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1.  A study on the determination of risk factors associated with babesiosis and prevalence of Babesia sp., by PCR amplification, in small ruminants from Southern Punjab (Pakistan) 
Babesiosis is a parasitic infection due to the multiplication of tick borne parasite, Babesia sp., in erythrocytes of host, which includes a wide variety of vertebrates including small ruminants causing decreased livestock output and hence economic losses. The objective of the present study was to establish a PCR based method for the detection of Babesia sp. in small ruminant population in Southern Punjab and to determine the risk factors involve in the spread of babesiosis. A total of 107 blood samples were collected from 40 sheep and 67 goats in seven districts of Southern Punjab from randomly selected herds. Data on the characteristics of the animals and the herd were collected through questionnaires. 36 blood samples (34% of total) produced the DNA fragment specific for 18S rRNA gene of Babesia sp., by PCR amplification, of which 20 were sheep and 16 were goats. Samples from all seven district contained Babesia positive samples and prevalence varied between 18 to 68%. It was observed that male animals (P = 0.009) and young animals under one year of age (P = 0.01) were more prone to the parasite. It was observed that herds consist of more than 15 animals (P = 0.007), composed of mixed species of small ruminants (P = 0.022), associated with dogs (P = 0.003) and dogs having ticks on their bodies (P = 0.011) were among the major risk factors for the spread of babesiosis in small ruminants.
doi:10.1051/parasite/2011183229
PMCID: PMC3671477  PMID: 21894263
sheep; goats; PCR amplification; Babesia sp; ovin; caprin; PCR; amplification; Babesia sp
2.  Analysis of microRNA signatures using size-coded ligation-mediated PCR 
Nucleic Acids Research  2011;39(12):e80.
The expression pattern and regulatory functions of microRNAs (miRNAs) are intensively investigated in various tissues, cell types and disorders. Differential miRNA expression signatures have been revealed in healthy and unhealthy tissues using high-throughput profiling methods. For further analyses of miRNA signatures in biological samples, we describe here a simple and efficient method to detect multiple miRNAs simultaneously in total RNA. The size-coded ligation-mediated polymerase chain reaction (SL-PCR) method is based on size-coded DNA probe hybridization in solution, followed-by ligation, PCR amplification and gel fractionation. The new method shows quantitative and specific detection of miRNAs. We profiled miRNAs of the let-7 family in a number of organisms, tissues and cell types and the results correspond with their incidence in the genome and reported expression levels. Finally, SL-PCR detected let-7 expression changes in human embryonic stem cells as they differentiate to neuron and also in young and aged mice brain and bone marrow. We conclude that the method can efficiently reveal miRNA signatures in a range of biological samples.
doi:10.1093/nar/gkr214
PMCID: PMC3130289  PMID: 21486750
3.  High dose intravenous colistin methanesulfonate therapy is associated with high rates of nephrotoxicity; a prospective cohort study from Saudi Arabia 
Background
Nephrotoxicity is an important adverse effect of colistin methanesulfonate (CMS) therapy. No data exist on rates and risk factors for colistin-related nephrotoxicity in Saudi Arabia (SA). We conducted a prospective cohort study to identify rates and risk factors for CMS nephrotoxicity in our patient population.
Methods
We prospectively included adult patients who received ≥48 hours of intravenous CMS therapy. Pregnant patients and those on renal replacement were excluded. Patients received 9 million units (mU) loading dose followed by 3 mU 8 hourly. In renal impairment, CMS dosing was adjusted according to calculated creatinine clearance (CrCl). Nephrotoxicity was defined as per RIFLE criteria (Risk, Injury, Failure, Loss and End-stage renal disease). Statistical analysis was performed using SPSS version 20.0 (IBM, Armonk, New York, USA). The study was approved by the institution’s Research Ethics Committee.
Results
A total of 67 patients were included in the study. Mean (±standard deviation) age was 57.5 (±24.0) years, Charlson Co-morbidity Score 2.88 (±2.39), CrCl 133.60 (±92.54) mL/min and serum albumin 28.65 (±4.45) g/L. Mean CMS dose was 0.11 (±0.04) mU/kg/day and mean total CMS dose received was 101.21 (±47.37) mU. Fifty-one (76.1%) patients developed RIFLE-defined nephrotoxicity. Mean total CMS dose and duration of therapy before onset of nephrotoxicity were 66.71 (±43.45) mU and 8.70 (±6.70) days, respectively. In bivariate analysis, patients with nephrotoxicity were significantly older (P 0.013) and had lower baseline serum albumin (P 0.008). Multivariate logistic regression identified serum albumin [odds ratio (OR) 0.72; 95% confidence interval (CI) 0.57–0.93; P 0.010] and intensive care admission (OR 16.38; 95% CI 1.37–195.55; P 0.027) as independent risk factors for CMS nephrotoxicity.
Conclusions
High dose intravenous CMS therapy is associated with high rates of nephrotoxicity in SA. Independent risk factors for colistin nephrotoxicity were baseline hypoalbuminemia and intensive care admission.
doi:10.1186/s12941-015-0062-8
PMCID: PMC4301664  PMID: 25591721
Colistin; Colistin methanesulfonate; CMS; Nephrotoxicity; Acute kidney injury; Saudi Arabia
4.  Hedgehog Signaling Requires Motile Cilia in the Sea Urchin 
A relatively small number of signaling pathways govern the early patterning processes of metazoan development. The architectural changes over time to these signaling pathways offer unique insights into their evolution. In the case of Hedgehog (Hh) signaling, two very divergent mechanisms of pathway transduction have evolved. In vertebrates, signaling relies on trafficking of Hh pathway components to nonmotile specialized primary cilia. In contrast, protostomes do not use cilia of any kind for Hh signal transduction. How these divergent lineages adapted such dramatically different ways of activating the signaling pathway is an unanswered question. Here, we present evidence that in the sea urchin, a basal deuterostome, motile cilia are required for embryonic Hh signal transduction, and the Hh receptor Smoothened (Smo) localizes to cilia during active Hh signaling. This is the first evidence that Hh signaling requires motile cilia and the first case of an organism requiring cilia outside of the vertebrate lineage.
doi:10.1093/molbev/mst176
PMCID: PMC3879447  PMID: 24124205
cell biology; evolution and development; cell signaling
5.  Examination of Bacterial Inhibition Using a Catalytic DNA 
PLoS ONE  2014;9(12):e115640.
Determination of accurate dosage of existing antibiotics and discovery of new antimicrobials or probiotics entail simple but effective methods that can conveniently track bacteria growth and inhibition. Here we explore the application of a previously reported fluorogenic E. coli-specific DNAzyme (catalytic DNA), RFD-EC1, as a molecular probe for monitoring bacterial inhibition exerted by antibiotics and for studying bacterial competition as a result of cohabitation. Because the DNAzyme method provides a convenient way to monitor the growth of E. coli, it is capable of determining the minimal inhibitory concentration (MIC) of antibiotics much faster than the conventional optical density (OD) method. In addition, since the target for RFD-EC1 is an extracellular protein molecule from E. coli, RFD-EC1 is able to identify pore-forming antibiotics or compounds that can cause membrane leakage. Finally, RFD-EC1 can be used to analyse the competition of cohabitating bacteria, specifically the inhibition of growth of E. coli by Bacillus subtilis. The current work represents the first exploration of a catalytic DNA for microbiological applications and showcases the utility of bacteria-sensing fluorogenic DNAzymes as simple molecular probes to facilitate antibiotic and probiotic research.
doi:10.1371/journal.pone.0115640
PMCID: PMC4274092  PMID: 25531274
6.  Optical coherence tomography – near infrared spectroscopy system and catheter for intravascular imaging 
Optics Express  2013;21(25):30849-30858.
Owing to its superior resolution, intravascular optical coherence tomography (IVOCT) is a promising tool for imaging the microstructure of coronary artery walls. However, IVOCT does not identify chemicals and molecules in the tissue, which is required for a more complete understanding and accurate diagnosis of coronary disease. Here we present a dual-modality imaging system and catheter that uniquely combines IVOCT with diffuse near-infrared spectroscopy (NIRS) in a single dual-modality imaging device for simultaneous acquisition of microstructural and compositional information. As a proof-of-concept demonstration, the device has been used to visualize co-incident microstructural and spectroscopic information obtained from a diseased cadaver human coronary artery.
doi:10.1364/OE.21.030849
PMCID: PMC3926541  PMID: 24514658
(110.4500) Optical coherence tomography; (170.6510) Spectroscopy, tissue diagnostics; (110.0113) Imaging through turbid media
7.  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)
8.  Rapid detection of single bacteria in unprocessed blood using Integrated Comprehensive Droplet Digital Detection 
Nature Communications  2014;5:5427.
Blood stream infection or sepsis is a major health problem worldwide, with extremely high mortality, which is partly due to the inability to rapidly detect and identify bacteria in the early stages of infection. Here we present a new technology termed ‘Integrated Comprehensive Droplet Digital Detection’ (IC 3D) that can selectively detect bacteria directly from milliliters of diluted blood at single-cell sensitivity in a one-step, culture- and amplification-free process within 1.5–4 h. The IC 3D integrates real-time, DNAzyme-based sensors, droplet microencapsulation and a high-throughput 3D particle counter system. Using Escherichia coli as a target, we demonstrate that the IC 3D can provide absolute quantification of both stock and clinical isolates of E. coli in spiked blood within a broad range of extremely low concentration from 1 to 10,000 bacteria per ml with exceptional robustness and limit of detection in the single digit regime.
Early detection of blood stream infections is essential for providing effective treatments. Here the authors present a system integrating DNAzyme sensors, droplet microfluidics and a high-throughput 3D particle counter that can detect specific, single bacterial cells in blood within a few hours.
doi:10.1038/ncomms6427
PMCID: PMC4243214  PMID: 25391809
9.  Hereditary angioedema: what the gastroenterologist needs to know 
Up to 93% of patients with hereditary angioedema (HAE) experience recurrent abdominal pain. Many of these patients, who often present to emergency departments, primary care physicians, general surgeons, or gastroenterologists, are misdiagnosed for years and undergo unnecessary testing and surgical procedures. Making the diagnosis of HAE can be challenging because symptoms and attack locations are often inconsistent from one episode to the next. Abdominal attacks are common and can occur without other attack locations. An early, accurate diagnosis is central to managing HAE. Unexplained abdominal pain, particularly when accompanied by swelling of the face and extremities, suggests the diagnosis of HAE. A family history and radiologic imaging demonstrating edematous bowel also support an HAE diagnosis. Once HAE is suspected, C4 and C1 esterase inhibitor (C1-INH) laboratory studies are usually diagnostic. Patients with HAE may benefit from recently approved specific treatments, including plasma-derived C1-INH or recombinant C1-INH, a bradykinin B2-receptor antagonist, or a kallikrein inhibitor as first-line therapy and solvent/detergent-treated or fresh frozen plasma as second-line therapy for acute episodes. Short-term or long-term prophylaxis with nanofiltered C1-INH or attenuated androgens will prevent or reduce the frequency and severity of episodes. Gastroenterologists can play a critical role in identifying and treating patients with HAE, and should have a high index of suspicion when encountering patients with recurrent, unexplained bouts of abdominal pain. Given the high rate of abdominal attacks in HAE, it is important for gastroenterologists to appropriately diagnose and promptly recognize and treat HAE, or refer patients with HAE to an allergist.
doi:10.2147/CEG.S50465
PMCID: PMC4242071  PMID: 25429234
hereditary angioedema; abdominal pain; diagnosis
10.  Use of chemotherapy at the end of life in Turkey 
BMC Palliative Care  2014;13(1):51.
Background
An increasing number of patients receive palliative chemotherapy near the end of life. The aim of this study is to evaluate the aggressiveness of chemotherapy in Turkish individuals near the end of life.
Methods
Patients diagnosed with solid tumors and died from 2010 to 2011 in the medical oncology department of Akdeniz University were included in the study. Data about the diagnosis, treatment details and imaging procedures were collected.
Results
Three hundred and seventy-three people with stage IV solid tumors died from 2010 to 2011 in our clinic. Eighty-nine patients (23.9%) patients underwent chemotherapy in the last month of life while 39 patients (10.5%) received chemotherapy in the last 14 days. The probability of undergoing chemotherapy in the last month of life was influenced by: age, ‘newly diagnosed’ patients, and performance status. There was no significant association of chemotherapy in the last month of life with gender and tumor type. Having a PET-CT scan did not alter the chemotherapy decision.
Conclusion
In conclusion, chemotherapy used in the last month of life in a tertiary care center of Turkey is high. Increasing quality of life should be a priority near the end of life and physicians should consider ceasing chemotherapy and direct the patient to early palliative care.
doi:10.1186/1472-684X-13-51
PMCID: PMC4247666  PMID: 25435808
Chemotherapy; End of life; Terminally ill; Cancer
11.  An Overview of Power Electronics Applications in Fuel Cell Systems: DC and AC Converters 
The Scientific World Journal  2014;2014:103709.
Power electronics and fuel cell technologies play an important role in the field of renewable energy. The demand for fuel cells will increase as fuel cells become the main power source for portable applications. In this application, a high-efficiency converter is an essential requirement and a key parameter of the overall system. This is because the size, cost, efficiency, and reliability of the overall system for portable applications primarily depend on the converter. Therefore, the selection of an appropriate converter topology is an important and fundamental aspect of designing a fuel cell system for portable applications as the converter alone plays a major role in determining the overall performance of the system. This paper presents a review of power electronics applications in fuel cell systems, which include various topology combinations of DC converters and AC inverters and which are primarily used in fuel cell systems for portable or stand-alone applications. This paper also reviews the switching techniques used in power conditioning for fuel cell systems. Finally, this paper addresses the current problem encountered with DC converters and AC inverter.
doi:10.1155/2014/103709
PMCID: PMC4244919  PMID: 25478581
12.  Effect of a Low Starch/Low Dairy Diet on Fat Oxidation in Overweight and Obese Women with Polycystic Ovary Syndrome 
Background
Polycystic ovary syndrome (PCOS) affects between 4%- 18% of reproductive-aged women and is associated with increased risk of obesity and obesity-related disease. PCOS is associated with hyperinsulinemia which is known to impair fat oxidation. Research shows that carbohydrates from dairy and starch-based foods cause greater postprandial insulin secretion than carbohydrates from non-starchy vegetables and fruits.
Objective
To determine whether an ad libitum 8-week low starch/low dairy diet would improve fasting and postprandial fat oxidation after a high saturated fat liquid meal (HSFLM) in overweight and obese women with PCOS.
Methods
Prospective 8-week dietary intervention using a low starch/low dairy diet in 10 women (BMI ≥25kg/m2 and ≤45kg/m2) with PCOS. Indirect calorimetry was used at fasting and for 5 hours following consumption of the HSFLM to determine respiratory exchange ratio (RER), macronutrient oxidation, and energy expenditure (EE) at week 0 and week 8.
Results
Participants had a reduction in body weight (−8.1±1.8kg, p<0.05) and fasting insulin (−19.5±8.9μg/mL, p<0.05) after dietary intervention; however, these were not significantly correlated with improved fat oxidation. There was a reduction in fasting RER, and fasting and postprandial CHO oxidation, and an increase in fasting and postprandial fat oxidation after adjusting for body weight. There was also significant difference in incremental area under the curve (iAUC) from pre- to post-diet for fat (0.06±0.00 g/kg/5hour; p<0.001) and carbohydrate oxidation (−0.29±0.06 g/kg/5hour; p<0.001), but not for RER or EE.
Conclusions
An 8-week low starch/low dairy diet increased fat oxidation in overweight and obese women with PCOS.
doi:10.1139/apnm-2014-0073
PMCID: PMC4211969  PMID: 25109619
PCOS; hyperinsulinemia; respiratory exchange ratio; RER; insulin resistance
13.  Tracking the Relative In Vivo Pharmacokinetics of Nanoparticles with PARACEST MRI 
Molecular pharmaceutics  2009;6(5):1409-1416.
A noninvasive assay that tracks the relative in vivo pharmacokinetics of two nanoparticles may accelerate the development of nanoparticles for biomedical applications, and may provide a method to select personalized nanomedicines for individual patients. To develop an in vivo competitive assay, two MRI contrast agents that could be selectively detected through paramagnetic chemical exchange saturation transfer (PARACEST) were conjugated to a second generation and fifth generation polyamidoamine (PAMAM) dendrimer. The CEST effects of each agent was calibrated relative to concentration. The effects of T1 relaxivities of these dendritic PARACEST magnetic resonance imaging (MRI) contrast agents were found to be negligible relative to their CEST effects with respect to changes in image contrast, which facilitated the measurement of the ratios of their chemical exchange lifetimes. Injection of both contrast agents into a mouse model of mammary carcinoma resulted in a temporal increase in the CEST effect from each agent in the flank tumor. Although the in vivo CEST effects could not be used to determine the absolute concentrations of each agent within the tumor, the ratio of the in vivo CEST effects was used to measure the ratio of the concentrations of the agents. This result demonstrated that the relative in vivo pharmacokinetics of two nanoparticles may be evaluated using PARACEST MRI.
doi:10.1021/mp900040u
PMCID: PMC4216567  PMID: 19298054
MRI; dendrimers; contrast agents; pharmacokinetics; breast cancer
14.  Next-generation sequencing of adrenocortical carcinoma reveals new routes to targeted therapies 
Journal of Clinical Pathology  2014;67(11):968-973.
Aims
Adrenocortical carcinoma (ACC) carries a poor prognosis and current systemic cytotoxic therapies result in only modest improvement in overall survival. In this retrospective study, we performed a comprehensive genomic profiling of 29 consecutive ACC samples to identify potential targets of therapy not currently searched for in routine clinical practice.
Methods
DNA from 29 ACC was sequenced to high, uniform coverage (Illumina HiSeq) and analysed for genomic alterations (GAs).
Results
At least one GA was found in 22 (76%) ACC (mean 2.6 alterations per ACC). The most frequent GAs were in TP53 (34%), NF1 (14%), CDKN2A (14%), MEN1 (14%), CTNNB1 (10%) and ATM (10%). APC, CCND2, CDK4, DAXX, DNMT3A, KDM5C, LRP1B, MSH2 and RB1 were each altered in two cases (7%) and EGFR, ERBB4, KRAS, MDM2, NRAS, PDGFRB, PIK3CA, PTEN and PTCH1 were each altered in a single case (3%). In 17 (59%) of ACC, at least one GA was associated with an available therapeutic or a mechanism-based clinical trial.
Conclusions
Next-generation sequencing can discover targets of therapy for relapsed and metastatic ACC and shows promise to improve outcomes for this aggressive form of cancer.
doi:10.1136/jclinpath-2014-202514
PMCID: PMC4215283  PMID: 25078331
Cancer Genetics; Endocrine Pathology; Molecular Pathology; Oncology; Gene Amplification
15.  Comorbidity Structure of Psychological Disorders in the Online e-PASS Data as Predictors of Psychosocial Adjustment Measures: Psychological Distress, Adequate Social Support, Self-Confidence, Quality of Life, and Suicidal Ideation 
Background
A relative newcomer to the field of psychology, e-mental health has been gaining momentum and has been given considerable research attention. Although several aspects of e-mental health have been studied, 1 aspect has yet to receive attention: the structure of comorbidity of psychological disorders and their relationships with measures of psychosocial adjustment including suicidal ideation in online samples.
Objective
This exploratory study attempted to identify the structure of comorbidity of 21 psychological disorders assessed by an automated online electronic psychological assessment screening system (e-PASS). The resulting comorbidity factor scores were then used to assess the association between comorbidity factor scores and measures of psychosocial adjustments (ie, psychological distress, suicidal ideation, adequate social support, self-confidence in dealing with mental health issues, and quality of life).
Methods
A total of 13,414 participants were assessed using a complex online algorithm that resulted in primary and secondary Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision) diagnoses for 21 psychological disorders on dimensional severity scales. The scores on these severity scales were used in a principal component analysis (PCA) and the resulting comorbidity factor scores were related to 4 measures of psychosocial adjustments.
Results
A PCA based on 17 of the 21 psychological disorders resulted in a 4-factor model of comorbidity: anxiety-depression consisting of all anxiety disorders, major depressive episode (MDE), and insomnia; substance abuse consisting of alcohol and drug abuse and dependency; body image–eating consisting of eating disorders, body dysmorphic disorder, and obsessive-compulsive disorders; depression–sleep problems consisting of MDE, insomnia, and hypersomnia. All comorbidity factor scores were significantly associated with psychosocial measures of adjustment (P<.001). They were positively related to psychological distress and suicidal ideation, but negatively related to adequate social support, self-confidence, and quality of life.
Conclusions
This exploratory study identified 4 comorbidity factors in the e-PASS data and these factor scores significantly predicted 5 psychosocial adjustment measures.
Trial Registration
Australian and New Zealand Clinical Trials Registry ACTRN121611000704998; http://www.anzctr.org.au/trial_view.aspx?ID=336143 (Archived by WebCite at http://www.webcitation.org/618r3wvOG).
doi:10.2196/jmir.3591
PMCID: PMC4259919  PMID: 25351885
comorbidity; comorbidity factors, comorbidity dimensions, structure of comorbidity; psychosocial adjustment; disorders; suicidal ideation; quality of life (QoL); self-confidence; distress; social support; online therapy; e-mental health; generalized anxiety disorder; obsessive-compulsive disorder; social anxiety disorder; posttraumatic stress disorder; PD; major depressive episode; anxiety disorders; insomnia, hypersomnia
16.  Posttreatment Attrition and Its Predictors, Attrition Bias, and Treatment Efficacy of the Anxiety Online Programs 
Background
Although relatively new, the field of e-mental health is becoming more popular with more attention given to researching its various aspects. However, there are many areas that still need further research, especially identifying attrition predictors at various phases of assessment and treatment delivery.
Objective
The present study identified the predictors of posttreatment assessment completers based on 24 pre- and posttreatment demographic and personal variables and 1 treatment variable, their impact on attrition bias, and the efficacy of the 5 fully automated self-help anxiety treatment programs for generalized anxiety disorder (GAD), social anxiety disorder (SAD), panic disorder with or without agoraphobia (PD/A), obsessive-compulsive disorder (OCD), and posttraumatic stress disorder (PTSD).
Methods
A complex algorithm was used to diagnose participants’ mental disorders based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision; DSM-IV-TR). Those who received a primary or secondary diagnosis of 1 of 5 anxiety disorders were offered an online 12-week disorder-specific treatment program. A total of 3199 individuals did not formally drop out of the 12-week treatment cycle, whereas 142 individuals formally dropped out. However, only 347 participants who completed their treatment cycle also completed the posttreatment assessment measures. Based on these measures, predictors of attrition were identified and attrition bias was examined. The efficacy of the 5 treatment programs was assessed based on anxiety-specific severity scores and 5 additional treatment outcome measures.
Results
On average, completers of posttreatment assessment measures were more likely to be seeking self-help online programs; have heard about the program from traditional media or from family and friends; were receiving mental health assistance; were more likely to learn best by reading, hearing and doing; had a lower pretreatment Kessler-6 total score; and were older in age. Predicted probabilities resulting from these attrition variables displayed no significant attrition bias using Heckman’s method and thus allowing for the use of completer analysis. Six treatment outcome measures (Kessler-6 total score, number of diagnosed disorders, self-confidence in managing mental health issues, quality of life, and the corresponding pre- and posttreatment severity for each program-specific anxiety disorder and for major depressive episode) were used to assess the efficacy of the 5 anxiety treatment programs. Repeated measures MANOVA revealed a significant multivariate time effect for all treatment outcome measures for each treatment program. Follow-up repeated measures ANOVAs revealed significant improvements on all 6 treatment outcome measures for GAD and PTSD, 5 treatment outcome measures were significant for SAD and PD/A, and 4 treatment outcome measures were significant for OCD.
Conclusions
Results identified predictors of posttreatment assessment completers and provided further support for the efficacy of self-help online treatment programs for the 5 anxiety disorders.
Trial Registration
Australian and New Zealand Clinical Trials Registry ACTRN121611000704998; http://www.anzctr.org.au/trial_view.aspx?ID=336143 (Archived by WebCite at http://www.webcitation.org/618r3wvOG).
doi:10.2196/jmir.3513
PMCID: PMC4211028  PMID: 25316533
posttreatment attrition; posttreatment predictors; treatment efficacy; online therapy; e-mental health; cognitive behavioral therapy; Internet interventions; fully automated; self-help; Web treatment; generalized anxiety disorder; obsessive compulsive disorder
17.  High Mortality of Red Sea Zooplankton under Ambient Solar Radiation 
PLoS ONE  2014;9(10):e108778.
High solar radiation along with extreme transparency leads to high penetration of solar radiation in the Red Sea, potentially harmful to biota inhabiting the upper water column, including zooplankton. Here we show, based on experimental assessments of solar radiation dose-mortality curves on eight common taxa, the mortality of zooplankton in the oligotrophic waters of the Red Sea to increase steeply with ambient levels of solar radiation in the Red Sea. Responses curves linking solar radiation doses with zooplankton mortality were evaluated by exposing organisms, enclosed in quartz bottles, allowing all the wavelengths of solar radiation to penetrate, to five different levels of ambient solar radiation (100%, 21.6%, 7.2%, 3.2% and 0% of solar radiation). The maximum mortality rates under ambient solar radiation levels averaged (±standard error of the mean, SEM) 18.4±5.8% h−1, five-fold greater than the average mortality in the dark for the eight taxa tested. The UV-B radiation required for mortality rates to reach ½of maximum values averaged (±SEM) 12±5.6 h−1% of incident UVB radiation, equivalent to the UV-B dose at 19.2±2.7 m depth in open coastal Red Sea waters. These results confirm that Red Sea zooplankton are highly vulnerable to ambient solar radiation, as a consequence of the combination of high incident radiation and high water transparency allowing deep penetration of damaging UV-B radiation. These results provide evidence of the significance of ambient solar radiation levels as a stressor of marine zooplankton communities in tropical, oligotrophic waters. Because the oligotrophic ocean extends across 70% of the ocean surface, solar radiation can be a globally-significant stressor for the ocean ecosystem, by constraining zooplankton use of the upper levels of the water column and, therefore, the efficiency of food transfer up the food web in the oligotrophic ocean.
doi:10.1371/journal.pone.0108778
PMCID: PMC4195651  PMID: 25309996
18.  First report of the presence of Acartia bispinosa Carl, 1907 (Copepoda, Calanoida) in a semi-enclosed Bay (Sharm El-Maya), northern Red Sea with some notes on its seasonal variation in abundance and body size 
ZooKeys  2014;95-118.
The calanoid copepod, Acartia bispinosa Carl, 1907, is reported for the first time in the Red Sea, where it is found to be an important copepod in the mesozooplankton community structure of the Sharm El-Maya Bay. Female and male are fully redescribed and illustrated of as the mouthparts of this species have never previously been described and figured. Acartia bispinosa was collected in the plankton samples throughout the year and showed two peaks of abundance, a pronounced one in April (4234 individuals m-3), and second smaller peak during November (1784 individuals m-3). The average total length of females varied between 1.32 and 1.53 mm at the end of June and January respectively. For males, the average total length fluctuated between 1.07 and 1.16 mm at end of June and March respectively. Temperature showed an inverse relationship with the body length (P > 0.001) and seemed to be one of the prime factors affecting the body length of both sexes.
doi:10.3897/zookeys.444.7633
PMCID: PMC4205734  PMID: 25349502
Copepods; Acartia bispinosa; morphology; seasonal abundance; body size; Red Sea
19.  A traceless Staudinger reagent to deliver diazirines 
Organic letters  2013;15(19):10.1021/ol402404n.
A triarylphosphine reagent that reacts with organic azides to install amide-linked diazirines is reported. This traceless Staudinger reagent reacts with complex organic azides to yield amide-linked diazirines, thus expanding the scope of the utility of both azide and diazirine chemistry.
doi:10.1021/ol402404n
PMCID: PMC3857746  PMID: 24059816
20.  Aberrantly expressed long noncoding RNAs in human intervertebral disc degeneration: a microarray related study 
Introduction
In addition to the well-known short noncoding RNAs such as microRNAs (miRNAs), increasing evidence suggests that long noncoding RNAs (lncRNAs) act as key regulators in a wide aspect of biologic processes. Dysregulated expression of lncRNAs has been demonstrated being implicated in a variety of human diseases. However, little is known regarding the role of lncRNAs with regards to intervertebral disc degeneration (IDD). In the present study we aimed to determine whether lncRNAs are differentially expressed in IDD.
Methods
An lncRNA-mRNA microarray analysis of human nucleus pulposus (NP) was employed. Bioinformatics prediction was also applied to delineate the functional roles of the differentially expressed lncRNAs. Several lncRNAs and mRNAs were chosen for quantitative real-time PCR (qRT-PCR) validation.
Results
Microarray data profiling indicated that 116 lncRNAs (67 up and 49 down) and 260 mRNAs were highly differentially expressed with an absolute fold change greater than ten. Moreover, 1,052 lncRNAs and 1,314 mRNAs were differentially expressed in the same direction in at least four of the five degenerative samples with fold change greater than two. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis for the differentially expressed mRNAs indicated a number of pathways, such as extracellular matrix (ECM)-receptor interaction. A coding-noncoding gene co-expression (CNC) network was constructed for the ten most significantly changed lncRNAs. Annotation terms of the coexpressed mRNAs were related to several known degenerative alterations, such as chondrocyte differentiation. Moreover, lncRNAs belonging to a particular subgroup were identified. Functional annotation for the corresponding nearby coding genes showed that these lncRNAs were mainly associated with cell migration and phosphorylation. Interestingly, we found that Fas-associated protein factor-1 (FAF1), which potentiates the Fas-mediated apoptosis and its nearby enhancer-like lncRNA RP11-296A18.3, were highly expressed in the degenerative discs. Subsequent qRT-PCR results confirmed the changes.
Conclusions
This is the first study to demonstrate that aberrantly expressed lncRNAs play a role in the development of IDD. Our study noted that up-regulated RP11-296A18.3 highly likely induced the over-expression of FAF1, which eventually promoted the aberrant apoptosis of disc cells. Such findings further broaden the understanding of the etiology of IDD.
Electronic supplementary material
The online version of this article (doi:10.1186/s13075-014-0465-5) contains supplementary material, which is available to authorized users.
doi:10.1186/s13075-014-0465-5
PMCID: PMC4201740  PMID: 25280944
21.  Magnetic Resonance Imaging Estimation of Longitudinal Relaxation Rate Change (ΔR1) in Dual Gradient Echo Sequences Using an Adaptive Model 
Magnetic Resonance Imaging (MRI) estimation of contrast agent concentration in fast pulse sequences such as Dual Gradient Echo (DGE) imaging is challenging. An Adaptive Neural Network (ANN) was trained with a map of contrast agent concentration estimated by Look-Locker (LL) technique (modified version of inversion recovery imaging) as a gold standard. Using a set of features extracted from DGE MRI data, an ANN was trained to create a voxel based estimator of the time trace of CA concentration. The ANN was trained and tested with the DGE and LL information of six Fisher rats using a K-Fold Cross-Validation (KFCV) method with 60 folds and 10500 samples. The Area Under the Receiver Operator Characteristic Curve (AUROC) for 60 folds was used for training, testing and optimization of the ANN. After training and optimization, the optimal ANN (4:7:5:1) produced maps of CA concentration which were highly correlated (r =0.89, P < 0.0001) with the CA concentration estimated by the LL technique. The estimation made by the ANN had an excellent overall performance (AUROC = 0.870).
doi:10.1109/IJCNN.2011.6033544
PMCID: PMC4181328  PMID: 25285243
22.  The Oxidative Stress Product Carboxyethylpyrrole Potentiates TLR2/TLR1 Inflammatory Signaling in Macrophages 
PLoS ONE  2014;9(9):e106421.
Oxidative stress is key in the pathogenesis of several diseases including age-related macular degeneration (AMD), atherosclerosis, diabetes, and Alzheimer's disease. It has previously been established that a lipid peroxidation product, carboxyethylpyrrole (CEP), accumulates in the retinas of AMD patients. Retinal infiltrating macrophages also accumulate in the retinas of both AMD patients and in a murine model of AMD. We therefore investigated the ability of CEP-adducts to activate innate immune signaling in murine bone-marrow derived macrophages (BMDMs). We found that CEP specifically synergizes with low-dose TLR2-agonists (but not agonists for other TLRs) to induce production of inflammatory cytokines. Moreover, CEP selectively augments TLR2/TLR1-signaling instead of TLR2/TLR6-signaling. These studies uncover a novel synergistic inflammatory relationship between an endogenously produced oxidation molecule and a pathogen-derived product, which may have implications in the AMD disease process and other oxidative stress-driven pathologies.
doi:10.1371/journal.pone.0106421
PMCID: PMC4153630  PMID: 25184331
23.  Suitability assessment of health education brochures in Qassim province, Kingdom of Saudi Arabia 
Background:
Health education is the cornerstone of primary health care. Health education materials distributed to the community should, therefore, be suitable and effective. The purpose of this study was to evaluate the health education brochures, designed and disseminated by Ministry of Health institutions in the Qassim province.
Materials and Methods:
The study was a cross-sectional review of health education brochures. We used a structured evaluation form, comprising general information on the brochures and a modified Suitability Assessment of Materials (SAM) score sheet. The SAM consisting of 22 criteria in six groups, includes content, literacy demands, graphics, layout/typography, learning stimulation/motivation, and cultural appropriateness. SAM criteria categorize written material into “superior,” “adequate” and “not suitable.” Two qualified consultant family physicians evaluated the brochures. Data were analyzed using Epi Info version 3.4 statistical package.
Results:
We evaluated 110 brochures, the majority of which addressed chronic health conditions such as mental health, diabetes mellitus and hypertension. Seventy-four (67.3%) brochures were evaluated as “adequate,” 34 (30.9%) as “not suitable” and 2 (1.8%) as “superior.” “Cultural appropriateness” was the highest scoring factor, with 92 (83.6%) brochures falling into either the “superior” or “adequate” category. With regard to “content,” 88 (80.0%) brochures fell into either the “superior” or “adequate” category. This was the second highest scoring factor. Graphics was the factor that scored the least. Seventy-five (68.2%) brochures were rated in this factor as “not suitable.”
Conclusions:
Although two-thirds of our brochures were considered “adequate,” the majority needed improvement to their graphics and learning stimulation factors. We recommend that guidelines for designing health education brochures should be formulated to improve the quality of health education brochures.
doi:10.4103/2230-8229.142974
PMCID: PMC4214009  PMID: 25374471
Brochure; health education; Qassim; Saudi Arabia; suitability
24.  Vascular endothelial growth factor trap-eye and trap technology: Aflibercept from bench to bedside 
Oman Journal of Ophthalmology  2014;7(3):112-115.
Anti-vascular endothelial growth factor (VEGF) currently used to treat eye diseases have included monoclonal antibodies, antibody fragments, and an aptamer. A different method of achieving VEGF blockade in retinal diseases includes the concept of a cytokine trap. Cytokine traps technology are being evaluated for the treatment of various diseases that are driven by excessive cytokine levels. Traps consist of two extracellular cytokine receptor domains fused together to form a human immunoglobulin G (IgG). Aflibercept/VEGF trap-eye (VTE) is a soluble fusion protein, which combines ligand-binding elements taken from the extracellular components of VEGF receptors 1 and 2 fused to the Fc portion of IgG. This protein contains all human amino acid sequences, which minimizes the potential for immunogenicity in human patients. This review presents the latest data on VTE in regard to the pharmacokinetics, dosage and safety, preclinical and clinical experiences. Method of the literature search: A systematic search of the literature was conducted on PubMed, Scopus, and Google Scholar with no limitation on language or year of publication databases. It was oriented to articles published for VTE in preclinical and clinical studies and was focused on the pharmacokinetics, dosage and safety of VTE.
doi:10.4103/0974-620X.142591
PMCID: PMC4220395  PMID: 25378873
Aflibercept (EYLEA®); anti-vascular endothelial growth factor agents; diabetic macular edema; neovascular age-related macular degeneration; vascular endothelial growth factor trap-eye
25.  A comparative study of mesenchymal stem cell transplantation with its paracrine effect on control of hyperglycemia in type 1 diabetic rats 
Background
Many studies suggested mesenchymal stem cells (MSCs) transplantation as a new approach to control hyperglycemia in type 1 diabetes mellitus through differentiation mechanism. In contrary others believed that therapeutic properties of MSCs is depends on paracrine mechanisms even if they were not engrafted. This study aimed to compare these two approaches in control of hyperglycemia in STZ-induced diabetic rats.
Methods
Animals were divided into five groups: normal; diabetic control; diabetic received MSCs; diabetic received supernatant of MSCs; diabetic received co-administration of MSCs with supernatant. Blood glucose, insulin levels and body weight of animals were monitored during experiment. Immunohistochemical and immunofluorescence analysis were performed to monitor functionality and migration of labeled-MSCs to pancreas.
Results
First administration of MSCs within the first 3 weeks could not reduce blood glucose, but second administration significantly reduced blood glucose after week four compared to diabetic controls. Daily injection of supernatant could not reduce blood glucose as efficient as MSCs. Interestingly; Co-administration of MSCs with supernatant significantly reduced blood glucose more than other treated groups. Insulin levels and body weight were significantly increased in MSCs + supernatant-treated animals compared to other groups. Immunohistological analysis showed an increase in number and size of islets per section respectively in supernatant, MSCs and MSCs + supernatant-treated groups.
Conclusion
Present study exhibited that repeated-injection of MSCs reduced blood glucose and increased serum insulin levels in recipient rats. Injection of supernatant could not reverse hyperglycemia as efficient as MSCs. Interestingly; co-administration of MSCs with supernatant could reverse hyperglycemia more than either group alone.
doi:10.1186/2251-6581-13-76
PMCID: PMC4329572
Hyperglycemia; Mesenchymal stem cells; Diabetes mellitus

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