Family caregiver: balancing home and work

To meet the growing need for home health-care workers, policymakers will have to find ways to ensure that the jobs provide reasonable wages, good benefits, and a clear career path.Population aging ; Baby boom generation ; Employment forecasting

Performance Practice in the Indeterminate Works of John Cage

The recordings of Cage\u27s indeterminate works such as Variations I, Fontana mix, Cartridge music, Variations II, and Variations III reveal certain traditions in their performance, in both form and style

“Fecal microbiome in epidemiologic studies” - Letter

We congratulate Sinha et al. on their recent report (1) comparing fecal sample collection methods for epidemiologic studies of the gut microbiome. These data contribute to the increasing body of literature describing robust methodological frameworks for specimen collection and processing (2, 3). However, their claim that fixation of stool using RNAlater® results in “considerable changes to the microbiome diversity” contrasts with previous findings (2, 3), including those from their earlier reports (4, 5). We have previously demonstrated that self-collected stool stabilized with RNAlater® or other fixatives yields high fidelity and reproducibility in compositional profiling of DNA and RNA from shotgun sequence data, compared to immediately-frozen specimens (3). Additionally, fixation offers several distinct advantages crucial for large-scale population-based studies: a straightforward self-collection procedure; sample stabilization without deep-freezing during shipping, receiving, and processing; and versatility for multiple molecular analyses. The authors’ finding that specimens preserved in RNAlater® had poor correlation with immediately frozen specimens (1) could be explained, for example, by improper fixation resulting from an excess of specimen relative to preservative volume (1–2 g:2.5 ml, compared to the manufacturer-recommended ratio of 1 g:5–10 ml; Thermo Fisher Scientific Inc., Waltham, MA)

Lack of association between the rs2294008 polymorphism in the prostate stem cell antigen gene and colorectal neoplasia : a case-control and immunohistochemical study

PMID: 22824379 [PubMed - indexed for MEDLINE] PMCID: PMC3500224 Free PMC ArticlePeer reviewedPublisher PD

Regulation of peptide import through phosphorylation of Ubr1, the ubiquitin ligase of the N-end rule pathway

Substrates of the N-end rule pathway include proteins with destabilizing N-terminal residues. These residues are recognized by E3 ubiquitin ligases called N-recognins. Ubr1 is the N-recognin of the yeast Saccharomyces cerevisiae. Extracellular amino acids or short peptides up-regulate the peptide transporter gene PTR2, thereby increasing the capacity of a cell to import peptides. Cup9 is a transcriptional repressor that down-regulates PTR2. The induction of PTR2 by peptides or amino acids involves accelerated degradation of Cup9 by the N-end rule pathway. We report here that the Ubr1 N-recognin, which conditionally targets Cup9 for degradation, is phosphorylated in vivo at multiple sites, including Ser300 and Tyr277. We also show that the type-I casein kinases Yck1 and Yck2 phosphorylate Ubr1 on Ser300, and thereby make possible (“prime”) the subsequent (presumably sequential) phosphorylations of Ubr1 on Ser296, Ser292, Thr288, and Tyr277 by Mck1, a kinase of the glycogen synthase kinase 3 (Gsk3) family. Phosphorylation of Ubr1 on Tyr277 by Mck1 is a previously undescribed example of a cascade-based tyrosine phosphorylation by a Gsk3-type kinase outside of autophosphorylation. We show that the Yck1/Yck2-mediated phosphorylation of Ubr1 on Ser300 plays a major role in the control of peptide import by the N-end rule pathway. In contrast to phosphorylation on Ser300, the subsequent (primed) phosphorylations, including the one on Tyr277, have at most minor effects on the known properties of Ubr1, including regulation of peptide import. Thus, a biological role of the rest of Ubr1 phosphorylation cascade remains to be identified

A New, Atypical Case of Cobalamin F Disorder Diagnosed by Whole Exome Sequencing

The Deciphering Developmental Disorders Study presents independent research commissioned by the Health Innovation Challenge Fund (HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (WT098051). The views expressed in this publication are those of the author(s) and not necessarily those of the Wellcome Trust or the Department of Health. The research team acknowledges the support of the National Institute for Health Research, through the Comprehensive Clinical Research Network.Peer reviewedPublisher PD

Long-term use of antibiotics and risk of colorectal adenoma

Objective—Recent evidence suggests that antibiotic use, which alters the gut microbiome, is associated with an increased risk of colorectal cancer. However, the association between antibiotic use and risk of colorectal adenoma, the precursor for the majority of colorectal cancers, has not been investigated. Design—We prospectively evaluated the association between antibiotic use at age 20–39 and 40–59 (assessed in 2004) and recent antibiotic use (assessed in 2008) with risk of subsequent colorectal adenoma among 16,642 women aged ≥60 enrolled in the Nurses’ Health Study who underwent at least one colonoscopy through 2010. We used multivariate logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Results—We documented 1,195 cases of adenoma. Increasing duration of antibiotic use at age 20–39 (Ptrend=0.002) and 40–59 (Ptrend=0.001) was significantly associated with an increased risk of colorectal adenoma. Compared to non-users, women who used antibiotics for ≥2 months between age 20–39 had a multivariable OR of 1.36 (95% CI: 1.03–1.79). Women who used ≥2 months of antibiotics between age 40–59 had a multivariable OR of 1.69 (95% CI: 1.24–2.31). The associations were similar for low-risk vs. high-risk adenomas (size ≥1 cm, or with tubulovillous/villous histology, or ≥3 detected lesions), but appeared modestly stronger for proximal compared with distal adenomas. In contrast, recent antibiotic use within the past 4 years was not associated with risk of adenoma (Ptrend=0.44). Conclusions—Long-term antibiotic use in early to middle adulthood was associated with increased risk of colorectal adenoma

Emollient product design: objective measurements of formulation structure, texture and performance, and subjective assessments of user acceptability

Background: The choice of prescribed emollients is usually based on cost and patient preference. Differences in formulations can affect user acceptability. Aim: To compare the physical performance, user acceptability and various product design features of two emollient gels that are prescribed in the UK and alleged to be therapeutically interchangeable because their formulations are described as having the same contents of oily ingredients. Results: We found that here are in fact significant measurable differences between the structure and performance of the two formulations, which materially affect their user acceptability. These differences are attributed to the use of different types of gelling agents and other ingredients of differing grades/quality and concentrations, and probably due to the formulations being made by different manufacturing processes. We also identified other product design features that are important to user appeal, including the type of container in which the formulations are presented, the type of dispensing devices provided, and the nature and form of the supplied user instructions. Conclusion: Patients and prescribers should be aware that there can be important differences in performance and user appeal between emollients, even between products that, superficially, may appear to be very similar. These important performance aspects should be characterized for new emollient introductions to encourage better informed product selection

Stability of the human faecal microbiome in a cohort of adult men

Characterizing the stability of the gut microbiome is important to exploit it as a therapeutic target and diagnostic biomarker. We metagenomically and metatranscriptomically sequenced the faecal microbiomes of 308 participants in the Health Professionals Follow-Up Study. Participants provided four stool samples—one pair collected 24–72 h apart and a second pair ~6 months later. Within-person taxonomic and functional variation was consistently lower than between-person variation over time. In contrast, metatranscriptomic profiles were comparably variable within and between subjects due to higher within-subject longitudinal variation. Metagenomic instability accounted for ~74% of corresponding metatranscriptomic instability. The rest was probably attributable to sources such as regulation. Among the pathways that were differentially regulated, most were consistently over- or under-transcribed at each time point. Together, these results suggest that a single measurement of the faecal microbiome can provide long-term information regarding organismal composition and functional potential, but repeated or short-term measures may be necessary for dynamic features identified by metatranscriptomics