The ASPREE Healthy Ageing Biobank: Methodology and participant characteristics.

ASPirin in Reducing Events in the Elderly (ASPREE), a placebo-controlled prevention trial of low dose aspirin, provided the opportunity to establish a biospecimen biobank from initially healthy persons aged 70+ years for future research. The ASPREE Healthy Ageing Biobank (ASPREE Biobank) collected, processed and stored blood and urine samples at -80degC or under nitrogen vapour at two timepoints, three years apart, from a willing subset of Australian ASPREE participants. Written informed consent included separate opt-in questions for biomarker and genetic testing.

Ensovibep, a SARS-CoV-2 antiviral designed ankyrin repeat protein, is safe and well tolerated in healthy volunteers: Results of a first-in-human, ascending single-dose Phase 1 study.

Aims: This study aimed to assess safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) effects of ensovibep, a designed ankyrin repeat protein antiviral being evaluated as a COVID-19 treatment, in healthy volunteers in a first-in-human ascending single-dose study.

Methods: Subjects were dosed intravenously, in a randomized double-blinded manner, with either ensovibep at 3, 9 or 20 mg/kg or with placebo, and followed until Day 100. PK and safety were assessed throughout the study duration.

Can butyrate prevent colon cancer? The AusFAP study: A randomised, crossover clinical trial.

Increased colonic butyrate from microbial fermentation of fibre may protect from colorectal cancer (CRC). Dietary butyrylated high amylose maize starch (HAMSB) delivers butyrate to the large bowel. The objective of this clinical trial (AusFAP) is to evaluate potential chemoprotective effects of HAMSB on polyposis in individuals with a genetic form of colon cancer, Familial Adenomatous Polyposis (FAP).

A haemagglutination test for rapid detection of antibodies to SARS-CoV-2.

Serological detection of antibodies to SARS-CoV-2 is essential for establishing rates of seroconversion in populations, and for seeking evidence for a level of antibody that may be protective against COVID-19 disease. Several high-performance commercial tests have been described, but these require centralised laboratory facilities that are comparatively expensive, and therefore not available universally. Red cell agglutination tests do not require special equipment, are read by eye, have short development times, low cost and can be applied at the Point of Care.

An acetate-yielding diet imprints an immune and anti-microbial programme against enteric infection.

Objectives: During gastrointestinal infection, dysbiosis can result in decreased production of microbially derived short-chain fatty acids (SCFAs). In response to the presence of intestinal pathogens, we examined whether an engineered acetate- or butyrate-releasing diet can rectify the deficiency of SCFAs and lead to the resolution of enteric infection.

Methods: We tested whether a high acetate- or butyrate-producing diet (HAMSA or HAMSB, respectively) condition infection in mice and assess its impact on host-microbiota interactions.

Broad and strong memory CD4 and CD8 T cells induced by SARS-CoV-2 in UK convalescent individuals following COVID-19.

The development of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines and therapeutics will depend on understanding viral immunity. We studied T cell memory in 42 patients following recovery from COVID-19 (28 with mild disease and 14 with severe disease) and 16 unexposed donors, using interferon-γ-based assays with peptides spanning SARS-CoV-2 except ORF1. The breadth and magnitude of T cell responses were significantly higher in severe as compared with mild cases.

Medically actionable pathogenic variants in a population of 13,131 healthy elderly individuals.

Purpose: To measure the prevalence of medically actionable pathogenic variants (PVs) among a population of healthy elderly individuals.

Methods: We used targeted sequencing to detect pathogenic or likely pathogenic variants in 55 genes associated with autosomal dominant medically actionable conditions, among a population of 13,131 individuals aged 70 or older (mean age 75 years) enrolled in the ASPirin in Reducing Events in the Elderly (ASPREE) trial. Participants had no previous diagnosis or current symptoms of cardiovascular disease, physical disability or dementia, and no current diagnosis of life-threatening cancer.

Broad and strong memory CD4 and CD8 T cells induced by SARS-CoV-2 in UK convalescent COVID-19 patients.

COVID-19 is an ongoing global crisis in which the development of effective vaccines and therapeutics will depend critically on understanding the natural immunity to the virus, including the role of SARS-CoV-2-specific T cells. We have conducted a study of 42 patients following recovery from COVID-19, including 28 mild and 14 severe cases, comparing their T cell responses to those of 16 control donors. We assessed the immune memory of T cell responses using IFNγ based assays with overlapping peptides spanning SARS-CoV-2 apart from ORF1.

Opioid Overdose and Naloxone Kit Distribution: A Quality Assurance Educational Program in the Primary Care Setting.

Problem: In 2014, there were approximately 200,000 incidents of an unintentional opioid overdose nationwide. The 2016 Centers for Disease Control and Prevention opioid prescription guidelines identified a knowledge deficit regarding opioid prescribing among primary care providers as a contributing factor to this epidemic.

Purpose: The purpose of this quality assurance project was to provide education on opioid overdose and distribution of naloxone kits through a presentation to primary care providers at Veterans Administration facilities in the southeast region of the United States.

Erratum: Gut microbial metabolites limit the frequency of autoimmune T cells and protect against type 1 diabetes.

This corrects the article DOI: 10.1038/ni.3713.

Gut microbial metabolites limit the frequency of autoimmune T cells and protect against type 1 diabetes.

Gut dysbiosis might underlie the pathogenesis of type 1 diabetes. In mice of the non-obese diabetic (NOD) strain, we found that key features of disease correlated inversely with blood and fecal concentrations of the microbial metabolites acetate and butyrate. We therefore fed NOD mice specialized diets designed to release large amounts of acetate or butyrate after bacterial fermentation in the colon.

Evaluation of Methylation Biomarkers for Detection of Circulating Tumor DNA and Application to Colorectal Cancer.

Solid tumors shed DNA into circulation, and there is growing evidence that the detection of circulating tumor DNA (ctDNA) has broad clinical utility, including monitoring of disease, prognosis, response to chemotherapy and tracking tumor heterogeneity. The appearance of ctDNA in the circulating cell-free DNA (ccfDNA) isolated from plasma or serum is commonly detected by identifying tumor-specific features such as insertions, deletions, mutations and/or aberrant methylation. Methylation is a normal cell regulatory event, and since the majority of ccfDNA is derived from white blood cells (WBC), it is important that tumour-specific DNA methylation markers show rare to no methylation events in WBC DNA.

Dietary butyrylated high-amylose starch reduces azoxymethane-induced colonic O(6)-methylguanine adducts in rats as measured by immunohistochemistry and high-pressure liquid chromatography.

O(6)-methyl guanine (O(6)MeG) adducts are major toxic, promutagenic, and procarcinogenic adducts involved in colorectal carcinogenesis. Resistant starch and its colonic metabolite butyrate are known to protect against oncogenesis in the colon. In this study, we hypothesized that a dietary intervention that specifically delivers butyrate to the large bowel (notably butyrylated high-amylose maize starch [HAMSB]) would reduce colonic levels of O(6)MeG in rats shortly after exposure to the deoxyribonucleic acid (DNA) alkylating agent azoxymethane (AOM) when compared with a low-amylose maize starch (LAMS).

RNA sequencing supports distinct reactive oxygen species-mediated pathways of apoptosis by high and low size mass fractions of Bay leaf (Lauris nobilis) in HT-29 cells.

Anti-proliferative and pro-apoptotic effects of Bay leaf (Laurus nobilis) in mammalian cancer and HT-29 adenocarcinoma cells have been previously attributed to effects of polyphenolic and essential oil chemical species. Recently, we demonstrated differentiated growth-regulating effects of high (HFBL) versus low molecular mass (LFBL) aqueous fractions of bay leaf and now confirm by comparative effects on gene expression, that HFBL and LFBL suppress HT-29 growth by distinct mechanisms. Induction of intra-cellular lesions including DNA strand breakage by extra-cellular HFBL, invoked the hypothesis that iron-mediated reactive oxygen species with capacity to penetrate cell membrane, were responsible for HFBL-mediated effects, supported by equivalent effects of HFBL in combination with γ radiation.

A two-gene blood test for methylated DNA sensitive for colorectal cancer.

Background: Specific genes are methylated with high frequency in colorectal neoplasia, and may leak into blood. Detection of multiple methylated DNA biomarkers in blood may improve assay sensitivity for colorectal cancer (CRC) relative to a single marker. We undertook a case-control study evaluating the presence of two methylation DNA markers, BCAT1 and IKZF1, in circulation to determine if they were complementary for detection of CRC.

A prediction model for colon cancer surveillance data.

Dynamic prediction models make use of patient-specific longitudinal data to update individualized survival probability predictions based on current and past information. Colonoscopy (COL) and fecal occult blood test (FOBT) results were collected from two Australian surveillance studies on individuals characterized as high-risk based on a personal or family history of colorectal cancer. Motivated by a Poisson process, this paper proposes a generalized nonlinear model with a complementary log-log link as a dynamic prediction tool that produces individualized probabilities for the risk of developing advanced adenoma or colorectal cancer (AAC).

Chronic administration of a microencapsulated probiotic enhances the bioavailability of orange juice flavanones in humans.

Orange juice (OJ) flavanones are bioactive polyphenols that are absorbed principally in the large intestine. Ingestion of probiotics has been associated with favorable changes in the colonic microflora. The present study examined the acute and chronic effects of orally administered Bifidobacterium longum R0175 on the colonic microflora and bioavailability of OJ flavanones in healthy volunteers.

Bioequivalence of n-3 fatty acids from microencapsulated fish oil formulations in human subjects.

Fish oil n-3 fatty acids (FA) have known health benefits. Microencapsulation stabilises and protects fish oil from oxidation, enabling its incorporation into foods. The aim of the present study was to compare the bioavailability of n-3 FA delivered as two microencapsulated fish oil-formulated powders or fish oil gel capsules (FOGC) taken with a flavoured milk in healthy participants.

Resistant starch alters colonic contractility and expression of related genes in rats fed a Western diet.

Background And Aim: Dietary fiber shortens gut transit time, but data on the effects of fiber components (including resistant starch, RS) on intestinal contractility are limited. We have examined RS effects in male Sprague-Dawley rats fed either a high-amylose maize starch (HAMS) or a wholemeal made from high-amylose wheat (HAW) on ileal and colonic contractility ex vivo and expression of genes associated with smooth muscle contractility.

Methods: Rats were fed diets containing 19 % fat, 20 % protein, and either low-amylose maize starch (LAMS), HAMS, wholemeal low-amylose wheat (LAW) or HAW for 11 week.

Ideal colonoscopic surveillance intervals to reduce incidence of advanced adenoma and colorectal cancer.

Background And Aims: There is limited information about the interplay between multiple risk factors contributing to the risk of advanced neoplasia. We determined the actual risk for advanced neoplasia in relation to lapsed time between colonoscopies in people enrolled in a structured surveillance program. This risk information can be used to guide the selection of optimal surveillance intervals.

Butyrylated starch affects colorectal cancer markers beneficially and dose-dependently in genotoxin-treated rats.

Population studies suggest that greater dietary fiber intake may lower colorectal cancer (CRC) risk, possibly through the colonic bacterial fermentative production of butyrate. Butyrylated starch delivers butyrate to the colon of humans with potential to reduce CRC risk but high doses may exacerbate risk through promoting epithelial proliferation. Here we report the effects of increasing dietary butyrylated high amylose maize starch (HAMSB) on azoxymethane (AOM) induced distal colonic DNA damage, cell proliferation, mucus layer thickness and apoptosis in rats.

Dietary supplementation of propionylated starch to domestic cats provides propionic acid as gluconeogenic substrate potentially sparing the amino acid valine.

In strict carnivorous domestic cats, a metabolic competition arises between the need to use amino acids for gluconeogenesis and for protein synthesis both in health and disease. The present study investigated the amino acid-sparing potential of propionic acid in cats using dietary propionylated starch (HAMSP) supplementation. A total of thirty cats were fed a homemade diet, supplemented with either HAMSP, acetylated starch (HAMSA) or celite (Control) for three adaptation weeks.