Miracle-dz/UniFAR-FTUs huggingface dataset:
A comparison of neuropsychiatric and cognitive profiles in delirium, dementia, comorbid delirium-dementia and cognitively intact controls

Purpose Delirium and dementia have overlapping features that complicate differential diagnosis. Delirium symptoms overshadow dementia symptoms when they co-occur, but delirium phenomenology in comorbid cases has not been compared to both conditions alone. Methods Consecutive adults with DSM-IV delirium, dementia, comorbid delirium-dementia and cognitively intact controls were assessed using the Revised Delirium Rating Scale (DRS-R98) and Cognitive Test for Delirium (CTD). Results Delirium and comorbid delirium-dementia groups had comparable DRS-R98 and CTD total scores, which were greater than in dementia or control groups. On the DRS-R98, multiple non-cognitive symptoms, inattention and disorientation were more severe in delirium groups compared with dementia-alone. Patients with dementia differed from both delirium groups on the CTD test of attention. Spatial span backwards was significantly lower in all patients with cognitive impairment (delirium, comorbid delirium-dementia, dementia alone) compared to controls, whereas spatial span forwards distinguished delirium groups from dementia. Conclusions Delirium phenomenology is similar with or without comorbid dementia. A wide range of neuropsychiatric symptoms distinguish delirium from dementia. Spatial span forward is disproportionately diminished in delirium suggesting usefulness as a differentiating screening test.
Triazole antifungal agents drug–drug interactions involving hepatic cytochrome P450

Introduction: Triazole antifungal agents are often prescribed as first-line therapy for candidemia, in non-neutropenic hosts and invasive pulmonary aspergillosis, and in critically ill patients who receive many concomitant medications. As substrates and inhibitors of cytochrome P450 (CYP), the triazoles can interact with many drugs, which may lead to enhanced toxicity of the concomitant medication(s) or ineffective antifungal treatment. Therefore, clinicians must understand the drug interaction profile of this class. Areas covered: This manuscript reviews the role of human hepatic CYP in triazole–drug interactions, illustrates how recent discoveries in pharmacogenetics and triazole metabolism impact our understanding of these interactions, and summarizes the most clinically important triazole–drug interactions. A search of English language, original research and scholarly reviews describing interactions between triazole antifungal agents and human CYP published from 1980 to present was undertaken using PubMed. Expert opinion: Triazoles interact with many drugs and the primary mechanism for these interactions is hepatic CYP. Many studies published in the past 2 decades characterize these interactions using the state-of-the-art methods of the time. However, advances in genotyping, improved analytical technology and bioanalytical methods, which enable accurate molecular identification and stereochemical analysis, have substantially added to the understanding of the role hepatic CYP plays in triazole–drug interactions in humans.
Fish consumption and myocardial infarction : a second prospective biomarker study from northern Sweden 1 – 4

Background: A beneficial role of fish consumption on the risk of myocardial infarction (MI) has been reported and is mostly ascribed to n23 (omega-3) fatty acids. However, fish also contains methylmercury, which may increase the risk of MI. Objective: The objective was to determine how fish consumption and erythrocyte concentrations of mercury (Ery-Hg) and selenium (Ery-Se) are related to the risk of MI and whether n23 fatty acids (eicosapentaenoic and docosahexaenoic acids) in plasma phospholipids (P-EPA+DHA) are protective. Design: This was a case-control study nested within the northern Sweden cohort, in which data and samples were collected prospectively. The study included 431 cases with an MI after data and sample collection, including 81 sudden cardiac deaths (SCDs) and 499 matched controls. Another 69 female cases with controls from a breast cancer screening registry were included in sex-specific analyses. Results: Odds ratios for the third compared with the first tertile were 0.65 (95% CI: 0.46, 0.91) for Ery-Hg, 0.75 (95% CI: 0.53, 1.06) for Ery-Se, and 0.78 (95% CI: 0.54, 1.11) for P-EPA+DHA. Ery-Hg and P-EPA+DHA were intercorrelated (Spearman’s R = 0.34). No association was seen for reported fish consumption. Multivariate modeling did not change these associations significantly. Sex-specific analyses showed no differences in risk associations. High concentrations of Ery-Se were associated with an increased risk of SCD. Conclusions: The biomarker results indicate a protective effect of fish consumption. No harmful effect of mercury was indicated in this low-exposed population in whom Ery-Hg and P-EPA+DHA were intercorrelated. Am J Clin Nutr 2011;93:27–36.
Management of glucocorticoid-induced osteoporosis in patients with rheumatoid arthritis: rates and predictors of care in an academic rheumatology practice.

OBJECTIVE To examine rheumatologists' management practices for patients with rheumatoid arthritis (RA) taking glucocorticoids seen at one academic medical rheumatology practice. METHODS All patients diagnosed with RA making at least 2 visits to the practice who were noted to be taking glucocorticoids on an index visit in January or February 1999 were included in a retrospective chart review. RESULTS Of the 623 eligible patients identified with RA, 236 patients were taking glucocorticoids at their index visit and were included in this study. The mean daily dosage of prednisone (or its equivalent) was 8.8 mg and the mean duration of use during the 2-year chart review was 15.4 months. Twenty-three percent of the study population underwent bone densitometry, and 42% were prescribed a medication that reduces bone loss (not including calcium and/or vitamin D). Calcium and/or vitamin D were noted on the medication lists of 25% of patients. Factors associated with not undergoing bone densitometry in adjusted logistic models included male patient sex and premenopausal status in women. No physician factors were significantly related to performing bone densitometry. Variables associated with not receiving prescription treatment of osteoporosis were male patient sex, premenopausal status, and having at least 1 comorbid condition. CONCLUSION Patients with RA taking oral glucocorticoids did not routinely undergo bone densitometry and/or receive prescription medications for osteoporosis. Men and premenopausal women were less likely to undergo bone densitometry and to receive a prescription medication for osteoporosis than postmenopausal women. Interventions to improve detection and prevention of glucocorticoid-induced osteoporosis are necessary.
Association of tenofovir exposure with kidney disease risk in HIV infection

Objective:Despite widespread HAART use, HIV disease remains associated with increased risk of kidney disease. Whether tenofovir use is associated with higher risk of kidney disease is controversial. Design:We evaluated the association of cumulative and ever exposure to tenofovir on kidney outcomes in 10 841 HIV-infected patients from the Veterans Health Administration who initiated antiretroviral therapy from 1997 to 2007. Methods:Cox proportional hazards and marginal structural models evaluated associations between tenofovir and time to first occurrence of proteinuria (two consecutive urine dipstick measurements ≥30 mg/dl), rapid decline in kidney function (≥3 ml/min per 1.73 m2 annual decline), and chronic kidney disease (CKD; estimated glomerular filtration rate <60 ml/min per 1.73 m2). Results:Median follow-up ranged from 3.9 years (proteinuria) to 5.5 years (CKD), during which 3400 proteinuria, 3078 rapid decline, and 533 CKD events occurred. After multivariable adjustment, each year of exposure to tenofovir was associated with 34% increased risk of proteinuria [95% confidence interval (CI) 25–45, P < 0.0001], 11% increased risk of rapid decline (3–18, P = 0.0033), and 33% increased risk of CKD (18–51, P < 0.0001). Preexisting renal risk factors did not appear to worsen the effects of tenofovir. Other antiretroviral drugs showed weaker or inconsistent associations with kidney disease events. Among those who discontinued tenofovir use, risk of kidney disease events did not appear to decrease during follow-up. Conclusion:Tenofovir exposure was independently associated with increased risk for three types of kidney disease events, and did not appear to be reversible. Because subtle kidney function decline affects long-term morbidity and mortality, the balance between efficacy and probable adverse effects requires further study.
Molecular Epidemiology of Methicillin-Resistant Staphylococcus aureus Bloodstream Isolates in Urban Detroit

ABSTRACT To gain a better understanding of epidemiology of resistance in Staphylococcus aureus, we describe the molecular epidemiology of methicillin-resistant Staphylococcus aureus bloodstream isolates in urban Detroit. Bloodstream isolates from July 2005 to February 2007 were characterized. Two hundred ten bloodstream isolates from 201 patients were evaluated. Patient characteristics were as follows: median age, 54 years; 56% male; and 71% African-American. Seventy-six percent of infections were health care associated, with 55% being community-onset infections and 21% hospital acquired, and 24% were community associated. The most common sources were skin/wound (25%), central venous catheters (24%), unknown source (20%), and endocarditis (9%). Ninety percent and 5% of isolates had a MIC of vancomycin of ≤1.0 mg/liter, using automated dilution testing and E-test, respectively. Six percent of isolates showed heteroresistance to vancomycin, all occurring with isolates having a vancomycin E-test MIC of ≥1.5 mg/liter. Results of pulsed-field gel electrophoresis showed 17 strain types. The predominant strains were USA100 (104 isolates) and USA300 (74 isolates). Forty-nine percent of the isolates had staphylococcal cassette chromosome mec II, and 56% had agr II. All USA300 isolates were positive for the Panton-Valentine leukocidin toxin genes and agr I. Forty-seven percent of USA300 bloodstream infections were health care associated (35% community onset and 12% hospital onset). USA300 strains were more common in injection drug users with skin/wound as the predominant source of infection. Thirty percent of the USA100 strains were closely related to vancomycin-resistant Staphylococcus aureus isolates. The results of this study show that vancomycin MICs using automated dilution testing with Vitek-2 and E-test were highly discordant. Most methicillin-resistant S. aureus strains causing bacteremia are health care associated, commonly have MICs of vancomycin that are high within the susceptible range are not detected by routine automated dilution testing, and have significant diversity of molecular characteristics. USA100 strains that are closely related to vancomycin-resistant S. aureus (VRSA) isolates and USA300 strains are common as causes of both hospital and community-onset infection. Infection control measures should focus not only on prevention of the spread of community strains in the hospital but also prevention of the spread of hospital strains associated with VRSA into the community.
The False Discovery Rate for Multiple Testing in Factorial Experiments

Identifying the important factors and effects is an important goal in the analysis of two-level fractional factorial experiments. In moderate and large experiments, the large number of potential effects presents problems of multiple statistical inference. In this work we apply the false discovery rate (FDR) idea in multiple inference to effect identification in factorial experiments. The FDR is the expected proportion of inert effects among those declared active, which we believe is a more relevant quantity to control than the probability of a single erroneous declaration, the criterion that has been adopted in previous studies. We show how to combine the control of FDR with popular methods for estimating contrast standard error in unreplicated experiments. We present simulations of unreplicated 16- and 32-run experiments that illustrate the improvements in power that can be obtained by controlling the FDR. We also analyze data from an actual 128-run experiment with replication, in which the FDR identifies many more active effects than other methods.
Transcriptional activation of the human epidermal growth factor receptor promoter by human p53

The human epidermal growth factor receptor (EGFR) promoter is activated by both wild-type and tumor-derived mutant p53. In this communication, we demonstrate that EGFR promoter sequence requirements for transactivation by wild-type and mutant p53 are different. Transient-expression assays with EGFR promoter deletions identified a wild-type human p53 response element, 5'-AGCTAGACGTCCGGGCAGCCCCCGGCG -3', from positions --265 to --239. Electrophoretic mobility shift analysis and DNase I footprinting assays indicated that wild-type p53 binds sequence specifically to the response element. Using circularly permuted DNA fragments containing the p53-binding site, we show that wild-type p53 binding induces DNA bending at this site. We further show that the EGFR promoter is also activated by tumor-derived p53 mutants p53-143A, p53-175H, p53-248W, p53-273H, and p53-281G. However, the transactivation by mutant p53 does not require the wild-type p53-binding site. The minimal EGFR promoter from positions --104 to --20 which does not contain the wild-type p53-binding site is transactivated by the p53 mutants but not by the wild-type protein, showing a difference in the mechanism of transactivation by wild-type and mutant p53. Transactivation of the EGFR promoter by p53 may represent a novel mechanism of cell growth regulation.
Synaptotagmin isoforms couple distinct ranges of Ca2+, Ba2+, and Sr2+ concentration to SNARE-mediated membrane fusion.

Ca2+-triggered exocytosis of synaptic vesicles is controlled by the Ca2+-binding protein synaptotagmin (syt) I. Fifteen additional isoforms of syt have been identified. Here, we compared the abilities of three syt isoforms (I, VII, and IX) to regulate soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)-mediated membrane fusion in vitro in response to divalent cations. We found that different isoforms of syt couple distinct ranges of Ca2+, Ba2+, and Sr2+ to membrane fusion; syt VII was approximately 400-fold more sensitive to Ca2+ than was syt I. Omission of phosphatidylserine (PS) from both populations of liposomes completely abrogated the ability of all three isoforms of syt to stimulate fusion. Mutations that selectively inhibit syt.target-SNARE (t-SNARE) interactions reduced syt stimulation of fusion. Using Sr2+ and Ba2+, we found that binding of syt to PS and t-SNAREs can be dissociated from activation of fusion, uncovering posteffector-binding functions for syt. Our data demonstrate that different syt isoforms are specialized to sense different ranges of divalent cations and that PS is an essential effector of Ca2+. syt action.
Physical Education Students’ Ownership, Empowerment, and Satisfaction With PE and Physical Activity

ABSTRACT Individuals experiencing a highly caring, task-involving, and low ego-involving exercise climate have reported greater ownership in exercise class and empowerment to exercise in general. Purpose: This study examined the relationship between ownership and empowerment in exercise, with 2 context-specific outcomes, satisfaction with physical education (PE) and physical activity, respectively. Given the mission of PE to foster individuals’ lifelong physical activity habit, the perceptions of high school students were collected for this study. Ownership in exercise was hypothesized to be significantly, positively correlated with students reporting satisfaction in PE more than their satisfaction in physical activity, whereas empowerment in exercise was hypothesized to be more strongly, positively correlated with students’ physical activity satisfaction. A second purpose of this study was to test the measurement quality of the updated Empowerment in Exercise Scale (EES; now 13 items). Method: High school students (N = 502, 43% female) in a Midwestern U.S. school district completed a survey. Results: Confirmatory factor analysis supported the internal measurement structure of the EES (λ = .62–.91; McDonald’s omega = .89) across student gender (strong invariance). Additionally, the structural equation modeling analysis revealed only 1 parameter moderated by the students’ gender (latent mean of ownership). The hypotheses were supported, such that ownership in exercise was more strongly correlated with PE satisfaction (r = .87) and empowerment in exercise had a stronger correlation with physical activity satisfaction (r = .92). Conclusion: These results support the beneficial effect a satisfying experience in PE can have on students’ satisfaction with physical activity outside of school.
Clinical and angiographic long-term follow-up of completely coiled intracranial aneurysms using endovascular technique.

OBJECT The anatomical evolution and clinical outcome of completely coiled intracranial aneurysms after endovascular embolization have rarely been studied separately. From their prospective database, the authors reviewed follow-up angiography and clinical outcome of 87 patients whose aneurysms were designated as 100% obliterated on immediate postembolization angiography. METHODS Ninety-one aneurysms (56 ruptured and 35 unruptured) in 87 patients were included in this study. Clinical outcome was evaluated using the Glasgow Outcome Scale. Follow-up angiographic findings were assessed and categorized as 1 of the following: no recanalization, recanalization with a neck remnant, or recanalization with a body remnant. For statistical analysis, the recanalization rate was correlated with: clinical presentation; the largest aneurysm diameter, aneurysm neck size, and dome-to-neck ratio; aneurysm location; and use of special techniques such as usage of a surface modified coil, balloon remodeling technique, or stent. RESULTS At the latest clinical evaluation (mean 34.3 months), 81 (93.1%) of the 87 patients (91 aneurysms) had good clinical outcomes (Glasgow Outcome Scale Score 5). The procedure-related morbidity rate (permanent neurological deficit) was 2.3% (2 of 87), and there were no procedure-related deaths. On the latest follow-up angiography (mean 26.4 months), the recanalization rate was 26.4% (24 of 91 aneurysms): 16 (17.6%) with neck remnants and 8 (8.8%) with body remnants. The neck size of the recanalized aneurysms was statistically significantly larger than that of the nonrecanalized aneurysms (p = 0.006), and aneurysms with wide necks (> or = 4 mm) had a higher recanalization rate than those with a narrow neck (< 4 mm) (p = 0.002). There was no bleeding after endovascular treatment during the follow-up period. CONCLUSIONS Completely coiled aneurysms after endovascular embolization demonstrated good clinical outcome, and there was no bleeding episode after endovascular treatment; however, there was a relatively high recanalization rate.
Molecular and Cellular Pathobiology Ampli fi cation of FRS 2 andActivation of FGFR / FRS 2 Signaling Pathway in High-Grade Liposarcoma

Fibroblast growth factor (FGF) receptor (FGFR) substrate 2 (FRS2) is an adaptor protein that plays a critical role in FGFR signaling. FRS2 is located on chromosome 12q13-15 that is frequently amplified in liposarcomas. The significance of FRS2 and FGFR signaling in high-grade liposarcomas is unknown. Herein, we first comparatively examined the amplification and expression ofFRS2withCDK4 andMDM2 in dedifferentiated liposarcoma (DDLS) and undifferentiated high-grade pleomorphic sarcoma (UHGPS). Amplification and expression of the three genes were identified in 90% to 100% (9–11 of 11) of DDLS, whereas that of FRS2,CDK4, andMDM2were observed in 55% (41 of 75), 48% (36 of 75), and 44% (33/75) of clinically diagnosed UHGPS, suggesting that these "UHGPS" may represent DDLS despite lacking histologic evidence of lipoblasts. Immunohistochemical analysis of phosphorylated FRS2 protein indicated that the FGFR/FRS2 signaling axis was generally activated in about 75% of FRS2positive high-grade liposarcomas. Moreover, we found that FRS2 and FGFRs proteins are highly expressed and functional in three high-grade liposarcoma cell lines: FU-DDLS-1, LiSa-2, and SW872. Importantly, the FGFR selective inhibitor NVP-BGJ-398 significantly inhibited the growth of FU-DDLS-1 and LiSa-2 cells with a concomitant suppression of FGFR signal transduction. Attenuation of FRS2 protein in FU-DDLS-1 and LiSa-2 cell lines decreased the phosphorylated extracellular signal–regulated kinase 1/2 and AKT and repressed cell proliferation. These findings indicate that analysis of FRS2 in combination with CDK4 and MDM2 will more accurately characterize pathologic features of high-grade liposarcomas. Activated FGFR/FRS2 signalingmay play a functional role in the development of high-grade liposarcomas, therefore, serve as a potential therapeutic target. Cancer Res; 73(4); 1298–307. 2012 AACR.
LUCID: A Quantitative Assay of ESCRT‐Mediated Cargo Sorting into Multivesicular Bodies

Endosomes are transportation nodes, mediating selective transport of soluble and transmembrane cargos to and from the Golgi apparatus, plasma membrane and lysosomes. As endosomes mature to become multivesicular bodies (MVBs), Endosomal Sorting Complexes Required for Transport (ESCRTs) selectively incorporate transmembrane cargos into vesicles that bud into the endosome lumen. Luminal vesicles and their cargoes are targeted for destruction when MVBs fuse with lysosomes. Common assays of endosomal luminal targeting, including fluorescence microscopy and monitoring of proteolytic cargo maturation, possess significant limitations. We present a quantitative assay system called LUCID (LUCiferase reporter of Intraluminal Deposition) that monitors exposure of chimeric luciferase‐cargo reporters to cytosol. Luciferase‐chimera signal increases when sorting to the endosome lumen is disrupted, and silencing of signal from the chimera depends upon luminal delivery of the reporter rather than proteolytic degradation. The system presents several advantages, including rapidity, microscale operation and a high degree of reproducibility that enables detection of subtle phenotypic differences. Luciferase reporters provide linear signal over an extremely broad dynamic range, allowing analysis of reporter traffic even at anemic levels of expression. Furthermore, LUCID reports transport kinetics when applied to inducible trafficking reporters.
Wnts as kidney tubule inducing factors 419 Wnts as kidney tubule inducing factors

Since the discovery that inductive tissue interactions regulate nephrogenesis, one of the aims has been to identify the molecules that mediate this induction. The small size of embryonic tissue has limited the possibilities to identify the inducers biochemically, even though such efforts were directed to study, e.g. neural induction (for a comprehensive review, Saxén and Toivonen, Primary embryonic induction, Academic Press, London, 1962). The rapid progress in molecular biology made it possible to identify genes from minute amounts of tissue and provided techniques to generate recombinant proteins to assay their action in classic experimental systems. This led to the identification of some signals that are involved in primary and secondary inductive interactions during embryogenesis. Here, we will review evidence suggesting that secreted signaling molecules from the Wnt gene family mediate kidney tubule induction.