Hyperfiltration and renal disease in glycogen storage disease, type I

Hyperfiltration and renal disease in glycogen storage disease, type I. A prospective study of 14 patients (ages 6 months to 33 years) with glycogen storage disease, Type I (GSD-I) was carried out in order to define the character and frequency of renal dysfunction. A marked increase in the glomerular filtration rate (GFR) was documented in virtually all subjects, with the mean GFR raised by approximately 50%, to the range of 170 ml/min/1.73m2. While this constituted the only renal abnormality found in the younger patients, a significant increase in urinary albumin excretion was seen in three teen-aged individuals; three patients over 20 years of age exhibited frank proteinuria (2 to 8 g/day). Renal biopsy on two of the proteinuric subjects revealed focal and global glomerulosclerosis and interstitial fibrosis. Evaluation of factors known to cause an increase in GFR did not define the precise etiology for its elevation in GSD-I. These studies suggest that: (1) glomerular damage and chronic renal disease are common in older patients with GSD-I; (2) the renal injury appears to be specifically related to GSD-I and is not secondary to the treatment of the disease; and (3) the natural history of the renal lesion in GSD-I may be analogous to that seen in insulin-dependent diabetes, with a “silent” period where hyperfiltration is the only demonstrable renal abnormality, followed by evidence of increasing glomerular damage progressing from microalbuminuria to frank proteinuria

Association between TriptanUse and Cardiac Contraindications in an Insured Migraine Population

Background Safety concerns exist when using triptansto treat patients with cardiac contraindications. –Triptans cause vasoconstriction, a safety concern for migraineurswith cardiovascular (CV) disease or other cardiac risk factors. –All triptans contain contraindications in their package inserts to avoid use in patients with cardiac conditions. •Previous research indicates that clinicians are less likely to prescribe triptansin patients with CV disease or CV risk factors. Limited research has examined the proportion of migraine patients with cardiovascular disease or those individuals who were concurrently treated with triptans

Disruption of cholinergic neurotransmission, within a cognitive challenge paradigm, is indicative of Aβ-related cognitive impairment in preclinical Alzheimer’s disease after a 27-month delay interval

Background Abnormal beta-amyloid (Aβ) is associated with deleterious changes in central cholinergic tone in the very early stages of Alzheimer’s disease (AD), which may be unmasked by a cholinergic antagonist (J Prev Alzheimers Dis 1:1–4, 2017). Previously, we established the scopolamine challenge test (SCT) as a “cognitive stress test” screening measure to identify individuals at risk for AD (Alzheimer’s & Dementia 10(2):262–7, 2014) (Neurobiol. Aging 36(10):2709-15, 2015). Here we aim to demonstrate the potential of the SCT as an indicator of cognitive change and neocortical amyloid aggregation after a 27-month follow-up interval. Methods Older adults (N = 63, aged 55–75 years) with self-reported memory difficulties and first-degree family history of AD completed the SCT and PET amyloid imaging at baseline and were then seen for cognitive testing at 9, 18, and 27 months post-baseline. Repeat PET amyloid imaging was completed at the time of the 27-month exam. Results Significant differences in both cognitive performance and in Aβ neocortical burden were observed between participants who either failed vs. passed the SCT at baseline, after a 27-month follow-up period. Conclusions Cognitive response to the SCT (Alzheimer’s & Dementia 10(2):262–7, 2014) at baseline is related to cognitive change and PET amyloid imaging results, over the course of 27 months, in preclinical AD. The SCT may be a clinically useful screening tool to identify individuals who are more likely to both have positive evidence of amyloidosis on PET imaging and to show measurable cognitive decline over several years

Characteristics of 263K Scrapie Agent in Multiple Hamster Species

Characteristics correlated better with host factors than with agent strain

Collision, Collusion and Coincidence: Pop Art’s Fairground Parallel

This article looks at parallel methods, motivations and modes of consumption between formative British pop art and British fairground art. I focus on two strands, the emergent critical work of the Independent Group and the school of artists based at the Royal College of Art under the nominal leadership of Peter Blake. I use iconographical and iconological methods to compare the content of the art, and then examine how pop art tried to create both a critical and playful distancing from established rules and practices of the artistic canon. I focus on non-institutional cultural groupings and diffuse production and consumption models

A plasmid DNA-launched SARS-CoV-2 reverse genetics system and coronavirus toolkit for COVID-19 research

The recent emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the underlying cause of Coronavirus Disease 2019 (COVID-19), has led to a worldwide pandemic causing substantial morbidity, mortality, and economic devastation. In response, many laboratories have redirected attention to SARS-CoV-2, meaning there is an urgent need for tools that can be used in laboratories unaccustomed to working with coronaviruses. Here we report a range of tools for SARS-CoV-2 research. First, we describe a facile single plasmid SARS-CoV-2 reverse genetics system that is simple to genetically manipulate and can be used to rescue infectious virus through transient transfection (without in vitro transcription or additional expression plasmids). The rescue system is accompanied by our panel of SARS-CoV-2 antibodies (against nearly every viral protein), SARS-CoV-2 clinical isolates, and SARS-CoV-2 permissive cell lines, which are all openly available to the scientific community. Using these tools, we demonstrate here that the controversial ORF10 protein is expressed in infected cells. Furthermore, we show that the promising repurposed antiviral activity of apilimod is dependent on TMPRSS2 expression. Altogether, our SARS-CoV-2 toolkit, which can be directly accessed via our website at https://mrcppu-covid.bio/, constitutes a resource with considerable potential to advance COVID-19 vaccine design, drug testing, and discovery science