In silico studies on the molecular interactions of steroid hormones and steroid hormone mimicking drugs in the androgen receptor binding cleft - Implications for prostate cancer treatment.

Occupancy of prostate cancer (PCa) cell androgen receptors (AR) signals proliferation, therefore testosterone biosynthesis inhibitors and AR antagonists are important PCa treatments. Conversely, androgen mimics (e.g.

The use of in silico molecular modelling to screen potential estrogen mimics as part of medicines and agrochemicals development and product license applications.

Estrogen mimics are a diverse group of synthetic and naturally occurring compounds that can interact with estrogen receptors (ERs) in animals, including humans. These interactions rely on key structural features of 17b-estradiol (E2) and if these molecular features are in a similar spatial arrangement on other compounds, they are likely to elicit an agonist (i.e.

Sixty years of conjecture over a urinary biomarker: a step closer to understanding the proposed link between anxiety and urinary pyrroles.

Objective: For over 60 years there has been conjecture about the identity of an Ehrlich's test positive pyrrole (Mauve Factor) reputed to be a biomarker for psychological disorders, including anxiety. We reviewed studies that attempt to identify Mauve Factor and subjected authentic standards of the 2 main candidates, kryptopyrrole and hydroxypyrrole, to the Ehrlich's reaction.

Methods: Modified Ehrlich's test for kryptopyrrole and hydroxypyrrole were applied to urine samples from 10 volunteers, anxious and nonanxious.

Could Microplastics Be a Driver for Early Onset Colorectal Cancer?

The incidence of colorectal cancer in those under 50 years of age (early onset colorectal cancer (EOCRC)) is increasing throughout the world. This has predominantly been an increase in distal colonic and rectal cancers, which are biologically similar to late onset colorectal cancer (LOCRC) but with higher rates of mucinous or signet ring histology, or poorly differentiated cancers. The epidemiology of this change suggests that it is a cohort effect since 1960, and is most likely driven by an environmental cause.

Healthcare workers' knowledge and attitudes towards sterilization and reuse of medical devices in primary and secondary care public hospitals in Nepal: A multi-centre cross-sectional survey.

Background: Healthcare facilities reprocess and sterilize reusable medical devices before each invasive clinical procedure, such as surgery, to prevent person-to-person or environmental transmission of pathogens through medical devices. We conducted a nationwide multi-centre cross-sectional survey in primary and secondary-care public hospitals in Nepal to assess the knowledge and attitudes of healthcare workers towards sterilization and reuse of medical devices.

Methods: We carried out a multi-centre cross-sectional survey comprising eleven primary-care (two district-level and nine district hospitals) and two secondary-care (zonal hospitals) public hospitals which covered all seven provinces of Nepal.

Quality of water for reprocessing of medical devices in healthcare facilities in Nepal.

Reusable medical devices are decontaminated and sterilized often many times by healthcare facilities across the globe. Reprocessing of medical devices comprises several processes and water plays an important role in some of these, including cleaning and steam sterilization. The water used is required to have certain qualities to ensure the effectiveness of the processes.

Compliance of primary and secondary care public hospitals with standard practices for reprocessing and steam sterilization of reusable medical devices in Nepal: findings from nation-wide multicenter clustered audits.

Background: Reusable medical devices in healthcare facilities are decontaminated and reprocessed following standard practices before each clinical procedure. Reprocessing of critical medical devices (those used for invasive clinical procedures) comprises several processes including sterilization, which provides the highest level of decontamination. Steam sterilization is the most used sterilization procedure across the globe.

Are over-the-counter fish oil supplements safe, effective and accurate with labelling? Analysis of 10 New Zealand fish oil supplements.

Aim: Fish oil supplements are regulated in New Zealand under the Dietary Supplement Regulations (Section 42, Food Act 1981) and therefore are not subject to the same level of scrutiny and regulations as medicines. We investigated accuracy of labelling, stated health benefits of fish oil supplements sold in New Zealand, and risks relating to possible mercury content.

Method: The amounts of omega-3 fatty acids contained per capsule were determined by an independent laboratory using gas chromatography on 10 of the most popular over-the-counter fish oil supplements sold in New Zealand and were compared with amounts stated on product labels.

Dietary isoflavone-induced, estrogen receptor-β-mediated proliferation of Caco-2 cells is modulated by gallic acid.

Dietary isoflavones and their biotransformation products (from food fermentation) are estrogen mimics which activate estrogen receptors (ER)α and ERβ. In silico molecular modelling is used to determine theoretical binding energies of genistein, daidzein and hydroxylated biotransformation products, and to investigate structure-binding energy relationships with ERβ. Results suggest that ligand hydroxyl arrangement determines binding energy and influences binding affinity.

Effectiveness of autoclaving in sterilizing reusable medical devices in healthcare facilities.

Medical devices are sterilized before being used for invasive clinical procedures such as surgery, to prevent pathogen transfer. Failure to sterilize medical devices properly presents a risk of healthcare-associated infections. Studies and reports have indicated that inadequately sterilized medical devices are one of the causes of a higher rate of healthcare-associated infections in developing countries.

Effectiveness of steam sterilization of reusable medical devices in primary and secondary care public hospitals in Nepal and factors associated with ineffective sterilization: A nation-wide cross-sectional study.

Background: Inadequate sterilization of reusable medical devices can lead to healthcare associated infections (HAIs) through person-to-person or environmental transmission of pathogens. Autoclaving (steam sterilization) is most commonly used for sterilizing medical devices in healthcare facilities. We conducted a nation-wide cross-sectional study to evaluate the effectiveness of steam sterilization practices in primary and secondary care public hospitals in Nepal and to identify factors associated with ineffective sterilization.

RETRACTED Are over-the-counter fish oil supplements safe, effective and accurate with labelling? Analysis of 10 New Zealand fish oil supplements.

RETRACTED.

Food flavonoid ligand structure/estrogen receptor-α affinity relationships - toxicity or food functionality?

In silico molecular modelling is used to study interactions between flavonoid phytoestrogens and estrogen receptor (ER)α. Twenty flavonoids from foods were studied; e.g.

The ketogenic diet as a potential treatment and prevention strategy for Alzheimer's disease.

The prevalence of Alzheimer's disease, a chronic neurodegenerative condition, is increasing as is the need for effective treatments and preventions. The underlying pathology of Alzheimer's is not yet fully understood, so existing research has focused on understanding the prominent features of the disease. These include amyloid plaques, which accumulate in the brains of those with Alzheimer's disease; impaired glucose metabolism; and neuronal cell death.

Intimate estrogen receptor-α/ligand relationships signal biological activity.

How does estrogen receptor-α bind its natural ligands - estrogens? How can other molecules mimic estrogens and elicit different estrogenic responses? The answers lie in a complex and intimate chemical biology between ligands and receptor. This delicate interaction at the ligand binding cleft signals, via conformational change, exposure of a specific new charge topography at a second site (Activation Function-2). This, in turn, attracts a regulatory protein which modulates gene expression and controls biological activity.

Are the amounts of vitamins in commercially available dietary supplement formulations relevant for the management of psychiatric disorders in children?

Aim: To investigate whether micronutrient supplements shown through research to have perceived benefits in the treatment of psychological/psychiatric symptoms in children have similar vitamin ingredients and doses to over-the-counter dietary supplements.

Methods: We conducted a systematic review to identify studies that used micronutrients for the treatment of psychological/psychiatric symptoms in children with documented benefits; 13 different supplements were identified that included vitamin ingredients. They were compared with the vitamin composition of 22 over-the-counter child-targeted supplements available in New Zealand.

Measurement of kidney cadmium in embalmed New Zealand cadavers.

Cadmium (Cd) is a toxic (carcinogenic) metal found in food because of its presence in the environment. New Zealand has elevated levels of Cd in soil due to the long term use of Cd-containing phosphate fertilisers. It is therefore likely that New Zealanders have a high Cd body burden which might have health implications.

New Zealand Malayan war veterans' exposure to dibutylphthalate is associated with an increased incidence of cryptorchidism, hypospadias and breast cancer in their children.

It is well known that the endocrine-disrupting chemical (EDC) dibutylphthalate (DBP) inhibits testosterone synthesis and can lead to feminisation in male laboratory animals. Moreover, it has long been speculated that human exposure would result in the similar effects, but this is difficult to study because specific human exposure cohorts are rare. We report increases in the incidences of hypospadias (p<0.

Estrogenicity of pyrethroid insecticide metabolites.

There is concern that insecticides are able to mimic the action of 17beta-estradiol by interaction with the human estrogen receptor. Pyrethroids are commonly used insecticides and several have been assessed for potential endocrine disrupting activity by various methods. It has been noted that some metabolites of pyrethroids, in particular, permethrin and cypermethrin, have chemical structures that are more likely to interact with the cellular estrogen receptor than the parent pyrethroid.

Ranking the risk of pesticide dietary intake.

Pesticide residues in various foods were assessed for the relative risk to the consumer. The analysis took into account criteria such as a pesticide's toxicity, usage, frequency of occurrence in foods, frequency of Maximum Residue Level (MRL) exceedances, and the overall risks of specific pesticide/food combinations. Examination of the top ten ranked pesticides for each criterion showed that there are no trends of commonality.

Bioactive isoflavones in functional foods: the importance of gut microflora on bioavailability.

Isoflavones present in soy may have risk and benefits to human health. Human gut microflora have been shown to exert metabolic activities on isoflavones, which influences bioavailability and bioactivity. Absorption of isoflavones is likely to occur in the small intestine where there is a diverse range of microfloral species able to hydrolyze conjugated isoflavones, releasing the bioactive aglycone for absorption or further metabolism and reconjugation.

Dietary exposure to xenoestrogens in New Zealand.

Continuing evidence of the feminising effects of xenoestrogens on a range of wildlife species increases the need to assess the human health risk of these estrogen mimics. We have estimated the exposure of New Zealand males, females and young men to a range of naturally occurring and synthetic xenoestrogens found in food. Only estrogenic compounds that act by interaction with the estrogen receptor have been included.