A New Approach Methodology (NAM) Based Assessment of Butylated hydroxytoluene (BHT) for Endocrine Disruption Potential.

Butylated hydroxytoluene (BHT) is a synthetic antioxidant widely used in many industrial sectors. BHT is a well-studied compound for which there are many favorable regulatory decisions. However, a recent opinion by the French Agency for Food, Environmental and Occupational Health and Safety (ANSES) hypothesizes a role for BHT in endocrine disruption (ANSES (2021).

Innovation Inspired by COVID: A Virtual Treatment Program for Patients With Mild Cognitive Impairment at Mayo Clinic.

Limited access to mental health and behavioral interventions is a public health issue that predated and is further worsened by coronavirus disease 2019 (COVID-19) social distancing restrictions. The Healthy Action to Benefit Independence and Thinking (HABIT) program is a cognitive rehabilitation and wellness program for patients with a diagnosis of mild cognitive impairment and their partners that involves groups of up to 32 people (16 dyads) at a time. Thus, the public health recommendation to avoid groups at the start of the COVID-19 pandemic immediately impacted our ability to offer this treatment protocol.

FutureTox IV Workshop Summary: Predictive Toxicology for Healthy Children.

FutureTox IV, a Society of Toxicology Contemporary Concepts in Toxicology workshop, was held in November 2018. Building upon FutureTox I, II, and III, this conference focused on the latest science and technology for in vitro profiling and in silico modeling as it relates to predictive developmental and reproductive toxicity (DART). Publicly available high-throughput screening data sets are now available for broad in vitro profiling of bioactivities across large inventories of chemicals.

A comparison of classical and 21st century genotoxicity tools: A proof of concept study of 18 chemicals comparing in vitro micronucleus, ToxTracker and genomics-based methods (TGx-DDI, whole genome clustering and connectivity mapping).

A key step in the risk assessment process of a substance is the assessment of its genotoxic potential. Irrespective of the industry involved, current approaches rely on combinations of two or three in vitro tests and while highly sensitive, their specificity is thought to be limited. A refined in vitro genotoxicity testing strategy with improved predictive capacity would be beneficial and "3R" friendly as it helps to avoid unnecessary in vivo follow-up testing.

Assessment of distance from skin surface to muscle for evaluation of the risk of inadvertent intramuscular insulin injection at potential injection sites among patients attending a tertiary care children's hospital in Sri Lanka-an observational study.

Background: Insulin therapy is essential for type 1 diabetes. While a reasonable glycemic control prevents complications, inadvertent intramuscular (IM) insulin injection results in hypoglycemia and fluctuations of blood glucose levels.

Objective: To assess the subcutaneous thickness (SCt) at the potential insulin injection sites, in order to determine the suitable needle length.

Use of connectivity mapping to support read across: A deeper dive using data from 186 chemicals, 19 cell lines and 2 case studies.

We previously demonstrated that the Connectivity Map (CMap) (Lamb et al., 2006) concept can be successfully applied to a predictive toxicology paradigm to generate meaningful MoA-based connections between chemicals (De Abrew et al., 2016).

Obstetric outcomes and effects on babies born to women treated for epilepsy during pregnancy in a resource limited setting: a comparative cohort study.

Background: Management of epilepsy during pregnancy in a resource-limited setting (RLS) is challenging. This study aimed to assess obstetric outcomes and effects on babies of women with epilepsy (WWE) exposed to Anti-epileptic drugs (AEDs) compared to non-exposed controls in a RLS.

Methods: Pregnant WWE were recruited from antenatal and neurology clinics of a tertiary care hospitals in Sri Lanka.

Grouping 34 Chemicals Based on Mode of Action Using Connectivity Mapping.

Connectivity mapping is a method used in the pharmaceutical industry to find connections between small molecules, disease states, and genes. The concept can be applied to a predictive toxicology paradigm to find connections between chemicals, adverse events, and genes. In order to assess the applicability of the technique for predictive toxicology purposes, we performed gene array experiments on 34 different chemicals: bisphenol A, genistein, ethinyl-estradiol, tamoxifen, clofibrate, dehydorepiandrosterone, troglitazone, diethylhexyl phthalate, flutamide, trenbolone, phenobarbital, retinoic acid, thyroxine, 1α,25-dihydroxyvitamin D3, clobetasol, farnesol, chenodeoxycholic acid, progesterone, RU486, ketoconazole, valproic acid, desferrioxamine, amoxicillin, 6-aminonicotinamide, metformin, phenformin, methotrexate, vinblastine, ANIT (1-naphthyl isothiocyanate), griseofulvin, nicotine, imidacloprid, vorinostat, 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD) at the 6-, 24-, and 48-hour time points for 3 different concentrations in the 4 cell lines: MCF7, Ishikawa, HepaRG, and HepG2 GEO (super series accession no.

A novel transcriptomics based in vitro method to compare and predict hepatotoxicity based on mode of action.

High-content data have the potential to inform mechanism of action for toxicants. However, most data to support this notion have been generated in vivo. Because many cell lines and primary cells maintain a differentiated cell phenotype, it is possible that cells grown in culture may also be useful in predictive toxicology via high-content approaches such as whole-genome microarray.

TCDD induces dermal accumulation of keratinocyte-derived matrix metalloproteinase-10 in an organotypic model of human skin.

The epidermis of skin is the first line of defense against the environment. A three dimensional model of human skin was used to investigate tissue-specific phenotypes induced by the environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Continuous treatment of organotypic cultures of human keratinocytes with TCDD resulted in intracellular spaces between keratinocytes of the basal and immediately suprabasal layers as well as thinning of the basement membrane, in addition to the previously reported hyperkeratinization.

Regulation of Bach2 by the aryl hydrocarbon receptor as a mechanism for suppression of B-cell differentiation by 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Exposure to the aryl hydrocarbon receptor (AHR) agonist, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alters B-cell differentiation and suppresses antibody production. Previous genomic studies in mouse B cells identified Bach2 as a direct target of the AHR. Bach2 is known to repress expression of Prdm1, a key transcription factor involved in B-cell differentiation, by binding to Maf elements (MAREs) in the regulatory regions of the gene.

An integrated genomic analysis of aryl hydrocarbon receptor-mediated inhibition of B-cell differentiation.

The aryl hydrocarbon receptor (AHR) agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alters differentiation of B cells and suppresses antibody production. A combination of whole-genome, microarray-based chromatin immunoprecipitation (ChIP-on-chip), and time course gene expression microarray analysis was performed on the mouse B-cell line CH12.LX following exposure to lipopolysaccharide (LPS) or LPS and TCDD to identify the primary and downstream transcriptional elements of B-cell differentiation that are altered by the AHR.

Is walking barefoot a risk factor for diabetic foot disease in developing countries?

Introduction: Walking barefoot is common in poorer developing countries which have large rural populations. Although high rates of foot injury could be expected among those who walk barefoot, walking barefoot as a risk factor for diabetic foot disease is rarely documented in the literature.

Methods: Two preliminary clinical studies were undertaken to investigate whether there is a causal link between walking barefoot and diabetic foot ulcers.

Patient mixed biphasic insulin in a diabetic clinic.

Introduction: Improved glycaemic control is possible with the use of multiple injections of premixed insulin. These are expensive, and not available in state hospitals.

Objectives: To study the cost, patient acceptance and efficacy of a patient mixed and administered combination of soluble and lente (biphasic) insulin administered twice a day.

An audit of structure, process and outcome of care of the diabetic clinic, National Hospital of Sri Lanka.

Aims: To audit the structure, process and outcome of care.

Setting: The diabetic clinic, National of Hospital Sri Lanka (NHSL).

Methods: A previously validated MCQ paper of 10 questions which assessed knowledge of diabetes on insulin therapy, dietary management, management during acute illness and management of emergencies was administered to all patients.