Carbamazepine-Induced Tics

A variety of movement disorders are known to occur in association with carbamazepine (CBZ) therapy in adults and children, but development of tics has been described infrequently and only in patients with underlying Tourette's syndrome or other movement disorders. We report 3 children with epilepsy who developed facial motor tics after initiation of CBZ for complex partial seizures. All 3 had documented CBZ blood levels in the therapeutic range at the time, and none had other symptoms or signs of clinical intoxication. Neurologic examinations were normal in 2 and showed developmental de lay of expressive language in the third. Brain imaging was normal in all. After development of the tics in 2, CBZ was continued at the same or higher dose, and the tics abated and then ceased spontaneously ≤6 months. In the third child, the tics ceased after CBZ discontinuation. These cases demonstrate that CBZ can induce simple motor tics in children. These idiosyncratic reactions may be transient and do not always necessitate drug discontinuation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66313/1/j.1528-1157.1993.tb02119.x.pd

Study of heterogeneous nucleation of eutectic Si in high-purity Al-Si alloys with Sr addition

The official published version can be accessed from the link below - Copyright @ 2010 The Minerals, Metals & Materials Society and ASM InternationalAl-5 wt pct Si master-alloys with controlled Sr and/or P addition/s were produced using super purity Al 99.99 wt pct and Si 99.999 wt pct materials in an arc melter. The master-alloy was melt-spun resulting in the production of thin ribbons. The Al matrix of the ribbons contained entrained Al-Si eutectic droplets that were subsequently investigated. Differential scanning calorimetry, thermodynamic calculations, and transmission electron microscopy techniques were employed to examine the effect of the Sr and P additions on eutectic undercoolings and nucleation phenomenon. Results indicate that, unlike P, Sr does not promote nucleation. Increasing Sr additions depressed the eutectic nucleation temperature. This may be a result of the formation of a Sr phase that could consume or detrimentally affect potent AlP nucleation sites.This work is financially supported by the Higher Education Commission of Pakistan and managerially supported from the OAD

Designing a Locally Manufacturable Wheelchair for Nepal

Persons with disabilities in developing countries often lack the basic equipment needed to assist them in their daily lives. International Nepal Fellowship (INF) is a Christian medical organization located in Nepal that provides medical care and assistance to people with disabilities and other conditions. Currently, INF imports expensive wheelchairs that undergo a prolonged border process before being received. INF has reached out to the Collaboratory to design a wheelchair that can withstand the challenges of Nepal’s terrain and can be manufactured from local materials. The Nepal Wheelchair team accepted this challenge and set out to design a wheelchair that can fulfill their needs. The team began by researching wheelchair models for inspiration and eventually settled on two preliminary designs. In January 2020, the team traveled to Pokhara, Nepal to gain feedback from the staff at INF and select a final design based on their comments. During this trip, the team acquired and brought back locally available materials and parts available in Nepal in order to construct a prototype. This year, prototyping has been completed for the following elements: the central frame, wheel lock, footrest, wheel mounting assemblies and armrest fixtures. As a result of knowledge gained during prototyping, some design changes to the wheelchair have been made. Moving forward, the team will test the overall prototype for durability and prepare a manufacturing manual for INF.https://mosaic.messiah.edu/engr2021/1010/thumbnail.jp

Revealing heterogeneous nucleation of primary Si and eutectic Si by AlP in hypereutectic Al-Si alloys

The heterogeneous nucleation of primary Si and eutectic Si can be attributed to the presence of AlP. Although P, in the form of AlP particles, is usually observed in the centre of primary Si, there is still a lack of detailed investigations on the distribution of P within primary Si and eutectic Si in hypereutectic Al-Si alloys at the atomic scale. Here, we report an atomic-scale experimental investigation on the distribution of P in hypereutectic Al-Si alloys. P, in the form of AlP particles, was observed in the centre of primary Si. However, no significant amount of P was detected within primary Si, eutectic Si and the Al matrix. Instead, P was observed at the interface between the Al matrix and eutectic Si, strongly indicating that P, in the form of AlP particles (or AlP ‘patch’ dependent on the P concentration), may have nucleated on the surface of the Al matrix and thereby enhanced the heterogeneous nucleation of eutectic Si. The present investigation reveals some novel insights into heterogeneous nucleation of primary Si and eutectic Si by AlP in hypereutectic Al-Si alloys and can be used to further develop heterogeneous nucleation mechanisms based on adsorption

Estimating trace deposition time with circadian biomarkers: a prospective and versatile tool for crime scene reconstruction

Linking biological samples found at a crime scene with the actual crime event represents the most important aspect of forensic investigation, together with the identification of the sample donor. While DNA profiling is well established for donor identification, no reliable methods exist for timing forensic samples. Here, we provide for the first time a biochemical approach for determining deposition time of human traces. Using commercial enzyme-linked immunosorbent assays we showed that the characteristic 24-h profiles of two circadian hormones, melatonin (concentration peak at late night) and cortisol (peak in the morning) can be reproduced from small samples of whole blood and saliva. We further demonstrated by analyzing small stains dried and stored up to 4 weeks the in vitro stability of melatonin, whereas for cortisol a statistically significant decay with storage time was observed, although the hormone was still reliably detectable in 4-week-old samples. Finally, we showed that the total protein concentration, also assessed using a commercial assay, can be used for normalization of hormone signals in blood, but less so in saliva. Our data thus demonstrate that estimating normalized concentrations of melatonin and cortisol represents a prospective approach for determining deposition time of biological trace samples, at least from blood, with promising expectations for forensic applications. In the broader context, our study opens up a new field of circadian biomarkers for deposition timing of forensic traces; future studies using other circadian biomarkers may reveal if the time range offered by the two hormones studied here can be specified more exactly

2D-electrophoresis and multiplex immunoassay proteomic analysis of different body fluids and cellular components reveal known and novel markers for extended fasting

Proteomic technologies applied for profiling human biofluids and blood cells are considered to reveal new biomarkers of exposure or provide insights into novel mechanisms of adaptation

Differential effects of selenium and knock-down of glutathione peroxidases on TNFα and flagellin inflammatory responses in gut epithelial cells

Selenium (Se) is essential for human health. Despite evidence that Se intake affects inflammatory responses, the mechanisms by which Se and the selenoproteins modulate inflammatory signalling, especially in the gut, are not yet defined. The aim of this work was to assess effects of altered Se supply and knock-down of individual selenoproteins on NF-κB activation in gut epithelial cells. Caco-2 cells were stably transfected with gene constructs expressing luciferase linked either to three upstream NF-κB response elements and a TATA box or only a TATA box. TNFα and flagellin activated NF-κB-dependent luciferase activity and increased IL-8 expression. Se depletion decreased expression of glutathione peroxidase1 (GPX1) and selenoproteins H and W and increased TNFα-stimulated luciferase activity, endogenous IL-8 expression and reactive oxygen species (ROS) production. These effects were not mimicked by independent knock-down of either GPX1, selenoprotein H or W; indeed, GPX1 knock-down lowered TNFα-induced NF-κB activation and did not affect ROS levels. GPX4 knock-down decreased NF-κB activation by flagellin but not by TNFα. We hypothesise that Se depletion alters the pattern of expression of multiple selenoproteins that in turn increases ROS and modulates NF-κB activation in epithelial cells, but that the effect of GPX1 knock-down is ROS-independent

Cultivation and sequencing of rumen microbiome members from the Hungate1000 Collection

Productivity of ruminant livestock depends on the rumen microbiota, which ferment indigestible plant polysaccharides into nutrients used for growth. Understanding the functions carried out by the rumen microbiota is important for reducing greenhouse gas production by ruminants and for developing biofuels from lignocellulose. We present 410 cultured bacteria and archaea, together with their reference genomes, representing every cultivated rumen-associated archaeal and bacterial family. We evaluate polysaccharide degradation, short-chain fatty acid production and methanogenesis pathways, and assign specific taxa to functions. A total of 336 organisms were present in available rumen metagenomic data sets, and 134 were present in human gut microbiome data sets. Comparison with the human microbiome revealed rumen-specific enrichment for genes encoding de novo synthesis of vitamin B 12, ongoing evolution by gene loss and potential vertical inheritance of the rumen microbiome based on underrepresentation of markers of environmental stress. We estimate that our Hungate genome resource represents â 1/475% of the genus-level bacterial and archaeal taxa present in the rumen. © 2018 Nature Publishing Group. All rights reserved

Cell Death by SecTRAPs: Thioredoxin Reductase as a Prooxidant Killer of Cells

BACKGROUND: SecTRAPs (selenium compromised thioredoxin reductase-derived apoptotic proteins) can be formed from the selenoprotein thioredoxin reductase (TrxR) by targeting of its selenocysteine (Sec) residue with electrophiles, or by its removal through C-terminal truncation. SecTRAPs are devoid of thioredoxin reductase activity but can induce rapid cell death in cultured cancer cell lines by a gain of function. PRINCIPAL FINDINGS: Both human and rat SecTRAPs killed human A549 and HeLa cells. The cell death displayed both apoptotic and necrotic features. It did not require novel protein synthesis nor did it show extensive nuclear fragmentation, but it was attenuated by use of caspase inhibitors. The redox active disulfide/dithiol motif in the N-terminal domain of TrxR had to be maintained for manifestation of SecTRAP cytotoxicity. Stopped-flow kinetics showed that NADPH can reduce the FAD moiety in SecTRAPs at similar rates as in native TrxR and purified SecTRAPs could maintain NADPH oxidase activity, which was accelerated by low molecular weight substrates such as juglone. In a cellular context, SecTRAPs triggered extensive formation of reactive oxygen species (ROS) and consequently antioxidants could protect against the cell killing by SecTRAPs. CONCLUSIONS: We conclude that formation of SecTRAPs could contribute to the cytotoxicity seen upon exposure of cells to electrophilic agents targeting TrxR. SecTRAPs are prooxidant killers of cells, triggering mechanisms beyond those of a mere loss of thioredoxin reductase activity