Evaluation of SAR for Amphotericin B Derivatives by Artificial Neural Network

Purpose: This study was designed to investigate the role of several descriptive structure-activity features in the antifungal drug, amphotericin B and analyze them by artificial neural networks. Method: Artificial neural networks (ANN) based on the back-propagation algorithm were applied to a structure-activity relationship (SAR) study for 17 amphotericin B derivatives with antifungal and membrane directed activity. A series of modified ANN architectures was made and the best result provided the ANN model for prediction of antifungal activity using the structural and biologic property descriptors. Results: The best architecture, in terms of cycles of calculation was 12-15-2. Among the most important factors were biological descriptors that correlated best with the model produced by ANN. Among the chemical and structural descriptors, positive charge on Y substitution was found to be the most important, followed by lack of availability of free carboxyl and parachor. Conclusion: This model is found to be useful to elucidate the structural requirements for the antifungal activity and can be applied in the design and activity prediction of the new amphotericin B derivatives. Keywords: Amphotericin B, SAR, Artificial Neural Network. > Tropical Journal of Pharmaceutical Research Vol. 4 (2) 2005: pp. 517-52

High risk genotype distribution of human papillomavirus (HPV) according to age groups in Iranian asymptomatic men

Background: The Human Papillomavirus (HPV) is one of the most common sexually transmitted viruses worldwide. HPV infection in men is a serious clinical issue as they could be considered as a reservoir for inadvertently transmitting infection to women. Moreover, genital HPV infection could be a source for anogenital cancers in men. Methods: This cross sectional study was conducted from January 2017 to December 2018. Four hundred fifteen asymptomatic men who were visited by specialists, referred to Nilou laboratory in terms of high risk (HR) HPV test testing. HR-HPV genotypes were detected using an approved assay which could discover HPV 16, HPV 18 and a pool of other high risk HPV genotypes as well as 16+ other HR and 18 + other HR (as multiple genotypes). SPSS software was used for statistical analysis. Results: The mean age was 33 ± 8.14 years. Specimens were referred to the laboratory by urologists, (n = 132, 32, 95CI: 25.0-39.4), dermatologists, (n = 104, 25, 95 CI: 19.1-30.9), gynecologists, (n = 75, 18, 95CI: 13.3-29.3) and other specialists (n = 104, 25, 95 CI:19.1-30.9). The overall prevalence of other HR HPV, HPV16, HPV18 and multiple genotypes were 54.2 (45/83), 25.3 (21/83), 3.6 (3/83) and 16.8 (14/83), respectively. The frequency of HR-HPV, HPV16 and HPV18 genotypes was the highest among 30-40 years old. Conclusion: The prevalence of HR-HPV infection among Iranian asymptomatic males was relatively high. Investigation on HPV infection in men as reservoir and transmission vehicle of HPV in addition to screening in women will improve the national public health provisions and will contribute to the application of infection control measurements at a national level. © 2020 The Author(s)

O-Band Subwavelength Grating Filters in a Monolithic Photonics Technology

The data communications industry has begun transitioning from electrical to optical interconnects in datacenters in order to overcome performance bottlenecks and meet consumer needs. To mitigate the costs associated with this change and achieve performance for 5G and beyond, it is crucial to explore advanced photonic devices that can enable high-bandwidth interconnects via wavelength-division multiplexing (WDM) in photonic integrated circuits. Subwavelength grating (SWG) filters have shown great promise for WDM applications. However, the small feature sizes necessary to implement these structures have prohibited them from penetrating into industrial applications. To explore the manufacturability and performance of SWG filters in an industrial setting, we fabricate and characterize O-band subwavelength grating filters using the monolithic photonics technology at GLOBALFOUNDRIES (GF). We demonstrate a low drop channel loss of -1.2 dB with a flat-top response, a high extinction ratio of -30 dB, a 3 dB channel width of 5 nm and single-source thermal tunability without shape distortion. This filter structure was designed using elements from the product design kit provided by GF and functions in a compact footprint of 0.002 mm2 with a minimum feature size of 150 nm.Comment: 4 pages, 3 figure

Acetolactate synthase regulatory subunits play divergent and overlapping roles in branched-chain amino acid synthesis and Arabidopsis development

Branched-chain amino acids (BCAAs) are synthesized by plants, fungi, bacteria, and archaea with plants being the major source of these amino acids in animal diets. Acetolactate synthase (ALS) is the first enzyme in the BCAA synthesis pathway. Although the functional contribution of ALS to BCAA biosynthesis has been extensively characterized, a comprehensive understanding of the regulation of this pathway at the molecular level is still lacking

Inhaled nitric oxide in premature infants: effect on tracheal aspirate and plasma nitric oxide metabolites

ObjectiveInhaled nitric oxide (iNO) is a potential new therapy for prevention of bronchopulmonary dysplasia and brain injury in premature infants. This study examined dose-related effects of iNO on NO metabolites as evidence of NO delivery.Study designA subset of 102 premature infants in the NO CLD trial, receiving 24 days of iNO (20 p.p.m. decreasing to 2 p.p.m.) or placebo, were analyzed. Tracheal aspirate (TA) and plasma samples collected at enrollment and at intervals during study gas were analyzed for NO metabolites.ResultiNO treatment increased NO metabolites in TA at 20 and 10 p.p.m. (1.7- to 2.3-fold vs control) and in plasma at 20, 10, and 5 p.p.m. (1.6- to 2.3-fold). In post hoc analysis, treated infants with lower metabolite levels at entry had an improved clinical outcome.ConclusioniNO causes dose-related increases in NO metabolites in the circulation as well as lung fluid, as evidenced by TA analysis, showing NO delivery to these compartments

Endotracheal tubes and fluid aspiration: An in vitro evaluation of new cuff technologies

© 2017 The Author(s). Background: Aspiration of subglottic secretions past the endotracheal tube (ETT) cuff is a prerequisite for developing ventilator-associated pneumonia (VAP). Subglottic secretion drainage (SSD) ETTs reduce aspiration of subglottic secretions and have demonstrated lower VAP rates. We compared the performance of seven SSD ETTs against a non-SSD ETT in preventing aspiration below inflated cuffs. Methods: ETTs were positioned vertically in 2 cm diameter cylinders. Four ml of a standard microbial suspension was added above inflated cuffs. After 1 h, aspiration was measured and ETTs demonstrating no leakage were subjected to rotational movement and evaluation over 24 h. Collected aspirated fluid was used to inoculate agar media and incubated aerobically at 37 °C for 24 h. The aspiration rate, volume and number of microorganisms that leaked past the cuff was measured. Experiments were repeated (×10) for each type of ETT, with new ETTs used for each repeat. Best performing ETTs were then tested in five different cylinder diameters (1.6, 1.8, 2.0, 2.2 and 2.4 cm). Experiments were repeated as above using sterile water. Volume and time taken for aspiration past the cuff was measured. Experiments were repeated (×10) for each type of ETT. Results were analysed using non-parametric tests for repeated measures. Results: The PneuX ETT prevented aspiration past the cuff in all experiments. All other ETTs allowed aspiration, with considerable variability in performance. The PneuX ETT was statistically superior in reducing aspiration compared to the SealGuard (p < 0.009), KimVent (p < 0.002), TaperGuard (p < 0.004), Lanz (p < 0.001), ISIS (p < 0.001), SACETT (p < 0.001) and Soft Seal (p < 0.001) ETTs. Of the 4 ETTs tested in differing cylinder sizes, the PneuX significantly reduced aspiration across the range of diameters compared to the SealGuard (p < 0.0001), TaperGuard (p < 0.0001) and KimVent (p < 0.0001) ETTs. Conclusions: ETTs showed substantial variation in fluid aspiration, relating to cuff material and design. Variability in performance was likely due to the random manner in which involutional folds form in the inflated ETT cuff. The PneuX ETT was the only ETT able to consistently prevent aspiration past the cuff in all experiments

The Heart Is an Early Target of Anthrax Lethal Toxin in Mice: A Protective Role for Neuronal Nitric Oxide Synthase (nNOS)

Anthrax lethal toxin (LT) induces vascular insufficiency in experimental animals through unknown mechanisms. In this study, we show that neuronal nitric oxide synthase (nNOS) deficiency in mice causes strikingly increased sensitivity to LT, while deficiencies in the two other NOS enzymes (iNOS and eNOS) have no effect on LT-mediated mortality. The increased sensitivity of nNOS−/− mice was independent of macrophage sensitivity to toxin, or cytokine responses, and could be replicated in nNOS-sufficient wild-type (WT) mice through pharmacological inhibition of the enzyme with 7-nitroindazole. Histopathological analyses showed that LT induced architectural changes in heart morphology of nNOS−/− mice, with rapid appearance of novel inter-fiber spaces but no associated apoptosis of cardiomyocytes. LT-treated WT mice had no histopathology observed at the light microscopy level. Electron microscopic analyses of LT-treated mice, however, revealed striking pathological changes in the hearts of both nNOS−/− and WT mice, varying only in severity and timing. Endothelial/capillary necrosis and degeneration, inter-myocyte edema, myofilament and mitochondrial degeneration, and altered sarcoplasmic reticulum cisternae were observed in both LT-treated WT and nNOS−/− mice. Furthermore, multiple biomarkers of cardiac injury (myoglobin, cardiac troponin-I, and heart fatty acid binding protein) were elevated in LT-treated mice very rapidly (by 6 h after LT injection) and reached concentrations rarely reported in mice. Cardiac protective nitrite therapy and allopurinol therapy did not have beneficial effects in LT-treated mice. Surprisingly, the potent nitric oxide scavenger, carboxy-PTIO, showed some protective effect against LT. Echocardiography on LT-treated mice indicated an average reduction in ejection fraction following LT treatment in both nNOS−/− and WT mice, indicative of decreased contractile function in the heart. We report the heart as an early target of LT in mice and discuss a protective role for nNOS against LT-mediated cardiac damage

The Arabidopsis thaliana F-box gene HAWAIIAN SKIRT is a new player in the microRNA pathway

In Arabidopsis, the F-box HAWAIIAN SKIRT (HWS) protein is important for organ growth. Loss of function of HWS exhibits pleiotropic phenotypes including sepal fusion. To dissect the HWS role, we EMS-mutagenized hws-1 seeds and screened for mutations that suppress hws-1 associated phenotypes. We identified shs-2 and shs-3 (suppressor of hws-2 and 3) mutants in which the sepal fusion phenotype of hws-1 was suppressed. shs-2 and shs-3 (renamed hst-23/hws-1 and hst-24/hws-1) carry transition mutations that result in premature terminations in the plant homolog of Exportin-5 HASTY (HST), known to be important in miRNA biogenesis, function and transport. Genetic crosses between hws-1 and mutant lines for genes in the miRNA pathway, also suppress the phenotypes associated with HWS loss of function, corroborating epistatic relations between the miRNA pathway genes and HWS. In agreement with these data, accumulation of miRNA is modified in HWS loss or gain of function mutants. Our data propose HWS as a new player in the miRNA pathway, important for plant growth

Systematic review of methods used in meta-analyses where a primary outcome is an adverse or unintended event

addresses: Peninsula College of Medicine and Dentistry, St Luke's Campus, University of Exeter, Exeter, UK. [email protected]: PMCID: PMC3528446types: Journal Article; Research Support, Non-U.S. Gov't© 2012 Warren et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Adverse consequences of medical interventions are a source of concern, but clinical trials may lack power to detect elevated rates of such events, while observational studies have inherent limitations. Meta-analysis allows the combination of individual studies, which can increase power and provide stronger evidence relating to adverse events. However, meta-analysis of adverse events has associated methodological challenges. The aim of this study was to systematically identify and review the methodology used in meta-analyses where a primary outcome is an adverse or unintended event, following a therapeutic intervention