No Evidence of HIV and SIV Sequences in Two Separate Lots of Polio Vaccines Used in the First U.S. Polio Vaccine Campaign

AbstractWe obtained sealed vials of two different polio vaccine lots, expiration date 1955, which were used in the first U.S. polio vaccine campaign. These early lots were pulled from the market because they contained live infectious poliovirus which caused polio in some of the vaccines. Theoretically, these vaccines could have contained other infectious retroviruses, including HIV. No viral sequences were detected using RT-PCR analyses with primers capable of amplifying chimpanzee SIV and HIV-1-related viruses nor with primers for macaque SIV, sooty mangabey SIV, and HIV-2-related viruses. Poliovirus sequences were readily amplified by RT-PCR, suggesting that the technique used would have detected SIV or HIV sequences, if present

U.S. Rail Transportation of Crude Oil: Background and Issues for Congress

This report discusses the challenges in the transportation of oil, as refineries that once received crude oil principally from oceangoing tankers are now seeing increasing deliveries by domestic transport. It also outlines possible issues for Congress including rail transport of oil versus pipelines, and the possible increase of oil spills from rail transport

Genome Sequence of the Human Abscess Isolate Streptococcus intermedius BA1

Streptococcus intermedius is a human pathogen with a propensity for abscess formation. We report a high-quality draft genome sequence of S. intermedius strain BA1, an isolate from a human epidural abscess. This sequence provides insight into the biology of S. intermedius and will aid investigations of pathogenicity

Central obesity as a precursor to the metabolic syndrome in the AusDiab study and Mauritius

Evidence from epidemiologic studies that central obesity precedes future metabolic change and does not occur concurrently with the appearance of the blood pressure, glucose, and lipid abnormalities that characterize the metabolic syndrome (MetS) has been lacking. Longitudinal surveys were conducted in Mauritius in 1987, 1992, and 1998, and in Australia in 2000 and 2005 (AusDiab). This analysis included men and women (aged 25 years) in three cohorts: AusDiab 2000&ndash;2005 (n = 5,039), Mauritius 1987&ndash;1992 (n = 2,849), and Mauritius 1987&ndash;1998 (n = 1,999). MetS components included waist circumference, systolic blood pressure, fasting and 2-h postload plasma glucose, high-density lipoprotein (HDL) cholesterol, triglycerides, and homeostasis model assessment of insulin sensitivity (HOMA-S) (representing insulin sensitivity). Linear regression was used to determine which baseline components predicted deterioration in other MetS components over 5 years in AusDiab and 5 and 11 years in Mauritius, adjusted for age, sex, and ethnic group. Baseline waist circumference predicted deterioration (P &lt; 0.01) in four of the other six MetS variables tested in AusDiab, five of six in Mauritius 1987&ndash;1992, and four of six in Mauritius 1987&ndash;1998. In contrast, an increase in waist circumference between baseline and follow-up was only predicted by insulin sensitivity (HOMA-S) at baseline, and only in one of the three cohorts. These results suggest that central obesity plays a central role in the development of the MetS and appears to precede the appearance of the other MetS components.<br /

Arcanolysin is a cholesterol-dependent cytolysin of the human pathogen Arcanobacterium haemolyticum

Arcanobacterium haemolyticum is an emerging human pathogen that causes pharyngitis, wound infections, and a variety of occasional invasive diseases. Since its initial discovery in 1946, this Gram positive organism has been known to have hemolytic activity, yet no hemolysin has been previously reported. A. haemolyticum also displays variable hemolytic activity on laboratory blood agar that is dependent upon which species the blood is derived. Here we describe a cholesterol-dependent cytolysin (CDC) secreted by A. haemolyticum, designated arcanolysin (aln), which is present in all strains (n = 52) tested by DNA dot hybridization. Among the known CDCs, ALN is most closely related to pyolysin (PLO) from Trueperella (formerly Arcanobacterium) pyogenes. The aln probe, however, did not hybridize to DNA from T. pyogenes. The aln open reading frame has a lower mol %G+C (46.7%) than the rest of the A. haemolyticum genome (53.1%) and is flanked by two tRNA genes, consistent with probable acquisition by horizontal transfer. The ALN protein (~ 64 kDa) contains a predicted signal sequence, a putative PEST sequence, and a variant undecapeptide within domain 4, which is typically important for function of the toxins. The gene encoding ALN was cloned and expressed in Escherichia coli as a functional recombinant toxin. Recombinant ALN had hemolytic activity on erythrocytes and cytolytic activity on cultured cells from human, rabbit, pig and horse origins but was poorly active on ovine, bovine, murine, and canine cells. ALN was less sensitive to inhibition by free cholesterol than perfringolysin O, consistent with the presence of the variant undecapeptide. ALN is a newly identified CDC with hemolytic activity and unique properties in the CDC family and may be a virulence determinant for A. haemolyticum

Prodromal dysfunction of a5GABA-A receptor modulated hippocampal ripples occurs prior to neurodegeneration in the TgF344-AD rat model of Alzheimer's disease

Decades of research attempting to slow the onset of Alzheimer's disease (AD) indicates that a better understanding of memory will be key to the discovery of effective therapeutic approaches. Here, we ask whether prodromal neural network dysfunction might occur in the hippocampal trisynaptic circuit by using α5IA (an established memory enhancer and selective negative allosteric modulator of extrasynaptic tonically active α5GABA-A receptors) as a probe drug in TgF344-AD transgenic rats, a model for β-amyloid induced early onset AD. The results demonstrate that orally bioavailable α5IA increases CA1 pyramidal cell mean firing rates during foraging and peak ripple amplitude during wakeful immobility in wild type F344 rats in a familiar environment. We further demonstrate that CA1 ripples in TgF344-AD rats are nonresponsive to α5IA by 9 months of age, prior to the onset of AD-like pathology and memory dysfunction. TgF344-AD rats express human β-amyloid precursor protein (with the Swedish mutation) and human presenilin-1 (with a Δ exon 9 mutation) and we found high serum Aβ42 and Aβ40 levels by 3 months of age. When taken together, this demonstrates, to the best of our knowledge, the first evidence for prodromal α5GABA-A receptor dysfunction in the ripple-generating hippocampal trisynaptic circuit of AD-like transgenic rats. As α5GABA-A receptors are found at extrasynaptic and synaptic contacts, we posit that negative modulation of α5GABA-A receptor mediated tonic as well as phasic inhibition augments CA1 ripples and memory consolidation but that this modulatory mechanism is lost at an early stage of AD onset.Published versio

AMELIE speeds Mendelian diagnosis by matching patient phenotype and genotype to primary literature

The diagnosis of Mendelian disorders requires labor-intensive literature research. Trained clinicians can spend hours looking for the right publication(s) supporting a single gene that best explains a patient’s disease. AMELIE (Automatic Mendelian Literature Evaluation) greatly accelerates this process. AMELIE parses all 29 million PubMed abstracts and downloads and further parses hundreds of thousands of full-text articles in search of information supporting the causality and associated phenotypes of most published genetic variants. AMELIE then prioritizes patient candidate variants for their likelihood of explaining any patient’s given set of phenotypes. Diagnosis of singleton patients (without relatives’ exomes) is the most time-consuming scenario, and AMELIE ranked the causative gene at the very top for 66% of 215 diagnosed singleton Mendelian patients from the Deciphering Developmental Disorders project. Evaluating only the top 11 AMELIE-scored genes of 127 (median) candidate genes per patient resulted in a rapid diagnosis in more than 90% of cases. AMELIE-based evaluation of all cases was 3 to 19 times more efficient than hand-curated database–based approaches. We replicated these results on a retrospective cohort of clinical cases from Stanford Children’s Health and the Manton Center for Orphan Disease Research. An analysis web portal with our most recent update, programmatic interface, and code is available at AMELIE.stanford.edu

RCRC Issue Briefs: Why Children Should Be the #1 Disaster Priority

The Resilient Children/Resilient Communities Initiative (RCRC) Issue Briefs, in this document, are designed to be used by the RCRC communities and all other communities who are seeking to elevate children’s disaster resilience to the attention of local, state, and federal legislators or other decision-makers. These reports can also be used by legislators and decision–makers at all levels of government as informative briefs to better understand the issues faced by communities in disasters within the context of COVID-19 and other disasters. Readers are encouraged to explore topics and voices that most resonate with their own community. To access an online and interactive version of RCRC Issue Briefs, please visit https://rcrctoolbox.org/rcrc-issue-briefs

Informes Temáticos RCRC: Porqué los Niños Deben Ser la Prioridad #1 en Desastres

Los Informes Temáticos RCRC, en este documento, están diseñados para ser utilizados por las comunidades de la iniciativa RCRC y todas las otras comunidades que buscan elevar la resiliencia de los niños ante desastres a la atención de legisladores locales, estatales y federales u otros responsables de la toma de decisiones. Estos informes también pueden ser utilizados por legisladores y responsables de la toma de decisiones en todos los niveles de gobierno como documentos informativos para comprender mejor los problemas que enfrentan las comunidades en desastres en el contexto de COVID-19 y otros desastres. Se anima a los lectores a explorar los temas y mensajes que más resuenan con su propia comunidad. Para acceder a una versión online e interactiva de los Informes Temáticos RCRC, visite https://rcrctoolbox.org/rcrc-issue-briefs-es/