Natural antibiotic discovery

Currently, there is a decline in the discovery of new antibiotics. Several important habitats that have yet to be fully exploited for antibioticproducing bacteria include water and the anterior nares. Therefore, antibiotic-producing bacteria isolated from these two environments were evaluated for antibiotic production, and using ribosome engineering, their activity was further enhanced. Five NW Pseudomonas sp. strains isolated from water were tested for antimicrobial activity against multidrug-resistant bacteria. The five strains were grown under various conditions, by which the growth medium significantly influenced the production of antimicrobials (p-value <0.001). All five strains were inhibitory to several indicator bacterium however, Pseudomonas sp. strain NW27 was inhibitory to S. aureus, E. faecium and A. baumannii. Bioinformatics analysis revealed that Pseudomonas sp. strain NW27 outperforms other strains in its ability to produce a variety of novel antimicrobials, including those related to viscosin, bananamide and syringomycin. Rifampicin-resistant Pseudomonas sp. strain NW27-A1 was isolated using 10 ug/ml rifampicin and showed significantly enhanced antimicrobial activity compared to the wild-type according to agar well diffusion assays (p-value <0.001). The MIC assay showed no significant change in the MIC of Pseudomonas sp. strain NW27-A1 compared to the wild-type (0.12 mg/ml versus 1.13 mg/ml respectively, p-value= 0.200). The active compounds were extracted from IV the supernatant of Pseudomonas sp. strain NW27-A1 using acetonitrile, and 0.23% of the units were recovered with a 1.28 fold purification. Several polar, active fractions were identified by HPLC, however the least polar fraction G significantly reduced the cellular metabolism of E. faecium E1162 by 99.65%. Moreover, bioinformatic analysis of metagenomic data suggested the ability of the commensal bacterium Dolosigranulum pigrum to produce several novel bacteriocins and a novel polyketide, that can inhibit S. aureus growth in the anterior nares. The supernatant of D. pigrum ATCC 51524 did not demonstrate considerable antimicrobial activity however, production of hydrogen peroxide was one mechanism associated with the exclusion of S. aureus in the anterior nares. However, rifampicin-resistant D. pigrum DP8rif10 successfully inhibited S. aureus JE2 when collected at 30 hours post-inoculation. Pseudomonas sp. strain NW27-A1 and D. pigrum DP8rif10 therefore offer a potential source of novel therapeutic approaches in the future

Integrated genome sequencing and gene expression analysis in the Stroke-Prone Spontaneously Hypertensive Rat

This research project attempts to identify the genetic determinants of SHRSP/Gla phenotypes by using mRNA and micro(mi)RNA expression profiling data, in combination with the genome sequence of the SHRSP/Gla and WKY/Gla, to facilitate human translational studies for hypertension and vice versa

Dissecting the genetic components of a quantitative trait locus for blood pressure and renal pathology on rat chromosome 3

Background: We have previously confirmed the importance of rat chromosome 3 (RNO3) genetic loci on blood pressure elevation, pulse pressure (PP) variability and renal pathology during salt challenge in the stroke-prone spontaneously hypertensive (SHRSP) rat. The aims of this study were to generate a panel of RNO3 congenic sub-strains to genetically dissect the implicated loci and identify positional candidate genes by microarray expression profiling and analysis of next-generation sequencing data. Method and results: A panel of congenic sub-strains were generated containing Wistar-Kyoto (WKY)-introgressed segments of varying size on the SHRSP genetic background, focused within the first 50 Mbp of RNO3. Haemodynamic profiling during salt challenge demonstrated significantly reduced systolic blood pressure, diastolic blood pressure and PP variability in SP.WKYGla3a, SP.WKYGla3c, SP.WKYGla3d and SP.WKYGla3e sub-strains. Only SBP and DBP were significantly reduced during salt challenge in SP.WKYGla3b and SP.WKYGla3f sub-strains, whereas SP.WKYGla3g rats did not differ in haemodynamic response to SHRSP. Those sub-strains demonstrating significantly reduced PP variability during salt challenge also demonstrated significantly reduced renal pathology and proteinuria. Microarray expression profiling prioritized two candidate genes for blood pressure regulation (Dnm1, Tor1b), localized within the common congenic interval shared by SP.WKYGla3d and SP.WKYGla3f strains, and one candidate gene for salt-induced PP variability and renal pathology (Rabgap1), located within the region unique to the SP.WKYGla3d strain. Comparison of next-generation sequencing data identified variants within additional positional genes that are likely to affect protein function. Conclusion: This study has identified distinct intervals on RNO3-containing genes that may be important for blood pressure regulation and renal pathology during salt challenge

Development and Validation of R-hf Risk Score in Acute Heart Failure Patients in the Middle East

Objectives: The Rajan’s heart failure (R-hf) score was proposed to aid risk stratification in heart failure patients. The aim of this study was to validate R-hf risk score in patients with acute decompensated heart failure. Methods: R-hf risk score is derived from the product estimated glomerular filtration rate (mL/min), left ventricular ejection fraction (%), and hemoglobin levels (g/dL) divided by N-terminal pro-brain natriuretic peptide (pg/mL). This was a multinational, multicenter, prospective registry of heart failure from seven countries in the Middle East. Univariable and multivariable logistic regression was applied. Results: A total of 776 patients (mean age = 62.0±14.0 years, 62.4% males; mean left ventricular ejection fraction = 33.0±14.0%) were included. Of these, 459 (59.1%) presented with acute decompensated chronic heart failure. The R-hf risk score group (≤ 5) was marginally associated with a higher risk of all-cause cumulative mortality at three months (adjusted odds ratio (aOR) = 4.28; 95% CI: 0.90–20.30; p =0.067) and significantly at 12 months (aOR = 3.84; 95% CI: 1.23–12.00; p =0.021) when compared to those with the highest R score group (≥ 50). Conclusions: Lower R-hf risk scores are associated with increased risk of all-cause cumulative mortality at three and 12 months

Squall: Scalable Real-time Analytics

Squall is a scalable online query engine that runs complex analytics in a cluster using skew-resilient, adaptive operators. Squall builds on state-of-the-art partitioning schemes and local algorithms, including some of our own. This paper presents the overview of Squall, including some novel join operators. The paper also presents lessons learned over the five years of working on this system, and outlines the plan for the proposed system demonstration

Association between alleles, haplotypes, and amino acid variations in HLA class II genes and type 1 diabetes in Kuwaiti children

Type 1 diabetes (T1D) is a complex autoimmune disorder that is highly prevalent globally. The interactions between genetic and environmental factors may trigger T1D in susceptible individuals. HLA genes play a significant role in T1D pathogenesis, and specific haplotypes are associated with an increased risk of developing the disease. Identifying risk haplotypes can greatly improve the genetic scoring for early diagnosis of T1D in difficult to rank subgroups. This study employed next-generation sequencing to evaluate the association between HLA class II alleles, haplotypes, and amino acids and T1D, by recruiting 95 children with T1D and 150 controls in the Kuwaiti population. Significant associations were identified for alleles at the HLA-DRB1, HLA-DQA1, and HLA-DQB1 loci, including DRB1*03:01:01, DQA1*05:01:01, and DQB1*02:01:01, which conferred high risk, and DRB1*11:04:01, DQA1*05:05:01, and DQB1*03:01:01, which were protective. The DRB1*03:01:01~DQA1*05:01:01~DQB1*02:01:01 haplotype was most strongly associated with the risk of developing T1D, while DRB1*11:04-DQA1*05:05-DQB1*03:01 was the only haplotype that rendered protection against T1D. We also identified 66 amino acid positions across the HLA-DRB1, HLA-DQA1, and HLA-DQB1 genes that were significantly associated with T1D, including novel associations. These results validate and extend our knowledge on the associations between HLA genes and T1D in Kuwaiti children. The identified risk alleles, haplotypes, and amino acid variations may influence disease development through effects on HLA structure and function and may allow early intervention via population-based screening efforts

Impact Of Covid-19 Lockdown On Smoking (Waterpipe And Cigarette) And Participants\u27 Bmi Across Various Sociodemographic Groups In Arab Countries In The Mediterranean Region

INTRODUCTION Tobacco smokers are at high risk of developing severe COVID-19. Lockdown was a chosen strategy to deal with the spread of infectious diseases; nonetheless, it influenced people\u27s eating and smoking behaviors. The main objective of this study is to determine the impact of the COVID-19 lockdown on smoking (waterpipe and cigarette) behavior and its associations with sociodemographic characteristics and body mass index. METHODS The data were derived from a large-scale retrospective cross-sectional study using a validated online international survey from 38 countries (n=37207) conducted between 17 April and 25 June 2020. The Eastern Mediterranean Region (WHO-EMR countries) data related to 10 Arabic countries that participated in this survey have been selected for analysis in this study. A total of 12433 participants were included in the analysis of this study, reporting their smoking behavior and their BMI before and during the COVID-19 lockdown. Descriptive and regression analyses were conducted to examine the association between smoking practices and the participant\u27s country of origin, sociodemographic characteristics, and BMI (kg/m2). RESULTS Overall, the prevalence rate of smoking decreased significantly during the lockdown from 29.8% to 23.5% (p\u3c0.05). The percentage of females who smoke was higher than males among the studied population. The highest smoking prevalence was found in Lebanon (33.2%), and the lowest was in Oman (7.9%). In Egypt, Kuwait, Lebanon, and Saudi Arabia, the data showed a significant difference in the education level of smokers before and during the lockdown (p\u3c0.05). Smokers in Lebanon had lower education levels than those in other countries, where the majority of smokers had a Bachelor\u27s degree. The findings show that the BMI rates in Jordan, Lebanon, Oman, and Saudi Arabia significantly increased during the lockdown (p\u3c0.05). The highest percentages of obesity among smokers before the lockdown were in Oman (33.3%), followed by Bahrain (28.4%) and Qatar (26.4%), whereas, during the lockdown, the percentage of obese smokers was highest in Bahrain (32.1%) followed by Qatar (31.3%) and Oman (25%). According to the logistic regression model, the odds ratio of smoking increased during the pandemic, whereas the odds ratio of TV watching decreased. This finding was statistically significant by age, gender, education level, country of residence, and work status. CONCLUSIONS Although the overall rates of smoking among the studied countries decreased during the lockdown period, we cannot attribute this change in smoking behavior to the lockdown. Smoking cessation services need to anticipate that unexpected disruptions, such as pandemic lockdowns, may be associated with changes in daily tobacco consumption. Public health authorities should promote the adoption of healthy lifestyles to reduce the long-term negative effects of the lockdown

In-hospital mortality in SARS-CoV-2 stratified by hemoglobin levels : a retrospective study

This study is to estimate in-hospital mortality in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients stratified by hemoglobin (Hb) level. Patients were stratified according to hemoglobin level into two groups, that is, Hb 100 g/L. A total of 6931 patients were included. Of these, 6377 (92%) patients had hemoglobin levels >100 g/L. The mean age was 44 ± 17 years, and 66% of the patients were males. The median length of overall hospital stay was 13 days [2; 31]. The remaining 554 (8%) patients had a hemoglobin level 100 g/L (52, 0.82%). Risk factors associated with increased mortality were determined by multi- variate analysis. The Kaplan-Meier survival analysis showed hemoglobin as a predictor of mortality. Cox proportional hazards regression coefficients for hemoglobin for the HB ≤ 100 category of hemoglobin were significant, B = 2.79, SE = 0.17, and HR = 16.34, p < 0.001. Multivariate logistic regression showed Hb < 100 g/L had a higher cumu- lative all-cause in-hospital mortality (22.4% vs. 0.8%; adjusted odds ratio [aOR], 0.33; 95% [CI]: [0.20–0.55]; p < 0.001). In this study, hemoglobin levels <100 g/L were found to be an independent predictor of in-hospital mortality