Screening for Alcohol use/abuse in the Primary Care Setting using the AUDIT-C and SBIRT (Screening, Brief Intervention, Referral to Treatment)

PURPOSE: The purpose of this study was to examine the feasibility of alcohol screening in the primary care setting to detect alcohol abuse or misuse using the AUDIT-C standardized screening tool and SBIRT. METHODS: This study design was a Quasi-Experimental intervention, one group post-test. Data was collected via retrospective chart review from the electronic medical records by the type of office visit; either new patient initial visit or annual well visit. The patient sample consisted of 25 participants for the study period of September 19th through October 10th, 2017. RESULTS: There were 37 patients eligible to participate in the study; annual visits or new patients. Two APRN providers tested the feasibility of using the tool. Of the 37 patients, 25 (n=25) received the AUDIT-C tool, and 23 scores were documented by the provider. Provider compliance in documenting was 92%. The sample was 80% female the mean age was 42.6. Almost nine percent scored high enough for a Brief Intervention. CONCLUSION: Feasibility of the AUDIT-C use in the primary care setting was shown. Providers were satisfied and felt they took away essential information they would not have otherwise had. More studies need to be done on a larger scale, incorporating more providers and more locations

Growth zoning of garnet porphyroblasts: grain boundary and microtopographic controls

Chemical zoning in the outer few 10s of microns of garnet porphyroblasts has been investigated to assess the scale of chemical equilibrium with matrix minerals in a pelitic schist. Garnet porphyroblasts from the Late Proterozoic amphibolite‐facies regional metamorphic mica schists from Glen Roy in the Scottish Highlands contain typical prograde growth zoning patterns. Edge compositions have been measured via a combination of analysis of traverses across the planar edges of porphyroblast surfaces coupled to X‐ray mapping of small areas within polished thin sections at the immediate edge of the porphyroblasts. These approaches reveal local variation in garnet composition, especially of grossular (Ca) and almandine (Fe) components, with a range at the edge from <7 mol% grs to >16 mol% grs, across distances of less then 50 mm. This small‐scale patchy compositional zoning is as much variation as the core‐rim compositional zoning across the whole of a 3 mm porphyroblast. Ca and Fe heterogeneity occurs on a scale suggesting a combination of inefficient diffusive exchange across grain boundaries during prograde growth and the evolving microtopography of the porphyroblast surface control garnet composition. The latter creates haloes of compositional zoning adjacent to some inclusions, which typically extend from the inclusion towards the porphyroblast edge during further growth. The lack of a consistent equilibrium composition at the garnet edge is also apparent in the internal zoning of the porphyroblast and so processes occurring during entrapment of some mineral inclusions have a profound influence on the overall chemical zoning. Garnet compositions and associated zoning patterns are widely used by petrologists to reconstruct P‐T‐t paths for crustal rocks. The evidence of extremely localized (10‐50 mm scale) equilibrium during growth further undermines these approaches

Cannabinoid exposure during zebra finch sensorimotor vocal learning persistently alters expression of endocannabinoid signaling elements and acute agonist responsiveness

<p>Abstract</p> <p>Background</p> <p>Previously we have found that cannabinoid treatment of zebra finches during sensorimotor stages of vocal development alters song patterns produced in adulthood. Such persistently altered behavior must be attributable to changes in physiological substrates responsible for song. We are currently working to identify the nature of such physiological changes, and to understand how they contribute to altered vocal learning. One possibility is that developmental agonist exposure results in altered expression of elements of endocannabinoid signaling systems. To test this hypothesis we have studied effects of the potent cannabinoid receptor agonist WIN55212-2 (WIN) on endocannabinoid levels and densities of CB₁immunostaining in zebra finch brain.</p> <p>Results</p> <p>We found that late postnatal WIN treatment caused a long-term global disregulation of both levels of the endocannabinoid, 2-arachidonyl glycerol (2-AG) and densities of CB₁immunostaining across brain regions, while repeated cannabinoid treatment in adults produced few long-term changes in the endogenous cannabinoid system.</p> <p>Conclusions</p> <p>Our findings indicate that the zebra finch endocannabinoid system is particularly sensitive to exogenous agonist exposure during the critical period of song learning and provide insight into susceptible brain areas.</p

ZMYND10 Is Mutated in Primary Ciliary Dyskinesia and Interacts with LRRC6

Defects of motile cilia cause primary ciliary dyskinesia (PCD), characterized by recurrent respiratory infections and male infertility. Using whole-exome resequencing and high-throughput mutation analysis, we identified recessive biallelic mutations in ZMYND10 in 14 families and mutations in the recently identified LRRC6 in 13 families. We show that ZMYND10 and LRRC6 interact and that certain ZMYND10 and LRRC6 mutations abrogate the interaction between the LRRC6 CS domain and the ZMYND10 C-terminal domain. Additionally, ZMYND10 and LRRC6 colocalize with the centriole markers SAS6 and PCM1. Mutations in ZMYND10 result in the absence of the axonemal protein components DNAH5 and DNALI1 from respiratory cilia. Animal models support the association between ZMYND10 and human PCD, given that zmynd10 knockdown in zebrafish caused ciliary paralysis leading to cystic kidneys and otolith defects and that knockdown in Xenopus interfered with ciliogenesis. Our findings suggest that a cytoplasmic protein complex containing ZMYND10 and LRRC6 is necessary for motile ciliary function

ZMYND10 Is Mutated in Primary Ciliary Dyskinesia and Interacts with LRRC6

Defects of motile cilia cause primary ciliary dyskinesia (PCD), characterized by recurrent respiratory infections and male infertility. Using whole-exome resequencing and high-throughput mutation analysis, we identified recessive biallelic mutations in ZMYND10 in 14 families and mutations in the recently identified LRRC6 in 13 families. We show that ZMYND10 and LRRC6 interact and that certain ZMYND10 and LRRC6 mutations abrogate the interaction between the LRRC6 CS domain and the ZMYND10 C-terminal domain. Additionally, ZMYND10 and LRRC6 colocalize with the centriole markers SAS6 and PCM1. Mutations in ZMYND10 result in the absence of the axonemal protein components DNAH5 and DNALI1 from respiratory cilia. Animal models support the association between ZMYND10 and human PCD, given that zmynd10 knockdown in zebrafish caused ciliary paralysis leading to cystic kidneys and otolith defects and that knockdown in Xenopus interfered with ciliogenesis. Our findings suggest that a cytoplasmic protein complex containing ZMYND10 and LRRC6 is necessary for motile ciliary function

Actin Dynamics Regulate Multiple Endosomal Steps during Kaposi's Sarcoma-Associated Herpesvirus Entry and Trafficking in Endothelial Cells

The role of actin dynamics in clathrin-mediated endocytosis in mammalian cells is unclear. In this study, we define the role of actin cytoskeleton in Kaposi's sarcoma-associated herpesvirus (KSHV) entry and trafficking in endothelial cells using an immunofluorescence-based assay to visualize viral capsids and the associated cellular components. In contrast to infectivity or reporter assays, this method does not rely on the expression of any viral and reporter genes, but instead directly tracks the accumulation of individual viral particles at the nuclear membrane as an indicator of successful viral entry and trafficking in cells. Inhibitors of endosomal acidification reduced both the percentage of nuclei with viral particles and the total number of viral particles docking at the perinuclear region, indicating endocytosis, rather than plasma membrane fusion, as the primary route for KSHV entry into endothelial cells. Accordingly, a viral envelope protein was only detected on internalized KSHV particles at the early but not late stage of infection. Inhibitors of clathrin- but not caveolae/lipid raft-mediated endocytosis blocked KSHV entry, indicating that clathrin-mediated endocytosis is the major route of KSHV entry into endothelial cells. KSHV particles were colocalized not only with markers of early and recycling endosomes, and lysosomes, but also with actin filaments at the early time points of infection. Consistent with these observations, transferrin, which enters cells by clathrin-mediated endocytosis, was found to be associated with actin filaments together with early and recycling endosomes, and to a lesser degree, with late endosomes and lysosomes. KSHV infection induced dynamic actin cytoskeleton rearrangements. Disruption of the actin cytoskeleton and inhibition of regulators of actin nucleation such as Rho GTPases and Arp2/3 complex profoundly blocked KSHV entry and trafficking. Together, these results indicate an important role for actin dynamics in the internalization and endosomal sorting/trafficking of KSHV and clathrin-mediated endocytosis in endothelial cells