Targeted recruitment of a histone H4-specific methyltransferase by the transcription factor YY1

[[abstract]]Methylation of specific residues within the N-terminal histone tails plays a critical role in regulating eukaryotic gene expression. Although great advances have been made toward identifying histone methyltransferases (HMTs) and elucidating the consequences of histone methylation, little is known about the recruitment of HMTs to regulatory regions of chromatin. Here we report that the sequence-specific DNA-binding transcription factor Yin Yang 1 (YY1) binds to and recruits the histone H4 (Arg 3)-specific methyltransferase, PRMT1, to a YY1-activated promoter. Our data confirm that histone methylation does not occur randomly but rather is a targeted event and provides one mechanism by which HMTs can be recruited to chromatin to activate gene expression

Preliminary report of hepatitis B virus genotype prevalence in Iran

Aim: To determine the prevalence of hepatitis B virus (HBV) genotypes in Iranian hepatitis B surface antigen (HBsAg) carriers, chronic hepatitis B and cirrhotic patients. Methods: A total of 109 HBsAg-positive patients were included in this study. HBV genotypes were determined by using INNO-LiPA methodology which is based on the reverse hybridization principle. Results: The distribution of patients with different stages of liver disease was as follows: 95 (86.4) chronic hepatitis, 11 (10) liver cirrhosis, and 3 (2.7) inactive carrier. Of the chronic hepatitis and liver cirrhosis patients, 26.4 were HBeAg-positive while 70 were HBeAg-negative. Genotype D was the only detected type found in all patients. Conclusion: Classifying HBV into genotypes has to be cost-effective and clinically relevant. Our study indicates that HBV genotype D prevails in the Mediterranean area, Near and Middle East, and South Asia. Continued efforts for understanding HBV genotype through international co-operation will reveal further virological diffierences of the genotypes and their clinical relevance. © 2006 The WJG Press. All rights reserved

Favorable results after conservative management of 316 valproate intoxicated patients

Valproic acid (VPA) is an effective antiepileptic drug widely used worldwide. Despite several studies indicating the usefulness of intravenous L-carnitine in the treatment of VPA poisoning, this drug is not readily available in Iran. The aim of this study was to determine whether supportive care without antidote would result in acceptable outcomes in VPA poisoned patients. Materials and Methods: In an observational, retrospective, single-center case series, all patients >12-year-old with VPA overdose who had referred to a tertiary center between 2009 and 2013 were consecutively enrolled. Patients� demographic and presenting features, physical examinations, clinical management, laboratory data, and outcomes were recorded. Results: A total of 316 patients were enrolled with pure VPA toxicity. The most common presenting signs/symptoms were drowsiness, nausea and vomiting, vertigo, and headache. In the course of the disease, 14 patients (4.4) were intubated and three (0.9) required hemodialysis with mean dialysis sessions of two. Fourteen patients were admitted to Intensive Care Unit, and seizures occurred in five. The initial level of consciousness was lower in patients with poor outcome. The median ingested dose of VPA in patients who required dialysis was significantly higher (20 vs. 6 g; P = 0.006). Multivariate analyses revealed that coma on presentation was associated with a worse outcome (P = 0.001; odds ratio = 61.5, 95 CI = 5.8-646.7). Conclusion: Prognosis of VPA poisoned patients appears to be good even with supportive care. According to our study, older age, ingestion of higher amounts of VPA and lower PCO2, HCO3, base excess, and CPK levels prone the patients to more severe toxicities in univariate analysis, but the main poor prognostic factor is coma on presentation in multivariate analysis. © 2015 Journal of Research in Medical Sciences

On-resin N-methylation of cyclic peptides for discovery of orally bioavailable scaffolds.

Backbone N-methylation is common among peptide natural products and has a substantial impact on both the physical properties and the conformational states of cyclic peptides. However, the specific impact of N-methylation on passive membrane diffusion in cyclic peptides has not been investigated systematically. Here we report a method for the selective, on-resin N-methylation of cyclic peptides to generate compounds with drug-like membrane permeability and oral bioavailability. The selectivity and degree of N-methylation of the cyclic peptide was dependent on backbone stereochemistry, suggesting that conformation dictates the regiochemistry of the N-methylation reaction. The permeabilities of the N-methyl variants were corroborated by computational studies on a 1,024-member virtual library of N-methyl cyclic peptides. One of the most permeable compounds, a cyclic hexapeptide (molecular mass = 755 Da) with three N-methyl groups, showed an oral bioavailability of 28% in rat

Clinically Significant Gains in Skillful Grasp Coordination by an Individual With Tetraplegia Using an Implanted Brain-Computer Interface With Forearm Transcutaneous Muscle Stimulation

© 2019 American Congress of Rehabilitation Medicine Objective: To demonstrate naturalistic motor control speed, coordinated grasp, and carryover from trained to novel objects by an individual with tetraplegia using a brain-computer interface (BCI)-controlled neuroprosthetic. Design: Phase I trial for an intracortical BCI integrated with forearm functional electrical stimulation (FES). Data reported span postimplant days 137 to 1478. Setting: Tertiary care outpatient rehabilitation center. Participant: A 27-year-old man with C5 class A (on the American Spinal Injury Association Impairment Scale) traumatic spinal cord injury Interventions: After array implantation in his left (dominant) motor cortex, the participant trained with BCI-FES to control dynamic, coordinated forearm, wrist, and hand movements. Main Outcome Measures: Performance on standardized tests of arm motor ability (Graded Redefined Assessment of Strength, Sensibility, and Prehension [GRASSP], Action Research Arm Test [ARAT], Grasp and Release Test [GRT], Box and Block Test), grip myometry, and functional activity measures (Capabilities of Upper Extremity Test [CUE-T], Quadriplegia Index of Function-Short Form [QIF-SF], Spinal Cord Independence Measure–Self-Report [SCIM-SR]) with and without the BCI-FES. Results: With BCI-FES, scores improved from baseline on the following: Grip force (2.9 kg); ARAT cup, cylinders, ball, bar, and blocks; GRT can, fork, peg, weight, and tape; GRASSP strength and prehension (unscrewing lids, pouring from a bottle, transferring pegs); and CUE-T wrist and hand skills. QIF-SF and SCIM-SR eating, grooming, and toileting activities were expected to improve with home use of BCI-FES. Pincer grips and mobility were unaffected. BCI-FES grip skills enabled the participant to play an adapted “Battleship” game and manipulate household objects. Conclusions: Using BCI-FES, the participant performed skillful and coordinated grasps and made clinically significant gains in tests of upper limb function. Practice generalized from training objects to household items and leisure activities. Motor ability improved for palmar, lateral, and tip-to-tip grips. The expects eventual home use to confer greater independence for activities of daily living, consistent with observed neurologic level gains from C5-6 to C7-T1. This marks a critical translational step toward clinical viability for BCI neuroprosthetics

Are serial hematocrit measurements sensitive enough to predict intra-abdominal injuries in blunt abdominal trama?

Objective: Routine serial hematocrit measurements are a component of the trauma evaluation for patients without serious injury identified on initial evaluation. We sought to determine whether serial hematocrit testing was useful in predicting the probable injuries in blunt abdominal trauma. Materials and method: We performed a prospective study of trauma patients admitted in our observation unit over a 12-month period. Patients routinely underwent serial hematocrit testing in 6-hour intervals (two hematocrit levels). We compared trauma patients with a hematocrit drop of 5 and 10 points or more to those without a significant hematocrit drop. Results: Five hundred forty-two isolated blunt abdominal trauma patients were admitted to observation unit, and 468 patients (86.35) had serial hematocrit during their 6-hour stay. Of these patients, 36.11 had a hematocrit drop of 5 or more and 12.61 a drop of 10 or more. Of patients with the hematocrit drop >10, 50.8 have had diagnostic manifestations of intra-abdominal injury in both ultrasonographic and computed tomography scanning (P5 and positive imaging. Conclusion: Although serial hematocrit testing may be useful in specific situations, routine use of serial hematocrit testing in trauma patients at a level I trauma center�s observation unit did not significantly aid in the prediction of occult injuries. © 2019 Mosaddegh et al

Electrocardiographic changes in patients with tramadol-induced idiosyncratic seizures

Objectives To assess ECG changes in patients with tramadol-induced seizure(s) and compare these changes in lower and higher than 500 mg tramadol doses as a main goal. Material and methods In an analytical-cross sectional manner over 1 year, 170 patients with idiosyncratic seizure(s) after using tramadol, were studied. Full data were recorded for each patient. ECGs were taken from all the patients on admission and 1 h later and were assessed for findings. Results 70 of 170 patients (41.2) had used lower than 500 mg doses of tramadol while 90 patients (52.9) were included in the high dose group. Rate of female patients in the high dose group was significantly higher. The average age of patients in the high dose group was significantly lower (22.04 vs 25.76). The high dose group had significantly higher heart rates. There was no history of cardiovascular diseases; two patients had previous history of seizure. No significant difference was shown between low dose and high dose groups from the point of ECG changes. Discussion and conclusion Using doses higher than 500 mg is more frequently seen in women, young people and those who have not experienced previous use of tramadol. Terminal S wave, sinus tachycardia, and terminal R wave in the lead aVR are among the most common ECG changes in tramadol users. © 2016 The Emergency Medicine Association of Turke

Structural Attributes and Photodynamics of Visible Spectrum Quantum Emitters in Hexagonal Boron Nitride

Newly discovered van der Waals materials like MoS2, WSe2, hexagonal boron nitride (h-BN), and recently C2N have sparked intensive research to unveil the quantum behavior associated with their 2D structure. Of great interest are 2D materials that host single quantum emitters. h-BN, with a band gap of 5.95 eV, has been shown to host single quantum emitters which are stable at room temperature in the UV and visible spectral range. In this paper we investigate correlations between h-BN structural features and emitter location from bulk down to the monolayer at room temperature. We demonstrate that chemical etching and ion irradiation can generate emitters in h-BN. We analyze the emitters' spectral features and show that they are dominated by the interaction of their electronic transition with a single Raman active mode of h-BN. Photodynamics analysis reveals diverse rates between the electronic states of the emitter. The emitters show excellent photo stability even under ambient conditions and in monolayers. Comparing the excitation polarization between different emitters unveils a connection between defect orientation and the h-BN hexagonal structure. The sharp spectral features, color diversity, room-temperature stability, long-lived metastable states, ease of fabrication, proximity of the emitters to the environment, outstanding chemical stability, and biocompatibility of h-BN provide a completely new class of systems that can be used for sensing and quantum photonics applications

Imaging of ependymomas: MRI and CT

The imaging features of intracranial and spinal ependymoma are reviewed with an emphasis on conventional magnetic resonance imaging (MRI), perfusion MRI and proton magnetic resonance spectroscopy, and computed tomography. Imaging manifestations of leptomeningeal dissemination of disease are described. Finally, salient imaging features obtained in the postoperative period to evaluate completeness of surgical resection, and thereafter for long-term surveillance for disease recurrence, are reviewed

Which executive functioning deficits are associated with AD/HD, ODD/CD and comorbid AD/HD+ODD/CD?

Item does not contain fulltextThis study investigated (1) whether attention deficit/hyperactivity disorder (AD/HD) is associated with executive functioning (EF) deficits while controlling for oppositional defiant disorder/conduct disorder (ODD/CD), (2) whether ODD/CD is associated with EF deficits while controlling for AD/HD, and (3)~whether a combination of AD/HD and ODD/CD is associated with EF deficits (and the possibility that there is no association between EF deficits and AD/HD or ODD/CD in isolation). Subjects were 99~children ages 6–12 years. Three putative domains of EF were investigated using well-validated tests: verbal fluency, working memory, and planning. Independent of ODD/CD, AD/HD was associated with deficits in planning and working memory, but not in verbal fluency. Only teacher rated AD/HD, but not parent rated AD/HD, significantly contributed to the prediction of EF task performance. No EF deficits were associated with ODD/CD. The presence of comorbid AD/HD accounts for the EF deficits in children with comorbid AD/HD+ODD/CD. These results suggest that EF deficits are unique to AD/HD and support the model proposed by R. A. Barkley (1997).17 p