Intra-amniotic antisense oligonucleotide treatment improves phenotypes in preclinical models of spinal muscular atrophy.

Neurological disorders with onset before or at birth are a leading cause of morbidity and mortality in infants and children. Prenatal treatment has the potential to reduce or prevent irreversible neuronal loss and facilitate normal neurodevelopment. We hypothesized that antisense oligonucleotides (ASOs) delivered to the amniotic fluid by intra-amniotic (IA) injection could safely distribute to the fetal central nervous system (CNS) and provide therapeutic benefit in the motor neuron disease spinal muscular atrophy (SMA), caused by mutations of the survival of motor neuron 1 gene (), leading to deficiency of SMN protein.

Adeno-Associated Virus Type 9-Mediated Gene Therapy of Choline Acetyltransferase-Deficient Mice.

The enzyme choline acetyltransferase (ChAT) synthesizes acetylcholine from acetyl-CoA and choline at the neuromuscular junction and at the nerve terminals of cholinergic neurons. Mutations in the ChAT gene () result in a presynaptic congenital myasthenic syndrome (CMS) that often associates with life-threatening episodes of apnea. Knockout mice for die at birth.

Poor Air Quality Is Linked to Stress in Honeybees and Can Be Compounded by the Presence of Disease.

Climate change-related extreme weather events have manifested in the western United States as warmer and drier conditions with an increased risk of wildfires. Honeybees, essential for crop pollination in California, are at the center of these extreme weather events. We associated the maximum daily temperature and air quality index values with the performance of colonies placed in wildfire-prone areas and determined the impact of these abiotic stressors on gene expression and histopathology.

A practical approach to the sampling, fixation, softening, and sectioning of whole honey bees for histologic evaluation.

The Western honey bee () is economically important as the primary managed pollinator of many agricultural crops and for the production of various hive-related commodities. Honey bees are not classically or thoroughly covered in veterinary pathology training programs. Given their unique anatomic and biological differences from the other species more traditionally evaluated by veterinary pathologists, establishing routine and consistent methods for processing samples for histology ensures accurate diagnostic and research conclusions.

Oculosystemic pneumocystosis in 2 sibling Chihuahuas.

Sibling female and male Chihuahuas were evaluated for a 9-month history of tachypnea that failed to respond to fenbendazole, doxycycline, amoxicillin-clavulanate, and prednisone. Physical examination identified tachypnea, hyperpnea, and harsh bronchovesicular lung sounds. Fundic examination disclosed diffuse chorioretinitis, manifested as multifocal chorioretinal granulomas in the female dog and occasional chorioretinal scars in the male dog.

Investigation of monotherapy and combined anticoronaviral therapies against feline coronavirus serotype II in vitro.

Objectives: Feline infectious peritonitis (FIP), caused by genetic mutants of feline enteric coronavirus known as FIPV, is a highly fatal disease of cats with no currently available vaccine or US Food and Drug Administration-approved cure. Dissemination of FIPV in affected cats results in a range of clinical signs, including cavitary effusions, anorexia, fever and lesions of pyogranulomatous vasculitis and perivasculitis, with or without central nervous system or ocular involvement. The objectives of this study were to screen an array of antiviral compounds for anti-FIPV (serotype II) activity, determine cytotoxicity safety profiles of identified compounds with anti-FIPV activity and strategically combine identified monotherapies to assess compound synergy against FIPV in vitro.

Application of neuropsychological criteria to classify mild cognitive impairment in the active study.

Comprehensive neuropsychological criteria (NP criteria) for mild cognitive impairment (MCI) has reduced diagnostic errors and better predicted progression to dementia than conventional MCI criteria that rely on a single impaired score and/or subjective report. This study aimed to implement an actuarial approach to classifying MCI in the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) study. ACTIVE study participants ( = 2,755) were classified as cognitively normal (CN) or as having MCI using NP criteria.

Identification of mild cognitive impairment in ACTIVE: algorithmic classification and stability.

Rates of mild cognitive impairment (MCI) have varied substantially, depending on the criteria used and the samples surveyed. The present investigation used a psychometric algorithm for identifying MCI and its stability to determine if low cognitive functioning was related to poorer longitudinal outcomes. The Advanced Cognitive Training of Independent and Vital Elders (ACTIVE) study is a multi-site longitudinal investigation of long-term effects of cognitive training with older adults.

Dual-task effects of simulated lane navigation and story recall in older adults with and without memory impairment.

While driving is a complex task, it becomes relatively automatic over time although unfamiliar situations require increased cognitive effort. Much research has examined driving risk in cognitively impaired elders and found little effect. This study assessed whether mildly memory impaired elders made disproportionate errors in driving or story recall, under simultaneous simulated driving and story recall.

Modeling change in memory performance and memory perceptions: findings from the ACTIVE study.

Within the context of the ACTIVE study, the current investigation explored the relationships between objective memory and two components of subjective memory (frequency of forgetting and use of external aids) over a five-year period. Relationships were assessed using parallel process latent growth curve models. Results indicated that changes in objective memory were associated with changes in perceived frequency of forgetting, but not with use of external aids (calendars, reminder notes) over time.

The use of the Modified Telephone Interview for Cognitive Status (TICS-M) in the detection of amnestic mild cognitive impairment.

Many screening tools for detecting cognitive decline require in-person assessment, which is often not cost-effective or feasible for those with physical limitations. The Modified Telephone Interview for Cognitive Status has been used for screening dementia, but little is known about its usefulness in detecting amnestic mild cognitive impairment. Community-dwelling participants (mean age=74.

Status of the glass sponge reefs in the Georgia Basin.

The purpose of this paper is to describe the status and general faunal composition of sponge reefs in the Georgia Basin (GB), British Columbia, Canada. Fourteen distinct deep-water glass sponge (Hexactinellid) reefs have been mapped using multibeam bathymetry and sidescan sonar in the GB. Seven of these have been surveyed visually using video from remotely operated vehicles (ROVs).

Changes in everyday function in individuals with psychometrically defined mild cognitive impairment in the Advanced Cognitive Training for Independent and Vital Elderly Study.

Objectives: To examine trajectories of change in everyday function for individuals with cognitive deficits suggestive of mild cognitive impairment (MCI).

Design: Using data from the longitudinal, multisite Advanced Cognitive Training for Independent and Vital Elderly Study allowed for post hoc classification of MCI status at baseline using psychometric definitions for amnestic MCI, nonamnestic MCI, multidomain MCI, and no MCI.

Setting: Six U.

Alzheimer disease with psychosis: excess cognitive impairment is restricted to the misidentification subtype.

Objective: Psychotic symptoms occur in 30%-60% of individuals with Alzheimer disease (AD) with psychosis (AD+P). AD+P identifies a distinct AD phenotype, with increased severity of cognitive impairment and a more rapid cognitive decline. Using factor and cluster analysis, we previously proposed two subtypes of patients with AD+P, one characterized by misidentifications and hallucinations (Misidentification), the other by persecutory delusions (Paranoid).

Psychotic symptoms in Alzheimer disease: evidence for subtypes.

Objective: Psychotic symptoms in Alzheimer disease (AD) identify a phenotype with distinct neurobiology and genetic architecture. The authors investigated whether AD with psychosis is homogeneous or is a composite of subtypes.

Methods: Authors performed factor and cluster analyses of the psychotic-symptom items of the CERAD Behavioral Rating Scale in 188 probable and possible AD subjects who have displayed at least one psychotic symptom.