The contextual interview: a cross-cutting patient-interviewing approach for social context.

Patient interviewing pedagogy in medical education has not evolved to comprehensively capture the biopsychosocial model of healthcare delivery. While gathering a patient's social history targets important aspects of social context it does not adequately capture and account for the real-time reassessment required to understand evolving factors that influence exposure to drivers of health inequities, social determinants of health, and access to supports that promote health. The authors offer a patient interviewing approach called the Contextual Interview (CI) that specifically targets dynamic and ever-changing social context information. To substantiate the use of the CI in medical education, the authors conducted a qualitative review of the Accreditation Council for Graduate Medical Education Milestones for primary care specialties (Family Medicine, Internal Medicine, and Pediatrics). Milestones were coded to the extent to which they reflected the learner's need to acknowledge, assess, synthesize and/or apply patient contextual data in real-time patient encounters. Approximately 1 in 5 milestones met the context-related and patient-facing criteria. This milestone review further highlights the need for more intentional training in eliciting meaningful social context data during patient interviewing. The CI as a cross-cutting, practical, time-conscious, and semi-structured patient interviewing approach that deliberately elicits information to improve the clinician's sense and understanding of a patient's social context. The authors reviewed future directions in researching adapted versions of the CI for undergraduate and graduate medical education.

Niche breadth of Amazonian trees increases with niche optimum across broad edaphic gradients.

Understanding how biotic interactions and environmental filtering mediated by soil properties shape plant community assembly is a major challenge in ecology, especially when studying complex and hyperdiverse ecosystems like tropical forests. To shed light on the influence of both factors, we examined how the edaphic optimum of species (their niche position) related to their edaphic range (their niche breadth) along different environmental gradients and how this translates into functional strategies. Here we tested four scenarios describing the shape of the niche breadth-niche position relationship, including one neutral scenario and three scenarios proposing different relative influences of abiotic and biotic factors on community assembly along a soil resource gradient. To do so, we used soil concentration data for five key nutrients (N, P, Ca, Mg, and K), along with accurate measurements of 14 leaf, stem, and root traits for 246 tree species inventoried in 101 plots located across Eastern (French Guiana) and Western (Peru) Amazonia. We found that species niche breadth increased linearly with species niche position along each soil nutrient gradient. This increase was associated with more resource acquisitive traits in the leaves and the roots for soil N, Ca, Mg, and K concentration, while it was negatively associated with wood density for soil P concentration. These observations agreed with one of our hypothetical scenarios in which species with resource conservation traits are confined to the most nutrient-depleted soils (abiotic filter), but they are outperformed by faster-growing species in more fertile conditions (biotic filter). Our results refine and strengthen support for niche theories of species assembly while providing an integrated approach to improving forest management policies.

A pioneer morphological and genetic study of the intertidal fauna of the Gerlache Strait (Antarctic Peninsula).

The underexplored intertidal ecosystems of Antarctica are facing rapid changes in important environmental factors. Associated with temperature increase, reduction in coastal ice will soon expose new ice-free areas that will be colonized by local or distant biota. To enable detection of future changes in faunal composition, a biodiversity baseline is urgently required. Here, we evaluated intertidal faunal diversity at 13 locations around the Gerlache Strait (western Antarctic Peninsula), using a combination of a quadrat approach, morphological identification and genetic characterization. Our data highlight a community structure comprising four generally distributed and highly abundant species (the flatworm Obrimoposthia wandeli, the bivalve Kidderia subquadrata, and the gastropods Laevilitorina umbilicata and Laevilitorina caliginosa) as well as 79 rarer and less widely encountered species. The most abundant species thrive in the intertidal zone due to their ability to either survive overwinter in situ or to rapidly colonize this zone when conditions allow. In addition, we confirmed the presence of multiple trophic levels at nearly all locations, suggesting that complex inter-specific interactions occur within these communities. Diversity indices contrasted between sampling locations (from 3 to 32 species) and multivariate approaches identified three main groups. This confirms the importance of environmental heterogeneity in shaping diversity patterns within the investigated area. Finally, we provide the first genetic and photographic baseline of the Antarctic intertidal fauna (106 sequences, 137 macrophotographs), as well as preliminary insights on the biogeography of several species. Taken together, these results provide a timely catalyst to assess the diversity and to inform studies of the potential resilience of these intertidal communities.

Clinical supervision within the primary care behavioral health model: What we know and where we need to go.

Community-based primary care settings play an important role in the provision of health care to vulnerable populations, as well as in primary care education. Much attention has been given to medical education in community-based primary care and as the need for workforce development grows for behavioral health in primary care, clinical supervision of prelicensure psychology learners in primary care will also need greater attention. Clinical supervision not only impacts learner professional development but also impacts the patient care learners provide. The purpose of this article is to give attention to clinical supervision within the primary care behavioral health (PCBH) model in the context of community-based primary care. The intersection of supervision approaches in specialty mental health care and medical education will be presented, as well as how these approaches can be combined when working with learners within PCBH. Additionally, challenges to clinical supervision in primary care will be discussed as well as solutions to improve not only workforce development in PCBH but also professional development for clinical supervisors in primary care. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

TYRO3 agonist as therapy for glomerular disease.

Podocyte injury and loss are key drivers of primary and secondary glomerular diseases, such as focal segmental glomerulosclerosis (FSGS) and diabetic kidney disease (DKD). We previously demonstrated the renoprotective role of protein S (PS) and its cognate tyrosine-protein kinase receptor, TYRO3, in models of FSGS and DKD and that their signaling exerts antiapoptotic and antiinflammatory effects to confer protection against podocyte loss. Among the 3 TAM receptors (TYRO3, AXL, and MER), only TYRO3 expression is largely restricted to podocytes, and glomerular TYRO3 mRNA expression negatively correlates with human glomerular disease progression. Therefore, we posited that the agonistic PS/TYRO3 signaling could serve as a potential therapeutic approach to attenuate glomerular disease progression. As PS function is not limited to TYRO3-mediated signal transduction but includes its anticoagulant activity, we focused on the development of TYRO3 agonists as an optimal therapeutic approach to glomerular disease. Among the small-molecule TYRO3 agonistic compounds screened, compound 10 (C-10) showed a selective activation of TYRO3 without any effects on AXL or MER. We also confirmed that C-10 directly binds to TYRO3, but not the other receptors. In vivo, C-10 attenuated proteinuria, glomerular injury, and podocyte loss in mouse models of Adriamycin-induced nephropathy and a db/db model of type 2 diabetes. Moreover, these renoprotective effects of C-10 were lost in Tyro3-knockout mice, indicating that C-10 is a selective agonist of TYRO3 activity that mitigates podocyte injury and glomerular disease. Therefore, C-10, a TYRO3 agonist, could be potentially developed as a new therapy for glomerular disease.

Mechanistic insights on novel small molecule allosteric activators of cGMP-dependent protein kinase PKG1α.

cGMP-dependent protein kinase (PKG) represents a compelling drug target for treatment of cardiovascular diseases. PKG1 is the major effector of beneficial cGMP signaling which is involved in smooth muscle relaxation and vascular tone, inhibition of platelet aggregation and signaling that leads to cardioprotection. In this study, a novel piperidine series of activators previously identified from an ultrahigh-throughput screen were validated to directly bind partially activated PKG1α and subsequently enhance its kinase activity in a concentration-dependent manner. Compounds from initial optimization efforts showed an ability to activate PKG1α independent of the endogenous activator, cGMP. We demonstrate these small molecule activators mimic the effect of cGMP on the kinetic parameters of PKG1α by positively modulating the KM of the peptide substrate and negatively modulating the apparent KM for ATP with increase in catalytic efficiency, kcat. In addition, these compounds also allosterically modulate the binding affinity of cGMP for PKG1α by increasing the affinity of cGMP for the high-affinity binding site (CNB-A) and decreasing the affinity of cGMP for the low-affinity binding site (CNB-B). We show the mode of action of these activators involves binding to an allosteric site within the regulatory domain, near the CNB-B binding site. To the best of our knowledge, these are the first reported non-cGMP mimetic small molecules shown to directly activate PKG1α. Insights into the mechanism of action of these compounds will enable future development of cardioprotective compounds that function through novel modes of action for the treatment of cardiovascular diseases.

Clinician's commentary to accompany "Implementing evidence-based practices in non-specialty mental health settings".

Comments on the original article by Wolk et al. (see record 2022-18591-001) regarding the implementation of evidence-based practices in non-specialty mental health settings. The authors both had tremendous gratitude for Wolk et al.'s (2022) ability to accurately describe and elucidate numerous difficulties that frontline workers experience, especially in nonspecialty mental health (SMH) settings, such as primary care where we work. With increased identification of implementation barriers, those working in non-SMH settings can mitigate these challenges via intentional strategizing upfront, considering settings' contexts (as suggested by Wolk et al.), and normalizing the need for ongoing troubleshooting. The authors appreciated the elucidation that the majority of those receiving support for mental health receive care in non-SMH settings. As much as it is imperative for those working in non-SMH settings to learn concepts illuminated from the mental health field via evidence-based (EB) practices, when it comes to reaching the masses and implementation strategies, the field might have much to learn from these non-SMH settings. When it comes to integration of siloed fields, all can benefit. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Functional susceptibility of tropical forests to climate change.

Tropical forests are some of the most biodiverse ecosystems in the world, yet their functioning is threatened by anthropogenic disturbances and climate change. Global actions to conserve tropical forests could be enhanced by having local knowledge on the forests' functional diversity and functional redundancy as proxies for their capacity to respond to global environmental change. Here we create estimates of plant functional diversity and redundancy across the tropics by combining a dataset of 16 morphological, chemical and photosynthetic plant traits sampled from 2,461 individual trees from 74 sites distributed across four continents together with local climate data for the past half century. Our findings suggest a strong link between climate and functional diversity and redundancy with the three trait groups responding similarly across the tropics and climate gradient. We show that drier tropical forests are overall less functionally diverse than wetter forests and that functional redundancy declines with increasing soil water and vapour pressure deficits. Areas with high functional diversity and high functional redundancy tend to better maintain ecosystem functioning, such as aboveground biomass, after extreme weather events. Our predictions suggest that the lower functional diversity and lower functional redundancy of drier tropical forests, in comparison with wetter forests, may leave them more at risk of shifting towards alternative states in face of further declines in water availability across tropical regions.

Tropical tree mortality has increased with rising atmospheric water stress.

Evidence exists that tree mortality is accelerating in some regions of the tropics1,2, with profound consequences for the future of the tropical carbon sink and the global anthropogenic carbon budget left to limit peak global warming below 2 °C. However, the mechanisms that may be driving such mortality changes and whether particular species are especially vulnerable remain unclear3-8. Here we analyse a 49-year record of tree dynamics from 24 old-growth forest plots encompassing a broad climatic gradient across the Australian moist tropics and find that annual tree mortality risk has, on average, doubled across all plots and species over the last 35 years, indicating a potential halving in life expectancy and carbon residence time. Associated losses in biomass were not offset by gains from growth and recruitment. Plots in less moist local climates presented higher average mortality risk, but local mean climate did not predict the pace of temporal increase in mortality risk. Species varied in the trajectories of their mortality risk, with the highest average risk found nearer to the upper end of the atmospheric vapour pressure deficit niches of species. A long-term increase in vapour pressure deficit was evident across the region, suggesting that thresholds involving atmospheric water stress, driven by global warming, may be a primary cause of increasing tree mortality in moist tropical forests.

Tropical tree growth sensitivity to climate is driven by species intrinsic growth rate and leaf traits.

A better understanding of how climate affects growth in tree species is essential for improved predictions of forest dynamics under climate change. Long-term climate averages (mean climate) drive spatial variations in species' baseline growth rates, whereas deviations from these averages over time (anomalies) can create growth variation around the local baseline. However, the rarity of long-term tree census data spanning climatic gradients has so far limited our understanding of their respective role, especially in tropical systems. Furthermore, tree growth sensitivity to climate is likely to vary widely among species, and the ecological strategies underlying these differences remain poorly understood. Here, we utilize an exceptional dataset of 49 years of growth data for 509 tree species across 23 tropical rainforest plots along a climatic gradient to examine how multiannual tree growth responds to both climate means and anomalies, and how species' functional traits mediate these growth responses to climate. We show that anomalous increases in atmospheric evaporative demand and solar radiation consistently reduced tree growth. Drier forests and fast-growing species were more sensitive to water stress anomalies. In addition, species traits related to water use and photosynthesis partly explained differences in growth sensitivity to both climate means and anomalies. Our study demonstrates that both climate means and anomalies shape tree growth in tropical forests and that species traits can provide insights into understanding these demographic responses to climate change, offering a promising way forward to forecast tropical forest dynamics under different climate trajectories.

Evidence of spatial genetic structure in a snow leopard population from Gansu, China.

Understanding the spatial structure of genetic diversity provides insights into a populations' genetic status and enables assessment of its capacity to counteract the effects of genetic drift. Such knowledge is particularly scarce for the snow leopard, a conservation flagship species of Central Asia mountains. Focusing on a snow leopard population in the Qilian mountains of Gansu Province, China, we characterised the spatial genetic patterns by incorporating spatially explicit indices of diversity and multivariate analyses, based on different inertia levels of Principal Component Analysis (PCA). We compared two datasets differing in the number of loci and individuals. We found that genetic patterns were significantly spatially structured and were characterised by a broad geographical division coupled with a fine-scale cline of differentiation. Genetic admixture was detected in two adjoining core areas characterised by higher effective population size and allelic diversity, compared to peripheral localities. The power to detect significant spatial relationships depended primarily on the number of loci, and secondarily on the number of PCA axes. Spatial patterns and indices of diversity highlighted the cryptic structure of snow leopard genetic diversity, likely driven by its ability to disperse over large distances. In combination, the species' low allelic richness and large dispersal ability result in weak genetic differentiation related to major geographical features and isolation by distance. This study illustrates how cryptic genetic patterns can be investigated and analysed at a fine spatial scale, providing insights into the spatially variable isolation effects of both geographic distance and landscape resistance.

Discovery of the First Non-cGMP Mimetic Small Molecule Activators of cGMP-Dependent Protein Kinase 1 α (PKG1α).

PKG1α is a central node in cGMP signaling. Current therapeutics that look to activate this pathway rely on elevation of cGMP levels and subsequent activation of PKG1α. Direct activation of PKG1α could potentially drive additional efficacy without associated side effects of blanket cGMP elevation. We undertook a high-throughput screen to identify novel activators. After triaging through numerous false positive hits, attributed to compound mediated oxidation and activation of PKG1α, a piperidine series of compounds was validated. The hit 1 was a weak activator with EC50 = 47 µM. The activity could be improved to single digit micromolar, as seen in compounds 21 and 25 (7.0 and 3.7 µM, respectively). Several compounds were tested in a pVASP cell-based assay, and for compounds with moderate permeability, good agreement was observed between the biochemical and functional assays. These compounds will function as efficient tools to further interrogate PKG1α biology.

Structural diversity and tree density drives variation in the biodiversity-ecosystem function relationship of woodlands and savannas.

Positive biodiversity-ecosystem function relationships (BEFRs) have been widely documented, but it is unclear if BEFRs should be expected in disturbance-driven systems. Disturbance may limit competition and niche differentiation, which are frequently posited to underlie BEFRs. We provide the first exploration of the relationship between tree species diversity and biomass, one measure of ecosystem function, across southern African woodlands and savannas, an ecological system rife with disturbance from fire, herbivores and humans. We used > 1000 vegetation plots distributed across 10 southern African countries and structural equation modelling to determine the relationship between tree species diversity and above-ground woody biomass, accounting for interacting effects of resource availability, disturbance by fire, tree stem density and vegetation type. We found positive effects of tree species diversity on above-ground biomass, operating via increased structural diversity. The observed BEFR was highly dependent on organismal density, with a minimum threshold of c. 180 mature stems ha-1 . We found that water availability mainly affects biomass indirectly, via increasing species diversity. The study underlines the close association between tree diversity, ecosystem structure, environment and function in highly disturbed savannas and woodlands. We suggest that tree diversity is an under-appreciated determinant of wooded ecosystem structure and function.

Tubular HIPK2 is a key contributor to renal fibrosis.

We previously used global Hipk2-null mice in various models of kidney disease to demonstrate the central role of homeodomain-interacting protein kinase 2 (HIPK2) in renal fibrosis development. However, renal tubular epithelial cell-specific (RTEC-specific) HIPK2 function in renal fibrogenesis has yet to be determined. Here, we show that modulation of tubular HIPK2 expression and activity affects renal fibrosis development in vivo. The loss of HIPK2 expression in RTECs resulted in a marked diminution of renal fibrosis in unilateral ureteral obstruction (UUO) mouse models and HIV-associated nephropathy (HIVAN) mouse models, which was associated with the reduction of Smad3 activation and downstream expression of profibrotic markers. Conversely, WT HIPK2 overexpression in RTECs accentuated the extent of renal fibrosis in the setting of UUO, HIVAN, and folic acid-induced nephropathy in mice. Notably, kinase-dead HIPK2 mutant overexpression or administration of BT173, an allosteric inhibitor of HIPK2-Smad3 interaction, markedly attenuated the renal fibrosis in these mouse models of kidney disease, indicating that HIPK2 requires both the kinase activity and its interaction with Smad3 to promote TGF-ß-mediated renal fibrosis. Together, these results establish an important RTEC-specific role of HIPK2 in kidney fibrosis and further substantiate the inhibition of HIPK2 as a therapeutic approach against renal fibrosis.

Essential Skills for Family Medicine Residents Practicing Integrated Behavioral Health A Delphi Study.

BACKGROUND AND OBJECTIVES: There are several trends compelling physicians to acquire team-based skills for interprofessional care. One underdeveloped area of team-based skills for physicians is integrated behavioral health (IBH) in primary care. We used a Delphi method to explore what skills were needed for residents to practice integrated behavioral health. METHODS: We conducted a literature review of IBH competencies and found 41 competencies across seven domains unique to physicians. Using a modified Delphi technique, we recruited family medicine educators to rate each competency as "essential," "compatible," or "irrelevant." We also shared findings from the Delphi study with a focus group for additional feedback. RESULTS: Twenty-one participants (12 physicians, nine behavioral health providers) completed all three rounds of the Delphi survey resulting in a list of 21 competencies. The focus group gave additional feedback. CONCLUSIONS: Participants chose skills that required physicians to share responsibilities across the entire care team, were not redundant with standard primary care, and necessitated strong communication ability. Many items were revised to reflect team-based care and a prescribed physician role as a team facilitator. Next steps include determining how these competencies fit with a variety of medical providers and creating effective training programs that develop competency in IBH.

Optimizing the choice of a spatial weighting matrix in eigenvector-based methods.

Eigenvector-mapping methods such as Moran's eigenvector maps (MEM) are derived from a spatial weighting matrix (SWM) that describes the relations among a set of sampled sites. The specification of the SWM is a crucial step, but the SWM is generally chosen arbitrarily, regardless of the sampling design characteristics. Here, we compare the statistical performances of different types of SWMs (distance-based or graph-based) in contrasted realistic simulation scenarios. Then, we present an optimization method and evaluate its performances compared to the arbitrary choice of the most-widely used distance-based SWM. Results showed that the distance-based SWMs generally had lower power and accuracy than other specifications, and strongly underestimated spatial signals. The optimization method, using a correction procedure for multiple tests, had a correct type I error rate, and had higher power and accuracy than an arbitrary choice of the SWM. Nevertheless, the power decreased when too many SWMs were compared, resulting in a trade-off between the gain of accuracy and the loss of power. We advocate that future studies should optimize the choice of the SWM using a small set of appropriate candidates. R functions to implement the optimization are available in the adespatial package and are detailed in a tutorial.

Antibacterial activity of male and female sperm-storage organs in ants.

Bacteria can damage sperm and thus reduce the reproductive success of both males and females; selection should therefore favour the evolution of antimicrobial protection. Eusocial hymenopterans might be particularly affected by such bacterial infections because of their mating ecology. In both sexes, mating is restricted to a short window early in the adult stage; there are no further chances to mate later in life. Males die shortly after mating, but queens use the acquired sperm to fertilise their eggs for years, sometimes decades. The reproductive success of both sexes is, thus, ultimately sperm-limited, which maintains strong selection for high sperm viability before and after storage. We tested the antibacterial activity of the contents of the male and female sperm-storage organs - the accessory testes and the spermatheca, respectively. As our study species, we used the bacterium Escherichia coli and the garden ant Lasius niger, whose queens can live for several decades. Our results provide the first empirical evidence that male and female sperm-storage organs display different antibacterial activity. While the contents of the accessory testes actually enhanced bacterial growth, the contents of the spermatheca strongly inhibited it. Furthermore, mating appears to activate the general immune system in queens. However, antimicrobial activity in both the spermatheca and the control tissue (head-thorax homogenate) declined rapidly post-mating, consistent with a trade-off between immunity and reproduction. Overall, this study suggests that ejaculates undergo an immune 'flush' at the time of mating, allowing storage of sperm cells free of bacteria.

Primary Care Behavioral Health (PCBH) Model Research: Current State of the Science and a Call to Action.

The Primary Care Behavioral Health (PCBH) model of service delivery is being used increasingly as an effective way to integrate behavioral health services into primary care. Despite its growing popularity, scientifically robust research on the model is lacking. In this article, we provide a qualitative review of published PCBH model research on patient and implementation outcomes. We review common barriers and potential solutions for improving the quantity and quality of PCBH model research, the vital data that need to be collected over the next 10 years, and how to collect those data.

Multiscale assemblage of an ectomycorrhizal fungal community: the influence of host functional traits and soil properties in a 10-ha miombo forest.

Ectomycorrhizal fungi (EMF) are highly diversified and dominant in a number of forest ecosystems. Nevertheless, their scales of spatial distribution and the underlying ecological processes remain poorly understood. Although most EMF are considered to be generalists regarding host identity, a preference toward functional strategies of host trees has never been tested. Here, the EMF community was characterised by DNA sequencing in a 10-ha tropical dry season forest-referred to as miombo-an understudied ecosystem from a mycorrhizal perspective. We used 36 soil parameters and 21 host functional traits (FTs) as candidate explanatory variables in spatial constrained ordinations for explaining the EMF community assemblage. Results highlighted that the community variability was explained by host FTs related to the 'leaf economics spectrum' (adjusted R(2) = 11%; SLA, leaf area, foliar Mg content), and by soil parameters (adjusted R(2) = 17%), notably total forms of micronutrients or correlated available elements (Al, N, K, P). Both FTs and soil generated patterns in the community at scales ranging from 75 to 375 m. Our results indicate that soil is more important than previously thought for EMF in miombo woodlands, and show that FTs of host species can be better predictors of symbiont distribution than taxonomical identity.