests were used for within and between group comparisons, and Chi-squared tests for nominal data.
Age, length of hospitalization, and TBSA burned were similar between groups. In both groups, muscle strength, lean body mass, and VO2 peak were significantly greater after exercise training than at baseline. The percent change in VO2 peak was significantly greater in the propranolol group than in the control group (P< 0.05).
Exercise-induced enhancements in muscle mass, strength, and VO2 peak are not impaired by propranolol. Moreover, propranolol improves the aerobic response to exercise in massively burned children.
PMCID: PMC3556196  PMID: 23084706
Beta blocker; rehabilitation; aerobic capacity; muscle strength; hypermetabolic response; hypercatabolic response
18.  Pulmonary Vein Morphology by Free-Breathing Whole Heart Magnetic Resonance Imaging at 3T vs. Breathhold Multi-Detector Computed Tomography 
This study compares pulmonary vein and left atrial anatomy using 3D free-breathing whole-heart magnetic resonance imaging (MR) at 3T and multi-detector computed tomography (MDCT).
Materials and Methods
Thirty three subjects (19 male, age 49±12 years) underwent free-breathing 3T MR and contrast-enhanced MDCT during inspiratory breath hold. Pulmonary vein parameters (ostial areas, diameters, angles) were measured.
All pulmonary veins and anomalies were identified by 3T MR and by MDCT. The right-sided pulmonary veins were directed more posteriorly, the right superior pulmonary vein more inferiorly, and the right inferior pulmonary vein more superiorly by 3T MR when compared with MDCT. The cross-sectional area, perimeters and minimum diameters of right-sided pulmonary vein ostia were significantly larger by MR, as were the maximum diameters of right and left inferior pulmonary veins. There were no significant differences between techniques in distance to first pulmonary vein branch.
Pulmonary vein measurements demonstrated significant differences in angulations and dimensions when 3T MR is compared with MDCT. These differences likely represent hemodynamic and respiratory variation during free-breathing with MR versus breath-holding with MDCT. MR imaging at 3T during free-breathing offers an alternate method to define pulmonary vein and left atrial anatomy without exposure to radiation.
PMCID: PMC3584192  PMID: 23172711
magnetic resonance imaging; multidetector computed tomography; atrium; pulmonary vein; vessels
19.  Gingival enlargement in different age groups during fixed Orthodontic treatment 
Background: During fixed orthodontic therapy, adolescents tend to have higher chances of gingivitis and gingival enlargement (GE) compared to adults. A cross sectional study was undertaken to evaluate the above hypothesis, by assessing GE in patients of different age groups receiving fixed orthodontic therapy.
Materials & Methods: Patients undergoing orthodontic treatment were selected by simple random sampling from the King Khalid University College of Dentistry out patient’s clinic of preventive dental sciences division to form the study group. Participant’s were divided into three age groups and GE was graded as 0, 1 and 2 as per the classification of the American Academy of Periodontology. Data were analyzed by using IBM SPSS version 16.0 (Statistical Package for Social Services, Chicago, IL, USA) and descriptive statistics were obtained. Differences in proportions were compared using the Chi-square test and the significance level was set at p ≤ 0.05.
Results: 62.3% (n=33) were males and 37.7% (n=20) were females. Group 1 had 21 patients (39.7%); Group 2 had 24 patients (45.3%) and Group 3 had 8 patients (15.1%).The highest frequency (48%) of GE was observed among the Group 1 age group (10-19 years). Differences in frequency of GE according to age groups were found to be statistically significant (p=0.046).Differences in GE according to the frequency of practicing oral hygiene measures were statistically significant (p<0.001).
Conclusion: Highest frequency of GE was observed among the adolescents. The patients who practiced oral hygiene measures more than three times daily did not have any GE. On the other hand, those who brushed and flossed only once daily had the highest percentage of grade 2 GE.
How to cite the article: Eid HA, Assiri HA, Kandyala R, Togoo RA, Turakhia VS. Gingival enlargement in different age groups during fixed Orthodontic treatment. J Int Oral Health 2014;6(1):1-4.
PMCID: PMC3959129  PMID: 24653595
Gingival enlargement; fixed orthodontic treatment; adolescents
20.  Occurrence of Urinary Tract Infection in Adolescent and Adult Women of Shanty Town in Dhaka City, Bangladesh 
Urinary tract infection (UTI) is commonly experienced by women of various age groups especially elderly ones. We planned to find out the prevalent microbial strains causing UTI in slum inhabitant adolescent and adult women in Dhaka City, Bangladesh.
Methods and materials
Urine sample was collected from 462 UTI suspected female subjects. Pathogenic bacteria were identified using standard microbiological tests, and antimicrobial sensitivity profiles of the pathogens were determined.
Bacteriuria was present in 9% of the subjects. A higher incidence (16.8%) of UTI was noted among adult women aged above 19 years. Escherichia coli (69%), Streptococcus spp. (15%) and Pseudomonas aeruginosa (7%) were more frequently isolated from the urine samples compared to Enterococcus faecalis (3%), Staphylococcus aureus (2%), Klebsiella pneumoniae (2%) and Hafnia alvei (2%). The E. coli isolates showed complete resistance to commonly used drugs, and 58% of these isolates were multidrug resistant (MDR). Minimum Inhibitory Concentration (MIC) values for ciprofloxacin ranged between 64µg/ml and 512µg/ml, and the Minimum Bactericidal Concentration (MBC) values against the isolates were 128µg/ml or above. Isolated strains of E. coli exhibited equal extent of ciprofloxacin resistance irrespective of the presence or absence of plasmid in them.
The extent of drug resistance among the uropathogens if ignored may render them uncontrollable. This study suggests regular monitoring of drug resistance phenotype of the UTI pathogens to reduce the morbidity of female UTI patients and offer better treatment strategy in the healthcare sectors of Bangladesh.
PMCID: PMC4006209  PMID: 24795516
Urinary tract infection (UTI); Multidrug resistance (MDR); Adolescent women
21.  N-acetyltransferase (nat) Is a Critical Conjunct of Photoperiodism between the Circadian System and Endocrine Axis in Antheraea pernyi 
PLoS ONE  2014;9(3):e92680.
Since its discovery in 1923, the biology of photoperiodism remains a mystery in many ways. We sought the link connecting the circadian system to an endocrine switch, using Antheraea pernyi. PER-, CLK- and CYC-ir were co-expressed in two pairs of dorsolateral neurons of the protocerebrum, suggesting that these are the circadian neurons that also express melatonin-, NAT- and HIOMT-ir. The results suggest that a melatonin pathway is present in the circadian neurons. Melatonin receptor (MT2 or MEL-1B-R)-ir in PTTH-ir neurons juxtaposing clock neurons suggests that melatonin gates PTTH release. RIA showed a melatonin rhythm with a peak four hours after lights off in adult brain both under LD16∶8 (LD) and LD12∶12 (SD), and both the peak and the baseline levels were higher under LD than SD, suggesting a photoperiodic influence. When pupae in diapause were exposed to 10 cycles of LD, or stored at 4°C for 4 months under constant darkness, an increase of NAT activity was observed when PTTH released ecdysone. DNA sequence upstream of nat contained E-boxes to which CYC/CLK could bind, and nat transcription was turned off by clk or cyc dsRNA. dsRNANAT caused dysfunction of photoperiodism. dsRNAPER upregulated nat transcription as anticipated, based on findings in the Drosophila melanogaster circadian system. Transcription of nat, cyc and clk peaked at ZT12. RIA showed that dsRNANAT decreased melatonin while dsRNAPER increased melatonin. Thus nat, a clock controlled gene, is the critical link between the circadian clock and endocrine switch. MT-binding may release PTTH, resulting in termination of diapause. This study thus examined all of the basic functional units from the clock: a photoperiodic counter as an accumulator of mRNANAT, to endocrine switch for photoperiodism in A. pernyi showing this system is self-complete without additional device especially for photoperiodism.
PMCID: PMC3965458  PMID: 24667367
22.  The Proinflammatory Cytokine High-Mobility Group Box-1 Mediates Retinal Neuropathy Induced by Diabetes 
Mediators of Inflammation  2014;2014:746415.
To test the hypothesis that increased expression of proinflammatory cytokine high-mobility group box-1 (HMGB1) in epiretinal membranes and vitreous fluid from patients with proliferative diabetic retinopathy and in retinas of diabetic rats plays a pathogenetic role in mediating diabetes-induced retinal neuropathy. Retinas of 1-month diabetic rats and HMGB1 intravitreally injected normal rats were studied using Western blot analysis, RT-PCR and glutamate assay. In addition, we studied the effect of the HMGB1 inhibitor glycyrrhizin on diabetes-induced biochemical changes in the retina. Diabetes and intravitreal injection of HMGB1 in normal rats induced significant upregulation of HMGB1 protein and mRNA, activated extracellular signal-regulated kinase 1 and 2 (ERK1/2), cleaved caspase-3 and glutamate; and significant downregulation of synaptophysin, tyrosine hydroxylase, glutamine synthetase, and glyoxalase 1. Constant glycyrrhizin intake from the onset of diabetes did not affect the metabolic status of the diabetic rats, but it significantly attenuated diabetes-induced upregulation of HMGB1 protein and mRNA, activated ERK1/2, cleaved caspase-3, and glutamate. In the glycyrrhizin-fed diabetic rats, the decrease in synaptophysin, tyrosine hydroxylase, and glyoxalase 1 caused by diabetes was significantly attenuated. These findings suggest that early retinal neuropathy of diabetes involves upregulated expression of HMGB1 and can be ameliorated by inhibition of HMGB1.
PMCID: PMC3964896  PMID: 24733965
23.  Epstein Barr virus: a prime candidate of breast cancer aetiology in Sudanese patients 
Breast cancer is the commonest cancer in Sudanese women. Reported genetic alterations in the form of mutations in tumor suppressors are low in frequencies and could not explain the peculiarities of the diseases including its focal nature. Potential contributors disease aetiology include oncogenic viruses such as Epstein-Barr virus (EBV), an established culprit of nasopharyngeal carcinoma, one of the most frequent cancers in Sudan.
In this study, DNA was extracted from malignant tissue samples and healthy tumour-free tissue from the same breast. Polymerase chain Reaction (PCR) was used to amplify two genes encoding for EBV viral proteins. The presence of Epstein-Barr virus and its cellular localization was confirmed by in situ hybridization (ISH) for Epstein-Barr encoded small RNAs (EBERs). Given the reported low frequency of mutations in BRCA1 and BRCA2 in Sudanese breast cancer patients, the methylation status of six tumor suppressor genes was investigated using methylation specific PCR. EBV genome was detected in 55.5% (n = 90) of breast cancer tissues as compared to 23% in control tissue samples (p = 0.0001). Using ISH, EBV signal was detected in all 18 breast cancer biopsies examined while all five normal breast tissue biopsies tested were negative for EBV. Of six tumour suppressor genes investigated BRCA1, BRCA2, and p14 appeared to be under strong epigenetic silencing.
In conclusion, we present evidence of a strong association between EBV and breast carcinoma in Sudanese patients, and considerable epigenetic silencing of tumor suppressors that may likely be an outcome or an association with viral oncogenesis.
PMCID: PMC3975647  PMID: 24607238
Sudan; Epstein Barr virus (EBV); Breast cancer; DNA methylation
24.  High-resolution vascular tissue characterization in mice using 55 MHz ultrasound hybrid imaging 
Ultrasonics  2012;53(3):727-738.
Ultrasound and Duplex ultrasonography in particular are routinely used to diagnose cardiovascular disease (CVD), which is the leading cause of morbidity and mortality worldwide. However, these techniques may not be able to characterize vascular tissue compositional changes due to CVD. This work describes an ultrasound-based hybrid imaging technique that can be used for vascular tissue characterization and the diagnosis of atherosclerosis. Ultrasound radiofrequency (RF) data were acquired and processed in time, frequency, and wavelet domains to extract six parameters including time integrated backscatter (TIB), time variance (Tvar), time entropy (TE), frequency integrated backscatter (FIB), wavelet root mean square value (Wrms), and wavelet integrated backscatter (WIB). Each parameter was used to reconstruct an image co-registered to morphological B-scan. The combined set of hybrid images were used to characterize vascular tissue in vitro and in vivo using three mouse models including control (C57BL/6), and atherosclerotic apolipoprotein E-knockout (APOE-KO) and APOE/A1 adenosine receptor double knockout (DKO) mice. The technique was tested using high-frequency ultrasound including single-element (center frequency = 55 MHz) and commercial array (center frequency = 40 MHz) systems providing superior spatial resolutions of 24 μm and 40 μm, respectively. Atherosclerotic vascular lesions in the APOE-KO mouse exhibited the highest values (contrast) of −10.11 ± 1.92 dB, −12.13 ± 2.13 dB, −7.54 ± 1.45 dB, −5.10 ± 1.06 dB, −5.25 ± 0.94 dB, and −10.23 ± 2.12 dB in TIB, Tvar, TE, FIB, Wrms, WIB hybrid images (n = 10, p < 0.05), respectively. Control segments of normal vascular tissue showed the lowest values of −20.20 ± 2.71 dB, −22.54 ± 4.54 dB, −14.94 ± 2.05 dB, −9.64 ± 1.34 dB, −10.20 ± 1.27 dB, and −19.36 ± 3.24 dB in same hybrid images (n = 6, p < 0.05). Results from both histology and optical images showed good agreement with ultrasound findings within a maximum error of 3.6% in lesion estimation. This study demonstrated the feasibility of a high-resolution hybrid imaging technique to diagnose atherosclerosis and characterize plaque components in mouse. In the future, it can be easily implemented on commercial ultrasound systems and eventually translated into clinics as a screening tool for atherosclerosis and the assessment of vulnerable plaques.
PMCID: PMC3639478  PMID: 23218908
High resolution ultrasound; Tissue characterization; Atherosclerosis; Signal and image processing
25.  Metabolomic Response of Calotropis procera Growing in the Desert to Changes in Water Availability 
PLoS ONE  2014;9(2):e87895.
Water availability is a major limitation for agricultural productivity. Plants growing in severe arid climates such as deserts provide tools for studying plant growth and performance under extreme drought conditions. The perennial species Calotropis procera used in this study is a shrub growing in many arid areas which has an exceptional ability to adapt and be productive in severe arid conditions.
We describe the results of studying the metabolomic response of wild C procera plants growing in the desert to a one time water supply. Leaves of C. procera plants were taken at three time points before and 1 hour, 6 hours and 12 hours after watering and subjected to a metabolomics and lipidomics analysis. Analysis of the data reveals that within one hour after watering C. procera has already responded on the metabolic level to the sudden water availability as evidenced by major changes such as increased levels of most amino acids, a decrease in sucrose, raffinose and maltitol, a decrease in storage lipids (triacylglycerols) and an increase in membrane lipids including photosynthetic membranes. These changes still prevail at the 6 hour time point after watering however 12 hours after watering the metabolomics data are essentially indistinguishable from the prewatering state thus demonstrating not only a rapid response to water availability but also a rapid response to loss of water.
Taken together these data suggest that the ability of C. procera to survive under the very harsh drought conditions prevailing in the desert might be associated with its rapid adjustments to water availability and losses.
PMCID: PMC3919747  PMID: 24520340

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