bluuebunny/crossref_metadata_2025 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

Objectives

To investigate patterns and predictors of use of antipsychotics in hospitalized adults.

Design

Retrospective cohort study.

Setting

Academic medical center.

Participants

Individuals 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.

Measurements

Use 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.

Results

The 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).

Conclusion

Antipsychotic 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

Objectives

To 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.

Design

Population‐based cohort study.

Setting

Olmsted County, Minnesota.

Participants

Olmsted County, Minnesota residents aged 60–89 in 2005.

Measurements

Longitudinal 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).

Results

Of 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.

Conclusion

The 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

Objectives

To evaluate whether fibroblast growth factor 23 (FGF‐23) is related to frailty and to characterize the nature of their joint association with mortality.

Design

Cross‐sectional analysis for frailty and longitudinal cohort analysis for mortality.

Setting

Cardiovascular Health Study.

Participants

Community‐dwelling individuals (N = 2,977; mean age 77.9 ± 4.7, 40% male, 83% white).

Measurements

The 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.

Results

Mean 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.

Conclusion

In 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

Objectives

To 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.

Design

Representative, population‐based study.

Setting

National Social Life, Health, and Aging Project.

Participants

Community‐dwelling U.S. adults aged 57 to 85.

Measurements

The 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.

Results

Two‐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.

Conclusion

Multisensory 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

Endocrine 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.

image

In 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

Some 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

There 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

Derivatives 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

We 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

Taking 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

ABSTRACT

Economic 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

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

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.
Dynamic prediction of risk of liver‐related outcomes in chronic hepatitis C using routinely collected data
Authors: Konerman M. A. , Brown M. , Zheng Y. , Lok A. S. F
Published: February 2016

Accuracy of risk assessments for clinical outcomes in patients with chronic liver disease has been limited given the nonlinear nature of disease progression. Longitudinal prediction models may more accurately capture this dynamic risk. The aim of this study was to construct accurate models of short‐ and long‐term risk of disease progression in patients with chronic hepatitis C by incorporating longitudinal clinical data. Data from the Hepatitis C Antiviral Long‐term Treatment Against Cirrhosis trial were analysed (n = 533 training cohort; n = 517 validation cohort). Outcomes included a composite liver outcome (liver‐related death, decompensation, hepatocellular carcinoma (HCC) or liver transplant), decompensation, HCC and overall mortality. Longitudinal models were constructed for risk of outcomes at 1, 3 and 5 years and compared with models using data at baseline only or baseline and a single follow‐up time point. A total of 25.1% of patients in the training and 20.8% in the validation cohort had an outcome during a median follow‐up of 6.5 years (range 0.5–9.2). The most important predictors were as follows: albumin, aspartate aminotransferase/alanine aminotransferase ratio, bilirubin, alpha‐fetoprotein and platelets. Longitudinal models outperformed baseline models with higher true‐positive rates and negative predictive values. The areas under the receiver‐operating characteristic curve for the composite longitudinal model were 0.89 (0.80–0.96), 0.83 (0.76–0.88) and 0.81 (0.75–0.87) for 1‐, 3‐, and 5‐year risk prediction, respectively. Model performance was retained for decompensation and overall mortality but not HCC. Longitudinal prediction models provide accurate risk assessments and identify patients in need of intensive monitoring and care.
Subcutaneous meloxicam suspension pharmacokinetics in mice and dose considerations for postoperative analgesia
Authors: Chen Patty H. , Boyd Kelli L. , Fickle Erin K. , Locuson Charles W.
Published: February 2016

Meloxicam is a cyclooxygenase (COX) inhibitor with a higher selectivity for cyclooxygenase‐2 (COX‐2) than for cyclooxygenase‐1 (COX‐1). In the laboratory setting, this nonsteroidal anti‐inflammatory drug (NSAID) is commonly selected for analgesia in mice and administered every 24 h. This study characterizes the plasma concentration achieved from a dose of 1.6 mg/kg of meloxicam administered once every 24 h subcutaneously for 72 h in male and female C57BL/6 mice. These values were compared, over time, to reference COX‐2 inhibition constants for meloxicam. No significant differences in trough plasma concentrations were noted between genders. The plasma concentrations were below the COX‐2 IC50 after 12 h. To maintain a plasma concentration at or above the COX‐2 whole blood IC50, the study results suggest an administration frequency of every 12 h when using a dose of 1.6 mg/kg in C57BL/6 mice.
Pharmacokinetics of dexmedetomidine, MK‐467, and their combination following intravenous administration in male cats
Authors: Pypendop B. H. , Honkavaara J. , Ilkiw J. E.
Published: February 2016

This study characterized the pharmacokinetics of dexmedetomidine, MK‐467, and their combination following intravenous bolus administration to cats. Seven 6‐ to‐year‐old male neutered cats, weighting 5.1 ± 0.7 kg, were used in a randomized, crossover design. Dexmedetomidine [12.5 (D12.5) and 25 (D25) μg/kg], MK‐467 [300 μg/kg (M300)] or dexmedetomidine (25 μg/kg) and MK‐467 [75, 150, 300 or 600 μg/kg—only the plasma concentrations in the 600 μg/kg group (D25M600) were analyzed] were administered intravenously, and blood was collected until 8 hours thereafter. Plasma drug concentrations were analyzed using liquid chromatography/mass spectrometry. A two‐compartment model best fitted the data. Median (range) volume of the central compartment (mL/kg), volume of distribution at steady state (mL/kg), clearance (mL min/kg) and terminal half‐life (min) were 342 (131–660), 829 (496–1243), 14.6 (9.6–22.7) and 48 (40–69) for D12.5; 296 (179–982), 1111 (908–2175), 18.2 (12.4–22.9) and 52 (40–76) for D25; 653 (392–927), 1595 (1094–1887), 22.7 (18.5–36.4) and 48 (35–60) for dexmedetomidine in D25M600; 117 (112–163), 491 (379–604), 3.0 (2.0‐4.5) and 122 (99‐139) for M300; and 147 (112‐173), 462 (403‐714), 2.8 (2.1–4.8) and 118 (97–172) for MK‐467 in D25M600. MK‐467 moderately but statistically significantly affected the disposition of dexmedetomidine, whereas dexmedetomidine minimally affected the disposition of MK‐467.
Deregulated hepatic microRNAs underlie the association between non‐alcoholic fatty liver disease and coronary artery disease
Authors: Braza‐Boïls Aitana , Marí‐Alexandre Josep , Molina Pilar , Arnau Miguel A. , Barceló‐Molina Moisés , Domingo Diana , Girbes Javier , Giner Juan , Martínez‐Dolz Luis , Zorio Esther
Published: February 2016

Background & Aims

Non‐alcoholic fatty liver disease (NAFLD) appears to be a new risk factor for the development of coronary artery disease (CAD). Members of a class of non‐coding RNAs, termed microRNAs (miRNAs), have been identified as post‐transcriptional regulators of cholesterol homoeostasis and can contribute to the development of NAFLD. The aims of this study were to (i) to assess the relationship between NAFLD and sudden cardiac death (SCD) from severe CAD in forensic autopsies and (ii) to quantify several hepatic miRNAs previously associated with lipid metabolism and NAFLD to correlate their expression with the presence of NAFLD, CAD, obesity parameters and postmortem lipid profile.

Methods

A total of 133 cases of autopsies with SCD and established CAD (patient group, CAD‐SCD) and 106 cases of non‐CAD sudden death (control group, non‐CAD‐SD) were included. miRNAs were quantified in frozen liver tissues.

Results

Males predominated in both groups. Patients more frequently exhibited NAFLD and necroinflammatory steatohepatitis (NASH) than controls (62% vs 26%, P = 0.001 and 42% vs 26%, P = 0.001 respectively). In both groups, the presence of NAFLD correlated with body mass index and abdominal circumference (P < 0.05). An increase in miR‐34a‐5p and a decrease in miR‐122‐5p and ‐29c‐3p in patients with NASH vs controls without NAFLD were observed (P < 0.05). Finally, significant correlations between miR‐122‐5p and unfavourable lipid profile and also hs‐CRP and miR‐34a‐5p were noted.

Conclusions

CAD is associated with NAFLD and NASH. The hepatic miRNAs studied appear to be associated with NAFLD severity and may promote CAD through lipid metabolism alteration and/or promotion of the systemic inflammation.
The People Against Themselves: Rethinking Popular
Constitutionalism
Authors: Beienburg Sean , Frymer Paul
Published: February 2016

In the course of reviewing Jed Shugerman's The People's
Courts: Pursuing Judicial Independence in America and
Bruce Ackerman's The Civil Rights Revolution, we
argue for a reassessment of the way that scholars think about popular
constitutionalism. In particular, we urge scholars to resist the tendency to
create a dichotomy between judicial interpretation of law and a set of
nonjudicial venues in which popular constitutionalism supposedly takes
place. Popular constitutionalism is temporally and contextually bound,
reflected in different forms and forums at different times in US political
history and always dependent on the interactions between these institutions.
By implication, this suggest that judges, rather than serving as obstacles
to popular understandings of law, can and have used various forms of
democratic authorization to strike down legislation violating both state and
federal constitutions, thus bridging judicial review and popular
constitutionalism with explicit support from the citizenry.
Signaling Unobservable Quality Choice through Price and Advertising: The Case with Competing Firms
Authors: Wu Fulan
Published: February 2016

This paper develops a model in which a firm can use price and advertising jointly as a signal of their private choice of quality, whereby quality is endogenously chosen by firms. The monopoly model reveals that there exists a unique equilibrium in which the monopolist chooses high quality but a higher level of advertising compared to the full‐information benchmark. The model is then extended to the case with competition of two imperfectly competitive firms. We find that if competition is not strong enough, then there exists a unique symmetric equilibrium in which both firms choose high quality. The equilibrium outcome shows that both firms will set lower prices and a higher level of advertising as compared to the monopoly case. Interestingly, we find that more competition might lead to a loss of social welfare due to the increasing level of advertising for quality signaling. The numerical results further demonstrate that as competition gets more intense from the monopoly, prices decrease initially, the level of advertising increases, and social welfare decreases, which may make a ban on advertising more recommendable after a certain threshold.
Performance‐Related Pay, Efficiency Wages and the Shape of the Tenure‐Earnings Profile
Authors: Sessions John G. , Skåtun John D.
Published: February 2016

Whilst it is well known that performance‐related pay (PRP) may increase wage inequality within a firm, there is an inter‐temporal lifecycle aspect that has been largely ignored in the literature. In this paper, we investigate theoretically how the introduction of PRP will influence the wage and remuneration profile over time. We develop a simple two‐period model of efficiency wages that rationalizes recent empirical findings suggesting PRP flattens the pay‐tenure profile. Such attenuation has important implications for the credibility of long‐term employment contracts as it suggests that agency rather than human capital considerations drive the profile.
Adherence to recommendations on lipid‐based nutrient supplement and iron and folic acid tablet consumption among pregnant and lactating women participating in a community health programme in northwest Bangladesh
Authors: Harding Kassandra L. , Matias Susana L. , Mridha Malay K. , Moniruzzaman Md. , Vosti Stephen A. , Hussain Sohrab , Dewey Kathryn G. , Stewart Christine P.
Published: February 2016

Limited knowledge exists on sustained adherence to small‐quantity lipid‐based nutrient supplements for pregnant and lactating women (LNS‐PL) and how this compares with that of other prenatal supplements. To address these gaps, a random subsample of women (n = 360) during pregnancy, early (6‐ to 12‐week post‐partum) and late (12‐ to 24‐week post‐partum) lactation, from an ongoing effectiveness trial in Bangladesh, was selected for in‐home interviews about LNS‐PL or iron/folic acid (IFA) use and preferences. Prevalence of high adherence (≥70% of the recommendation) based on self‐reported supplement consumption was 67%, 68% and 81% among LNS‐PL recipients during pregnancy, early and late lactation, and was 87% and 71% among IFA recipients during pregnancy and early lactation, respectively (P = 0.044). Programmatic factors (e.g. distribution and visits by programme staff) were consistently statistically significantly associated with reported high adherence. Among LNS‐PL recipients, high overall supplement acceptability score [odds ratio (OR): 8.62; 95% confidence interval (CI) 3.53, 20.83] and use of reminder techniques (OR: 4.41; 95%CI 1.65, 11.76) were positively associated, and reported vomiting at enrollment was negatively associated (OR: 0.34; 95%CI 0.14, 0.80), with reported high adherence. Selected women (n = 16) and key informants (n = 18) participated in in‐depth interviews about perceptions and acceptability of LNS‐PL. Women perceived benefits of taking LNS‐PL, but some faced barriers to consumption including aversion to odour and taste during pregnancy, forgetfulness and disruptions in supply. To achieve high adherence, results from this study suggest that maternal supplementation programmes should focus on programmatic barriers and consider incorporating reminder techniques. Organoleptic acceptability of LNS‐PL, particularly during pregnancy, may also need to be addressed.
Elderly woman with exaggerated startle reflex and unconscious drop attack
Authors: Neshige Shuichiro , Kobayashi Katsuya , Shimotake Akihiro , Iemura Tomoki , Matsumoto Riki , Nishinaka Kazuto , Matsumoto Masayasu , Takahashi Ryosuke , Ikeda Akio
Published: February 2016

Exaggerated startle reflex is an abnormal phenomenon originating from the caudal brainstem in which unheralded sensory stimuli evoke massive, generalized motor responses. Some patients with exaggerated startle reflex are reported to fall during startle. We report a sporadic case of exaggerated startle reflex with unconscious drop attack elicited by unexpected auditory stimuli as late‐onset involuntary movements. It is clinically important as one of the underlying diseases presenting unconscious drop attack, especially for older adults.
Novel nervous system mechanisms in visceral pain
Authors: De Winter B. Y. , Deiteren A. , De Man J. G.
Published: February 2016

Visceral hypersensitivity is an important factor underlying abdominal pain in functional gastrointestinal disorders such as irritable bowel syndrome (IBS) and can result from aberrant signaling from the gut to the brain or vice versa. Over the last two decades, research has identified several selective, intertwining pathways that underlie IBS‐related visceral nociception, including specific receptors on afferent and efferent nerve fibers such as transient receptor potential channels (TRP) channels, opioid, and cannabinoid receptors. In this issue of Neurogastroenterology and Motility Gil et al. demonstrate that in an animal model with reduced descending inhibitory control, the sympathetic nervous system outflow is enhanced, contributing to visceral and somatic hypersensitivity. They also provide evidence that interfering with the activation of adrenergic receptors on sensory nerves can be an interesting new strategy to treat visceral pain in IBS. This mini‐review places these findings in a broader perspective by providing an overview of promising novel mechanisms to alter the nervous control of visceral pain interfering with afferent or efferent neuronal signaling.
Impact of duration of contact lens wear on the structure and function of the meibomian glands
Authors: Alghamdi Waleed M. , Markoulli Maria , Holden Brien A. , Papas Eric B.
Published: February 2016

Purpose

To investigate the effects of the duration of contact lens (CL) wear on the meibomian glands (MGs), eyelid and tear film.

Methods

This was a cross‐sectional study of CL wearers and non‐wearers (NWs) aged between 18 and 35 years. The sample comprised of: (i) Three groups of CL wearers of different duration profiles (short, moderate and long experience of CL wear); (ii) a group of previous CL wearers (PWs) who had ceased wear for at least 6 months prior to the present study; (iii) healthy non‐wearers as a control group. Study procedures were conducted in the order from least invasive to most invasive as follows: symptom assessment, lipid assessment, non‐invasive break‐up time, tear meniscus area, tear osmolarity and evaporation, Phenol red thread, MG expressibility, ocular surface and eyelid assessments, meibography, Marx line and lid wiper assessment using lissamine green. For statistical comparison of continuous data, one‐way analysis of variance was used with Bonferroni post‐hoc correction, where appropriate. Kruskal–Wallis test and Pearson Chi‐Square respectively were used for ordinal and categorical variables.

Results

A total of 100 participants (49 males and 51 females; mean age ± SD: 25.4 ± 4.1) were enrolled across the five groups, such that each was composed of 20 age/sex matched individuals. Significant differences between the study groups were found for MG expressibility (p < 0.001), number of plugged orifices (p = 0.001), number of expressed orifices (p < 0.001), MG dropout (p = 0.001), Marx line score (p < 0.001), palpebral redness (p = 0.003), and roughness (p = 0.002), non‐invasive break‐up time (p < 0.001), Phenol red thread (p = 0.005), and tear meniscus area (p = 0.029). For all these variables, the NW group was statistically different from all other groups. Duration of wear was not a significant factor, except for Marx line score which was different in PWs compared to those with longer experience of CL wear (p = 0.03)

Conclusion

Alterations to MG morphology and function accompany contact lens wear. Although these changes onset during the first 2 years of wear, prolonged CL exposure beyond this point does not appear to be associated with further modification. Cessation of wear for at up to 6 months does not lead to resolution.
Trophic niche ontogeny and palaeoecology of early Toarcian Stenopterygius (Reptilia: Ichthyosauria)
Authors: Dick Daniel G. , Schweigert Günter , Maxwell Erin E.
Published: February 2016

Reconstructing ecological niche shifts during ontogeny in extinct animals with no living analogues is difficult without exceptional fossil collections. Here we demonstrate how a previously identified ontogenetic shift in the size and shape of the dentition in the early Toarcian ichthyosaur Stenopterygius quadriscissus accurately predicts a particular dietary shift. The smallest S. quadriscissus fed on small, burst‐swimming fishes, with a steady shift towards faster moving fish and cephalopods with increasing body size. Larger adult specimens appear to have been completely reliant on cephalopods, with fish completely absent from gut contents shortly after onset of sexual maturity. This is consistent with a previously proposed ontogenetic niche shift based on tooth shape and body size, corroborating the idea that dental ontogeny may be a useful predictor of dietary shifts in marine reptiles. Applying the theoretical framework used here to other extinct species will improve the resolution of palaeoecological reconstructions, where appropriate sample sizes exist.
Imbricate radial sculpture: a convergent feature within externally shelled cephalopods
Authors: Radtke Gregor , Keupp Helmut
Published: February 2016

Radial sculptural elements (e.g. ribs, lirae), formed by imbrication of two succeeding shell lamellae are found in members of both the Nautiloidea (Cymatoceras) and Ammonoidea (Phylloceratinae and Aspidoceratinae). Their formation involves periodic cessation of shell growth due to weak to moderate withdrawal of the shell secreting mantle. The radial lirae (0.5–1.5 mm in width) of Phylloceratinae and Aspidoceratinae (AspidocerasandPseudowaagenia) are created by the succession of sigmoid lamellae of the organic periostracum or of the outer prismatic layer, respectively. Each lira has a characteristic adorally‐projecting, scythe‐like appendage, arising from its crest. The prismatic lirae ofAspidocerasandPseudowaageniaare analogous to the larger scaled pseudoribs ofCymatoceras. Garland‐like lamellae of the outer prismatic layer form the radial lirae ofMirosphinctesandEpaspidoceras(Aspidoceratinae), but these lack a conspicuous, projecting scythe‐like appendage. Additional prismatic cement is formed within adoral, oval hollow spaces of scythe‐appendage‐bearing lirae, either through diagenetic crystal growth, remote biomineralization or as a component of the dorsal shell. In Aspidoceratinae these prismatic infillings are replaced by a continuous herringbone layer, accompanied by a reduction of the lirae.
Efficacy and Safety of Gabapentin vs. Carbamazepine in the Treatment of Trigeminal Neuralgia: A Meta‐Analysis
Authors: Yuan Min , Zhou Huang‐yan , Xiao Zhi‐long , Wang Wei , Li Xue‐li , Chen Shen‐jian , Yin Xiao‐ping , Xu Li‐jun
Published: February 2016

To evaluate the safety and efficacy of gabapentin in comparison with carbamazepine in the treatment of trigeminal neuralgia, a meta‐analysis of randomized controlled trials was performed. Two reviewers independently selected studies, assessed study quality, and extracted data. Sixteen randomized controlled trials that included 1,331 patients were assessed. The meta‐analysis showed that the total effective rate of gabapentin therapy group was similar with carbamazepine therapy group (OR = 1.600, 95% CI 1.185, 2.161, P = 0.002). While the effective rate of gabapentin therapy for 4 weeks was higher than that of carbamazepine therapy (OR = 1.495, 95% CI 1.061, 2.107, P = 0.022, heterogeneity: x2 = 7.12, P = 0.625, I2 = 0.0%), the life satisfaction improvement is also better in the gabapentin therapy group after a 4‐week treatment (SMD = 0.966, 95% CI 0.583, 1.348, P < 0.001). Furthermore, our meta‐analysis suggested that the adverse reaction rate of gabapentin therapy group was significantly lower than that of carbamazepine therapy group (OR = 0.312, 95% CI 0.240, 0.407, P < 0.001). In conclusion, present trials comparing gabapentin with carbamazepine are all poor in terms of methodological quality. Based on the available evidence, it is not possible to draw conclusions regarding the efficacy and side effects of gabapentin being superior to carbamazepine.
The Role of Health Locus of Control in Evaluating Depression and Other Comorbidities in Patients with Chronic Pain Conditions, A Cross‐Sectional Study
Authors: Wong Harry J. , Anitescu Magdalena
Published: February 2016

Objective

Chronic pain is significantly influenced by behavioral, cognitive, and emotional factors. Few studies have investigated the health locus of control (HLC)—one's belief regarding where control over one's health lies—as it relates to patients with chronic pain. The purpose of this prospective, cross‐sectional study was to examine the relationship between depression and health/pain locus of control (HLC) in adult patients with persistent pain.

Material and Methods

A series of questionnaires was administered to chronic pain patients, and these questionnaires were scored and analyzed. Patients were categorized into 3 groups based on health locus of control (internal, chance, powerful‐others), which were examined with respect to their depression scores using analysis of variance.

Results

A total of 131 patients completed the study: 33% belonged to the internal group, 39% in the chance group, and 28% in the powerful‐others group. The 3 groups had depression scores of 40 (SD = 8), 47 (SD = 10), and 42 (SD = 8), respectively. We found significant difference in depressions scores between the chance group and the internal group (P < 0.005) with the chance group having higher depression scores compared to the internal group.

Conclusions

The study shows that patients with an internal locus of control are less depressed compared to patients with fatalistic views on their health/pain in the chance group. The chance dimension of the Multidimensional Health Locus of Control scale was found to be a potential predictor of psychiatric comorbidities such as depression in the chronic pain patient population.
Focal Mechanical Vibration Does not Change Laser‐Pain Perception and Laser‐Evoked Potentials: A Pilot Study
Authors: Pazzaglia Costanza , Camerota Filippo , Celletti Claudia , Minciotti Ileana , Testani Elisa , Padua Luca , Valeriani Massimiliano
Published: February 2016

Background

Nonpainful tactile and electrical stimulation of the large myelinated fibers reduces spontaneous pain and the amplitude of laser‐evoked potentials (LEPs), which represent the most reliable technique to assess the nociceptive pathway function. Focal mechanical vibration stimulates the Aβ afferents selectively; thus, it is conceivable its action on nociceptive pathways.

Aim

The aim of this study was to investigate the effect of vibratory stimuli, activating either both muscle and skin receptors or cutaneous afferents only on the LEPs and subjective laser‐pain rating.

Methods

Ten healthy volunteers were studied. The subjects were evaluated in two different sessions to test muscle and skin receptors or cutaneous afferents only. In each session, LEPs were recorded to stimulation of the dorsal hand skin in radial and ulnar territory bilaterally, while the vibratory stimulus was delivered on the radial territory of the right forearm.

Results

The results showed a substantial stability of the potential N1 and N2/P2 after the two protocols, with a declining trend from the initial to the last test of the same session, probably due to habituation. Accordingly, the laser‐pain perception did not change during the experimental setting.

Conclusions

We conclude that a vibratory stimulus is ineffective in reducing the laser‐evoked potentials and laser‐pain perception.
Inadvertent Intradiscal Injection with TFESI Utilizing Kambin's Retrodiscal Approach in the Treatment of Acute Lumbar Radiculopathy
Authors: Trinh Kevin H. , Gharibo Christopher G. , Aydin Steve M.
Published: February 2016

Introduction

There is very strong evidence for the efficacy of transforaminal epidural steroid injection (TFESI) in relieving lumbar radicular pain due to a herniated disk. However, case studies have documented paralysis as a potential complication from this approach as the artery of Adamkiewicz may traverse within the subpedicular “safe triangle.” Kambin's retrodiscal approach has been postulated as a safe means to the transforaminal approach to avoid the artery of Adamkiewicz.

Case Presentation

A 51‐year‐old woman presented with right‐sided lumbar radicular pain at the L3–L4 and L4–L5 level secondary to a herniated disk. As conservative therapies failed to improve her radicular back pain, the patient opted to proceed with an epidural steroid injection. She subsequently underwent a right L3–L4 and L4–L5 transforaminal epidural steroid injection via Kambin's retrodiscal approach. Although anteroposterior and lateral views revealed optimal needle placement, live and postcontrast fluoroscopy revealed an unavoidable and inadvertent intradiscal spread.

Conclusion

Kambin's approach is at the level of the intervertebral disk and may increase the incidence of intradiscal needle entry and injection.