A Novel Clinical Decision Support System Using Improved Adaptive Genetic Algorithm for the Assessment of Fetal Well-Being

A novel clinical decision support system is proposed in this paper for evaluating the fetal well-being from the cardiotocogram (CTG) dataset through an Improved Adaptive Genetic Algorithm (IAGA) and Extreme Learning Machine (ELM). IAGA employs a new scaling technique (called sigma scaling) to avoid premature convergence and applies adaptive crossover and mutation techniques with masking concepts to enhance population diversity. Also, this search algorithm utilizes three different fitness functions (two single objective fitness functions and multi-objective fitness function) to assess its performance. The classification results unfold that promising classification accuracy of 94% is obtained with an optimal feature subset using IAGA. Also, the classification results are compared with those of other Feature Reduction techniques to substantiate its exhaustive search towards the global optimum. Besides, five other benchmark datasets are used to gauge the strength of the proposed IAGA algorithm

Persistence of W135 Neisseria meningitidis Carriage in Returning Hajj Pilgrims: Risk for Early and Late Transmission to Household Contacts

After an outbreak of meningococcal disease caused by Neisseria meningitidis W135, associated with the Hajj pilgrimage in 2001, 15% of returning vaccinated pilgrims carried a single W135 clone, and 55% were still carriers 6 months later. Transmission to 8% of their unvaccinated household contacts occurred within a few weeks, but no late transmission took place. Public health interventions are needed to protect household contacts

Otological manifestations of temporal bone fractures

Background: Temporal bone fractures are caused by high intensity trauma and can result in various facial and cochleovestibular sequelae, which can affect the quality of life. The aim was to study about the various otological manifestations of temporal bone fractures in head trauma patients. Methods: Descriptive study of 82 patients was conducted in the Department of Otorhinolaryngology, Government T D Medical College, Alappuzha from April 2019 to March 2021. All patients with radiological evidence of temporal bone fractures were taken for study and their symptoms and signs were compared among otic capsule sparing (OCS) and otic capsule violating (OCV) type fractures. Data was analysed statistically using SPSS version 22 and p value calculated using chi-square test. Results: Majority of the patients were in the 20–40-year age group. Male to female ratio was 8.1:1. The most common aetiology was road traffic accidents (RTAs) n=74 (90.24%). The incidence of tinnitus (p value=0.02), vertigo (p value=0.007), facial palsy (p value=0.0004), CSFO (p value=0.0002), nystagmus (p value=0.0065) and sensorineural hearing loss (SNHL) (p value=0.00001) were found to be more in OCV type fractures and their association was found to be statistically significant. The incidence of TM perforation (p value=0.01), conductive hearing loss (CHL) (p value=0.0008) and EAC laceration (p value=0.04) was more in OCS type fractures and was statistically significant. Conclusion: Rapid diagnosis of temporal bone fractures is crucial as it enables effective initial management aimed at avoiding the facial and cochleovestibular sequelae that can adversely affect the quality of life

High fructose Corn Syrup recast glucose transporter-5, Wnt, NF-κB signalling and mitochondrial apoptosis in an animal model of oral oncogenesis

Background: Wnt signalling pathway, is mediated by members of T-cell factor (TCF) transcription factors family, is essential for the control of epithelial cell proliferation and death. Glucose transporter-5 (GLUT5), fructose-specific transporter, is also important in allowing transcellular fructose uptake. The goal of this work to determine how the High fructose Corn Syrup (HFCS) affected Wingless-related integration site (Wnt) and Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signalling in the 7,12 –dimethylbenzaanthracene (DMBA)-induced hamster buccal pouch carcinogenesis (HBPCs) model. Methods: Four groups of hamsters were created. For 12 weeks, 0.5 % DMBA was applied 3 times/week to the left side buccal pouches of the hamsters in groups (2 & 4). Additionally, the animals in groups (3 & 4) were given through drinking water of HFCS 25 %. The control animals were from group 1. By using western blot analysis, signalling network markers of the GLUT-5, Wnt, TCF-4, GSK-3β and NF-κB as well as mitochondrial apoptotic pathway marker expression B-cell lymphoma protein 2 (Bcl-2)-associated X (Bax) and cyclooxygenase – 2 (COX-2) was assessed. Results: Drinking water uptake of 25% HFCS encouraged progress of HBP carcinomas by constitutive stimulating of the Wnt pathway via GSK-3β overexpression. HFCS suppressed Wnt signalling which contributed the NF-κB attenuation and changes the signalling markers in apoptotic network. Conclusions: Our hypothesis suggests a mechanically crosstalk between Wnt and NF-κB signalling pathways in HBP carcinomas that is developed by HFCS. HFCS that targets the Wnt pathway and its downstream signalling mediators could be additive reason for cancer development

Use of Mycobacterial Interspersed Repetitive Unit-Variable-Number Tandem Repeat Typing To Examine Genetic Diversity of Mycobacterium tuberculosis in Singapore

Strain typing using variable-number tandem repeats of mycobacterial interspersed repetitive units (MIRU-VNTR) is a powerful tool for studying the epidemiology and genetic relationships of Mycobacterium tuberculosis isolates. For this study, isolates from 291 patients in Singapore were genotyped by this method. One hundred sixty-six distinct MIRU-VNTR patterns were detected. One hundred sixty-two strains were grouped into 1 of 35 different MIRU-VNTR clusters and 131 isolates were unique. In this sample collection, 9 of the 12 MIRU-VNTR loci were moderately or highly discriminative according to their allelic diversities. The Hunter-Gaston discriminatory index was 0.975, indicating the high power of discrimination of MIRU-VNTR typing. By direct comparisons with previously typed MIRU-VNTR patterns and by genetic relationship analyses, we could identify and clearly define four epidemic groups of M. tuberculosis in our sample, corresponding to the W/Beijing, East-Africa-Indian, Haarlem, and Delhi genotype families. Furthermore, MIRU-VNTR typing was able to clearly distinguish ancestral and modern M. tuberculosis strains as defined by TbD1 genomic deletion analysis. These results indicate that MIRU-VNTR typing can be a useful first-line tool for studying the genetic diversity of M. tuberculosis isolates in a large urban setting such as Singapore

Characterization of Ancestral Mycobacterium tuberculosis by Multiple Genetic Markers and Proposal of Genotyping Strategy

Sixty-eight ancestral Mycobacterium tuberculosis isolates were previously identified by using the tuberculosis-specific deletion 1 (TbD1) PCR and mycobacterial interspersed-repetitive-unit-variable-number tandem repeat (MIRU-VNTR) typing (Y. J. Sun, R. Bellamy, A. S. G. Lee, S. T. Ng, S. Ravindran, S.-Y. Wong, C. Locht, P. Supply, and N. I. Paton, J. Clin. Microbiol. 42:1986-1993, 2004). These TbD1(+) ancestral isolates were further characterized and typed in this study by IS6110 restriction fragment length polymorphism (RFLP) typing, VNTR typing using exact tandem repeats (VNTR-ETR), and spoligotyping of the direct-repeat region. To our knowledge, this is the first characterization of this genogroup by multiple genetic markers based on a fairly large sample size. In this genogroup, all spoligotypes were characterized by the absence of spacers 29 to 32 and 34. In addition, VNTR-ETR typing could add further resolution to the clustered isolates identified by MIRU-VNTR, and the combination of MIRU-VNTR and VNTR-ETR, called MIRU-ETR, showed the highest discriminatory power for these strains compared to IS6110 RFLP typing and spoligotyping alone. However, MIRU-ETR appeared to still cluster some probably epidemiologically unrelated strains, as judged by IS6110 RFLP divergence. Therefore, a typing strategy based on stepwise combination of MIRU-ETR and IS6110 RFLP is proposed to achieve maximal discrimination for unrelated TbD1(+) strains. This typing strategy may be useful in areas where TbD1(+) ancestral strains are prevalent

Immunoassay-Compatible Inactivation of SARS-CoV-2 in Plasma Samples for Enhanced Handling Safety

10.1021/acsomega.2c02585ACS OMEGA72925510-25520complete

Pharmacokinetics-Pharmacodynamics Analysis of Bicyclic 4-Nitroimidazole Analogs in a Murine Model of Tuberculosis

<div><p>PA-824 is a bicyclic 4-nitroimidazole, currently in phase II clinical trials for the treatment of tuberculosis. Dose fractionation pharmacokinetic-pharmacodynamic studies in mice indicated that the driver of PA-824 <i>in</i><i>vivo</i> efficacy is the time during which the free drug concentrations in plasma are above the MIC (<i>fT_>MIC</i>). In this study, a panel of closely related potent bicyclic 4-nitroimidazoles was profiled in both <i>in</i><i>vivo</i> PK and efficacy studies. In an established murine TB model, the efficacy of diverse nitroimidazole analogs ranged between 0.5 and 2.3 log CFU reduction compared to untreated controls. Further, a retrospective analysis was performed for a set of seven nitroimidazole analogs to identify the PK parameters that correlate with <i>in</i><i>vivo</i> efficacy. Our findings show that the <i>in</i><i>vivo</i> efficacy of bicyclic 4-nitroimidazoles correlated better with lung PK than with plasma PK. Further, nitroimidazole analogs with moderate-to-high volume of distribution and Lung to plasma ratios of >2 showed good efficacy. Among all the PK-PD indices, total lung <i>T_>MIC</i> correlated the best with <i>in</i><i>vivo</i> efficacy (<i>r_s</i> = 0.88) followed by lung C_max/MIC and AUC/MIC. Thus, lung drug distribution studies could potentially be exploited to guide the selection of compounds for efficacy studies, thereby accelerating the drug discovery efforts in finding new nitroimidazole analogs.</p></div