Mutty, Christopher

Despite special challenges in the medical treatment of women with epilepsy, in particular preclinical animal studies were focused on males for decades and females have only recently moved into the focus of scientific interest. The intrahippocampal kainic acid (IHKA) mouse model of temporal lobe epilepsy (TLE) is one of the most studied models in males reproducing electroencephalographic (EEG) and histopathological features of human TLE. Hippocampal paroxysmal discharges (HPDs) were described as drug resistant focal seizures in males...

In the quest for novel treatments for patients with drug-resistant seizures, poor water solubility of potential drug candidates is a frequent obstacle. Literature indicated that the highly efficient solvent dimethyl sulfoxide (DMSO) may have a confounding influence in epilepsy research, reporting both pro- and antiepileptic effects. In this study, we aim to clarify the effects of DMSO on epileptiform activity in one of the most frequently studied models of chronic epilepsy, the intrahippocampal kainic acid (IHKA) mouse model, and in a model of acute seizures...

CASE: We report a case of a rare "floating fibula" ankle injury characterized by dislocation of the proximal tibiofibular joint (PTFJ), syndesmosis disruption, complete deltoid disruption, and tibiotalar dislocation without fibula fracture in a 44-year-old man. Imaging includes preoperative and postoperative radiographs and CT scans. Treatment involved reduction and screw fixation of the syndesmosis and PTFJ with planned screw removal. A successful clinical and radiographic outcome was achieved at the 15-month follow-up...

The development of curative treatments for mitochondrial diseases, which are often caused by mutations in mitochondrial DNA (mtDNA) that impair energy metabolism and other aspects of cellular homoeostasis, is hindered by an incomplete understanding of the underlying biology and a scarcity of cellular and animal models. Here we report the design and application of a library of double-stranded-DNA deaminase-derived cytosine base editors optimized for the precise ablation of every mtDNA protein-coding gene in the mouse mitochondrial genome...

Mitochondria contain a specific translation machinery for the synthesis of mitochondria-encoded respiratory chain components. Mitochondrial tRNAs (mt-tRNAs) are also generated from the mitochondrial DNA and, similar to their cytoplasmic counterparts, are post-transcriptionally modified. Here, we find that the RNA methyltransferase METTL8 is a mitochondrial protein that facilitates 3-methyl-cytidine (m3 C) methylation at position C32 of the mt-tRNASer(UCN) and mt-tRNAThr . METTL8 knockout cells show a reduction in respiratory chain activity, whereas overexpression increases activity...

Mitochondria contain their own translation apparatus which enables them to produce the polypeptides encoded in their genome. The mitochondrially-encoded RNA components of the mitochondrial ribosome require various post-transcriptional processing steps. Additional protein factors are required to facilitate the biogenesis of the functional mitoribosome. We have characterized a mitochondrially-localized protein, YbeY, which interacts with the assembling mitoribosome through the small subunit. Loss of YbeY leads to a severe reduction in mitochondrial translation and a loss of cell viability, associated with less accurate mitochondrial tRNASer(AGY) processing from the primary transcript and a defect in the maturation of the mitoribosomal small subunit...

Focal epilepsy represents one of the most common chronic CNS diseases. The high incidence of drug resistance, devastating comorbidities, and insufficient responsiveness to surgery pose unmet medical challenges. In the quest of novel, disease-modifying treatment strategies of neuropeptides represent promising candidates. Here, we provide the "proof of concept" that gene therapy by adeno-associated virus (AAV) vector transduction of preprodynorphin into the epileptogenic focus of well-accepted mouse and rat models for temporal lobe epilepsy leads to suppression of seizures over months...

In the lower extremity, compartment syndrome has been associated with fractures of the tibial plateau, shaft, and plafond. The patient was an 89-year-old male driver involved in a T-bone type motor vehicle accident. He sustained a closed transverse fibular shaft fracture and initially had fullness in his anterior/lateral compartments but no pain with passive and active range of motion of his ankle. Because of previous cardiac stenting, he was on dual anticoagulation therapy. Serial examination demonstrated tense compartments with notable pain during ankle range of motion...

Current literature is limited with respect to the proximal tibiofibular joint (PTFJ) and clinical conditions relating to the PTFJ. Diagnosis and treatment of conditions that affect the PTFJ are not well described and are a topic of debate among many physicians. This manuscript aims to review and summarize the most recent literature that relates to traumatic dislocations, fractures, chronic instability, and osteoarthritis, with a focus on both diagnostic and treatment strategies of these conditions. We also review PTFJ anatomy, biomechanics, and the clinical presentation of some common PTFJ conditions...

BACKGROUND: Few data exist on regional systems of care for the treatment of ST-segment-elevation myocardial infarction (STEMI) in developing countries. Our objective was to describe temporal trends in 30-day mortality and identify predictors of mortality among STEMI patients enrolled in a prospective registry in Brazil. METHODS AND RESULTS: From January 2011 to June 2013, 520 patients who received initial STEMI care at 23 nonspecialized public health units or hospitals, some of whom were transferred to a public cardiology referral center, were identified through a regional STEMI network supported by telemedicine and the local prehospital emergency medical service...

For AO 44-B2 ankle fractures of uncertain stability, the current diagnostic standard is to obtain a gravity stress radiograph, but some have advocated for the use of weight-bearing radiographs. The primary aim was to compare measures of medial clear space (MCS) on weight-bearing cone beam computed tomography (CBCT) scans versus gravity stress radiographs for determining the state of stability of ankle fractures classified as AO SER 44-B2 or Weber B. The secondary aim was to evaluate the details offered by CBCT scans with respect to other findings that may be relevant to patient care...

BACKGROUND: Diagnosis and treatment of acute or impending compartment syndrome (ACS) remains a clinical challenge. ACS is a clinical diagnosis, and may be associated with variation in its definition, as well as individual threshold for fasciotomy. We examined regional and state variation in rates of lower extremity fasciotomy associated with operatively managed tibia fractures. METHODS: A total of 313,344 surgically treated tibia fractures were identified via Current Procedural Terminology (CPT) codes using PearlDiver, a private-payer medical record database...

PURPOSE: We determined whether naturally-occurring lenticular myopia in English Springer spaniels (ESS) has a genetic component. METHODS: Streak retinoscopy was performed on 226 related ESS 30 minutes after the onset of pharmacologic mydriasis and cycloplegia. A pedigree was constructed to determine relationships between affected offspring and parents. Estimation of heritability was done in a Bayesian analysis (facilitated by the MCMCglmm package of R) of refractive error in a model, including terms for sex and coat color...

Donor site morbidity and complication rate using the reamer-irrigator-aspirator (RIA) system for intramedullary, non-structural autogenous bone graft harvesting were investigated in a retrospective chart and radiographic review at a University affiliated Level-1 Trauma Centre. 204 RIA procedures in 184 patients were performed between 1/1/2007 and 12/31/2010. RIA-indication was bone graft harvesting in 201 (98.5%), and intramedullary irrigation and debridement in 3 (1.5%) cases. Donor sites were: femur - antegrade 175, retrograde 4, tibia - antegrade 7, retrograde 18...

PURPOSE: To determine the effect of progressive addition lenses (PALs) and single vision lenses (SVLs) on peripheral defocus in myopic children, and to compare the effect of myopic versus hyperopic peripheral defocus on foveal myopia progression. METHODS: Eighty-four myopic children aged 6 to 11 years with spherical equivalent (SE) cycloplegic autorefraction between -0.75 diopters (D) and -4.50 D were randomly assigned to wear SVLs or PALs. Aberrometry measurements of the eye and spectacles were made centrally, 30° nasally, temporally, and superiorly, and 20° inferiorly on the retina using a Complete Ophthalmic Analysis System for Vision Research (COAS-VR)...

BACKGROUND: DNA methylation is a common regulator of gene expression, including acting as a regulator of developmental events and behavioral changes in adults. Using the unique system of genetic caste determination in Pogonomyrmex barbatus, we were able to document changes in DNA methylation during development, and also across both ancient and contemporary hybridization events. METHODOLOGY/PRINCIPAL FINDINGS: Sodium bisulfite sequencing demonstrated in vivo methylation of symmetric CG dinucleotides in P...

PURPOSE: Experimental models of human myopia have been developed using animals of various species. However, most of these are an induced rather than a spontaneous, naturally occurring myopia. This study was conducted to evaluate whether the spontaneous myopia found in three canine breeds was axial in nature and therefore similar to humans. METHODS: Refractive error was measured by cycloplegic retinoscopy and ocular components by A-scan ultrasound (ocular axial dimensions) and videophakometry (corneal and lens radii and powers) in 83 dogs of three breeds [English Springer Spaniels (n = 33), Toy Poodles (n = 36), and Collies (n = 14)]...

Tibial plateau fractures are complex injuries that can affect both knee function and stability. In the past, surgeons have relied on radiographs, viewboxes, tracing paper, and scaled acetate templates to formulate a preoperative plan. With the advent of digital radiography, viewboxes, and standard radiographs are no longer routinely available. The availability of a digital format for preoperative planning has helped to address this, but fragment manipulation and implant templating are not features of most digital radiography systems...

BACKGROUND: Diaphyseal and distal femoral fractures are painful injuries that are frequently seen in patients requiring a trauma work-up in the hospital emergency department prior to definitive management. The purpose of this study was to determine whether a femoral nerve block administered in the emergency department could provide better pain relief for patients with femoral fractures than currently used pain management practices. METHODS: Patients who presented with an acute diaphyseal or distal femoral fracture were identified as potential candidates for this study...

OBJECTIVE: To assess the refractive state of eyes in various breeds of dogs to identify breeds susceptible to ametropias. ANIMALS: 1,440 dogs representing 90 breeds. PROCEDURES: In each dog, 1 drop of 1% cyclopentolate or 1% tropicamide was applied to each eye, and a Canine Eye Registration Foundation examination was performed. Approximately 30 minutes after drops were administered, the refractive state of each eye was assessed via streak retinoscopy...