Barriers to infection prevention and control in patients' homes.

While there is a lot of emphasis on the need for good infection prevention and control practices and acute care, the increasing complexity of patients being cared for in their own homes means that there is an increased risk for infection. Good practice is required by community nurses to minimise this risk. Patients' own homes can present particular challenges in complying with good practice and this article looks at some of the barriers to optimum infection prevention and control precautions in this setting.

Gender-Typed Personality Qualities and African American Youth's School Functioning.

Numerous studies document sex differences in African American girls' and boys' academic achievement and motivation, but little is known about how the enactment of gender, such as in the forms of gendered behaviors, attitudes, or personal-social qualities, is related to school functioning. To advance understanding of African American adolescents' academic experiences, this study examined the longitudinal linkages between stereotypically feminine (i.e., expressive) and stereotypically masculine (i.e., instrumental) personality characteristics and school adjustment. The moderating effects of youth's ethnic identity and school racial composition also were tested. Participants were 352 African American youth (50.1% girls; mean age at Time 1 = 12.04 years; SD= 2.03) who participated in annual home interviews. Net of biological sex, expressive traits (kind, sensitive) were positively related to school self-esteem and school bonding for both girls and boys, but youth with higher levels of instrumentality (independent, competitive) exhibited sharper declines in academic achievement across adolescence. School racial composition moderated the effects of instrumentality at the between-person level, such that instrumentality was positively related to school self-esteem only for youth who attended schools with fewer African American students. These results highlight the importance of incorporating gendered personality traits, rather than biological sex alone, into theoretical accounts of African American youth's school functioning.

Infection prevention in care homes: the role of community nurses.

Community nurses are often in the position of providing clinical services to residents in the care home sector. In doing so, they need to consider the factors that increase the risk of infection in these residents and how these might be addressed. They also need to be mindful of the collaborative approach required and any training needs of staff working there in relation to services they have provided.

Age and Race Differences in Racial Stereotype Awareness and Endorsement.

Age and race differences in race stereotype awareness and endorsement were examined in 382 Black and White fourth, sixth, and eighth graders. Youth reported their own beliefs and their perceptions of adults' beliefs about racial differences in ability in two domains: academics and sports. Children's own endorsement of race stereotypes was highly correlated with their perceptions of adults' race stereotypes. Blacks reported stronger traditional sports stereotypes than Whites, and fourth- and sixth-grade Blacks reported roughly egalitarian academic stereotypes. At every grade level, Whites reported academic stereotypes that favored Whites, and sixth and eighth grade Whites reported sports stereotypes that favored Blacks. Results support the tenets of status theory and have implications for identity development and achievement motivation in adolescents.

An anti-PCSK9 antibody reduces LDL-cholesterol on top of a statin and suppresses hepatocyte SREBP-regulated genes.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a promising therapeutic target for treating coronary heart disease. We report a novel antibody 1B20 that binds to PCSK9 with sub-nanomolar affinity and antagonizes PCSK9 function in-vitro. In CETP/LDLR-hemi mice two successive doses of 1B20, administered 14 days apart at 3 or 10 mpk, induced dose dependent reductions in LDL-cholesterol (≥ 25% for 7-14 days) that correlated well with the extent of PCSK9 occupancy by the antibody. In addition, 1B20 induces increases in total plasma antibody-bound PCSK9 levels and decreases in liver mRNA levels of SREBP-regulated genes PCSK9 and LDLR, with a time course that parallels decreases in plasma LDL-cholesterol (LDL-C). Consistent with this observation in mice, in statin-responsive human primary hepatocytes, 1B20 lowers PCSK9 and LDLR mRNA levels and raises serum steady-state levels of antibody-bound PCSK9. In addition, mRNA levels of several SREBP regulated genes involved in cholesterol and fatty-acid synthesis including ACSS2, FDPS, IDI1, MVD, HMGCR, and CYP51A1 were decreased significantly with antibody treatment of primary human hepatocytes. In rhesus monkeys, subcutaneous (SC) dosing of 1B20 dose-dependently induces robust LDL-C lowering (maximal ~70%), which is correlated with increases in target engagement and total antibody-bound PCSK9 levels. Importantly, a combination of 1B20 and Simvastatin in dyslipidemic rhesus monkeys reduced LDL-C more than either agent alone, consistent with a mechanism of action that predicts additive effects of anti-PCSK9 agents with statins. Our results suggest that antibodies targeting PCSK9 could provide patients powerful LDL lowering efficacy on top of statins, and lower cardiovascular risk.

Exposure to violence and socioemotional adjustment in low-income youth: an examination of protective factors.

Using a sample of 391 low-income youth ages 13-17, this study investigated the potential moderating effects of school climate, participation in extracurricular activities, and positive parent-child relations on associations between exposure to violence (i.e., witnessing violence and violent victimization) and adolescent socioemotional adjustment (i.e., internalizing and externalizing problems). Exposure to violence was related to both internalizing and externalizing problems. High levels of participation in extracurricular activities and positive parent-child relations appeared to function as protective factors, weakening the positive association between exposure to violence and externalizing problems. Contrary to prediction, school climate did not moderate associations between exposure to violence and socioemotional adjustment. Further, none of the hypothesized protective factors moderated the association between exposure to violence and internalizing problems.

Gender differences in motivational pathways to college for middle class African American youths.

Using a sample of predominantly middle-class African American adolescents and parents (N = 424), the authors tested a path model linking parental expectations for children's future educational attainment, youths' motivation during Grade 11, and youths' subsequent on-time postsecondary educational progress. Parents' expectations were positively related to adolescents' educational attainment aspirations, attainment expectations, utility values (i.e., beliefs about the usefulness of education), and perceptions of racial barriers to upward mobility. Relationships between parents' expectations and youths' aspirations and expectations were mediated by youths' perceptions of parents' expectations. For boys, but not girls, Grade 11 educational expectations and utility values each uniquely predicted college attendance 1 year after high school graduation. In addition, boys' perceptions of racial barriers were negatively related to subsequent postsecondary progress through their influence on values. Findings underscore the importance of academic achievement motivation as a developmental resource for African American boys and suggest that boys are especially likely to benefit from interventions promoting positive motivational beliefs.

A PCSK9-binding antibody that structurally mimics the EGF(A) domain of LDL-receptor reduces LDL cholesterol in vivo.

Proprotein convertase subtilisin-like/kexin type 9 (PCSK9) regulates LDL cholesterol levels by inhibiting LDL receptor (LDLr)-mediated cellular LDL uptake. We have identified a fragment antigen-binding (Fab) 1D05 which binds PCSK9 with nanomolar affinity. The fully human antibody 1D05-IgG2 completely blocks the inhibitory effects of wild-type PCSK9 and two gain-of-function human PCSK9 mutants, S127R and D374Y. The crystal structure of 1D05-Fab bound to PCSK9 reveals that 1D05-Fab binds to an epitope on the PCSK9 catalytic domain which includes the entire LDLr EGF(A) binding site. Notably, the 1D05-Fab CDR-H3 and CDR-H2 loops structurally mimic the EGF(A) domain of LDLr. In a transgenic mouse model (CETP/LDLr-hemi), in which plasma lipid and PCSK9 profiles are comparable to those of humans, 1D05-IgG2 reduces plasma LDL cholesterol to 40% and raises hepatic LDLr protein levels approximately fivefold. Similarly, in healthy rhesus monkeys, 1D05-IgG2 effectively reduced LDL cholesterol 20%-50% for over 2 weeks, despite its relatively short terminal half-life (t(1/2) = 3.2 days). Importantly, the decrease in circulating LDL cholesterol corresponds closely to the reduction in free PCSK9 levels. Together these results clearly demonstrate that the LDL-lowering effect of the neutralizing anti-PCSK9 1D05-IgG2 antibody is mediated by reducing the amount of PCSK9 that can bind to the LDLr.

A proprotein convertase subtilisin-like/kexin type 9 (PCSK9) C-terminal domain antibody antigen-binding fragment inhibits PCSK9 internalization and restores low density lipoprotein uptake.

PCSK9 binds to the low density lipoprotein receptor (LDLR) and leads to LDLR degradation and inhibition of plasma LDL cholesterol clearance. Consequently, the role of PCSK9 in modulating circulating LDL makes it a promising therapeutic target for treating hypercholesterolemia and coronary heart disease. Although the C-terminal domain of PCSK9 is not involved in LDLR binding, the location of several naturally occurring mutations within this region suggests that it has an important role for PCSK9 function. Using a phage display library, we identified an anti-PCSK9 Fab (fragment antigen binding), 1G08, with subnanomolar affinity for PCSK9. In an assay measuring LDL uptake in HEK293 and HepG2 cells, 1G08 Fab reduced 50% the PCSK9-dependent inhibitory effects on LDL uptake. Importantly, we found that 1G08 did not affect the PCSK9-LDLR interaction but inhibited the internalization of PCSK9 in these cells. Furthermore, proteolysis and site-directed mutagenesis studies demonstrated that 1G08 Fab binds a region of beta-strands encompassing Arg-549, Arg-580, Arg-582, Glu-607, Lys-609, and Glu-612 in the PCSK9 C-terminal domain. Consistent with these results, 1G08 fails to bind PCSK9DeltaC, a truncated form of PCSK9 lacking the C-terminal domain. Additional studies revealed that lack of the C-terminal domain compromised the ability of PCSK9 to internalize into cells, and to inhibit LDL uptake. Together, the present study demonstrate that the PCSK9 C-terminal domain contribute to its inhibition of LDLR function mainly through its role in the cellular uptake of PCSK9 and LDLR complex. 1G08 Fab represents a useful new tool for delineating the mechanism of PCSK9 uptake and LDLR degradation.

Mothers' Academic Gender Stereotypes and Education-Related Beliefs About Sons and Daughters in African American Families.

The role of African American mothers' academic gender stereotype endorsement in shaping achievement-related expectations for and perceptions of their own children was examined. Mothers (N = 334) of 7th and 8th graders completed measures of expectations for their children's future educational attainment, perceptions of their children's academic competence, and academic gender stereotypes. Consistent with hypotheses, mothers held less favorable expectations for sons and perceived sons to be less academically competent than daughters. In addition, mothers reported stereotypes favoring girls over boys in academic domains; stereotype endorsement, in turn, was related to mothers' educational expectations for and beliefs about the academic competence of their own children, even with youths' actual achievement controlled. Negative stereotypes about the academic abilities of African American boys may create a negative feedback loop, thereby contributing to the maintenance of the gender gap in African Americans' educational outcomes.

Does endorsement of physical discipline matter? Assessing moderating influences on the maternal and child psychological correlates of physical discipline in African American families.

Using longitudinal data from a subsample of 890 African American families in the Child Development Supplement of the Panel Study of Income Dynamics, this study examined whether maternal endorsement of physical discipline moderates the link between (a) maternal psychological distress and spanking frequency and (b) spanking frequency and child depressive symptoms. As predicted, physical discipline administered by nonendorsing mothers was more strongly linked to maternal psychological distress than physical discipline administered by endorsing mothers. Also in keeping with the authors' hypothesis, the relation between spanking frequency and child-reported depressive symptoms was stronger for children of nonendorsing mothers than for children of endorsing mothers. In particular, the positive relation between physical discipline and children's depressive symptoms was significant only for children of nonendorsing mothers. These findings suggest that within-group variation in African American mothers' attitudes about physical discipline partially regulates the conditions under which these mothers use physical discipline and the probability that physical discipline contributes to depressive symptoms in children. Conclusions and implications for future research are discussed.