What is the prevalence of current alcohol dependence and how is it measured for Indigenous people in Australia, New Zealand, Canada and the United States of America? A systematic review

Background Alcohol affects Indigenous communities globally that have been colonised. These effects are physical, psychological, financial and cultural. This systematic review aims to describe the prevalence of current (12-month) alcohol dependence in Indigenous Peoples in Australia, New Zealand, Canada and the United States of America, to identify how it is measured, and if tools have been validated in Indigenous communities. Such information can help inform estimates of likely treatment need. Methods A systematic search of the literature was completed in six electronic databases for reports on current alcohol dependence (moderate to severe alcohol use disorder) published between 1 January 1989–9 July 2020. The following data were extracted: (1) the Indigenous population studied; country, (2) prevalence of dependence, (3) tools used to screen, assess or diagnose current dependence, (4) tools that have been validated in Indigenous populations to screen, assess or diagnose dependence, and (5) quality of the study, assessed using the Appraisal Tool for Cross-Sectional Studies. Results A total of 11 studies met eligibility criteria. Eight were cross-sectional surveys, one cohort study, and two were validation studies. Nine studies reported on the prevalence of current (12-month) alcohol dependence, and the range varied widely (3.8–33.3% [all participants], 3–32.8% [males only], 1.3–7.6% [females only]). Eight different tools were used and none were Indigenous-specific. Two tools have been validated in Indigenous (Native American) populations. Conclusion Few studies report on prevalence of current alcohol dependence in community or household samples of Indigenous populations in these four countries. Prevalence varies according to sampling method and site (for example, specific community versus national). Prior work has generally not used tools validated in Indigenous contexts. Collaborations with local Indigenous people may help in the development of culturally appropriate ways of measuring alcohol dependence, incorporating local customs and values. Tools used need to be validated in Indigenous communities, or Indigenous-specific tools developed, validated and used. Prevalence findings can inform health promotion and treatment needs, including funding for primary health care and specialist treatment services

Alcohol dependence in a community sample of Aboriginal and Torres Strait Islander Australians : Harms, getting help and awareness of local treatments

Background Few studies have examined links between current alcohol dependence and specific harms among Indigenous Australians. We investigated these associations as well as help seeking for drinking, awareness of local treatments and recommendations to help family or friends cut down or stop drinking in two Indigenous communities. Methods A representative sample of Indigenous Australians was surveyed in one urban and one remote community in South Australia. Data were collected via the Grog Survey App. Participants were dependent if they reported two or more symptoms of alcohol dependence (ICD-11). Pearson chi-square tests were used to describe relationships between employment by gender, and dependence by awareness of medicines and local treatment options. Multivariate logistic regressions were used to predict the odds of dependent drinkers experiencing harms and getting help for drinking, controlling for age, gender, schooling and income. Results A total of 775 Indigenous Australians took part in the study. After controlling for confounders, dependent drinkers were nearly eight times more likely to report a harm and nearly three times more likely to get help for their drinking—compared with non-dependent drinkers. Participants recommended accessing local support from an Aboriginal alcohol and other drugs worker, or a detoxification/ rehabilitation service. Discussion and conclusions More support and funding is needed for Indigenous Australians to ensure local treatment options for dependent drinkers are readily available, appropriate and accessible. Involvement of local Aboriginal or Torres Strait Islander health professionals in delivery of care can help ensure that it is appropriate to an individual’s culture and context

“My journey map”: Developing a qualitative approach to mapping young people’s progress in residential rehabilitation

Young people with substance misuse issues are at risk of harm from significant negative health and life events. Contemporary research notes both a historical failure to recognize the unique needs of adolescents, and the ongoing need for dedicated adolescent treatment programs and outcome measures. It is concerning that there is so little literature assessing the quality, availability, and effectiveness of adolescent-focused treatment programs, and no adolescent-specific measurement tools centered on a young person’s progress in residential treatment. This article reports on the process of developing a qualitative approach to mapping progress in treatment over time. The research seeks to develop an approach that captures, at three points in time and from multiple viewpoints, the progress of young people in four residential rehabilitation services located in New South Wales and Western Australia, across several dimensions of the personal and social aspects of life. Our aim is to develop an approach that is accessible to the alcohol and other drug workforce, and that informs the development of a psychometrically robust quantitative measure of progress that is meaningful and useful both to practitioners and to the young people themselves

'The Drug Survey App': a protocol for developing and validating an interactive population survey tool for drug use among Aboriginal and Torres Strait Islander Australians.

BACKGROUND: Disadvantage and transgenerational trauma contribute to Aboriginal and Torres Strait Islander (Indigenous) Australians being more likely to experience adverse health consequences from alcohol and other drug use than non-Indigenous peoples. Addressing these health inequities requires local monitoring of alcohol and other drug use. While culturally appropriate methods for measuring drinking patterns among Indigenous Australians have been established, no similar methods are available for measuring other drug use patterns (amount and frequency of consumption). This paper describes a protocol for creating and validating a tablet-based survey for alcohol and other drugs ("The Drug Survey App"). METHODS: The Drug Survey App will be co-designed with stakeholders including Indigenous Australian health professionals, addiction specialists, community leaders, and researchers. The App will allow participants to describe their drug use flexibly with an interactive, visual interface. The validity of estimated consumption patterns, and risk assessments will be tested against those made in clinical interviews conducted by Indigenous Australian health professionals. We will then trial the App as a population survey tool by using the App to determine the prevalence of substance use in two Indigenous communities. DISCUSSION: The App could empower Indigenous Australian communities to conduct independent research that informs local prevention and treatment efforts

Biased allosteric modulation at the CaS receptor engendered by structurally diverse calcimimetics

Background and Purpose Clinical use of cinacalcet in hyperparathyroidism is complicated by its tendency to induce hypocalcaemia, arising partly from activation of calcium-sensing receptors (CaS receptors) in the thyroid and stimulation of calcitonin release. CaS receptor allosteric modulators that selectively bias signalling towards pathways that mediate desired effects [e.g. parathyroid hormone (PTH) suppression] rather than those mediating undesirable effects (e.g. elevated serum calcitonin), may offer better therapies. Experimental Approach We characterized the ligand-biased profile of novel calcimimetics in HEK293 cells stably expressing human CaS receptors, by monitoring intracellular calcium (Ca2+i) mobilization, inositol phosphate (IP)1 accumulation, ERK1/2 phosphorylation (pERK1/2) and receptor expression. Key Results Phenylalkylamine calcimimetics were biased towards allosteric modulation of Ca2+i mobilization and IP1 accumulation. S,R-calcimimetic B was biased only towards IP1 accumulation. R,R-calcimimetic B and AC-265347 were biased towards IP1 accumulation and pERK1/2. Nor-calcimimetic B was unbiased. In contrast to phenylalkylamines and calcimimetic B analogues, AC-265347 did not promote trafficking of a loss-of-expression, naturally occurring, CaS receptor mutation (G670E). Conclusions and Implications The ability of R,R-calcimimetic B and AC-265347 to bias signalling towards pERK1/2 and IP1 accumulation may explain their suppression of PTH levels in vivo at concentrations that have no effect on serum calcitonin levels. The demonstration that AC-265347 promotes CaS receptor receptor signalling, but not trafficking reveals a novel profile of ligand-biased modulation at CaS receptors The identification of allosteric modulators that bias CaS receptor signalling towards distinct intracellular pathways provides an opportunity to develop desirable biased signalling profiles in vivo for mediating selective physiological responses

Discrimination as a frame-of-reference effect in overlapping friendship communities of ethnically diverse youth

Objectives: To what extent is the frame of reference of overlapping friendship communities important for young people’s feelings of discrimination and subjective wellbeing? That is, do youth feel better or worse to the extent that they feel less or more discrimination than their friends? Methods: Participants (N=898; Mage=14.13; SDage=3.37; 46% females; 46% Whites; 20% Indigenous; 34% other minorities) were high school students of three ethnically diverse, low SES public schools in New South Wales, Australia. Cross-sectional data were collected to measure felt discrimination, mental health, subjective wellbeing, social support and nominations of close friends. A state-of-the-art method of clustering links was used to identify overlapping friendship communities, and multiple membership multilevel models were run to examine whether community level discrimination moderated the link between individual level discrimination and wellbeing. Results: When the community level discrimination was low, there was no wellbeing related cost or benefit of individual level discrimination. But when the community level discrimination was high, individuals in those communities who themselves felt low discrimination had better wellbeing than individuals who themselves felt high discrimination. Conclusions: We provide evidence for a frame-ofreference effect involving discrimination. Individuals’ relative standing in their friendship communities with high group-level discrimination reliably predicted the individuals’ wellbeing levels, regardless of ethnicity. The results highlight the importance of identifying overlapping friendship communities for understanding the dynamics of discrimination and wellbeing of ethnically diverse youth

Pathophysiologic Changes in Extracellular pH Modulate Parathyroid Calcium-Sensing Receptor Activity and Secretion via a Histidine-Independent Mechanism

The calcium-sensing receptor (CaR) modulates renal calcium reabsorption and parathyroid hormone (PTH) secretion and is involved in the etiology of secondary hyperparathyroidism in CKD. Supraphysiologic changes in extracellular pH (pH(o)) modulate CaR responsiveness in HEK-293 (CaR-HEK) cells. Therefore, because acidosis and alkalosis are associated with altered PTH secretion in vivo, we examined whether pathophysiologic changes in pH(o) can significantly alter CaR responsiveness in both heterologous and endogenous expression systems and whether this affects PTH secretion. In both CaR-HEK and isolated bovine parathyroid cells, decreasing pH(o) from 7.4 to 7.2 rapidly inhibited CaR-induced intracellular calcium (Ca(2+)(i)) mobilization, whereas raising pH(o) to 7.6 potentiated responsiveness to extracellular calcium (Ca(2+)(o)). Similar pH(o) effects were observed for Ca(2+)(o)-induced extracellular signal-regulated kinase phosphorylation and actin polymerization and for L-Phe-induced Ca(2+)(i) mobilization. Intracellular pH was unaffected by acute 0.4-unit pH(o) changes, and the presence of physiologic albumin concentrations failed to attenuate the pH(o)-mediated effects. None of the individual point mutations created at histidine or cysteine residues in the extracellular domain of CaR attenuated pH(o) sensitivity. Finally, pathophysiologic pH(o) elevation reversibly suppressed PTH secretion from perifused human parathyroid cells, and acidosis transiently increased PTH secretion. Therefore, pathophysiologic pH(o) changes can modulate CaR responsiveness in HEK-293 and parathyroid cells independently of extracellular histidine residues. Specifically, pathophysiologic acidification inhibits CaR activity, thus permitting PTH secretion, whereas alkalinization potentiates CaR activity to suppress PTH secretion. These findings suggest that acid-base disturbances may affect the CaR-mediated control of parathyroid function and calcium metabolism in vivo

Testing Protein Leverage in Lean Humans: A Randomised Controlled Experimental Study

A significant contributor to the rising rates of human obesity is an increase in energy intake. The ‘protein leverage hypothesis’ proposes that a dominant appetite for protein in conjunction with a decline in the ratio of protein to fat and carbohydrate in the diet drives excess energy intake and could therefore promote the development of obesity. Our aim was to test the ‘protein leverage hypothesis’ in lean humans by disguising the macronutrient composition of foods offered to subjects under ad libitum feeding conditions. Energy intakes and hunger ratings were measured for 22 lean subjects studied over three 4-day periods of in-house dietary manipulation. Subjects were restricted to fixed menus in random order comprising 28 foods designed to be similar in palatability, availability, variety and sensory quality and providing 10%, 15% or 25% energy as protein. Nutrient and energy intake was calculated as the product of the amount of each food eaten and its composition. Lowering the percent protein of the diet from 15% to 10% resulted in higher (+12±4.5%, p = 0.02) total energy intake, predominantly from savoury-flavoured foods available between meals. This increased energy intake was not sufficient to maintain protein intake constant, indicating that protein leverage is incomplete. Urinary urea on the 10% and 15% protein diets did not differ statistically, nor did they differ from habitual values prior to the study. In contrast, increasing protein from 15% to 25% did not alter energy intake. On the fourth day of the trial, however, there was a greater increase in the hunger score between 1–2 h after the 10% protein breakfast versus the 25% protein breakfast (1.6±0.4 vs 25%: 0.5±0.3, p = 0.005). In our study population a change in the nutritional environment that dilutes dietary protein with carbohydrate and fat promotes overconsumption, enhancing the risk for potential weight gain

Group evaluations as self-group distancing:Ingroup typicality moderates evaluative intergroup bias in stigmatized groups

Outgroup favoritism among members of stigmatized groups can be seen as a form of self-group distancing. We examined how intergroup evaluations in stigmatized groups vary as a function of ingroup typicality. In Studies 1 and 2, Black participants (N = 125,915;N = 766) more strongly preferred light-skinned or White relative to dark-skinned or Black individuals the lighter their own skin tone. In Study 3, overweight participants (N = 147,540) more strongly preferred normal-weight relative to overweight individuals the lower their own body weight. In Study 4, participants with disabilities (N = 35,058) more strongly preferred non-disabled relative to disabled individuals the less visible they judged their own disability. Relationships between ingroup typicality and intergroup evaluations were at least partially mediated by ingroup identification (Studies 2 and 3). A meta-analysis across studies yielded an average effect size ofr= .12. Furthermore, higher ingroup typicality was related to both ingroup and outgroup evaluations. We discuss ingroup typicality as an individual constraint to self-group distancing among stigmatized group members and its relation to intergroup evaluations