Publications by authors named "Farhana Islam"

23 Publications

  • Page 1 of 1

Factors associated with severe sepsis in diarrheal adults and their outcome at an urban hospital, Bangladesh: A retrospective analysis.

PLoS One 2021 20;16(9):e0257596. Epub 2021 Sep 20.

Nutrition and Clinical Services Division (NCSD), International Centre for Diarhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.

Background: To describe factors associated with severe sepsis in diarrheal adults and their outcomes and offender in blood and stool to understand their interplay as clinical features of sepsis and severe diarrhea often overlap.

Methods And Results: We used this retrospective chart analysis employing an unmatched case-control design to study critically ill diarrheal adults aged ≥18 years treated in ICU of Dhaka hospital, icddr,b between January 2011 to December 2015. Of 8,863 in-patient diarrheal adults, 350 having severe sepsis were cases and an equal number of randomly selected non-septic patients were the controls. Cases died significantly more (14.9% vs 4.6%, p = <0.001) than controls. 69% of the cases progressed to septic shock. In logistic regression analysis, steroid intake, ileus, acute kidney injury (AKI), metabolic acidosis, and hypocalcemia were significantly associated with severe sepsis in diarrheal adults (all, p<0.05). 12% of cases (40/335) had bacteremia. Streptococcus pneumoniae [9 (22.5%)] was the single most common pathogen and gram-negatives [27 (67.5%)] were prevailing as a group.

Conclusion: Diarrheal adults who had ileus, AKI, metabolic acidosis, hypocalcemia, and also took steroids were found to have an association with severe sepsis. Strikingly, gram-negative were the predominant bacteria among the diarrheal adults having severe sepsis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0257596PLOS
September 2021

Pharmacogenetics-Guided Advances in Antipsychotic Treatment.

Clin Pharmacol Ther 2021 09 18;110(3):582-588. Epub 2021 Aug 18.

Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.

Pharmacogenetics (PGx) research over the past 2 decades has produced extensive evidence for the influence of genetic factors on the efficacy and tolerability of antipsychotic treatment. However, the application of these findings to optimize treatment outcomes for patients in clinical practice has been limited. This paper presents a meta-review of key PGx findings related to antipsychotic response and common adverse effects, including antipsychotic-induced weight gain, tardive dyskinesia (TD), and clozapine-induced agranulocytosis (CIAG), and highlights advances and challenges in clinical implementation. Most robust findings from candidate gene and genomewide association studies were reported for associations between polymorphisms in CYP2D6 and exposure and response to specific antipsychotics. As a result, product labels and guidelines from various PGx expert groups have provided selection and dosing recommendations based on CYP2D6 metabolizer phenotypes for commonly prescribed antipsychotics. Other interesting genetic targets include DRD2 for antipsychotic response, SLC18A2 for TD, and the human leukocyte antigen (HLA) genes, HLA-DQB1 and HLA-B, for CIAG. Well-designed studies using large, well-characterized samples that leverages international collaborations are needed to validate previous findings, as well as discover new genetic variants involved in antipsychotic response and adverse effects.
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http://dx.doi.org/10.1002/cpt.2339DOI Listing
September 2021

Therapeutic Potential, Synthesis, Patent evaluation and SAR studies of thieno[3,2-d]pyrimidine derivatives: Recent updates.

Curr Drug Targets 2021 May 25. Epub 2021 May 25.

Division of Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, Duquesne University, 600 Forbes Avenue, Pittsburgh, Pennsylvania 15282, United States.

Thieno[3,2-d]pyrimidine ring framework comprises a significant class of heterocyclics that serve as a promising platform showing different pharmacological activities. The interest in thieno[3,2-d]pyrimidine cores for pharmaceutical products makes this scaffold an exceptionally helpful building block for organic chemistry. This review presents current research on thieno[3,2-d]pyrimidines and elucidates their biological importance in anti-cancer, anti-infectious, anti-convulsant, anti-diabetic, CNS, and osteoporosis drug discoveries. Patents on the thieno[3,2-d]pyrimidines are also elaborated as a piece of useful information. Here we additionally focus on the synthesis of this vital ring and the discovery of new thieno[3,2-d]pyrimidines.
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http://dx.doi.org/10.2174/1389450122666210526094047DOI Listing
May 2021

Pharmacogenetic/Pharmacogenomic Tests for Treatment Prediction in Depression.

Adv Exp Med Biol 2021 ;1305:231-255

Pharmacogenetics Research Clinic, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Canada.

Genetic factors play a significant but complex role in antidepressant (AD) response and tolerability. During recent years, there is growing enthusiasm in the promise of pharmacogenetic/pharmacogenomic (PGx) tools for optimizing and personalizing treatment outcomes for patients with major depressive disorder (MDD). The influence of pharmacokinetic and pharmacodynamic genes on response and tolerability has been investigated, including those encoding the cytochrome P450 superfamily, P-glycoprotein, monoaminergic transporters and receptors, intracellular signal transduction pathways, and the stress hormone system. Genome-wide association studies are also identifying new genetic variants associated with AD response phenotypes, which, combined with methods such as polygenic risk scores (PRS), is opening up new avenues for novel personalized treatment approaches for MDD. This chapter describes the basic concepts in PGx of AD response, reviews the major pharmacokinetic and pharmacodynamic genes involved in AD outcome, discusses PRS as a promising approach for predicting AD efficacy and tolerability, and addresses key challenges to the development and application of PGx tests.
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http://dx.doi.org/10.1007/978-981-33-6044-0_13DOI Listing
April 2021

Novel pyrazolo[4,3-d]pyrimidine microtubule targeting agents (MTAs): Synthesis, structure-activity relationship, in vitro and in vivo evaluation as antitumor agents.

Bioorg Med Chem Lett 2021 06 9;41:127923. Epub 2021 Mar 9.

Division of Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, Duquesne University, 600 Forbes Avenue, Pittsburgh, PA 15282, United States. Electronic address:

The design, synthesis, and biological evaluation of a series novel N1‑methyl pyrazolo[4,3-d]pyrimidines as inhibitors of tubulin polymerization and colchicine binding were described here. Synthesis of target compounds involved alkylation of the pyrazolo scaffold, which afforded two regioisomers. These were separated, characterized and identified with H NMR and NOESY spectroscopy. All compounds, except 10, inhibited [H]colchicine binding to tubulin, and the potent inhibition was similar to that obtained with CA-4. Compounds 9 and 11-13 strongly inhibited the polymerization of tubulin, with IC values of 0.45, 0.42, 0.49 and 0.42 μM, respectively. Compounds 14-16 inhibited the polymerization of tubulin with IC near ∼1 μM. Compounds 9, 12, 13 and 16 inhibited MCF-7 breast cancer cell lines and circumvented βIII-tubulin mediated cancer cell resistance to taxanes and other MTAs, and compounds 9-17 circumvented Pgp-mediated drug resistance. In the standard NCI testing protocol, compound 9 exhibited excellent potency with low to sub nanomolar GI values (≤10 nM) against most tumor cell lines, including several multidrug resistant phenotypes. Compound 9 was significantly (P < 0.0001) better than paclitaxel at reducing MCF-7 TUBB3 (βIII-tubulin overexpressing) tumors in a mouse xenograft model. Collectively, these studies support the further preclinical development of the pyrazolo[4,3-d]pyrimidine scaffold as a new generation of tubulin inhibitors and 9 as an anticancer agent with advantages over paclitaxel.
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http://dx.doi.org/10.1016/j.bmcl.2021.127923DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113149PMC
June 2021

Genome-wide analysis suggests the importance of vascular processes and neuroinflammation in late-life antidepressant response.

Transl Psychiatry 2021 02 15;11(1):127. Epub 2021 Feb 15.

Institute of Medical Science, University of Toronto, Toronto, ON, Canada.

Antidepressant outcomes in older adults with depression is poor, possibly because of comorbidities such as cerebrovascular disease. Therefore, we leveraged multiple genome-wide approaches to understand the genetic architecture of antidepressant response. Our sample included 307 older adults (≥60 years) with current major depression, treated with venlafaxine extended-release for 12 weeks. A standard genome-wide association study (GWAS) was conducted for post-treatment remission status, followed by in silico biological characterization of associated genes, as well as polygenic risk scoring for depression, neurodegenerative and cerebrovascular disease. The top-associated variants for remission status and percentage symptom improvement were PIEZO1 rs12597726 (OR = 0.33 [0.21, 0.51], p = 1.42 × 10) and intergenic rs6916777 (Beta = 14.03 [8.47, 19.59], p = 1.25 × 10), respectively. Pathway analysis revealed significant contributions from genes involved in the ubiquitin-proteasome system, which regulates intracellular protein degradation with has implications for inflammation, as well as atherosclerotic cardiovascular disease (n = 25 of 190 genes, p = 8.03 × 10, FDR-corrected p = 0.01). Given the polygenicity of complex outcomes such as antidepressant response, we also explored 11 polygenic risk scores associated with risk for Alzheimer's disease and stroke. Of the 11 scores, risk for cardioembolic stroke was the second-best predictor of non-remission, after being male (Accuracy = 0.70 [0.59, 0.79], Sensitivity = 0.72, Specificity = 0.67; p = 2.45 × 10). Although our findings did not reach genome-wide significance, they point to previously-implicated mechanisms and provide support for the roles of vascular and inflammatory pathways in LLD. Overall, significant enrichment of genes involved in protein degradation pathways that may be impaired, as well as the predictive capacity of risk for cardioembolic stroke, support a link between late-life depression remission and risk for vascular dysfunction.
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http://dx.doi.org/10.1038/s41398-021-01248-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884410PMC
February 2021

Contributions of cholinergic receptor muscarinic 1 and CYP1A2 gene variants on the effects of plasma ratio of clozapine/N-desmethylclozapine on working memory in schizophrenia.

J Psychopharmacol 2021 01 4;35(1):31-39. Epub 2020 Nov 4.

Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Canada.

Background: Clozapine has heterogenous efficacy in enhancing working memory in schizophrenia. We have previously hypothesized that this is due to opposing effects of clozapine and its metabolite, N-desmethylclozapine, at the muscarinic M1 receptor and demonstrated that a lower clozapine/-desmethylclozapine ratio is associated with better working memory than clozapine or -desmethylclozapine levels alone.

Aims: In this study, we expanded the above hypothesis to explore whether genetic variation in the cholinergic receptor muscarinic 1 gene, encoding the M1 receptor, affects the relationship between clozapine/-desmethylclozapine and working memory. Further, we explored whether CYP1A2 gene variants affect the ratio of clozapine/-desmethylclozapine and by this, working memory performance.

Methods: We evaluated two functionally significant single nucleotide polymorphisms, rs1942499 and rs2075748, in cholinergic receptor muscarinic 1, with the haplotype T-A associated with lower transcriptional activity than the haplotype C-G. Further, we examined *1F, with *1F/*1F conferring high inducibility in the presence of smoking.

Results: In a sample of 30 patients with schizophrenia on clozapine monotherapy, clozapine/-desmethylclozapine was correlated with working memory only in non-carriers of the haplotype T-A of the gene. Interaction of genotype and smoking status significantly affected clozapine concentrations, but there were no significant effects of genotype and smoking status on the relationship between clozapine/-desmethylclozapine on working memory.

Conclusions: Our finding that the relationship between clozapine/-desmethylclozapine and working memory is specific to patients with potentially higher transcription of M1 receptor (i.e. non-carriers of the haplotype T-A of ) supports a cholinergic mechanism underlying this relationship.
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http://dx.doi.org/10.1177/0269881120946288DOI Listing
January 2021

Prevalence of NPHS2 gene R229Q polymorphism in Bangladeshi children with nephrotic syndrome.

Heliyon 2020 Oct 20;6(10):e05317. Epub 2020 Oct 20.

Department of Clinical Pharmacy and Pharmacology, Faculty of Pharmacy, University of Dhaka, Dhaka, 1000, Bangladesh.

Background: Limited and contradictory pharmacogenetic studies of gene R229Q polymorphism in nephrotic syndrome (NS) children of different ethnicities steered us to investigate the genotype frequency and associated risk of this polymorphism in Bangladeshi NS children.

Methods: A prospective case-control study was conducted which comprised a total of 142 children having nephrotic syndrome (NS), divided into 2 groups: case group consisted of 40 children with steroid-resistant nephrotic syndrome (SRNS), and control group involved 102 children with steroid-sensitive nephrotic syndrome (SSNS). Both were genotyped by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method for R229Q polymorphism.

Results: The results indicate the presence of R229Q polymorphism in 27.50% of SRNS and 12.75% of SSNS children. SRNS children possess 2.94-fold greater risk (p = 0.025) of carrying Arg/Gln genotype compared to SSNS children. Moreover, R229Q variant in SRNS children was observed as in a compound heterozygous form with p.Ala297Val located in exon 8. Age of onset (4-6 years) presents as a significant contributing factor (adjusted OR = 1.06; 95% CI = 1.023-1.094; p = 0.001) for SRNS susceptibility in Bangladeshi children. Contrarily, though the incidence of SRNS was higher in male children than female (80% vs 20%), gender remains to be a neutral factor (p = 0.257) in relation to SRNS susceptibility.

Conclusion: Compound heterozygosity of p.R229Q gene variant with p.Ala297Val may cause pathogenic SRNS in Bangladeshi children. Large scale studies are warranted to establish the genotype-phenotype correlation. It is recommended to screen for p.R229Q first and, if positive, for p.Ala297Val in Bangladeshi SRNS children.
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http://dx.doi.org/10.1016/j.heliyon.2020.e05317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578689PMC
October 2020

Cholera and Pancreatic Cholera: Is VIP the Common Pathophysiologic Factor?

Trop Med Infect Dis 2020 Jul 2;5(3). Epub 2020 Jul 2.

Department of Immunology and Microbial Diseases, Albany Medical College, Albany, NY 12208, USA.

Background: Cholera remains a major global health problem, causing high output diarrhea leading to severe dehydration and shock in developing countries. We aimed to determine whether vasoactive intestinal polypeptide (VIP), the mediator of pancreatic cholera syndrome, has a role in the pathophysiology of human cholera.

Methods: We conducted a prospective observational study of cholera cases hospitalized with severe dehydration. Plasma and stool water levels of VIP were measured just after admission, after complete rehydration (3-4 h), at 24 h post-rehydration and at discharge after diarrhea ceased.

Results: In total, 23 cholera patients were examined between January and August 2018. The geometric mean of stool VIP (sVIP) and plasma VIP (pVIP) on admission were 207.67 and 8.34 pmol/L, respectively. pVIP values were all within the normal range (
Conclusions: The data suggest that VIP, which is released by intestinal nerves, may play an important role in human choleragenesis, and inhibitors of intestinal VIP merit testing for potential therapeutic benefits.
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http://dx.doi.org/10.3390/tropicalmed5030111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7559706PMC
July 2020

SMAD2 rs4940086 heterozygosity increases the risk of cervical cancer development among the women in Bangladesh.

Mol Biol Rep 2020 Jul 7;47(7):5033-5040. Epub 2020 Jun 7.

Department of Clinical Pharmacy and Pharmacology, Faculty of Pharmacy, University of Dhaka, Dhaka, 1000, Bangladesh.

SMAD2 is a critical signal transducer molecule in the TGFβ- SMAD pathway which is also known for its tumor suppressor role. Genetic variations in SMAD2 render cells insensitive to its anti-proliferative signals leading to tumor formation. In this study, we demonstrate the impact of single nucleotide polymorphisms (SNPs) of SMAD2 (rs4940086 and rs8085335) on cervical cancer risk development in Bangladeshi population. 132 cervical cancer patients and 98 control volunteers were enrolled in the study and genotyped utilizing polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The association between cervical cancer susceptibility and the chosen SNPs were evaluated through multiple logistic regression. SMAD2 rs4940086 heterozygous genotype (T/C) was associated with a 3.89 times higher risk of cervical cancer development (P = 0.001, AOR 3.89, 95% CI 1.777-8.513). The T/C and C/C genotypes in combination also significantly elevated cervical cancer risk (P = 0.035, AOR 1.876, 95% CI 1.047-3.364). Urban cancer patients had a significantly higher chance of carrying the rs4940086 polymorphism as compared to rural cancer patients (P = 0.045, OR 2.59 95% CI 1.02-6.59). SMAD2 rs8085335 heterozygous variant (A/G) demonstrated modest effects in increasing cervical cancer susceptibility (P = 0.594, AOR 1.247, 95% CI 0.554-2.809). Our results suggest that polymorphic variations in SMAD2, particularly rs4940086, can potentially elevate cervical cancer susceptibility in Bangladeshi women.
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http://dx.doi.org/10.1007/s11033-020-05572-7DOI Listing
July 2020

Design, synthesis and biological evaluation of novel pyrrolo[2,3-d]pyrimidine as tumor-targeting agents with selectivity for tumor uptake by high affinity folate receptors over the reduced folate carrier.

Bioorg Med Chem 2020 06 6;28(12):115544. Epub 2020 May 6.

Division of Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, Duquesne University, 600 Forbes Avenue, Pittsburgh, PA 15282, United States. Electronic address:

Tumor-targeted 6-substituted pyrrolo[2,3-d]pyrimidine benzoyl compounds based on 2 were isosterically modified at the 4-carbon bridge by replacing the vicinal (C11) carbon by heteroatoms N (4), O (5) or S (6), or with an N-substituted formyl (7), trifluoroacetyl (8) or acetyl (9). Replacement with sulfur (6) afforded the most potent KB tumor cell inhibitor, ~6-fold better than the parent 2. In addition, 6 retained tumor transport selectivity via folate receptor (FR) α and -β over the ubiquitous reduced folate carrier (RFC). FRα-mediated cell inhibition for 6 was generally equivalent to 2, while the FRβ-mediated activity was improved by 16-fold over 2. N (4) and O (5) substitutions afforded similar tumor cell inhibitions as 2, with selectivity for FRα and -β over RFC. The N-substituted analogs 7-9 also preserved transport selectivity for FRα and -β over RFC. For FRα-expressing CHO cells, potencies were in the order of 8 > 7 > 9. Whereas 8 and 9 showed similar results with FRβ-expressing CHO cells, 7 was ~16-fold more active than 2. By nucleoside rescue experiments, all the compounds inhibited de novo purine biosynthesis, likely at the step catalyzed by glycinamide ribonucleotide formyltransferase. Thus, heteroatom replacements of the CH in the bridge of 2 afford analogs with increased tumor cell inhibition that could provide advantages over 2, as well as tumor transport selectivity over clinically used antifolates including methotrexate and pemetrexed.
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http://dx.doi.org/10.1016/j.bmc.2020.115544DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7327796PMC
June 2020

Pharmacogenetic Implications for Antidepressant Pharmacotherapy in Late-Life Depression: A Systematic Review of the Literature for Response, Pharmacokinetics and Adverse Drug Reactions.

Am J Geriatr Psychiatry 2020 06 3;28(6):609-629. Epub 2020 Feb 3.

Institute of Medical Science, University of Toronto (VSM, BHM, DJM), Toronto, ON, Canada; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (VSM, FI, MM, BHM, DJM), Toronto, ON, Canada; Department of Pharmacology (FI, DJM), University of Toronto, Toronto, ON, Canada; Department of Psychiatry (BHM, DJM), University of Toronto, Toronto, ON, Canada. Electronic address:

Affecting up to 15% of older adults, late-life depression (LLD) is characterized by the occurrence of depressive symptoms after the age of 50-65 years and maybe pathophysiologically distinct from depression in younger adults. Therefore, LLD is challenging to treat, and predictive genetic testing might be essential to improve treatment in this vulnerable population. The current review aims to provide a summary of the literature exploring genetic associations with antidepressant treatment outcomes in late-life. We conducted a systematic search of three integrated electronic databases. We identified 29 articles investigating genetic associations with antidepressant treatment outcomes, pharmacokinetic parameters, and adverse drug reactions in older adults. Given the small number of investigations conducted in older adults, it is difficult to conclude the presence or absence of genetic associations with the outcomes of interest. In sum, the most substantial amount of evidence exists for the CYP2D6 metabolizer status, SLC6A4 5-HTTLPR, and BDNF rs6265. These findings are consistent in the literature when not restricting to older adults, suggesting that similar treatment recommendations may be provided for older adults regarding genetic variation, such as those outlined for CYP2D6 by the Clinical Pharmacogenetics Implementation Consortium. Nonetheless, further studies are required in well-characterized samples, including genome-wide data, to validate if similar treatment adjustments are appropriate in older adults, given that there appear to be significant effects of genetic variation on antidepressant treatment factors.
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http://dx.doi.org/10.1016/j.jagp.2020.01.007DOI Listing
June 2020

Validation study of microRNAs previously associated with antidepressant response in older adults treated for late-life depression with venlafaxine.

Prog Neuropsychopharmacol Biol Psychiatry 2020 06 16;100:109867. Epub 2020 Jan 16.

Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Pharmacology & Toxicology, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada. Electronic address:

Background: MicroRNAs (miRNAs) are small 22 nucleotides long, non-coding RNAs that are potential biomarkers for antidepressant treatment response. We aimed to replicate previous associations of miRNAs with antidepressant treatment response in a sample of older adults diagnosed with late-life depression.

Methods: Our sample included 184 older adults diagnosed with moderately severe depression that received open-label venlafaxine (up to 300 mg/day) for approximately 12 weeks. We quantified miRNA expression levels at baseline and week 12 for miRNAs miR-1202, miR-135a-5p, miR-16-5p, miR-146a-5p, miR-146b-5p, miR-425-3p, and miR-24-3p to explore their association with remission status, response trajectories, and time-to-remission.

Results: At T0 and T12, there were no differences in miRNA expression levels between remitters and non-remitters. However, remitters showed a trend toward higher baseline miR-135a-5p (Median = 11.3 [9.9, 15.7], p = .083). Prior to correction, baseline miR-135a-5p expression levels showed an association with remission status (OR = 1.8 [1.0, 3.3], p = .037). Individuals with higher baseline miR-135a-5p showed better response trajectories (F = 4.5, FDR-corrected p = 4.4 × 10), particularly at weeks 10 and 12 (p < .05). In addition, individuals with higher miR-135a-5p expression reached remission faster than those with lower expression (HR = 0.6 [0.4, 0.9], FDR-corrected p = .055).

Limitations: Although the sample size was relatively modest, our findings are consistent with the literature suggesting that higher miR-135a-5p levels may be associated with better antidepressant treatment response.

Conclusions: However, the miRNA signature of antidepressant response in older adults may be different as compared to younger adults.
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http://dx.doi.org/10.1016/j.pnpbp.2020.109867DOI Listing
June 2020

Usability and acceptability of four systematic review automation software packages: a mixed method design.

Syst Rev 2019 06 20;8(1):145. Epub 2019 Jun 20.

Institute for Evidence-Based Healthcare, Bond University, Gold Coast, Australia.

Aim: New software packages help to improve the efficiency of conducting a systematic review through automation of key steps in the systematic review. The aim of this study was to gather qualitative data on the usability and acceptability of four systematic review automation software packages (Covidence, SRA-Helper for EndNote, Rayyan and RobotAnalyst) for the citation screening step of a systematic review.

Methods: We recruited three volunteer systematic reviewers and asked them to use allocated software packages during citation screening. They then completed a 12-item online questionnaire which was tailored to capture data for the software packages used.

Findings: All four software packages were reported to be easy or very easy to learn and use. SRA-Helper for EndNote was most favoured by participants for screening citations and Covidence for resolving conflicts. Overall, participants reported that SRA-Helper for EndNote would be their software package of choice, primarily due to its efficiency.

Conclusion: This study identified a number of considerations which systematic reviewers can use as a basis of their decision which software to use when performing the citation screening and dispute resolution steps of a systematic review.
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http://dx.doi.org/10.1186/s13643-019-1069-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6587262PMC
June 2019

Probiotics for preventing acute otitis media in children.

Cochrane Database Syst Rev 2019 06 18;6:CD012941. Epub 2019 Jun 18.

Centre for Research in Evidence-Based Practice (CREBP), Bond University, 14 University Drive, Gold Coast, Queensland, Australia, 4229.

Background: Acute otitis media (AOM), or acute middle ear infection, is one of the most frequently occurring childhood diseases, and the most common reason given for prescribing antibiotics in this age group. Guidelines often recommend antibiotics as first-line treatment for severe AOM. However, antibiotics also lead to antibiotic resistance, so preventing episodes of AOM is an urgent priority.

Objectives: To assess the effects of probiotics to prevent the occurrence and reduce the severity of acute otitis media in children.

Search Methods: We searched CENTRAL, PubMed, Embase, and three other databases (October 2018), two trial registers (October 2018), and conducted a backwards and forwards citation analysis (August 2018). We did not apply any language, publication date, or publication status restrictions.

Selection Criteria: Randomised controlled trials (RCTs) of children (aged up to 18 years), comparing probiotics with placebo, usual care, or no probiotic.

Data Collection And Analysis: Two review authors independently assessed the eligibility of trials for inclusion and risk of bias of the included trials, and extracted data using pre-piloted data extraction forms. We analysed dichotomous data as either risk ratio (RR) or odds ratios (OR) and continuous data as mean differences (MD).

Main Results: We included 17 RCTs involving 3488 children, of which 16 RCTs were included in the meta-analyses. Of the 16 RCTs that reported the mean age of children, mean age overall was 2.4 years; in 4 RCTs the mean age of children participating in the trial was less than 1 year old; in 2 RCTs the mean age was between 1 and 2 years old; and in 10 RCTs the mean age was older than 2 years. Probiotic strains evaluated by the trials varied, with 11 of the included RCTs evaluating Lactobacillus-containing probiotics, and six RCTs evaluating Streptococcus-containing probiotics.The proportion of children (i.e. the number of children in each group) experiencing one or more episodes of AOM during the treatment was lower for those taking probiotics (RR 0.77, 95% confidence interval (CI) 0.63 to 0.93; 16 trials; 2961 participants; number needed to treat for an additional beneficial outcome (NNTB) = 10; moderate-certainty evidence).Post hoc subgroup analysis found that among children not prone to otitis media, a lower proportion of children receiving probiotics experienced AOM (RR 0.64, 95% CI 0.49 to 0.84; 11 trials; 2227 participants; NNTB = 9; moderate-certainty evidence). However, among children who were otitis prone, there was no difference between probiotic and comparator groups (RR 0.97, 95% CI 0.85 to 1.11; 5 trials; 734 participants; high-certainty evidence). The test for subgroup differences was significant (P = 0.007).None of the included trials reported on the severity of AOM.The proportion of children experiencing adverse events did not differ between the probiotic and comparator groups (OR 1.54, 95% CI 0.60 to 3.94; 4 trials; 395 participants; low-certainty evidence).Probiotics decreased the proportion of children taking antibiotics for any infection (RR 0.66, 95% CI 0.51 to 0.86; 8 trials; 1768 participants; NNTB = 8; moderate-certainty evidence). Test for subgroup differences (use of antibiotic specifically for AOM, use of antibiotic for infections other than AOM) was not significant.There was no difference in the mean number of school days lost (MD -0.95, 95% CI -2.47 to 0.57; 5 trials; 1280 participants; moderate-certainty evidence). There was no difference between groups in the level of compliance in taking the intervention (RR 1.02, 95% CI 0.99 to 1.05; 5 trials; 990 participants).Probiotics decreased the proportion of children having other infections (RR 0.75, 95% CI 0.65 to 0.87; 11 trials; 3610 participants; NNTB = 12; moderate-certainty evidence). Test for subgroup differences (acute respiratory infections, gastrointestinal infections) was not significant.Probiotic strains trialled and their dose, frequency, and duration of administration varied considerably across studies, which likely contributed to the substantial levels of heterogeneity. Sensitivity testing of funnel plots did not reveal publication bias.

Authors' Conclusions: Probiotics may prevent AOM in children not prone to AOM, but the inconsistency of the subgroup analyses suggests caution in interpreting these results. Probiotics decreased the proportion of children taking antibiotics for any infection. The proportion of children experiencing adverse events did not differ between the probiotic and comparator groups. The optimal strain, duration, frequency, and timing of probiotic administration still needs to be established.
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http://dx.doi.org/10.1002/14651858.CD012941.pub2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6580359PMC
June 2019

Phenol-selective mass spectrometric analysis of jet fuel.

Analyst 2017 Aug;142(17):3278-3284

Department of Chemistry, University of Victoria, PO Box 1700 STN CSC, Victoria, BC V8W 2Y2, Canada.

Bromobenzyl compounds react selectively with phenols via the Williamson ether synthesis. An imidazolium charge-tagged bromobenzyl compound can be used to reveal phenol impurities in jet fuel by analysis via electrospray ionization mass spectrometry. The complex matrix as revealed by Cold EI GC/MS analysis is reduced to a few simple sets of compounds in the charge-tagged ESI mass spectrum, primarily substituted phenols and thiols. Examination of jet fuels treated by different refinery methods reveals the efficacy of these approaches in removing these contaminants.
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http://dx.doi.org/10.1039/c7an00908aDOI Listing
August 2017

Brain-Derived Neurotrophic Factor Expression in Individuals With Schizophrenia and Healthy Aging: Testing the Accelerated Aging Hypothesis of Schizophrenia.

Curr Psychiatry Rep 2017 Jul;19(7):36

Division of Geriatric Psychiatry, Department of Psychiatry, University of Toronto, Toronto, ON, Canada.

Purpose Of Review: Schizophrenia has been hypothesized to be a syndrome of accelerated aging. Brain plasticity is vulnerable to the normal aging process and affected in schizophrenia: brain-derived neurotrophic factor (BDNF) is an important neuroplasticity molecule. The present review explores the accelerated aging hypothesis of schizophrenia by comparing changes in BDNF expression in schizophrenia with aging-associated changes.

Recent Findings: Individuals with schizophrenia show patterns of increased overall mortality, metabolic abnormalities, and cognitive decline normally observed later in life in the healthy population. An overall decrease is observed in BDNF expression in schizophrenia compared to healthy controls and in older individuals compared to a younger cohort. There is a marked decrease in BDNF levels in the frontal regions and in the periphery among older individuals and those with schizophrenia; however, data for BDNF expression in the occipital, parietal, and temporal cortices and the hippocampus is inconclusive. Accelerated aging hypothesis is supported based on frontal regions and peripheral studies; however, further studies are needed in other brain regions.
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http://dx.doi.org/10.1007/s11920-017-0794-6DOI Listing
July 2017

Inhibition of Wnt signalling dose-dependently impairs the acquisition and expression of amphetamine-induced conditioned place preference.

Behav Brain Res 2017 05 9;326:217-225. Epub 2017 Mar 9.

Centre for Neuroscience Studies, Queen's University, Kingston, ON, Canada; Department of Psychology, Queen's University, Kingston, ON, Canada. Electronic address:

The mechanisms by which dopaminergic neurotransmission in the nucleus accumbens (NAc) is involved in incentive learning produced by rewarding stimuli remain unclear. Recently, Wnt signalling has been implicated in synaptic plasticity and learning and memory. Functional interactions between Wnt and dopamine (DA) signalling has been demonstrated using in vitro and tissue physiology approaches, however there remains a lack of in vivo research into the involvement of Wnt in DA-mediated learning in behaving animals. The present study assessed the role of Wnt signalling in DA-mediated incentive learning using the conditioned place preference (CPP) paradigm. We hypothesized that inhibition of Wnt with intra-NAc microinjections of Wnt palmitoylation inhibitor IWP-2 will dose-dependently block the acquisition and expression of amphetamine (AMPH)-induced CPP in rats. Intra-NAc IWP-2 (0.001, 0.05, 1.0 but not 0.0001μg/0.5μl/side) prior to conditioning with AMPH (20.0μg/0.5μl/side) blocked acquisition of CPP. Intra-NAc IWP-2 (0.05, 0.5, 1.0 but not 0.001μg/0.5μl/side) during test following conditioning with AMPH blocked expression but at a higher dose than was need to block acquisition. Sensitization of locomotor activity to AMPH was observed during conditioning and this effect was blocked in groups given IWP-2 prior to AMPH. However, intra-NAc IWP-2 during conditioning did not block the locomotor stimulant effects of AMPH. These results implicate Wnt in DA-mediated incentive learning and suggest that Wnt signalling may be more important for the acquisition of CPP then for its expression. However, mechanisms by which Wnt and DA signalling pathways interact to influence DA-mediated reward-related learning remain to be elucidated.
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http://dx.doi.org/10.1016/j.bbr.2017.03.016DOI Listing
May 2017

Selective mass spectrometric analysis of thiols using charge-tagged disulfides.

Analyst 2016 Oct 8;141(19):5520-6. Epub 2016 Jul 8.

Department of Chemistry, University of Victoria, P.O. Box 3065, Victoria, BC V8W3V6, Canada.

A simple chemical derivatization technique was developed for electrospray ionization mass spectrometry (ESI-MS) in which thiols and disulfides may be selectively analyzed in a complex matrix and easily characterized. These reagents enhance detection of thiols and disulfides solely due to the nature of the charge-tag derivatization agent and therefore does not require an isotopically labelled substrate. The charged disulfides readily and exclusively react with thiols in a complex matrix in a short amount of time. Furthermore, the synthesis of these reagents is simple and results in a highly pure and stable reagent. The efficacy of this reaction was demonstrated using on-line monitoring, while the scope and usefulness of the reaction was demonstrated in petroleum fractions.
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http://dx.doi.org/10.1039/c6an01210hDOI Listing
October 2016

Tribal formulations for treatment of pain: a study of the Bede community traditional medicinal practitioners of Porabari Village in Dhaka District, Bangladesh.

Afr J Tradit Complement Altern Med 2012 1;10(1):26-34. Epub 2012 Oct 1.

Faculty of Life Sciences, University of Development Alternative, Dhanmondi, Dhaka-1205, Bangladesh.

The Bedes form one of the largest tribal or indigenous communities in Bangladesh and are popularly known as the boat people or water gypsies because of their preference for living in boats. They travel almost throughout the whole year by boats on the numerous waterways of Bangladesh and earn their livelihood by selling sundry items, performing jugglery acts, catching snakes, and treating village people by the various riversides with their traditional medicinal formulations. Life is hard for the community, and both men and women toil day long. As a result of their strenuous lifestyle, they suffer from various types of pain, and have developed an assortment of formulations for treatment of pain in different parts of the body. Pain is the most common reason for physician consultation in all parts of the world including Bangladesh. Although a number of drugs are available to treat pain, including non-steroidal, steroidal, and narcotic drugs, such drugs usually have side-effects like causing bleeding in the stomach over prolonged use (as in the case of rheumatic pain), or can be addictive. Moreover, pain arising from causes like rheumatism has no proper treatment in allopathic medicine. It was the objective of the present study to document the formulations used by the Bede traditional practitioners for pain treatment, for they claim to have used these formulations over centuries with success. Surveys were conducted among a large Bede community, who reside in boats on the Bangshi River by Porabari village of Savar area in Dhaka district of Bangladesh. Interviews of 30 traditional practitioners were conducted with the help of a semi-structured questionnaire and the guided field-walk method. It was observed that the Bede practitioners used 53 formulations for treatment of various types of pain, the main ingredient of all formulations being medicinal plants. Out of the 53 formulations, 25 were for treatment of rheumatic pain, either exclusively, or along with other types of body pain. A total of 65 plants belonging to 39 families were used in the formulations. The Fabaceae family provided 7 plants followed by the Solanaceae family with 4 plants. 47 out of the 53 formulations were used topically, 5 formulations were orally administered, and 1 formulation had both topical and oral uses. 8 formulations for treatment of rheumatic pain contained Calotropis gigantea, suggesting that the plant has strong potential for further scientific studies leading to discovery of novel efficacious compounds for rheumatic pain treatment.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3746354PMC
http://dx.doi.org/10.4314/ajtcam.v10i1.5DOI Listing
April 2014

Medicinal plants used for treatment of diabetes by the Marakh sect of the Garo tribe living in Mymensingh district, Bangladesh.

Afr J Tradit Complement Altern Med 2012 2;9(3):380-5. Epub 2012 Apr 2.

Faculty of Life Sciences, University of Development Alternative, Dhanmondi, Dhaka-1205, Bangladesh.

Diabetes mellitus is an endocrinological disorder arising from insulin deficiency or due to ineffectiveness of the insulin produced by the body. This results in high blood glucose and with time, to neurological, cardiovascular, retinal and renal complications. It is a debilitating disease and affects the population of every country of the world. Around 200 million people of the world suffer from this disease and this figure is projected to rise to 300 million in the coming years. The disease cannot be cured with allopathic medicine as the drugs used do not restore normal glucose homeostasis and moreover have side-effects. On the other hand, traditional medicinal practitioners of various countries claim to cure diabetes or at least alleviate the major symptoms and progression of this disease through administration of medicinal plants. The Garos are an indigenous community of Bangladesh, who still follow their traditional medicinal practices. Their traditional medicinal formulations contain a number of plants, which they claim to be active antidiabetic agents. Since observation of indigenous practices have led to discovery of many modern drugs, it was the objective of the present study to conduct a survey among the Marakh sect of the Garos residing in Mymensingh district of Bangladesh to find out the medicinal plants that they use for treatment of diabetes. It was found that the tribal practitioners of the Marakh sect of the Garos use twelve medicinal plants for treatment of diabetes. These plants were Lannea coromandelica, Alstonia scholaris, Catharanthus roseus, Enhydra fluctuans, Terminalia chebula, Coccinia grandis, Momordica charantia, Cuscuta reflexa, Phyllanthus emblica, Syzygium aqueum, Drynaria quercifolia, and Clerodendrum viscosum. A review of the scientific literature demonstrated that almost all the plants used by the Garo tribal practitioners have reported antidiabetic and/or antioxidant properties and have enormous potential for possible development of new and efficacious antidiabetic drugs.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3746667PMC
http://dx.doi.org/10.4314/ajtcam.v9i3.12DOI Listing
March 2014

Formation of tellurium nanocrystals during anaerobic growth of bacteria that use Te oxyanions as respiratory electron acceptors.

Appl Environ Microbiol 2007 Apr 2;73(7):2135-43. Epub 2007 Feb 2.

.S. Geological Survey, Menlo Park, California 94025, USA.

Certain toxic elements support the metabolism of diverse prokaryotes by serving as respiratory electron acceptors for growth. Here, we demonstrate that two anaerobes previously shown to be capable of respiring oxyanions of selenium also achieve growth by reduction of either tellurate [Te(VI)] or tellurite [Te(IV)] to elemental tellurium [Te(0)]. This reduction achieves a sizeable stable-Te-isotopic fractionation (isotopic enrichment factor [epsilon] = -0.4 to -1.0 per ml per atomic mass unit) and results in the formation of unique crystalline Te(0) nanoarchitectures as end products. The Te(0) crystals occur internally within but mainly externally from the cells, and each microorganism forms a distinctly different structure. Those formed by Bacillus selenitireducens initially are nanorods ( approximately 10-nm diameter by 200-nm length), which cluster together, forming larger ( approximately 1,000-nm) rosettes composed of numerous individual shards ( approximately 100-nm width by 1,000-nm length). In contrast, Sulfurospirillum barnesii forms extremely small, irregularly shaped nanospheres (diameter < 50 nm) that coalesce into larger composite aggregates. Energy-dispersive X-ray spectroscopy and selected area electron diffraction indicate that both biominerals are composed entirely of Te and are crystalline, while Raman spectroscopy confirms that they are in the elemental state. These Te biominerals have specific spectral signatures (UV-visible light, Raman) that also provide clues to their internal structures. The use of microorganisms to generate Te nanomaterials may be an alternative for bench-scale syntheses. Additionally, they may also generate products with unique properties unattainable by conventional physical/chemical methods.
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http://dx.doi.org/10.1128/AEM.02558-06DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1855670PMC
April 2007

Role of metal-reducing bacteria in arsenic release from Bengal delta sediments.

Nature 2004 Jul;430(6995):68-71

Department of Earth Sciences and Williamson Research Centre for Molecular Environmental Science, The University of Manchester, Manchester M13 9PL, UK.

The contamination of ground waters, abstracted for drinking and irrigation, by sediment-derived arsenic threatens the health of tens of millions of people worldwide, most notably in Bangladesh and West Bengal. Despite the calamitous effects on human health arising from the extensive use of arsenic-enriched ground waters in these regions, the mechanisms of arsenic release from sediments remain poorly characterized and are topics of intense international debate. We use a microscosm-based approach to investigate these mechanisms: techniques of microbiology and molecular ecology are used in combination with aqueous and solid phase speciation analysis of arsenic. Here we show that anaerobic metal-reducing bacteria can play a key role in the mobilization of arsenic in sediments collected from a contaminated aquifer in West Bengal. We also show that, for the sediments in this study, arsenic release took place after Fe(III) reduction, rather than occurring simultaneously. Identification of the critical factors controlling the biogeochemical cycling of arsenic is one important contribution to fully informing the development of effective strategies to manage these and other similar arsenic-rich ground waters worldwide.
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http://dx.doi.org/10.1038/nature02638DOI Listing
July 2004
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