bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of left ventricular reverse remodeling in patients with severe aortic regurgitation undergoing aortic valve replacement: Comparison between diameters and volumes
Authors: Ong Géraldine , Redfors Bjorn , Crowley Aaron , Abdel‐Qadir Husam , Harrington Alana , Liu Yangbo , Lafrenière‐Roula Myriam , Leong‐Poi Howard , Peterson Mark D. , Connelly Kim A.
Published: November 2017

Background

In patients with severe aortic regurgitation (AR), the left ventricular ejection fraction (LVEF) and left ventricle (LV) size are crucial for determining clinical prognosis and timing of valve intervention. In clinical practice, LV internal diameters obtained at end‐diastole are used to assess the degree of LV dilatation. Whether quantification of LV volumes would provide more robust information as compared to LV linear dimensions is unknown.

Methods

We retrospectively analyzed preoperative and postoperative transthoracic echocardiograms of patients who underwent aortic valve replacement (AVR) for severe AR. Indexed linear LV end‐diastolic and end‐systolic diameters along with indexed LV end‐diastolic and end‐systolic volumes were obtained as per current guidelines. Post‐AVR LV reverse remodeling, defined as ≥10% reduction in measures of LV volumes (Teichholz and Simpson's methods), was determined. Positive and negative agreement was calculated between the volume‐ and diameter‐based LV reverse remodeling.

Results

Sixty‐two consecutive patients were included. Nine patients (17%) without LV reverse remodeling based on Teichholz were reclassified as having LV reverse remodeling based on Simpson (positive agreement 0.846 [95% CI 0.772, 0.921], negative agreement 0.200 [95% CI −0.350, 0.435]). Left ventricle (LV) reverse remodeling assessed by the Teichholz method was underestimated by a mean of 31 mL/m2 (β = −0.65 [95% CI −1.06 to −0.24], P = .003) compared to Simpson method.

Conclusion

Compared to the volume‐based method, diameter‐based LV measurement incorrectly identified LV reverse remodeling post‐AVR in 17% of patients with severe AR. Left ventricle (LV) volume may be a better measure to assess LV remodeling post‐AVR than LV diameter‐based measurements.
Negative bubbles: What happens after a crash
Authors: Goetzmann William N. , Kim Dasol
Published: November 2017

We study crashes using data from 101 global stock markets from 1692 to 2015. Extremely large, annual stock market declines are typically followed by positive returns. This is not true for smaller declines. This pattern does not appear to be driven by institutional frictions, financial crises, macroeconomic shocks, political conflicts, or survivorship issues.
Connectivity in a Karst System Using Electrical Resistivity Tomography and Network Theory
Authors: Gómez‐Nicolás Mariana , Rebolledo‐Vieyra Mario , Canto‐Lugo Efrain , Huerta‐Quintanilla Rodrigo , Ochoa‐Sandoval Pablo
Published: November 2017

The Ring of Cenotes (RC) is an alignment of numerous cenotes (sinkholes) in a semicircular form (with a radius of 100 km) located in northwestern Yucatán, México. The formation roughly coincides with a concentric ring that corresponds to a buried structure, which has been identified as the product of a meteor impact, known as the Chicxulub crater. Secondary permeability generated by the fracturing and faulting of the sedimentary sequence in the Chicxulub crater has favored the karstification process and therefore the development of underground rivers that transport water from the mainland to the sea.

This study implements the network theory to study the hydrological connectivity between a group of 11 cenotes within the RC. Eight electrical resistivity tomography transects were used as an empirical basis. Each transect was acquired directly in the field using the SuperSting R1/IP equipment with a dipole‐dipole configuration. An adapted version of the reliability algorithm for communication networks was used as a theoretical model.

We found evidence of the existence of water cavities in the study area. We made a network from the data and assigned connection probabilities among cenotes as a function of the separation length and the number of water cavities, as well as their size.
Mid‐term outcomes and complications of total knee arthroplasty in haemophilic arthropathy: A review of consecutive 131 knees between 2006 and 2015 in a single institute
Authors: Song S. J. , Bae J. K. , Park C. H. , Yoo M. C. , Bae D. K. , Kim K. I.
Published: November 2017

Introduction

Although total knee arthroplasty (TKA) in haemophilic arthropathy can reduce severe joint pain and improve functional disability, it is technically demanding.

Aim

To evaluate mid‐term outcomes and complications of TKA in haemophilic arthropathy.

Methods

This study retrospectively reviewed 131 consecutive primary TKAs in a single institute. The mean age was 41.0 years old, and the mean follow‐up period was 6.8 years. Clinical and radiographic results were evaluated. Complications were categorized according to the classification system of the Knee Society for TKA complications.

Results

The average Western Ontario and McMaster Universities Arthritis Index (WOMAC) score improved from 66.0 to 24.2. The average flexion contracture significantly decreased from 17.3° to 4.7°, but the average pre‐ and postoperative maximum flexion did not differ (80.9° vs 85.6°, respectively). The average mechanical axis was varus 5.2° preoperatively and valgus 0.3° postoperatively. The coronal positions of the femoral and tibial components and the sagittal positions of these components were within ±3° in 83.2%, 89.3%, 63.4% and 73.3% of cases, respectively. Complications occurred in 17 knees (13.0%): hemarthrosis (n = 7), medial collateral ligament injury (n = 1), stiffness (n = 2), deep periprosthetic joint infection (PJI) (n = 3) and periprosthetic fracture (n = 4).

Conclusions

The mid‐term results of TKA in haemophilic arthropathy were satisfactory in pain relief, improved function and decreased flexion contracture. Bleeding and PJI continue to be major concerns for TKA in haemophilic arthropathy, and risk of periprosthetic fracture must be taken into account for patient education and appropriate prevention.
Antagonistic Relationship Between VEP Potentiation and Gamma Power in Visual Snow Syndrome
Authors: Luna Sebastian , Lai Daniel , Harris Alison
Published: November 2017

Objective

Using a “double‐pulse” adaptation paradigm, in which two stimuli are presented in quick succession, this study examines the neural mechanisms underlying potentiation of the visual evoked potential (VEP) in visual snow syndrome.

Background

Visual snow is a persistent visual disturbance characterized by rapid flickering dots throughout the visual field. Like the related condition of migraine with aura, visual snow has been hypothesized to arise from abnormal neuronal responsiveness, as demonstrated by a lack of typical VEP habituation to repeated visual stimulation. Yet the exact neural mechanisms underlying this effect remain unclear. Previous “double‐pulse” experiments suggest that typical VEP habituation reflects disruptive gamma‐band (50‐70 Hz) neural oscillations, possibly driven by inhibitory interneurons. Given that migraine has been associated with reduced cortical inhibition, we propose here that visual snow may likewise reflect diminished inhibitory activity, resulting in decreased gamma power following initial visual stimulation and concomitant potentiation of the subsequent VEP response.

Methods

We compared VEP responses to double‐pulse adaptation in a 22‐year‐old man with a 2‐year history of visual snow versus a group of age‐ and gender‐matched controls (N = 5). The patient does not have a comorbid diagnosis of episodic migraine or migraine with aura, and controls had no personal or family history of migraine.

Results

In contrast to the pattern of habituation observed in controls, visual snow was associated with persistent potentiation of the VEP response. Consistent with our predictions, time‐frequency analysis revealed reduced gamma‐band power following the initial stimulus in visual snow relative to controls.

Conclusions

These results support an antagonistic interplay between gamma power and rapid neural adaptation, shedding new light on the neural mechanisms of VEP potentiation in visual snow.
Association Between Migraine and Suicidal Behaviors: A Nationwide Study in the USA
Authors: Friedman Lauren E. , Zhong Qiu‐Yue , Gelaye Bizu , Williams Michelle A. , Peterlin B. Lee
Published: November 2017

Background

Recent studies show migraineurs are at an increased risk of developing suicidal behaviors, even after controlling for comorbid depression. However, previous research has not examined the impact of psychiatric mood disorders on suicidal behaviors in migraineurs within a nationally representative sample.

Objective

A cross‐sectional study was used to investigate the association between migraine and suicidal behaviors and determine whether psychiatric comorbidities modify this association in a nationwide inpatient cohort.

Methods

We analyzed the Nationwide Inpatient Sample of hospitalizations compiled from USA billing data. Migraine, suicidal behaviors, and psychiatric disorders were identified based on the International Classification of Diseases, 9th Revision, Clinical Modification diagnosis codes from hospitalization discharges (2007‐2012). Weighted national estimates were used to estimate odds ratios (OR) and 95% confidence intervals (CI).

Results

156,172,826 hospitalizations were included, of which 1.4% had a migraine diagnosis and 1.6% had a diagnosis of suicidal behavior. Migraineurs had a 2.07‐fold increased odds of suicidal behaviors (95%CI: 1.96‐2.19) compared with non‐migraineurs. We repeated analyses after stratifying by depression, anxiety, or posttraumatic stress disorder (PTSD). Among hospitalizations with depression, migraine was associated with a 20% reduced odds of suicidal behaviors (95%CI: 0.76‐0.85). Among hospitalizations without depression, migraine was associated with 2.35‐fold increased odds of suicidal behaviors (95%CI: 2.20‐2.51). In stratified analyses, we noted that among hospitalizations with anxiety, migraineurs had slightly increased odds of suicidal behaviors (OR: 1.07, 95%CI: 1.02‐1.13). Among hospitalizations without anxiety, migraine was associated with a 2.06‐fold increased odds of suicidal behaviors (95%CI: 1.94‐2.20). Similarly, in analyses stratified by PTSD, migraine was not associated with an increased risk of suicidal behaviors (OR: 1.00, 95%CI: 0.94‐1.07) among those with PTSD. However, the odds of suicidal behaviors were increased among hospitalizations without PTSD (OR: 1.95, 95%CI: 1.84‐2.08).

Conclusion

Chronic conditions that do not affect the current hospitalization may not have been reported. The presence of psychiatric diagnoses influences associations of suicidal behaviors with migraine in a national inpatient sample. Migraineurs with diagnosed comorbid psychiatric disorders may be receiving care that mitigates their risk for suicidal behaviors.
The Second Generation in Chile: Negotiating Identities, Rights, and Public Policy
Authors: Pavez‐Soto Iskra , Chan Carol
Published: November 2017

This article presents the first study of children born in Chile to at least one migrant parent – the “second‐generation”. Based on a mixed methods and child‐centred approach, this article discusses institutional and experiential aspects of boundary and identity‐making in Chile regarding race and nationality. We first review quantitative data from the state regarding the second‐generation. Building on insights from comparative research on European states’ second‐generation integration policies, we suggest how gathering targeted Census data in Chile can inform the long‐term evaluation of state policies and programs for socio‐cultural inclusion in education and labour. We also present qualitative data from interviews with ten second‐generation children between ages eight to thirteen, born to parents from Peru and Ecuador. We attend to how they negotiate being perceived as “foreign” and/or “Chilean”. Their position in‐between the two categories is an important starting point for policies and discourse to expand notions of citizenship and belonging.
Quantifying the hidden healthcare cost of diabetes mellitus in Australian hospital patients
Authors: Karahalios Amalia , Somarajah Gowri , Hamblin Peter S. , Karunajeewa Harin , Janus Edward D.
Published: November 2017

Background

Diabetes mellitus in hospital inpatients is most commonly present as a comorbidity rather than as the primary diagnosis. In some hospitals, the prevalence of comorbid diabetes mellitus across all inpatients exceeds 30%, which could add to complexity of care and resource utilisation. However, whether and to what extent comorbid diabetes mellitus contributes indirectly to greater hospitalisation costs is ill‐defined.

Aim

To determine the attributable effect of comorbid diabetes mellitus on hospital resource utilisation in a General Internal Medical service in Melbourne, Australia.

Methods

We extracted data from a database of all General Internal Medical discharge episodes from July 2012 to June 2013. We fitted multivariable regression models to compare patients with diabetes mellitus to those without diabetes mellitus with respect to hospitalisation cost, length of stay, admissions per year and inpatient mortality.

Results

Of 4657 patients 1519 (33%) had diabetes mellitus, for whom average hospitalisation cost (AUD9910) was higher than those without diabetes mellitus (AUD7805). In multivariable analysis, this corresponded to a 1.22‐fold (95% confidence interval (CI) 1.12–1.33, P < 0.001) higher cost. Mean length of stay for those with diabetes was 8.2 days versus 6.8 days for those without diabetes, with an adjusted 1.19‐fold greater odds (95% CI 1.06–1.33, P = 0.001) of staying an additional day. Number of admissions and mortality were similar.

Conclusion

Comorbid diabetes mellitus adds significantly to hospitalisation duration and costs in medical inpatients. Moreover, diabetes mellitus patients with chronic complications had a greater‐still cost and hospitalisation duration compared to those without diabetes mellitus.
A phylogeny of kingfishers reveals an Indomalayan origin and elevated rates of diversification on oceanic islands
Authors: Andersen Michael J. , McCullough Jenna M. , Mauck William M. , Smith Brian Tilston , Moyle Robert G.
Published: November 2017

Aim

Kingfishers are the most species‐rich family in the avian order, Coraciiformes. Their modern distribution is largely pantropical; however, global species diversity is unevenly distributed. For example, 19 of the 114 kingfisher species occur in New Guinea, whereas only six species occur in the entire New World. This disparity in diversity suggests regions with high species richness could represent the ancestral range of the family. Furthermore, some clades of kingfishers (Ceyx,Todiramphus) are thought to be the product of rapid insular radiations. Here, we investigated the biogeographical history and speciation dynamics of the Alcedinidae using a fully sampled molecular phylogeny.

Location

Global.

Taxon

Kingfishers (Aves: Coraciiformes: Alcedinidae).

Methods

We inferred a time‐calibrated, species‐level phylogeny of kingfishers fromDNAsequences. Our data set comprised up to five Sanger‐sequenced gene regions for all species (one mitochondrial, one nuclear exon and three nuclear introns), plus genus‐level sampling of thousands of ultraconserved elements. We estimated ancestral ranges of kingfishers and explored macroevolutionary rate shifts and diversification rates across the phylogeny.

Results

We recovered a well‐supported phylogeny of kingfishers that includes 34 species whose phylogenetic relationships were not previously known. The pygmy‐kingfishers (subfamily Alcedininae) sit on a long branch, sister to all other kingfishers: subfamilies Cerylinae and Halcyoninae. Crown‐group kingfishers originated in the Indomalayan region approximately 27 Ma with subsequent colonizations into Africa (six times), the New World (twice) and Australasia (representing several major radiations).

Main conclusions

Oceanic islands of Wallacea, the Philippines and Oceania promoted multiple, independent radiations in three species‐rich genera:Ceyx,ActenoidesandTodiramphus. In particular,Todiramphusshowed patterns consistent with explosive and recent diversification relative to the background speciation rate of non‐Todiramphuskingfishers, which we attribute to recent colonization of the vast archipelagos of Wallacea and the Pacific.
Causes and predictors of 30‐day readmission after cardiovascular implantable electronic devices implantation: Insights from Nationwide Readmissions Database
Authors: Ahmad Shahzad , Munir Muhammad Bilal , Sharbaugh Michael S. , Althouse Andrew D. , Pasupula Deepak Kumar , Saba Samir
Published: November 2017

Introduction

Readmissions are a burden on health care resources and have negative impact on patients. Cardiovascular implantable electronic devices (CIEDs) are frequently used in the management of rhythm disorders and advanced heart failure. We assessed 30‐day readmissions in patients admitted for CIED implantation in a sample of United States patients.

Methods

Data were extracted from Nationwide Readmissions Database for calendar year 2013. Patients admitted for CIED implantation were identified using ICD‐9 codes. Patients <18 years of age, with missing data, who died during hospitalization or discharged in December were excluded. Primary endpoint was all‐cause 30‐day readmission rate. Factors associated with 30‐day readmissions were identified and examined using multivariate logistic regression.

Results

We identified 320,783 admissions for CIED implantations. After applying exclusion criteria, 290,420 patients were included in final analysis, out of whom 45,467 (15.7%) patients were readmitted within 30 days. Readmitted patients were younger and had more comorbidities. Septicemia (5.1%), pneumonia (3.4%), CHF (2.35%), and paroxysmal ventricular tachycardia (2.3%) were common primary causes of 30‐day readmission. Young age, female gender, key comorbidities, weekend admissions, and admission to medium and large size hospital were independent predictors of 30‐day readmissions.

Conclusion

In our study, 15.7% patients were readmitted within 30 days of an index admission for CIED implantation. Most readmissions were due to infectious or cardiovascular causes. There is a need to identify patients at risk for readmission to improve outcomes and curb the cost of care.
States as Gatekeepers in EU Asylum Politics: Explaining the Non‐adoption of a Refugee Quota System
Authors: Zaun Natascha
Published: November 2017

Building on Moravcsik's Liberal Intergovernmentalism, I offer an explanation of the non‐decision on permanent EU refugee quotas. Some traditionally influential Member States in EU asylum politics, such as Germany, Austria and Sweden, received large numbers of refugees and faced strong domestic pressures to engage other Member States in responsibility‐sharing. Yet, governments of Member States with small application numbers (among whom several Eastern European governments were particularly vocal) had incentives to undercut responsibility‐sharing to avoid similar pressures. Having a better alternative to the potentially negotiated agreement, these governments successfully blocked the introduction of permanent refugee quotas. Besides explaining the absence of an effective response to one of the root causes of the asylum crisis (unequal strains) through asymmetrical interdependence, the article further develops Liberal Intergovernmentalist arguments and shows how national electorates influence positions taken by governments at the EU level when they are mobilized by right‐wing populist parties.
Aeromonas caviae inhibits hepatic enzymes of the phosphotransfer network in experimentally infected silver catfish: Impairment on bioenergetics
Authors: Baldissera M D , Souza C F , Verdi C M , dos Santos K L M , Da Veiga M L , da Rocha M I U M , Santos R C V , Vizzotto B S , Baldisserotto B
Published: November 2017

Several studies have been demonstrated that phosphotransfer network, through the adenylate kinase (AK) and pyruvate kinase (PK) activities, allows for new perspectives leading to understanding of disease conditions associated with disturbances in energy metabolism, metabolic monitoring and signalling. In this sense, the aim of this study was to evaluate whether experimental infection by Aeromonas caviae alters hepatic AK and PK activities of silver catfish Rhamdia quelen. Hepatic AK and PK activities decreased in infected animals compared to uninfected animals, as well as the hepatic adenosine triphosphate (ATP) levels. Also, a severe hepatic damage was observed in the infected animals due to the presence of dilation and congestion of vessels, degeneration of hepatocytes and loss of liver parenchyma architecture and sinusoidal structure. Therefore, we have demonstrated, for the first time, that experimental infection by A. caviae inhibits key enzymes linked to the communication between sites of ATP generation and ATP utilization. Moreover, the absence of a reciprocal compensatory mechanism between these enzymes contributes directly to hepatic damage and for a severe energetic imbalance, which may contribute to disease pathophysiology.
The high prevalence of pathogenic Vibrio harveyi with multiple antibiotic resistance in scale drop and muscle necrosis disease of the hybrid grouper, Epinephelus fuscoguttatus (♀) × E. lanceolatus (♂), in China
Authors: Zhu Z M , Dong C F , Weng S P , He J G
Published: November 2017

Scale drop and muscle necrosis disease with high mortality widely occurred recently in the hybrid grouper (Epinephelus fuscoguttatus ♀ × E. lanceolatus ♂), a crucial cultured marine fish species in China. In this study, 30 Harveyi clade isolates of 27 Vibrio harveyi strains were isolated from diseased hybrid groupers in the south‐east and north‐east coastal areas of China. A total of 22 V. harveyi strains were determined to be pathogenic, and most challenged fish died within 2 days of infection; surviving individuals exhibited scale drop and deep dermal lesions as naturally diseased fish. Although five typical virulence genes, including luxR, toxRVh, chiA, serine protease and vhh widely existed in V. harveyi, no obvious correlation was established between virulent strains and virulence genes harboured in them. Furthermore, multiple antibiotic resistance was widely exhibited in Harveyi clade strains, particularly for penicillins, polypeptides, lincomycins, acetylspiramycin, streptomycin, metronidazole and bacitracin. And the multiple antibiotic resistance indices were gradually decreased from southern to northern areas of China. This study demonstrated that the pathogenic V. harveyi with multiple antibiotic resistance is highly prevalent in hybrid grouper in China, which requires particular attention.
Additive effects of PNPLA3 and TM6SF2 on the histological severity of non‐alcoholic fatty liver disease
Authors: Koo Bo Kyung , Joo Sae Kyung , Kim Donghee , Bae Jeong Mo , Park Jeong Hwan , Kim Jung Ho , Kim Won
Published: November 2017

Background and Aim

We investigated the effects of PNPLA3 rs738409, TM6SF2 rs58542926, and MBOAT7‐TMC4 rs641738 variants on metabolic phenotypes and their combined effects on the histological severity of non‐alcoholic fatty liver disease (NAFLD).

Methods

We genotyped rs738409, rs58542926, and rs641738 in biopsy‐proven NAFLD patients (n = 416) and healthy controls (n = 109). Homeostasis model assessment of insulin resistance and adipose tissue insulin resistance were calculated.

Results

The rs738409 and rs58542926 variants, but not rs641738, were associated not only with non‐alcoholic steatohepatitis (NASH) (odds ratio [OR], 2.00; 95% confidence interval [CI], 1.46–2.73 and OR, 1.91; 95% CI, 1.04–3.51) but also with significant fibrosis (≥ F2) (OR, 1.53; 95% CI, 1.11–2.11 and OR, 1.88; 95% CI, 1.02–3.46) in NAFLD, even after adjustment for metabolic risk factors. Of both variants, only rs738409 was associated with homeostasis model assessment of insulin resistance and adipose tissue insulin resistance even in healthy controls (P = 0.046 and 0.002, respectively) as well as in the entire study cohort (P = 0.016 and 0.048, respectively). PNPLA3 and TM6SF2 risk variants additively increased the risk of NASH and significant fibrosis (OR per risk allele, 2.03; 95% CI, 1.50–2.73 and 1.61; 95% CI, 1.19–2.17). Even in subjects with low insulin resistance, the risk of NASH or significant fibrosis increased as the number of risk alleles increased (P = 0.008 and 0.020, respectively).

Conclusions

PNPLA3 and TM6SF2 determine the risk of NASH and significant fibrosis, even after adjustment for insulin resistance, and exert an additive effect on NASH and significant fibrosis.
Fatal toxoplasmosis in a southern muriqui (Brachyteles arachnoides) from São Paulo state, Brazil: Pathological, immunohistochemical, and molecular characterization
Authors: Santos Stéfanie Vanessa , Pena Hilda F.J. , Talebi Mauricio G. , Teixeira Rodrigo H.F. , Kanamura Cristina T. , Diaz‐Delgado Josué , Gennari Solange M. , Catão‐Dias José Luiz
Published: November 2017

We report the pathological, immunohistochemical, and molecular features of fatal acute systemic toxoplasmosis in an adult, female, free‐living southern muriqui (Brachyteles arachnoides) from São Paulo state, Brazil. PCR‐RFLP genotyping analysis identified the #21 genotype ofToxoplasma gondii. This represents the first report of acute toxoplasmosis involving this genotype in humans and animals.
The non‐peptidic δ‐opioid receptor agonist Tan‐67 mediates neuroprotection post‐ischemically and is associated with altered amyloid precursor protein expression, maturation and processing in mice
Authors: Min Jia‐Wei , Liu Yanying , Wang David , Qiao Fangfang , Wang Hongmin
Published: November 2017

Tan‐67 is a selective non‐peptidic δ‐opioid receptor (DOR) agonist that confers neuroprotection against cerebral ischemia/reperfusion (I/R)‐caused neuronal injury in pre‐treated animals. In this study, we examined whether post‐ischemic administration of Tan‐67 in stroke mice is also neuroprotective and whether the treatment affects expression, maturation and processing of the amyloid precursor protein (APP). A focal cerebral I/R model in mice was induced by middle cerebral artery occlusion for 1 h and Tan‐67 (1.5, 3 or 4.5 mg/kg) was administered via the tail vein at 1 h after reperfusion. Alternatively, naltrindole, a selective DOR antagonist (5 mg/kg), was administered 1 h before Tan‐67 treatment. Our results showed that post‐ischemic administration of Tan‐67 (3 mg/kg or 4.5 mg/kg) was neuroprotective as shown by decreased infarct volume and neuronal loss following I/R. Importantly, Tan‐67 improved animal survival and neurobehavioral outcomes. Conversely, naltrindole abolished Tan‐67 neuroprotection in infarct volume. Tan‐67 treatment also increased APP expression, maturation and processing in the ipsilateral penumbral area at 6 h but decreased APP expression and maturation in the same brain area at 24 h after I/R. Tan‐67‐induced increase in APP expression was also seen in the ischemic cortex at 24 h following I/R. Moreover, Tan‐67 attenuated BACE‐1 expression, β‐secretase activity and the BACE cleavage of APP in the ischemic cortex at 24 h after I/R, which was abolished by naltrindole. Our data suggest that Tan‐67 is a promising DOR‐dependent therapeutic agent for treating I/R‐caused disorder and that Tan‐67‐mediated neuroprotection may be mediated via modulating APP expression, maturation and processing, despite an uncertain causative relationship between the altered APP and the outcomes observed.

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The impact of shift work on intensive care nurses’ lives outside work: A cross‐sectional study
Authors: Jensen Hanne Irene , Larsen Jette West , Thomsen Tina Damgaard
Published: November 2017

Aims and objectives

To examine how shift work affects intensive care nurses’ lives outside work.

Background

Shift work is unavoidable for many nurses. When attempting to minimise negative effects of shift work, it is important to identify areas which affect nurses working shifts.

Design

A cross‐sectional study.

Methods

A questionnaire survey among Danish intensive care nurses concerning experiences with shift work and family life, spare time activities, sleep and health.

Results

A total of 114 nurses (88%) participated. Shift work was found to influence the opportunities for spare time activities, and about 25% of both evening‐ and night‐shift groups found that working shifts sometimes led to social isolation. A total of 58% of nurses working evening shifts sometimes to very often experienced having trouble falling asleep when working shifts. Night‐shift workers had a higher percentage of physical and mental symptoms when working shifts compared with evening‐shift workers, with mood swings and headaches being the most common. The median score for thriving on working shifts was 8 (IQR 5–9) for evening‐shift workers and 8 (IQR 7–9) for night‐shift workers (scale 0–10 with 10 being the highest level of thriving).

Conclusion

Shift workers reported that working shifts had a negative impact on life outside work. Opportunities for participating in spare time activities and difficulties falling asleep after shifts were the main issues for evening‐shift workers, whereas physical symptoms such as headaches and mood swings were more dominant among night‐shift workers. Despite the negative effects, the participants generally thrived on working shifts.

Relevance to clinical practice

By identifying modifiable areas which negatively influence life outside work when working shifts, it will be possible subsequently to plan interventions aimed at decreasing the negative effects. Interventions may include nurses having increased influence on their work schedules and education in sleep hygiene and dietary habits.
Repeated MitraClip procedure in patients with recurrent MR after a successful first procedure: Limitations and outcome
Authors: Curio Jonathan , Reinthaler Markus , Kasner Mario , Al‐Hindwan Haitham Saleh Ali , Baeckemo‐Johansson Johan , Neumann Tim , Jacobs Stephan , Lauten Alexander , Landmesser Ulf
Published: November 2017

Objectives

The present study aimed to evaluate the outcome and potential limitations of a repeated MitraClip procedure (ReClip).

Background

The MitraClip procedure has emerged as a treatment option in high surgical risk patients suffering from severe mitral regurgitation (MR). However, despite successful initial repair a significant number of patients develops severe recurrent MR.

Methods

Patients undergoing a ReClip procedure in our institution were retrospectively identified. Baseline data and the procedural outcome were assessed to identify potential limitations of such procedures.

Results

Fifteen out of 234 patients undergoing a mitral‐valve repair with the MitraClip device (Abbott Vascular) underwent a ReClip due to recurrent MR. In 11 patients, a MR reduction of at least one degree without causing mitral valve stenosis (trans‐mitral mean gradient ≥5 mmHg) was achieved by performing a ReClip. After 1 year, two patients developed severe recurrent MR again. Pulmonary artery pressures significantly decreased after the procedure in individuals with successful repair (MR reduction of at least one degree and mitral valve mean gradient <5 mmHg).

Conclusion

A ReClip procedure may be feasible in patients with recurrent MR but the risk benefit ratio should be carefully balanced against other treatment options.
Oral insulin delivery: existing barriers and current counter-strategies
Authors: Gedawy Ahmed , Martinez Jorge , Al-Salami Hani , Dass Crispin R
Published: November 2017

Objectives

The chronic and progressive nature of diabetes is usually associated with micro- and macrovascular complications where failure of pancreatic β-cell function and a general condition of hyperglycaemia is created. One possible factor is failure of the patient to comply with and adhere to the prescribed insulin due to the inconvenient administration route. This review summarizes the rationale for oral insulin administration, existing barriers and some counter-strategies trialled.

Key findings

Oral insulin mimics the physiology of endogenous insulin secreted by pancreas. Following the intestinal absorption of oral insulin, it reaches the liver at high concentration via the portal vein. Oral insulin on the other hand has the potential to protect pancreatic β-cells from autoimmune destruction. Structural modification, targeting a particular tissue/receptor, and the use of innovative pharmaceutical formulations such as nanoparticles represent strategies introduced to improve oral insulin bioavailability. They showed promising results in overcoming the hurdles facing oral insulin delivery, although delivery is far from ideal.

The use of advanced pharmaceutical technologies and further research in particulate carrier system delivery predominantly nanoparticle utilization would offer useful tools in delivering insulin via the oral route which in turn would potentially improve diabetic patient compliance to insulin and the overall management of diabetes.
Evaluating bioequivalence of meloxicam tablets: is in-vitro dissolution test overdiscriminating?
Authors: Jin Chan , Zhao Chenyao , Shen Dachao , Dong Wenxiang , Liu Hongzhuo , He Zhonggui
Published: November 2017

Objectives

The aim of the study was to assess the impact of the differences in dissolution profiles of meloxicam tablets on the in-vivo bioavailability parameters after oral administration.

Methods

Compare in-vitro dissolution testing in the recommended media to evaluate in-vivo bioequivalence outcomes for the Biopharmaceutics Classification System Class II weak acidic drugs. Nine Beagle dogs received a single oral administration of each formulation (7.5 mg) in a three-way crossover design.

Key findings

The dissolution of meloxicam from both test products showed marked differences with that from the reference tablet in pH 1.0, 4.5 and 6.8 media at 50 or 75 rpm. Both formulations exhibiting slow or fast dissolution were then compared with the reference product for in-vivo bioequivalence study. Both products were bioequivalent with the reference tablet in either extent or rate of oral absorption. It indicated that the dissolution profiles which discriminated between the formulations in vitro did not accurately predict the in-vivo bioequivalence outcomes.

Conclusions

Comparative dissolution profiles using similarity factor (f2) in the recommended media should be relaxed to fulfil the requirements for the development, scale-up and postapproval changes to immediate release oral solid dosage forms of meloxicam.
Transport of valine across the small intestinal epithelium in pigs fed different valine levels and Bacillus subtilis
Authors: Blaabjerg K. , Nørgaard J. V. , Nielsen B. , Cantor M. D. , Derkx P. , Sehested J. , Poulsen H. D.
Published: November 2017

Mutants of Bacillus subtilis overproducing valine (B. subtilis VAL) could be an approach to supply pigs dietary valine (Val). In the study, 18 gilts were fed: (i) negative diet with a standardized ileal digestible (SID) Val:Lys of 0.63:1 (Neg); (ii) Neg added B. subtilis VAL (1.28 × 1011 cfu/kg as‐fed) or; (iii) Neg added L‐Val to a Val:Lys of 0.69:1. Using the Ussing chamber method, the study aimed to investigate whether (i) the diets affect intestinal transport of additions of 0, 5, 10 or 20 mmol Val/L from the mucosal to the serosal side and (ii) the B. subtilis VAL contributes to a net transport of Val produced in situ. The results showed that the Isc (ΔIscVal) and release of Val to the serosal side solution (Srel; μmol cm−2 min−1) increased with Val addition (linear and quadratic, p < .0001) but was similar for 5, 10 or 20 mmol Val/L and not affected by diet. No net transport of in situ produced Val by B. subtilis VAL was detected. In conclusion, feeding a Val‐deficient diet with or without B. subtilis VAL or a Val sufficient diet did not affect the Val transport across intestinal epithelia. No in situ Val production by B. subtilis VAL was observed in the Ussing chambers.
Quality of life in adolescents with hepatitis C treated with sofosbuvir and ribavirin
Authors: Younossi Z. M. , Stepanova M. , Schwarz K. B. , Wirth S. , Rosenthal P. , Gonzalez‐Peralta R. , Murray K. , Henry L. , Hunt S.
Published: November 2017

Chronic HCV infection has been associated with impairment of HRQL in both adults and paediatric patients. Our aim was to assess the HRQL of HCV‐positive children treated with SOF + RBV. The data for this post hoc analysis were collected in a phase 2 open‐label multinational study that evaluated safety and efficacy of SOF (400 mg/day) plus RBV (weight‐based up to 1400 mg/day) for 12 or 24 weeks in adolescents with chronic HCV (GS‐US‐334‐1112). Patients and their parents/guardians completed the PedsQL‐4.0‐SF‐15 questionnaire at baseline, at the end of treatment and in post‐treatment follow‐up. We included 50 adolescents with HCV genotype 2 and 3 without cirrhosis (14.8 ± 1.9 years; male: 58%; treatment‐naïve: 82%; vertically transmitted HCV: 70%). After treatment, 100% of patients with HCV genotype 2 and 95% with genotype 3 achieved SVR‐12. During treatment with SOF + RBV, there were no significant decrements in any of patients’ self‐reported or parent‐proxy‐reported PRO scores regardless of treatment duration (all P > .05). After treatment cessation, we recorded a statistically significant improvement in patients’ self‐reported Social Functioning score by post‐treatment week 12: on average, +4.8 points on a 0‐100 scale (P = .02). By post‐treatment week 24, parent‐proxy‐reported School Functioning score increased by, on average, +13.0 points (P = .0065). In multivariate analysis, history of abdominal pain and psychiatric disorders were predictive of impaired HRQL in adolescents with HCV (P < .05). Adolescents with HCV do not seem to experience any HRQL decrement during treatment with SOF + RBV and experience some improvement of their HRQL scores after achieving SVR.
A direct role for hepatitis B virus X protein in inducing mitochondrial membrane permeabilization
Authors: Lee H‐R. , Cho Y. Y. , Lee G. Y. , You D‐g. , Yoo Y. D. , Kim Y. J.
Published: November 2017

Hepatitis B virus X protein (HBx) acts as a multifunctional protein that regulates intracellular signalling pathways during HBV infection. It has mainly been studied in terms of its interaction with cellular proteins. Here, we show that HBx induces membrane permeabilization independently of the mitochondrial permeability transition pore complex. We generated mitochondrial outer membrane‐mimic liposomes to observe the direct effects of HBx on membranes. We found that HBx induced membrane permeabilization, and the region comprising the transmembrane domain and the mitochondrial‐targeting sequence was sufficient for this process. Membrane permeabilization was inhibited by nonselective channel blockers or by N‐(n‐nonyl)deoxynojirimycin (NN‐DNJ), a viroporin inhibitor. Moreover, NN‐DNJ inhibited HBx‐induced mitochondrial depolarization in Huh‐7 cells. Based on the results of this study, we can postulate that the HBx protein itself is sufficient to induce mitochondrial membrane permeabilization. Our finding provides important information for a strategy of HBx targeting during HBV treatment.
Great and rapid HBsAg decline in patients with on‐treatment hepatitis flare in early phase of potent antiviral therapy
Authors: Jeng W.‐J. , Chen Y.‐C. , Liaw Y.‐F.
Published: November 2017

HBsAg decline during nucleos(t)ide analogue therapy in chronic hepatitis B with lower pretherapy ALT is usually small and slow. This study aimed to investigate why ~10% of such patients showed “rapid HBsAg decline” ≥0.5 log10 IU/mL by month 6 of therapy. Patients with persistent pretherapy ALT <5X ULN who had qHBsAg at baseline, months 6 and 12 of entecavir or tenofovir therapy were studied. “On‐treatment ALT elevation” was defined as >10% increase above baseline to >2X ULN during first 6 months of therapy. Of the 256 patients treated, 51 experienced transient “on‐treatment ALT elevation” [group A], including 30 (11.7%) with ALT elevation to 2‐5X ULN [group A‐1] and 21 (8.2%) flared to >5X ULN [group A‐2]. The magnitude of qHBsAg decline and rate of “rapid HBsAg decline” by month 6 was significantly greater and more frequent in group A (−0.446 vs −0.042 log10 IU/mL; 45.1 vs 8.8%, respectively, P = 0.000) than in the remaining 205 patients without on‐treatment ALT elevation (group B), being greatest in patients with hepatitis flare (group A‐2: −0.559 log10 IU/mL and 57.1%, respectively). In patients with therapy ≥2 years, patients with “on‐treatment ALT elevation” also showed significantly greater annual HBsAg decline, more frequent to <100 IU/mL and 4 times higher HBsAg seroclearance rate. “On‐treatment ALT elevation,” especially flare >5X ULN, during entecavir therapy or tenofovir therapy may enhance/accelerate HBsAg decline, suggesting the effect of immune restoration upon potent viral suppression.
Improved performance of quantitative collagen parameters versus standard histology in longitudinal assessment of nonadvanced liver fibrosis for chronic hepatitis B
Authors: Wang Y. , Liang X. , Yang J. , Wang H. , Tan D. , Chen S. , Cheng J. , Chen Y. , Sun J. , Rong F. , Yang W. , Liu H. , Liu Z. , Zheng Y. , Liang J. , Li S. , Liu Z. , Hou J.
Published: November 2017

Monitoring longitudinal nonadvanced fibrosis is a more common scenario in management of chronic hepatitis B (CHB), for which, however, current evaluation methods generally lack sufficient performance. We conducted a proof‐of‐concept study to evaluate the performance of quantitative fibrous collagen parameters (q‐FP) in the assessment. Data sets from a prior CHB trial (NCT00962533) with mostly mild‐to‐moderate fibrosis participants were used for this study. 301 subjects with paired liver biopsies were consecutively included. Of these, 139 subjects were used to establish the test and the rest for internal validation. Fibrosis change between baseline and week 104 of treatment was blindly assessed with q‐FP and was compared with Ishak fibrosis staging. There were 70% and 93% subjects with Ishak F0‐2 at baseline and week 104, respectively. For the test of the subjects, q‐FP and Ishak staging showed no difference in determining the incidence of fibrosis regression (68% vs 67%; difference = 0.7%, P = 1.00). Q‐FP demonstrated that the regression was independently associated with the antiviral efficacy endpoint (OR 3.0, 95% CI 1.4‐6.5, P = .005), but Ishak failed the detection (OR 0.6, 95% CI 0.3‐1.3, P = .24). Moreover, q‐FP directly revealed a higher fibrosis‐resistance to antiviral treatment in virus genotypes C vs B and in males vs females. These results were confirmed in the validation subjects. Additionally, a functional model built on the test subjects showed an accuracy of 82% in stratifying fibrosis reversibility of the validation subjects. In conclusion, q‐FP could have improved efficiency and accuracy in the longitudinal assessment of mild‐to‐moderate CHB fibrosis, indicating a potential alternative to current evaluation methodologies.
The Role of Emotion in Land Regulation: An Empirical Study of Online Advocacy in Authoritarian Asia
Authors: Gillespie John
Published: November 2017

Scholarly interest about online advocacy in authoritarian settings is rapidly growing. With one of Asia's most active social media, Vietnam offers a promising site to investigate how online advocates navigate around state censorship to influence regulatory decisionmaking. Much research about online advocacy focuses on rational discourse, and fails to ask why satire and ridicule can change regulatory outcomes when reasoned debate fails. This article considers two cases studies where online advocates changed regulatory outcomes in Vietnam. It investigates why the regulators were sensitive to moral censure in social media, and responded to appeals for solidarity, but were reluctant to engage in rational public deliberation. These findings reveal insights into how online advocacy can trigger emotional responses in officials that transform the regulatory environment. The article concludes that rather than constituting cognitive missteps, emotions are integral to government regulation in Vietnam.
Systematic review and meta‐analysis of algorithms used to identify drug‐induced liver injury (DILI) in health record databases
Authors: Tan Eng Hooi , Low En Xian Sarah , Dan Yock Young , Tai Bee Choo
Published: November 2017

Background & Aims

Drug induced liver injury (DILI) is largely underreported, leading to underestimation of its burden. Electronic detection of DILI in healthcare databases shows promise to overcome the issues of spontaneous reporting. The performance of detection algorithms may vary because of inconsistent DILI definition and detection criteria. We performed a systematic review and meta‐analysis to identify the DILI detection criteria used in health record databases and determine the performance characteristics of the detection algorithms.

Methods

We searched PubMed, EMBASE and Scopus for studies that utilized laboratory threshold criteria to identify DILI cases. Validation studies were included in the meta‐analysis. Data were abstracted using standardized forms and quality was assessed using modified Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS‐2) criteria. We evaluate the performance characteristics of the detection algorithm by obtaining the pooled estimate of the positive predictive value (PPV) assuming a random effects model.

Results

A total of 29 studies met the inclusion criteria for the systematic review; 25 of these studies (n = 35 948) had PPV estimates for performing the meta‐analysis. The PPV of DILI detection algorithms was low, ranging from 1.0% to 40.2%, with a pooled estimate of 14.6% (95% CI 10.7‐18.9). Algorithms that performed better had prespecified exclusion diagnoses as well as drugs of interest to minimize false positives.

Conclusion

Algorithm performance varied with different case definitions of DILI attributed to different laboratory threshold criteria, diagnosis codes, and study drugs.
Loss of dendritic connectivity in southern California's urban riverscape facilitates decline of an endemic freshwater fish
Authors: Richmond Jonathan Q. , Backlin Adam R. , Galst‐Cavalcante Carey , O'Brien John W. , Fisher Robert N.
Published: November 2017

Life history adaptations and spatial configuration of metapopulation networks allow certain species to persist in extreme fluctuating environments, yet long‐term stability within these systems relies on the maintenance of linkage habitat. Degradation of such linkages in urban riverscapes can disrupt this dynamic in aquatic species, leading to increased extinction debt in local populations experiencing environment‐related demographic flux. We used microsatellites and mtDNA to examine the effects of collapsed network structure in the endemic Santa Ana sucker Catostomus santaanae of southern California, a threatened species affected by natural flood–drought cycles, “boom‐and‐bust” demography, hybridization and presumed artificial transplantation. Our results show a predominance of drift‐mediated processes in shaping population structure and that reverse mechanisms for counterbalancing the genetic effects of these phenomena have dissipated with the collapse of dendritic connectivity. We use approximate Bayesian models to support two cases of artificial transplantation and provide evidence that one of the invaded systems better represents the historic processes that maintained genetic variation within watersheds than any remaining drainages where C. santaanae is considered native. We further show that a stable dry gap in the northern range is preventing genetic dilution of pure C. santaanae persisting upstream of a hybrid assemblage involving a non‐native sucker and that local accumulation of genetic variation in the same drainage is influenced by position within the network. This work has important implications for declining species that have historically relied on dendritic metapopulation networks to maintain source–sink dynamics in phasic environments, but no longer possess this capacity in urban‐converted landscapes.