Intra- and Interrater Reliability of CT- versus MRI-Based Cochlear Duct Length Measurement in Pediatric Cochlear Implant Candidates and Its Impact on Personalized Electrode Array Selection.

Background: Radiological high-resolution computed tomography-based evaluation of cochlear implant candidates' cochlear duct length (CDL) has become the method of choice for electrode array selection. The aim of the present study was to evaluate if MRI-based data match CT-based data and if this impacts on electrode array choice.

Methods: Participants were 39 children.

Measuring 25-hydroxyvitamin D in cats: comparison of a whole-blood lateral flow assay, 2 dried-blood-spot tests, and serum LC-MS/MS.

Measuring 25-hydroxyvitamin D (25D) can be a challenge in veterinary medicine because of laboratory accessibility and required sample volume. We compared 2 dried-blood-spot (DBS) tests and a lateral flow assay (LFA) to the gold standard, liquid chromatography-tandem mass spectrometry (LC-MS/MS). We hypothesized that there would be good agreement among the tests, within a clinically significant limit of agreement of ± 25 nmol/L.

Fecal identification markers impact the feline fecal microbiota.

Fecal diagnostics are a mainstay of feline medicine, and fecal identification markers help to distinguish individuals in a multi-cat environment. However, the impact of identification markers on the fecal microbiota are unknown. Given the increased interest in using microbiota endpoints to inform diagnosis and treatment, the objective of this study was to examine the effects of orally supplemented glitter and crayon shavings on the feline fecal microbiota (amplicon sequencing of 16S rRNA gene V4 region).

Physical activity is associated with increased resting-state functional connectivity in networks predictive of cognitive decline in clinically unimpaired older adults.

Introduction: Physical activity (PA) promotes resilience with respect to cognitive decline, although the underlying mechanisms are not well understood. We examined the associations between objectively measured PA and resting-state functional connectivity magnetic resonance imaging (rs-fcMRI) across seven anatomically distributed neural networks.

Methods: rs-fcMRI, amyloid beta (Aβ) positron emission tomography (PET), PA (steps/day × 1 week), and longitudinal cognitive (Preclinical Alzheimer's Cognitive Composite) data from 167 cognitively unimpaired adults (ages 63 to 90) were used.

Ribodysgenesis: sudden genome instability in the yeast Saccharomyces cerevisiae arising from RNase H2 cleavage at genomic-embedded ribonucleotides.

Ribonucleotides can be incorporated into DNA during replication by the replicative DNA polymerases. These aberrant DNA subunits are efficiently recognized and removed by Ribonucleotide Excision Repair, which is initiated by the heterotrimeric enzyme RNase H2. While RNase H2 is essential in higher eukaryotes, the yeast Saccharomyces cerevisiae can survive without RNase H2 enzyme, although the genome undergoes mutation, recombination and other genome instability events at an increased rate.

[Teletherapy after cochlear implantation during the COVID-19 pandemic].

Background: Due to the COVID-19 pandemic, digitalization in healthcare grew rapidly. Auditory training after cochlear implantation usually takes place face-to-face but social distancing interferes with this therapeutic approach.

Materials And Methods: In follow-up treatment, 42 adult cochlear implant (CI) users aged 53.

Association of Digital Clock Drawing With PET Amyloid and Tau Pathology in Normal Older Adults.

Objective: To determine whether a digital clock-drawing test, DCTclock, improves upon standard cognitive assessments for discriminating diagnostic groups and for detecting biomarker evidence of amyloid and tau pathology in clinically normal older adults (CN).

Methods: Participants from the Harvard Aging Brain Study and the PET laboratory at Massachusetts General Hospital were recruited to undergo the DCTclock, standard neuropsychological assessments including the Preclinical Alzheimer Cognitive Composite (PACC), and amyloid/tau PET imaging. Receiver operating curve analyses were used to assess diagnostic and biomarker discriminability.

Developmental stages in microbiota, bile acids, and clostridial species in healthy puppies.

Background: The fecal microbiota, fecal bile acid concentrations, and abundance of Clostridium perfringens and Clostridium difficile are altered in acute and chronic gastrointestinal disease in adult dogs. However, less is known in young puppies.

Hypothesis/objectives: To determine composition of the fecal microbiota, assess development of fecal bile acid profiles, and determine the abundance of Clostridial species in puppies, young adult dogs, and adult dogs.

Intrachromosomal Recombination in Yeast.

Spontaneous and induced mitotic recombinations are driven by lesions such as single-strand nicks and gaps and double-strand breaks in the genome. For regions of the genome that are not repetitive, spontaneous recombination rates are too low to be detected by simple screening and require reporters where a recombination product can be selected. This chapter describes commonly used types of reporters where a gene is duplicated as direct repeats and both copies are mutated with different mutations, rendering the cell defective for the gene and auxotrophic for the gene product.

Postinjury Engagement With the Police and Access to Care Among Victims of Violent Street Crime: Does Criminal History Matter?

This study examines whether victims of violent street crimes who are known to the police as past offenders, when compared with victims with no arrest history, have different outcomes related to receipt of victim and health-related services, while taking into consideration whether or not police responded to the victimization incident. The sample is comprised of 103 men and women between the age of 18 and 40 living in one Mid-Atlantic city who were victims of street violence within the year before study recruitment. Logistic regression was used to assess the impact of police response to the victimization incident on receipt of victim services, and receipt of victim services on engagement with counseling and mental health services.

Associations of Physical Activity and β-Amyloid With Longitudinal Cognition and Neurodegeneration in Clinically Normal Older Adults.

Importance: In the absence of disease-modifying therapies for Alzheimer disease, there is a critical need to identify modifiable risk factors that may delay the progression of Alzheimer disease.

Objective: To examine whether physical activity moderates the association of β-amyloid (Aβ) burden with longitudinal cognitive decline and neurodegeneration in clinically normal individuals and to examine whether these associations are independent of vascular risk.

Design, Setting, And Participants: This longitudinal observational study included clinically normal participants from the Harvard Aging Brain Study.

Genome instability consequences of RNase H2 Aicardi-Goutières syndrome alleles.

The RNase H2 complex is a conserved heterotrimeric enzyme that degrades RNA:DNA hybrids and promotes excision of rNMPs misincorporated during DNA replication. Failure to remove ribonucleotides from DNA leads to genomic instability in yeast and humans. The monogenic Aicardi-Goutières syndrome (AGS) results from mutation in one of several genes, among which are those encoding the RNase H2 subunits.

Guidelines for DNA recombination and repair studies: Mechanistic assays of DNA repair processes.

Genomes are constantly in flux, undergoing changes due to recombination, repair and mutagenesis. , many of such changes are studies using reporters for specific types of changes, or through cytological studies that detect changes at the single-cell level. Single molecule assays, which are reviewed here, can detect transient intermediates and dynamics of events.

Vascular Risk and β-Amyloid Are Synergistically Associated with Cortical Tau.

Objective: Neuropathological studies have demonstrated that cerebrovascular disease and Alzheimer disease (AD) pathology frequently co-occur in older adults. The extent to which cerebrovascular disease influences the progression of AD pathology remains unclear. Leveraging newly available positron emission tomography (PET) imaging, we examined whether a well-validated measure of systemic vascular risk and β-amyloid (Aβ) burden have an interactive association with regional tau burden.

Genomic Copy-Number Loss Is Rescued by Self-Limiting Production of DNA Circles.

Copy-number changes generate phenotypic variability in health and disease. Whether organisms protect against copy-number changes is largely unknown. Here, we show that Saccharomyces cerevisiae monitors the copy number of its ribosomal DNA (rDNA) and rapidly responds to copy-number loss with the clonal amplification of extrachromosomal rDNA circles (ERCs) from chromosomal repeats.

Interactive Associations of Vascular Risk and β-Amyloid Burden With Cognitive Decline in Clinically Normal Elderly Individuals: Findings From the Harvard Aging Brain Study.

Importance: Identifying asymptomatic individuals at high risk of impending cognitive decline because of Alzheimer disease is crucial for successful prevention of dementia. Vascular risk and β-amyloid (Aβ) pathology commonly co-occur in older adults and are significant causes of cognitive impairment.

Objective: To determine whether vascular risk and Aβ burden act additively or synergistically to promote cognitive decline in clinically normal older adults; and, secondarily, to evaluate the unique influence of vascular risk on prospective cognitive decline beyond that of commonly used imaging biomarkers, including Aβ burden, hippocampal volume, fludeoxyglucose F18-labeled (FDG) positron emission tomography (PET), and white matter hyperintensities, a marker of cerebrovascular disease.

Genome instabilities arising from ribonucleotides in DNA.

Genomic DNA is transiently contaminated with ribonucleotide residues during the process of DNA replication through misincorporation by the replicative DNA polymerases α, δ and ε, and by the normal replication process on the lagging strand, which uses RNA primers. These ribonucleotides are efficiently removed during replication by RNase H enzymes and the lagging strand synthesis machinery. However, when ribonucleotides remain in DNA they can distort the DNA helix, affect machineries for DNA replication, transcription and repair, and can stimulate genomic instabilities which are manifest as increased mutation, recombination and chromosome alterations.

Increased Spontaneous Recombination in RNase H2-Deficient Cells Arises From Multiple Contiguous rNMPs and Not From Single rNMP Residues Incorporated by DNA Polymerase Epsilon.

Ribonucleotides can become embedded in DNA from insertion by DNA polymerases, failure to remove Okazaki fragment primers, R-loops that can prime replication, and RNA/cDNA-mediated recombination. RNA:DNA hybrids are removed by RNase H enzymes. Single rNMPs in DNA are removed by RNase H2 and if they remain on the leading strand, can lead to mutagenesis in a Top1-dependent pathway.

Multifunctional roles of Saccharomyces cerevisiae Srs2 protein in replication, recombination and repair.

The Saccharomyces cerevisiae Srs2 DNA helicase has important roles in DNA replication, recombination and repair. In replication, Srs2 aids in repair of gaps by repair synthesis by preventing gaps from being used to initiate recombination. This is considered to be an anti-recombination role.

T-Cells Underlie Some but Not All of the Cerebellar Pathology in a Neonatal Rat Model of Congenital Lymphocytic Choriomeningitis Virus Infection.

Lymphocytic choriomeningitis virus (LCMV) infection during pregnancy injures the human fetal brain. Neonatal rats inoculated with LCMV are an excellent model of congenital LCMV infection because they develop cerebellar injuries similar to those in humans. To evaluate the role of T-lymphocytes in LCMV-induced cerebellar pathology, congenitally athymic rats, deficient in T-lymphocytes were compared with euthymic rats.

Neuropsychological characterization of three adolescent females with anti-NMDA receptor encephalitis in the acute, post-acute, and chronic phases: an inter-institutional case series.

Objective: Anti-N-methyl-D-aspartate (anti-NMDA) receptor encephalitis is an acute, immune-mediated paraneoplastic syndrome that often presents with psychobehavioral changes, abnormal movements, autonomic instability, seizures, and cognitive dysfunction. While the disease continues to be more readily identified and appropriately treated, the course of cognitive deficits from the acute to post-acute to chronic phase has not been well described, particularly in the pediatric population. This case series describes the neuropsychological functioning of three adolescent females with anti-NMDA receptor encephalitis from its early presentation to long-term follow-up.

Roles of DNA helicases and Exo1 in the avoidance of mutations induced by Top1-mediated cleavage at ribonucleotides in DNA.

The replicative DNA polymerases insert ribonucleotides into DNA at a frequency of approximately 1/6500 nucleotides replicated. The rNMP residues make the DNA backbone more susceptible to hydrolysis and can also distort the helix, impeding the transcription and replication machineries. rNMPs in DNA are efficiently removed by RNaseH2 by a process called ribonucleotides excision repair (RER).