3-Nitrotriazole-based piperazides as potent antitrypanosomal agents

publisher: Elsevier articletitle: 3-Nitrotriazole-based piperazides as potent antitrypanosomal agents journaltitle: European Journal of Medicinal Chemistry articlelink: http://dx.doi.org/10.1016/j.ejmech.2015.08.042 content_type: article copyright: Copyright © 2015 Elsevier Masson SAS. All rights reserved.publisher: Elsevier articletitle: 3-Nitrotriazole-based piperazides as potent antitrypanosomal agents journaltitle: European Journal of Medicinal Chemistry articlelink: http://dx.doi.org/10.1016/j.ejmech.2015.08.042 content_type: article copyright: Copyright © 2015 Elsevier Masson SAS. All rights reserved.publisher: Elsevier articletitle: 3-Nitrotriazole-based piperazides as potent antitrypanosomal agents journaltitle: European Journal of Medicinal Chemistry articlelink: http://dx.doi.org/10.1016/j.ejmech.2015.08.042 content_type: article copyright: Copyright © 2015 Elsevier Masson SAS. All rights reserved.publisher: Elsevier articletitle: 3-Nitrotriazole-based piperazides as potent antitrypanosomal agents journaltitle: European Journal of Medicinal Chemistry articlelink: http://dx.doi.org/10.1016/j.ejmech.2015.08.042 content_type: article copyright: Copyright © 2015 Elsevier Masson SAS. All rights reserved

Discovery of potent nitrotriazole-based antitrypanosomal agents: In vitro and in vivo evaluation

publisher: Elsevier articletitle: Discovery of potent nitrotriazole-based antitrypanosomal agents: In vitro and in vivo evaluation journaltitle: Bioorganic & Medicinal Chemistry articlelink: http://dx.doi.org/10.1016/j.bmc.2015.08.014 content_type: article copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.publisher: Elsevier articletitle: Discovery of potent nitrotriazole-based antitrypanosomal agents: In vitro and in vivo evaluation journaltitle: Bioorganic & Medicinal Chemistry articlelink: http://dx.doi.org/10.1016/j.bmc.2015.08.014 content_type: article copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.publisher: Elsevier articletitle: Discovery of potent nitrotriazole-based antitrypanosomal agents: In vitro and in vivo evaluation journaltitle: Bioorganic & Medicinal Chemistry articlelink: http://dx.doi.org/10.1016/j.bmc.2015.08.014 content_type: article copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.publisher: Elsevier articletitle: Discovery of potent nitrotriazole-based antitrypanosomal agents: In vitro and in vivo evaluation journaltitle: Bioorganic & Medicinal Chemistry articlelink: http://dx.doi.org/10.1016/j.bmc.2015.08.014 content_type: article copyright: Copyright © 2015 Elsevier Ltd. All rights reserved

Acoustic Sensing and Ultrasonic Drug Delivery in Multimodal Theranostic Capsule Endoscopy

Video capsule endoscopy (VCE) is now a clinically accepted diagnostic modality in which miniaturized technology, an on-board power supply and wireless telemetry stand as technological foundations for other capsule endoscopy (CE) devices. However, VCE does not provide therapeutic functionality, and research towards therapeutic CE (TCE) has been limited. In this paper, a route towards viable TCE is proposed, based on multiple CE devices including important acoustic sensing and drug delivery components. In this approach, an initial multimodal diagnostic device with high-frequency quantitative microultrasound that complements video imaging allows surface and subsurface visualization and computer-assisted diagnosis. Using focused ultrasound (US) to mark sites of pathology with exogenous fluorescent agents permits follow-up with another device to provide therapy. This is based on an US-mediated targeted drug delivery system with fluorescence imaging guidance. An additional device may then be utilized for treatment verification and monitoring, exploiting the minimally invasive nature of CE. While such a theranostic patient pathway for gastrointestinal treatment is presently incomplete, the description in this paper of previous research and work under way to realize further components for the proposed pathway suggests it is feasible and provides a framework around which to structure further work

A review of the methodological features of systematic reviews in maternal medicine

Background In maternal medicine, research evidence is scattered making it difficult to access information for clinical decision making. Systematic reviews of good methodological quality are essential to provide valid inferences and to produce usable evidence summaries to guide management. This review assesses the methodological features of existing systematic reviews in maternal medicine, comparing Cochrane and non-Cochrane reviews in maternal medicine. Methods Medline, Embase, Database of Reviews of Effectiveness (DARE) and Cochrane Database of Systematic Reviews (CDSR) were searched for relevant reviews published between 2001 and 2006. We selected those reviews in which a minimum of two databases were searched and the primary outcome was related to the maternal condition. The selected reviews were assessed for information on framing of question, literature search and methods of review. Results Out of 2846 citations, 68 reviews were selected. Among these, 39 (57%) were Cochrane reviews. Most of the reviews (50/68, 74%) evaluated therapeutic interventions. Overall, 54/68 (79%) addressed a focussed question. Although 64/68 (94%) reviews had a detailed search description, only 17/68 (25%) searched without language restriction. 32/68 (47%) attempted to include unpublished data and 11/68 (16%) assessed for the risk of missing studies quantitatively. The reviews had deficiencies in the assessment of validity of studies and exploration for heterogeneity. When compared to Cochrane reviews, other reviews were significantly inferior in specifying questions (OR 20.3, 95% CI 1.1–381.3, p = 0.04), framing focussed questions (OR 30.9, 95% CI 3.7- 256.2, p = 0.001), use of unpublished data (OR 5.6, 95% CI 1.9–16.4, p = 0.002), assessment for heterogeneity (OR 38.1, 95%CI 2.1, 688.2, p = 0.01) and use of meta-analyses (OR 3.7, 95% CI 1.3–10.8, p = 0.02). Conclusion This study identifies areas which have a strong influence on maternal morbidity and mortality but lack good quality systematic reviews. Overall quality of the existing systematic reviews was variable. Cochrane reviews were of better quality as compared to other reviews. There is a need for good quality systematic reviews to inform practice in maternal medicine

Quality assurance for Chinese herbal formulae: standardization of IBS-20, a 20-herb preparation

<p>Abstract</p> <p>Background</p> <p>The employment of well characterized test samples prepared from authenticated, high quality medicinal plant materials is key to reproducible herbal research. The present study aims to demonstrate a quality assurance program covering the acquisition, botanical validation, chemical standardization and good manufacturing practices (GMP) production of IBS-20, a 20-herb Chinese herbal formula under study as a potential agent for the treatment of irritable bowel syndrome.</p> <p>Methods</p> <p>Purity and contaminant tests for the presence of toxic metals, pesticide residues, mycotoxins and microorganisms were performed. Qualitative chemical fingerprint analysis and quantitation of marker compounds of the herbs, as well as that of the IBS-20 formula was carried out with high-performance liquid chromatography (HPLC). Extraction and manufacture of the 20-herb formula were carried out under GMP. Chemical standardization was performed with liquid chromatography-mass spectrometry (LC-MS) analysis. Stability of the formula was monitored with HPLC in real time.</p> <p>Results</p> <p>Quality component herbs, purchased from a GMP supplier were botanically and chemically authenticated and quantitative HPLC profiles (fingerprints) of each component herb and of the composite formula were established. An aqueous extract of the mixture of the 20 herbs was prepared and formulated into IBS-20, which was chemically standardized by LC-MS, with 20 chemical compounds serving as reference markers. The stability of the formula was monitored and shown to be stable at room temperature.</p> <p>Conclusion</p> <p>A quality assurance program has been developed for the preparation of a standardized 20-herb formulation for use in the clinical studies for the treatment of irritable bowel syndrome (IBS). The procedures developed in the present study will serve as a protocol for other poly-herbal Chinese medicine studies.</p

Using Latent Class Analyses to Examine Health Disparities among Young Children in Socially Disadvantaged Families during the COVID-19 Pandemic

Rising income inequality is strongly linked to health disparities, particularly in regions where uneven distribution of wealth and income has long been a concern. Despite emerging evidence of COVID-19-related health inequalities for adults, limited evidence is available for children and their parents. This study aimed to explore subtypes of families of preschoolers living in the disadvantaged neighborhoods of Hong Kong based on patterns of family hardship and to compare their patterns of parenting behavior, lifestyle practices, and wellbeing during the COVID-19 pandemic. Data were collected from 1338 preschoolers and their parents during March to June 2020. Latent class analysis was performed based on 11 socioeconomic and disease indicators. Multivariate logistic regressions were used to examine associations between identified classes and variables of interest during the COVID-19 pandemic. Four classes of family hardship were identified. Class 1 (45.7%) had the lowest disease and financial burden. Class 2 (14.0%) had the highest financial burden. Class 3 (5.9%) had the highest disease burden. Class 4 (34.5%) had low family income but did not receive government welfare assistance. Class 1 (low hardship) had lower risks of child maltreatment and adjustment problems than Class 2 (poverty) and Class 3 (poor health). However, children in Class 1 (low hardship) had higher odds of suffering psychological aggression and poorer physical wellbeing than those in Class 4 (low income), even after adjusting for child age and gender. The findings emphasize the need to adopt flexible intervention strategies in the time of large disease outbreak to address diverse problems and concerns among socially disadvantaged families

Associations between childhood maltreatment and psychiatric disorders: analysis from electronic health records in Hong Kong

There has been a lack of high-quality evidence concerning the association between childhood maltreatment and psychiatric diagnoses particularly for Axis II disorders. This study aimed to examine the association between childhood maltreatment exposure and Axis I and Axis II psychiatry disorders using electronic health records. In this study, the exposed group (n = 7473) comprised patients aged 0 to 19 years with a first-time record of maltreatment episode between January 1, 2001 and December 31, 2010, whereas the unexposed group (n = 26,834) comprised individuals of the same gender and age who were admitted into the same hospital in the same calendar year and month but had no records of maltreatment in the Hong Kong Clinical Data Analysis and Reporting System (CDARS). Data on their psychiatric diagnoses recorded from the date of admission to January 31, 2019 were extracted. A Cox proportional hazard regression model was fitted to estimate the hazard ratio (HR, plus 95% CIs) between childhood maltreatment exposure and psychiatric diagnoses, adjusting for age at index visit, sex, and government welfare recipient status. Results showed that childhood maltreatment exposure was significantly associated with subsequent diagnosis of conduct disorder/ oppositional defiant disorder (adjusted HR, 10.99 [95% CI 6.36, 19.01]), attention deficit hyperactivity disorder (ADHD) (7.28 [5.49, 9.65]), and personality disorders (5.36 [3.78, 7.59]). The risk of psychiatric disorders following childhood maltreatment did not vary by history of childhood sexual abuse, age at maltreatment exposure, and gender. Individuals with a history of childhood maltreatment are vulnerable to psychiatric disorders. Findings support the provision of integrated care within the primary health care setting to address the long-term medical and psychosocial needs of individuals with a history of childhood maltreatment

Improved ground-state modulation characteristics in 1.3 μm InAs/GaAs quantum dot lasers by rapid thermal annealing

We investigated the ground-state (GS) modulation characteristics of 1.3 μm InAs/GaAs quantum dot (QD) lasers that consist of either as-grown or annealed QDs. The choice of annealing conditions was determined from our recently reported results. With reference to the as-grown QD lasers, one obtains approximately 18% improvement in the modulation bandwidth from the annealed QD lasers. In addition, the modulation efficiency of the annealed QD lasers improves by approximately 45% as compared to the as-grown ones. The observed improvements are due to (1) the removal of defects which act as nonradiative recombination centers in the QD structure and (2) the reduction in the Auger-related recombination processes upon annealing

Anaerobic utilization of pectinous substrates at extremely haloalkaline conditions by Natranaerovirga pectinivora gen. nov., sp. nov., and Natranaerovirga hydrolytica sp. nov., isolated from hypersaline soda lakes

Anaerobic enrichments at pH 10, with pectin and polygalacturonates as substrates and inoculated with samples of sediments of hypersaline soda lakes from the Kulunda Steppe (Altai, Russia) demonstrated the potential for microbial pectin degradation up to soda-saturating conditions. The enrichments resulted in the isolation of six strains of obligately anaerobic fermentative bacteria, which represented a novel deep lineage within the order Clostridiales loosely associated with the family Lachnospiraceae. The isolates were rod-shaped and formed terminal round endospores. One of the striking features of the novel group is a very narrow substrate spectrum for growth, restricted to galacturonic acid and its polymers (e.g. pectin). Acetate and formate were the final fermentation products. Growth was possible in a pH range from 8 to 10.5, with an optimum at pH 9.5–10, and in a salinity range from 0.2 to 3.5 M Na+. On the basis of unique phenotypic properties and distinct phylogeny, the pectinolytic isolates are proposed to be assigned to a new genus Natranaerovirga with two species N. hydrolytica (APP2T=DSM24176T=UNIQEM U806T) and N. pectinivora (AP3T=DSM24629T=UNIQEM U805T)