bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antipsychotic Use in Hospitalized Adults: Rates, Indications, and Predictors
Authors: Herzig Shoshana J. , Rothberg Michael B. , Guess Jamey R. , Stevens Jennifer P. , Marshall John , Gurwitz Jerry H. , Marcantonio Edward R. 
Published: February 2016

ObjectivesTo investigate patterns and predictors of use of antipsychotics in hospitalized adults.DesignRetrospective cohort study.SettingAcademic medical center.ParticipantsIndividuals aged 18 and older hospitalized from August 2012 to August 2013, excluding those admitted to obstetrics and gynecology or psychiatry or with a psychotic disorder.MeasurementsUse was ascertained from pharmacy charges. Potentially excessive dosing was defined using guidelines for long‐term care facilities. A review of 100 records was performed to determine reasons for use.ResultsThe cohort included 17,775 admissions with a median age 64; individuals could have been admitted more than once during the study period. Antipsychotics were used in 9%, 55% of which were initiations. The most common reasons for initiation were delirium (53%) and probable delirium (12%). Potentially excessive dosing occurred in 16% of admissions exposed to an antipsychotic. Of admissions with antipsychotic initiation, 26% were discharged on these medications. Characteristics associated with initiation included age 75 and older (relative risk (RR) = 1.4, 95% confidence interval (CI) = 1.2–1.7), male sex (RR = 1.2, 95% CI = 1.1–1.4), black race (RR = 0.8, 95% CI = 0.6–0.96), delirium (RR = 4.8, 95% CI = 4.2–5.7), dementia (RR = 2.1, 95% CI = 1.7–2.6), admission to a medical service (RR = 1.2, 95% CI = 1.1–1.4), intensive care unit stay (RR = 2.1, 95% CI = 1.8–2.4), and mechanical ventilation (RR = 2.0, 95% CI = 1.7–2.4). In individuals who were initiated on an antipsychotic, characteristics associated with discharge on antipsychotics were age 75 and older (RR = 0.6, 95% CI = 0.4–0.7), discharge to any location other than home (RR = 2.5, 95% CI = 1.8–3.3), and class of in‐hospital antipsychotic exposure (RR = 1.6, 95% CI = 1.1–2.3 for atypical vs typical; RR = 2.7, 95% CI = 1.9–3.8 for both vs typical).ConclusionAntipsychotic initiation and use were common during hospitalization, most often for delirium, and individuals were frequently discharged on these medications. Several predictors of use on discharge were identified, suggesting potential targets for decision support tools that would be used to prompt consideration of ongoing necessity.
Frailty Trajectories in an Elderly Population‐Based Cohort
Authors: Chamberlain Alanna M. , Finney Rutten Lila J. , Manemann Sheila M. , Yawn Barbara P. , Jacobson Debra J. , Fan Chun , Grossardt Brandon R. , Roger Véronique L. , St. Sauver Jennifer L. 
Published: February 2016

ObjectivesTo identify distinct frailty trajectories (clusters of individuals following a similar progression of frailty over time) in an aging population and to estimate associations between frailty trajectories and emergency department visits, hospitalizations, and all‐cause mortality.DesignPopulation‐based cohort study.SettingOlmsted County, Minnesota.ParticipantsOlmsted County, Minnesota residents aged 60–89 in 2005.MeasurementsLongitudinal changes in frailty between 2005 and 2012 were measured by constructing a yearly Rockwood frailty index incorporating body mass index, 17 comorbidities, and 14 activities of daily living. The frailty index measures variation in health status as the proportion of deficits present of the 32 considered (range 0–1).ResultsOf the 16,443 Olmsted County residents aged 60–89 in 2005, 12,270 (74.6%) had at least 3 years of frailty index measures and were retained for analysis. The median baseline frailty index increased with age (0.11 for 60–69, 0.14 for 70–79, 0.19 for 80–89). Three distinct frailty trajectories were identified in individuals aged 60–69 at baseline and two trajectories in those aged 70–79 and 80–89. Within each decade of age, increasing frailty trajectories were associated with greater risks of emergency department visits, hospitalization, and all‐cause mortality, even after adjustment for baseline frailty index.ConclusionThe number of frailty trajectories differed according to age. Within each age group, those in the highest frailty trajectory had greater healthcare use and worse survival. Frailty trajectories may offer a way to target aging individuals at high risk of hospitalization or death for therapeutic or preventive interventions.
Fibroblast Growth Factor‐23 and Frailty in Elderly Community‐Dwelling Individuals: The Cardiovascular Health Study
Authors: Beben Tomasz , Ix Joachim H. , Shlipak Michael G. , Sarnak Mark J. , Fried Linda F. , Hoofnagle Andrew N. , Chonchol Michel , Kestenbaum Bryan R. , de Boer Ian H. , Rifkin Dena E. 
Published: February 2016

ObjectivesTo evaluate whether fibroblast growth factor 23 (FGF‐23) is related to frailty and to characterize the nature of their joint association with mortality.DesignCross‐sectional analysis for frailty and longitudinal cohort analysis for mortality.SettingCardiovascular Health Study.ParticipantsCommunity‐dwelling individuals (N = 2,977; mean age 77.9 ± 4.7, 40% male, 83% white).MeasurementsThe predictor was serum FGF‐23 concentration (C‐terminal enzyme‐linked immunosorbent assay), and the outcomes were frailty status (determined according to frailty phenotype criteria of weight loss, weakness, exhaustion, slowness, and low physical activity) and mortality. Multinomial logistic regression was used to assess the cross‐sectional association between FGF‐23 and frailty and prefrailty, adjusting for demographic characteristics, cardiovascular disease and risk factors, and kidney markers. Proportional hazards Cox proportional hazards regression was used to assess the association between FGF‐23, frailty, and all‐cause mortality.ResultsMean estimated glomerular filtration rate (eGFR) was 64 ± 17 mL/min per 1.73 m2. Median FGF‐23 was 70.3 RU/mL (interquartile range 53.4–99.2); 52% were prefrail, and 13% were frail. After multivariate adjustment, each doubling in FGF‐23 concentration was associated with 38% (95% confidence interval (CI) = 17–62%) higher odds of frailty than of nonfrailty and 16% (95% CI = 3–30%) higher odds of prefrailty. FGF‐23 (hazard ratio (HR) = 1.16, 95% CI = 1.10–1.23) and frailty (HR = 1.82, 95% CI = 1.57–2.12) were independently associated with mortality, but neither association was meaningfully attenuated when adjusted for the other.ConclusionIn a large cohort of older adults, higher FGF‐23 was independently associated with prevalent frailty and prefrailty. FGF‐23 and frailty were independent and additive risk factors for mortality. FGF‐23 may be a marker for functional outcomes.
Global Sensory Impairment in Older Adults in the United States
Authors: Correia Camil , Lopez Kevin J. , Wroblewski Kristen E. , Huisingh‐Scheetz Megan , Kern David W. , Chen Rachel C. , Schumm L P. , Dale William , McClintock Martha K. , Pinto Jayant M. 
Published: February 2016

ObjectivesTo determine whether there may be a common mechanism resulting in global sensory impairment of the five classical senses (vision, smell, hearing, touch, and taste) in older adults.DesignRepresentative, population‐based study.SettingNational Social Life, Health, and Aging Project.ParticipantsCommunity‐dwelling U.S. adults aged 57 to 85.MeasurementsThe frequency with which impairment co‐occurred across the five senses was estimated as an integrated measure of sensory aging. It was hypothesized that multisensory deficits would be common and reflect global sensory impairment that would largely explain the effects of age, sex, and race on sensory dysfunction.ResultsTwo‐thirds of subjects had two or more sensory deficits, 27% had just one, and 6% had none. Seventy‐four percent had impairment in taste, 70% in touch, 22% in smell, 20% in corrected vision, and 18% in corrected hearing. Older adults, men, African Americans, and Hispanics had greater multisensory impairment (all P < .01). Global sensory impairment largely accounted for the effects of age, sex, and race on the likelihood of impairment in each of the five senses.ConclusionMultisensory impairment is prevalent in older U.S. adults. These data support the concept of a common process that underlies sensory aging across the five senses. Clinicians assessing individuals with a sensory deficit should consider further evaluation for additional co‐occurring sensory deficits.
Fibroblast growth factor 23 signaling in hippocampal cells: impact on neuronal morphology and synaptic density
Authors: Hensel Niko , Schön Anne , Konen Timo , Lübben Verena , Förthmann Benjamin , Baron Olga , Grothe Claudia , Leifheit‐Nestler Maren , Claus Peter , Haffner Dieter 
Published: February 2016

AbstractEndocrine fibroblast growth factor 23 (FGF23) is predominantly secreted by osteocytes and facilitates renal phosphate excretion. However, FGF23 is also present in cerebrospinal fluid. In chronic kidney disease, FGF23 serum levels are excessively elevated and associated with learning and memory deficits. Structural plasticity of the hippocampus such as formation of new synapses or an altered dendritic arborization comprises a cellular and morphological correlate of memory formation. Therefore, we hypothesize that FGF23 alters hippocampal neuron morphology and synapses. To address this, we prepared primary murine hippocampal cultures and incubated them with recombinant FGF23 alone or together with a soluble isoform of its co‐receptor α‐Klotho. Neuronal expression of a fluorescent reporter allowed for a detailed evaluation of the neuronal morphology by Sholl analysis. Additionally, we evaluated synaptic density, identified by stainings, for synaptic markers. We show an enhanced number of primary neurites combined with a reduced arborization, resulting in a less complex morphology of neurons treated with FGF23. Moreover, FGF23 enhances the synaptic density in a FGF‐receptor (FGF‐R) dependent manner. Finally, we addressed the corresponding signaling events downstream of FGF‐R employing a combination of western blots and quantitative immunofluorescence. Interestingly, FGF23 induces phospholipase Cγ activity in primary hippocampal neurons. Co‐application of soluble α‐Klotho leads to activation of the Akt‐pathway and modifies FGF23‐impact on neuronal morphology and synaptic density. Compared with other FGFs, this alternative signaling pattern is a possible reason for differential effects of FGF23 on hippocampal neurons and may thereby contribute to learning and memory deficits in chronic kidney disease patients.
imageIn this study, we show that fibroblast growth factor 23 inhibits neuronal ramification and enhances the synaptic density in primary hippocampal cultures accompanied by phospholipase Cγ‐activation. Co‐application of the co‐receptor α‐Klotho leads to an Akt‐activation and further modifies neuronal morphology and number of synapses. Those effects provide a mechanistic basis for memory deficits in patients suffering from chronic kidney disease (CKD) characterized by excessively elevated FGF23 levels as well as memory deficits.
Musculoskeletal architecture of the prey capture apparatus in salamandrid newts with multiphasic lifestyle: does anatomy change during the seasonal habitat switches?
Authors: Heiss Egon , Handschuh Stephan , Aerts Peter , Van Wassenbergh Sam 
Published: February 2016

AbstractSome newt species change seasonally between an aquatic and a terrestrial life as adults, and are therefore repeatedly faced with different physical circumstances that affect a wide range of functions of the organism. For example, it has been observed that seasonally habitat‐changing newts display notable changes in skin texture and tail fin anatomy, allowing one to distinguish an aquatic and a terrestrial morphotype. One of the main functional challenges is the switch between efficient aquatic and terrestrial prey capture modes. Recent studies have shown that newts adapt quickly by showing a high degree of behavioral flexibility, using suction feeding in their aquatic stage and tongue prehension in their terrestrial stage. As suction feeding and tongue prehension place different functional demands on the prey capture apparatus, this behavioral flexibility may clearly benefit from an associated morphological plasticity. In this study, we provide a detailed morphological analysis of the musculoskeletal system of the prey capture apparatus in the two multiphasic newt species Ichthyosaura alpestris and Lissotriton vulgaris by using histological sections and micro‐computed tomography. We then test for quantitative changes of the hyobranchial musculoskeletal system between aquatic and terrestrial morphotypes, The descriptive morphology of the cranio‐cervical musculoskeletal system provides new insights on form and function of the prey capture apparatus in newts, and the quantitative approach shows hypertrophy of the hyolingual musculoskeletal system in the terrestrial morphotype of L. vulgaris but hypertrophy in the aquatic morphotype of I. alpestris. It was therefore concluded that the seasonal habitat shifts are accompanied by a species‐dependent muscular plasticity of which the potential effect on multiphasic feeding performance in newts remains unclear.
Stereological assessment of sexual dimorphism in the rat liver reveals differences in hepatocytes and Kupffer cells but not hepatic stellate cells
Authors: Marcos Ricardo , Lopes Célia , Malhão Fernanda , Correia‐Gomes Carla , Fonseca Sónia , Lima Margarida , Gebhardt Rolf , Rocha Eduardo 
Published: February 2016

AbstractThere is long‐standing evidence that male and female rat livers differ in enzyme activity. More recently, differences in gene expression profiling have also been found to exist; however, it is still unclear whether there is morphological expression of male/female differences in the normal liver. Such differences could help to explain features seen at the pathological level, such as the greater regenerative potential generally attributed to the female liver. In this paper, hepatocytes (HEP), Kupffer cells (KC) and hepatic stellate cells (HSC) of male and female rats were examined to investigate hypothesised differences in number, volume and spatial co‐localisation of these cell types. Immunohistochemistry and design‐based stereology were used to estimate total numbers, numbers per gram and mean cell volumes. The position of HSC within lobules (periportal vs. centrilobular) and their spatial proximity to KC was also assessed. In addition, flow cytometry was used to investigate the liver ploidy. In the case of HEP and KC, differences in the measured cell parameters were observed between male and female specimens; however, no such differences were detected for HSC. Female samples contained a higher number of HEP per gram, with more binucleate cells. The HEP nuclei were smaller in females, which was coincident with more abundant diploid particles in these animals. The female liver also had a greater number of KC per gram, with a lower percentage of KC in the vicinity of HSC compared with males. In this study, we document hitherto unknown morphological sexual dimorphism in the rat liver, namely in HEP and KC. These differences may account for the higher regenerative potential of the female liver and lend weight to the argument for considering the rat liver as a sexually dimorphic organ.
Risk‐Sharing or Risk‐Taking? Counterparty Risk, Incentives, and Margins
Authors: BIAIS BRUNO , HEIDER FLORIAN , HOEROVA MARIE 
Published: February 2016

ABSTRACTDerivatives activity, motivated by risk‐sharing, can breed risk‐taking. Bad news about the risk of an asset underlying a derivative increases protection sellers' expected liability and undermines their risk‐prevention incentives. This limits risk‐sharing, creates endogenous counterparty risk, and can lead to contagion from news about the hedged risk to the balance sheet of protection sellers. Margin calls after bad news can improve protection sellers' incentives and in turn enhance risk‐sharing. Central clearing can provide insurance against counterparty risk but must be designed to preserve risk‐prevention incentives.
Corporate Scandals and Household Stock Market Participation
Authors: GIANNETTI MARIASSUNTA , WANG TRACY YUE 
Published: February 2016

ABSTRACTWe show that, after the revelation of corporate fraud in a state, household stock market participation in that state decreases. Households decrease holdings in fraudulent as well as nonfraudulent firms, even if they do not hold stocks in fraudulent firms. Within a state, households with more lifetime experience of corporate fraud hold less equity. Following the exogenous increase in fraud revelation due to Arthur Andersen's demise, states with more Arthur Andersen clients experience a larger decrease in stock market participation. We provide evidence that the documented effect is likely to reflect a loss of trust in the stock market.
The Simple Geometry of ‘Linearism’. Metaphors of the Nation in the Radical Falangist Discourse of the Immediate Postwar Period in Spain
Authors: Box Zira 
Published: February 2016

AbstractTaking as a point of departure the understanding that metaphors, as linguistic expressions, indicate the thought processes of those who formulate them, the present article explores a specific metaphor that formed part of the discourse of radical Falangism: the definition of the Spanish nation as straight, upright, linear or vertical, in opposition to another Spain that had to be combatted, and which was portrayed as twisted. The argument put forward here is that, by analysing the various metaphorical expressions that arose in the wake of the identification of Spain with an image of linearity, it is possible to examine aspects of Falange nationalism that bring into relief the ideal of a sombre, spare, masculine and austere Spain.
EVALUATING THE EXPECTED WELFARE GAIN FROM INSURANCE
Authors: Harrison Glenn W. , Ng Jia Min 
Published: February 2016

ABSTRACTEconomic theory tells us how to evaluate the expected welfare gain from insurance products on offer to individuals. If we know the risk preferences of the individual, and subjective beliefs about loss contingencies and likelihood of payout, there is a certainty equivalent of the risky insurance policy that can be compared to the certain insurance premium. This simple logic extends to nonstandard models of risk preferences, such as those in which individuals exhibit “optimism” or “pessimism” about loss contingencies in their evaluation of the risky insurance policy. We illustrate the application of these basic ideas about the welfare evaluation of insurance policies in a controlled laboratory experiment. We estimate the risk preferences of individuals from one task, and separately present the individual with a number of insurance policies in which loss contingencies are objective. We then estimate the expected consumer surplus gained or foregone from observed take‐up decisions. There is striking evidence of foregone expected consumer surplus from incorrect take‐up decisions. Indeed, the metric of take‐up itself, widely used in welfare evaluations of insurance products, provides a qualitatively incorrect guide to the expected welfare effects of insurance.
Chemosensitization of doxorubicin in multidrug-resistant cells by unimolecular micelles via increased cellular accumulation and apoptosis
Authors: Wang Meng , Han Min , Li Ying , Jin Yi , Gao Jian-Qing 
Published: February 2016

Abstract

Objectives
Unimolecular micelles were prepared by modification of polyamidoamine (PAMAM) dendrimers using Pluronic F127 (PF127), which is expected to reverse multidrug resistance (MDR). And the reversal mechanisms have been studied.

Methods
Characterization of the products was carried on. MTT assay was used to evaluate the cytotoxicity of the DOX-loaded conjugates. Cellular uptake study was measured by confocal laser scanning microscope and flow cytometry. Apoptosis assay was identified by Annexin V-FITC/PI apoptosis assay and Hoechst 33 342 staining.

Key findings
Improved cytotoxicity of DOX-loaded conjugates in MCF-7/ADR cells (as much as 33-fold according to the IC50 values) was observed in contrast with that of free DOX. The DOX-loaded conjugates induced a much quicker and 100% uptake in MCF-7/ADR cells, and more than fivefold accumulation of DOX-loaded conjugates was observed compared with free DOX. Apoptosis assay showed that DOX-loaded conjugates decreased the cell viability from 81.87 ± 5.94% to 54.83 ± 3.63% (DOX concentration 2 μg/ml). At 48 h, more accumulation and distribution in the nuclei were observed after treatment with DOX-loaded conjugates.

Conclusions
PF127-PAMAM conjugates showed superiority in the treatment of MCF-7/ADR, which implied the potential vehicles of anticancer drugs for the reversal of MDR.
Regulation of cancer-related genes – Cyp1a1, Cyp1b1, Cyp19, Nqo1 and Comt – expression in β-naphthoflavone-treated mice by miroestrol
Authors: Chatuphonprasert Waranya , Jarukamjorn Kanokwan , Putalun Waraporn 
Published: February 2016

Abstract

Objective
The effects of miroestrol (MR), an active phytoestrogen from Pueraria candollei var. mirifica, on expression of cancer-related genes were determined.

Methods
Seven-week-old female ICR mice (n = 5 each) were subcutaneously administered estradiol (E2, 0.5 mg/kg/day) or MR (0.5 or 5 mg/kg/day) daily for 7 days. Some were given ER or MR in combination with β-naphthoflavone (BNF, 30 mg/kg/day) for the last 3 days. The expression of cancer-related genes including cytochrome P450 1A (Cyp1a), cytochrome P450 1B1 (Cyp1b1), aromatase P450 (Cyp19), NAD(P)H: quinone oxidoreductase 1 (Nqo1) and catechol-O-methyltransferase (Comt) were evaluated.

Key findings
In the presence of BNF, MR suppressed hepatic CYP1A1 activity and CYP1A2 activity, expression of CYP1B1 mRNA and expression of CYP1A1/2 and CYP1B1 protein. E2, by contrast, did not. MR restored expression levels of hepatic NQO1 and uterine COMT in BNF-treated mice. Furthermore, MR increased expression of uterine CYP19 to the same extent as E2.

Conclusion
MR may be superior to E2 as it downregulates expression of CYP1. Moreover, MR normalized expression of both NQO1 and COMT, the protective enzymes, in murine liver and uteri. These results support the use of MR as an alternative supplement for menopausal women, MR having the extra benefit of reducing cancer risk.