Sbf/MTMR13 coordinates PI(3)P and Rab21 regulation in endocytic control of cellular remodeling.

Cells rely on the coordinated regulation of lipid phosphoinositides and Rab GTPases to define membrane compartment fates along distinct trafficking routes. The family of disease-related myotubularin (MTM) phosphoinositide phosphatases includes catalytically inactive members, or pseudophosphatases, with poorly understood functions. We found that Drosophila MTM pseudophosphatase Sbf coordinates both phosphatidylinositol 3-phosphate (PI(3)P) turnover and Rab21 GTPase activation in an endosomal pathway that controls macrophage remodeling. Sbf dynamically interacts with class II phosphatidylinositol 3-kinase and stably recruits Mtm to promote turnover of a PI(3)P subpool essential for endosomal trafficking. Sbf also functions as a guanine nucleotide exchange factor that promotes Rab21 GTPase activation associated with PI(3)P endosomes. Of importance, Sbf, Mtm, and Rab21 function together, along with Rab11-mediated endosomal trafficking, to control macrophage protrusion formation. This identifies Sbf as a critical coordinator of PI(3)P and Rab21 regulation, which specifies an endosomal pathway and cortical control

RNA-seq reveals post-transcriptional regulation of Drosophila insulin-like peptide dilp8 and the neuropeptide-like precursor Nplp2 by the exoribonuclease Pacman/XRN1

Ribonucleases are critically important in many cellular and developmental processes and defects in their expression are associated with human disease. Pacman/XRN1 is a highly conserved cytoplasmic exoribonuclease which degrades RNAs in a 5' - 3' direction. In Drosophila, null mutations in pacman result in small imaginal discs, a delay in onset of pupariation and lethality during the early pupal stage. In this paper, we have used RNA-seq in a genome-wide search for mRNAs misregulated in pacman null wing imaginal discs. Only 4.2% of genes are misregulated ±>2-fold in pacman null mutants compared to controls, in line with previous work showing that Pacman has specificity for particular mRNAs. Further analysis of the most upregulated mRNAs showed that Pacman post-transcriptionally regulates the expression of the secreted insulin-like peptide Dilp8. Dilp8 is related to human IGF-1, and has been shown to co-ordinate tissue growth with developmental timing in Drosophila. The increased expression of Dilp8 is consistent with the developmental delay seen in pacman null mutants. Our analysis, together with our previous results, show that the normal role of this exoribonuclease in imaginal discs is to suppress the expression of transcripts that are crucial in apoptosis and growth control during normal development

Herschel Observations and Updated Spectral Energy Distributions of Five Sunlike Stars with Debris Disks

Observations from the Herschel Space Observatory have more than doubled the number of wide debris disks orbiting Sunlike stars to include over 30 systems with R > 100 AU. Here we present new Herschel PACS and re-analyzed Spitzer MIPS photometry of five Sunlike stars with wide debris disks, from Kuiper belt size to R > 150 AU. The disk surrounding HD 105211 is well resolved, with an angular extent of >14" along the major axis, and the disks of HD 33636, HD 50554, and HD 52265 are extended beyond the PACS PSF size (50% of energy enclosed within radius 4.23"). HD 105211 also has a 24-micron infrared excess that was previously overlooked because of a poorly constrained photospheric model. Archival Spitzer IRS observations indicate that the disks have small grains of minimum radius ~3 microns, though the minimum grain gradius is larger than the radiation pressure blowout size in all systems. If modeled as single-temperature blackbodies, the disk temperatures would all be <60 K. Our radiative transfer models predict actual disk radii approximately twice the radius of model blackbody disks. We find that the Herschel photometry traces dust near the source population of planetesimals. The disk luminosities are in the range 0.00002 <= L/L* <= 0.0002, consistent with collisions in icy planetesimal belts stirred by Pluto-size dwarf planets.Comment: Accepted for publication in ApJ. 18 pages, including 10 figures and 3 table

A systematic review and critical appraisal of quality indicators to assess optimal palliative care for older people with dementia

© The Author(s) 2019Background: A challenge for commissioners and providers of end-of-life care in dementia is to translate recommendations for good or effective care into quality indicators that inform service development and evaluation. Aim: To identify and critically evaluate quality indicators for end-of-life care in dementia. Results: We found 8657 references, after de-duplication. In all, 19 publications describing 10 new and 3 updated sets of indicators were included in this review. Ultimately, 246 individual indicators were identified as being relevant to dementia end-of-life care and mapped against EAPC guidelines. Conclusions: We systematically derived and assessed a set of quality indicators using a robust framework that provides clear definitions of aspects of palliative care, which are dementia specific, and strengthens the theoretical underpinning of new complex interventions in end-of-life care in dementia.Peer reviewedFinal Published versio

Clinical Characteristics and Outcomes Among Individuals With Spinal Implant Infections: A Descriptive Study.

Little is known about the clinical presentation and outcomes associated with spinal implant infections. Here, we describe a single center's experience in a retrospective cohort of 109 individuals with spinal implant infections, including clinical, microbiological, therapeutic, and outcome data

Striving toward team-based continuity: provision of same-day access and continuity in academic primary care clinics

Abstract Background An important goal of the patient-centered medical home is increasing timely access for urgent needs, while maintaining continuity. In academic primary care clinics, meeting this goal, along with training medical residents and associated professionals, is challenging. Methods The aim of this study was to understand how academic primary care clinics provide continuity to patients requesting same-day access and identify factors that may affect site-level success. We conducted qualitative interviews from December 2013–October 2014 with primary care leadership involved with residency programs at 19 Veterans Health Administration academically-affiliated medical centers. Interview recordings were transcribed verbatim. To analyze the data, we created comprehensive, structured transcript summaries for each site. Site summaries were then entered into NVivo 10 software and coded by main categories to facilitate within-case and cross-case analyses. Themes and patterns across sites were identified using matrix analysis. Results Interviewees found it challenging to provide continuity for same-day in-person visits. Most sites took a team-based approach to ensure continuity and provide coverage for same-day access, notably using NPs, PAs, and RNs in their coverage algorithms. Further, they reported several adaptations that increased multiple types of continuity for walk-in patients, urgent care between in-person visits, and follow-up care. While this study focused on longitudinal continuity, both by individual PCPs or by a team of professionals, informational continuity and continuity of supervision, as well as, to a lesser extent, relational and management continuity, were also addressed in our interviews. Finally, most interviewees reported clinic intention to provide patient-centered, team-based care and a robust educational experience for trainees, and endeavored to structure their clinics in ways that align these two missions. Conclusions In contending with the tension between providing continuity and educating new clinicians, clinics have re-conceptualized continuity as team-based, creating alternative strategies to same-day visits with a usual provider, coupled with communication strategies. Understanding the effect of these strategies on different types of continuity as well as patient experience and outcomes are key next steps in the further development and dissemination of effective models for improving continuity and the transition to team-based care in the academic clinic setting.https://deepblue.lib.umich.edu/bitstream/2027.42/148210/1/12913_2019_Article_3943.pd

Effectiveness of exercise interventions for adults over 65 with moderate-to-severe dementia in community settings: a systematic review

PurposeTo conduct a systematic review of the literature to evaluate the effectiveness of exercise interventions for people with moderate-to-severe dementia in community settings.MethodsEight electronic databases (MEDLINE, Embase, CINAHL, AMED, PsycINFO, PEDro, The Cochrane Library and BNI) were searched from inception to July 2018. Snowball searching identified additional articles not identified initially. Articles were included if they: reported randomised or quasi-randomised controlled trials comparing exercise with usual care or no treatment; and involved people over 65 with moderate-to-severe dementia in community settings. Outcome measures of interest were strength, endurance, mobility, mood and quality of life. Titles and abstracts of all studies were screened by one reviewer. Two reviewers independently screened full text articles for all eligible studies, extracted data and assessed quality and risk of bias.ResultsEight studies with 819 participants were included. Interventions were variable in terms of content, duration and frequency. There was some evidence exercise programmes may improve physical function of people with moderate-to-severe dementia, with significant effects seen for gait speed and endurance, and a trend towards improvement in strength. There was little evidence to suggest exercise programmes improve mood. Most studies were of low quality.ConclusionExercise was associated with improvements in gait speed and endurance for older people with moderate-to-severe dementia living in the community, but the quality of evidence was low. There was no conclusive evidence regarding effect on strength or mood. Findings are limited by the quality of the available evidence

Religiousness worldwide: translation of the Duke University Religion Index into 20 languages and validation across 27 nations

Religiousness and spirituality are important in the study of psychology for several reasons: They are central to identity and values; they have been reported as being positively associated with health and well-being; and they capture (and perhaps lead to) the largest measurable psychological differences between societies. At five items, the Duke University Religion Index (DUREL) is an efficient measure, which advantageously distinguishes between religious sentiment and activity, and between formal versus private involvement. This project extends its internal validation throughout the world, with formal tests of measurement invariance in three languages in Namibia (Study 1) and in a global sample of 26 countries (Study 2). Results confirmed a two-subscale factorial structure of Religious Activity (combining organizational and non-organizational activities) and Intrinsic Religiosity in Namibia and in half of the 26-country samples. In 13 other countries, fit was best for a one-factor model. Fit was problematic where there was too little intra-national variance: in China and Japan, where religious involvement is universally low, and in Tanzania, where it is universally high. Scalar measurement invariance was found for the one-factor structure across 13 samples and for the two-factor structure across 11 samples. External validation of the scale is examined using psychological and sociodemographic variables. This validation of the DUREL supports its use across contexts, facilitating increased attention to this important aspect of both personality and culture

Religiousness worldwide: translation of the Duke University Religion Index into 20 languages and validation across 27 nations

Religiousness and spirituality are important in the study of psychology for several reasons: They are central to identity and values; they have been reported as being positively associated with health and well-being; and they capture (and perhaps lead to) the largest measurable psychological differences between societies. At five items, the Duke University Religion Index (DUREL) is an efficient measure, which advantageously distinguishes between religious sentiment and activity, and between formal versus private involvement. This project extends its internal validation throughout the world, with formal tests of measurement invariance in three languages in Namibia (Study 1) and in a global sample of 26 countries (Study 2). Results confirmed a two-subscale factorial structure of Religious Activity (combining organizational and non-organizational activities) and Intrinsic Religiosity in Namibia and in half of the 26-country samples. In 13 other countries, fit was best for a one-factor model. Fit was problematic where there was too little intra-national variance: in China and Japan, where religious involvement is universally low, and in Tanzania, where it is universally high. Scalar measurement invariance was found for the one-factor structure across 13 samples and for the two-factor structure across 11 samples. External validation of the scale is examined using psychological and sociodemographic variables. This validation of the DUREL supports its use across contexts, facilitating increased attention to this important aspect of both personality and culture