A real-world clinical validation for AI-based MRI monitoring in multiple sclerosis.

Modern management of MS targets No Evidence of Disease Activity (NEDA): no clinical relapses, no magnetic resonance imaging (MRI) disease activity and no disability worsening. While MRI is the principal tool available to neurologists for monitoring clinically silent MS disease activity and, where appropriate, escalating treatment, standard radiology reports are qualitative and may be insensitive to the development of new or enlarging lesions. Existing quantitative neuroimaging tools lack adequate clinical validation.

Do Plant Isolates Have a Role in Method Suitability and Growth Promotion Testing in the Microbiology Laboratory? Is It a Matter of Science versus Compliance?

In response to regulatory citations for not including plant isolates in method suitability and growth promotion testing of microbiological culture media, the authors make the case that the compendial designated cultures meet the requirements of the official tests and are sufficiently representative of the most frequently identified environmental isolates. It was our conclusion that this compliance request lacks scientific justification. The scope of this review was largely directed to the growth promotion and suitability testing requirements for USP <60>, <61>, <62>, and <71>.

Prevalence and Factors Associated with Sarcopenia in Patients on Maintenance Dialysis in Australia-A Single Centre, Cross-Sectional Study.

Sarcopenia is associated with significant morbidity and mortality in patients with chronic kidney disease. The prevalence of sarcopenia in the dialysis population varies from 4% to 63%. However, the prevalence and risk factors of sarcopenia in the Australian dialysis population remain uncertain.

Controls to Minimize Disruption of the Pharmaceutical Supply Chain During the COVID-19 Pandemic.

This article reviews currently available scientific literature related to the epidemiology, infectivity, survival, and susceptibility to disinfectants of Coronaviruses, in the context of the controls established to meet good manufacturing practice (GMP) regulations and guidance, and the public health guidance issued specifically to combat the COVID-19 pandemic. The possible impact of the COVID-19 pandemic on the pharmaceutical supply chain is assessed and recommendations are listed for risk mitigation steps to minimize supply disruption to pharmaceutical drug products. Areas addressed include a brief history of the COVID-19 viral pandemic, a description of the virus, the regulatory response to the pandemic, the screening of employees, the persistence of the virus on inanimate surfaces, cleaning and disinfection of manufacturing facilities, the use of GMP-mandated personal protective equipment to counter the spread of the disease, the role of air changes in viral clearance, and approaches to risk assessment and mitigation.

APOE4 is Associated with Differential Regional Vulnerability to Bioenergetic Deficits in Aged APOE Mice.

The ε4 allele of apolipoprotein E (APOE) is the dominant genetic risk factor for late-onset Alzheimer's disease (AD). However, the reason for the association between APOE4 and AD remains unclear. While much of the research has focused on the ability of the apoE4 protein to increase the aggregation and decrease the clearance of Aβ, there is also an abundance of data showing that APOE4 negatively impacts many additional processes in the brain, including bioenergetics.

Integrity of White Matter is Compromised in Mice with Hyaluronan Deficiency.

Brain white matter is the means of efficient signal propagation in brain and its dysfunction is associated with many neurological disorders. We studied the effect of hyaluronan deficiency on the integrity of myelin in murine corpus callosum. Conditional knockout mice lacking the hyaluronan synthase 2 were compared with control mice.

Distal limb pathologic conditions in horses treated with sleeve-style digital cryotherapy (285 cases).

Digital cryotherapy (DC) is frequently used as laminitis prophylaxis for horses. While DC with ice-water slurries is reported to be safe for up to 48 h, the safety of sleeve-style digital cryotherapy (SSDC) with ice in direct contact with the distal limb has not been evaluated. Our objective was to determine the incidence of distal limb pathologic conditions (DLPC) among horses treated with SSDC.

Aberrant development of intrinsic brain activity in a rat model of caregiver maltreatment of offspring.

Caregiver maltreatment induces vulnerability to later-life psychopathology. Clinical and preclinical evidence suggest changes in prefrontal and limbic circuitry underlie this susceptibility. We examined this question using a rat model of maternal maltreatment and methods translated from humans, resting-state functional magnetic resonance imaging (R-fMRI).

Stimulation-induced transient changes in neuronal activity, blood flow and N-acetylaspartate content in rat prefrontal cortex: a chemogenetic fMRS-BOLD study.

Brain activation studies in humans have shown the dynamic nature of neuronal N-acetylaspartate (NAA) and N-acetylaspartylglutamate (NAAG) based on changes in their MRS signals in response to stimulation. These studies demonstrated that upon visual stimulation there was a focal increase in cerebral blood flow (CBF) and a decrease in NAA or in the total of NAA and NAAG signals in the visual cortex, and that these changes were reversed upon cessation of stimulation. In the present study we have developed an animal model in order to explore the relationships between brain stimulation, neuronal activity, CBF and NAA.

Longitudinal magnetic resonance imaging reveals striatal hypertrophy in a rat model of long-term stimulant treatment.

Stimulant treatment is highly effective in mitigating symptoms associated with attention-deficit/hyperactivity disorder (ADHD), though the neurobiological underpinnings of this effect have not been established. Studies using anatomical magnetic resonance imaging (MRI) in children with ADHD have suggested that long-term stimulant treatment may improve symptoms of ADHD in part by stimulating striatal hypertrophy. This conclusion is limited, however, as these studies have either used cross-sectional sampling or did not assess the impact of treatment length on their dependent measures.

Cognitive Impairment, Neuroimaging, and Alzheimer Neuropathology in Mouse Models of Down Syndrome.

Down syndrome (DS) is the most common non-lethal genetic condition that affects approximately 1 in 700 births in the United States of America. DS is characterized by complete or segmental chromosome 21 trisomy, which leads to variable intellectual disabilities, progressive memory loss, and accelerated neurodegeneration with age. During the last three decades, people with DS have experienced a doubling of life expectancy due to progress in treatment of medical comorbidities, which has allowed this population to reach the age when they develop early onset Alzheimer's disease (AD).

Selective reduction of cerebral cortex GABA neurons in a late gestation model of fetal alcohol spectrum disorder.

Fetal alcohol spectrum disorders (FASD) are associated with cognitive and behavioral deficits, and decreased volume of the whole brain and cerebral cortex. Rodent models have shown that early postnatal treatments, which mimic ethanol toxicity in the third trimester of human pregnancy, acutely induce widespread apoptotic neuronal degeneration and permanent behavioral deficits. However, the lasting cellular and anatomical effects of early ethanol treatments are still incompletely understood.

N-acetyl-L-histidine, a Prominent Biomolecule in Brain and Eye of Poikilothermic Vertebrates.

N-acetyl-L-histidine (NAH) is a prominent biomolecule in brain, retina and lens of poikilothermic vertebrates. In fish lens, NAH exhibits an unusual compartmentalized metabolism. It is synthesized from L-histidine (His) and acetyl Co-enzyme A.

Histological correlation of diffusional kurtosis and white matter modeling metrics in cuprizone-induced corpus callosum demyelination.

The cuprizone mouse model is well established for studying the processes of both demyelination and remyelination in the corpus callosum, and it has been utilized together with diffusion tensor imaging (DTI) to investigate myelin and axonal pathology. Although some underlying morphological mechanisms contributing to the changes in diffusion tensor (DT) metrics have been identified, the understanding of specific associations between histology and diffusion measures remains limited. Diffusional kurtosis imaging (DKI) is an extension of DTI that provides metrics of diffusional non-Gaussianity, for which an associated white matter modeling (WMM) method has been developed.

Glutamatergic transmission aberration: a major cause of behavioral deficits in a murine model of Down's syndrome.

Trisomy 21, or Down's syndrome (DS), is the most common genetic cause of intellectual disability. Altered neurotransmission in the brains of DS patients leads to hippocampus-dependent learning and memory deficiency. Although genetic mouse models have provided important insights into the genes and mechanisms responsible for DS-specific changes, the molecular mechanisms leading to memory deficits are not clear.

In vivo Proton NMR spectroscopy of genetic mouse models BALB/cJ and C57BL/6By: variation in hippocampal glutamate level and the metabotropic glutamate receptor, subtype 7 (Grm7) gene.

Glutamatergic neurotransmission in the brain is modulated by metabotropic glutamate receptors (mGluR). In recent studies, we identified a cis-regulated variant of a gene (Grm7) which codes for mGluR subtype 7 (mGluR7), a presynaptic inhibitory receptor. The genetic variant derived from the BALB/cJ mouse strain (Grm7 (BALB/cJ)) codes for higher abundance of mGluR7 mRNA in the hippocampus than the C57BL/6By strain-derived variant (Grm7 (C57BL/6By)).

Functional connectivity fMRI in mouse brain at 7T using isoflurane.

Although many resting state fMRI human studies have been published, the number of such rodent studies is considerably less. The reason for this is the severe technical challenge of high magnetic field small rodent imaging. Local magnetic field susceptibility changes at air tissue boundaries cause image distortion and signal losses.

Canavan disease, a rare early-onset human spongiform leukodystrophy: insights into its genesis and possible clinical interventions.

The brain contains high concentrations of the amino acid N-acetyl-l-aspartate (NAA) and its' glutamate adduct N-acetyl-l-aspartylglutamate (NAAG), both synthesized primarily by and stored in neurons. Upon depolarization both are exported to extracellular fluid (ECF) with NAA targeted to oligodendrocytes and NAAG targeted to astrocytes where they are hydrolyzed by specific enzymes. While the functions of these substances are incompletely known, their unique tri-cellular metabolism is apparently vital to normal brain function.

Burkholderia cepacia: This Decision Is Overdue.

Unlabelled: This is the third in a series of seven articles discussing the Recall Root Cause Research project conducted by the Division of Manufacturing and Product Quality, Center for Drug Evaluation and Research. This paper reviews the regulatory and scientific impact of a common and recurring opportunistic pathogen, Burkholderia cepacia. B.

Stimulation-induced decreases in the diffusion of extra-vascular water in the human visual cortex: a window in time and space on mechanisms of brain water transport and economy.

In a human magnetic resonance diffusion-weighted imaging (DWI) investigation at 3 T and high diffusion sensitivity weighting (b = 1,800 s/mm(2)), which emphasizes the contribution of water in the extra-vascular compartment and minimizes that of the vascular compartment, we observed that visual stimulation with a flashing checkerboard at 8 Hz for a period of 600 s in eight subjects resulted in significant increases in DWI signals (mean +2.70%, range +0.51 to 8.

Impaired magnocellular/dorsal stream activation predicts impaired reading ability in schizophrenia.

In healthy humans, passage reading depends upon a critical organizing role played by the magnocellular/dorsal visual pathway. In a recent study, we found a significant correlation between orthographic reading deficits in schizophrenia and deficits in contrast sensitivity to low spatial frequency stimuli, suggesting an underlying magnocellular processing abnormality. The interrelationship between magnocellular dysfunction and passage reading impairments in schizophrenia was investigated in 21 patients with schizophrenia and 17 healthy control volunteers using behavioral and functional MRI (fMRI) based measures.

Murine diffusion imaging using snapshot interleaved EPI acquisition at 7T.

Diffusion tensor imaging (DTI) is a powerful magnetic resonance imaging tool for quantitative assessment of white matter micro structure. The majority of DTI methods employ Echo Planar Imaging (EPI) because it is insensitive to motion. However, EPI suffers from distortions and signal losses induced by inhomogeneities in magnetic field susceptibility.

State-dependent functional connectivity of rat olfactory system assessed by fMRI.

Functional connectivity between the piriform cortex and limbic and neocortical areas was assessed using functional magnetic resonance imaging (fMRI) of urethane anesthetized rats that spontaneously cycled between slow-wave and fast-wave states. Slow-wave and fast-wave states were determined indirectly through monitoring of respiration rate, which was confirmed to co-vary with state as determined by electrophysiological recordings. Previous electrophysiological data have suggested that the piriform cortex shifts between responsiveness to afferent odor input during fast-wave states and enhanced functional connectivity with limbic areas during slow-wave state.