Kidney Function in Hypertensive Patients with Left Ventricular Hypertrophy.

BACKGROUND: Impairment of kidney function is one of the long-term sequelae of hypertension and it contributes to increased morbidity and mortality in hypertensive patients. Left ventricular hypertrophy (LVH) is a common complication of hypertension which can worsen the outcome in affected patients. This study was designed to compare kidney function in hypertensive patients with LVH with that in hypertensive patients without LVH. METHODS: The study was conducted among hypertensive patients attending cardiology clinics at two tertiary hospitals in Nigeria. A questionnaire was used to obtain demographic and clinical information from the participants. Kidney function was determined by measuring serum urea and creatinine, urinary creatinine and microalbumin. Echocardiography was performed to detect LVH. Results of kidney function tests were compared between participants who had LVH and those who did not. RESULTS: Of the 105 participants recruited, 58 (55.2%) were males. The median age of all participants was 52 (interquartile range (IQR) 40-61) years and LVH was confirmed in 48 (45.7%) of them. Participants with LVH were older (55 vs 49 years; p=0.02) but had lower weight (74 vs 78 kg; p=0.04). Participants without LVH had higher microalbuminuria (5.2 vs 4.05 mg/dl; p=0.03), lower estimated glomerular filtration rate (62 vs 92 ml/min/1.73 m2; p=0.004), and higher stages of CKD. CONCLUSION: Hypertensive patients with LVH had lower levels of microalbuminuria, higher estimated GFR, and lower stages of CKD compared to those with no LVH.

CONTEXTE: L'altération de la fonction rénale est l'une des séquelles à long terme de l'hypertension et contribue à une morbidité et une mortalité accrues chez les patients hypertendus. L'hypertrophie ventriculaire gauche (HVG) est une complication fréquente de l'hypertension qui peut aggraver le pronostic chez les patients concernés. Cette étude visait à comparer la fonction rénale chez les patients hypertendus avec HVG à celle des patients hypertendus sans HVG. MÉTHODES: L'étude a été menée auprès de patients hypertendus fréquentant des cliniques de cardiologie dans deux hôpitaux tertiaires au Nigeria. Un questionnaire a été utilisé pour obtenir des informations démographiques et cliniques auprès des participants. La fonction rénale a été déterminée en mesurant l'urée sérique et la créatinine, la créatinine urinaire et la microalbuminurie. Une échocardiographie a été réalisée pour détecter l'HVG. Les résultats des tests de fonction rénale ont été comparés entre les participants présentant une HVG et ceux qui n'en présentaient pas. RÉSULTATS: Sur les 105 participants recrutés, 58 (55,2 %) étaient des hommes. L'âge médian de tous les participants était de 52 ans (plage interquartile (IQR) de 40 à 61) et l'HVG a été confirmée chez 48 (45,7 %) d'entre eux. Les participants avec une HVG étaient plus âgés (55 vs 49 ans ; p=0,02) mais avaient un poids plus faible (74 vs 78 kg ; p=0,04). Les participants sans HVG avaient une microalbuminurie plus élevée (5,2 vs 4,05 mg/dl ; p=0,03), un taux de filtration glomérulaire estimé plus bas (62 vs 92 ml/min/1,73 m2; p=0,004) et des stades plus élevés de maladie rénale chronique. CONCLUSION: Les patients hypertendus avec HVG présentaient des niveaux plus faibles de microalbuminurie, un taux de filtration glomérulaire estimé plus élevé et des stades plus bas de la maladie rénale chronique par rapport à ceux sans HVG. MOTS-CLÉS: Hypertrophie ventriculaire gauche, Hypertension, Fonction rénale, Maladie rénale chroniqu.

Prevalence and Risk Factors of Urolithiasis Among the Population of Hail, Saudi Arabia.

Background Urolithiasis is the formation of calculi in the urinary system. It is a public health concern worldwide that can lead to serious long-term consequences. Age, gender, dietary habits, and physical activity levels are all factors that increase the risk of urolithiasis formation. Furthermore, the presence of comorbid medical conditions such as diabetes and hypertension are other major risk factors. Among the most prominent determinants that raise the likelihood of acquiring urolithiasis is exposure to high temperatures, especially in middle-aged men. Consequently, Saudi residents are two and a half times more prone than the global average to develop urolithiasis, especially those in the Kingdom's hottest regions. Methodology This cross-sectional study assessed the self-reported prevalence and non-nutritional risk factors of urolithiasis among the population of Hail, Saudi Arabia, through an electronic questionnaire. The questionnaire contained 16 questions divided into three categories. Participants' permission was obtained before completing the questionnaire. The Statistical Package for Social Sciences (SPSS) version 22 (IBM Corp., Armonk, NY, USA) was used to analyze the data. Results Of the 1150 participants with a mean age of 26.3 ± 12.8 years old, nearly half were males (50.9%). Urolithiasis was detected among 158 (13.7%) participants. The following factors showed significant relation with having urolithiasis: increased age, male gender, a low level of education, diabetes, hypertension, and hyperthyroidism. A family history of renal stones was also associated with double the risk of having urolithiasis. Conclusion The results showed a high prevalence of urolithiasis in the Hail region, with many risk factors associated with it. It is important to support and promote awareness campaigns that address the critical risk factors of urolithiasis. Further studies should be conducted to arrive at a better understanding of the association between non-nutritional risk factors and developing urolithiasis.

Sex Hormone-Binding Globulin Level Enhances Prediction of Gestational Diabetes Mellitus in a Sub-Saharan African Population.

BACKGROUND: The burden of Gestational Diabetes Mellitus (GDM) in the Sub-Saharan African region has been on the rise despite increased diagnosis and treatment. Current risk factor-based prediction approaches in the region lack strong predictive value, hence the need for effective early prediction and preventive interventions. AIM: The aim of this study was to assess the diagnostic improvement in prediction of GDM by the addition of Sex Hormone-Binding Globulin (SHBG) assay to current approaches which assess early pregnancy maternal clinical risk factors in the study population. METHODS: This was a multi-centre hospital-based prospective observational study carried out over a period of 18 months in which serum SHBG levels were assayed and maternal clinical risk factors for GDM evaluated in a cohort of 271 pregnant women at 9 to 16 weeks gestational age. These participants were subsequently tested for GDM using a diagnostic 75g oral glucose tolerance test (OGTT) at 24 to 28 weeks of gestation. RESULTS: Clinical risk factor-based prediction approach had a diagnostic sensitivity of 59.6%, specificity of 69.4% and an area under the ROC curve of 0.758 (95% CI = 0.686, 0.830; p < 0.001). Following addition of SHBG assay to the maternal risk factors as predictors of GDM, the diagnostic sensitivity increased to 70.2%, specificity to 76.3% and there was a significant increase in the area under the ROC curve of 0.061 (95% CI = 0.006, 0.117; p = 0.030). CONCLUSION: Current maternal clinical risk factor-based GDM prediction approach in early pregnancy lacks strong predictive value in the study population. Thus, addition of biochemical predictors like SHBG may improve early prediction of GDM and enable timely intervention.

CONTEXTE: Le fardeau du diabète sucré gestationnel (DG) dans la région de l'Afrique subsaharienne est en augmentation malgré l'augmentation des diagnostics et des traitements. Les approches actuelles de prédiction basées sur les facteurs de risque dans la région ont des performances médiocres, d'où la nécessité d'une prédiction précoce efficace et d'une intervention préventive.OBJECTIF: L'objectif de cette étude était d'évaluer l'amélioration diagnostique de la prédiction du DG par l'ajout du dosage de la globuline liant les hormones sexuelles (SHBG) à l'approche actuelle qui évalue les facteurs de risque cliniques maternels en début de grossesse dans la population étudiée. METHODES: Il s'agissait d'une étude observationnelle prospective multicentrique en milieu hospitalier menée sur une période de 18 mois au cours de laquelle les taux sériques de SHBG ont été dosés et les facteurs de risque cliniques maternels de DG évalués dans une cohorte de 271 femmes enceintes de 9 à 16 semaines d'âge gestationnel. Ces participants ont ensuite été testés pour le DG à l'aide d'un test de diagnostic oral de tolérance au glucose (OGTT) de 75 g entre 24 et 28 semaines de gestation. RESULTATS: L'approche de prédiction basée sur les facteurs de risque clinique avait une sensibilité diagnostique de 59.6 %, une spécificité de 69.4 % et une aire sous la courbe ROC de 0.758 (IC à 95 % = 0.686, 0.830 ; p < 0.001). Suite à l'ajout du test SHBG aux facteurs de risque maternels en tant que facteurs prédictifs de DG, la sensibilité diagnostique est passée à 70.2 %, la spécificité à 76.3 % et il y a eu une augmentation significative de l'aire sous la courbe ROC de 0.061 (IC à 95 % = 0.006, 0.117; p = 0.030). CONCLUSION: L'approche actuelle de prédiction du DSG basée sur les facteurs de risque cliniques maternels en début de grossesse a de faibles performances dans la population étudiée. Ainsi, l'ajout de prédicteurs biochimiques comme SHBG peut améliorer la prédiction précoce du DG et permettre une intervention rapide. Mots-clés: Âge gestationnel, Diabète gestationnel, Facteurs de risque cliniques maternels, Prédiction, Sex hormone-binding globulin (SHBG), Afrique subsaharienne.

A Novel Tool for Real-time Estimation of Epidemiological Parameters of Communicable Diseases Using Contact-Tracing Data: Development and Deployment.

BACKGROUND: The Surveillance Outbreak Response Management and Analysis System (SORMAS) contains a management module to support countries in their epidemic response. It consists of the documentation, linkage, and follow-up of cases, contacts, and events. To allow SORMAS users to visualize data, compute essential surveillance indicators, and estimate epidemiological parameters from such network data in real-time, we developed the SORMAS Statistics (SORMAS-Stats) application. OBJECTIVE: This study aims to describe the essential visualizations, surveillance indicators, and epidemiological parameters implemented in the SORMAS-Stats application and illustrate the application of SORMAS-Stats in response to the COVID-19 outbreak. METHODS: Based on findings from a rapid review and SORMAS user requests, we included the following visualization and estimation of parameters in SORMAS-Stats: transmission network diagram, serial interval (SI), time-varying reproduction number R(t), dispersion parameter k, and additional surveillance indicators presented in graphs and tables. We estimated SI by fitting lognormal, gamma, and Weibull distributions to the observed distribution of the number of days between symptom onset dates of infector-infectee pairs. We estimated k by fitting a negative binomial distribution to the observed number of infectees per infector. Furthermore, we applied the Markov Chain Monte Carlo approach and estimated R(t) using the incidence data and the observed SI computed from the transmission network data. RESULTS: Using COVID-19 contact-tracing data of confirmed cases reported between July 31 and October 29, 2021, in the Bourgogne-Franche-Comté region of France, we constructed a network diagram containing 63,570 nodes. The network comprises 1.75% (1115/63,570) events, 19.59% (12,452/63,570) case persons, and 78.66% (50,003/63,570) exposed persons, including 1238 infector-infectee pairs and 3860 transmission chains with 24.69% (953/3860) having events as the index infector. The distribution with the best fit to the observed SI data was a lognormal distribution with a mean of 4.30 (95% CI 4.09-4.51) days. We estimated a dispersion parameter k of 21.11 (95% CI 7.57-34.66) and an effective reproduction number R of 0.9 (95% CI 0.58-0.60). The weekly estimated R(t) values ranged from 0.80 to 1.61. CONCLUSIONS: We provide an application for real-time estimation of epidemiological parameters, which is essential for informing outbreak response strategies. The estimates are commensurate with findings from previous studies. The SORMAS-Stats application could greatly assist public health authorities in the regions using SORMAS or similar tools by providing extensive visualizations and computation of surveillance indicators.

SF3B1 homeostasis is critical for survival and therapeutic response in T cell leukemia.

The production of noncanonical mRNA transcripts is associated with cell transformation. Driven by our previous findings on the sensitivity of T cell acute lymphoblastic leukemia (T-ALL) cells to SF3B1 inhibitors, we identified that SF3B1 inhibition blocks T-ALL growth in vivo with no notable associated toxicity. We also revealed protein stabilization of the U2 complex component SF3B1 via deubiquitination. Our studies showed that SF3B1 inhibition perturbs exon skipping, leading to nonsense-mediated decay and diminished levels of DNA damage response-related transcripts, such as the serine/threonine kinase CHEK2, and impaired DNA damage response. We also identified that SF3B1 inhibition leads to a general decrease in R-loop formation. We further demonstrate that clinically used SF3B1 inhibitors synergize with CHEK2 inhibitors and chemotherapeutic drugs to block leukemia growth. Our study provides the proof of principle for posttranslational regulation of splicing components and associated roles and therapeutic implications for the U2 complex in T cell leukemia.

Sub-Inhibitory Concentrations of Chlorhexidine Induce Resistance to Chlorhexidine and Decrease Antibiotic Susceptibility in Neisseria gonorrhoeae.

Objectives: Chlorhexidine digluconate (chlorhexidine) and Listerine® mouthwashes are being promoted as alternative treatment options to prevent the emergence of antimicrobial resistance in Neisseria gonorrhoeae. We performed in vitro challenge experiments to assess induction and evolution of resistance to these two mouthwashes and potential cross-resistance to other antimicrobials. Methods: A customized morbidostat was used to subject N. gonorrhoeae reference strain WHO-F to dynamically sustained Listerine® or chlorhexidine pressure for 18 days and 40 days, respectively. Cultures were sampled twice a week and minimal inhibitory concentrations (MICs) of Listerine®, chlorhexidine, ceftriaxone, ciprofloxacin, cefixime and azithromycin were determined using the agar dilution method. Isolates with an increased MIC for Listerine® or chlorhexidine were subjected to whole genome sequencing to track the evolution of resistance. Results: We were unable to increase MICs for Listerine®. Three out of five cultures developed a 10-fold increase in chlorhexidine MIC within 40 days compared to baseline (from 2 to 20 mg/L). Increases in chlorhexidine MIC were positively associated with increases in the MICs of azithromycin and ciprofloxacin. Low-to-higher-level chlorhexidine resistance (2-20 mg/L) was associated with mutations in NorM. Higher-level resistance (20 mg/L) was temporally associated with mutations upstream of the MtrCDE efflux pump repressor (mtrR) and the mlaA gene, part of the maintenance of lipid asymmetry (Mla) system. Conclusion: Exposure to sub-lethal chlorhexidine concentrations may not only enhance resistance to chlorhexidine itself but also cross-resistance to other antibiotics in N. gonorrhoeae. This raises concern regarding the widespread use of chlorhexidine as an oral antiseptic, for example in the field of dentistry.

Comparison of the Diagnostic Relevance of Albumin Creatinine Ratio Versus Cystatin C in Assessment of Cardiovascular Complication in Type 2 Diabetics.

BACKGROUND: In a bid to reduce cardiovascular complication(s), surrogate markers such asAlbumin-creatinine ratio and Cystatin C (Cys-C) are being evaluated in order to enhance early management of cardiovascular complications of diabetes mellitus. AIM: Evaluation of the diagnostic relevance of Cystatin- C versusAlbumin-creatinine ratio in assessment of cardiovascular complications (CVC). METHODS: One hundred and two type 2 diabetic patients and 100 control subjects of same age range were recruited for this study. These were further classified according to cardiovascular complications. Cystatin-C, Microalbuminuria, serum creatinine, HBA1c and HBA1c were analysed with standard methods. RESULTS: The mean concentrations of Cys-C, Microalbuminuria and Albumin-creatinine ratio showed significant increase (p<0.05) in those with cardiovascular complication compared to those without cardiovascular complication. The ROC (receiver operator curve) showed thatAlbumin-creatinine ratio (ACR) had significant sensitivity to cardiovascular complication while Cystatin-C showed no significant sensitivity to cardiovascular complications. Logistic binary regression shows a significant association of ACR with cardiovascular complications unlike Cys-C which showed no significant association (p<0.05). CONCLUSION: Cys-C and Albumin-Creatinine ratio increased in diabetics and further deranges with cardiovascular complications. However, Albumin-creatinine ratio showed more diagnostic sensitivity to cardiovascular complications compared to cystatin-C.

CONTEXTE: Dans le but de réduire les complications cardiovasculaires, des marqueurs de substitution tels que le rapport albumine-créatinine et la cystatine C (Cys-C) sont en cours d'évaluation afin d'améliorer la prise en charge précoce des complications cardiovasculaires du diabète sucré. BUT: Évaluation de la pertinence diagnostique du rapport CystatineC versus Albumine-créatinine dans l'évaluation des complications cardiovasculaires (CVC). MÉTHODES: Cent deux patients diabétiques de type 2 et 100 sujets témoins de la même tranche d'âge ont été recrutés pour cette étude. Ceux-ci ont été classés en fonction des complications cardiovasculaires. La cystatine-C, la microalbuminurie, la créatinine sérique, HBA1c et TSH ont été analysées avec des méthodes standard. RÉSULTATS: Les concentrations moyennes de Cys-C, de microalbuminurie et de rapport albumine-créatinine ont montré une augmentation significative (p <0,05) chez les personnes souffrant de complications cardiovasculaires par rapport à celles sans complications cardiovasculaires. La ROC (courbe de l'opérateur du récepteur) a montré que le rapport albuminecréatinine (ACR) avait une sensibilité significative aux complications cardiovasculaires tandis que la cystatine-C n'a montré aucune sensibilité significative aux complications cardiovasculaires. La régression logistique binaire montre une association significative de l'ACR avec des complications cardiovasculaires contrairement à Cys-C qui n'a montré aucune association significative (p <0,05). CONCLUSION: Le rapport Cys-C et albumine-créatinine a augmenté chez les diabétiques et dérange davantage avec des complications cardiovasculaires. Cependant, le rapport albumine-créatinine a montré une plus grande sensibilité diagnostique aux complications cardiovasculaires par rapport à la cystatine-C. MOTS CLÉS: Cystatine-C; Rapport albumine-créatinine; Diabète sucré, maladies cardiovasculaires.

Anterior cruciate ligament injury patterns and their relationship to fatigue and physical fitness levels - a cross-sectional study.

ABSTRACT: Anterior cruciate ligament (ACL) injury is one of the most common knee injuries that leads to many consequences such as early osteoarthritis and knee joint instability.To explore the association of the types of ACL tear (complete and partial) and side of injury (dominant vs nondominate) with types of playing surfaces, sports, shoes, and mechanism of injuries as well as to determine whether higher levels of fatigue and physical fitness are risk factors for complete ACL tear.This cross-sectional study used a questionnaire to collect information from young male adults with a confirmed ACL injury who were attending rehabilitation programs. The outcomes of interest were patterns of ACL injury, levels of fatigue before the injury on a 0 to 10 scale, and levels of physical fitness (hours per week). Mann-Whitney U and Kruskal Wallis tests were used to assess the differences between groups, while the odds ratios were calculated to evaluate risk factors for complete ACL tear.One hundred thirteen young male adults with a confirmed ACL injury were enrolled. Most of the reported ACL injuries in this study were complete tear (80.5%) and occurred more frequently in the dominant leg (74.6%) due to noncontact mechanism (63.6%). More ACL injuries happened while playing soccer (97.2%) on artificial turf (53.3%). The level of fatigue before ACL injury was significantly higher in partial ACL tear injuries compared to complete ACL tear injuries (P = .014). For every 1-point increase in the level of fatigue on a 0-10 scale, there was a 25% reduction in complete ACL injury risk (P = .023).The pattern of ACL types of tear and side of injury varies in different playing surfaces and mechanisms of injuries. Higher levels of fatigue seem to be associated with a partial tear of the ACL and reduction of a complete ACL tear risk factor.

Horizontally acquired papGII-containing pathogenicity islands underlie the emergence of invasive uropathogenic Escherichia coli lineages.

Escherichia coli is the leading cause of urinary tract infection, one of the most common bacterial infections in humans. Despite this, a genomic perspective is lacking regarding the phylogenetic distribution of isolates associated with different clinical syndromes. Here, we present a large-scale phylogenomic analysis of a spatiotemporally and clinically diverse set of 907 E. coli isolates, including 722 uropathogenic E. coli (UPEC) isolates. A genome-wide association approach identifies the (P-fimbriae-encoding) papGII locus as the key feature distinguishing invasive UPEC, defined as isolates associated with severe UTI, i.e., kidney infection (pyelonephritis) or urinary-source bacteremia, from non-invasive UPEC, defined as isolates associated with asymptomatic bacteriuria or bladder infection (cystitis). Within the E. coli population, distinct invasive UPEC lineages emerged through repeated horizontal acquisition of diverse papGII-containing pathogenicity islands. Our findings elucidate the molecular determinants of severe UTI and have implications for the early detection of this pathogen.

Identification of mcr-8 in Clinical Isolates From Qatar and Evaluation of Their Antimicrobial Profiles.

This study was performed to investigate the genotypic causes of colistin resistance in 18 colistin-resistant Klebsiella pneumoniae (n = 13), Escherichia coli (n = 3) and Pseudomonas aeruginosa (n = 2) isolates from patients at the Hamad General Hospital, Qatar. MIC testing for colistin was performed using Phoenix (BD Biosciences, Heidelberg, Germany) and then verified with SensiTest Colistin (Liofilchem, Zona Ind. le, Italy). Strains determined to be resistant (MIC > 4-16 µg/mL) were then whole-genome sequenced (MiSeq, Illumina, Inc.). Sequences were processed and analysed using BacPipe v1.2.6, a bacterial whole genome sequencing analysis pipeline. Known chromosomal modifications were determined using CLC Genomics Workbench v.9.5.3 (CLCbio, Denmark). Two K. pneumoniae isolates (KPN-15 and KPN-19) harboured mcr-8.1 on the IncFII(K) plasmids, pqKPN-15 and pqKPN-19, and belonged to ST383 and ST716, respectively. One E. coli isolate harboured mcr-1.1 on the IncI2 plasmid pEC-12. The other 15 isolates harboured known chromosomal mutations linked to colistin resistance in the PhoPQ two-component system. Also, three K. pneumoniae strains (KPN-9, KPN-10 and KPN-15) showed disruptions due to IS elements in mgrB. To our knowledge, this marks the first description of mcr-8.1 in K. pneumoniae of human origin in Qatar. Currently, more research is necessary to trace the source of mcr-8.1 and its variants in humans in this region.

BacPipe: A Rapid, User-Friendly Whole-Genome Sequencing Pipeline for Clinical Diagnostic Bacteriology.

Despite rapid advances in whole genome sequencing (WGS) technologies, their integration into routine microbiological diagnostics has been hampered by the lack of standardized downstream bioinformatics analysis. We developed a comprehensive and computationally low-resource bioinformatics pipeline (BacPipe) enabling direct analyses of bacterial whole-genome sequences (raw reads or contigs) obtained from second- or third-generation sequencing technologies. A graphical user interface was developed to visualize real-time progression of the analysis. The scalability and speed of BacPipe in handling large datasets was demonstrated using 4,139 Illumina paired-end sequence files of publicly available bacterial genomes (2.9-5.4 Mb) from the European Nucleotide Archive. BacPipe is integrated in EBI-SELECTA, a project-specific portal (H2020-COMPARE), and is available as an independent docker image that can be used across Windows- and Unix-based systems. BacPipe offers a fully automated "one-stop" bacterial WGS analysis pipeline to overcome the major hurdle of WGS data analysis in hospitals and public-health and for infection control monitoring.

The lichen symbiosis re-viewed through the genomes of Cladonia grayi and its algal partner Asterochloris glomerata.

BACKGROUND: Lichens, encompassing 20,000 known species, are symbioses between specialized fungi (mycobionts), mostly ascomycetes, and unicellular green algae or cyanobacteria (photobionts). Here we describe the first parallel genomic analysis of the mycobiont Cladonia grayi and of its green algal photobiont Asterochloris glomerata. We focus on genes/predicted proteins of potential symbiotic significance, sought by surveying proteins differentially activated during early stages of mycobiont and photobiont interaction in coculture, expanded or contracted protein families, and proteins with differential rates of evolution. RESULTS: A) In coculture, the fungus upregulated small secreted proteins, membrane transport proteins, signal transduction components, extracellular hydrolases and, notably, a ribitol transporter and an ammonium transporter, and the alga activated DNA metabolism, signal transduction, and expression of flagellar components. B) Expanded fungal protein families include heterokaryon incompatibility proteins, polyketide synthases, and a unique set of G-protein α subunit paralogs. Expanded algal protein families include carbohydrate active enzymes and a specific subclass of cytoplasmic carbonic anhydrases. The alga also appears to have acquired by horizontal gene transfer from prokaryotes novel archaeal ATPases and Desiccation-Related Proteins. Expanded in both symbionts are signal transduction components, ankyrin domain proteins and transcription factors involved in chromatin remodeling and stress responses. The fungal transportome is contracted, as are algal nitrate assimilation genes. C) In the mycobiont, slow-evolving proteins were enriched for components involved in protein translation, translocation and sorting. CONCLUSIONS: The surveyed genes affect stress resistance, signaling, genome reprogramming, nutritional and structural interactions. The alga carries many genes likely transferred horizontally through viruses, yet we found no evidence of inter-symbiont gene transfer. The presence in the photobiont of meiosis-specific genes supports the notion that sexual reproduction occurs in Asterochloris while they are free-living, a phenomenon with implications for the adaptability of lichens and the persistent autonomy of the symbionts. The diversity of the genes affecting the symbiosis suggests that lichens evolved by accretion of many scattered regulatory and structural changes rather than through introduction of a few key innovations. This predicts that paths to lichenization were variable in different phyla, which is consistent with the emerging consensus that ascolichens could have had a few independent origins.

The endotracheal tube microbiome associated with Pseudomonas aeruginosa or Staphylococcus epidermidis.

Ventilator-associated pneumonia (VAP) is one of the commonest hospital-acquired infections associated with high mortality. VAP pathogenesis is closely linked to organisms colonizing the endotracheal tube (ETT) such as Staphylococcus epidermidis and Pseudomonas aeruginosa, the former a common commensal with pathogenic potential and the latter a known VAP pathogen. However, recent gut microbiome studies show that pathogens rarely function alone. Hence, we determined the ETT microbial consortium co-colonizing with S. epidermidis or P. aeruginosa to understand its importance in the development of VAP and for patient prognosis. Using bacterial 16S rRNA and fungal ITS-II sequencing on ETT biomass showing presence of P. aeruginosa and/or S. epidermidis on culture, we found that presence of P. aeruginosa correlated inversely with patient survival and with bacterial species diversity. A decision tree, using 16S rRNA and patient parameters, to predict patient survival was generated. Patients with a relative abundance of Pseudomonadaceae <4.6% and of Staphylococcaceae <70.8% had the highest chance of survival. When Pseudomonadaceae were >4.6%, age of patient <66.5 years was the most important predictor of patient survival. These data indicate that the composition of the ETT microbiome correlates with patient prognosis, and presence of P. aeruginosa is an important predictor of patient outcome.

Design, Synthesis and Qualitative Structure Activity Relationship Evaluations of Quinoline-Based Bisarylimidazoles as Antibacterial Motifs.

BACKGROUND: The emergence of drug-resistant bacteria in clinical practice has propelled a concerted effort to find new classes of antibiotics that will circumvent current modes of resistance. We previously described a set of imidazopyridine antibacterial leads that contain a core composed of benzimidazole and a central phthalic acid linker. These compounds showed potent antibacterial properties against a wide range of Gram-positive and Gram-negative bacteria. In this respect, we conducted a systematic exploration of new disubstituted imidazole functionalities on quinoline 4-position as the central linker, to determine the factors that direct the potent antibacterial activity. We found that some of the newly synthesized compounds possessed more potent activity compared to currently available medications. The newly synthesized compounds were screened against several clinical isolates and Staphylococcus aureus, including the methicillinresistant (MRSA) and the methicillin-sensitive (MSAA). METHODS: The goal of this work is to undertake rigorous testing of new hybrid scaffolds of quinoline flanked by diaryl imidazoles and their structure-activity against a range of bacterial strains. Described herein is the account of the modification of the central linker region, the imidazole functionality, and substituents at the 4-position of the quinoline, and their effect on the antibacterial potency of the resulting derivatives. Our efforts here have been driven by previous reports on the applications of Pfitzinger cyclization protocol. This complexity-generating reaction transforms a relatively simple substrate, into a more complex products with the potential for diversification via functionalization of the resultant acid. RESULTS: We identified compounds that possess potent and broad-spectrum antibacterial activities against clinical isolates and drug resistant strains. Structure-Activity relationships of these compounds were further explored to determine the crucial structural features needed to enhance their antibacterial activity. In this respect, it was found that, hydrophobic and electron-withdrawing moieties, such as halogens, were required on each end of the isoquinoline-based bisaryl imidazole hybrid motifs to produce broad-spectrum activity against the tested strains. Thus, molecules containing halophenyl or pyridyl arms were found more potent than molecules containing thiophene and/or electron-releasing groups on the phenyl arms, which showed much less antibacterial activity against the tested strains. CONCLUSION: In summary, 4-(4,5-diphenyl-1H-imidazol-2-yl)-2-phenylquinoline systems can be assembled efficiently through the Pfitzinger ring expansion- condensation strategy. This approach appears to hold considerable synthetic utility. The particular value of such a synthetic route resides on the conciseness and efficiency through which imidazo-quinoline construction can be synthesized from structurally simple and accessible acetophenone precursors.

Pharmacological properties of diacetolol (M & B 16,942), a major metabolite of acebutolol.

Diacetolol (M & B 16,942), the major metabolite of the beta-adrenoceptor blocking agent, has been compared pharmacologically with acebutolol. In vitro, the beta-adrenoceptor blocking potency of diacetolol was less than that of acebutolol but its cardioselectivity (atrial relative to tracheal tissue) was greater. In the anaesthetized cat both agents had closely similar beta-adrenoceptor blocking potency and cardioselectivity. Diacetolol had weak intrinsic sympathomimetic activity (ISA), and no significant membrane-stabilizing activity (MSA). It did not restore sinus rhythm to anaesthetized dogs with ouabain-induced arrhythmias but was similar to acebutolol in preventing arrhythmia induced by adrenaline/methylchloroform in anaesthetized cats. It is concluded that, in experimental animals, diacetolol has beta-adrenoceptor blocking properties and ISA similar to the parent compound but differs in its lack of MSA.