Low Neural Exosomal Levels of Cellular Survival Factors in Alzheimer\u27s Disease

Transcription factors that mediate neuronal defenses against diverse stresses were quantified in plasma neural-derived exosomes of Alzheimer\u27s disease or frontotemporal dementia patients and matched controls. Exosomal levels of low-density lipoprotein receptor-related protein 6, heat-shock factor-1, and repressor element 1-silencing transcription factor all were significantly lower in Alzheimer\u27s disease patients than controls (P \u3c 0.0001). In frontotemporal dementia, the only significant difference was higher levels of repressor element 1-silencing transcription factor than in controls. Exosomal transcription factors were diminished 2-10 years before clinical diagnosis of Alzheimer\u27s disease. Low exosomal levels of survival proteins may explain decreased neuronal resistance to Alzheimer\u27s disease neurotoxic proteins

Parents\u27 Goals: An Analysis of Therapist Reasoning

Purpose: Illustrate the use of DDDM to develop parent-identified goals for occupational therapy and to identify underlying sensory integration factors hypothesized to be impacting participation

The vitamin D binding protein axis modifies disease severity in Lymphangioleiomyomatosis

Background: Lymphangioleiomyomatosis (LAM) is a rare disease of women. Decline in lung function is variable making appropriate targeting of therapy difficult. We used unbiased serum proteomics to identify markers associated with outcome in LAM. Methods: 101 women with LAM and 22 healthy controls were recruited from the National Centre for LAM (Nottingham, UK). 152 DNA and serum samples with linked lung function and outcome data were obtained from patients in the NHLBI LAM Registry (USA). Proteomic analysis was performed on a discovery cohort of 50 LAM and 20 control sera using a SCIEX SWATH mass spectrometric workflow. Protein levels were quantitated by ELISA and SNPs in GC encoding Vitamin D Binding Protein (VTDB) genotyped. Results: Proteomic analysis showed VTDB was 2.6 fold lower in LAM than controls. Serum VTDB was lower in progressive compared with stable LAM (p=0.001) and correlated with diffusing capacity (p=0.01). Median time to death or lung transplant was reduced by 46 months in those with CC genotypes at rs4588 and 38 months in those with non-A containing haplotypes at rs7041/4588 (p=0.014 and 0.008 respectively). Conclusions: The VTDB axis is associated with disease severity and outcome, and GC genotype could help predict transplant free survival in LAM

Bovine Tuberculosis in Free-Ranging Carnivores from Michigan

During a survey of carnivores and omnivores for bovine tuberculosis conducted in Michigan (USA) since 1996, Mycobacterium bovis was cultured from lymph nodes pooled from six coyotes (Canis latrans) (four adult female, two adult male), two adult male raccoons (Procyon lotor), one adult male red fox (Vulpes vulpes), and one 1.5-yr-old male black bear (Ursus americanus). One adult, male bobcat (Felis rufus) with histologic lesions suggestive of tuberculosis was negative on culture but positive for organisms belonging to the Mycobacterium tuberculosis complex when tested by polymerase chain reaction. All the tuberculous animals were taken from three adjoining counties where M. bovis is known to be endemic in the free-ranging white-tailed deer (Odocoileus virginianus) population. There were two coyotes, one raccoon, one red fox, and one bobcat infected in Alpena county. Montmorency County had two coyotes and one raccoon with M. bovis. Two coyotes and a bear were infected from Alcona County. These free-ranging carnivores/omnivores probably became infected with M. bovis through consumption of tuberculous deer. Other species included in the survey were opossum (Didelphis virginiana), gray fox (Urocyon cinereoargenteus), and badger (Taxidea taxus); these were negative for M. bovis

Suicide Prevention in an Emergency Department Population: The ED-SAFE Study

Importance: Suicide is a leading cause of deaths in the United States. Although the emergency department (ED) is an opportune setting for initiating suicide prevention efforts, ED-initiated suicide prevention interventions remain underdeveloped. Objective: To determine whether an ED-initiated intervention reduces subsequent suicidal behavior. Design, Setting, and Participants: This multicenter study of 8 EDs in the United States enrolled adults with a recent suicide attempt or ideation and was composed of 3 sequential phases: (1) a treatment as usual (TAU) phase from August 2010 to December 2011, (2) a universal screening (screening) phase from September 2011 to December 2012, and (3) a universal screening plus intervention (intervention) phase from July 2012 to November 2013. Interventions: Screening consisted of universal suicide risk screening. The intervention phase consisted of universal screening plus an intervention, which included secondary suicide risk screening by the ED physician, discharge resources, and post-ED telephone calls focused on reducing suicide risk. Main Outcomes and Measures: The primary outcome was suicide attempts (nonfatal and fatal) over the 52-week follow-up period. The proportion and total number of attempts were analyzed. Results: A total of 1376 participants were recruited, including 769 females (55.9%) with a median (interquartile range) age of 37 (26-47) years. A total of 288 participants (20.9%) made at least 1 suicide attempt, and there were 548 total suicide attempts among participants. There were no significant differences in risk reduction between the TAU and screening phases (23% vs 22%, respectively). However, compared with the TAU phase, patients in the intervention phase showed a 5% absolute reduction in suicide attempt risk (23% vs 18%), with a relative risk reduction of 20%. Participants in the intervention phase had 30% fewer total suicide attempts than participants in the TAU phase. Negative binomial regression analysis indicated that the participants in the intervention phase had significantly fewer total suicide attempts than participants in the TAU phase (incidence rate ratio, 0.72; 95% CI, 0.52-1.00; P = .05) but no differences between the TAU and screening phases (incidence rate ratio, 1.00; 95% CI, 0.71-1.41; P = .99). Conclusions and Relevance: Among at-risk patients in the ED, a combination of brief interventions administered both during and after the ED visit decreased post-ED suicidal behavior

Chemical Abundances of Seven Irregular and Three Tidal Dwarf Galaxies in the M81 Group

We have derived nebular abundances for 10 dwarf galaxies belonging to the M81 Group, including several galaxies which do not have abundances previously reported in the literature. For each galaxy, multiple H \ii regions were observed with GMOS-N at the Gemini Observatory in order to determine abundances of several elements (oxygen, nitrogen, sulfur, neon, and argon). For seven galaxies, at least one H \ii region had a detection of the temperature sensitive [OIII] $\lambda$4363 line, allowing a "direct" determination of the oxygen abundance. No abundance gradients were detected in the targeted galaxies and the observed oxygen abundances are typically in agreement with the well known metallicity-luminosity relation. However, three candidate "tidal dwarf" galaxies lie well off this relation, UGC 5336, Garland, and KDG 61. The nature of these systems suggests that UGC 5336 and Garland are indeed recently formed systems, whereas KDG 61 is most likely a dwarf spheroidal galaxy which lies along the same line of sight as the M81 tidal debris field. We propose that these H \ii regions formed from previously enriched gas which was stripped from nearby massive galaxies (e.g., NGC 3077 and M81) during a recent tidal interaction.Comment: 37 pages, 10 figures, accepted for publication in ApJ. Slit positions in Table 2 have been update

A GALEX Ultraviolet Imaging Survey of Galaxies in the Local Volume

We present results from a GALEX ultraviolet (UV) survey of a complete sample of 390 galaxies within ~11 Mpc of the Milky Way. The UV data are a key component of the composite Local Volume Legacy (LVL), an ultraviolet-to-infrared imaging program designed to provide an inventory of dust and star formation in nearby spiral and irregular galaxies. The ensemble dataset is an especially valuable resource for studying star formation in dwarf galaxies, which comprise over 80% of the sample. We describe the GALEX survey programs which obtained the data and provide a catalog of far-UV (~1500 Angstroms) and near-UV (~2200 Angstroms) integrated photometry. General UV properties of the sample are briefly discussed. We compute two measures of the global star formation efficiency, the SFR per unit HI gas mass and the SFR per unit stellar mass, to illustrate the significant differences that can arise in our understanding of dwarf galaxies when the FUV is used to measure the SFR instead of H-alpha. We find that dwarf galaxies may not be as drastically inefficient in coverting gas into stars as suggested by prior H-alpha studies. In this context, we also examine the UV properties of late-type dwarf galaxies that appear to be devoid of star formation because they were not detected in previous H-alpha narrowband observations. Nearly all such galaxies in our sample are detected in the FUV, and have FUV SFRs that fall below the limit where the H-alpha flux is robust to Poisson fluctuations in the formation of massive stars. The UV colors and star formation efficiencies of H-alpha-undetected, UV-bright dwarf irregulars appear to be relatively unremarkable with respect to those exhibited by the general population of star-forming galaxies.Comment: submitted to ApJS, revised per referee's comments; accepted Oct. 30 w/o further revision; 37 pages; figure 6 omitted due to size; figure available from http://users.obs.carnegiescience.edu/jlee/paper

The vitamin D binding protein axis modifies disease severity in Lymphangioleiomyomatosis

Background: Lymphangioleiomyomatosis (LAM) is a rare disease of women. Decline in lung function is variable making appropriate targeting of therapy difficult. We used unbiased serum proteomics to identify markers associated with outcome in LAM. Methods: 101 women with LAM and 22 healthy controls were recruited from the National Centre for LAM (Nottingham, UK). 152 DNA and serum samples with linked lung function and outcome data were obtained from patients in the NHLBI LAM Registry (USA). Proteomic analysis was performed on a discovery cohort of 50 LAM and 20 control sera using a SCIEX SWATH mass spectrometric workflow. Protein levels were quantitated by ELISA and SNPs in GC encoding Vitamin D Binding Protein (VTDB) genotyped. Results: Proteomic analysis showed VTDB was 2.6 fold lower in LAM than controls. Serum VTDB was lower in progressive compared with stable LAM (p=0.001) and correlated with diffusing capacity (p=0.01). Median time to death or lung transplant was reduced by 46 months in those with CC genotypes at rs4588 and 38 months in those with non-A containing haplotypes at rs7041/4588 (p=0.014 and 0.008 respectively). Conclusions: The VTDB axis is associated with disease severity and outcome, and GC genotype could help predict transplant free survival in LAM