Genomic selection relies on single nucleotide polymorphisms (SNP), which are often collected using medium-density SNP arrays. In mink, no such array is available; instead, genotyping by sequencing (GBS) can be used to generate marker information. Here, we evaluated the effect of genomic selection for mink using GBS. We compared the estimated breeding values (EBV) from single-step genomic best linear unbiased prediction models (SSGBLUP) to the EBV from ordinary pedigree-based BLUP models. We analyzed seven size and quality traits from the live grading of brown mink. The phenotype data consisted of ~20,600 records for the seven traits from the mink born between 2013 and 2016. Genotype data included 2,103 mink born between 2010 and 2014, mostly breeding animals. In total, 28,336 SNP markers from 391 scaffolds were available for genomic prediction. The pedigree file included 29,212 mink. The predictive ability was assessed by the correlation (r) between progeny trait deviation (PTD) and EBV, and the regression ofiction in mink, demonstrating the potential of GBS for genomic selection in livestock species.

To estimate the transmission rate of carbapenemase-producing Enterobacteriaceae (CPE) in households with recently hospitalized CPE carriers.

We conducted a prospective case-ascertained cohort study. We identified the presence of CPE in stool samples from index subjects, household contacts and companion animals and environmental samples at regular intervals. Linked transmissions were identified by WGS. A Markov model was constructed to estimate the household transmission potential of CPE.

Ten recently hospitalized index patients and 14 household contacts were included. There were seven households with one contact, two households with two contacts, and one household with three contacts. Index patients were colonized with blaOXA-48-like (n = 4), blaKPC-2 (n = 3), blaIMP (n = 2), and blaNDM-1 (n = 1), distributed among divergent species of Enterobacteriaceae. After a cumulative follow-up time of 9.0 years, three family members (21.4%, 3/14) acquired four different types of CPE in the community (hazard rate of 0.22/year). The probability of CPE transmission from an index patient to a household contact was 10% (95% CI 4%-26%).

We observed limited transmission of CPE from an index patient to household contacts. Larger studies are needed to understand the factors associated with household transmission of CPE and identify preventive strategies.

We observed limited transmission of CPE from an index patient to household contacts. Larger studies are needed to understand the factors associated with household transmission of CPE and identify preventive strategies.

Chronic intermittent hypoxia (CIH) is a major determinant in OSA cardiovascular morbidity and this effect is influenced by age. The objective of the present study was to assess the differential molecular mechanisms at gene level expression involved in the cardiovascular remodeling induced by CIH according to chronological age.

Two-month and 18-month old mice (N=8 each) were subjected to CIH or normoxia for 8-weeks. Total mRNA was extracted from left ventricle myocardium and aortic arch, and gene expression of 46 intermediaries of aging, oxidative stress and inflammation was measured by quantitative real time PCR.

Cardiac gene expression of Nrf2 (2.05-fold increase, p<0.001), Sod2 (1.9-fold increase, p=0.035), Igf1r (1.4-fold increase, p=0.028), Mtor (1.8-fold increase, p=0.06), Foxo3 (1.5-fold increase, p=0.020), Sirt4, Sirt6, and Sirt7 (1.3-fold increase, p=0.012; 1.1-fold change, p=0.031; 1.3-fold change, p=0.029) was increased after CIH in young mice, but not in old mice. In aortic tissue, eNOS was reduced in young mice (p<0.001), Nrf2 was reduced in 80% (p<0.001) in young mice and in 45% (p=0.07) in old mice, as its downstream antioxidant target Sod2 (82% reduced, p<0.001). IL33.

CIH effect in gene expression is organ-dependent, and is modulated by age. CIH increased transcriptional expression of genes involved in cardioprotection and cell survival in young, but not in old mice. In aortic tissue, CIH reduced gene expression related to an antioxidant response in both young and old mice, suggesting vascular oxidative stress and a pro-aging process.

CIH effect in gene expression is organ-dependent, and is modulated by age. CIH increased transcriptional expression of genes involved in cardioprotection and cell survival in young, but not in old mice. In aortic tissue, CIH reduced gene expression related to an antioxidant response in both young and old mice, suggesting vascular oxidative stress and a pro-aging process.

Neighborhood disadvantage is associated with poor sleep, which may contribute to and exacerbate racial and socioeconomic health disparities. Most prior work has been cross-sectional and thus it has not been possible to estimate causal effects.

We leveraged a natural experiment opportunity in two low-income, predominantly African American Pittsburgh, PA neighborhoods, following a randomly selected cohort of households (n = 676) between 2013 and 2016. One of the neighborhoods received substantial public and private investments (housing, commercial) over the study period, while the other socio-demographically similar neighborhood received far fewer investments. Primary analyses used a difference-in-difference analysis based on neighborhood, to examine changes in actigraphy-assessed sleep duration, efficiency, and wakefulness after sleep onset (WASO), and self-reported sleep quality. Secondary analyses examined whether residents’ proximity to investments, regardless of neighborhood, was associated with changefor public health and policy efforts focused on investing in historically disinvested neighborhoods.Competing risk data are frequently interval-censored, that is, the exact event time is not observed but only known to lie between two examination time points such as clinic visits. In addition to interval censoring, another common complication is that the event type is missing for some study participants. In this article, we propose an augmented inverse probability weighted sieve maximum likelihood estimator for the analysis of interval-censored competing risk data in the presence of missing event types. The estimator imposes weaker than usual missing at random assumptions by allowing for the inclusion of auxiliary variables that are potentially associated with the probability of missingness. The proposed estimator is shown to be doubly robust, in the sense that it is consistent even if either the model for the probability of missingness or the model for the probability of the event type is misspecified. Extensive Monte Carlo simulation studies show good performance of the proposed method even under a large amount of missing event types. The method is illustrated using data from an HIV cohort study in sub-Saharan Africa, where a significant portion of events types is missing. The proposed method can be readily implemented using the new function ciregic_aipw in the R package intccr.Ca2+/calmodulin (CaM)-dependent protein kinase Iδ (CaMKIδ) is a Ser/Thr kinase that plays pivotal roles in Ca2+ signalling. CaMKIδ is activated by Ca2+/CaM-binding and phosphorylation at Thr180 by CaMK kinase (CaMKK). In this study, we characterized four splice variants of mouse CaMKIδ (mCaMKIδs a, b, c and d) found by in silico analysis. Recombinant mCaMKIδs expressed in Escherichia coli were phosphorylated by CaMKK; however, only mCaMKIδ-a and c showed protein kinase activities towards myelin basic protein in vitro, with mCaMKIδ-b and mCaMKIδ-d being inactive. Although mCaMKIδ-a and mCaMKIδ-c underwent autophosphorylation in vitro, only mCaMKIδ-c underwent autophosphorylation in 293T cells. Site-directed mutagenesis showed that the autophosphorylation site is Ser349, which is found in the C-terminal region of only variants c and b (Ser324). Furthermore, phosphorylation of these sites (Ser324 and Ser349) in mCaMKIδ-b and c was more efficiently catalyzed by cAMP-dependent protein kinase in vitro and in cellulo as compared to the autophosphorylation of mCaMKIδ-c. Thus, variants of mCaMKIδ possess distinct properties in terms of kinase activities, autophosphorylation and phosphorylation by another kinase, suggesting that they play physiologically different roles in murine cells.

Colorectal cancer screening program using a fecal immunochemical test aims to reduce morbidity and mortality through early detection. Although screening participation is free-of-charge, almost 40% of the invited individuals choose not to participate. To bring new insight into how non-participation can be identified and targeted, we examined the association between marital status and screening participation; with a focus on partner concordance in participation and sex differences.

This nationwide cross-sectional study included all Danish citizens aged 50-74 years, who were invited to colorectal cancer screening between 2014 and 2017. Logistic regression analysis was used to estimate odds ratio (OR) of participation while adjusting for sociodemographic variables.

A total of 1909662 individuals were included in the analysis of which 62.7% participated in the screening program. Participation was highest among women. Stratified by marital status, screening participation was markedly lower in widowed (61.5%),potentially benefit from considering the role of partner concordance.

Assessment of early outcomes in patients with normal preoperative left ventricular ejection fraction (LVEF) in whom venoarterial extracorporeal membrane oxygenation (VA-ECMO) was implanted for postcardiotomy cardiogenic shock (PCCS) during the first postoperative 48 h.

Retrospective single-centre analysis in adult patients with normal LVEF, who received VA-ECMO support for PCCS from May 1998 to May 2018. The primary outcome was 30-day perioperative mortality during the index hospitalization.

A total of 62125 adult patients underwent cardiac surgery at our institution during the study period. Among them, 173 patients (0.3%) with normal preoperative LVEF required VA-ECMO for PCCS. Among them, 71 (41.1%) patients presented PCCS due to coronary malperfusion and in 102 (58.9%) patients, no evident cause was found for PCCS. Median duration of VA-ECMO support was 5 days (interquartile range 2-8 days). A total of 135 (78.0%) patients presented VA-ECMO-related complications and the overall 30-day perioperative my of the cases. The implantation of VA-ECMO before development of tissue hypoperfusion and the control of VA-ECMO-associated complications are the most important prognostic factors in PCCS patients. Lactate levels may help guide timing of VA-ECMO implantation and define the extent of therapeutic effort.

Risk factors for and long-term outcomes following detection of varicella zoster virus (VZV) DNA in the cerebrospinal fluid (CSF) are unknown.

We performed a nationwide population-based cohort study of all Danish residents who had VZV DNA detected in the CSF by polymerase chain reaction (PCR) between 1 January 1997 and 1 March 2016 (VZV cohort; n = 517) and an age- and sex- matched comparison cohort from the general Danish population (n = 9823). We examined potential risk factors and mortality, neurologic morbidity, psychiatric morbidity, redemption of medicine prescribed for the nervous system and social outcomes.

Prior hospital admission, redemption of immunosuppressive medicine, comorbidity and immunosuppressive conditions were associated with detection of VZV DNA in the CSF. Mortality was increased in the VZV cohort, especially during the first year of observation and among patients with encephalitis. Patients in the VZV cohort had an increased risk of dementia and epilepsy. The redemption of antiepileptics and antidepressants was increased in the VZV cohort.