Owner satisfaction and prognosis for return to work after pancarpal arthrodesis in working dogs in the United Kingdom: a retrospective study (2011-2020).

Background: Pancarpal arthrodesis (PCA) is a commonly performed procedure in the UK. However, it is not known whether working dogs in the UK and other European countries with carpal injuries that have undergone unilateral PCA are able to return to working ability as determined by the owner. Medical records from a referral hospital in the UK were reviewed retrospectively for cases of working dogs treated using unilateral PCA.

Stargardt macular dystrophy and therapeutic approaches.

Stargardt macular dystrophy (Stargardt disease; STGD1; OMIM 248200) is the most prevalent inherited macular dystrophy. STGD1 is an autosomal recessive disorder caused by multiple pathogenic sequence variants in the large gene (OMIM 601691). Major advances in understanding both the clinical and molecular features, as well as the underlying pathophysiology, have culminated in many completed, ongoing and planned human clinical trials of novel therapies.

VLDL receptor gene therapy for reducing atherogenic lipoproteins.

Over the past 40 years, there has been considerable research into the management and treatment of atherogenic lipid disorders. Although the majority of treatments and management strategies for cardiovascular disease (CVD) center around targeting low-density lipoprotein cholesterol (LDL-C), there is mounting evidence for the residual CVD risk attributed to high triglyceride (TG) and lipoprotein(a) (Lp(a)) levels despite the presence of lowered LDL-C levels. Among the biological mechanisms for clearing TG-rich lipoproteins, the VLDL receptor (VLDLR) plays a key role in the trafficking and metabolism of lipoprotein particles in multiple tissues, but it is not ordinarily expressed in the liver.

Screening of Anaesthetics in Adult Zebrafish () for the Induction of Euthanasia by Overdose.

Zebrafish are often euthanized by overdose of anaesthesia. However, fish may have aversion towards some anaesthetics, and protocol efficacy varies between species. Using wild type adult , we assessed time to loss of opercular beat, righting, and startle reflexes during induction of anaesthetic overdose by either tricaine (0.

Orbital atherectomy for treating calcified iliac artery disease to enable large bore device delivery: A case series report.

The current standard of care for the treatment of flow-limiting calcific iliac artery disease is balloon angioplasty and subsequent stent placement. However, the presence of calcified lesions may prevent adequate stent expansion or impede the delivery of large bore devices, such as those for transcatheter aortic valve replacement or endovascular aneurysm repair implants. Plaque modification through vessel preparation with orbital atherectomy may enable stent expansion and subsequent proper large device delivery with low rates of procedural complications.

Dementia assessment and management in primary care settings: a survey of current provider practices in the United States.

Background: Primary care providers (PCPs) are typically the first to screen and evaluate patients for neurocognitive disorders (NCDs), including mild cognitive impairment and dementia. However, data on PCP attitudes and evaluation and management practices are sparse. Our objective was to quantify perspectives and behaviors of PCPs and neurologists with respect to NCD evaluation and management.

Impact of a Nutrition-Focused Quality Improvement Intervention on Hospital Length of Stay.

Background: Despite its high prevalence, malnutrition in hospitalized patients often goes unrecognized and undertreated.

Local Problem: A hospital system sought to improve nutrition care by implementing a quality improvement initiative. Nurses screened patients upon admission using the Malnutrition Screening Tool and initiated oral nutrition supplements for patients at risk.

Rescue of Learning and Memory Deficits in the Human Nonsyndromic Intellectual Disability Cereblon Knock-Out Mouse Model by Targeting the AMP-Activated Protein Kinase-mTORC1 Translational Pathway.

A homozygous nonsense mutation in the cereblon () gene results in autosomal recessive, nonsyndromic intellectual disability that is devoid of other phenotypic features, suggesting a critical role of CRBN in mediating learning and memory. In this study, we demonstrate that adult male knock-out () mice exhibit deficits in hippocampal-dependent learning and memory tasks that are recapitulated by focal knock-out of Crbn in the adult dorsal hippocampus, with no changes in social or repetitive behavior. Cellular studies identify deficits in long-term potentiation at Schaffer collateral CA1 synapses.

The Brain Health Assessment for Detecting and Diagnosing Neurocognitive Disorders.

Background/objectives: Brief cognitive screens lack the sensitivity to detect mild cognitive impairment (MCI) or support differential diagnoses. The objective of this study was to validate the 10-minute, tablet-based University of California, San Francisco (UCSF) Brain Health Assessment (BHA) to overcome these limitations.

Design: Cross-sectional.

Frequency of frontotemporal dementia gene variants in , , and in academic versus commercial laboratory cohorts.

Background: Frontotemporal lobar degeneration (FTLD) is a leading cause of dementia, and elucidating its genetic underpinnings is critical. FTLD research centers typically recruit patient cohorts that are limited by the center's specialty and the ways in which its geographic location affects the ethnic makeup of research participants. Novel sources of data are needed to get population estimates of the contribution of variants in known FTLD-associated genes.

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

We developed a rules-based scoring system to classify DNA variants into five categories including pathogenic, likely pathogenic, variant of uncertain significance (VUS), likely benign, and benign. Over 16,500 pathogenicity assessments on 11,894 variants from 338 genes were analyzed for pathogenicity based on prediction tools, population frequency, co-occurrence, segregation, and functional studies collected from internal and external sources. Scores were calculated by trained scientists using a quantitative framework that assigned differential weighting to these five types of data.

Molecular combing compared to Southern blot for measuring D4Z4 contractions in FSHD.

We compare molecular combing to Southern blot in the analysis of the facioscapulohumeral muscular dystrophy type 1 locus (FSHD1) on chromosome 4q35-qter (chr 4q) in genomic DNA specimens sent to a clinical laboratory for FSHD testing. A de-identified set of 87 genomic DNA specimens determined by Southern blot as normal (n = 71), abnormal with D4Z4 macrosatellite repeat array contractions (n = 7), indeterminate (n = 6), borderline (n = 2), or mosaic (n = 1) was independently re-analyzed by molecular combing in a blinded fashion. The molecular combing results were identical to the Southern blot results in 75 (86%) of cases.

A brief review of recent Charcot-Marie-Tooth research and priorities.

This brief review of current research progress on Charcot-Marie-Tooth (CMT) disease is a summary of discussions initiated at the Hereditary Neuropathy Foundation (HNF) scientific advisory board meeting on November 7, 2014. It covers recent published and unpublished in vitro and in vivo research. We discuss recent promising preclinical work for CMT1A, the development of new biomarkers, the characterization of different animal models, and the analysis of the frequency of gene mutations in patients with CMT.

The allelic spectrum of Charcot-Marie-Tooth disease in over 17,000 individuals with neuropathy.

We report the frequency, positive rate, and type of mutations in 14 genes (PMP22, GJB1, MPZ, MFN2, SH3TC2, GDAP1, NEFL, LITAF, GARS, HSPB1, FIG4, EGR2, PRX, and RAB7A) associated with Charcot-Marie-Tooth disease (CMT) in a cohort of 17,880 individuals referred to a commercial genetic testing laboratory. Deidentified results from sequencing assays and multiplex ligation-dependent probe amplification (MLPA) were analyzed including 100,102 Sanger sequencing, 2338 next-generation sequencing (NGS), and 21,990 MLPA assays. Genetic abnormalities were identified in 18.

Mechanism, prevalence, and more severe neuropathy phenotype of the Charcot-Marie-Tooth type 1A triplication.

Copy-number variations cause genomic disorders. Triplications, unlike deletions and duplications, are poorly understood because of challenges in molecular identification, the choice of a proper model system for study, and awareness of their phenotypic consequences. We investigated the genomic disorder Charcot-Marie-Tooth disease type 1A (CMT1A), a dominant peripheral neuropathy caused by a 1.

Lack of association between autism and anti-GM1 ganglioside antibody.

Forty of 54 children with autism were reported to have an elevated antibody response to GM1 ganglioside that correlated with disease severity. Antiganglioside autoantibodies, especially those directed at GM1, are known to be associated with and play a pathogenic role in some immune-mediated peripheral neuropathies. The presumed link between autism and anti-GM1 antibodies, therefore, implies that testing may identify a sizable subset of patients who would benefit from immunomodulatory therapy.

Relationships among grocery nutrition label users and consumers' attitudes and behavior toward restaurant menu labeling.

In the United States (US), based on the 2010 Affordable Care Act, restaurant chains and similar retail food establishments with 20 or more locations are required to begin implementing calorie information on their menus. As enacting of the law begins, it is important to understand its potential for improving consumers' healthful behaviors. Therefore, the objective of this study was to explore relationships among users of grocery nutrition labels and attitudes toward restaurant menu labeling, along with the caloric content of their restaurant menu selection.

Markers of Celiac Disease and Gluten Sensitivity in Children with Autism.

Objective: Gastrointestinal symptoms are a common feature in children with autism, drawing attention to a potential association with celiac disease or gluten sensitivity. However, studies to date regarding the immune response to gluten in autism and its association with celiac disease have been inconsistent. The aim of this study was to assess immune reactivity to gluten in pediatric patients diagnosed with autism according to strict criteria and to evaluate the potential link between autism and celiac disease.

Behavioral characterization of cereblon forebrain-specific conditional null mice: a model for human non-syndromic intellectual disability.

A nonsense mutation in the human cereblon gene (CRBN) causes a mild type of autosomal recessive non-syndromic intellectual disability (ID). Animal studies show that crbn is a cytosolic protein with abundant expression in the hippocampus (HPC) and neocortex (CTX). Its diverse functions include the developmental regulation of ion channels at the neuronal synapse, the mediation of developmental programs by ubiquitination, and a target for herpes simplex type I virus in HPC neurons.

Mutations in FLVCR1 cause posterior column ataxia and retinitis pigmentosa.

The study of inherited retinal diseases has advanced our knowledge of the cellular and molecular mechanisms involved in sensory neural signaling. Dysfunction of two specific sensory modalities, vision and proprioception, characterizes the phenotype of the rare, autosomal-recessive disorder posterior column ataxia and retinitis pigmentosa (PCARP). Using targeted DNA capture and high-throughput sequencing, we analyzed the entire 4.

Temporal and spatial mouse brain expression of cereblon, an ionic channel regulator involved in human intelligence.

A mild form of autosomal recessive, nonsyndromal intellectual disability (ARNSID) in humans is caused by a homozygous nonsense mutation in the cereblon gene (mutCRBN). Rodent crbn protein binds to the intracellular C-terminus of the large conductance Ca(2+)-activated K(+)channel (BK(Ca)). An mRNA variant (human SITE 2 INSERT or mouse strex) of the BK(Ca) gene (KCNMA1) that is normally expressed during embryonic development is aberrantly expressed in mutCRBN human lymphoblastoid cell lines (LCLs) as compared to wild-type (wt) LCLs.

A nonverbal learning disability in a case of central hypoventilation syndrome without a PHOX2B gene mutation.

This study examines the neuropsychological profile of a boy with congenital central hypoventilation syndrome (CCHS) without a paired-like homeobox gene (PHOX2B) mutation. CCHS is a rare disorder of autonomic nervous system development characterized by an impaired ventilatory response to hypercarbia and hypoxemia. Mild intellectual deficits are common but a specific cognitive profile is not established in CCHS.