Association of sul genes and class 1 integron with trimethoprimsulfamethoxazole Resistance in Stenotrophomonas maltophilia clinical isolates in Zagazig University, Egypt

Background: Stenotrophomonas maltophilia (S.maltophilia) is an intrinsically drug resistant    opportunistic pathogen associated with serious infections in humans. Acquired resistance to   trimethoprim-sulfamethoxazole (SXT,co-trimoxazole), the main stay of therapy against S. maltophilia ,has made its treatment more problematic. Objectives: This work aimed to determine the occurrence  of SXT resistance among S. maltophilia isolated from Zagazig University Hospitals in Egypt and to   assess the association of sul genes and integron1 with SXT-resistant isolates.Material and Methods: Thirty-two S.maltophilia isolates were identified in this study during the   period from 2013 to 2015. Screening of SXT-resistant isolates was done by Kirby-Bauer method.  Minimum inhibitory concentration(MIC) values for SXT were determined by agar dilution. S. maltophilia isolates were tested for the presence of sul1, sul2, sul3, and int 1 genes by multiplex polymerase chain reaction.Results: Amongst the 32 S. maltophilia isolates, 12(37.5%) were resistant to SXT. All SXT-resistant isolates were found to harbor sul1 gene and integron1. One of these isolates had sul2 gene  (1/12,8.3%). Meanwhile, sul3 gene was not detected in any of the SXT-resistant isolates. Only 2 of the 20 SXT-susceptible isolates was found to yield positive PCR results for sul1 gene, one of them gave positive result for class 1 Integron. The association of sul genes and Integrin1 with resistance to SXT had a statistically significant difference( P<0.0001). Conclusion: Our study indicated a high frequency of SXT resistance among clinical S.maltophilia isolates from Zagazig University Hospitals, in which sul genes and class 1 integron were found to have a major role.Keywords: Stenotrophomonas maltophilia; Sulphamethoxazole-trimethoprim-resistant; Multiplex  PCR; sul genes; Integron

Performance characteristics of enzyme linked immunosorbent assay and rapid immunochromatographic test for routine screening of human norovirus

Noroviruses (NoV) are identified as the major cause of epidemic and sporadic acute gastroenteritis. Controlling the spread of the disease needs early recognition of NoV. This study investigated the  contribution of norovirus to sporadic cases of pediatric gastroenteritis in Zagazig University Hospitals and studied the performance characteristics of enzyme linked immunosorbent assay(EIA) and  immunochromatographic (ICT) assay for their ability to detect NoV. Two hundred stool specimens werecollected from pediatric patients with acute gastroenteritis. Samples were tested for Norovirus presence by reverse transcription PCR (RT-PCR), ICT kit and EIA. 27% of the samples showed the 338-bp portion of the RNA-dependent RNA polymerase (RdRp) gene of both Norovirus genogroups I and II by RT-PCR. The ICT assay showed high specificity (97.94%) and high sensitivity (85.18%). The EIA  showed high specificity (93.8%) but low sensitivity (64.8%). In conclusion, the high detection rate of NoV as the cause of diarrhea in children reported in this study supports their addition in screenings to  identify sporadic cases of acute gastroenteritis. The ICT and RIA Norovirus kits may be useful for rapid screening of stool samples from patients with acute gastroenteritis. However, RT-PCR should be  considered for negative samples to be confirmed.Key words: Norovirus, pediatric gastroenteritis, RNA-dependent RNA polymerase (RdRp) gene,  enzyme linked immunosorbent assay, immunochromatographic assay, Sensitivity, Specificity.Abbreviations: NoV , Noroviruses; EIA, enzyme linked immunosorbent assay; ICT,  immunochromatographic; RT-PCR, reverse transcription PCR; RdRp, RNA-dependent RNA polymerase; ORFs, open reading frames

Poly-l-Lactic Acid Nanofiber–Polyamidoamine Hydrogel Composites: Preparation, Properties, and Preliminary Evaluation as Scaffolds for Human Pluripotent Stem Cell Culturing

none13siGualandi, Chiara; Bloise, Nora; Mauro, Nicolò; Ferruti, Paolo; Manfredi, Amedea; Sampaolesi, Maurilio; Liguori, Anna; Laurita, Romolo; Gherardi, Matteo; Colombo, Vittorio; Visai, Livia; Focarete, Maria Letizia; Ranucci, ElisabettaGualandi, Chiara; Bloise, Nora; Mauro, Nicolò; Ferruti, Paolo; Manfredi, Amedea; Sampaolesi, Maurilio; Liguori, Anna; Laurita, Romolo; Gherardi, Matteo; Colombo, Vittorio; Visai, Livia; Focarete, Maria Letizia; Ranucci, Elisabett

Automated Planning of Concrete Joint Layouts with 4D-BIM

Concrete pouring represents a major critical path activity that is often affected by design limitations, structural considerations and on-site operational constraints. As such, meticulous planning is required to ensure that both the aesthetic and structural integrity of joints between cast in-situ components is achieved. Failure to adequately plan concrete pouring could lead to structural defects, construction rework or structural instability, all having major financial implications. Given the inherent complexity of large-scale construction projects, the ‘manual planning’ of concrete pouring is a challenging task and prone to human errors. Against this backdrop, this study developed 4D Building Information Management (BIM) approach to facilitate automated concrete joint positioning solution (as a proof of concept) for design professionals and contractors. The study first developed structural model in Revit, then extracted spatial information regarding all construction joints and linked them to dynamic Microsoft (MS) Excel and Matlab spreadsheets using integration facilitated by Dynamo software. Midspan points of each beam as well as floor perimeter information were gathered via codes developed in MS Excel macros. Based on the Excel outputs, Matlab programming was used to determine best concreating starting points and directions, and daily allowed concrete volume, considering limitations due to cold joints. These information were then pushed back to Revit via Dynamo in order to develop daily concrete scheduling. The developed automated programme framework offers a cost-effective and accurate methodology to address the limitations and inefficiencies of traditional methods of designing construction joints and planning pours. This framework extends the body of knowledge by introducing innovative solutions to integrate structural design considerations, constructional procedures and operational aspects for mitigating human error, and providing a novel, yet technically sound, basis for further application of BIM in structural engineering

The contribution of 7q33 copy number variations for intellectual disability

Copy number variations (CNVs) at the 7q33 cytoband are very rarely described in the literature, and almost all of the cases comprise large deletions affecting more than just the q33 segment. We report seven patients (two families with two siblings and their affected mother and one unrelated patient) with neurodevelopmental delay associated with CNVs in 7q33 alone. All the patients presented mild to moderate intellectual disability (ID), dysmorphic features, and a behavioral phenotype characterized by aggressiveness and disinhibition. One family presents a small duplication in cis affecting CALD1 and AGBL3 genes, while the other four patients carry two larger deletions encompassing EXOC4, CALD1, AGBL3, and CNOT4. This work helps to refine the phenotype and narrow the minimal critical region involved in 7q33 CNVs. Comparison with similar cases and functional studies should help us clarify the relevance of the deleted genes for ID and behavioral alterations.FEDER funds, through the Competitiveness Factors Operational Programme (COMPETE), and by National funds, through the Foundation for Science and Technology (FCT), under the scope of the projects PIC/IC/83026/2007, PIC/IC/83013/2007, and POCI-01-0145-FEDER-007038. This work has also been funded by the project NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER)info:eu-repo/semantics/publishedVersio

Application of Biomarkers in Cancer Risk Management: Evaluation from Stochastic Clonal Evolutionary and Dynamic System Optimization Points of View

Aside from primary prevention, early detection remains the most effective way to decrease mortality associated with the majority of solid cancers. Previous cancer screening models are largely based on classification of at-risk populations into three conceptually defined groups (normal, cancer without symptoms, and cancer with symptoms). Unfortunately, this approach has achieved limited successes in reducing cancer mortality. With advances in molecular biology and genomic technologies, many candidate somatic genetic and epigenetic “biomarkers” have been identified as potential predictors of cancer risk. However, none have yet been validated as robust predictors of progression to cancer or shown to reduce cancer mortality. In this Perspective, we first define the necessary and sufficient conditions for precise prediction of future cancer development and early cancer detection within a simple physical model framework. We then evaluate cancer risk prediction and early detection from a dynamic clonal evolution point of view, examining the implications of dynamic clonal evolution of biomarkers and the application of clonal evolution for cancer risk management in clinical practice. Finally, we propose a framework to guide future collaborative research between mathematical modelers and biomarker researchers to design studies to investigate and model dynamic clonal evolution. This approach will allow optimization of available resources for cancer control and intervention timing based on molecular biomarkers in predicting cancer among various risk subsets that dynamically evolve over time

Conserved expression and functions of PDE4 in rodent and human heart

PDE4 isoenzymes are critical in the control of cAMP signaling in rodent cardiac myocytes. Ablation of PDE4 affects multiple key players in excitation–contraction coupling and predisposes mice to the development of heart failure. As little is known about PDE4 in human heart, we explored to what extent cardiac expression and functions of PDE4 are conserved between rodents and humans. We find considerable similarities including comparable amounts of PDE4 activity expressed, expression of the same PDE4 subtypes and splicing variants, anchoring of PDE4 to the same subcellular compartments and macromolecular signaling complexes, and downregulation of PDE4 activity and protein in heart failure. The major difference between the species is a fivefold higher amount of non-PDE4 activity in human hearts compared to rodents. As a consequence, the effect of PDE4 inactivation is different in rodents and humans. PDE4 inhibition leads to increased phosphorylation of virtually all PKA substrates in mouse cardiomyocytes, but increased phosphorylation of only a restricted number of proteins in human cardiomyocytes. Our findings suggest that PDE4s have a similar role in the local regulation of cAMP signaling in rodent and human heart. However, inhibition of PDE4 has ‘global’ effects on cAMP signaling only in rodent hearts, as PDE4 comprises a large fraction of the total cardiac PDE activity in rodents but not in humans. These differences may explain the distinct pharmacological effects of PDE4 inhibition in rodent and human hearts

Increased Short-Term Variability of the QT Interval in Professional Soccer Players: Possible Implications for Arrhythmia Prediction

BACKGROUND: Sudden cardiac death in competitive athletes is rare but it is significantly more frequent than in the normal population. The exact cause is seldom established and is mostly attributed to ventricular fibrillation. Myocardial hypertrophy and slow heart rate, both characteristic changes in top athletes in response to physical conditioning, could be associated with increased propensity for ventricular arrhythmias. We investigated conventional ECG parameters and temporal short-term beat-to-beat variability of repolarization (STV(QT)), a presumptive novel parameter for arrhythmia prediction, in professional soccer players. METHODS: Five-minute 12-lead electrocardiograms were recorded from professional soccer players (n = 76, all males, age 22.0±0.61 years) and age-matched healthy volunteers who do not participate in competitive sports (n = 76, all males, age 22.0±0.54 years). The ECGs were digitized and evaluated off-line. The temporal instability of beat-to-beat heart rate and repolarization were characterized by the calculation of short-term variability of the RR and QT intervals. RESULTS: Heart rate was significantly lower in professional soccer players at rest (61±1.2 vs. 72±1.5/min in controls). The QT interval was prolonged in players at rest (419±3.1 vs. 390±3.6 in controls, p<0.001). QTc was significantly longer in players compared to controls calculated with Fridericia and Hodges correction formulas. Importantly, STV(QT) was significantly higher in players both at rest and immediately after the game compared to controls (4.8±0.14 and 4.3±0.14 vs. 3.5±0.10 ms, both p<0.001, respectively). CONCLUSIONS: STV(QT) is significantly higher in professional soccer players compared to age-matched controls, however, further studies are needed to relate this finding to increased arrhythmia propensity in this population

'Omic approaches to preventing or managing metastatic breast cancer

Early detection of metastasis-prone breast cancers and characterization of residual metastatic cancers are important in efforts to improve management of breast cancer. Applications of genome-scale molecular analysis technologies are making these complementary approaches possible by revealing molecular features uniquely associated with metastatic disease. Assays that reveal these molecular features will facilitate development of anatomic, histological and blood-based strategies that may enable detection prior to metastatic spread. Knowledge of these features also will guide development of therapeutic strategies that can be applied when metastatic disease burden is low, thereby increasing the probability of a curative response

Методология синтеза архитектуры программно-технического комплекса автоматизированной системы мониторинга обстановки

Предложен подход к проектированию архитектуры программно-технического комплекса автоматизированной системы мониторинга обстановки в реальном времени, основанный на классификации решаемых функциональных задач на основе методов кластерного анализа и выбранного множества признаков подобия. Разработанный подход позволяет из множества функций системы выделить подобные (по определенным признакам) и объединить их в архитектурные компоненты (унифицированные функциональные модули).Запропоновано підхід до проектування архітектури центру обробки інформації автоматизованої системи моніторингу середовища в реальному часі, що заснований на класифікації функціональних задач на підставі методів кластерного аналізу і обраної множини ознак схожості. Розроблений підхід дозволяє вибрати із множини функцій системи схожі (за певними ознаками) і поєднати їх в архітектурні компоненти (уніфіковані функціональні модулі).The approach to designing architecture of the information processing complex of the automated real time conditions monitoring system based on classification of functional tasks on the basis of methods of cluster analysis and the chosen set of similarity attributes is offered. The developed approach allows to allocate from a set of functions the systems similar (on certain attributes) and to unite them in architectural components (unified functional modules)