Exploring Antimicrobial Features for New Imidazo[4,5-b]pyridine Derivatives Based on Experimental and Theoretical Study.

5-bromopyridine-2,3-diamine reacted with benzaldehyde to afford the corresponding 6-Bromo-2-phenyl-3H-imidazo[4,5-b]pyridine (1). The reaction of the latter compound (1) with a series of halogenated derivatives under conditions of phase transfer catalysis solid-liquid (CTP) allows the isolation of the expected regioisomers compounds (2-8). The alkylation reaction of (1) gives, each time, two regioisomers, N3 and N4; in the case of ethyl bromoactate, the reaction gives, at the same time, the three N1, N3 and N4 regioisomers. The structures of synthesized compounds were elucidated on the basis of different spectral data (1H NMR, 13C NMR), X-Ray diffraction and theoretical study using the DFT method, and confirmed for each compound. Hirshfeld surface analysis was used to determine the intermolecular interactions responsible for the stabilization of the molecule. Density functional theory was used to optimize the compounds, and the HOMO-LUMO energy gap was calculated, which was used to examine the inter/intra molecular charge transfer. The molecular electrostatic potential map was calculated to investigate the reactive sites that were present in the molecule. In order to determine the potential mode of interactions with DHFR active sites, the three N1, N3 and N4 regioisomers were further subjected to molecular docking study. The results confirmed that these analogs adopted numerous important interactions, with the amino acid of the enzyme being targeted. Thus, the most docking efficient molecules, 2 and 4, were tested in vitro for their antibacterial activity against Gram-positive bacteria (Bacillus cereus) and Gram-negative bacteria (Escherichia coli). Gram-positive bacteria were more sensitive to the action of these compounds compared to the Gram-negative, which were much more resistant.

Effects of Smokeless Tobacco Samples from Tabuk Saudi Arabia on Nitric Oxide Production: A Potential Risk for Cancer and Cardiovascular Diseases.

BACKGROUND: Smokeless tobacco (SLT) is traditionally used in Middle East countries. The several toxic constituents with potential carcinogenicity make it a serious human health risk. Literature regarding their effects on cardiac and cancer disease is lacking in Saudi Arabia. OBJECTIVE: This study was conducted to investigate the adverse effect of 11 different samples of widely used SLT varieties from the Tabuk region - Saudi Arabia, on Nitric Oxide (NO) level and their potential risk on cardiovascular health, etiology and/or progression of cancers. METHODS: Samples were collected from Tabuk, KSA and analyzed by the GC-MS technique. Nitric oxide inhibition was performed using J774.2 macrophages by the Griess method. The retrieved crystallized structure of human inducible nitric oxide synthase (iNOS) from Brookhaven Protein Data Bank Repository PDB I.D: 3E7G with 2.20Å resolution was further prepared by structure using the MOE.2019 tool. The compounds abstracted from 11 different Shammah varieties were sketched by the MOE-Builder tool. Minimization for both receptor and compounds was performed via AMBER99 and MMFF99X force field implemented in MOE. RESULTS: Nine samples (4 - 11) showed a potent suppressive effect on NO production with IC50 values ranging between (16.9-20.4 µg/mL), respectively. The samples (1 & 2) exhibited a moderate level of inhibition with IC50 ranging between 33.2 and 57.4 µg/mL, respectively. Interestingly, sample 4 consisting of compounds (13-15, 19-26, 28) that mostly belongs to the group fatty acid ester and phthalic acid ester showed the most potent suppressive effect. Molecular docking results revealed that the current local SLT constituents presented noticeable potency in different extract samples. CONCLUSION: Variable suppressive effects on NO were detected in the current SLT samples, where sample 4 was the most potent among all. The extract of the latter exhibited molecular interaction with the first shell amino acid residues of Inducible nitric oxide synthase (iNOS), which may anchor the plasticity and selectivity of the compounds present in it. The samples (4 -11) showed a potent inhibitory effect on the NO, where compound 26 (Phthalic acid ester) is common, and its adequate concentration may account for augmented biological activity. These results may effectively highlight their adverse effects on cardiovascular health and etiology and/or progression of cancer and may help in strengthening the social and governmental efforts in minimizing the use of these substances.

An Application for Measuring and Analyzing the Level of Performance Accuracy for Health Services Quality Indicators by Using Six-Sigma: A Study Case of Government Hospitals in Khartoum State.

The study aimed at acknowledging the Six Sigma methodology and the existence of the essential components for the application, as well as reducing the time for completing the operations, reducing the error rate to the lowest possible level, and improving the quality of operations. For this objective, the analytical descriptive methodology was used on a sample consisted of 300 administrative and medical staff from Khartoum State Hospitals (Khartoum, Omdurman, Bahri). To this end, a questionnaire was used for collecting data and for analyzing it and achieving the results of the study by using the statistical analysis package (SPSS). The study deduced a number of results, the most important of which are that the items of commitment and supreme command support for the senior leadership and the methods of abundant human resources on quality control, and the application of the Six Sigma methodology in government hospitals in Khartoum state achieved a satisfactory level, while continuous improvement paragraphs, processes, and systems on quality control and the application of Six Sigma methodology achieved high quality. There is a significant effect on the extent of commitment and support of the higher leadership on quality control and the application of the Six Sigma methodology. Similarly, there is a statistically significant effect on the application of continuous improvement methods on quality control and Six Sigma methodology. Also, there is a statistically significant effect on the application of the abundance of human resources methods variable on quality control and the application of Six Sigma methodology in governmental hospitals in Khartoum state. The study recommended to take interest in the Six Sigma methodology and assure the possibility of using it in Khartoum State's hospitals because of its scientific and practical importance in improving the quality of services and provided processes, and the need to provide qualified financial and human resources for using and developing Six Sigma methodology in hospitals, as well as great attention in training and providing departments heads with full knowledge of Six Sigma methodology and the fundamentals on which Six Sigma methodology, is based on its importance for hospitals. The study also recommended associating the promotions system in government hospitals in Khartoum state with the quality control program.

Risk-taking behaviours among fishermen in Morocco by the evaluation of "ordalique" functioning.

BACKGROUND: The aim was to investigate the potential fishermen's psychological functioning which induces risk-taking behaviours by evaluating the ordalique functioning. MATERIALS AND METHODS: This cross-sectional epidemiological study was conducted in three ports of northern Morocco in 2016 and concerned 1413 traditional fishermen working in small embarkations and 1049 administrative staff working in the maritime sector on land. Both groups were male, comparable for age and educational level. The survey support was an individual questionnaire covering socio-demographic characteristics, toxic habits and ordalique functioning questionnaire (le questionnaire de fonctionnement ordalique, QFO). It is composed of 42 items and four dimensions which are evaluated: risk-taking, transgression, positive representation of risk-taking and believes. RESULTS: The prevalence of the ordalique behaviour and its four dimensions was significantly higher among traditional fishermen than administrative staff on land; 66.4% vs. 33.6% (p < 0.0001) for risk-taking, 65.2% vs. 34.8% (p < 0.0001) for transgression, 60.4% vs. 39.6% (p < 0.0001) for positive representation, 59.8% vs. 51.2% (p < 0.0001) for believes. For all range ages, the prevalence of ordalique functioning was higher among fishermen than administrative staff on land. Among fishermen, the prevalence of the was significantly higher among the under 40 years old (69.1% vs. 54.7%, p < 0.0001). The prevalence of toxic habits among ordalique fishermen was significantly greater than no-ordalique ones: tobacco (54.5% vs. 48.6%, p < 0.035), alcohol (42.8% vs. 32.4%, p < 0.0001), cannabis (34.8% vs. 26.6%, p < 0.0001), psychotropic drugs (13.8% vs. 10.4%, p < 0.081) and a combination of toxic habits (27.7% vs. 19.6%, p < 0.0001). CONCLUSIONS: Ordalique behaviour among fishermen may explain the partial failure of preventive measures in this sector. Risk-taking behaviours into account in the safety system could reduce occupational hazards in the fishery.

Anti-mullerian hormone as a predictor of ovarian reserve and ovarian response in IVF women from Gaza strip.

UNLABELLED: Back ground: Careful evaluation of patients and proper treatment with right techniques are essential for successful outcome of assisted reproduction. To obtain satisfactory results, it is necessary to assess ovarian reserve before planning treatment. OBJECTIVE: To evaluate anti-mullerian hormone as a predictor of fertility potential in terms of ovarian reserve and ovarian response reflected by antral follicles and mature oocyte counts in response to menotrophin stimulation in in vitro fertilization (IVF) women from Gaza Strip. MATERIALS AND METHODS: This prospective cohort study consisted of 81 women (mean age 28.7 years) attending IVF at Al-Basma Fertility Center in Gaza City. Blood withdrawal for antimullerian hormone measurement was performed in all the patients and the number of oocytes and embryos were recorded. RESULTS: The total number of retrieved oocytes was inversely associated with age (12.5±4.5, 11.0±5.4 and 6.9±4.7 at age ≤25, 26-35 and >35 years, respectively (F=4.793 and p=0.011). The ovarian response to Menotrophin (FSH 75IU, LH 75 IU) stimulation was better for younger age. There was a significant positive association between ovarian response in terms of total number of oocytes and antimullerian hormone levels. The maximum level of antimullerian hormone was observed in females who achieved positive pregnancies (4.5±2.5 ng/mL) followed by negative pregnancies (2.9±1.8 ng/mL) with significant differences (F=6.862 and p=0.002). Correlation coefficient revealed that the number of mature oocytes showed strong positive correlation with the antimullerian hormone levels (r=0.469, p=0.001). CONCLUSION: Anti-mullerian hormone can be used in IVF programs as a good predictor of ovarian reserve and ovarian response.

Pilot investigation of hyaluronate injections for first metacarpal-carpal (MC-C) osteoarthritis.

Hyaluronate intraarticular injections are widely used for treatment of pain associated with osteoarthritis of the knee, but there is no published literature on its use in osteoarthritis of the hand. We describe an open-label, baseline-controlled pilot study in which 5 weekly injections of 10 mg sodium hyaluronate (molecular weight 500-730 kDa) in 1 mL was used to treat 16 patients with osteoarthritic first metacarpal-carpal (MC-C) joints. The injections were performed easily and were well tolerated. Mean pain score at 5 months after the last injection, on a 10-point visual analog scale, decreased from 4.74 to 2.56 at rest. Pain on use decreased from 5.91 to 4.33. Pinch strength and a short questionnaire on hand function did not significantly change. The results of this small pilot study suggest that intraarticular injections into the first MC-C joint are easily administered, well tolerated, and could be an effective treatment option for patients with osteoarthritis of this joint. Further investigation using larger, blind controlled clinical studies are warranted.