A Review of Public Sector Engagement in Age-Friendly Community Initiatives.

The global age-friendly cities and communities (AFCC) movement has centered on the involvement of the public sector, calling on high-ranking authorities to commit to improving the built, social, and service environments of their localities. This interpretive review aimed to advance understanding of the ways in which the public sector is involved in AFCC efforts. Based on emergent themes from peer-reviewed articles from the United States and Canada published since 2010, we derived a two-dimensional framework for conceptualizing variability in public sector involvement, encompassing the internal/external (a) locus of responsibility for cross-sector change and (b) target for cross-sector change. We discuss implications for research, policy, practice, and further knowledge development in AFCC implementation.

Contextualized understandings of dairy farmers' perspectives on antimicrobial use and regulation in Alberta, Canada.

Antimicrobial resistance (AMR) has been largely attributed to antimicrobial use (AMU). To achieve judicious AMU, much research and many policies focus on knowledge translation and behavioral change mechanisms. To address knowledge gaps in contextual drivers of decisions made by dairy farmers concerning AMU, we conducted ethnographic fieldwork to investigate one community's understanding of AMU, AMR, and associated regulations in the dairy industry in Alberta, Canada. This included participation in on-farm activities and observations of relevant interactions on dairy farms in central Alberta for 4 mo. Interviews were conducted with 25 dairy farmers. The interviews were analyzed using thematic analysis and yielded several key findings. Many dairy farmers in this sample: (1) value their autonomy and hope to maintain agency regarding AMU; (2) have shared cultural and immigrant identities which may inform their perspectives of future AMU regulation as it relates to their farming autonomy; (3) feel that certain AMU policies implemented in other contexts would be impractical in Alberta and would constrain their freedom to make what they perceive to be the best animal welfare decisions; (4) believe that their knowledge and experience are undervalued by consumers and policy makers; (5) are concerned that the public does not have a complex understanding of dairy farming and, consequently, worry that AMU policy will be based on misguided consumer concerns; and (6) are variably skeptical of a link between AMU in dairy cattle and AMR in humans due to their strict adherence to milk safety protocols that is driven by their genuine care for the integrity of the product. A better understanding of the sociocultural and political-economic infrastructure that supports such perceptions is warranted and should inform efforts to improve AMU stewardship and future policies regarding AMU.

Views of Western Canadian dairy producers on calf rearing: An interview-based study.

Calf rearing practices differ among farms, including feeding and weaning methods. These differences may relate to how dairy producers view these practices and evaluate their own success. The aim of this study was to investigate perspectives of dairy producers on calf rearing, focusing on calf weaning and how they characterized weaning success. We interviewed dairy producers from 16 farms in Western Canada in the following provinces: British Columbia (n = 12), Manitoba (n = 2), and Alberta (n = 2). Participants were asked to describe their heifer calf weaning and rearing practices, and what they viewed as successes and challenges in weaning and rearing calves. Interviews were recorded, transcribed, and subjected to qualitative analysis from which we identified the following 4 major themes: (1) reliance on calf-based measures (e.g., health, growth, and behavior), (2) management factors and personal experiences (e.g., ease, consistency, and habit), (3) environmental factors (e.g., facilities and equipment), and (4) external support (e.g., advice and educational opportunities). These results provided insight into how dairy producers view calf weaning and rearing, and may help inform the design of future research and knowledge transfer projects aimed at improving management practices on dairy farms.

Emergent Challenges and Opportunities to Sustaining Age-friendly Initiatives: Qualitative Findings from a Canadian Age-friendly Funding Program.

Age-friendly initiatives often are motivated by a single funding injection from national or sub-national governments, frequently challenging human and financial resources at the community level. To address this problem, this paper examines the challenges and opportunities to sustaining age-friendly programs in the context of a Canadian age-friendly funding program. Based on a qualitative thematic content analysis of interview data with 35 age-friendly committee members drawn from 11 communities, results show that age-friendly sustainability may be conceptualized as an implementation gap between early development stages and long-term viability. Consistent over-dependence on volunteers and on committees' limited capacity may create burnout, limiting sustainability and the extent to which communities can truly become "age-friendly". To close this implementation gap while still remaining true to the grass-roots intention of the global age-friendly agenda, sustainable initiatives should include community champions, multi-disciplinary and cross-sector collaborations, and systemic municipal involvement.

Potential Impact and Cost-Effectiveness of Condomless-Sex-Concentrated PrEP in KwaZulu-Natal Accounting for Drug Resistance.

INTRODUCTION: Oral preexposure prophylaxis (PrEP) in the form of tenofovir-disoproxil-fumarate/emtricitabine is being implemented in selected sites in South Africa. Addressing outstanding questions on PrEP cost-effectiveness can inform further implementation. METHODS: We calibrated an individual-based model to KwaZulu-Natal to predict the impact and cost-effectiveness of PrEP, with use concentrated in periods of condomless sex, accounting for effects on drug resistance. We consider (1) PrEP availability for adolescent girls and young women aged 15-24 years and female sex workers, and (2) availability for everyone aged 15-64 years. Our primary analysis represents a level of PrEP use hypothesized to be attainable by future PrEP programs. RESULTS: In the context of PrEP use in adults aged 15-64 years, there was a predicted 33% reduction in incidence and 36% reduction in women aged 15-24 years. PrEP was cost-effective, including in a range of sensitivity analyses, although with substantially reduced (cost) effectiveness under a policy of ART initiation with efavirenz- rather than dolutegravir-based regimens due to PrEP undermining ART effectiveness by increasing HIV drug resistance. CONCLUSIONS: PrEP use concentrated during time periods of condomless sex has the potential to substantively impact HIV incidence and be cost-effective.

Views of American animal and dairy science students on the future of dairy farms and public expectations for dairy cattle care: A focus group study.

Students completing advanced degrees in dairy or animal science may go on to have a major impact on the food animal agriculture industries. The aim of this study was to better understand student views of the future of dairying, including changes in practices affecting animal care on farms as well as perceived public perceptions. We conducted 6 focus group sessions with undergraduate students enrolled in the 2019 US Dairy Education and Training Consortium held in Clovis, New Mexico, and used explorative key word analysis of written notes and thematic analysis of the semi-structured discussions. Some "must-haves" of future animal care on dairy farms included increased use of technology, group housing of calves, and adequate facilities, including enrichment. Students also discussed their views of public expectations regarding animal care on dairy farms, and measures that they felt must be put into place to address these expectations in the coming years. Although the influence of the public was highlighted by the students, they were not always certain what specific values the public holds and doubted the feasibility and practicality of some expectations, such as providing pasture access or keeping the calf and cow together. They further demonstrated uncertainty about how best to align the directions of the industry with public expectations. Although they felt that public education could be used to demonstrate the legitimacy of dairy practices, they also believed that the industry should strive to find compromises and work toward meeting public expectations. Deciding what animal welfare considerations (e.g., naturalness, affective states, or animal health) were most relevant was a challenge for the students, perhaps reflecting diverging messages received during their own education.

Serologic Follow-up of Middle East Respiratory Syndrome Coronavirus Cases and Contacts-Abu Dhabi, United Arab Emirates.

Background: Although there is evidence of person-to-person transmission of Middle East respiratory syndrome coronavirus (MERS-CoV) in household and healthcare settings, more data are needed to describe and better understand the risk factors and transmission routes in both settings, as well as the extent to which disease severity affects transmission. Methods: A seroepidemiological investigation was conducted among MERS-CoV case patients (cases) and their household contacts to investigate transmission risk in Abu Dhabi, United Arab Emirates. Cases diagnosed between 1 January 2013 and 9 May 2014 and their household contacts were approached for enrollment. Demographic, clinical, and exposure history data were collected. Sera were screened by MERS-CoV nucleocapsid protein enzyme-linked immunosorbent assay and indirect immunofluorescence, with results confirmed by microneutralization assay. Results: Thirty-one of 34 (91%) case patients were asymptomatic or mildly symptomatic and did not require oxygen during hospitalization. MERS-CoV antibodies were detected in 13 of 24 (54%) case patients with available sera, including 1 severely symptomatic, 9 mildly symptomatic, and 3 asymptomatic case patients. No serologic evidence of MERS-CoV transmission was found among 105 household contacts with available sera. Conclusions: Transmission of MERS-CoV was not documented in this investigation of mostly asymptomatic and mildly symptomatic cases and their household contacts. These results have implications for clinical management of cases and formulation of isolation policies to reduce the risk of transmission.

Relationship Between Mood, Thinking, and Walking: A Systematic Review Examining Depressive Symptoms, Executive Function, and Gait.

Prior literature has proposed that the coexistence of late-life depression, executive dysfunction and impaired gait speed may constitute a specific phenotype in older adults with a possible shared brain mechanism. All three conditions are independently associated with negative health outcomes including impaired function, risk of falling, and reduced quality of life. However, the existence, etiology, and implications of having all three conditions as a unitary triad remain unclear. This systematic review examined the literature to assess the consistency of this triad and to explore the possible role of frontal-subcortical circuitry in its etiology. English language literature that assessed mood, executive function, and gait speed using a validated tool in human participants over age 65 were included for this review. Following the PRISMA guidelines, 15 studies including 11,213 participants met criteria for inclusion in this study. The triad's existence was supported by 12 of the 15 studies (80%), including 4 longitudinal studies involving 368 participants. A prevalence of 17% was reported in one population study. The three included intervention studies provided mixed results regarding the benefit of pharmacologic and exercise interventions. Two studies assessed the association between presence of white matter hyperintensities and the triad, with one study finding a significant longitudinal relationship with periventricular white matter hyperintensities. Vascular risk factors were also commonly associated with this triad. Taken together, the relationship between this triad, the vascular depression hypothesis, and frontal-subcortical pathology is suggested. Further longitudinal research is needed to further clarify the etiology and clinical relevance of this concomitant prescence oflate-life depression, executive dysfunction and impaired gait speed.

Design and Rationale for the Endothelin-1 Receptor Antagonism in the Prevention of Microvascular Injury in Patients with non-ST Elevation Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention (ENDORA-PCI) Trial.

PURPOSE: Peri-procedural myocardial infarction (PMI) occurs in a small but significant portion of patients undergoing percutaneous intervention (PCI). The underlying mechanisms are complex and may include neurohormonal activation and release of vasoactive substances resulting in disruption of the coronary microcirculation. Endothelin in particular has been found in abundance in atherosclerotic plaques and in systemic circulation following PCI, and may be a potential culprit for PMI through its action on microvascular vasoconstriction, and platelet and neutrophil activation. In this study we aim to characterize the behavior of the coronary microcirculation during a PCI with the index of microvascular resistance (IMR) and the effect of peri-procedural endothelin antagonism. METHODS: The ENDORA-PCI trial is a randomized, double-blind, placebo-controlled, single-center clinical trial designed to evaluate the efficacy of endothelin antagonism in attenuating the peri-procedural rise in IMR as a surrogate marker for PMI. The patients of interest are those with non-ST elevation acute coronary syndrome (NSTEACS) undergoing PCI, and we aim to recruit 52 patients overall to give the study a power of 80 % at an α level of 5 %. Patients will be randomized in a 1:1 fashion to either Ambrisentan, an endothelin antagonist, or placebo, prior to their PCI. IMR will be measured before and after PCI. The primary endpoint is the difference in peri-procedural changes in patients' IMR between the two groups. CONCLUSION: The ENDORA-PCI study will investigate whether endothelin antagonism with Ambrisentan attenuates the peri-procedural rise in IMR in patients with NSTEACS undergoing PCI, and thus potentially the risk of PMI.

Mortality after fluid bolus in African children with severe infection.

BACKGROUND: The role of fluid resuscitation in the treatment of children with shock and life-threatening infections who live in resource-limited settings is not established. METHODS: We randomly assigned children with severe febrile illness and impaired perfusion to receive boluses of 20 to 40 ml of 5% albumin solution (albumin-bolus group) or 0.9% saline solution (saline-bolus group) per kilogram of body weight or no bolus (control group) at the time of admission to a hospital in Uganda, Kenya, or Tanzania (stratum A); children with severe hypotension were randomly assigned to one of the bolus groups only (stratum B). All children received appropriate antimicrobial treatment, intravenous maintenance fluids, and supportive care, according to guidelines. Children with malnutrition or gastroenteritis were excluded. The primary end point was 48-hour mortality; secondary end points included pulmonary edema, increased intracranial pressure, and mortality or neurologic sequelae at 4 weeks. RESULTS: The data and safety monitoring committee recommended halting recruitment after 3141 of the projected 3600 children in stratum A were enrolled. Malaria status (57% overall) and clinical severity were similar across groups. The 48-hour mortality was 10.6% (111 of 1050 children), 10.5% (110 of 1047 children), and 7.3% (76 of 1044 children) in the albumin-bolus, saline-bolus, and control groups, respectively (relative risk for saline bolus vs. control, 1.44; 95% confidence interval [CI], 1.09 to 1.90; P=0.01; relative risk for albumin bolus vs. saline bolus, 1.01; 95% CI, 0.78 to 1.29; P=0.96; and relative risk for any bolus vs. control, 1.45; 95% CI, 1.13 to 1.86; P=0.003). The 4-week mortality was 12.2%, 12.0%, and 8.7% in the three groups, respectively (P=0.004 for the comparison of bolus with control). Neurologic sequelae occurred in 2.2%, 1.9%, and 2.0% of the children in the respective groups (P=0.92), and pulmonary edema or increased intracranial pressure occurred in 2.6%, 2.2%, and 1.7% (P=0.17), respectively. In stratum B, 69% of the children (9 of 13) in the albumin-bolus group and 56% (9 of 16) in the saline-bolus group died (P=0.45). The results were consistent across centers and across subgroups according to the severity of shock and status with respect to malaria, coma, sepsis, acidosis, and severe anemia. CONCLUSIONS: Fluid boluses significantly increased 48-hour mortality in critically ill children with impaired perfusion in these resource-limited settings in Africa. (Funded by the Medical Research Council, United Kingdom; FEAST Current Controlled Trials number, ISRCTN69856593.).

A review of valve surgery for rheumatic heart disease in Australia.

BACKGROUND: Globally, rheumatic heart disease (RHD) remains an important cause of heart disease. In Australia it particularly affects older non-Indigenous Australians and Aboriginal Australians and/or Torres Strait Islander peoples. Factors associated with the choice of treatment for advanced RHD remain variable and poorly understood. METHODS: The Australian and New Zealand Society of Cardiac and Thoracic Surgeons Cardiac Surgery Database was analysed. Demographics, co-morbidities, pre-operative status and valve(s) affected were collated and associations with management assessed. RESULTS: Surgical management of 1384 RHD and 15843 non-RHD valve procedures was analysed. RHD patients were younger, more likely to be female and Indigenous Australian, to have atrial fibrillation (AF) and previous percutaneous balloon valvuloplasty (PBV). Surgery was performed on one valve in 64.5%, two valves in 30.0% and three valves in 5.5%. Factors associated with receipt of mechanical valves in RHD were AF (OR 2.69) and previous PBV (OR 1.98) and valve surgery (OR 3.12). Predictors of valve repair included being Indigenous (OR 3.84) and having fewer valves requiring surgery (OR 0.10). Overall there was a significant increase in the use of mitral bioprosthetic valves over time. CONCLUSIONS: RHD valve surgery is more common in young, female and Indigenous patients. The use of bioprosthetic valves in RHD is increasing. Given many patients are female and younger, the choice of valve surgery and need for anticoagulation has implications for future management of RHD and related morbidity, pregnancy and lifestyle plans.

Fetal alcohol spectrum disorder: development of consensus referral criteria for specialist diagnostic assessment in Australia.

BACKGROUND: Fetal alcohol spectrum disorder (FASD) is known to be under-recognised in Australia. The use of standard methods to identify when to refer individuals who may have FASD for specialist assessment could help improve the identification of this disorder. The purpose of this study was to develop referral criteria for use in Australia. METHOD: An online survey about FASD screening and diagnosis in Australia, which included 23 statements describing criteria for referral for fetal alcohol syndrome (FAS) and FASD based on published recommendations for referral in North America, was sent to 139 health professionals who had expertise or involvement in FASD screening or diagnosis. Survey findings and published criteria for referral were subsequently reviewed by a panel of 14 investigators at a consensus development workshop where criteria for referral were developed. RESULTS: Among the 139 health professionals who were sent the survey, 103 (74%) responded, and 90 (65%) responded to the statements on criteria for referral. Over 80% of respondents agreed that referral for specialist evaluation should occur when there is evidence of significant prenatal alcohol exposure, defined as 7 or more standard drinks per week and at least 3 standard drinks on any one day, and more than 70% agreed with 13 of the 16 statements that described criteria for referral other than prenatal alcohol exposure. Workshop participants recommended five independent criteria for referral: confirmed significant prenatal alcohol exposure; microcephaly and confirmed prenatal alcohol exposure; 2 or more significant central nervous system (CNS) abnormalities and confirmed prenatal alcohol exposure; 3 characteristic FAS facial anomalies; and 1 characteristic FAS facial anomaly, growth deficit and 1 or more CNS abnormalities. CONCLUSION: Referral criteria recommended for use in Australia are similar to those recommended in North America. There is a need to develop resources to raise awareness of these criteria among health professionals and evaluate their feasibility, acceptability and capacity to improve the identification of FASD in Australia.

Selective laser sintered versus carbon fiber passive-dynamic ankle-foot orthoses: a comparison of patient walking performance.

Selective laser sintering (SLS) is a well-suited additive manufacturing technique for generating subject-specific passive-dynamic ankle-foot orthoses (PD-AFOs). However, the mechanical properties of SLS PD-AFOs may differ from those of commonly prescribed carbon fiber (CF) PD-AFOs. Therefore, the goal of this study was to determine if biomechanical measures during gait differ between CF and stiffness-matched SLS PD-AFOs. Subject-specific SLS PD-AFOs were manufactured for ten subjects with unilateral lower-limb impairments. Minimal differences in gait performance occurred when subjects used the SLS versus CF PD-AFOs. These results support the use of SLS PD-AFOs to study the effects of altering design characteristics on gait performance.

Flexible working arrangements in healthcare: a comparison between managers of shift workers and 9-to-5 employees.

OBJECTIVE: This study examined healthcare managers' perceptions of flexible working arrangements and implementation barriers. BACKGROUND: Work-life conflict can lead to negative health implications, but flexible working arrangements can help manage this conflict. Little research has examined its implementation in 24/7/365 healthcare organizations or within groups of employees working 9 AM to 5 PM (9-5) versus shift-work hours. METHODS: Questionnaires regarding perceptions to, benefits of, and barriers against flexible working arrangements were administered to managers of 9-5 workers and shift workers in an Atlantic Canadian healthcare organization. RESULTS: Few differences in perceptions and benefits of flexible working arrangements were found between management groups. However, results indicate that the interaction with patients and/or the immediacy of tasks being performed are barriers for shift-work managers. CONCLUSIONS: The nature of healthcare presents barriers for managers implementing flexible working arrangements, which differ only based on whether the job is physical (shift work) versus desk related (9-5 work).

Correction of false memory for associated word lists by collaborating groups.

Collaborative inhibition is often observed for both correct and false memories. However, research examining the mechanisms by which collaborative inhibition occurs, such as retrieval disruption, reality monitoring, or group filtering, is lacking. In addition, the creation of the nominal groups (i.e., groups artificially developed by combining individuals' recall) necessary for examining collaborative inhibition do not use statistical best practices. Using the Deese-Roediger-McDermott paradigm, we examined percentages of correct and false memories in individuals, collaborative interactive groups, and correctly created nominal groups, as well as the processes that the collaborative interactive groups used to determine which memories to report. Results showed evidence of the collaborative inhibition effect. In addition, analyses of the collaborative interactive groups' discussions found that these groups wrote down almost all presented words but less than half of nonpresented critical words, after discussing them, with nonpresented critical words being stated to the group with lower confidence and rejected by other group members more often. Overall, our findings indicated support for the group filtering hypothesis.

"I've Got a Lot of Other Things I Do": The Nuances of Digital Engagement among Older People.

As Western society becomes increasingly digitally dependent and many older adults actively engage in the online world, understanding the experiences of those who largely do not use digital technology in their daily lives is crucial. Individual interviews were conducted (pre-pandemic) with 23 older adults who, based on self-identification, did not regularly use digital technology, exploring how their experiences as limited digital technology users may have impacted their daily lives. An iterative collaborative qualitative analysis demonstrated three main themes: internet concerns, frustrations with digital technology, and conflicting motivators to use digital technology. Findings suggest that addressing digital concerns and providing effective digital skill learning opportunities may encourage some older adults to become more digitally engaged. However, as people, including older adults, can be uninterested in using these technologies, organizations and institutions should work to offer ways to support people of all ages who are not engaged online.

Patterns of HIV treatment preferences among people with diverse demographic, social, and behavioral characteristics who are living with HIV in the United States.

BACKGROUND: New dosage form and frequency options may improve HIV treatment outcomes and reduce disparities in access and use. METHODS: People with HIV (PWH) in the US completed a demographic and discrete choice experiment survey of preference for 13 hypothetical HIV treatment options: daily and weekly oral tablets; 1-, 3-, or 6-monthly injections by self or a health care provider; yearly implant; or combinations. Best-worst scaling and a latent class model were used to analyze overall preference choices and for groups of individuals with similar patterns of preferences; the model also predicted uptake of products. RESULTS: Among the diverse 829 respondents, weekly oral tablets and 6-monthly injections by an HCP were significantly more favored than daily oral tablets. Convenience of the treatment and being tired of taking pills were the top drivers of preference responses. Latent class analysis identified four groups of respondents with distinct preference patterns; approximately two-thirds belonged to groups strongly preferring products other than daily oral tablets. The modelled uptake of a monthly pill, yearly implant, 6-monthly Health Care Provider (HCP) injection, oral daily pill, and 3-monthly HCP injection were 24%, 24%, 24%, 18%, and 11%, respectively. CONCLUSIONS: Patterns of HIV medication preference can inform development of new forms of HIV therapy products as the majority of patients do not prefer the currently most available treatment option of daily oral tablets. Looking beyond population-level preferences and into similar groups of PWH increases the ability to develop patient-centered products to fill gaps in care and increase treatment effectiveness.

Postnatally-transmitted HIV-1 Envelope variants have similar neutralization-sensitivity and function to that of nontransmitted breast milk variants.

BACKGROUND: Breastfeeding is a leading cause of infant HIV-1 infection in the developing world, yet only a minority of infants exposed to HIV-1 via breastfeeding become infected. As a genetic bottleneck severely restricts the number of postnatally-transmitted variants, genetic or phenotypic properties of the virus Envelope (Env) could be important for the establishment of infant infection. We examined the efficiency of virologic functions required for initiation of infection in the gastrointestinal tract and the neutralization sensitivity of HIV-1 Env variants isolated from milk of three postnatally-transmitting mothers (n = 13 viruses), five clinically-matched nontransmitting mothers (n = 16 viruses), and seven postnatally-infected infants (n = 7 postnatally-transmitted/founder (T/F) viruses). RESULTS: There was no difference in the efficiency of epithelial cell interactions between Env virus variants from the breast milk of transmitting and nontransmitting mothers. Moreover, there was similar efficiency of DC-mediated trans-infection, CCR5-usage, target cell fusion, and infectivity between HIV-1 Env-pseudoviruses from nontransmitting mothers and postnatal T/F viruses. Milk Env-pseudoviruses were generally sensitive to neutralization by autologous maternal plasma and resistant to breast milk neutralization. Infant T/F Env-pseudoviruses were equally sensitive to neutralization by broadly-neutralizing monoclonal and polyclonal antibodies as compared to nontransmitted breast milk Env variants. CONCLUSION: Postnatally-T/F Env variants do not appear to possess a superior ability to interact with and cross a mucosal barrier or an exceptional resistance to neutralization that define their capability to initiate infection across the infant gastrointestinal tract in the setting of preexisting maternal antibodies.

Paternally inherited gsα mutation impairs adipogenesis and potentiates a lean phenotype in vivo.

Paternally inherited inactivating mutations of the GNAS gene have been associated with a rare and disabling genetic disorder, progressive osseous heteroplasia, in which heterotopic ossification occurs within extraskeletal soft tissues, such as skin, subcutaneous fat, and skeletal muscle. This ectopic bone formation is hypothesized to be caused by dysregulated mesenchymal progenitor cell differentiation that affects a bipotential osteogenic-adipogenic lineage cell fate switch. Interestingly, patients with paternally inherited inactivating mutations of GNAS are uniformly lean. Using a mouse model of Gsα-specific exon 1 disruption, we examined whether heterozygous inactivation of Gnas affects adipogenic differentiation of mesenchymal precursor cells from subcutaneous adipose tissues (fat pad). We found that paternally inherited Gsα inactivation (Gsα(+/p-) ) impairs adipogenic differentiation of adipose-derived stromal cells (ASCs). The Gsα(+/p-) mutation in ASCs also decreased expression of the adipogenic factors CCAAT-enhancer-binding protein (C/EBP)ß, C/EBPα, peroxisome proliferator-activated receptor gamma, and adipocyte protein 2. Impaired adipocyte differentiation was rescued by an adenylyl cyclase activator, forskolin, and provided evidence that Gsα-cAMP signals are necessary in early stages of this process. Supporting a role for Gnas in adipogenesis in vivo, fat tissue weight and expression of adipogenic genes from multiple types of adipose tissues from Gsα(+/p-) mice were significantly decreased. Interestingly, the inhibition of adipogenesis by paternally inherited Gsα mutation also enhances expression of the osteogenic factors, msh homeobox 2, runt-related transcription factor 2, and osteocalcin. These data support the hypothesis that Gsα plays a critical role in regulating the balance between fat and bone determination in soft tissues, a finding that has important implications for a wide variety of disorders of osteogenesis and adipogenesis.

Recommendations from a consensus development workshop on the diagnosis of fetal alcohol spectrum disorders in Australia.

BACKGROUND: Fetal alcohol spectrum disorders (FASD) are underdiagnosed in Australia, and health professionals have endorsed the need for national guidelines for diagnosis. The aim of this study was to develop consensus recommendations for the diagnosis of FASD in Australia. METHODS: A panel of 13 health professionals, researchers, and consumer and community representatives with relevant expertise attended a 2-day consensus development workshop to review evidence on the screening and diagnosis of FASD obtained from a systematic literature review, a national survey of health professionals and community group discussions. The nominal group technique and facilitated discussion were used to review the evidence on screening and diagnosis, and to develop consensus recommendations for the diagnosis of FASD in Australia. RESULTS: The use of population-based screening for FASD was not recommended. However, there was consensus support for the development of standard criteria for referral for specialist diagnostic assessment. Participants developed consensus recommendations for diagnostic categories, criteria and assessment methods, based on the adaption of elements from both the University of Washington 4-Digit Diagnostic Code and the Canadian guidelines for FASD diagnosis. Panel members also recommended the development of resources to: facilitate consistency in referral and diagnostic practices, including comprehensive clinical guidelines and assessment instruments; and to support individuals undergoing assessment and their parents or carers. CONCLUSIONS: These consensus recommendations provide a foundation for the development of guidelines and other resources to promote consistency in the diagnosis of FASD in Australia. Guidelines for diagnosis will require review and evaluation in the Australian context prior to national implementation as well as periodic review to incorporate new knowledge.