University General - Research Publications
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Mid-infrared Magnetic Mirror Based on a Hybrid Metal/Dielectric Metasurface
We propose a hybrid metal/dielectric metasurface that functions as a mid-infrared magnetic mirror. It consists amorphous silicon cuboids on gold. The physical mechanism is explained by image theory. Measured reflection spectra agree with simulations.
Systematic review of pharmacogenomics and adverse drug reactions in paediatric oncology patients.
Many paediatric patients with cancer experience significant chemotherapy side effects. Predisposition to drug reactions is governed by single nucleotide polymorphisms (SNPs). We performed a systematic review of the literature from 2006 through 2016. Outcomes of interest included patient characteristics, cancer type drug of interest, genes investigated, toxicity identified and genetic polymorphisms implicated. The primary toxicities studied were neurotoxicity cardiotoxicity, osteonecrosis, and thromboembolism and hypersensitivity reactions. The retrieved studies were grouped according to toxicity reported and SNP associations. This review highlights the discoveries to date in pharmacogenomics and paediatric oncology along with highlighting some of the important limitations in the area.
Atopy in people aged 40 years and over: Relation to airflow limitation.
BACKGROUND: Previous studies have reached conflicting conclusions about the role of atopy as a risk factor for COPD. In part, this is attributable to variation in the definitions of airflow limitation and the treatment of people with asthma. OBJECTIVE: To establish whether there is any independent association between atopy and post-bronchodilator airflow limitation in the general population aged 40 years and over. METHODS: A cross-sectional survey was conducted in a general population sample of 2415 people aged 40 years and over in Australia. A history of ever being diagnosed with asthma was elicited by questionnaire. Atopy was defined as any skin prick test weal to common aeroallergens ≥4 mm. Airflow limitation was defined as post-bronchodilator spirometric (FEV1 /FVC) ratio <lower limit of normal. Analyses were adjusted for potential confounding due to age, sex, smoking, race and socio-economic status. RESULTS: The prevalence of atopy, ever diagnosed asthma and post-bronchodilator airflow obstruction was 44.8%, 19.3% and 7.5%, respectively. In the population as a whole, atopy was associated with lower FEV₁ (adjusted difference -0.068L, 95% confidence interval (CI) -0.104 to -0.032), FVC (adj. difference -0.043L, 95% CI -0.086 to -0.0009) and post-bronchodilator FEV₁/FVC ratio (adj. difference -0.011, 95% CI -0.017 to -0.0055). The effect of atopy on lung function was no longer apparent when participants who reported ever diagnosed asthma were excluded (FEV₁ -0.011L, [95% CI -0.05 to 0.028L], FVC -0.012L [95% CI -0.060 to 0.036] and FEV₁/FVC ratio -0.0012 [95% CI -0.0072 to 0.0047L]). CONCLUSION AND CLINICAL RELEVANCE: The apparent association between atopy and post-bronchodilator airflow limitation in the general population appears to be explained by the association between atopy and having ever diagnosed asthma and the effect of asthma on lung function.
Short-term (48hours) intravenous serelaxin infusion has no effect on myogenic tone or vascular remodeling in rat mesenteric arteries
BACKGROUND: Short-term IV sRLX (recombinant human relaxin-2) infusion enhances endothelium-dependent relaxation in mesenteric arteries. This is initially underpinned by increased NO followed by a transition to prostacyclin. The effects of short-term IV sRLX treatment on pressure-induced myogenic tone and vascular remodeling in these arteries are unknown. Therefore, we investigated the effects of sRLX infusion on pressure-induced myogenic tone and passive mechanical wall properties in mesenteric arteries. METHODS: Mesenteric artery myogenic tone and passive mechanics were examined after 48-hours and 10-days infusion of sRLX. Potential mechanisms of action were assessed by pressure myography, qPCR, and Western blot analysis. RESULTS: Neither 48-hours nor 10-days sRLX treatment had significant effects on myogenic tone, passive arterial wall stiffness, volume compliance, or axial lengthening. However, in 48-hours sRLX -treated rats, incubation with the NO synthase blocker L-NAME significantly increased myogenic tone (P<.05 vs placebo), demonstrating an increased contribution of NO to the regulation of myogenic tone. eNOS dimerization, but not phosphorylation, was significantly upregulated in the arteries of sRLX -treated rats. CONCLUSION: In mesenteric arteries, 48-hours sRLX treatment upregulates the role of NO in the regulation of myogenic tone by enhancing eNOS dimerization, without altering overall myogenic tone or vascular remodeling.
Dietary analysis and nutritional counselling for caries prevention in dental practise: a pilot study
BACKGROUND: Dental practitioners agree that dietary counselling is essential for caries prevention; however, they provide advice infrequently due to a lack of confidence and competence. This study aimed to improve practises through an online training module exploring the use of a brief counselling method, and a diet assessment of caries risk form. METHODS: Dental practitioners (N = 41) completed a survey on current practises and confidence in providing dietary advice, followed by an online training module. Ten practitioners were involved in recruiting patients, eliciting a diet assessment of caries risk, and using brief counselling techniques with these patients. Patients were followed up at 6 months for a risk assessment review. Dental practitioners also completed a 6-month follow-up survey exploring changes in confidence and perceived barriers. RESULTS: Dental hygienists' confidence improved significantly following the intervention (P < 0.025). Patients showed a significant reduction in high-risk behaviour pertaining to quantity and timing of sugar intake, and significant trends in improvement of behaviours relating to frequency, exposure time and drinking style (P < 0.05). CONCLUSIONS: It appears that a simple online learning module can improve hygienists' confidence in dietary advice provision, and have a positive impact on patient behaviour change, within a relatively short time-frame.
Younger age is a risk factor for regrowth and recurrence of nonfunctioning pituitary macroadenomas: Results from a single Australian centre.
OBJECTIVE: The natural history of nonfunctioning pituitary macroadenomas (NFPMA) after surgical resection is variable, with guidelines unable to define the duration of radiological follow-up. In this first Australian series, we identify risk factors for regrowth/recurrence of NFPMA to assist with guiding recommendations for long-term follow-up. DESIGN: Retrospective analysis of all radiotherapy-naïve cases with NFPMA resected between 1995 and 2013. PATIENTS: One hundred and twenty-three cases had both ≥2 postoperative scans and ≥12-month follow-up. MEASUREMENTS: Regrowth was defined as any sustained increase in diameter of residual adenoma or recurrence as any new adenoma occurring post complete resection on serial pituitary MRI. RESULTS: Median follow-up time was 48 months (interquartile range [IQR]: 31-86). Overall regrowth/recurrence occurred in 29% (36/123). Regrowth occurred in 40% (30/76) at a median time of 44.5 months (IQR 22-80) compared to recurrence of 12.5% (6/48; P=.003), occurring at a median time of 48 months (IQR 12-96; P=.7). Further treatment was required in 66.7% and 56.7%, respectively (=1.0). Risk factors for regrowth/recurrence by multivariate analysis were presence of residual disease and younger age at presentation. The longest time for regrowth was 168 months (14 years) and recurrence 156 months (13 years). CONCLUSIONS: Presence of postoperative residual adenoma and younger age at presentation are the main predictors of regrowth/recurrence in NFPMA. Long-term serial imaging is required to detect regrowth and recurrence in younger patients and those with residual disease. Most regrowth/recurrences will occur within 10 years of follow-up.
Age at onset and persistence of eczema are related to subsequent risk of asthma and hay fever from birth to 18 years of age
BACKGROUND: Few studies have simultaneously addressed the importance of age of onset and persistence of eczema for the subsequent development of asthma and hay fever, particularly into early adulthood. METHODS: A high-risk birth cohort was recruited comprising 620 infants, who were then followed up frequently until 2 years of age, annually from age 3 to 7, then at 12 and 18 years, to document any episodes of eczema, current asthma, and hay fever. The generalized estimation equation technique was used to examine asthma and hay fever outcomes at 6 (n = 325), 12 (n = 248) and 18 (n = 240) years, when there was consistency of associations across the follow-ups. RESULTS: Very early-onset persistent (onset <6 months, still present from 2 to 5 years) eczema was related to current asthma (adjusted OR = 3.2 [95% CI = 1.7-6.1]), as was very early-onset remitting eczema (onset <6 months but not present from 2-5 years, OR = 2.7, 95% CI = 1.0-7.2) and early-onset persistent eczema (onset from 6-24 months, OR = 2.3, 95% CI = 1.2-4.7). Late-onset eczema (commenced from 2-5 years) was associated with increased risk of asthma at 12 years (OR = 3.0, 95% CI=1.1-8.2) but not at age 6 years. Only very early-onset persistent eczema was associated with increased risk of hay fever (aOR = 2.4, 95% CI = 1.4-4.1). CONCLUSION AND CLINICAL RELEVANCE: Eczema which commences in early infancy and persists into toddler years is strongly associated with asthma, and to a lesser extent hay fever, in high-risk children. If these associations are causal, prevention of early-life eczema might reduce the risk of respiratory allergy.
Can additional N fertiliser ameliorate the elevated CO2-induced depression in grain and tissue N concentrations of wheat on a high soil N background?
Elevated COâ stimulates crop yields but leads to lower tissue and grain nitrogen concentrations [N], raising concerns about grain quality in cereals. To test whether N fertiliser application above optimum growth requirements can alleviate the decline in tissue [N], wheat was grown in a Free Air COâ Enrichment facility in a lowâ rainfall cropping system on high soil N. Crops were grown with and without addition of 50â 60Â kg N/ha in 12 growing environments created by supplemental irrigation and two sowing dates over 3Â years. Elevated COâ increased yield and biomass (on average by 25%) and decreased biomass [N] (3%â 9%) and grain [N] (5%). Nitrogen uptake was greater (20%) in crops grown under elevated COâ . Additional N supply had no effect on yield and biomass, confirming high soil N. Small increases in [N] with N addition were insufficient to offset declines in grain [N] under elevated COâ . Instead, N application increased the [N] in straw and decreased N harvest index. The results suggest that conventional addition of N does not mitigate grain [N] depression under elevated COâ , and lend support to hypotheses that link decreases in crop [N] with biochemical limitations rather than N supply.
High serum vitamin D level correlates with better prognostic indicators in primary melanoma: A pilot study
BACKGROUND/OBJECTIVES: Sunlight is a major risk factor for cutaneous melanoma. However, its interaction with melanoma is complex. In particular, vitamin D is a UVB-derived hormone that has been shown to have anti-cancer effects. In this retrospective pilot study we sought to determine an association between the clinicopathological features of melanoma and the patients' corresponding serum vitamin D level. METHODS: In total, 109 primary melanomas diagnosed between 2001 and 2013 were retrospectively identified from our institutional database with a corresponding 25-hydroxyvitamin D3 level estimated within 6 months of diagnosis. Tumour, clinical (age, sex, tumour location) and pathological (thickness, mitosis, ulceration, Clark level, subtype, metastatic status) parameters were correlated with vitamin D. For statistical analysis, an unpaired Student's t-test and anova was used for categorical variables, and Spearman's correlation for continuous variables. RESULTS: Vitamin D level was inversely associated with Breslow thickness as a dichotomous, categorical and continuous variable. The association remained significant when controlled for patient's age and sex (P = 0.026). Vitamin D was higher in non-ulcerated tumours compared with ulcerated tumours (P = 0.006) and in tumours with mitotic rate <1/mm2 compared with ≥1/mm2 (P = 0.036). A significant association was found between vitamin D level and tumour histological subtype (P = 0.019). On subgroup analysis, significant associations were found between superficial spreading melanoma (SSM) and nodular melanoma (P = 0.026), and SSM and acral lentiginous melanoma (P = 0.007). CONCLUSION: A high vitamin D status may benefit prognosis in patients diagnosed with primary melanoma. A prospective cohort analysis with a large sample and controlled for other vitamin D confounders would validate these findings.
Low-dose rituximab and concurrent adjuvant therapy for pemphigus: Protocol and single-centre long-term review of nine patients
Pemphigus is an autoimmune B-cell mediated blistering disease associated with significant morbidity and mortality. Rituximab has proven effective for the treatment of steroid-refractory pemphigus, although there is controversy over the optimum dosing protocol. Additionally, effective disease control often requires long-term immunosuppression, even in disease-free periods. We present a case series of a single-centre long-term follow up of nine patients with pemphigus, treated with two 500-mg doses of rituximab separated by 14 days along with concurrent adjuvant therapy. In all these patients, low-dose rituximab resulted in B-cell depletion, along with a reduction in blistering disease. Three of these patients required repeat dosing cycles due to either relapsed disease or incomplete disease control following the first dosing cycle, and have remained disease free up to 154 weeks thus far. Six patients developed minor infections during the course of their treatment, but no major complications were observed.
Breast milk polyunsaturated fatty acids: associations with adolescent allergic disease and lung function
BACKGROUND: It has been hypothesized that n-3 PUFA in breast milk may assist immune and lung development. There are very limited data on possible long-term effects on allergic disease and lung function. The aim was to investigate associations of n-3 and n-6 PUFA levels in colostrum and breast milk with allergic disease and lung function at ages 12 and 18 years. METHODS: Polyunsaturated fatty acids were measured in 194 colostrum samples and in 118 three-month expressed breast milk samples from mothers of children enrolled in the Melbourne Atopy Cohort (MACS) Study, a high-risk birth cohort study. Associations with allergic diseases, skin prick tests and lung function assessed at 12 and 18 years were estimated using multivariable regression. RESULTS: Higher levels of n-3 but not n-6 PUFAs in colostrum were associated with a trend towards increased odds of allergic diseases, with strong associations observed for allergic rhinitis at 12 (OR = 5.69[95% CI: 1.83,17.60] per weight%) and 18 years (4.43[1.46,13.39]) and eczema at 18 years (9.89[1.44, 68.49]). Higher levels of colostrum n-3 PUFAs were associated with reduced sensitization (3.37[1.18, 9.6]), mean FEV1 (-166 ml [-332, -1]) and FEV1 /FVC ratio (-4.6%, [-8.1, -1.1]) at 12 years. CONCLUSION: Higher levels of colostrum n-3 PUFAs were associated with increased risks of allergic rhinitis and eczema up to 18 years, and sensitization and reduced lung function at 12 years. As residual confounding may have caused these associations, they should be replicated, but these results could indicate that strategies that increase maternal n-3 PUFA intake may not aid in allergic disease prevention.
Beyond the Storm: Comparison of Clinical Factors, Arrhythmogenic Substrate, and Catheter Ablation Outcomes in Structural Heart Disease Patients With versus Those Without a History of Ventricular Tachycardia Storm.
AIMS: Catheter ablation can be lifesaving in ventricular tachycardia (VT) storm, but the underlying substrate in patients with storm is not well characterized. We sought to compare the clinical factors, substrate, and outcomes differences in patients with sustained monomorphic VT who present for catheter ablation with VT storm versus those with a nonstorm presentation. METHODS: Consecutive ischemic (ICM; n = 554) or nonischemic cardiomyopathy patients (NICM; n = 369) with a storm versus nonstorm presentation were studied (ICM storm 186; NICM storm 101). RESULTS: In ICM, storm compared with nonstorm patients had significantly lower left ventricular (LV) ejection fraction (EF), greater number of antiarrhythmic drug (AAD) failures, slower VTs, greater number of scarred LV segments, higher incidence of anterior, septal, and apical endocardial LV scar (all P < 0.05). However, outcomes in follow-up were similar (12-month ventricular arrhythmia [VA]-free survival: 51% vs. 52%, P = 0.6; survival free of death/transplant 75% vs. 87%, P = 0.7). In addition to the above differences, NICM storm patients were also older; however, the extent and distribution of scar was similar except for a higher incidence of lateral endocardial scar in storm patients (P = 0.05). VA-free survival (36% vs. 47%, P = 0.004) and survival free of death/transplant, however, were worse in NICM storm than nonstorm patients (72% vs. 88%, P = 0.001). NICM storm patients had worse VA-free survival than ICM storm patients. CONCLUSION: There are differences in clinical factors and scar patterns in patients undergoing VT ablation who present with VT storm versus those with a nonstorm presentation. Clinical outcomes are worse in NICM storm patients.
Does serelaxin treatment alter passive mechanical wall properties in small resistance arteries?
The peptide hormone relaxin is recognized for its connective tissue remodeling actions in the reproductive tract during pregnancy and parturition, but it also has vascular remodeling actions independent of pregnancy. Recombinant human relaxin (serelaxin) treatment in male and non-pregnant female rodents enhances passive arterial compliance in the renal vasculature. This review focuses on serelaxin's actions on passive mechanical wall properties in small arteries and highlights the diversity of responses to serelaxin treatment in rodents. Different experimental approaches (duration of serelaxin treatment, rat strain, age) and animal models of disease (obesity, hypertension) will be considered. Most studies in young rodents demonstrate that serelaxin treatment fails to alter passive compliance in resistance-size arteries (mesenteric and femoral arteries and cerebral parenchymal arterioles), suggesting that serelaxin's beneficial effects are minimal in healthy animals. Short-term serelaxin treatment (5d) in aged, obese, and spontaneously hypertensive rats (SHRs) is largely without effect on passive mechanical wall properties. However, a longer duration of serelaxin treatment in SHRs (14d) enhances passive compliance in large muscular arteries as well as resistance-size arteries. In conclusion, serelaxin is capable of vascular remodeling. Its actions are vascular bed-dependent, more prominent in disease, and likely requires a longer duration of treatment to be effective.
Sites With Small Impedance Decrease During Catheter Ablation for Atrial Fibrillation Are Associated With Recovery of Pulmonary Vein Conduction
OBJECTIVE: To correlate impedance decrease during atrial fibrillation (AF) ablation with lesion durability and PV conduction recovery demonstrated during redo procedures. BACKGROUND: Markers of successful ablation beyond acute conduction block are needed to improve durability of pulmonary vein (PV) isolation (PVI). Local impedance decrease resulting from ablation is a real-time marker of tissue heating and is correlated with lesion creation. METHODS: Impedance changes associated with point-by-point radiofrequency ablation in the PV antra were recorded during 167 consecutive first-time AF ablations. During clinically indicated redo procedures, sites of recovered PV conduction were identified, and were correlated with the impedance change achieved during ablation at these locations during the initial procedure. RESULTS: Redo procedures were performed in 28 patients, in whom 19 sites of recovered PV conduction were documented. Most sites of PV reconnection (58%) occurred along the posterior PV antra. Ablation resulting in impedance decrease <10 ohms during the initial procedure was present in 89% (17/19) of sites with conduction recovery. Regions with adjacent ablation resulting in impedance decrease <10 ohms were associated with a higher rate of conduction recovery (37% vs. 1.5%, P < 0.001). Likewise, patients with PV conduction recovery demonstrated during redo procedure (Group 1) had larger regions where ablation resulted in <10 ohm impedance decrease than patients without PV conduction recovery (Group 2) (21.9 ± 15.5 mm vs. 11.5 ± 2.1 mm, P < 0.01). CONCLUSION: Recovered PV conduction occurs predominantly in regions where adjacent ablation applications result in impedance decreases <10 ohms. Impedance-guided ablation strategies may improve durability of PVI.
Vascular actions of relaxin: nitric oxide and beyond
The peptide hormone relaxin regulates the essential maternal haemodynamic adaptations in early pregnancy through direct actions on the renal and systemic vasculature. These vascular actions of relaxin occur mainly through endothelium-derived NO-mediated vasodilator pathways and improvements in arterial compliance in small resistance-size arteries. This work catalysed a plethora of studies which revealed quite heterogeneous responses across the different regions of the vasculature, and also uncovered NO-independent mechanisms of relaxin action. In this review, we first describe the role of endogenous relaxin in maintaining normal vascular function, largely referring to work in pregnant and male relaxin-deficient animals. We then discuss the diversity of mechanisms mediating relaxin action in different vascular beds, including the involvement of prostanoids, VEGF, endothelium-derived hyperpolarisation and antioxidant activity in addition to the classic NO-mediated vasodilatory pathway. We conclude the review with current perspectives on the vascular remodelling capabilities of relaxin. LINKED ARTICLES: This article is part of a themed section on Recent Progress in the Understanding of Relaxin Family Peptides and their Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.10/issuetoc.
Depression and anger in fathers of unsettled infants: A community cohort study
AIM: To examine the relationship between unsettled infant behaviour and fathers' depressive symptoms, cognitions surrounding infant sleep (anger, doubt), and personal sleep, in a community cohort. METHODS: Data were collected from 102 fathers of healthy infants at 4 weeks, 4 months and 6 months of age. Measures included father report of infant sleep and crying problems, depressive symptoms, cognitions about infant sleep and own sleep quality and quantity. Data were analysed using adjusted regression models. RESULTS: Sleep problems at 4 months of age were associated with increased depressive symptoms (adjusted mean difference 2.64 (1.27-4.00)), doubt (adjusted mean difference 1.82 (0.40-3.25)), anger (adjusted mean difference 1.86 (0.51-3.20)), poor personal sleep quantity (adjusted odds ratio (OR) 0.21; 95% confidence interval (CI) 0.09-0.51) and quality (adjusted OR 0.20; 95% CI 0.08-0.51); and at 6 months of age, with increased depressive symptoms (adjusted mean difference 2.56 (1.28-3.84)), anger (adjusted mean difference 1.63 (0.40-2.87)), poor personal sleep quantity (adjusted OR 0.14; 95% CI 0.05-0.38) and quality (adjusted OR 0.28; 95% CI 0.11-0.72). Infant cry problems at 4 months were associated with increased anger (adjusted mean difference 1.98 (0.60-3.36)) and doubt (adjusted mean difference 1.55 (0.05-3.05)); and at 6 months, with increased depressive symptoms (adjusted mean difference 3.04 (1.59-4.69)), anger (adjusted mean difference 2.73 (1.29-4.17)) and less personal sleep (adjusted OR 0.22; 95% CI 0.07-0.71). CONCLUSION: Fathers of unsettled infants reported greater anger towards their infant and increased depressive symptoms by 4 months infant age, with these symptoms persisting 2 months later. Evidence-based interventions are needed for these fathers.
Human glandular organoid formation in murine engineering chambers after collagenase digestion and flow cytometry isolation of normal human breast tissue single cells
Women with high mammographic density (MD) are at increased risk of breast cancer (BC) after adjustment for age and body mass index. We have developed a murine biochamber model in which both high MD (HMD) and low MD (LMD) tissue can be propagated. Here, we tested whether cells isolated by collagenase digestion and fluorescence-activated cell sorting (FACS) from normal breast can be reconstituted in our biochamber model, which would allow cell-specific manipulations to be tested. Fresh breast tissue was collected from women (n = 7) undergoing prophylactic mastectomy. The tissue underwent collagenase digestion overnight and, in some cases, additional FACS enrichment to obtain mature epithelial, luminal progenitor, mammary stem, and stromal cells. Cells were then transferred bilaterally into biochambers in SCID mice (n = 5-7) and incubated for 6 weeks, before harvesting for histological analyses, and immunohistochemical staining for cytokeratins (CK), vimentin, Ki-67, murine macrophages, and Cleaved Caspase-3. Biochambers inoculated with single cells after collagenase digestion or with flow cytometry contained glandular structures of human origin (human vimentin-positive), which expressed CK-14 and pan-CK, and were proliferating (Ki-67-positive). Glandular structures from the digested tissues were smaller than those in chambers seeded with finely chopped intact mammary tissue. Mouse macrophage infiltration was higher in the chambers arising from digested tissues. Pooled single cells and FACS fractionated cells were viable in the murine biochambers and formed proliferating glandular organoids of human origin. This is among the first report to demonstrate the success of formed human glandular organoids from isolated primary mammary cells in the murine biochamber model.
Cancer beliefs in ethnic minority populations: a review and meta-synthesis of qualitative studies
People from ethnic minorities often experience poorer cancer outcomes, possibly due to later presentation to healthcare and later diagnosis. We aimed to identify common cancer beliefs in minority populations in developed countries, which can affect symptom appraisal and help seeking for symptomatic cancer. Our systematic review found 15 relevant qualitative studies, located in the United Kingdom (six), United States (five), Australia (two) and Canada (two) of African, African-American, Asian, Arabic, Hispanic and Latino minority groups. We conducted a meta-synthesis that found specific emotional reactions to cancer, knowledge and beliefs and interactions with healthcare services as contributing factors in help seeking for a cancer diagnosis. These findings may be useful to inform the development of interventions to facilitate cancer diagnosis in minority populations.
Attitudes and barriers to providing dietary advice: perceptions of dental hygienists and oral health therapists
OBJECTIVES: Effective dietary counselling in a dental setting can significantly reduce the risk of oral disease. However, studies suggest that dental professionals are not instigating dietary advice on a regular basis, and there is a lack of current information of the barriers experienced that limit the delivery of dietary advice. The aim of this study was to investigate the current attitudes and practice behaviours of dental hygienists and oral health therapists in NSW, Australia, regarding dietary advice, and identify the barriers that limit its delivery. METHODS: A convenience sample of dental hygienists and oral health therapists were surveyed using a mail-out questionnaire. The questionnaire investigated the demographic data of participants, the attitudes and practice behaviours of participants, the perceived barriers and current dietary resources accessed by participants. RESULTS: Of 987 dental hygienists and oral health therapists, 426 participants responded. The study results suggest that many dental hygienists and oral health therapists have positive beliefs regarding the importance of dietary counselling. However, there are a multitude of barriers preventing the delivery of dietary advice; these include time, patient compliance, patient knowledge of nutrition topics, personal counselling skills and practitioners' knowledge of nutrition. CONCLUSION: Whilst dental hygienists and oral health therapists recognize the importance of diet and have positive attitudes towards providing dietary advice to patients, this study identified many barriers preventing implementation in practice. This information may be used to develop targeted strategies aimed at overcoming these barriers and improving behaviours.
Antibody responses following incident anal and penile infection with human papillomavirus in teenage men who have sex with men
Men who have sex with men (MSM) are at risk for human papillomavirus (HPV)-related anal cancer. Few data exist on antibody responses following incident anogenital infection with HPV in teenage MSM. A cohort of 200 MSM aged 16-20 years from Melbourne, Australia were assessed at baseline, 3, 6 and 12 months. At each visit anal and penile swabs were collected for HPV DNA and serum for HPV antibodies for genotypes 6, 11, 16 and 18 (Merck's Multiplex Assays using Luminex). The main outcome, seroconversion, was defined as the detection of HPV antibodies following a negative antibody result for the same HPV type at baseline. The seroincidence rates for HPV types 6, 11, 16 and 18 were: 19 (95% CI 12-26), 7 (3-12), 4 (1-8) and 6 (3-11) per 100 person-years, respectively. Men who experienced incident anal HPV infections from types 6/11 were significantly more likely to develop serum antibodies to the same HPV type(s) than those who experienced incident anal infections from types 16/18 [73 vs. 18%, odds ratio (OR) = 15, 95% CI: 2-118]. The median time between incident anal HPV infection and seroconversion for HPV 6, 11, 16 and 18 was: 91, 38, 161 and 182 days, respectively. Antibody responses against HPV types 6/11 were significantly more likely to occur following incident anal compared with incident penile infection with HPV types 6/11 (OR = 6, 95% CI: 2-21). The likelihood of antibody responses following anogenital HPV infections depends on the HPV type and site of infection.
Hormonal evaluation in relation to phenotype and genotype in 286 patients with a disorder of sex development from Indonesia
OBJECTIVE: The objective of this study was to determine the aetiological spectrum of disorders of sex development (DSD) in a large cohort of underprivileged and undiagnosed patients from Indonesia. METHODS: A total of 286 patients with atypical external and/or internal genitalia were evaluated using clinical, hormonal, molecular genetic and histological parameters. RESULTS: The age (years) at presentation was 0-0·5 in 41 (14·3%), >0·5-12 in 181 (63·3%) and >12 in 64 cases (22·4%). 46,XY DSD was most common (68·2%, n = 195), 46,XX DSD was found in 23·4% (n = 67) and sex chromosomal DSD in 8·4% (n = 24). In 61·2% of 46,XX DSD patients, 17·9% of 46,XY DSD patients and all sex chromosome DSD patients (29·4% in total), a final diagnosis was reached based on genetic or histological gonadal tissue evaluation. 17-hydroxyprogesterone and androstenedione levels were the most distinctive parameters in 46,XX DSD patients. In 46,XY DSD, diagnostic groups were identified based on the external masculinization score: androgen action disorder (AAD), unknown male undermasculinization (UMU), and gonadal dysgenesis (GD). LH, FSH and testosterone levels were most informative especially in the older age group. HCG tests were of no additional value as no patients with androgen synthesis disorders were found. Hormonal profiles of patients with sex chromosome DSD and a Y-chromosome sequence containing karyotype showed high levels of LH and FSH, and low levels of AMH, inhibin B and testosterone compared with the normal male range. Gene mutations were found in all patients with CAH, but in only 24·5% and 1·8% of patients with AAD and UMU. In 32% of 46,XY GD patients, copy number variants of different genes were found. CONCLUSION: A stepwise diagnostic approach led to a molecularly or histologically proven final diagnosis in 29·4% of the patients. The most informative parameters were serum levels of 17-hydroxyprogesterone and androstenedione in 46,XX DSD patients, and serum LH, FSH and testosterone levels in 46,XY DSD patients.
Risk factors associated with incident sexually transmitted infections in HIV-positive patients in the Australian HIV Observational Database: a prospective cohort study
OBJECTIVES: We established a subcohort of HIV-positive individuals from 10 sexual health clinics within the Australian HIV Observational Database (AHOD). The aim of this study was to assess demographic and other factors that might be associated with an incident sexually transmitted infection (STI). METHODS: The cohort follow-up was from March 2010 to March 2013, and included patients screened at least once for an STI. We used survival methods to determine time to first new and confirmed incident STI infection (chlamydia, gonorrhoea, syphilis or genital warts). Factors evaluated included sex, age, mode of HIV exposure, year of AHOD enrolment, hepatitis B or C coinfection, time-updated CD4 cell count, time-updated HIV RNA viral load, and prior STI diagnosis. RESULTS: There were 110 first incident STI diagnoses observed over 1015 person-years of follow-up, a crude rate of 10.8 [95% confidence interval (CI) 9.0-13.0] per 100 person-years. Factors independently associated with increased risk of incident STI included younger age [≥ 50 vs. 30-39 years old, adjusted hazards ratio (aHR) 0.4; 95% CI 0.2-0.8; P < 0.0001]; prior STI infection (aHR 2.5; 95% CI 1.6-3.8; P < 0.001), and heterosexual vs. men who have sex with men (MSM) as the likely route of exposure (aHR 0.2; 95% CI 0.1-0.6; P < 0.001). CONCLUSIONS: In this cohort of individualsbeing treated with antiretroviral drugs, those who were MSM, who were 30-39 years old, and who had a prior history of STI, were at highest risk of a further STI diagnosis.
Why attend a memory clinic? What do patients and their families want and/or expect?
OBJECTIVE: To explore which symptoms led people to seek a memory clinic assessment and what they wanted and expected from that assessment. Did the patient and family want and/or expect diagnostic disclosure and, if so, why? METHODS: Patients scheduled for memory clinic appoint-ments received two questionnaires by post prior to clinic attendance - one for the patient, one for the next-of- kin - regarding symptomatology, wants, expectations and rationale. RESULTS: Ninety-two per cent of patients (n = 47) and 88% (n = 43) of next-of-kin wanted the patient to be informed of the diagnosis; 84% (n = 43) of patients and 86% (n = 42) of next-of-kin expected the patient to be informed. Rationales for diagnostic disclosure were categorised under themes of planning, treatment, information, coping strategies and rights. CONCLUSIONS: Patients and families want diagnostic disclosure in order to plan, receive treatment, receive help and learn strategies to cope. This knowledge is seen as the patient's right.
The frequency of mucosal-associated invariant T cells is selectively increased in dermatitis herpetiformis
BACKGROUND/OBJECTIVES: Mucosal-associated invariant T (MAIT) cells are a novel subset of innate-like T-cells that are enriched in mucosal tissues. Their presence in human skin has only recently been recognised. We describe the expression of skin-tropic molecules on human skin MAIT cells at steady state and investigate their contribution to various dermatoses with known T-cell involvement. METHODS: To examine the expression of skin-tropic molecules by MAIT cells at steady state, we performed a flow cytometric analysis of blood and skin samples from healthy donors. To investigate any potential wider contribution of MAIT cells to skin disease, we examined psoriasis, alopecia areata and dermatitis herpetiformis biopsies using immunofluorescent staining to identify the proportion of T-cells expressing MAIT cell surface markers. RESULTS: We found that MAIT cells constituted a small population of T-cells in normal human skin, similar to the percentage found in peripheral blood. Like other skin T-cells, skin MAIT cells expressed high levels of the skin-associated markers, cutaneous lymphocyte antigen and CD103. In psoriasis and alopecia areata the proportion of MAIT cells was similar to that found in normal skin, but in dermatitis herpetiformis it was significantly elevated. CONCLUSIONS: The expression of skin-tropic molecules by skin MAIT cells is consistent with their resident status in normal human skin. Our results suggest that MAIT cells may play a role in the pathogenesis of dermatitis herpetiformis.
Time-dependent activation of prostacyclin and nitric oxide pathways during continuous i.v. infusion of serelaxin (recombinant human H2 relaxin)
BACKGROUND AND PURPOSE: In the RELAX-AHF trial, a 48 h i.v. serelaxin infusion reduced systemic vascular resistance in patients with acute heart failure. Consistent with preclinical studies, serelaxin augments endothelial vasodilator function in rat mesenteric arteries. Little is known about the contribution of endothelium-derived relaxing factors after a longer duration of continuous serelaxin treatment. Here we have assessed vascular reactivity and mechanistic pathways in mesenteric arteries and veins and the aorta after 48 or 72 h continuous i.v. infusion of serelaxin. EXPERIMENTAL APPROACH: Male rats were infused with either placebo or serelaxin (13.3 μg·kg(-1) ·h(-1) ) via the jugular vein using osmotic minipumps. Vascular function was assessed using wire myography. Changes in gene and protein expression and 6-keto PGF1α levels were determined by quantitative PCR, Western blot and ELISA respectively. KEY RESULTS: Continuous i.v. serelaxin infusion augmented endothelium-dependent relaxation in arteries (mesenteric and aorta) but not in mesenteric veins. In mesenteric arteries, 48 h i.v. serelaxin infusion increased basal NOS activity, associated with increased endothelial NOS (eNOS) expression. Interestingly, phosphorylated-eNOS(Ser1177) , eNOS and basal NOS activity were reduced in mesenteric arteries following 72 h serelaxin treatment. At 72 h, serelaxin treatment improved bradykinin-mediated relaxation through COX2-derived PGI2 production. CONCLUSIONS AND IMPLICATIONS: Continuous i.v. serelaxin infusion enhanced endothelial vasodilator function in arteries but not in veins. The underlying mediator at 48 h was NO but there was a transition to PGI2 by 72 h. Activation of the PGI2 -dependent pathway is key to the prolonged vascular response to serelaxin treatment.
Is There a Role for the ThinPrep Imaging System in Reporting Anal Cytology?
BACKGROUND: The ThinPrep Imaging System (TIS) is an accurate time-saving method of reading cervical ThinPrep slides in screening programs. As anal and cervical cytology are morphologically similar, TIS can potentially be used for anal cytology. We assessed the performance of TIS on anal ThinPrep slides from homosexual men in a natural history study of human papillomavirus-related anal abnormalities. METHODS: Four hundred nineteen anal cytology slides were processed by TIS and classified by a cytologist as either No further review (slide archived) or Manual review (slide requiring full manual screen). The results were compared with the original manual screening report for all slides and specifically for those screening episodes accompanied by a high-grade squamous intraepithelial lesion (HSIL) on concurrent biopsy. RESULTS: One hundred seventy six of 419 (42.0%) slides were classified as No further review, with a trend of decreasing proportions as the degree of severity of the cytological abnormality increased. Thirteen (27.7%) slides with an original unsatisfactory report were classified as No further review. Eighty two (92.1%) of those with biopsy HSIL and cytological abnormality were classified for Manual review, including all 45 (100%) with cytological HSIL. CONCLUSION: The cervical algorithm of TIS performed best on anal samples when HSIL was present both cytologically and histologically. The 27.7% unsatisfactory slides classified as No further review may indicate need for use of different criteria from cervical cytology. Because of the high prevalence of abnormalities, and hence the large proportion of slides needing manual review, the cytologist time-saving would compare unfavorably with use of TIS in cervical screening.
FcRn mediates fast recycling of endocytosed albumin and IgG from early macropinosomes in primary macrophages
(COMPANY BIOLOGISTS LTD, 2020-03-01)
The neonatal Fc receptor (FcRn) rescues albumin and IgG from degradation following endocytosis and thereby extends the half-life of these plasma proteins. However, the pathways for the uptake of these soluble FcRn ligands, and the recycling itinerary of the FcRn-ligand complexes, have not been identified in primary cells. Here, we have defined the recycling of human albumin and IgG in primary mouse macrophages selectively expressing the human FcRn. Albumin is internalised by macropinocytosis; in the absence of FcRn, internalised albumin is rapidly degraded, while in the presence of FcRn albumin colocalises to SNX5-positive membrane domains and is partitioned into tubules emanating from early macropinosomes for delivery in transport carriers to the plasma membrane. Soluble monomeric IgG was also internalised by macropinocytosis and rapidly recycled by the same pathway. In contrast, the fate of IgG bound to surface Fcγ receptors differed from monomeric IgG endocytosed by macropinocytosis. Overall, our findings identify a rapid recycling pathway for FcRn ligands from early macropinosomes to the cell surface of primary cells.
Changes in the modes of twin birth in Victoria, 1983-2015
OBJECTIVES: To examine changes in the modes of delivery of twins in Victoria over 33 years. DESIGN: Retrospective population-based study. SETTING, PARTICIPANTS: All twin births in Victoria, 1 January 1983 - 31 December 2015. MAJOR OUTCOMES: Mode of birth (vaginal, planned or unplanned caesarean delivery); indications for caesarean delivery. RESULTS: During 1983-2015, 32 187 twin pregnancies ended in live or stillbirths in Victoria. The proportion of twins born by caesarean delivery increased from 24% (156 twin deliveries) in 1983 to 71% (782 deliveries) in 2015. The proportion of twin births by planned caesarean delivery with twin pregnancy as the sole indication for caesarean delivery increased across this period from 1.8% (12 twin deliveries) to 21% (231 deliveries). The proportion of twin births by caesarean delivery and the proportion of caesarean twin deliveries with twin pregnancy as the principal indication each differed between Victorian regions. CONCLUSION: During 1983-2015, the proportion of twins born in Victoria by caesarean delivery increased almost threefold, mostly because caesarean delivery has become the preferred mode of birth for twin pregnancies. Regional differences in the delivery of twins suggest that the number of caesarean deliveries can be reduced with appropriate system and training support.
Initiation of vasopressor infusions via peripheral versus central access in patients with early septic shock: A retrospective cohort study
OBJECTIVE: To assess whether the initiation of vasopressor infusions via peripheral venous catheters (PVC) compared to central venous catheters (CVC) in ED patients with early septic shock was associated with differences in processes of care and outcomes. METHODS: We conducted a post-hoc analysis of the ARISE trial. We compared participants who had a vasopressor infusion first commenced via a PVC versus a CVC. The primary outcome was 90 day mortality. RESULTS: We studied 937 participants. Of these, 389 (42%) had early vasopressor infusion commenced via a PVC and 548 (58%) via a CVC. Trial participants who received a vasopressor infusion via a PVC were more severely ill, with higher median (interquartile range [IQR]) Acute Physiology And Chronic Health Evaluation (APACHE II) scores (17 [13-23] versus 16 [12-21], P = 0.003), and higher median (IQR) lactate (mmol/L) (3.6 [1.9-5.8] versus 2.5 [1.5-4.5], P < 0.001). After adjusting for baseline covariates, the estimated odds ratio for mortality for PVC-treated patients was 1.26 (95% confidence interval 0.95-1.67, P = 0.11). Trial participants who had vasopressors commenced via PVC had a shorter median (IQR) time to commencement of antimicrobials (55 [32-96] versus 71.5 [39-119] min, P < 0.001) and a shorter median (IQR) time to commencement of vasopressors (2.4 [1.3-3.9] versus 4.9 [3.5-6.6] h, P < 0.001). CONCLUSION: The practice of commencing a vasopressor infusion via a PVC was common in the ARISE trial and more frequent in trial participants with higher severity of illness. Commencement of a vasopressor infusion via a PVC was associated with some improvements in processes of care and, after adjustment, was not associated with an increased risk of death.
Resident perceptions of opportunity for communication and contribution to care planning in residential aged care
BACKGROUND AND AIM: Irrespective of age, communication is a tool of expression and a key daily activity meeting the human need for social interaction and connection. The introduction of consumer-directed care (CDC) emphasises the importance of communication to provide consumers with the opportunity to exercise choice over the care they receive. As consumer-directed care progresses, it is hypothesised that the feasibility of shared decision-making and care planning in residential aged care will be largely determined by the communication opportunities afforded to the residents. Therefore, the aim of this study was to explore resident perceptions of the opportunities they have to communicate, including the opportunity to express their care preferences and contribute opinions about their care. DESIGN: A qualitative inductive design was adopted. METHODS: An individual interview format was used to gather the perspectives of 102 residents. Data were analysed using qualitative content analysis to generate themes illustrating patterns in participant views. FINDINGS: Overall, residents desired increased involvement in their care planning and increased opportunity for more meaningful communication and social opportunities. Residents described the negative impact of the communication difficulties they face on their communication and the need for support and activities to be tailored to residents' individual communication needs. CONCLUSIONS: To facilitate resident participation in CDC and meet resident desire for increased social communication, further investment in resources to support resident-staff communication and accommodate residents' individual communication needs is required. IMPLICATIONS FOR PRACTICE: By highlighting communication as a stand-alone activity and a priority of residents, the findings of this study raise the profile of communication and demonstrate the need for explicit allocation of care time and specialist services to support resident-staff communication and social communication in residential aged care. Such support must be tailored to meet residents' individual communication needs and be coupled with increased staff training in providing communication support. Without facilitating resident communication and increasing the opportunity to communicate, shared decision-making and care planning in residential aged care consistent with person-centred and consumer-directed models of care will be limited.
Tranexamic acid modulates the cellular immune profile after traumatic brain injury in mice without hyperfibrinolysis
BACKGROUND: Traumatic brain injury (TBI) is known to promote immunosuppression, making patients more susceptible to infection, yet potentially exerting protective effects by inhibiting central nervous system (CNS) reactivity. Plasmin, the effector protease of the fibrinolytic system, is now recognized for its involvement in modulating immune function. OBJECTIVE: To evaluate the effects of plasmin and tranexamic acid (TXA) on the immune response in wild-type and plasminogen-deficient (plg-/- ) mice subjected to TBI. METHODS: Leukocyte subsets in lymph nodes and the brain in mice post TBI were evaluated by flow cytometry and in blood with a hemocytometer. Immune responsiveness to CNS antigens was determined by Enzyme-linked Immunosorbent Spot (ELISpot) assay. Fibrinolysis was determined by thromboelastography and measuring D-dimer and plasmin-antiplasmin complex levels. RESULTS: Plg-/- mice, but not plg+/+ mice displayed increases in both the number and activation of various antigen-presenting cells and T cells in the cLN 1 week post TBI. Wild-type mice treated with TXA also displayed increased cellularity of the cLN 1 week post TBI together with increases in innate and adaptive immune cells. These changes occurred despite the absence of systemic hyperfibrinolysis or coagulopathy in this model of TBI. Importantly, neither plg deficiency nor TXA treatment enhanced the autoreactivity within the CNS. CONCLUSION: In the absence of systemic hyperfibrinolysis, plasmin deficiency or blockade with TXA increases migration and proliferation of conventional dendritic cells (cDCs) and various antigen-presenting cells and T cells in the draining cervical lymph node (cLN) post TBI. Tranexamic acid might also be clinically beneficial in modulating the inflammatory and immune response after TBI, but without promoting CNS autoreactivity.
Common mechanisms of executive attention underlie executive function and effortful control in children
Executive Function (EF) and Effortful Control (EC) have traditionally been viewed as distinct constructs related to cognition and temperament during development. More recently, EF and EC have been implicated in top-down self-regulation - the goal-directed control of cognition, emotion, and behavior. We propose that executive attention, a limited-capacity attentional resource subserving goal-directed cognition and behavior, is the common cognitive mechanism underlying the self-regulatory capacities captured by EF and EC. We addressed three related questions: (a) Do behavioral ratings of EF and EC represent the same self-regulation construct? (b) Is this self-regulation construct explained by a common executive attention factor as measured by performance on cognitive tasks? and (c) Does the executive attention factor explain additional variance in attention deficit hyperactivity disorder (ADHD) problems to behavioral ratings of self-regulation? Measures of performance on complex span, general intelligence, and response inhibition tasks were obtained from 136 preadolescent children (M = 11 years, 10 months, SD = 8 months), along with self- and parent-reported EC, and parent-reported EF, and ADHD problems. Results from structural equation modeling demonstrated that behavioral ratings of EF and EC measured the same self-regulation construct. Cognitive tasks measured a common executive attention factor that significantly explained 30% of the variance in behavioral ratings of self-regulation. Executive attention failed to significantly explain additional variance in ADHD problems beyond that explained by behavioral ratings of self-regulation. These findings raise questions about the utility of task-based cognitive measures in research and clinical assessment of self-regulation and psychopathology in developmental samples.
The Interplay Between Multisensory Associative Learning and IQ in Children
This study assessed the developmental profile of unisensory and multisensory processes, and their contribution to children's intellectual abilities (8- and 11-year olds, N = 38, compared to adults, N = 19) using a simple audiovisual detection task and three incidental associative learning tasks with different sensory signals: visual-verbal with pseudowords, novel audiovisual, and visual-visual. The level of immaturity throughout childhood was dependent on both, the sensory signal type and the task. Associative learning was significantly enhanced with verbal sounds, compared to novel audiovisual and unisensory visual learning. Visual-verbal learning was also the best predictor of children's general intellectual abilities. The results demonstrate a separate developmental trajectory for visual and verbal multisensory processes and independent contributions to the development of cognitive abilities throughout childhood.
Communal responsibility: a history of health collectives in Australia
Healthcare encompasses multiple discourses to which health professionals, researchers, patients, carers and lay individuals contribute. Networks of patients and non-professionals often act collectively to build capacity, enhance access to resources, develop understanding and improve provision of care. This article explores the concept of health collectives and three notable examples that have had an enduring and profound impact in the Australian context.
Sexually transmissible infections among transgender men and women attending Australian sexual health clinics.
OBJECTIVES: To estimate rates of HIV infection, chlamydia, gonorrhoea, and infectious syphilis in transgender men and women in Australia; to compare these rates with those for cisgender people. DESIGN: Cross-sectional, comparative analysis of de-identified health data. SETTING, PARTICIPANTS: We analysed data for 1260 transgender people (404 men, 492 women, 364 unrecorded gender), 78 108 cisgender gay and bisexual men, and 309 740 cisgender heterosexual people who attended 46 sexual health clinics across Australia during 2010-2017. MAIN OUTCOME MEASURES: First-visit test positivity for sexually transmitted infections (STIs), stratified by patient group and year; demographic and behavioural factors associated with having STIs. RESULTS: 14 of 233 transgender men (6.0%) and 34 of 326 transgender women (10%) tested during first clinic visits were chlamydia-positive; nine transgender men (4%) and 28 transgender women (8.6%) were gonorrhoea-positive. One of 210 tested transgender men (0.5%) and ten of 324 tested transgender women (3.1%) were diagnosed with infectious syphilis; 14 transgender men (3.5%) and 28 transgender women (5.7%) were HIV-positive at their first visit. The only significant change in prevalence of an STI among transgender patients during the study period was the increased rate of gonorrhoea among transgender women (from 3.1% to 9.8%). Compared with cisgender gay and bisexual men, transgender men were less likely (adjusted odds ratio [aOR], 0.46; 95% CI, 0.29-0.71; P = 0.001) and transgender women as likely (aOR, 0.98; 95% CI, 0.73-1.32; P = 0.92) to be diagnosed with a bacterial STI; compared with heterosexual patients, transgender men were as likely (aOR, 0.72; 95% CI, 0.46-1.13; P = 0.16) and transgender women more likely (aOR, 1.56; 95% CI, 1.16-2.10; P = 0.003) to receive a first-visit bacterial STI diagnosis. CONCLUSIONS: The epidemiology of STIs in transgender people attending Australian sexual health clinics differs from that of cisgender patients. Gender details must be captured by health data systems to facilitate appropriate delivery of sexual health care.