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

Is Adherence to Imatinib Mesylate Treatment Among Patients with Chronic Myeloid Leukemia Associated with Better Clinical Outcomes in Qatar?

Background: Despite the revolutionary success of introducing tyrosine kinase inhibitors (TKIs), such as imatinib mesylate (IM), for treating chronic myeloid leukemia (CML), a substantial proportion of patients' treatments fail. Aim: This study investigates the correlation between patient adherence and failure of TKIs' treatment in a follow-up study. Methods: This is a follow-up study of a new cohort of CML patients. Adherence to IM is assessed using the Medication Event Monitoring System (MEMS 6 TrackCap, AARDEX Ltd). The 9-item Morisky Medication Adherence Scale, medication possession ratio (MPR) calculation, and the electronic medical records are used for identifying potential factors that influence adherence. Clinical outcomes are assessed according to the European LeukemiaNet 2013 guidelines via reverse transcriptase quantitative polymerase chain reaction measurement of the level of BCR-ABL1 transcripts in peripheral blood. Response is classified at the hematological, cytogenetic, and molecular levels into optimal, suboptimal, or failure. Results: A total of 36 CML patients (5 citizens and 31 noncitizen residents) consented to participate in the study. The overall mean MEMS score was 89. Of the 36 patients, 22 (61%) were classified as adherent (mean: 95) and 14 (39%) were classified as nonadherent (mean: 80.2). Adherent patients were significantly more likely to obtain optimal response (95%) compared to the nonadherent group (14.3%; P < 0.0001). The rate of poor adherence was as high as 39% using MEMS, which correlates with 37% treatment failure rate. The survey results show that 97% of patients increased the IM dose by themselves when they felt unwell and 31% of them took the missing IM dose when they remembered. Other factors known to influence adherence show that half of patients developed one or more side effects, 65% of patients experienced lack of funds, 13% of patients declared unavailability of the drug in the NCCCR pharmacy, and 72% of patients believed that IM would cure the disease. The MPR results reveal that 16% of patients had poor access to treatment through the hospital pharmacy. Discussion and conclusion: This is the first prospective study to evaluate CML patients' adherence and response to IM in Qatar. The high rate of treatment failure observed in Qatar is explained by poor adherence. An economic factor (unaffordable drug prices) is one of the main causes of nonadherence and efforts should be made locally to improve access to medication for cancer diseases. Other risk factors associated with poor adherence could be improved by close monitoring and dose adjustment. Monitoring risk factors for poor adherence and patient education that include direct communication between the health-care teams, doctors, nurses, pharmacists, and patients are essential components for maximizing the benefits of TKI therapy and could rectify this problem. The preliminary results show that patients' response to treatment may be directly linked to patients' adherence to treatment. However, further in-depth and specific analysis may be necessary in a larger cohort

Coupling of CFD and semiempirical methods for designing three-phase condensate separator: case study and experimental validation

This study presents an approach to determine the dimensions of three-phase separators. First, we designed different vessel configurations based on the fluid properties of an Iranian gas condensate field. We then used a comprehensive computational fluid dynamic (CFD) method for analyzing the three-phase separation phenomena. For simulation purposes, the combined volume of fluid–discrete particle method (DPM) approach was used. The discrete random walk (DRW) model was used to include the effect of arbitrary particle movement due to variations caused by turbulence. In addition, the comparison of experimental and simulated results was generated using different turbulence models, i.e., standard k–ε, standard k–ω, and Reynolds stress model. The results of numerical calculations in terms of fluid profiles, separation performance and DPM particle behavior were used to choose the optimum vessel configuration. No difference between the dimensions of the optimum vessel and the existing separator was found. Also, simulation data were compared with experimental data pertaining to a similar existing separator. A reasonable agreement between the results of numerical calculation and experimental data was observed. These results showed that the used CFD model is well capable of investigating the performance of a three-phase separator

Preclinical Models of Brain Metastasis

Research at the Brain Metastasis Group is supported by MINECO grants MINECO-Retos SAF2017-89643-R (M.V.), Bristol-Myers Squibb- Melanoma Research Alliance Young Investigator Award 2017 (498103) (M.V.), Beug Foundation’s Prize for Metastasis Research 2017 (M.V.), Fundación Ramón Areces (CIVP19S8163) (M.V.), Worldwide Cancer Research (19-0177) (M.V.), H2020-FETOPEN (828972)N

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

Minimal information for studies of extracellular vesicles 2018 (MISEV2018):a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe