Support of parenting in undergraduate medical training in New Zealand.

PURPOSE: This research assessed support for parents studying undergraduate medicine at a New Zealand medical school and identified requirements for additional support. METHOD: Support documentation was sourced from Student Affairs and university and medical school websites. The Medical Deans of Australia and New Zealand Medical Students Outcome and Longitudinal tracking Project was retrospectively examined for data specific to medical student parents. Student parents and medical school staff were also surveyed for their knowledge and perceptions around organisation and effectiveness of available support, and suggestions for additional support. RESULTS: Parents and expectant parents formed a consistent, likely growing sub-group studying medicine from 2008 to 2020, yet no formal student parent support policy existed until 2019. Prior to this, 67% of student parents and 47% of staff lacked knowledge of available support. Since 2020, calls for greater visibility of parenting policies and flexibility in the curriculum have been operationalised by the medical school. CONCLUSION: Formalising policies and procedures, maximising access to parenting support resources and introducing flexibility in medical curricula can help students balancing families and medical training. This is relevant for sustainability of medicine as a career option for medical students wanting children, especially considering over half of all medical students are female.

The health status alters the pituitary function and reproduction of mice in a Cxcr2-dependent manner.

Microbiota and chronic infections can affect not only immune status, but also the overall physiology of animals. Here, we report that chronic infections dramatically modify the phenotype of Cxcr2 KO mice, impairing in particular, their reproduction ability. We show that exposure of Cxcr2 KO females to multiple types of chronic infections prevents their ability to cycle, reduces the development of the mammary gland and alters the morphology of the uterus due to an impairment of ovary function. Mammary gland and ovary transplantation demonstrated that the hormonal contexture was playing a crucial role in this phenomenon. This was further evidenced by alterations to circulating levels of sex steroid and pituitary hormones. By analyzing at the molecular level the mechanisms of pituitary dysfunction, we showed that in the absence of Cxcr2, bystander infections affect leukocyte migration, adhesion, and function, as well as ion transport, synaptic function behavior, and reproduction pathways. Taken together, these data reveal that a chemokine receptor plays a direct role in pituitary function and reproduction in the context of chronic infections.

Health professional education and practice in preventing and controlling infections in New Zealand: a review to inform strategies for enhancing practitioner competencies and patient safety.

Objective: Quality assurance for reducing infections is a key objective of the WHO's global action plan targeting antimicrobial resistance, yet no studies have employed a multifaceted approach to review health professional education and practice in infection prevention and control (IPC). This study completed such a review. Methods and analysis: New Zealand medical and nursing curricula were analysed for IPC-related teaching and assessment. Clinicians (undergraduate to senior) received peer-expert evaluation while performing procedures demonstrating IPC competencies. Patient and clinician self-evaluation followed. Hospital IPC practice monitoring was also reviewed. Results: Medical curricula had approximately twice the total IPC-related theory compared with nursing (79.71 vs 41.66 hours), emphasising microbiology. IPC theory in nursing curricula was applied, emphasising health and safety. Junior nursing students were rigorously taught (16.17 hours) and assessed (2.91 hours) in practical IPC competencies, whereas little practical instruction (2.62 hours) and no formal assessment existed for junior medical students. IPC teaching chiefly occurred during medical students' senior clinical years, and was opportunistic, rotation-specific or in introductory sessions. Senior medical and nursing students were expected to be IPC-proficient but no formal assessment occurred. Peer review generally revealed satisfactory practice, however both professions had lapses with hand hygiene, asepsis and incorrect donning, removal and use of personal protective equipment. Clinician confidence in providing and being peer-reviewed for best IPC practice, and patients' confidence in receiving best IPC care, was positively associated with clinician experience. Trainee interns, whose confidence in IPC practice was not matched by the same desire for monitoring/feedback as senior colleagues, were the exception. Conclusion: Multifaceted approaches to IPC quality assurance have utility in identifying gaps, reducing infection transmission and reassuring staff and patients.

In Vivo Quantitation of Estrogen Receptor ß Subtype Expression in Ovarian Surface Epithelium Using Immunofluorescence Profiling and Confocal Microscopy.

Immunohistochemistry using formalin-fixed, paraffin-embedded tissue, chromogen label, and light microscopy has traditionally been used to semiquantify estrogen receptor (ER) to guide diagnosis and management of breast cancer. Quantitation of ER for this purpose currently only assesses levels of the ER-alpha subtype. Considerable variability in results reported has been due to protocol and fixation variability, intraobserver and interobserver variability, and different scoring systems and thresholds for scoring ER positivity. Results can also vary with low expression levels of ER. ER-beta expression is reduced in breast and ovarian cancers and requires quantitation.Herein we describe a novel approach to quantifying ERß using older mouse ovarian surface epithelium, where ERß is expressed at lower levels than ERα and is therefore harder to detect. We use an antibody highly specific to the ERß1 isoform, together with immunofluorescence, confocal microscopy, and imaging and statistical software to achieve clear, reproducible, and unbiased quantitation of ERß.

Xenobiotics and the Glucocorticoid Receptor.

Glucocorticoid Receptor (GR) is present in virtually every human cell type. Representing a nuclear receptor superfamily, GR has several different isoforms essentially acting as ligand-dependent transcription factors, regulating glucocorticoid-responsive gene expression in both a positive and a negative manner. Although the natural ligand of the Glucocorticoid Receptor, glucocorticoids (GC) represent only some of the multiple ligands for GR. Xenobiotics, ubiquitous in the environment, bind to GR and are also capable of activating or repressing GR gene expression, thereby modulating GR cell and tissue-specific downstream effects in a multitude of ways that include responses to inflammatory, allergic, metabolic, neoplastic and autoimmune processes. Many xenobiotics, if inadequately metabolized by xenobiotic metabolizing enzymes and not wholly eliminated, could have deleterious toxic effects with potentially lethal consequences. This review examines GR, the genomic and non-genomic actions of natural and synthetic GC and the body's handling of xenobiotic compounds, before reviewing what is presently known about GR's interactions with many of the more commonly encountered and some of the less well known GR-associated xenobiotics. GR promiscuity and crosstalk with other signaling pathways is discussed, alongside novel roles for GR that include mood disorder and addiction. A knowledge of GR interactions with xenobiotics is increasingly relevant when considering aging populations and the related prevalence of neoplastic disease, together with growing concerns around human exposure to mixtures of chemicals in the environment. Furthermore, escalating rates of obesity, Type 2 diabetes; autoimmune, allergy, addiction and mood disorder-related pathologies, require novel targeted interventions and GR appears a promising pharmacological candidate.

The potential for chemical mixtures from the environment to enable the cancer hallmark of sustained proliferative signalling.

The aim of this work is to review current knowledge relating the established cancer hallmark, sustained cell proliferation to the existence of chemicals present as low dose mixtures in the environment. Normal cell proliferation is under tight control, i.e. cells respond to a signal to proliferate, and although most cells continue to proliferate into adult life, the multiplication ceases once the stimulatory signal disappears or if the cells are exposed to growth inhibitory signals. Under such circumstances, normal cells remain quiescent until they are stimulated to resume further proliferation. In contrast, tumour cells are unable to halt proliferation, either when subjected to growth inhibitory signals or in the absence of growth stimulatory signals. Environmental chemicals with carcinogenic potential may cause sustained cell proliferation by interfering with some cell proliferation control mechanisms committing cells to an indefinite proliferative span.

Repeat estradiol exposure differentially regulates protein expression patterns for estrogen receptor and E-cadherin in older mouse ovarian surface epithelium: implications for replacement and adjuvant hormone therapies?

BACKGROUND: Estrogen replacement therapy increases risk for ovarian epithelial cancer, a cancer of mainly older women, yet the response of older ovarian surface epithelium (OSE) to repeat estrogen exposure overtime has not been studied. We have previously reported significant reductions in estrogen receptor (ER) protein expression, particularly the ERß1 isoform, in older mouse OSE following a single depot estradiol injection. The current study examined OSE from older mice following a single, and repeat estradiol injection, given 14 days apart over 28 days. METHODS: Cohorts of mice were sacrificed 48 hours following each estradiol injection, and at three other equidistant time points. Serum and ovarian tissue estradiol concentration was correlated to immunohistochemical and morphometric parameters used to identify evidence of OSE hyperplasia and hypertrophy. Using immunohistochemistry, E-cadherin expression was investigated in OSE 48 hours following both estradiol injections, while ERα and ERß1 expression was examined in OSE following repeat estradiol exposure only. RESULTS: First exposure to exogenous estradiol resulted in OSE hypertrophy and hyperplasia, and high levels of E-cadherin expression. In contrast, repeat estradiol exposure resulted in no OSE hyperplasia or hypertrophy, low levels of E-cadherin expression, high ERα and reduced ERß1 protein expression in OSE, and low stromal ERα expression. Blood and ovarian tissue estradiol levels following repeat estradiol injection were half those recorded after a first dose equivalent injection, but remained significantly elevated above controls. CONCLUSION: Repeat estradiol exposure leads to accumulation of estradiol in ovarian tissue, differentially regulating protein expression patterns for E-cadherin in OSE and ER in OSE and stroma.

Novel approaches to quantify estradiol-induced loss of ERß1 protein in older mouse ovarian surface epithelium: new tools to assess the role of ER protein subtypes in predisposing to ovarian epithelial cancer?

Loss of estrogen receptor-beta (ERß) occurs in ovarian epithelial cancer (OEC), a cancer of mainly older women. OEC is linked epidemiologically to hormone replacement therapy, predominantly with estrogen-only formulations. This study introduces a novel, non-biased method to quantify levels of estradiol-induced loss of ERß1 protein, and defines, for the first time, normal OSE expression patterns for ERα and ERß1 with advancing age. Older (7-10 months) Swiss Webster mice were injected with estradiol valerate (EV) while age-matched diestrous controls received oil. Mice were culled after 48 h, and blood and one ovary were frozen for estradiol RIA. Contralateral ovaries were paraffin-embedded for immunohistochemistry. Subsets of serial sections, triple-labeled with immunofluroescent tags, were imaged with confocal microscopy to provide optimal visualization of ER protein subtype expression in OSE. Immunofluorescence emission profiles distinct to ERß1 in OSE were standardized and quantified in control mice then compared to profiles from EV-exposed mice. Estradiol levels were significantly elevated in EV-treated mice, both in blood (p < 0.0001) and ovarian tissue (p < 0.001), resulting in 11-fold reduction in OSE expression of ERß1 protein (p < 0.0001). In aging OSE, expression patterns of both ER subtypes varied within cells and with cell shape. ER co-localization appeared predominantly cytoplasmic and was infrequent in columnar compared to cuboidal-shaped OSE cells. Immunofluorescence emission profiling and multiple-label immunofluorescent tagging of ER using confocal microscopy, provides sharp definition of ER locus enabling concurrent qualitative and quantitative analysis of ER protein. It offers significant potential for assessing ER protein subtype status in predisposition to OEC.