Inhibitory effect of lupeol, quercetin, and solasodine on Rhizopus oryzae: A molecular docking and dynamic simulation study.

BACKGROUND: Mucormycosis is an infection caused by fungi belonging to the order Mucorales. Rhizopus oryzae is one of the most prevalent organisms identified in mucormycosis patients. Because it spreads quickly through the blood vessels, this opportunistic illness has an exceptionally high fatality rate, even when vigorous treatment is administered. Nonetheless, it has a high tolerance to antifungal medicines, limiting treatment options. As a result, improved methods for preventing and treating mucormycosis are desperately needed. Hence, this study was aimed at assessing the effect of lupeol, quercetin, and solasodine against mucormycosis based on computational approaches. METHODS: The Rhizopus oryzae RNA-dependent RNA polymerase (RdRp) was the target for the design of drugs against the deadly mucormycosis. The three-dimensional structure of the RdRp was modelled with a Swiss model and validated using PROCHECK, VERIFY 3D, and QMEAN. Using the Schrodinger maestro module, a molecular docking study was performed between RdRp and the antimicrobial phytochemicals lupeol, quercetin, and solasodine. A molecular dynamics (MD) simulation study was used to assess the stability and interaction of the RdRp with these phytochemicals. RESULTS: The RdRp protein binds strongly to lupeol (-7.2 kcal/mol), quercetin (-9.1 kcal/mol), and solasodine (-9.6 kcal/mol), according to molecular docking assessment based on the lowest binding energy, confirmation, and bond interaction. Simulations suggest that lupeol, quercetin, and solasodine complexes with RdRp and showed stable confirmation with minimal fluctuation throughout the 200 nanoseconds based on the RMSD and RMSF trajectory assessments. CONCLUSION: The molecular docking and MD simulation investigation improved our understanding of phytochemical-RdRp interactions. Due to its high affinity for RdRp, solasodine may be a better treatment option for mucormycosis.

Antimicrobial stewardship in the Western Cape: A situational analysis of existing facility-level initiatives.

BACKGROUND: Antimicrobial resistance (AMR) is a growing problem worldwide. With the current occurrence of pan-resistant bacterial infections and a paucity of novel antimicrobials in development, the world has entered a post-antibiotic era, in which previously treatable, common infections can become fatal. Antimicrobial stewardship (AMS), defined as 'co-ordinated interventions to ensure appropriate and rational use of antimicrobials', aims to decrease rates of AMR. OBJECTIVES: To co-ordinate AMS in Western Cape Province. The National Department of Health (NDoH) has identified AMS as a key strategic objective, and the Western Cape has formed a provincial AMS committee. However, not much is known regarding current AMS activities in health facilities in the province. METHODS: A self-administered, email questionnaire was sent to specific staff at all district, regional and tertiary hospitals in the 6 health districts of the Western Cape - 47 facilities in total, of which 35 (74.4%) responded. Respondents included pharmacists, managers, doctors, nurses, infection prevention and control practitioners, as well as quality assurance practitioners. The number of facilities implementing AMS were determined, as well as the composition of AMS committees and the nature and frequency of team activities. Barriers to facility-level AMS were explored. Support and outreach activities were assessed, as well as facilities' needs and expectations of the provincial AMS committee. RESULTS: Approximately half of all responding hospitals (n=19; 54.3%) had active AMS committees. Double the proportion of metropolitan (83.3%) than rural facilities (39.1%) had committees. Stewardship activities included antimicrobial prescription chart reviews and audits, AMS ward rounds, antimicrobial restriction policies and training. Most committees included a pharmacist and an infection prevention and control practitioner. More than a third of hospitals (36.1%) did not review their antimicrobial consumption data on a regular basis. Just over half of the hospitals (n=18; 51.4%) did not review AMR patterns. CONCLUSIONS: Despite the need for effective AMS, there is limited information on AMS in South Africa. Most assistance is required in rural areas and smaller hospitals with low numbers of staff and greater numbers of transient rotating junior staff. Information management support, multidisciplinary teamwork and clinical governance are required to enable regular and ongoing AMS in facilities. Rural and smaller facilities require greater support to establish effectively functioning AMS committees.

Predicting permeability changes with injecting CO2 in coal seams during CO2 geological sequestration: A comparative study among six SVM-based hybrid models.

CO2 geological sequestration and enhanced coal bed methane extraction is a significant CO2 utilization approach with dual-meaning of energy and environment, and coal permeability is considered as one of the critical parameters for evaluating this method. To better predict permeability changes with injecting CO2 in coal seams, six SVM-based hybrid models integrating support vector machine (SVM) with intelligent optimization algorithms are proposed and compared, SVM is used for the relationship modelling between CO2 permeability and its influencing variables, and six intelligent optimization algorithms, including artificial bee colony (ABC), cuckoo search (CS), particle swarm optimization (PSO), differential evolution (DE), gray wolf optimizer (GWO), DE-GWO, are used for the hyper-parameters tuning. A total of 125 data samples for CO2 permeability are retrieved from the reported studies to train and verify the proposed models. The input variables for the predictive models include CO2 injection pressure, effective stress, temperature, buried depth and coal rank, and the corresponding output variable is CO2 permeability. The predictive model performance is evaluated and compared by correlation coefficient (R), root mean square error (RMSE) and mean absolute error (MAE). The predictive results denote that the prediction performance of the six hybrid models from high to low is DEGWO-SVM, GWO-SVM, PSO-SVM, CS-SVM, DE-SVM, ABC-SVM, and the DEGWO-SVM hybrid model is recommended to predict permeability changes with injecting CO2 in coal seams. At the same time, the mean impact value (MIV) is used to investigate the relative importance of each input variable. The relative importance scores of CO2 injection pressure, effective stress, temperature, buried depth and coal rank are 0.0248, 0.4617, 0.0211, 0.1102, and 0.3822, respectively. The research results have important guiding significance for CO2 permeability prediction and CO2 sequestration in coal seams.

Prenatal exposure to bisphenol-A altered miRNA-224 and protein expression of aromatase in ovarian granulosa cells concomitant with elevated serum estradiol levels in F1 adult offspring.

This study was aimed to predict bisphenol-A (BPA)-responsive miRNA's using an in silico approach and to study their expression in granulosa cells of animals exposed prenatally to BPA. Pregnant Wistar rats were exposed to BPA through water (25 µg/L, 250 µg/L, and 2.5 mg/L) during gestation. The expression of miRNA-133b, miRNA-378 and miRNA-224 were analyzed in ovarian granulosa cells. BPA affected the postnatal developmental landmarks such as weight of the pups at birth and reduced anogenital distance. BPA exposed animals showed elevated serum estradiol (E2) levels, while follicle-stimulating hormone levels were reduced. The expression of miRNA-224 and aromatase protein levels were found to be increased. This preliminary finding reveals the impact of early life exposure to BPA on the long-term ovarian functions that may be mediated through miRNA-based granulosa cell response. Besides, it is also a compelling indicator for the subclinical response that could have important consequences on female fertility.

A cross-sectional study of confidence in minor surgical skills amongst junior dentists.

INTRODUCTION: To work in the National Health Service (NHS) as a dentist, the practitioner needs to be on the UK dental "performer's list". To apply for access to this list and work as a General Dental Practitioner (GDP), dentists must be qualified from the European Economic Area (EEA) or, those trained in the UK, must undertake Dental Foundation Training (DFT). Dentists interested in further taught learning or pursuing specialist training must continue working as "Dental Core Trainees" (DCTs). Most of these jobs are available in Oral and Maxillofacial Surgery (OMFS) Units and require dentists to undertake unsupervised surgical procedures. It is currently estimated that over 400 "junior dentists" undertake DCT a year. It is the aim of this study to ascertain whether confidence in simple surgical procedures improves when compared to GDPs of similar experience. METHODS: One hundred and two junior dentists, 34 DFTs, 20 DCT1s, 21 DCT2s and 27 second and third year post-DFT GDPs all working across the Midlands, UK, had Likert scale responses about confidence in 14 minor surgical skills assessed. Results were analysed to ascertain whether gender, year group and number of extractions had any effect on confidence. CONCLUSIONS: We conclude that confidence in minor surgical procedures improves significantly when undertaking DCT OMFS posts, with the most significant improvement in confidence occurring within the first 6 months. Dental Core Trainees become significantly more confident in their surgical ability within the first 6 months when compared to GDPs with longer postgraduate experience.

A Study of Permeability Changes Due to Cold Fluid Circulation in Fractured Geothermal Reservoirs.

Reservoir behavior due to injection and circulation of cold fluid is studied with a shear displacement model based on the distributed dislocation technique, in a poro-thermoelastic environment. The approach is applied to a selected volume of Soultz geothermal reservoir at a depth range of 3600 to 3700 m. Permeability enhancement and geothermal potential of Soultz geothermal reservoir are assessed over a stimulation period of 3 months and a fluid circulation period of 14 years. This study-by shedding light onto another source of uncertainty-points toward a special role for the fracture surface asperities in predicting the shear dilation of fractures. It was also observed that thermal stress has a significant impact on changing the reservoir stress field. The effect of thermal stresses on reservoir behavior is more evident over longer circulation term as the rock matrix temperature is significantly lowered. Change in the fracture permeability due to the thermal stresses can also lead to the short circuiting between the injection and production wells which in turn decreases the produced fluid temperature significantly. The effect of thermal stress persists during the whole circulation period as it has significant impact on the continuous increase in the flow rate due to improved permeability over the circulation period. In the current study, taking into account the thermal stress resulted in a decrease of about 7 °C in predicted produced fluid temperature after 14 years of cold fluid circulation; a difference which notably influences the potential prediction of an enhanced geothermal system.

A Model of Stimulus-Specific Adaptation in Neuromorphic Analog VLSI.

Stimulus-specific adaptation (SSA) is a phenomenon observed in neural systems which occurs when the spike count elicited in a single neuron decreases with repetitions of the same stimulus, and recovers when a different stimulus is presented. SSA therefore effectively highlights rare events in stimulus sequences, and suppresses responses to repetitive ones. In this paper we present a model of SSA based on synaptic depression and describe its implementation in neuromorphic analog very-large-scale integration (VLSI). The hardware system is evaluated using biologically realistic spike trains with parameters chosen to reflect those of the stimuli used in physiological experiments. We examine the effect of input parameters and stimulus history upon SSA and show that the trends apparent in the results obtained in silico compare favorably with those observed in biological neurons.

A gestation- and postnatal age-based reference chart for assessing renal function in extremely premature infants.

OBJECTIVE: A single value of plasma creatinine cannot be used to define renal dysfunction in premature babies, as levels are influenced by gestation and postnatal age. The aim of this study was to create reference ranges for plasma creatinine in cohort of extremely premature infants. STUDY DESIGN: Retrospective analysis of plasma creatinine levels in the first 8 weeks of life from 161 consecutively admitted premature infants 28 weeks gestation. RESULT: Babies were divided into three groups according to gestation. Peak (10th, 90th percentiles) creatinine levels were 132 (106,162) in 22 to 24 weeks gestational infants, 127 (89,151) in those from 25 to 26 weeks and 110 (87,134) in those from 27 to 28 weeks (P<0.001). Creatinine at birth was similar across the groups with levels increasing during the first few days. It decreases thereafter before reaching stable levels by 5 weeks of age. CONCLUSION: Gestation- and age-based reference charts should be used for interpretation of creatinine values in extremely premature babies.

Assessment of the educational environment at the College of Medicine of King Saud University, Riyadh.

We used an Arabic translation (revised in our college) of the Dundee Ready Education Environment Measure (DREEM) inventory to assess the educational environment at the College of Medicine in King Saud University, Riyadh. Over 500 questionnaires were distributed and 222 were analysed. Scores were: 45.0% overall; 40.7% for students' perception of learning, 48.2% for perception of teachers, 46.3% for academic self-perception, 44.4% for perception of atmosphere, and 46.1% for social self-perception. Scores for first year students were significantly higher than the others. Scores for pre-clinical students were also significantly higher than those of students in clinical years. Sex was not a statistically significant variable.

Assessment of the accuracy of death certification at two referral hospitals.

BACKGROUND: Death certification is a vital source of information used in mortality statistics worldwide to assess the health of the general population. This study focuses on the consistency of information between the death reports and the clinical records (files) of deceased patients in two hospitals: the King Khalid University Hospital (KKUH) and King Fahad National Guard hospital (KFNGH) in Saudi Arabia. METHODS: A random sample of the records of 157 deceased patients' registered in 2002 in the two hospitals was retrospectively reviewed independently to determine the underlying cause of death and compare them with death reports. It was also to check the accuracy of the translation from English in to Arabic. RESULTS: It was found that the underlying cause of death was misdiagnosed in 80.3% of the death reports. When the two hospitals were compared, no significant difference was observed (p>0.05). In addition, 81.8% of the accurate (correct) death reports in both hospitals were of patients who had died of a malignant disease. However, the translation of the underlying cause of death in KFNGH was correct in 86.1% of the death reports, while in KKUH it was only 25%, which is highly statistically significant (p<0.0001). CONCLUSION: With the limitation of studying only a small number of cases, these results indicate a discrepancy between the file and death reports in relation to the cause of death. Also, the translation of the cause of death was inconsistent in the two hospitals. Hence, there is a real need to adopt suitable measures to improve the quality of death certification.

Assessment of the educational environment at the College of Medicine of King Saud University, Riyadh

We used an Arabic translation [revised in our college] of the Dundee Ready Education Environment Measure [DREEM] inventory to assess the educational environment at the College of Medicine in King Saud University, Riyadh. Over 500 questionnaires were distributed and 222 were analysed. Scores were: 45.0% overall; 40.7% for students' perception of learning, 48.2% for perception of teachers, 46.3% for academic self-perception, 44.4% for perception of atmosphere, and 46.1% for social self-perception. Scores for first year students were significantly higher than the others. Scores for pre-clinical students were also significantly higher than those of students in clinical years. Sex was not a statistically significant variable

Conformational Angles DataBase (CADB-3.0).

Transitions in amino-acid conformation angles tend to accompany various structural modifications in protein structures. Thus, to benefit the modeling of protein structures, the Conformation Angles DataBase (CADB-3.0) has been updated to visualize the conformational angles in varied regions (fully, generously, additionally and disallowed regions). In addition, options are provided to display the angles in the secondary structural elements (alpha-helix, beta-sheet and 3(10)-helix) of the Ramachandran plot. The database is being updated periodically and can be accessed over the World Wide Web at the following URL: http://cluster.physics.iisc.ernet.in/cadb/.

Ramachandran plot on the web (2.0).

The Ramachandran plot displays the main chain conformation angles (Phi and Psi) of the polypeptide chain of a protein molecule. The paper reports the updated version of the Ramachandran plot web server and has several improved options for displaying the conformation angles in various regions. In addition, options are provided to display the conformation angles in various secondary structural elements and regions within the user specified Phi and Psi values in the plot. The updated version is accessible at the following URL: http://dicsoft1.physics.iisc.ernet.in/rp/.

Histological and laboratory features of patients undergoing liver biopsy at a university hospital in Central Saudi Arabia.

OBJECTIVE: To identify the most common liver pathologies seen in our center, to find the prevalence of advanced fibrosis and cirrhosis in patients with chronic hepatitis B and C, and to correlate the histological and laboratory features of the most common diseases and compare between them. METHODS: Liver biopsy procedures performed in our Gastroenterology Unit at King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia were traced from records between the years 1997-2003. Clinical, histopathological, and laboratory features were recorded. RESULTS: We identified 574 liver biopsies during the study period. Of the 502 included patients, males were 58.6%. The mean age of the patients was 43.5 years. Approximately half of the biopsies (49%) were performed for patients with hepatitis C, followed by hepatitis B, for which 17% of the biopsies were performed. Patients with hepatitis B were approximately 10 years younger than patients with hepatitis C (p = 0.01). They were 10% more likely to be males. In terms of fibrosis, only approximately 17% of patients with hepatitis B and 27% of patients with hepatitis C had advanced fibrosis. CONCLUSION: Most liver biopsies performed in our center are performed for patients with hepatitis C. Rates of advanced fibrosis in our series are significantly lower than what was previously reported in other studies.

CADB-2.0: Conformation Angles Database.

The Conformation Angles Data Base (CADB) is a comprehensive, authoritative and timely knowledge base with a powerful query engine developed to facilitate the retrieval of information related to the conformational angles (main chain and side chain) of the amino-acid residues present in non-redundant (both 25 and 90%) data sets. The updated version has improved options for determining the dependency of the conformation angles of a particular residue upon the flanking residues, doublet analysis, triplet analysis and analysis of a particular protein structure. It is worth mentioning that for all options a user-friendly and convenient Java graphical user interface (GUI) has been provided to display the output on the client machine. The database is accessible at the URL http://cluster.physics.iisc.ernet.in/cadb/ or http://144.16.71.148/cadb/.

A FAST pattern matching algorithm.

The advent of digital computers has made the routine use of pattern-matching possible in various applications. This has also stimulated the development of many algorithms. In this paper, we propose a new algorithm that offers improved performance compared to those reported in the literature so far. The new algorithm has been evolved after analyzing the well-known algorithms such as Boyer-Moore, Quick-search, Raita, and Horspool. The overall performance of the proposed algorithm has been improved using the shift provided by the Quick-search bad-character and by defining a fixed order of comparison. These result in the reduction of the character comparison effort at each attempt. The best- and the worst- case time complexities are also presented in this paper. Most importantly, the proposed method has been compared with the other widely used algorithms. It is interesting to note that the new algorithm works consistently better for any alphabet size.

Side-chain conformation angles of amino acids: effect of temperature factor cut-off.

The paper presents the analysis of the side-chain conformation angles of amino acids in 90% non-identical protein structures. The analysis has been carried out using 113,699 residues, which is higher compared to the previous studies. In the present study, one more quality check, namely, temperature factor cut-off, has been introduced in addition to resolution and R-factor cut-offs. Due to this, the present calculation reveals the approximate values for the minimum and the maximum of the three-rotameric states of chi1. In addition, the conformation angles chi2 and chi3 have been addressed with the improved data set. The results reported here could be of use in protein modeling.

SEM (Symmetry Equivalent Molecules): A web-based GUI to generate and visualize the macromolecules.

SEM, Symmetry Equivalent Molecules, is a web-based graphical user interface to generate and visualize the symmetry equivalent molecules (proteins and nucleic acids). In addition, the program allows the users to save the three-dimensional atomic coordinates of the symmetry equivalent molecules in the local machine. The widely recognized graphics program RasMol has been deployed to visualize the reference (input atomic coordinates) and the symmetry equivalent molecules. This program is written using CGI/Perl scripts and has been interfaced with all the three-dimensional structures (solved using X-ray crystallography) available in the Protein Data Bank. The program, SEM, can be accessed over the World Wide Web interface at http://dicsoft2.physics.iisc.ernet.in/sem/ or http://144.16.71.11/sem/.

CAP: conformation angles package-displaying the conformation angles of side chains in proteins.

SUMMARY: A graphics package has been developed to display all side chain conformation angles of the user selected residue in a given protein structure. The proposed package is incorporated with all the protein structures (solved using X-ray diffraction and NMR spectroscopy) available in the Protein Data Bank. The package displays the multiple conformations adopted by a single amino acid residue whose structure is solved and refined at very high resolution. In addition, it shows the percentage distribution of the side chain conformation angles in different rotameric states. AVAILABILITY: http://144.16.71.146/cap/