Substance use and depression in home visiting clients: Home visitor perspectives on addressing clients’ needs

Substance use and depression are prevalent among mothers enrolled in home visiting programs and are significant risk factors for child maltreatment, yet most home visiting programs are staffed by workers who lack the training and clinical skills to address these risks. Emanating from one state network's interest in advancing its practice in this area, the current study surveyed 159 home visitors on their current practices, training, knowledge, and perceived self‐efficacy, and perceived system‐ and client‐level barriers regarding client substance use and depression. Home visitors reported managing maternal depression more extensively than substance use, though overall management of both risk areas was low. More training was associated with more extensive management of both risk domains, as was greater home visitor knowledge and self‐efficacy. Implications for the development of strategies to improve home visitor management of client behavioral health risks, including enhanced skills‐based training and supervision, are discussed.     

Expression of a cloned denV gene of bacteriophage T4 in Escherichia coli.

A 713-base-pair Hae III fragment from bacteriophage T4 encompassing the denV gene with its preceding promoter has been cloned in a pBR322-derived positive-selection vector and introduced into a variety of DNA repair-deficient uvr and rec and uvr,rec Escherichia coli strains. The denV gene was found to be expressed, probably from its own promoter, causing pyrimidine dimer incision-deficient uvrA, uvrB, uvrC strains to be rescued by the denV gene. A uvrD (DNA helicase II) strain was also complemented, but to a lesser extent. A wild-type strain did not seem to be affected at the UV doses tested. Surprisingly, all recA, recB, and recC strains tested also showed an increased UV resistance, perhaps by reinforcement of the intact uvr system in these strains. Complementation of denV- T4 strains and host-cell reactivation of lambda phage was also observed in denV+ E. coli strains. Equilibrium sedimentation showed that DNA repair synthesis occurred in a UV-irradiated uvrA E. coli strain carrying the cloned denV gene. Southern blotting confirmed our earlier results [Valerie, K., Henderson, E. E. & de Riel, J. K. (1984) Nucleic Acids Res. 12, 8085-8096] that the denV gene is located at 64 kilobases on the T4 map. Phage T2 (denV-) did not hybridize to a denV-specific probe.     

Knockout of Lmod2 results in shorter thin filaments followed by dilated cardiomyopathy and juvenile lethality

Leiomodin 2 (Lmod2) is an actin-binding protein that has been implicated in the regulation of striated muscle thin filament assembly; its physiological function has yet to be studied. We found that knockout of Lmod2 in mice results in abnormally short thin filaments in the heart. We also discovered that Lmod2 functions to elongate thin filaments by promoting actin assembly and dynamics at thin filament pointed ends. Lmod2-KO mice die as juveniles with hearts displaying contractile dysfunction and ventricular chamber enlargement consistent with dilated cardiomyopathy. Lmod2-null cardiomyocytes produce less contractile force than wild type when plated on micropillar arrays. Introduction of GFP-Lmod2 via adeno-associated viral transduction elongates thin filaments and rescues structural and functional defects observed in Lmod2-KO mice, extending their lifespan to adulthood. Thus, to our knowledge, Lmod2 is the first identified mammalian protein that functions to elongate actin filaments in the heart; it is essential for cardiac thin filaments to reach a mature length and is required for efficient contractile force and proper heart function during development.Striated muscle cells contain arrays of protein filaments assembled into contractile units that are nearly crystalline in structure. Efficient contraction at the molecular level is predicated upon accurate overlap of actin-containing thin and myosin-containing thick filaments. Therefore, proper control of filament assembly is absolutely critical.In striated muscle it is currently thought that the thin-filament pointed end capping protein tropomodulin (Tmod) is the predominant regulator of thin filament length, with Tmod1 being the sole isoform expressed in cardiomyocytes (1). Extensive in vitro work has revealed that Tmod1 uses two actin- and two tropomyosin-binding sites to associate with the end of the thin filament and to prevent addition or loss of actin monomers, thereby controlling length of the thin filament (2–7). Tmod1 is essential for life; Tmod1-KO mice are embryonic lethal because of cardiac defects (8–11).Identification of additional but structurally different members of the Tmod family of proteins, the leiomodins (Lmods), raises the possibility that thin filament lengths are not regulated solely by Tmod at thin filament pointed ends (12). Although there are three Lmod genes (Lmod1–3), Lmod2 and 3 are expressed in striated muscle with Lmod2 being the predominant isoform in cardiac muscle and Lmod3 the predominant isoform in skeletal muscle (12–16). The Lmods share ∼40% sequence identity at the protein level with the Tmods but do not contain a recognizable second tropomyosin-binding domain and have an additional C-terminal extension that includes a proline-rich region and an actin-binding Wiskott–Aldrich syndrome protein homology 2 (WH2) domain (12, 17). Lmod2 has been proposed to be the long-sought muscle actin filament nucleator because it robustly nucleates actin filament formation in vitro (because of its three actin-binding sites) and is reportedly required for proper sarcomere assembly in cultured cardiomyocytes (17). Like Tmod1, Lmod2 assembly at the pointed end of the thin filament requires association with tropomyosin; however unlike Tmod1, Lmod2 assembly also is dependent on contractility and the availability of polymerizable actin (18). Although part of the Tmod family of proteins, Lmod2 does not demonstrate actin filament-capping activity, and its overexpression displaces Tmod1; it is not known if this displacement is a direct or indirect effect (13). Nevertheless, Lmod2 overexpression results in the elongation of thin filaments in cells in culture (13). Limited data regarding the function of Lmod2 suggest it could play an important role in sarcomeric actin assembly, but the physiological function of Lmod2 has yet to be studied.Here we show that Lmod2 functions as an actin filament elongation factor in the heart. Our search for the mechanism by which Lmod2 functions revealed that Lmod2 promotes actin assembly and dynamics at the pointed end of the thin filament, is not necessary for myofibrillogenesis, but is required for thin filaments to attain a mature length. Our results also indicate that Lmod2 is essential for normal heart function and suggest that dysregulation of the thin filament length is causative for dilated cardiomyopathy (DCM).     

High mammographic density is associated with an increase in stromal collagen and immune cells within the mammary epithelium

Introduction

Mammographic density (MD), after adjustment for a women’s age and body mass index, is a strong and independent risk factor for breast cancer (BC). Although the BC risk attributable to increased MD is significant in healthy women, the biological basis of high mammographic density (HMD) causation and how it raises BC risk remain elusive. We assessed the histological and immunohistochemical differences between matched HMD and low mammographic density (LMD) breast tissues from healthy women to define which cell features may mediate the increased MD and MD-associated BC risk.

Methods

Tissues were obtained between 2008 and 2013 from 41 women undergoing prophylactic mastectomy because of their high BC risk profile. Tissue slices resected from the mastectomy specimens were X-rayed, then HMD and LMD regions were dissected based on radiological appearance. The histological composition, aromatase immunoreactivity, hormone receptor status and proliferation status were assessed, as were collagen amount and orientation, epithelial subsets and immune cell status.

Results

HMD tissue had a significantly greater proportion of stroma, collagen and epithelium, as well as less fat, than LMD tissue did. Second harmonic generation imaging demonstrated more organised stromal collagen in HMD tissues than in LMD tissues. There was significantly more aromatase immunoreactivity in both the stromal and glandular regions of HMD tissues than in those regions of LMD tissues, although no significant differences in levels of oestrogen receptor, progesterone receptor or Ki-67 expression were detected. The number of macrophages within the epithelium or stroma did not change; however, HMD stroma exhibited less CD206⁺ alternatively activated macrophages. Epithelial cell maturation was not altered in HMD samples, and no evidence of epithelial–mesenchymal transition was seen; however, there was a significant increase in vimentin⁺/CD45⁺ immune cells within the epithelial layer in HMD tissues.

Conclusions

We confirmed increased proportions of stroma and epithelium, increased aromatase activity and no changes in hormone receptor or Ki-67 marker status in HMD tissue. The HMD region showed increased collagen deposition and organisation as well as decreased alternatively activated macrophages in the stroma. The HMD epithelium may be a site for local inflammation, as we observed a significant increase in CD45⁺/vimentin⁺ immune cells in this area.

Electronic supplementary material

The online version of this article (doi:10.1186/s13058-015-0592-1) contains supplementary material, which is available to authorized users.