Poxviruses package viral redox proteins in lateral bodies and modulate the host oxidative response.

All poxviruses contain a set of proteinaceous structures termed lateral bodies (LB) that deliver viral effector proteins into the host cytosol during virus entry. To date, the spatial proteotype of LBs remains unknown. Using the prototypic poxvirus, vaccinia virus (VACV), we employed a quantitative comparative mass spectrometry strategy to determine the poxvirus LB proteome. We identified a large population of candidate cellular proteins, the majority being mitochondrial, and 15 candidate viral LB proteins. Strikingly, one-third of these are VACV redox proteins whose LB residency could be confirmed using super-resolution microscopy. We show that VACV infection exerts an anti-oxidative effect on host cells and that artificial induction of oxidative stress impacts early and late gene expression as well as virion production. Using targeted repression and/or deletion viruses we found that deletion of individual LB-redox proteins was insufficient for host redox modulation suggesting there may be functional redundancy. In addition to defining the spatial proteotype of VACV LBs, these findings implicate poxvirus redox proteins as potential modulators of host oxidative anti-viral responses and provide a solid starting point for future investigations into the role of LB resident proteins in host immunomodulation.

Creld1 regulates myocardial development and function.

CRELD1 (Cysteine-Rich with EGF-Like Domains 1) is a risk gene for non-syndromic atrioventricular septal defects in human patients. In a mouse model, Creld1 has been shown to be essential for heart development, particularly in septum and valve formation. However, due to the embryonic lethality of global Creld1 knockout (KO) mice, its cell type-specific function during peri- and postnatal stages remains unknown. Here, we generated conditional Creld1 KO mice lacking Creld1 either in the endocardium (KOTie2) or the myocardium (KOMyHC). Using a combination of cardiac phenotyping, histology, immunohistochemistry, RNA-sequencing, and flow cytometry, we demonstrate that Creld1 function in the endocardium is dispensable for heart development. Lack of myocardial Creld1 causes extracellular matrix remodeling and trabeculation defects by modulation of the Notch1 signaling pathway. Hence, KOMyHC mice die early postnatally due to myocardial hypoplasia. Our results reveal that Creld1 not only controls the formation of septa and valves at an early stage during heart development, but also cardiac maturation and function at a later stage. These findings underline the central role of Creld1 in mammalian heart development and function.

Vaccinia virus subverts xenophagy through phosphorylation and nuclear targeting of p62.

Autophagy is an essential degradation program required for cell homeostasis. Among its functions is the engulfment and destruction of cytosolic pathogens, termed xenophagy. Not surprisingly, many pathogens use various strategies to circumvent or co-opt autophagic degradation. For poxviruses, it is known that infection activates autophagy, which however is not required for successful replication. Even though these complex viruses replicate exclusively in the cytoplasm, autophagy-mediated control of poxvirus infection has not been extensively explored. Using the prototypic poxvirus, vaccinia virus (VACV), we show that overexpression of the xenophagy receptors p62, NDP52, and Tax1Bp1 restricts poxvirus infection. While NDP52 and Tax1Bp1 were degraded, p62 initially targeted cytoplasmic virions before being shunted to the nucleus. Nuclear translocation of p62 was dependent upon p62 NLS2 and correlated with VACV kinase mediated phosphorylation of p62 T269/S272. This suggests that VACV targets p62 during the early stages of infection to avoid destruction and further implies that poxviruses exhibit multi-layered control of autophagy to facilitate cytoplasmic replication.

Director of nursing current job tenure and past experience and quality of care in nursing homes.

BACKGROUND: Directors of nursing (DONs) are central to quality of care in nursing homes (NHs) because of their role in coordinating and overseeing nursing care. Research is needed to test the association between DON characteristics and quality using large, representative samples of NHs and global measures of quality. One such measure is the quality measure (QM) rating from the Centers for Medicare & Medicaid Services' Five-Star Quality Rating, which aggregates 10 individual QMs into a single rating. PURPOSE: This study examined whether DON current job tenure or past experience (a) differed across levels of the QM rating, (b) was associated with QM ratings, and (c) was associated with any of the individual 10 QM scores that comprise QM ratings. METHODOLOGY: Data for a nationally representative sample of 1,174 NHs were obtained from the 2004 National Nursing Home Survey, publicly reported QMs, and an Area Resource File. Wald tests were used to test differences in mean DON current job tenure and past experience across levels of the QM rating. Multinomial logistic and Poisson regression analyses were used to examine the association between DON current job tenure and past experience and QM ratings and QM scores, respectively, controlling for selected market and organizational characteristics. FINDINGS: Nursing homes with longer DON current job tenure tended to have higher QM ratings. Longer DON current job tenure was associated with higher QM ratings and lower QM scores for several individual QMs, suggesting higher quality. The past experience of the DON did not differ across levels of the QM rating and was not associated with QM ratings or QM scores. PRACTICE IMPLICATIONS: This study highlights the need for owners and administrators to support DONs as they either the transition into the role of the DON for the first time or learn to effectively fulfill their role in a new NH.

Work-related and personal predictors of COVID-19 transmission: evidence from the UK and USA.

OBJECTIVE: To develop evidence of work-related and personal predictors of COVID-19 transmission. SETTING AND RESPONDENTS: Data are drawn from a population survey of individuals in the USA and UK conducted in June 2020. BACKGROUND METHODS: Regression models are estimated for 1467 individuals in which reported evidence of infection depends on work-related factors as well as a variety of personal controls. RESULTS: The following themes emerge from the analysis. First, a range of work-related factors are significant sources of variation in COVID-19 infection as indicated by self-reports of medical diagnosis or symptoms. This includes evidence about workplace types, consultation about safety and union membership. The partial effect of transport-related employment in regression models makes the chance of infection over three times more likely while in univariate analyses, transport-related work increases the risk of infection by over 40 times in the USA. Second, there is evidence that some home-related factors are significant predictors of infection, most notably the sharing of accommodation or a kitchen. Third, there is some evidence that behavioural factors and personal traits (including risk preference, extraversion and height) are also important. CONCLUSIONS: The paper concludes that predictors of transmission relate to work, transport, home and personal factors. Transport-related work settings are by far the greatest source of risk and so should be a focus of prevention policies. In addition, surveys of the sort developed in this paper are an important source of information on transmission pathways within the community.

Implementation and Evaluation of LVN LEAD. A leadership and supervisory training program for nursing home charge nurses.

Licensed practical/vocational nurses (LVNs) play an important role in U.S. nursing homes, with primary responsibility for supervising unlicensed nursing home staff. Research has shown that the relationship between charge nurses and certified nursing assistants (CNAs) has a significant impact on CNA job satisfaction and turnover as well as quality of care, yet nurses rarely receive supervisory training. The purpose of this project was to develop, pilot, and evaluate a leadership/supervisory training program for LVNs. Upon completion of the training program, many LVNs expressed and demonstrated a new understanding of their supervisory leadership and supervisory responsibilities. Directors of staff development are a potential vehicle for supporting LVNs' development as supervisors.

Testing mediation in nursing research: beyond Baron and Kenny.

BACKGROUND: R. M. Baron and D. A. Kenny (1986) defined mediation and described how to perform statistical tests of mediation hypotheses. Their approach to testing mediation has been used extensively in the nursing literature. However, many statisticians have identified problems with the Baron and Kenny approach. PURPOSE: The aim of this paper is to critically evaluate alternative approaches to testing mediation. APPROACH: The Baron and Kenny approach and its shortcomings are briefly reviewed. A critical analysis of 17 alternate methods in three categories is then presented: (a)causal steps, (b) difference in coefficients, and (c) product of coefficients. The evaluation focuses on Type I error rate control, power, ease of computation, and versatility of use. RESULTS: Of the methods that control Type I error rate adequately, the joint significance test of [alpha] and [beta], the asymmetric distribution of products test, and the test of the products using the percentile bootstrap method are the most powerful tests of mediation. Of these three, the joint significance test of [alpha] and [beta] is superior due to its computational ease and versatility of use. DISCUSSION: Knowledge development in nursing will benefit from continued research testing mediation models. Nurse researchers could move beyond the Baron and Kenny approach to utilize more robust tests of mediation.

Rising mean incomes for whom?

Not everybody is benefiting equally from rising mean incomes. We discuss the mean-income population share (MPS), the population percentage of earners below mean income, whose evolution can capture how representative rising mean values are for middle income households. Tracking MPS and its associated income share MIS over time indicates to what extent economic growth is inclusive of both the middle and the bottom of the income distribution. We characterize MPS and MIS analytically under different growth scenarios and compare their parametric estimation using micro-level and grouped income data. Our empirical application with panel data of 16 high- and middle-income countries shows that in the last decades rising mean incomes have mostly not favored middle income households in relative perspective, while the overall welfare effects of the changes in MPS and the correlation structure with the Gini coefficient are mixed.

Synthesis of hydroxyl-functionalized N-heterocyclic carbene gold(i) complexes and peptide conjugates.

The synthesis and characterization of a series of new cationic gold(i) complexes with hydroxyl-functionalized N-heterocyclic carbene (NHC) ligands is described. They are valuable building blocks for further derivatization: as a first example, coupling with amino acids and a dipeptide, respectively, successfully results in amino acid and peptide conjugates that are hard to obtain by other synthetic routes.

Responding to poor-quality care during research in nursing homes.

For nurse researchers, responding appropriately to resident abuse is straightforward: The abuse must be reported. However, responding to care that is of poor quality-where care practices are problematic but do not meet the definition of reportable abuse-is not so straightforward. Decision making may be influenced by ethical and professional principles, as well as self-interest to complete a research project. The purpose of this article is to provoke a dialogue about a dilemma faced by many researchers conducting research in long-term care: responding to poor-quality care that does not meet the state's definition of resident abuse. We will accomplish this by providing a real-life situation faced by a novice researcher conducting her first funded research project, identifying some of the important considerations and possible responses by nurse researchers. Optimally, nurse researchers will develop a plan for responding to poor care before beginning the study.