Preliminary Anticonvulsant and Toxicity Screening of Substituted Benzylidenehydrazinyl- N

Keeping in view the structural requirements suggested in the pharmacophore model for anticonvulsant activity, a new series of 3-(2-(substitutedbenzylidene)hydrazinyl)-N-(substituted benzo[d]thiazol-2-yl)-propanamides were synthesized with aromatic hydrophobic aryl ring (A), NH–C=O as hydrogen bonding domain (HBD), nitrogen atom as electron donor (D), and phenyl as distal aryl ring (C). Synthesized compounds were characterized by FTIR, 1H NMR, 13C NMR, mass spectroscopy, and elemental analysis. Preliminary in vivo anticonvulsant screening (phase I) was performed by two most adopted seizure models, maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ). Based on anticonvulsant screening results, two compounds, 5h and 5p, were found to be most active; they exhibited activity comparable to standard drugs phenytoin (PHY) and carbamazepine (CBZ). These active compounds were subjected to phase II and phase III screening, where they displayed much higher protective index (PI) in comparison to the standard drugs. In phase IV screening, the bioavailability of active compounds was assessed on oral administration. Further, preliminary safety profiles of 5h and 5p were evaluated by the neurotoxicity testing and liver enzyme estimation

KINETIC AND KINEMATIC ANALYSIS OF RECURVE ARCHERY SHOOTING TECHNIQUE

The study investigated shooting techniques of the archers with kinetic and kinematic methods. Twenty-seven archers of different skill levels have been involved into the current study to investigate both muscular activation strategies of nine muscles and some kinematic data on drawing hand side. A statistical significant difference (p0.05) in the time-dependent exchange values of the angle of the joints, a difference was detected in the graphical sense. Elite archers use distal muscles less but proximal and axial muscles more, and mid-level and novice archers use distal muscles more to pull the bowstring. This was interpreted to be the most important factor affecting the horizontal oscillation (lateral diflection) of bowstring

A case of urinary tract infection caused by Raoultella planticola after a urodynamic study

AbstractHere we report the case of a patient who developed urinary tract infection after a urodynamic study. The causative agent was Raoultella planticola, a rare opportunistic pathogen that usually invades immunocompromised patients. While a urinary tract infection with R. planticola has been previously described, this is the first report in which an R. planticola infection developed after a urodynamic study. We postulate that the mechanism of infection was direct invasion of the urinary tract from contaminated urodynamic study equipment. Here, we discuss the role played by isotonic solutions in facilitating bacterial reproduction

DEVELOPMENTAL DIFFERENCES OF KINEMATIC AND MUSCULAR ACTIVATION PATTERNS IN INSTEP SOCCER KICK

The aim of the study was to evaluate kinematic and muscular activation differences amongst different age groups of soccer players. Thirty male youth soccer players were divided into 3 groups according to their age (age 12-13; age 14-15; age 16-17). There were significant differences in ball velocities and isokinetic strength values amongst groups. Angular and linear velocities of hip, knee, ankle and toe were also significantly different (

Anticonvulsant evaluation of 2-pyrazolines carrying naphthyl moiety: An insight into synthesis and molecular docking study

A series of N-substituted-3-(napthalen-2-yl)-5-substituted phenyl-4,5-dihydropyrazole-1-carbothioamide derivatives (4a-n) were synthesized with the view of structural requirements of pharmacophore for potential anticonvulsant agents. The synthesized compounds were assayed intraperitoneally (i.p.) and subcutaneously (s.c.) in mice against seizures induced by MES and scPTZ methods, respectively. Neurologic deficit was evaluated by rotarod method. Among the tested compounds, 4g, 4i, 4j and 4n emerged as the most active molecule in the MES model at a dose of 30 mg/kg at 0.5h comparable to standardscarbamazepine and phenytoin. In the scPTZ test,4e and 4l were found to be most active compounds at the lowest dose of 30 mg/kg at 0.5h, in the management of the convulsive disorder. Molecular docking studies of the titled compounds were also donewith 3D crystal structure of human cytosolic branched chain amino transferase (hBCATc) enzyme and compound 4e was found to have five hydrogen bond interactions with the most important active site residues.In neurotoxicity studies, except compounds 4b, 4c, 4h and 4k, rest of the compounds showed no sign of toxicity

Genomic analysis of DNA binding and gene regulation by homologous nucleoid-associated proteins IHF and HU in Escherichia coli K12.

IHF and HU are two heterodimeric nucleoid-associated proteins (NAP) that belong to the same protein family but interact differently with the DNA. IHF is a sequence-specific DNA-binding protein that bends the DNA by over 160°. HU is the most conserved NAP, which binds non-specifically to duplex DNA with a particular preference for targeting nicked and bent DNA. Despite their importance, the in vivo interactions of the two proteins to the DNA remain to be described at a high resolution and on a genome-wide scale. Further, the effects of these proteins on gene expression on a global scale remain contentious. Finally, the contrast between the functions of the homo- and heterodimeric forms of proteins deserves the attention of further study. Here we present a genome-scale study of HU- and IHF binding to the Escherichia coli K12 chromosome using ChIP-seq. We also perform microarray analysis of gene expression in single- and double-deletion mutants of each protein to identify their regulons. The sequence-specific binding profile of IHF encompasses ∼30% of all operons, though the expression of <10% of these is affected by its deletion suggesting combinatorial control or a molecular backup. The binding profile for HU is reflective of relatively non-specific binding to the chromosome, however, with a preference for A/T-rich DNA. The HU regulon comprises highly conserved genes including those that are essential and possibly supercoiling sensitive. Finally, by performing ChIP-seq experiments, where possible, of each subunit of IHF and HU in the absence of the other subunit, we define genome-wide maps of DNA binding of the proteins in their hetero- and homodimeric forms

Evaluation of abdominal computed tomography findings in patients with COVID-19: a multicenter study

PURPOSE: To evaluate the frequency of abdominal computed tomography (CT) findings in patients with coronavirus disease-2019 (COVID-19) and interrogate the relationship between abdominal CT findings and patient demographic features, clinical findings, and laboratory test results as well as the CT atherosclerosis score in the abdominal aorta. METHODS: This study was designed as a multicenter retrospective study. The abdominal CT findings of 1.181 patients with positive abdominal symptoms from 26 tertiary medical centers with a positive polymerase chain-reaction test for severe acute respiratory syndrome coronavirus 2 were reviewed. The frequency of ischemic and non-ischemic CT findings as well as the association between CT findings, clinical features, and abdominal aortic calcific atherosclerosis score (AA-CAS) were recorded. RESULTS: Ischemic and non-ischemic abdominal CT findings were detected in 240 (20.3%) and 328 (27.7%) patients, respectively. In 147 patients (12.4%), intra-abdominal malignancy was present. The most frequent ischemic abdominal CT findings were bowel wall thickening (n = 120; 10.2%) and perivascular infiltration (n = 40; 3.4%). As for non-ischemic findings, colitis (n = 91; 7.7%) and small bowel inflammation (n = 73; 6.2%) constituted the most frequent disease processes. The duration of hospital stay was found to be higher in patients with abdominal CT findings than in patients without any positive findings (13.8 ± 13 vs. 10.4 ± 12.8 days, P < 0.001). The frequency of abdominal CT findings was significantly higher in patients who did not survive the infection than in patients who were discharged after recovery (41.7% vs. 27.4%, P < 0.001). Increased AA-CAS was found to be associated with a higher risk of ischemic conditions in abdominal CT examinations. CONCLUSION: Abdominal symptoms in patients with COVID-19 are usually associated with positive CT findings. The presence of ischemic findings on CT correlates with poor COVID-19 outcomes. A high AA-CAS is associated with abdominal ischemic findings in patients with COVID-19

Comparative analysis of MTP -493G/T and ABCG2 34G/A polymorphisms and theirs expression in HIV-associated lipodystrophy patients

HIV-associated lipodystrophy (HIVLD) is a metabolic condition with an irregularity in the production of lipoprotein particles, and its occurrence varies among HIV-infected patients. MTP and ABCG2 genes have a role in the transport of lipoproteins. The polymorphisms of MTP -493G/T and ABCG2 34G/A affect its expression and influence the secretion and transportation of lipoproteins. Hence, we investigated the MTP -493G/T and ABCG2 34G/A polymorphisms in 187 HIV-infected patients (64 with HIVLD and 123 without HIVLD) along with 139 healthy controls using polymerase chain reaction (PCR)-restriction fragment length polymorphism and expression analysis using real-time PCR. ABCG2 34A allele showed an insignificantly reduced risk of LDHIV severity [P = 0.07, odds ratio (OR) = 0.55]. MTP -493T allele exhibited a non-significantly reduced risk for the development of dyslipidemia (P = 0.08, OR = 0.71). In patients with HIVLD, the ABCG2 34GA genotype was linked with impaired low-density lipoprotein levels and showed a reduced risk for LDHIV severity (P = 0.04, OR = 0.17). In patients without HIVLD, the ABCG2 34GA genotype was associated with impaired triglyceride levels with marginal significance and showed an increased risk for the development of dyslipidemia (P = 0.07, OR = 2.76). The expression level of MTP gene was 1.22-fold decreased in patients without HIVLD compared with that in patients with HIVLD. ABCG2 gene was upregulated 2.16-fold in patients with HIVLD than in patients without HIVLD. In conclusion, MTP -493C/T polymorphism influences the expression level of MTP in patients without HIVLD. Individuals without HIVLD having ABCG2 34GA genotype with impaired triglyceride levels may facilitate dyslipidemia risk

Genetic Circuits Specifying the Lifetime and Speed of Biological Rhythms

Biological rhythms are ubiquitous in nature. Examples include daily cycles of rest and activity observed among most living organisms and annual cycles of hibernation and migration observed among animals and birds. However, the timekeeping mechanisms that underlie the vast majority of biological rhythms are not well understood. I chose the molting cycle of C. elegans as a scientific model to study this problem. C. elegans molt 4 times at regular time intervals. Each life stage of the animal consists of the intermolt, a 6 – 8 h period of feeding and locomotion, which is followed by the molt, and a 2 h period of sleep-like quiescence and remodeling of the exoskeleton. I found that transcriptional–post-transcriptional feedback loops among the conserved nuclear hormone receptor NHR-23 and the let-7 family of miRNAs govern both the pace of the molting cycle and the total number of molts. The negative feedback loop acts within a genetic oscillator – the molting cycle timer – to schedule the timing of reiterative molts and within an hourglass timer to schedule the extinction of the molting cycle in adulthood. Knockdown of nhr-23 slowed down the pace of the cycle, whereas forced expression of nhr-23 or inactivation of let-7s accelerated the pace of the cycle. Interactions between NHR-23 and let-7s drive the cyclical expression of nhr-23, let-7s and scores of downstream targets necessary for the process of molting. I also found that the oscillatory expression of nhr-23 is dampened in regular increments over the course of larval development; the dampening was dependent upon the activity of let-7s. Moreover, forced expression of nhr-23 was sufficient to trigger extra molts in sexually mature animals. I propose that the incremental dampening brings the levels of nhr-23 below a critical threshold, preventing entry into another molt. Both the core components and cis-regulatory elements of this timekeeping mechanism are conserved from nematodes to humans. Going further, I identified additional genes and molecules that either act upstream of NHR-23 and let-7s or in independent pathways to control the number of molts in C. elegans. An as-yet-unidentified hormone is thought to control molting by acting as a ligand for NHR-23. Consistent with this model, I show that dietary supplementation of cholesterol is necessary for forced expression of NHR-23 to trigger extra molts. Thus, cholesterol or a cholesterol-derivative might act as a native ligand for NHR-23. Using a reverse genetics approach, I also uncovered genes that might act in pathways for synthesis of the ligand. My findings might lead to discovery of a hormone that promotes molting in C. elegans—a long-standing question in the field. Further examination of how the molecular and genetic interactions uncovered in this thesis regulate the molting cycle could lead to a better understanding of developmental clocks, as well as the circadian clock and related sleep, metabolic and psychiatric disorders