Fluro(quinolones) is an important class of antibiotic used widely in both human and veterinary medicine. Resistance to fluro(quinolones) can be acquired by either chromosomal point mutations or ...plasmid-mediated quinolone resistance (PMQR). There is a lack of studies on the prevalence of PMQR in organisms from environmental sources in Bangladesh. In this study, we investigated the occurrence of PMQR genes in E. coli from various water sources and analysed associations between multi-drug resistance (MDR) and resistance to extended spectrum β-lactam antibiotics. We analysed 300 E. coli isolates from wastewaters of urban live-bird markets (n = 74) and rural households (n = 80), rural ponds (n = 71) and river water samples (n = 75) during 2017-2018. We isolated E. coli by filtering 100 ml of water samples through a 0.2μm cellulose membrane and incubating on mTEC agar media followed by identification of isolated colonies using biochemical tests. We selected one isolate per sample for detection of PMQR genes by multiplex PCR and tested for antibiotic susceptibility by disc diffusion. Clonal relatedness of PMQR-positive isolates was evaluated by enterobacterial repetitive intergenic consensus-PCR (ERIC-PCR). About 66% (n = 199) of E. coli isolates harbored PMQR-genes, predominantly qnrS (82%, n = 164) followed by aac(6')-lb-cr (9%, n = 17), oqxAB (7%, n = 13), qnrB (6%, n = 11) and qepA (4%, n = 8). Around 68% (n = 135) of PMQR-positive isolates were MDR and 92% (n = 183) were extended spectrum β-lactamase (ESBL)-producing of which the proportion of positive samples was 87% (n = 159) for blaCTX-M-1' 34% (n = 62) for blaTEM, 9% (n = 16) for blaOXA-1, blaOXA-47 and blaCMY-2, and 2% (n = 4) for blaSHV. Further, 16% (n = 32) of PMQR-positive isolates were resistant to carbapenems of which 20 isolates carried blaNDM-1. Class 1 integron (int1) was found in 36% (n = 72) of PMQR-positive E. coli isolates. PMQR genes were significantly associated with ESBL phenotypes (p≤0.001). The presence of several PMQR genes were positively associated with ESBL and carbapenemase encoding genes such as qnrS with blaCTXM-1 (p<0.001), qnrB with blaTEM (p<0.001) and blaOXA-1 (p = 0.005), oqxAB and aac(6')-lb-cr with blaSHV and blaOXA-1 (p<0.001), qnrB with blaNDM-1 (p<0.001), aac(6')-lb-cr with blaOXA-47 (p<0.001) and blaNDM-1 (p = 0.002). Further, int1 was found to correlate with qnrB (p<0.001) and qepA (p = 0.011). ERIC-PCR profiles allowed identification of 84 of 199 isolates with 85% matching profiles which were further grouped into 33 clusters. Only 5 clusters had isolates (n = 11) with identical ERIC-PCR profiles suggesting that PMQR-positive E. coli isolates are genetically heterogeneous. Overall, PMQR-positive MDR E. coli were widely distributed in aquatic environments of Bangladesh indicating poor wastewater treatment and highlighting the risk of transmission to humans and animals.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Obesity is a chronic disease, warranting long-term medical intervention. We evaluated effects of testosterone (T) therapy (Th) in men with T deficiency with normal weight, overweight and obesity on ...anthropometric and metabolic parameters, compared with untreated men.
Hypogonadal men (n = 823) with total T ≤ 12.1 nmol/L (age: 60.6 ± 7.0 years) participated in an ongoing registry study. Among these men 474 (57.6%) were obese, 286 (34.8%) overweight and 63 (7.7%) had normal weight. T undecanoate injections were administered to 428 men and 395 remained untreated. Anthropometric and metabolic parameters were measured at least twice a year and changes adjusted for confounding factors to account for baseline differences between groups.
Long-term TTh in hypogonadal men, irrespective of weight at baseline, produced improvements in body weight, waist circumference (WC) and body mass index (BMI). Furthermore, TTh decreased fasting blood glucose and HbA
and improved lipid profiles. Gradual decreases in blood pressure (systolic and diastolic) and pulse pressure occurred in men treated with T in each group. Marked reductions in mortality and major cardiovascular events were recorded in men receiving TTh.
Our findings demonstrate that TTh produces reductions in weight, WC, and BMI. There were 77 (19.5%) deaths in the untreated groups and 23 (5.4%) in the T-groups. Based on these findings we suggest that long-term TTh in overweight and obese hypogonadal men produces progressive and sustained clinically meaningful weight loss and that TTh may contribute to reductions in mortality and incident major adverse cardiovascular events.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract The cytokine tumour necrosis factor α (TNF) is a well known member of the TNF superfamily consisting of at least 18 ligands and 29 different receptors involved in numerous cellular ...processes. TNF signals through two distinct receptors TNFR1 and TNFR2 thereby controlling expression of cytokines, immune receptors, proteases, growth factors and cell cycle genes which in turn regulate inflammation, survival, apoptosis, cell migration, proliferation and differentiation. Since expression of TNF was discovered in amnion and placenta many studies demonstrated the presence of the cytokine and its receptors in the diverse human reproductive tissues. Whereas TNF has been implicated in ovulation, corpus luteum formation and luteolysis, this review focuses on the functions of TNF in human placental, endometrial and decidual cell types of normal tissues and also discusses its role in endometrial and gestational diseases. Physiological levels of the cytokine could be important for balancing cell fusion and apoptotic shedding of villous trophoblasts and to limit trophoblast invasion into maternal decidua. Regulation of the TNF/TNFR system by steroid hormones also suggests a role in uterine function including menstrual cycle-dependent destruction and regeneration of endometrial tissue. Aberrant levels of TNF, however, are associated with diverse reproductive diseases such as amniotic infections, recurrent spontaneous abortions, preeclampsia, preterm labour or endometriosis. Hence, concentrations, receptor distribution and length of stimulation determine whether TNF has beneficial or adverse effects on female reproduction and pregnancy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
A dataset was compiled to examine the psychosomatic impact of COVID-19′s e-learning digital tools on Jordanian university students’ well-being. In response to the state of emergency imposed by ...COVID-19, Jordanian universities switched to the online learning model as an alternative to traditional face-to-face education. The researchers designed a questionnaire that consists of two main sections; the first section included demographic information including gender, level/year, age, and cumulative average (GPA). The second section comprised five main constructs: (1) use of digital tools (mobile phone, laptop, i-pad) before and after COVID-19, (2) sleeping habits before and after COVID-19, (3) social interaction, (4) psychological state, and (5) academic performance. The researchers contacted different instructors teaching compulsory courses at four public and private universities and asked them to distribute the electronic questionnaire. Using the snowball sampling method, the questionnaire was delivered to students studying at the selected universities, and a total of 775 responses were received. The data were analyzed according to Likert's five-point scale, where frequencies and percentages were calculated. The data will be useful for researchers interested in studying the relationship between the e-learning model and psychosomatic disorders. Policymakers can use the data to identify university students’ emotional and psychological needs and propose practical solutions for their educational well-being.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Bacterial membrane lipids are critical for membrane bilayer formation, cell division, protein localization, stress responses, and pathogenesis. Despite their critical roles, membrane lipids have not ...been fully elucidated for many pathogens. Here, we report the discovery of a novel cationic glycolipid, lysyl-glucosyl-diacylglycerol (Lys-Glc-DAG), which is synthesized in high abundance by the bacterium Streptococcus agalactiae (Group B Streptococcus, GBS). To our knowledge, Lys-Glc-DAG is more positively charged than any other known lipids. Lys-Glc-DAG carries 2 positive net charges per molecule, distinct from the widely described lysylated phospholipid lysyl-phosphatidylglycerol (Lys-PG) that carries one positive net charge due to the presence of a negatively charged phosphate moiety. We use normal phase liquid chromatography (NPLC) coupled with electrospray ionization (ESI) high-resolution tandem mass spectrometry (HRMS/MS) and genetic approaches to determine that Lys-Glc-DAG is synthesized by the enzyme MprF in GBS, which covalently modifies the neutral glycolipid Glc-DAG with the cationic amino acid lysine. GBS is a leading cause of neonatal meningitis, which requires traversal of the endothelial blood-brain barrier (BBB). We demonstrate that GBS strains lacking mprF exhibit a significant decrease in the ability to invade BBB endothelial cells. Further, mice challenged with a GBSΔmprF mutant developed bacteremia comparably to wild-type (WT) infected mice yet had less recovered bacteria from brain tissue and a lower incidence of meningitis. Thus, our data suggest that Lys-Glc-DAG may contribute to bacterial uptake into host cells and disease progression. Importantly, our discovery provides a platform for further study of cationic lipids at the host-pathogen interface.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
CMV infection is a common complication in patients undergoing hematopoietic-cell transplantation. The incidence of CMV infection was 23 percentage points lower with prophylactic letermovir, a ...CMV–terminase complex inhibitor, than with placebo, with only low-level toxic effects.
The nighttime limb intensity of diffuse auroral emission of CO2+ (B2Σu+ ‐ X2πg) Ultraviolet Doublet (UVD) is observed in the northern hemisphere of Mars during 17–21 December 2014 from Imaging ...Ultraviolet Spectrograph instrument onboard Mars Atmosphere and Volatile Evolution. We have used hybrid model and four‐dimensional yield spectrum approach based on Monte Carlo simulation to calculate the ionization rate, limb intensity, and ion and electron densities of diffuse aurora due to precipitation of solar energetic particle and proton‐hydrogen (H+‐H) fluxes in the nighttime ionosphere of Mars. It is found that the production rates of atmospheric ions (CO2+, N2+, and O+) are dominant in the upper ionosphere at about 100–150 km due to impact of H+‐H. The solar energetic particle formed auroral ionosphere (CO2+, NO+, and O+) in the middle ionosphere between 50 and 100 km due to precipitation of monoenergetic electrons of energies 25 to 100 keV. The simulated limb intensities of CO2+UVD due to impact of H+‐H and auroral electrons are compared with Imaging Ultraviolet Spectrograph observations. Our model results are overestimating the observations, but 100 keV electrons deposited maximum energy around 75 km, closer to the observed altitude of the maximum emission. The densities of upper ionosphere (O2+, NO+, and CO2+) due to impact of H+‐H are smaller by one to two orders of magnitude than that produced by auroral electrons in the middle ionosphere.
Key Points
Causative mechanisms of diffuse aurora
SEP electron and H+‐H precipitation on Mars
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The present study investigates the influence of digital technology, instructional and assessment quality, economic status and psychological state, and course type on Jordanian university students’ ...attitudes towards online learning during the COVID-19 emergency transition to online learning. A survey of 4,037 undergraduate students representing four Jordanian public and private universities revealed that personal challenges (such as economic and psychological stress) decreased students’ willingness to learn online in the future, while the quality of the online experience (including instructional and assessment quality) improved their attitudes towards learning online in the future. Students also believed that Arts & Humanities courses were better suited for online teaching/learning than Sciences courses, a difference that persisted after controlling for personal challenges and the quality of the online learning experience.
Bacterial infections are a major cause of morbidity and mortality worldwide and the rise of antibiotic resistance necessitates development of alternative treatments. Pathogen adhesins that bind to ...host cells initiate disease pathogenesis and represent potential therapeutic targets. We have shown previously that the BspC adhesin in Group B Streptococcus (GBS), the leading cause of bacterial neonatal meningitis, interacts with host vimentin to promote attachment to brain endothelium and disease development. Here we determined that the BspC variable (V-) domain contains the vimentin binding site and promotes GBS adherence to brain endothelium. Site directed mutagenesis identified a binding pocket necessary for GBS host cell interaction and development of meningitis. Using a virtual structure-based drug screen we identified compounds that targeted the V-domain binding pocket, which blocked GBS adherence and entry into the brain in vivo. These data indicate the utility of targeting the pathogen-host interface to develop anti-virulence therapeutics.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Group B
(GBS) colonizes the female reproductive tract (FRT) and causes adverse pregnancy outcomes and invasive disease following vertical transmission to the fetus or newborn. Despite this major ...public health burden, the mechanisms of GBS FRT colonization are understudied. A recent transposon sequencing screen identified GBS factors contributing to vaginal colonization and ascending spread, including a putative DNA-cytosine methyltransferase (Dcm). We constructed a Δ
deletion strain and confirmed that
contributes to murine FRT colonization. Investigation of the evolutionary origin of the
gene reveals that it is widely distributed across GBS and is encoded as part of a prophage genome that displays evidence of horizontal transfer between GBS strains. We further show that Dcm contributes to 5mC methylation and global regulation of genes involved in carbohydrate metabolism, transcription regulation, and known adhesins and metabolic factors involved in GBS colonization. Interestingly, GBS genes that are induced in the presence of the highly glycosylated vaginal mucin MUC5B were significantly downregulated in the ∆
mutant. Furthermore, the ∆
mutant exhibited reduced binding to immobilized mucin and was attenuated in its ability to grow on numerous carbon sources including the carbohydrates found on mucins. While the ∆
mutant displayed enhanced clearance from the FRT in wild-type mice, there was no significant difference in
mice, indicating that Dcm-mediated regulation requires MUC5B to promote GBS colonization. This is the first report to characterize the impact of a DNA methyltransferase on GBS gene regulation and FRT colonization. IMPORTANCE Group B
(GBS) colonizes the female reproductive tract (FRT) in one-third of women, and carriage leads to numerous adverse pregnancy outcomes including the preterm premature rupture of membranes, chorioamnionitis, and stillbirth. The presence of GBS in the FRT during pregnancy is also the largest predisposing factor for the transmission of GBS and invasive neonatal diseases, including pneumonia, sepsis, and meningitis. The factors contributing to GBS colonization are still being elucidated. Here, we show for the first time that GBS transcription is regulated by an orphan DNA cytosine methyltransferase (Dcm). Many GBS factors are regulated by Dcm, especially those involved in carbohydrate transport and metabolism. We show that GBS persistence in the FRT is dependent on the catabolism of sugars found on the vaginal mucin MUC5B. Collectively, this work highlights the regulatory importance of a DNA methyltransferase and identifies both host and bacterial factors required for GBS colonization.
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