The relationship between self-reported alcohol intake and the morbidities managed by GPs in Australia

BACKGROUND: One in five Australians consume alcohol at risky or harmful levels. Most (85%) attend a general practitioner at least once a year, giving opportunity for detecting and providing brief interventions for reducing alcohol-related harm. Historically, detection rates of problem drinking have been low in general practice, producing lower prevalence estimates of heavy drinking than expected from population surveys. METHOD: The BEACH program collects data from 100 consecutive patient consultations with 1000 GPs annually. For 40 consecutive encounters, GPs ask adult patients three questions on alcohol consumption (AUDIT-C). This paper reports the problems managed and treatments provided at encounters with heavy and non-heavy drinkers, grouped by their response to the 3rd question, and compares the two groups before and after standardisation for age and sex. Heavy drinking was defined as having 6 or more standard drinks at least once a week or more often. RESULTS: Heavy drinking was reported by 7.3% patients overall; more prevalent among men (13.8%) than women (3.9%); and among Indigenous patients (18.5%). Prevalence was highest in young adults (18–24 years)(12.7%) and decreased with age. Patients from a non-English speaking background were less likely to be heavy drinkers. Heavy drinkers had more problems managed at encounters, more chronic problems, physical injuries and psychological problems (particularly depression) managed than non-heavy drinkers. They were less likely to have respiratory complaints, ischaemic heart disease or diabetes managed. CONCLUSION: Heavy drinkers are more likely than non- or light drinkers to see their GP for management of chronic problems, psychological problems and physical injuries. However, the wide range of morbidity managed in heavy drinkers means that relying on clinical impression alone to detect this group will not suffice and should be augmented with routine screening. Given the pressures of general practice, finding efficient methods of screening for alcohol problems remains a priority

Factors influencing billing status in general practice

The document attached has been archived with permission from the editor of the Medical Journal of Australia. An external link to the publisher’s copy is included.Robert W Pegram, Lisa Valent

Integrin signaling modulates AQP2 trafficking via Arg-Gly-Asp (RGD) motif.

Aquaporin-2 (AQP2) increases the water permeability of renal collecting ducts in response to vasopressin. Vasopressin stimulation is accompanied by a profound remodeling of actin cytoskeleton whose dynamics are regulated by crosstalk between intracellular and extracellular signals. Here, we report that AQP2 contains a conserved RGD domain in its external C-loop. Co-immunoprecipitation experiments demonstrated that AQP2 binds integrin β1 in renal tissue and in MCD4 cells. To investigate the role of this interaction on AQP2 trafficking, cells were exposed to synthetic RGD-containing peptides, GRGDNP or GRGDSP, able to bind certain integrins. Incubation with these peptides increased the membrane expression of AQP2 in the absence of hormonal stimulation as assessed by confocal analysis and cell surface biotinylation. To identify the signals underlying the effects of peptides on AQP2 trafficking, some possible intracellular messengers were evaluated. Exposure of MCD4 cells to GRGDNP increased intracellular cAMP as assessed by FRET studies while GRGDSP increased intracellular calcium concentration. Taken together, these data propose integrins as new players controlling the cellular localization of AQP2, via two distinct signal transduction pathways dependent on cAMP and calcium respectively

Differential modulation of intracellular Ca2+ responses associated with calcium-sensing receptor activation in renal collecting duct cells.

In this work, we studied G protein-coupled Extracellular Calcium Sensing Receptor (CaR) signaling in mouse cortical collecting duct cells (MCD4) expressing endogenous CaR. Intracellular [Ca2+] measurements performed with real time video imaging revealed that CaR stimulation with 5mM Ca2+, 300µM Gd3+ and with 10µM of specific allosteric modulator NPS-R 568, all resulted in an increase in [Ca2+]i although displaying different features. Specifically, Ca2+ as well as stimulation with NPS-R 568 induced a rapid peak of [Ca2+]i while stimulation with Gd3+ induced transient intracellular Ca2+ oscillations. PLC inhibition completely abolished any [Ca2+]i increase after stimulation with CaR agonists. Inhibition of Rho or Rho kinase (ROK) abolished [Ca2+]i oscillations induced by Gd3+, while the peak induced by high Ca2+ was similar to control. Conversely, emptying the intracellular calcium stores abolished the response to Gd3+. On the other hand, the inhibition of calcium influx did not alter calcium changes. We conclude that in our cell model, CaR stimulation with distinct agonists activates two distinct transduction pathways, both PLC-dependent. The transient cytosolic Ca2+ oscillations produced by Gd3+ are modulated by Rho-Rho kinase signaling, whereas the rapid peak of intracellular Ca2+ in response to 5mM [Ca2+]o is mainly due to PLC/IP3 pathway activation

Pre-service teachers’ approaches to gender-nonconforming children in preschool and primary school: Clinical and educational implications

Corrective approaches taken by teachers towards gender nonconformity in childhood may increase the gender pressure that children feel, negatively affecting well-being and development. This study was aimed at assessing whether the approaches of 305 pre-service preschool and primary school teachers towards gender nonconformity in childhood are influenced by sexist and homophobic attitudes and feelings. The results indicated that the majority of the sample would adopt a supportive and affirmative approach towards gender nonconformity in childhood. Notwithstanding, the results also showed that sexism influenced the likelihood of adopting corrective approaches only to gender-nonconforming primary school children, whilst homophobia was positively associated with adoption of a corrective approach to gender nonconformity in both preschool and primary school children. Suggestions for educational and clinical practice are discussed

Changes in longer consultations for children in general practice

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97524/1/jpc12157.pd

AQP5 is expressed in type-B intercalated cells in the collecting duct system of the rat, mouse and human kidney.

We screened human kidney-derived multipotent CD133+/CD24+ ARPCs for the possible expression of all 13 aquaporin isoforms cloned in humans. Interestingly, we found that ARPCs expressed both AQP5 mRNA and mature protein. This novel finding prompted us to investigate the presence of AQP5 in situ in kidney. We report here the novel finding that AQP5 is expressed in human, rat and mouse kidney at the apical membrane of type-B intercalated cells. AQP5 is expressed in the renal cortex and completely absent from the medulla. Immunocytochemical analysis using segment- and cell type-specific markers unambiguously indicated that AQP5 is expressed throughout the collecting system at the apical membrane of type-B intercalated cells, where it co-localizes with pendrin. No basolateral AQPs were detected in type-B intercalated cells, suggesting that AQP5 is unlikely to be involved in the net trans-epithelial water reabsorption occurring in the distal tubule. An intriguing hypothesis is that AQP5 may serve an osmosensor for the composition of the fluid coming from the thick ascending limb. Future studies will unravel the physiological role of AQP5 in the kidney

Calcium-Sensing Receptor and Aquaporin 2 Interplay in Hypercalciuria-Associated Renal Concentrating Defect in Humans. An In Vivo and In Vitro Study

One mechanism proposed for reducing the risk of calcium renal stones is activation of the calcium-sensing receptor (CaR) on the apical membranes of collecting duct principal cells by high luminal calcium. This would reduce the abundance of aquaporin-2 (AQP2) and in turn the rate of water reabsorption. While evidence in cells and in hypercalciuric animal models supports this hypothesis, the relevance of the interplay between the CaR and AQP2 in humans is not clear. This paper reports for the first time a detailed correlation between urinary AQP2 excretion under acute vasopressin action (DDAVP treatment) in hypercalciuric subjects and in parallel analyzes AQP2-CaR crosstalk in a mouse collecting duct cell line (MCD4) expressing endogenous and functional CaR. In normocalciurics, DDAVP administration resulted in a significant increase in AQP2 excretion paralleled by an increase in urinary osmolality indicating a physiological response to DDAVP. In contrast, in hypercalciurics, baseline AQP2 excretion was high and did not significantly increase after DDAVP. Moreover DDAVP treatment was accompanied by a less pronounced increase in urinary osmolality. These data indicate reduced urinary concentrating ability in response to vasopressin in hypercalciurics. Consistent with these results, biotinylation experiments in MCD4 cells revealed that membrane AQP2 expression in unstimulated cells exposed to CaR agonists was higher than in control cells and did not increase significantly in response to short term exposure to forskolin (FK). Interestingly, we found that CaR activation by specific agonists reduced the increase in cAMP and prevented any reduction in Rho activity in response to FK, two crucial pathways for AQP2 translocation. These data support the hypothesis that CaR–AQP2 interplay represents an internal renal defense to mitigate the effects of hypercalciuria on the risk of calcium precipitation during antidiuresis. This mechanism and possibly reduced medulla tonicity may explain the lower concentrating ability observed in hypercalciuric patients