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1.  Study protocol: differential effects of diet and physical activity based interventions in pregnancy on maternal and fetal outcomes—individual patient data (IPD) meta-analysis and health economic evaluation 
Systematic Reviews  2014;3:131.
Background
Pregnant women who gain excess weight are at risk of complications during pregnancy and in the long term. Interventions based on diet and physical activity minimise gestational weight gain with varied effect on clinical outcomes. The effect of interventions on varied groups of women based on body mass index, age, ethnicity, socioeconomic status, parity, and underlying medical conditions is not clear. Our individual patient data (IPD) meta-analysis of randomised trials will assess the differential effect of diet- and physical activity-based interventions on maternal weight gain and pregnancy outcomes in clinically relevant subgroups of women.
Methods/design
Randomised trials on diet and physical activity in pregnancy will be identified by searching the following databases: MEDLINE, EMBASE, BIOSIS, LILACS, Pascal, Science Citation Index, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, and Health Technology Assessment Database. Primary researchers of the identified trials are invited to join the International Weight Management in Pregnancy Collaborative Network and share their individual patient data. We will reanalyse each study separately and confirm the findings with the original authors. Then, for each intervention type and outcome, we will perform as appropriate either a one-step or a two-step IPD meta-analysis to obtain summary estimates of effects and 95% confidence intervals, for all women combined and for each subgroup of interest. The primary outcomes are gestational weight gain and composite adverse maternal and fetal outcomes. The difference in effects between subgroups will be estimated and between-study heterogeneity suitably quantified and explored. The potential for publication bias and availability bias in the IPD obtained will be investigated. We will conduct a model-based economic evaluation to assess the cost effectiveness of the interventions to manage weight gain in pregnancy and undertake a value of information analysis to inform future research.
Systematic review registration
PROSPERO 2013: CRD42013003804
doi:10.1186/2046-4053-3-131
PMCID: PMC4228083  PMID: 25370505
Individual patient data meta-analysis; Diet and physical activity; Pregnancy; Weight gain
2.  Late coronary artery and tricuspid valve injury post pectus excavatum surgery 
We report the surgical case of a 25-year old man admitted because of progressive dyspnoea and stabbing chest pain, who had undergone a pectus excavatum correction using a retrosternal strut 8 years previously. The computerized tomography scan showed that the right tip of the pectus bar had migrated across his right ventricle and tricuspid valve into the right atrium. Intraoperatively, it was confirmed that in its path, the right coronary artery and the posterior leaflet of the tricuspid valve had been damaged. After removing the bar and repairing the tricuspid valve, the patient made a full recovery.
doi:10.1093/icvts/ivt280
PMCID: PMC3781801  PMID: 23832922
Pectus excavatum; Tricuspid valve; Coronary artery
3.  Structural Basis of Binding and Rationale for the Potent Urease Inhibitory Activity of Biscoumarins 
BioMed Research International  2014;2014:935039.
Urease belongs to a family of highly conserved urea-hydrolyzing enzymes. A common feature of these enzymes is the presence of two Lewis acid nickel ions and reactive cysteine residue in the active sites. In the current study we examined a series of biscoumarins 1–10 for their mechanisms of inhibition with the nickel containing active sites of Jack bean and Bacillus pasteurii ureases. All these compounds competitively inhibited Jack bean urease through interaction with the nickel metallocentre, as deduced from Michaelis-Menten kinetics, UV-visible absorbance spectroscopic, and molecular docking simulation studies. Some of the compounds behaved differently in case of Bacillus pasteurii urease. We conducted the enzyme kinetics, UV-visible spectroscopy, and molecular docking results in terms of the known protein structure of the enzyme. We also evaluated possible molecular interpretations for the site of biscoumarins binding and found that phenyl ring is the major active pharmacophore. The excellent in vitro potency and selectivity profile of the several compounds described combined with their nontoxicity against the human cells and plants suggest that these compounds may represent a viable lead series for the treatment of urease associated problems.
doi:10.1155/2014/935039
PMCID: PMC4176650  PMID: 25295281
4.  The CROWN Initiative: journal editors invite researchers to develop core outcomes in women’s health 
Clinical trials, systematic reviews and guidelines compare beneficial and non-beneficial outcomes following interventions. Often, however, various studies on a particular topic do not address the same outcomes, making it difficult to draw clinically useful conclusions when a group of studies is looked at as a whole. This problem was recently thrown into sharp focus by a systematic review of interventions for preterm birth prevention, which found that among 103 randomised trials, no fewer than 72 different outcomes were reported. There is a growing recognition among clinical researchers that this variability undermines consistent synthesis of the evidence, and that what is needed is an agreed standardised collection of outcomes - a "core outcomes set" - for all trials in a specific clinical area. Recognising that the current inconsistency is a serious hindrance to progress in our specialty, the editors of over 50 journals related to women's health have come together to support The CROWN (CoRe Outcomes in WomeN's health) Initiative.
doi:10.1186/1746-4358-9-9
PMCID: PMC4104682  PMID: 25050130
Research design/standards; Treatment outcome; Endpoint determination/standards; Clinical trials; Systematic reviews; Guidelines; Bias (Epidemiology); Evidence-based medicine; Consensus
5.  The CROWN initiative: journal editors invite researchers to develop core outcomes in women’s health 
Reproductive Health  2014;11:42.
Clinical trials, systematic reviews and guidelines compare beneficial and non-beneficial outcomes following interventions. Often, however, various studies on a particular topic do not address the same outcomes, making it difficult to draw clinically useful conclusions when a group of studies is looked at as a whole. This problem was recently thrown into sharp focus by a systematic review of interventions for preterm birth prevention, which found that among 103 randomised trials, no fewer than 72 different outcomes were reported. There is a growing recognition among clinical researchers that this variability undermines consistent synthesis of the evidence, and that what is needed is an agreed standardised collection of outcomes - a "core outcomes set" - for all trials in a specific clinical area. Recognising that the current inconsistency is a serious hindrance to progress in our specialty, the editors of over 50 journals related to women's health have come together to support The CROWN (CoRe Outcomes in WomeN's health) Initiative.
doi:10.1186/1742-4755-11-42
PMCID: PMC4104729  PMID: 25048583
Research design/standards; Treatment outcome; Endpoint determination/standards; Clinical trials; Systematic reviews; Guidelines; Bias (Epidemiology); Evidence-based medicine; Consensus
6.  The CROWN Initiative: journal editors invite researchers to develop core outcomes in women’s health 
BMC Women's Health  2014;14:75.
Clinical trials, systematic reviews and guidelines compare beneficial and non-beneficial outcomes following interventions. Often, however, various studies on a particular topic do not address the same outcomes, making it difficult to draw clinically useful conclusions when a group of studies is looked at as a whole. This problem was recently thrown into sharp focus by a systematic review of interventions for preterm birth prevention, which found that among 103 randomised trials, no fewer than 72 different outcomes were reported. There is a growing recognition among clinical researchers that this variability undermines consistent synthesis of the evidence, and that what is needed is an agreed standardised collection of outcomes - a “core outcomes set” - for all trials in a specific clinical area. Recognising that the current inconsistency is a serious hindrance to progress in our specialty, the editors of over 50 journals related to women’s health have come together to support The CROWN (CoRe Outcomes in WomeN’s health) Initiative.
doi:10.1186/1472-6874-14-75
PMCID: PMC4080758  PMID: 24993666
Research design/standards; Treatment outcome; Endpoint determination/standards; Clinical trials; Systematic reviews; Guidelines; Bias (Epidemiology); Evidence-based medicine; Consensus
7.  The CROWN initiative: journal editors invite researchers to develop core outcomes in women’s health 
Clinical trials, systematic reviews and guidelines compare beneficial and non-beneficial outcomes following interventions. Often, however, various studies on a particular topic do not address the same outcomes, making it difficult to draw clinically useful conclusions when a group of studies is looked at as a whole. This problem was recently thrown into sharp focus by a systematic review of interventions for preterm birth prevention, which found that among 103 randomised trials, no fewer than 72 different outcomes were reported. There is a growing recognition among clinical researchers that this variability undermines consistent synthesis of the evidence, and that what is needed is an agreed standardised collection of outcomes - a “core outcomes set” - for all trials in a specific clinical area. Recognising that the current inconsistency is a serious hindrance to progress in our specialty, the editors of over 50 journals related to women’s health have come together to support The CROWN (CoRe Outcomes in WomeN’s health) Initiative.
doi:10.1186/1471-2393-14-199
PMCID: PMC4066690  PMID: 24957208
Research design/standards; Treatment outcome; Endpoint determination/standards; Clinical trials; Systematic reviews; Guidelines; Bias (Epidemiology); Evidence-based medicine; Consensus
8.  Use of labour induction and risk of cesarean delivery: a systematic review and meta-analysis 
Background:
Induction of labour is common, and cesarean delivery is regarded as its major complication. We conducted a systematic review and meta-analysis to investigate whether the risk of cesarean delivery is higher or lower following labour induction compared with expectant management.
Methods:
We searched 6 electronic databases for relevant articles published through April 2012 to identify randomized controlled trials (RCTs) in which labour induction was compared with placebo or expectant management among women with a viable singleton pregnancy. We assessed risk of bias and obtained data on rates of cesarean delivery. We used regression analysis techniques to explore the effect of patient characteristics, induction methods and study quality on risk of cesarean delivery.
Results:
We identified 157 eligible RCTs (n = 31 085). Overall, the risk of cesarean delivery was 12% lower with labour induction than with expectant management (pooled relative risk [RR] 0.88, 95% confidence interval [CI] 0.84–0.93; I2 = 0%). The effect was significant in term and post-term gestations but not in preterm gestations. Meta-regression analysis showed that initial cervical score, indication for induction and method of induction did not alter the main result. There was a reduced risk of fetal death (RR 0.50, 95% CI 0.25–0.99; I2 = 0%) and admission to a neonatal intensive care unit (RR 0.86, 95% CI 0.79–0.94), and no impact on maternal death (RR 1.00, 95% CI 0.10–9.57; I2 = 0%) with labour induction.
Interpretation:
The risk of cesarean delivery was lower among women whose labour was induced than among those managed expectantly in term and post-term gestations. There were benefits for the fetus and no increased risk of maternal death.
doi:10.1503/cmaj.130925
PMCID: PMC4049989  PMID: 24778358
9.  Approaches to Increase Arsenic Awareness in Bangladesh: An Evaluation of an Arsenic Education Program 
The objective of this study was to design and evaluate a household-level arsenic education and well water arsenic testing intervention to increase arsenic awareness in Bangladesh. The authors randomly selected 1,000 study respondents located in 20 villages in Singair, Bangladesh. The main outcome was the change in knowledge of arsenic from baseline to follow-up 4 to 6 months after the household received the intervention. This was assessed through a pre- and postintervention quiz concerning knowledge of arsenic. Respondents were between 18 and 102 years of age, with an average age of 37 years; 99.9% were female. The knowledge of arsenic quiz scores for study participants were significantly higher at follow-up compared with baseline. The intervention was effective in increasing awareness of the safe uses of arsenic-contaminated water and dispelling the misconception that boiling water removes arsenic. At follow-up, nearly all respondents were able to correctly identify the meaning of a red (contaminated) and green (arsenic safe) well relative to arsenic (99%). The educational program also significantly increased the proportion of respondents who were able to correctly identify the health implications of arsenic exposure. However, the intervention was not effective in dispelling the misconceptions in the population that arsenicosis is contagious and that illnesses such as cholera, diarrhea, and vomiting could be caused by arsenic. Further research is needed to develop effective communication strategies to dispel these misconceptions. This study demonstrates that a household-level arsenic educational program can be used to significantly increase arsenic awareness in Bangladesh.
doi:10.1177/1090198112454735
PMCID: PMC3696588  PMID: 22984214
10.  Protocol study: sexual and reproductive health knowledge, information-seeking behaviour and attitudes among Saudi women: a questionnaire survey of university students 
Reproductive Health  2014;11:34.
Background
Sexual and reproductive health (SRH), a basic right for women worldwide, is infrequently researched in countries in the Middle East and North Africa (MENA). No empirical studies of SRH among Saudi women exist. This protocol describes a study to explore the SRH knowledge, information-seeking behaviour and attitudes of Saudi female university students.
Methods/Design
This study will administer a questionnaire survey to female students at 13 universities in Riyadh, Saudi Arabia. The questionnaire was developed following a literature search to identify relevant content, with psychometrically tested tools used when available. The content layout and the wording and order of the questions were designed to minimize the risk of bias. The questionnaire has been translated into Arabic and piloted in preparation for administration to the study sample. Ethical approval for the study has been granted (reference no. QMREC2012/54). After questionnaire administration, the data will be collated, analysed and reported anonymously. The findings will be published in compliance with reporting guidelines for survey research.
Discussion
This study will be the first to provide fundamental information concerning Saudi females university students SRH knowledge and information needs.
doi:10.1186/1742-4755-11-34
PMCID: PMC4113201  PMID: 24885041
Sexual health; Reproductive health; Knowledge; Awareness; Information; University; Students; Saudi Arabia
11.  Comparative Studies of Salivary and Blood Sialic Acid, Lipid Peroxidation and Antioxidative Status in Oral Squamous Cell Carcinoma (OSCC) 
Objective : Oral squamous cell carcinoma (OSCC) is considered to be a serious life threatening issue for almost two decades. The objective of this study was to evaluate the over production of lipid peroxidation (LPO) byproducts and disturbances in antioxidant defense system in the pathogenesis of oral cancer.
Methods : Lipid peroxidation and antioxidant status in OSCC patients were estimated and compared the sensitivity and specificity of circulating biomarkers (MDA, Sialic acid, Catalase, SOD, GSH and Neuraminidase) with β-2 microglobulin (β-2MG) at different thresholds in blood and saliva using receiver operating characteristics (ROC) curve design.
R esults : Our results showed that the levels of MDA and Sialic acid were significantly increased in plasma of OSCC patients as compared to healthy subjects whereas antioxidant level was significantly decreased.
Conclusion : ROC analysis indicated that MDA in saliva is a better diagnostic tool as compared to MDA in blood and β-2MG in blood is better diagnostic marker as compared to β-2MG level in saliva.
doi:10.12669/pjms.303.4985
PMCID: PMC4048487  PMID: 24948960
Neoplastic; Squamous Cell Carcinoma; Lipid peroxidation; MDA
12.  Longitudinal assessment of chlorpyrifos exposure and self-reported neurological symptoms in adolescent pesticide applicators 
BMJ Open  2014;4(3):e004177.
Objectives
Occupational exposure of organophosphorus pesticides, such as chlorpyrifos (CPF), in adolescents is of particular concern because of the potential vulnerability of the developing neurological system. The objectives of this study were to examine how neurological symptoms reported over the application season vary across time, whether these effects are reversible postapplication and if there are associations between CPF biomarkers and neurological symptoms in an adolescent study population.
Setting
The longitudinal study was conducted in two agricultural districts of Menoufia Governorate, Egypt between April 2010 and January 2011.
Participants
Male adolescent participants, including CPF applicators (n=57) and non-applicators (n=38), were recruited.
Primary and secondary outcome measures
Self-reported data for 25 neurological symptoms were collected at 32 time points over the 8-month period before, during and after the application season. Additionally, urine and blood samples were collected to measure urine trichloro-2-pyridinol (TCPy), a CPF-specific biomarker and blood cholinesterase activity.
Results
Applicators and non-applicators report the highest numbers of symptoms during the application season, followed by a reduction in symptoms after the application ended. Applicators reported a greater percentage of neurological symptoms, relative to baseline, than non-applicators after accounting for potential covariates. Among the applicators, cumulative TCPy was positively and significantly associated with the average percentage of symptoms (B=4.56, 95% CI 3.29 to 5.84; p<0.001). Significant associations (p=0.03–0.07) between the change in butyrylcholinesterase activity from the preapplication to the postapplication season and several domains of neurological symptoms were also found, even after adjusting for potential covariates.
Conclusions
These observations demonstrate changes in the reporting of symptoms across the application season, showing an increase in symptom reporting during application and recovery following the end of pesticide application. These findings reinforce the growing concern regarding the neurotoxic health effects of CPF in adolescent applicators in developing countries and the need for developing and implementing intervention programmes.
doi:10.1136/bmjopen-2013-004177
PMCID: PMC3948636  PMID: 24595133
13.  Longitudinal Assessment of Chlorpyrifos Exposure and Effect Biomarkers in Adolescent Egyptian Agricultural Workers 
Chlorpyrifos (CPF) is applied seasonally in Egypt by adolescent agricultural workers and the extent of occupational exposure and the potential for environmental CPF exposure in this population is poorly understood. Adolescent pesticide applicators (n=57; 12–21 years of age) and age matched non-applicators (n=38) from the same villages were followed for 10 months in 2010, spanning pre-application through post-application. Eight urine and 5 blood samples were collected from participants within this time period. Blood acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) (exposure/effect biomarker) and urine 3,5,6-trichloro-2-pyridinol (TCPy) (exposure biomarker) were used to assess occupational CPF exposures in pesticide applicators and environmental exposures in non-applicators. Applicators demonstrated significantly higher TCPy concentration and BChE depression than non-applicators throughout CPF application. This difference persisted for 4–7 weeks after the cessation of agricultural spraying. However, both groups exhibited significantly elevated TCPy and depressed BChE, compared to their respective baseline. The peak TCPy levels during the spray season (95% confidence interval) for non-applicators and applicators reached 16.8 (9.87–28.5) and 137 (57.4–329) ug/g creatinine, respectively. BChE levels (95% confidence intervals) during the spray were 1.47 (1.28–1.68) for non-applicators and 0.47 (0.24–0.94) U/ml for applicators. The longitudinal assessment of CPF biomarkers provided robust measures of exposure and effect throughout CPF application in adolescents and revealed significant exposures in both applicators and non-applicators. Biomarker data in the non-applicators, which mirrored that of the applicators, indicated that non-applicators received environmental CPF exposures. This suggests that similar exposures may occur in other residents of this region during periods of pesticide application.
doi:10.1038/jes.2012.113
PMCID: PMC3926695  PMID: 23321857
chlorpyrifos; acetylcholinesterase; butyrylcholinesterase; TCPy; occupational exposure; environmental exposure
14.  Synthesis of Brominated 2-Phenitidine Derivatives as Valuable Inhibitors of Cholinesterases for the Treatment of Alzheimer’s Disease 
The present study reports the synthesis of a series N-substituted derivatives of brominated 2-phenitidine. First, the reaction of 2-phenitidine (1) with benzenesulfonyl chloride (2) in aqueous media yielded N-(2-ethoxyphenyl) benzenesulfonamide (3), which was then subjected to bromination with bromine in the presence of glacial acetic acid to give N-(4,5-dibromo-2-ethoxyphenyl) benzenesulfonamide (4). Secondly, the product (4) on further treatment with alkyl/aryl halides (5a-l) in the presence of lithium hydride (LiH) produced twelve new derivatives of N-substituted sulfonamides (6a-l). These were characterized by 1H-NMR spectrum and screened against acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and lipoxygenase (LOX) and were found to be valuable inhibitors of butyrylcholinesterase (BChE) and acetylcholinesterase (AChE). Few of them were also active against LOX.
PMCID: PMC3985256  PMID: 24734059
2-phenitidine; Sulfonamide; Bromination; Acetylcholinesterase; Bytyrylcholinesterase; Lipoxygenase; 1H-NMR
15.  Study of PKRBD in HCV genotype 3a infected patients in response to interferon therapy in Pakistani population 
Virology Journal  2013;10:352.
Background
Hepatitis C virus (HCV) is a major cause of liver cirrhosis and hepatocellular carcinoma and infects about 3% world population. Response to interferon therapy depends upon the genotype of the virus and factors associated with the host. Despite a good response to interferon therapy, a considerable number of genotype 3a infected patients remains unalleviated.
Results
In total forty-nine patients including twenty-five non-responders (non-SVR) and twenty-four responders (SVR) were recruited. Patients were tested for viral status at different intervals and the isolated RNA was sequenced for the NS5A region in both groups. The comparison of PKRBD of HCV between the SVR and non-SVR patients did not confirm any significant difference in the number of mutations. However, when the sequence downstream to the PKRBD of NS5A was compared, two important statistically significant mutations were observed; at positions 2309 (Ala to Ser) and 2326 (Gly to Ala). These mutations were then analysed for tertiary protein structure and important structural changes were observed. Statistically significant difference was also observed when age groups of patients were compared; younger patients showed better response than the older ones.
Conclusions
The region between PKRBD and IRRDR may be important for prediction of response to IFN therapy for genotype 3a. ISDR and PKRBD have not shown any involvement in treatment response. Further functional analyses of these findings can help in understanding the involvement of the NS5A region in interferon treatment of HCV-3a infected patients.
doi:10.1186/1743-422X-10-352
PMCID: PMC4029318  PMID: 24321105
16.  Bladder pain syndrome: validation of simple tests for diagnosis in women with chronic pelvic pain: BRaVADO study protocol 
Reproductive Health  2013;10:61.
Background
Bladder pain syndrome (BPS), a condition with no gold standard diagnosis, comprises of a cluster of signs and symptoms. Bladder filling pain and bladder wall tenderness are two basic clinical features, present in a high number of sufferers. This study will validate the performance of these simple tests for BPS in women with chronic pelvic pain (CPP).
Methods/design
We will conduct a prospective test validation study amongst women with unexplained CPP presenting to gynaecology outpatient clinics. Two index tests will be performed: patient reported bladder filling pain and bladder wall tenderness on internal pelvic bimanual examination. A final diagnosis of BPS will be made by expert consensus panel. We will assess the rates of index tests in women with CPP; evaluate the correlation between index tests and Pelvic Pain Urgency/ Frequency (PUF) questionnaire results; and determine index test sensitivity and specificity using a range of analytical methods. Assuming a 50% prevalence of BPS and an 80% power approximately 152 subjects will be required exclude sensitivity of < 55% at 70% sensitivity.
Discussion
The results of this test validation study will be used to identify whether a certain combination of signs and symptoms can accurately diagnose BPS.
Trial registration
ISRCTN13028601
doi:10.1186/1742-4755-10-61
PMCID: PMC4176137  PMID: 24304546
Bladder pain syndrome; Chronic pelvic pain; Consensus panel; Latent class analysis; Test validation
18.  Percutaneous vesicoamniotic shunting versus conservative management for fetal lower urinary tract obstruction (PLUTO): a randomised trial 
Lancet  2013;382(9903):1496-1506.
Summary
Background
Fetal lower urinary tract obstruction (LUTO) is associated with high perinatal and long-term childhood mortality and morbidity. We aimed to assess the effectiveness of vesicoamniotic shunting for treatment of LUTO.
Methods
In a randomised trial in the UK, Ireland, and the Netherlands, women whose pregnancies with a male fetus were complicated by isolated LUTO were randomly assigned by a central telephone and web-based randomisation service to receive either the intervention (placement of vesicoamniotic shunt) or conservative management. Allocation could not be masked from clinicians or participants because of the invasive nature of the intervention. Diagnosis was by prenatal ultrasound. The primary outcome was survival of the baby to 28 days postnatally. All primary analyses were done on an intention-to-treat basis, but these results were compared with those of an as-treated analysis to investigate the effect of a fairly large proportion of crossovers. We used Bayesian methods to estimate the posterior probability distribution of the effectiveness of vesicoamniotic shunting at 28 days. The study is registered with the ISRCTN Register, number ISRCTN53328556.
Findings
31 women with singleton pregnancies complicated by LUTO were included in the trial and main analysis, with 16 allocated to the vesicoamniotic shunt group and 15 to the conservative management group. The study closed early because of poor recruitment. There were 12 livebirths in each group. In the vesicoamniotic shunt group one intrauterine death occurred and three pregnancies were terminated. In the conservative management group one intrauterine death occurred and two pregnancies were terminated. Of the 16 pregnancies randomly assigned to vesicoamniotic shunting, eight neonates survived to 28 days, compared with four from the 15 pregnancies assigned to conservative management (intention-to-treat relative risk [RR] 1·88, 95% CI 0·71–4·96; p=0·27). Analysis based on treatment received showed a larger effect (3·20, 1·06–9·62; p=0·03). All 12 deaths were caused by pulmonary hypoplasia in the early neonatal period. Sensitivity analysis in which non-treatment-related terminations of pregnancy were excluded made some slight changes to point estimates only. Bayesian analysis in which the trial data were combined with elicited priors from experts suggested an 86% probability that vesicoamniotic shunting increased survival at 28 days and a 25% probability that it had a large, clinically important effect (defined as a relative increase of 55% or more in the proportion of neonates who survived). There was substantial short-term and long-term morbidity in both groups, including poor renal function—only two babies (both in the shunt group) survived to 2 years with normal renal function. Seven complications occurred in six fetuses from the shunt group, including spontaneous ruptured membranes, shunt blockage, and dislodgement. These complications resulted in four pregnancy losses.
Interpretation
Survival seemed to be higher in the fetuses receiving vesicoamniotic shunting, but the size and direction of the effect remained uncertain, such that benefit could not be conclusively proven. Our results suggest that the chance of newborn babies surviving with normal renal function is very low irrespective of whether or not vesicoamniotic shunting is done.
Funding
UK National Institute of Health Research, Wellbeing of Women, Hannah Eliza Guy Charity (Birmingham Children's Hospital Charity).
doi:10.1016/S0140-6736(13)60992-7
PMCID: PMC3898962  PMID: 23953766
19.  Identification of etiological agents by LPA and PCR in childhood meningitis 
Pakistan Journal of Medical Sciences  2013;29(5):1162-1166.
Objectives: To determine the etiological agents by Latex Particle Agglutination (LPA) and Polymerase Chain Reaction (PCR) in patients admitted with Cerebrospinal Fluid (CSF) culture negative bacterial meningitis
Methods: This descriptive case series was conducted at National Institute of Child Health, Karachi from January 2010 to December 2012. Patients meeting the WHO case definition of suspected meningitis from one month to 59 months of age were included in the study. CSF examination and culture was carried out on every patient and CSF culture negative patients were enrolled. Demographic data, clinical signs & symptoms and laboratory findings were entered into the proforma. Data was analyzed using statistical package for social sciences (SPSS) version 17. P-value <0.05 was taken as significant.
Results: A total of 166 patients were included. Male were 96 and female were 76 with the male to female ratio of 1.26. The mean age of patient was ± SD 14.6 ± 14.5 months. The etiological agents identified by LPA were in 26/166 (15.66%) cases and the organisms were H. influenzae type b 10 cases, streptococcus pneumoniae 15 cases and meningococcus only one case respectively. The organisms identified by PCR were in 65/166 (39.15%) cases and the isolates were H. influenzae type b 16 cases, streptococcus pneumoniae 48 cases and meningococcus 01 case respectively.
Conclusion: LPA and PCR are superior and useful diagnostic tools in microbiology. They can be used for rapid etiological diagnosis of bacterial meningitis for the early administration of proper antibiotic.
Abbreviation: LPA = Latex Particle Agglutination, PCR = Polymerase Chain Reaction, CSF = Cerebrospinal Fluid, CNS = Central Nervous System.
PMCID: PMC3858925  PMID: 24353712
Etiological Agents; Meningitis
20.  On-the-Job Evidence-Based Medicine Training for Clinician-Scientists of the Next Generation 
The Clinical Biochemist Reviews  2013;34(2):93-103.
Clinical scientists are at the unique interface between laboratory science and frontline clinical practice for supporting clinical partnerships for evidence-based practice. In an era of molecular diagnostics and personalised medicine, evidence-based laboratory practice (EBLP) is also crucial in aiding clinical scientists to keep up-to-date with this expanding knowledge base. However, there are recognised barriers to the implementation of EBLP and its training. The aim of this review is to provide a practical summary of potential strategies for training clinician-scientists of the next generation.
Current evidence suggests that clinically integrated evidence-based medicine (EBM) training is effective. Tailored e-learning EBM packages and evidence-based journal clubs have been shown to improve knowledge and skills of EBM. Moreover, e-learning is no longer restricted to computer-assisted learning packages. For example, social media platforms such as Twitter have been used to complement existing journal clubs and provide additional post-publication appraisal information for journals.
In addition, the delivery of an EBLP curriculum has influence on its success. Although e-learning of EBM skills is effective, having EBM trained teachers available locally promotes the implementation of EBM training. Training courses, such as Training the Trainers, are now available to help trainers identify and make use of EBM training opportunities in clinical practice. On the other hand, peer-assisted learning and trainee-led support networks can strengthen self-directed learning of EBM and research participation among clinical scientists in training. Finally, we emphasise the need to evaluate any EBLP training programme using validated assessment tools to help identify the most crucial ingredients of effective EBLP training.
In summary, we recommend on-the-job training of EBM with additional focus on overcoming barriers to its implementation. In addition, future studies evaluating the effectiveness of EBM training should use validated outcome tools, endeavour to achieve adequate power and consider the effects of EBM training on learning environment and patient outcomes.
PMCID: PMC3799223  PMID: 24151345
22.  Benzimidazole, coumrindione and flavone derivatives as alternate UV laser desorption ionization (LDI) matrices for peptides analysis 
Background
Matrix-assisted laser desorption/ionization (MALDI) is a soft ionization mass spectrometric technique, allowing the analysis of bio-molecules and other macromolecules. The matrix molecules require certain characteristic features to serve in the laser desorption/ionization mechanism. Therefore, only a limited number of compounds have been identified as ultraviolet- laser desorption/ionization (UV-LDI) matrices. However, many of these routine matrices generate background signals that useful information is often lost in them. We have reported flavones, coumarindione and benzimidazole derivatives as alternate UV-LDI matrices.
Results
Thirty one compounds have been successfully employed by us as matrices for the analysis of low molecular weight (LMW) peptides (up to 2000 Da). Two peptides, bradykinin and renin substrate tetra-decapeptide were analyzed by using the newly developed matrices. The MS measurements were made after mixing the matrix solution with analyte by using dried droplet sample preparation procedures. The synthesized matrix materials showed better S/N ratios and minimal background signals for low mass range. Furthermore, pico molar concentrations of [Glu1]-fibrinopeptide B human could be easily analyzed with these matrices. Finally, BSA-digest was analyzed and identified through database search against Swiss-Prot by using Mascot.
Conclusions
These results validate the good performance of the synthesized UV-laser desorption/ionization (LDI) matrices for the analysis of low molecular weight peptides.
doi:10.1186/1752-153X-7-77
PMCID: PMC3680071  PMID: 23621998
MALDI-MS; LDI matrix; Benzimidazole derivatives; Coumarin derivatives; Flavones; Peptides
23.  1-(2-Methyl-5-nitro-1H-imidazol-1-yl)acetone 
In the mol­ecule of the title compound, C7H9N3O3, the nitro and carbonyl groups are tilted with respect to the imidazole ring by 9.16 (6) and 65.47 (7)°, respectively. Neighbouring chains are linked via C—H⋯N and C—H⋯O hydrogen bonds forming two-dimensional slab-like networks lying parallel to (01-1).
doi:10.1107/S1600536813006569
PMCID: PMC3629604  PMID: 23634091
24.  (E)-2,4-Dimethyl-N′-(2-methyl­benzyl­idene)benzohydrazide 
In the title benzoyl­hydrazide derivative, C17H18N2O, the dihedral angle between the benzene rings is 88.45 (8)° and the azomethine double bond adopts an E conformation. In the crystal, mol­ecules are linked by N—H⋯O and C—H⋯O hydrogen bonds, forming a chain along the b axis.
doi:10.1107/S1600536813004388
PMCID: PMC3588470  PMID: 23476582
25.  5-Chloro-2-(4-meth­oxy­phen­yl)-1,3-benzo­thia­zole 
In the title compound, C14H10ClNOS, the dihedral angle between the benzothia­zole ring system and the meth­oxy-substituted benzene ring is 8.76 (16)°. In the crystal, mol­ecules are stacked in columns along the c axis and no significant inter­molecular inter­actions are observed.
doi:10.1107/S1600536813001955
PMCID: PMC3588450  PMID: 23476550

Results 1-25 (113)