bluuebunny/crossref_metadata_2025 huggingface dataset:
Surgical and Pathological Changes after Radiofrequency Ablation of Thyroid Nodules
Authors: Dobrinja Chiara , Bernardi Stella , Fabris Bruno , Eramo Rita , Makovac Petra , Bazzocchi Gabriele , Piscopello Lanfranco , Barro Enrica , de Manzini Nicolò , Bonazza Deborah , Pinamonti Maurizio , Zanconati Fabrizio , Stacul Fulvio
Published: July 2015

Background. Radiofrequency ablation (RFA) has been recently advocated as an effective technique for the treatment of symptomatic benign thyroid nodules. It is not known to what extent it may affect any subsequent thyroid surgery and/or histological diagnosis.Materials and Methods. RFA was performed on 64 symptomatic Thy2 nodules (benign nodules) and 6 symptomatic Thy3 nodules (follicular lesions/follicular neoplasms). Two Thy3 nodules regrew after the procedure, and these patients accepted to undergo a total thyroidectomy. Here we present how RFA has affected the operation and the final pathological features of the surgically removed nodules.Results and Conclusions. RFA is effective for the treatment of Thy2 nodules, but it should not be recommended as first-line therapy for the treatment of Thy3 nodules (irrespective of their mutational status), as it delays surgery in case of malignancy. Moreover, it is unknown whether RFA might promote residual tumor progression or neoplastic progression of Thy3 lesions. Nevertheless, here we show for the first time that one session of RFA does not affect subsequent thyroid surgery and/or histological diagnosis.
Right-to-Left Shunt Does Not Increase the Incidence of Silent Lacunar Infarcts in Patients with Migraine
Authors: Du Wei , Wu Xiujuan , Xing Yingqi , Geng Yunlong , Bai Jing , Song Xiaonan
Published: July 2015

Right-to-left shunt (RLS) is associated with cryptogenic stroke and migraine. Herein we investigated the relationship between RLS and silent lacunar infarcts in patients with migraine. A total of 263 patients with migraine who met eligibility criteria were enrolled from January 2010 to December 2011, among which 127 subjects fell into RLS group. Baseline demographics were comparable between RLS and non-RLS groups (P>0.05). The incidence of silent lacunar infarcts in RLS group was not significantly different from that of the non-RLS group (25.2% versus 21.3%,P>0.05). Furthermore, we found that the incidence of silent lacunar infarcts in permanent and latent RLS subgroups was comparable with non-shunt RLS subgroup (28.6% versus 24% versus 21.3%,P>0.05). Similarly, the incidence of silent lacunar infarcts in the non-RLS group, mild-shunt group, and large-shunt group was also comparable (21.3% versus 23.8% versus 29.3%,P>0.05). In addition, RLS did not increase the incidence of silent lacunar infarcts in migraine patients with elder age (<50 years age group: 15.8% versus 17.9%; ≥50 years age group: 53.1% versus 37.5%, bothP>0.05). In conclusion, RLS does not increase the incidence of silent lacunar infarcts in patients with migraine. Further prospective studies are warranted to validate this finding.
Improving Breakdown Voltage for a Novel SOI LDMOS with a Lateral Variable Doping Profile on the Top Interface of the Buried Oxide Layer
Authors: Jin Jingjing , Hu Shengdong , Chen Yinhui , Tan Kaizhou , Luo Jun , Zhou Feng , Chen Zongze , Huang Ye
Published: July 2015

In order to achieve a high breakdown voltage (BV) for the SOI (Silicon-On-Insulator) power device in high voltage ICs, a novel high voltage n-channel lateral double-diffused MOS (LDMOS) with a lateral variable interface doping profile (LVID) placed at the interface between the SOI layer and the buried-oxide (BOX) layer (LVID SOI) is researched. Its breakdown mechanism is investigated theoretically, and its structure parameters are optimized and analyzed by 2D simulation software MEDICI. In the high voltage blocking state, the high concentration ionized donors in the depleted LVID make the surface electric field of SOI layer (ES) more uniform and enhance the electric field of BOX layer (EI), which can prevent the lateral premature breakdown and result in a higher BV. Compared with the conventional uniformly doped (UD) SOI LDMOS,EIof the optimized LVID SOI LDMOS is enhanced by 79% from 119 V/μm to 213 V/μm, and BV is increased by 33.4% from 169 V to 227 V. Simulations indicate that the method of LVID profile can significantly improve breakdown voltage for the SOI LDMOS.
Referral Practices for Cognitive Behavioral Therapy for Insomnia: A Survey Study
Authors: Conroy Deirdre A. , Ebben Matthew R.
Published: July 2015

This study examined referring practices for cognitive behavioral therapy for insomnia (CBTI) by physicians at University of Michigan Hospitals and Weill Cornell Medical College of Cornell University. A five-item questionnaire was sent via email that inquired about the physician’s patient load, number of patients complaining of insomnia, percent referred for CBTI, and impressions of what is the most effective method for improving sleep quality in their patients with insomnia. The questionnaire was completed by 239 physicians. More physicians believed a treatment other than CBTI and/or medication was most effective (N= 83). “Sleep hygiene” was recommended by a third of the sample. The smallest number of physicians felt that CBTI alone was the most effective treatment (N= 22). Additional physician education is needed.
Mathematical Modeling of Dual Intake Transparent Transpired Solar Collector
Authors: Semenou Thomas , Rousse Daniel R. , Le Lostec Brice , Nouanegue Hervé F. , Paradis Pierre-Luc
Published: July 2015

Nowadays, in several types of commercial or institutional buildings, a significant rise of transpired solar collectors used to preheat the fresh air of the building can be observed. Nevertheless, when the air mass flow rate is low, the collector efficiency collapses and a large amount of energy remains unused. This paper presents a simple yet effective mathematical model of a transparent transpired solar collector (TTC) with dual intake in order to remove stagnation problems in the plenum and ensure a better thermal efficiency and more heat recovery. A thermal model and a pressure loss model were developed. Then, the combined model was validated with experimental data from the Solar Rating and Certification Corporation (SRCC). The results show that the collector efficiency can be up to 70% and even 80% regardless of operating conditions. The temperature gain is able to reach 20°K when the solar irradiation is high.
Cattle Uterus: A Novel Animal Laboratory Model for Advanced Hysteroscopic Surgery Training
Authors: Ewies Ayman A. A. , Khan Zahid R.
Published: July 2015

In recent years, due to reduced training opportunities, the major shift in surgical training is towards the use of simulation and animal laboratories. Despite the merits of Virtual Reality Simulators, they are far from representing the real challenges encountered in theatres. We introduce the “Cattle Uterus Model” in the hope that it will be adopted in training courses as a low cost and easy-to-set-up tool. It adds new dimensions to the advanced hysteroscopic surgery training experience by providing tactile sensation and simulating intraoperative difficulties. It complements conventional surgical training, aiming to maximise clinical exposure and minimise patients’ harm.
Multivariate Quantitative Multifactor Dimensionality Reduction for Detecting Gene-Gene Interactions
Authors: Yu Wenbao , Kwon Min-Seok , Park Taesung
Published: July 2015

Objectives: To determine gene-gene interactions and missing heritability of complex diseases is a challenging topic in genome-wide association studies. The multifactor dimensionality reduction (MDR) method is one of the most commonly used methods for identifying gene-gene interactions with dichotomous phenotypes. For quantitative phenotypes, the generalized MDR or quantitative MDR (QMDR) methods have been proposed. These methods are known as univariate methods because they consider only one phenotype. To date, there are few methods for analyzing multiple phenotypes. Methods: To address this problem, we propose a multivariate QMDR method (Multi-QMDR) for multivariate correlated phenotypes. We summarize the multivariate phenotypes into a univariate score by dimensional reduction analysis, and then classify the samples accordingly into high-risk and low-risk groups. We use different ways of summarizing mainly based on the principal components. Multi-QMDR is model-free and easy to implement. Results: Multi-QMDR is applied to lipid-related traits. The properties of Multi- QMDR were investigated through simulation studies. Empirical studies show that Multi-QMDR outperforms existing univariate and multivariate methods at identifying causal interactions. Conclusions: The Multi-QMDR approach improves the performance of QMDR when multiple quantitative phenotypes are available.
Model-Based Multifactor Dimensionality Reduction for Rare Variant Association Analysis
Authors: Fouladi Ramouna , Bessonov Kyrylo , Van Lishout François , Van Steen Kristel
Published: July 2015

Genome-wide association studies have revealed a vast amount of common loci associated to human complex diseases. Still, a large proportion of heritability remains unexplained. The extent to which rare genetic variants (RVs) are able to explain a relevant portion of the genetic heritability for complex traits leaves room for several debates and paves the way to the collection of RV databases and the development of novel analytic tools to analyze these. To date, several statistical methods have been proposed to uncover the association of RVs with complex diseases, but none of them is the clear winner in all possible scenarios of study design and assumed underlying disease model. The latter may involve differences in the distributions of effect sizes, proportions of causal variants, and ratios of protective to deleterious variants at distinct regions throughout the genome. Therefore, there is a need for robust scalable methods with acceptable overall performance in terms of power and type I error under various realistic scenarios. In this paper, we propose a novel RV association analysis strategy, which satisfies several of the desired properties that a RV analysis tool should exhibit.
Mendelian Randomization versus Path Models: Making Causal Inferences in Genetic Epidemiology
Authors: Ziegler Andreas , Mwambi Henry , König Inke R.
Published: July 2015

Objective: The term Mendelian randomization is popular in the current literature. The first aim of this work is to describe the idea of Mendelian randomization studies and the assumptions required for drawing valid conclusions. The second aim is to contrast Mendelian randomization and path modeling when different ‘omics' levels are considered jointly. Methods: We define Mendelian randomization as introduced by Katan in 1986, and review its crucial assumptions. We introduce path models as the relevant additional component to the current use of Mendelian randomization studies in ‘omics'. Real data examples for the association between lipid levels and coronary artery disease illustrate the use of path models. Results: Numerous assumptions underlie Mendelian randomization, and they are difficult to be fulfilled in applications. Path models are suitable for investigating causality, and they should not be mixed up with the term Mendelian randomization. In many applications, path modeling would be the appropriate analysis in addition to a simple Mendelian randomization analysis. Conclusions: Mendelian randomization and path models use different concepts for causal inference. Path modeling but not simple Mendelian randomization analysis is well suited to study causality with different levels of ‘omics' data.
Susceptibility-Weighted MRI for Deep Brain Stimulation: Potentials in Trajectory Planning
Authors: Hertel Frank , Husch Andreas , Dooms Georges , Bernard Florian , Gemmar Peter
Published: July 2015

Background: Deep brain stimulation (DBS) trajectory planning is mostly based on standard 3-D T1-weighted gadolinium-enhanced MRI sequences (T1-Gd). Susceptibility-weighted MRI sequences (SWI) show neurovascular structures without the use of contrast agents. The aim of this study was to investigate whether SWI might be useful in DBS trajectory planning. Methods: We performed bilateral DBS planning using conventional T1-Gd images of 10 patients with different kinds of movement disorders. Afterwards, we matched SWI sequences and compared the visibility of vascular structures in both imaging modalities. Results: By analyzing 100 possible trajectories, we found a potential vascular conflict in 13 trajectories based on T1-Gd in contrast to 53 in SWI. Remarkably, all vessels visible in T1-Gd were also depicted in SWI, whereas SWI showed many additional vascular structures which could not be identified in T1-Gd. Conclusion/Discussion: The sensitivity for detecting neurovascular structures for DBS planning seems to be significantly higher in SWI. As SWI does not require a contrast agent, we suggest that SWI may be a valuable alternative to T1-Gd MRI for DBS trajectory planning. Furthermore, the data analysis suggests that vascular interactions of DBS trajectories might be more frequent than expected from the very low incidence of symptomatic bleedings. The explanation for this is currently the subject of debate and merits further studies.
A Recombinant Sal k 1 Isoform as an Alternative to the Polymorphic Allergen from Salsola kali Pollen for Allergy Diagnosis
Authors: Mas Salvador , Boissy Patrice , Monsalve Rafael I. , Cuesta-Herranz Javier , Díaz-Perales Araceli , Fernández Javier , Colás Carlos , Rodríguez Rosalía , Barderas Rodrigo , Villalba Mayte
Published: July 2015

Background: The incidence of Amaranthaceae pollen allergy has increased due to the desertification occurring in many countries. In some regions of Spain, Salsola kali is the main cause of pollinosis, at almost the same level as olive and grass pollen. Sal k 1 - the sensitization marker of S. kali pollinosis - is used in clinical diagnosis, but is purified at a low yield from pollen. We aimed to produce a recombinant (r)Sal k 1 able to span the structural and immunological properties of the natural isoforms from pollen, and validate its potential use for diagnosis. Methods: Specific cDNA was amplified by PCR, cloned into the pET41b vector and used to transform BL21 (DE3) Escherichia coli cells. Immunoblotting, ELISA, basophil activation and skin-prick tests were used to validate the recombinant protein against Sal k 1 isolated from pollen. Sera and blood cells from S. kali pollen-sensitized patients and specific monoclonal and polyclonal antisera were used. Results: rSal k 1 was produced in bacteria with a yield of 7.5 mg/l of cell culture. The protein was purified to homogeneity and structural and immunologically validated against the natural form. rSal k 1 exhibited a higher IgE cross-reactivity with plant-derived food extracts such as peanut, almond or tomato than with pollen sources such as Platanus acerifolia and Oleaceae members. Conclusions: rSal k 1 expressed in bacteria retains intact structural and immunological properties in comparison to the pollen-derived allergen. It spans the immunological properties of most of the isoforms found in pollen, and it might substitute natural Sal k 1 in clinical diagnosis.
Off-Hour Admission and Outcomes in Patients with Acute Intracerebral Hemorrhage in the INTERACT2 Trial
Authors: Sato Shoichiro , Arima Hisatomi , Heeley Emma , Hirakawa Yoichiro , Delcourt Candice , Lindley Richard I. , Robinson Thompson , Huang Yining , Morgenstern Lewis , Stapf Christian , Wang Jiguang , Chalmers John , Anderson Craig S. ,   for the INTERACT2 Investigators
Published: July 2015

Background: Conflicting data exist of an association between off-hour (weekend, holiday, or night-time) hospital admission and adverse outcome in intracerebral hemorrhage (ICH). We determined the association between off-hour admissions and poor clinical outcome, and of any differential effect of early intensive blood pressure (BP) lowering treatment between off- and on-hour admissions, among participants of the Intensive BP Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2). Methods: Subsidiary analysis of INTERACT2, a multinational, multicenter, clinical trial of patients with spontaneous ICH with elevated systolic BP, randomly assigned to intensive (target systolic BP <140 mm Hg) or guideline-based (<180 mm Hg) BP management. Primary outcome was death or major disability (modified Rankin scale of 3-6) at 90 days. Off-hour admission was defined as night-time (4:30 p.m. to 8:30 a.m.) on weekdays, weekends (Saturday and Sunday), and public holidays in each participating country. Results: Of 2,794 patients with information on the primary outcome, 1,770 (63%) were admitted to study centers during off-hours. Off-hour admission was not associated with risk of poor outcome at 90 days (53% off-hour vs. 55% on-hour; p = 0.49), even after adjustment for comorbid risk factors (odds ratio 0.92; 95% CI 0.76-1.12). Consistency exists in the effects of intensive BP lowering between off- and on-hour admission (p = 0.85 for homogeneity). Conclusions: Off-hour admission was not associated with increased risks of death or major disability among trial protocol participants with acute ICH. Intensive BP lowering can provide similar treatment effect irrespective of admission hours.
The Basophil Activation Test: A Sensitive Test in the Diagnosis of Allergic Immediate Hypersensitivity to Pristinamycin
Authors: Viel Sébastien , Garnier Lorna , Joly Elodie , Rouzaire Paul , Nosbaum Audrey , Pralong Pauline , Faudel Amélie , Rioufol Catherine , Bienvenu Françoise , Bienvenu Jacques , Berard Frédéric
Published: July 2015

Immediate hypersensitivity (IHS) reactions to macrolides and to macrolide-derived antibiotics like pristinamycin are uncommon. In this context, there is little data available to appreciate the true value of biological tools regarding the diagnosis of immediate allergy to pristinamycin. Here we assess the clinical usefulness of the basophil activation test (BAT) to differentiate allergic from nonallergic IHS to pristinamycin. Thirty-six patients were tested with skin tests as the gold standard and BAT. The BAT achieved a sensitivity of 76% and a specificity of 100%, implying an absence of false positive results. Multicenter studies remain to be performed to better define the sensitivity, specificity and interlaboratory variation of BAT in the diagnosis of allergy to pristinamycin and macrolides.
Progressive Multiple Cavernous Angiomas after Radiotherapy in a Pediatric Patient with Medulloblastoma: A Case Report
Authors: Chai Yong-Hyun , Jung Tae-Young , Lee Kyung-Hwa , Kim Seul-Kee
Published: July 2015

Background: We report a case of progressive multiple cavernous angiomas. Patient and Method: A 16-year-old boy presented with a 2-month history of headache and dizziness. Six years earlier, he underwent surgery for cerebellar medulloblastoma and subsequent chemoradiotherapy according to the M-051 protocol of the Korean Society of Pediatric Neuro-Oncology. Follow-up brain magnetic resonance imaging (MRI) revealed a tiny hemorrhage on the cerebellum 3 months after 23.4-Gy craniospinal and 32.4-Gy boost radiotherapy. Result: The multiple hemorrhagic lesions had progressively developed on the whole brain without any symptoms for 6 years. On admission, MRI revealed a 1.5-cm enlarged mass with subacute hemorrhage on the right frontal area. The mass was totally removed and diagnosed as cavernous angioma. However, 5 months later, the patient complained of a headache. MRI revealed 1.4- and 0.7-cm enlarged masses on the left frontal and right temporal areas with internal hemorrhage, respectively. The left frontal mass was totally removed, and the histopathological finding was suggestive of cavernous angioma. Conclusion: This case showed early-developed multiple hemorrhagic lesions after radiotherapy, which had been progressive and were associated with some symptomatic cavernous angiomas. Pediatric patients with brain radiotherapy should undergo radiological check-up to identify vascular lesions, especially symptomatic patients.
Inhibitory Effect of Apigenin on Pharmacokinetics of Venlafaxine in vivo and in vitro
Authors: Zhan Yun-yun , Liang Bing-qing , Gu Er-min , Hu Xiao-xia , Lin Dan , Hu Guo-xin , Zheng Zhi-qiang
Published: July 2015

Objective: This study was conducted to investigate the effects of orally administered apigenin on the pharmacokinetics of venlafaxine (VEN) in rats and on the metabolism of VEN in human and rat liver microsomes in vitro. Methods: Ten healthy male SD rats were randomly divided into 2 groups: A group (control group), B group (a single dose of 250 mg/kg apigenin). A single dose of 20 mg/kg VEN was administered orally 30 min after administration of apigenin (250 mg/kg). VEN plasma levels were measured by HPLC with fluorescence detection, and pharmacokinetic parameters were calculated by DAS 3.0 software. Results: The single dose of 250 mg/kg apigenin significantly increased the AUC0-t of VEN by 40.9% (p < 0.05) and obviously increased the peak plasma concentration (Cmax) of VEN (p < 0.05). Furthermore, apigenin showed inhibitory effect on human and rat microsomes and the IC50 of apigenin was 58.37 and 25.73 μmol/l, respectively. Conclusions: Our results indicated that an intake of apigenin could increase VEN plasma levels and some of its pharmacokinetic parameters (AUC, Tmax). Thus, more attention should be paid when VEN was administrated combined with apigenin.
Inhibition of Kv7/M Channel Currents by the Local Anesthetic Chloroprocaine
Authors: Zhang Fan , Cheng Yanxin , Li Hong , Jia Qingzhong , Zhang Hailin , Zhao Senming
Published: July 2015

Background: Chloroprocaine is a local ester anesthetic, producing excellent sensory block in clinical use. The Kv7/M potassium channel plays an important role in the control of neuronal excitability. In this study, we investigated the effects of the local anesthetic chloroprocaine on Kv7/M channels as well as the effect of retigabine on chloroprocaine-induced seizures. Methods: A perforated whole-cell patch technique was used to record Kv7 currents from HEK293 cells and M-type currents from rat dorsal root ganglion (DRG) neurons. Results: Chloroprocaine produced a number of effects on Kv7.2/Kv7.3 currents, including a lowering of current amplitudes, a rightward shift in the voltage-dependent activation curves, and a slowing of channel activation. Chloroprocaine had a more selective inhibitory effect on the homomeric Kv7.3 and heteromeric Kv7.2/Kv7.3 channels than on the homomeric Kv7.2 channel. Chloroprocaine also inhibited native M channel currents and induced a depolarization of the DRG neuron membrane potential. Conclusion: Taken together, the findings indicate that chloroprocaine concentration dependently inhibited Kv7/M channel currents.
Validation of Diagnoses of Transient Ischemic Attack in the Swedish Stroke Register (Riksstroke) TIA-Module
Authors: Buchwald Fredrik , Ström Jakob O. , Norrving Bo , Petersson Jesper
Published: July 2015

Background: In 2010, the Swedish Stroke Register (Riksstroke; RS) established a module for transient ischemic attacks (RS-TIA). We report a diagnostic validation study of patients included in RS-TIA. Methods: During the first year, 7,825 patients were registered at 59 out of 74 Swedish hospitals. A time-based TIA definition was applied. A sample of 180 patients (30 patients each from 6 hospitals), with a similar distribution of age and sex as in RS-TIA, was prepared. Two independent observers assessed medical records for quality of documentation and assigned a diagnosis of likely, possible, unlikely TIA or ischemic stroke, according to prespecified criteria. Results: The 2 observers agreed in 77% of cases that the event was a likely or possible TIA, in 3% that the event was an ischemic stroke, and in 2% that the event was an unlikely TIA. The observers disagreed in 8% of patients on TIA vs. ischemic stroke, and in 11% on a vascular vs. non-vascular cause. Quality of documentation was fair. Conclusions: There was interobserver agreement on diagnosis of TIA in the majority of patients included in RS-TIA. Diagnostic accuracy may be further improved by more systematic documentation of symptoms and signs.
Subclinical Thyroid Dysfunction and Depressive Symptoms among the Elderly: A Prospective Cohort Study
Authors: Blum Manuel R. , Wijsman Liselotte W. , Virgini Vanessa S. , Bauer Douglas C. , den Elzen Wendy P.J. , Jukema J. Wouter , Buckley Brendan M. , de Craen Anton J.M. , Kearney Patricia M. , Stott David J. , Gussekloo Jacobjin , Westendorp Rudi G.J. , Mooijaart Simon P. , Rodondi Nicolas ,   on behalf of the PROSPER study group
Published: July 2015

Background: Subclinical hypothyroidism has been associated with depressive symptoms in cross-sectional studies, but prospective data and data on subclinical hyperthyroidism are scarce. Methods: In the Leiden substudy of the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER), thyroid-stimulating hormone and free T4 levels were measured at baseline and repeated after 6 months in adults aged 70-82 years with preexisting cardiovascular disease or known cardiovascular risk factors to define persistent thyroid functional status. Main outcome measures were depressive symptoms, assessed with the Geriatric Depression Scale 15 (GDS-15) at baseline and after 3 years. All analyses were adjusted for age, gender and education. Results: In 606 participants (41% women; mean age 75 years) without antidepressant medication, GDS-15 scores at baseline did not differ for participants with subclinical hypothyroidism (n = 47; GDS-15 score 1.75, 95% CI 1.29-2.20, p = 0.53) or subclinical hyperthyroidism (n = 13; GDS-15 score 1.64, 95% CI 0.78-2.51, p = 0.96) compared to euthyroid participants (n = 546; mean GDS-15 score 1.60, 95% CI 1.46-1.73). After 3 years, compared to the euthyroid participants, changes in GDS-15 scores did not differ for participants with subclinical hypothyroidism (ΔGDS-15 score -0.03, 95% CI -0.50 to 0.44, p = 0.83), while subclinical hyperthyroidism was associated with an increase in GDS scores (ΔGDS-15 score 1.13, 95% CI 0.32-1.93, p = 0.04). All results were similar for persistent subclinical thyroid dysfunction. Conclusions: In this largest prospective study on the association of persistent subclinical thyroid dysfunction and depression, subclinical hypothyroidism was not associated with increased depressive symptoms among older adults at high cardiovascular risk. Persistent subclinical hyperthyroidism might be associated with increased depressive symptoms, which requires confirmation in a larger prospective study.
Acute Kidney Injury Facilitates Hypocalcemia by Exacerbating the Hyperphosphatemic Effect of Muscle Damage in Rhabdomyolysis
Authors: Higaki Masato , Tanemoto Masayuki , Shiraishi Takeshi , Taniguchi Kei , Fujigaki Yoshihide , Uchida Shunya
Published: July 2015

Background/Aims: Hypocalcemia is an important complication of rhabdomyolysis for which several pathogenic factors, including acute kidney injury (AKI), have been proposed. To gain insight regarding the hypocalcemic roles of AKI in rhabdomyolysis, we retrospectively examined patients with rhabdomyolysis. Methods: Of 28,387 patients admitted to the Department of Internal Medicine, 51 patients met the inclusion criteria for the study. Serum calcium was analyzed based on laboratory data including indicators of AKI, serum creatine kinase (CK) and serum inorganic phosphate (iP). Results: Twenty-two patients (43%) had hypocalcemia. Compared with patients without hypocalcemia, they had a higher prevalence of AKI (82 vs. 55%; p = 0.046), higher levels of peak CK (39,100 ± 50,600 vs. 9,800 ± 11,900 IU/l; p = 0.003) and higher levels of peak iP (1.77 ± 1.10 vs. 1.10 ± 0.35 mmol/l; p = 0.007). Indicators of AKI were correlated with peak CK and peak iP and were not significant variables in the regression analysis for hypocalcemia. Peak CK and peak iP were not correlated with each other. Impaired phosphate use by muscle contributed to the increased iP. Conclusion: These findings indicate that muscle damage is the primary hypocalcemic factor in rhabdomyolysis. AKI facilitated hypocalcemia by exacerbating the hyperphosphatemic effects of muscle damage. Aggressive hydration, which could increase oxygen supply and subsequently repair phosphate use in muscle, might reduce the incidence of hypocalcemia in rhabdomyolysis.
Adrenergic Repression of the Epigenetic Reader MeCP2 Facilitates Cardiac Adaptation in Chronic Heart Failure
Authors: Mayer Sandra C. , Gilsbach Ralf , Preissl Sebastian , Monroy Ordonez Elsa Beatriz , Schnick Tilman , Beetz Nadine , Lother Achim , Rommel Carolin , Ihle Hannah , Bugger Heiko , Rühle Frank , Schrepper Andrea , Schwarzer Michael , Heilmann Claudia , Bönisch Ulrike , Gupta Shashi Kumar , Wilpert Jochen , Kretz Oliver , von Elverfeldt Dominik , Orth Joachim , Aktories Klaus , Beyersdorf Friedhelm , Bode Christoph , Stiller Brigitte , Krüger Markus , Thum Thomas , Doenst Torsten , Stoll Monika , Hein Lutz
Published: July 2015

Rationale:

In chronic heart failure, increased adrenergic activation contributes to structural remodeling and altered gene expression. Although adrenergic signaling alters histone modifications, it is unknown, whether it also affects other epigenetic processes, including DNA methylation and its recognition.

Objective:

The aim of this study was to identify the mechanism of regulation of the methyl-CpG–binding protein 2 (MeCP2) and its functional significance during cardiac pressure overload and unloading.

Methods and Results:

MeCP2 was identified as a reversibly repressed gene in mouse hearts after transverse aortic constriction and was normalized after removal of the constriction. Similarly, MeCP2 repression in human failing hearts resolved after unloading by a left ventricular assist device. The cluster
miR-212/132
was upregulated after transverse aortic constriction or on activation of α
1
- and β
1
-adrenoceptors and
miR-212/132
led to repression of MeCP2. Prevention of MeCP2 repression by a cardiomyocyte-specific, doxycycline-regulatable transgenic mouse model aggravated cardiac hypertrophy, fibrosis, and contractile dysfunction after transverse aortic constriction. Ablation of MeCP2 in cardiomyocytes facilitated recovery of failing hearts after reversible transverse aortic constriction. Genome-wide expression analysis, chromatin immunoprecipitation experiments, and DNA methylation analysis identified mitochondrial genes and their transcriptional regulators as MeCP2 target genes. Coincident with its repression, MeCP2 was removed from its target genes, whereas DNA methylation of MeCP2 target genes remained stable during pressure overload.

Conclusions:

These data connect adrenergic activation with a microRNA—MeCP2 epigenetic pathway that is important for cardiac adaptation during the development and recovery from heart failure.
Dual Activation of TRIF and MyD88 Adaptor Proteins by Angiotensin II Evokes Opposing Effects on Pressure, Cardiac Hypertrophy, and Inflammatory Gene Expression
Authors: Singh Madhu V. , Cicha Michael Z. , Meyerholz David K. , Chapleau Mark W. , Abboud François M.
Published: July 2015

Hypertension is recognized as an immune disorder whereby immune cells play a defining role in the genesis and progression of the disease. The innate immune system and its component toll-like receptors are key determinants of the immunologic outcome through their proinflammatory response. Toll-like receptor–activated signaling pathways use several adaptor proteins of which adaptor proteins myeloid differentiation protein 88 (MyD88) and toll-interleukin receptor domain–containing adaptor protein–inducing interferon-β (TRIF) define 2 major inflammatory pathways. In this study, we compared the contributions of MyD88 and TRIF adaptor proteins to angiotensin II (Ang II)–induced hypertension and cardiac hypertrophy in mice. Deletion of MyD88 did not prevent cardiac hypertrophy and the pressor response to Ang II tended to increase. Moreover, the increase in inflammatory gene expression (
Tnfa, Nox4
, and
Agtr1a
) was significantly greater in the heart and kidney of MyD88-deficient mice when compared with wild-type mice. Thus, pathways involving MyD88 may actually restrain the inflammatory responses. However, in mice with nonfunctional TRIF (
Trif

mut

mice), Ang II–induced hypertension and cardiac hypertrophy were abrogated, and proinflammatory gene expression in heart and kidneys was unchanged or decreased. Our results indicate that Ang II induces activation of a proinflammatory innate immune response, causing hypertension and cardiac hypertrophy. These effects require functional adaptor protein TRIF-mediated pathways. However, the common MyD88-dependent signaling pathway, which is also activated simultaneously by Ang II, paradoxically exerts a negative regulatory influence on these responses.
Thinking with Crocodiles: An Iconic Animal at the Intersection of Early-Modern Religion and Natural Philosophy
Authors: Weinreich Spencer J.
Published: July 2015

This paper seeks to explore how culturally and religiously significant animals could shape discourses in which they were deployed, taking the crocodile as its case study. Beginning with the textual and visual traditions linking the crocodile with Africa and the Middle East, I read sixteenth- and seventeenth-century travel narratives categorizing American reptiles as “crocodiles” rather than “alligators,” as attempts to mitigate the disruptive strangeness of the Americas. The second section draws on Ann Blair’s study of “Mosaic Philosophy” to examine scholarly debates over the taxonomic identity of the biblical Leviathan. I argue that the language and analytical tools of natural philosophy progressively permeated religious discourse. Finally, a survey of more than 25 extant examples of the premodern practice of displaying crocodiles in churches, as well as other crocodilian elements in Christian iconography, provides an explanation for the ubiquity of crocodiles in Wunderkammern, as natural philosophy appropriated ecclesial visual vocabularies.
From Farce to Tragedy
Authors: Zeron Carlos
Published: July 2015

This article relates the story of the rivalry between Portuguese, Brazilian, and foreign Jesuits in the province of Brazil, seeking to identify when, how, and why an internal dispute became enmeshed in the Society of Jesus’s relationship with the outside world. In fact, the riots caused by the 1680 enactment of the charter of freedom of the Indians not only deepened divisions among Jesuits in Brazil, but also involved representatives of residents, governors, and the Portuguese crown in the Society’s internal affairs. António Vieira’s defeat in this dispute contributed to the broader defeat of the colonial tutelage project implemented by Manuel da Nóbrega beginning in the mid-sixteenth century (and which Vieira still advocated in his last political text, in 1694), as well as to the suspension of the aforementioned charter.
The Linsenmaier Chrysididae collection housed in the Natur-Museum Luzern (Switzerland) and the main results of the related GBIF Hymenoptera Project (Insecta)
Authors: ROSA PAOLO , BERNASCONI MARCO VALERIO , WYNIGER DENISE
Published: July 2015

Historical notes on Walter Linsenmaier, his entomological career and his Chrysididae collection are given. The purpose of this article is to supply the main results obtained during the GBIF digitalization project and the subsequent reorganization of the Chrysididae collection housed in the Natur-Museum Luzern (Switzerland); we also provide the complete list of the 720 taxa described by the Swiss author (species-group and genus-group names). Observations on the type material is given. A new synonymy (valid name is first) is proposed for: C. consanguinea Mocsáry, 1889 = C. consanguinea iberica Linsenmaier, 1959, syn. nov.; C. pyrophana Dahlbom, 1854 = C. pyrophana var. orionea Linsenmaier, 1951, syn. nov.; Hedychridium elegantulum du Buysson, 1887 = H. hybridum Linsenmaier, 1959, syn. nov.; H. perpunctatum Balthasar, 1953 = H. insequosum Linsenmaier, 1959, syn. nov.; Euchroeus (Pseudospinolia) incrassatus (Spinola, 1838) = E. (P.) humboldti jerichoensis Linsenmaier, 1959, syn. nov. A new replacement name Chrysis vulcanica Rosa, nom. nov. is proposed for Chrysis brevicollis Linsenmaier, 1987, nom praeocc., nec Mocsáry, 1899. The lectotype of Chrysis auriceps Linsenmaier, 1959 is designated.
A new genus and species of Tarsonemidae (Acari: Heterostigmata) from the Atlantic Forest, Brazil
Authors: LOFEGO ANTONIO C. , DEMITE PETERSON R. , MORAES GILBERTO J. de
Published: July 2015

Kaliszewskia ochoai gen. nov., sp. nov. (Tarsonemidae: Tarsoneminae: Tarsonemini) is described from adult females, collected on Blepharocalix salicifolius (Kunth) O.Berg and Plinia sp. (Myrtaceae), from the Atlantic Forest in Brazil.
On the Use of Running Trends as Summary Statistics for Univariate Time Series and Time Series Association
Authors: Trottini Mario , Isabel Maria , Aguiar Vigo , Palazón Santiago Belda
Published: July 2015

Given a time series, running trends analysis (RTA) involves evaluating least squares trends over overlapping time windows of L consecutive time points, with overlap by all but one observation. This produces a new series called the “running trends series,” which is used as summary statistics of the original series for further analysis. In recent years, RTA has been widely used in climate applied research as summary statistics for time series and time series association. There is no doubt that RTA might be a useful descriptive tool, but, despite its general use in applied research, precisely what it reveals about the underlying time series is unclear and, as a result, its interpretation is unclear too. This paper contributes to such interpretation in two ways: 1) an explicit formula is obtained for the set of time series with a given series of running trends, making it possible to show that running trends, alone, perform very poorly as summary statistics for univariate time series and time series association; and 2) an equivalence is established between RTA and the estimation of a (possibly nonlinear) trend component of the underlying time series using a weighted moving average filter. Such equivalence provides a solid ground for RTA implementation and interpretation/validation. In this respect, the authors propose as diagnostic tools for RTA 1) the plot of the original series, with RTA trend estimation superposed, 2) the average R2 value and the percentage of statistically significant running trends across windows, and 3) the plot of the running trends series with the corresponding confidence intervals.
Cell Therapy for Critical Limb Ischemia
Authors: Liew Aaron , Bhattacharya Vish , Shaw James , Stansby Gerard
Published: July 2015

Early-phase trials showed the feasibility and potential efficacy of cell therapy in patients with critical limb ischemia (CLI). For systematic review, randomized controlled trials (RCTs) of cell therapy versus no cell therapy in CLI were searched from PubMed and the Cochrane library databases. Outcome measures included major amputation, complete ulcer healing, ankle–brachial index (ABI), and all-cause mortality. Data were pooled using 16 RCTs, involving 774 patients. Compared with no cell therapy, cell therapy significantly reduced major amputation (odds ratio [OR]: 0.54; 95% CI: 0.34-0.87: P = .01) and improved ulcer healing (OR: 2.90; 95% confidence interval [CI]: 1.44-5.82; P < .01) and ABI (OR: 5.91; 95% CI: 1.85-18.86: P < .01). Peripheral blood-derived mononuclear cells (PB-MNCs; OR: 0.29; 95% CI: 0.12-0.72; P < .01) and bone marrow concentrate (OR: 0.44; 95% CI: 0.21-0.93; P = .03) significantly lowered the risk of major amputation. The PB-MNCs also significantly increased ulcer healing (OR: 5.77; 95% CI: 1.77-18.87; P < .01). All-cause mortality was similar in both groups (OR: 0.78; 95% CI: 0.44-1.40; P = .41). However, all estimates were nonsignificant following reanalysis using placebo-controlled RCTs only. Cell therapy remains a potential therapeutic option in CLI, but further larger placebo-controlled RCTs are needed.
The impact of change in albumin assay on reference intervals, prevalence of ‘hypoalbuminaemia’ and albumin prescriptions
Authors: Coley-Grant Deon , Herbert Mike , Cornes Michael P , Barlow Ian M , Ford Clare , Gama Rousseau
Published: July 2015

Background

We studied the impact on reference intervals, classification of patients with hypoalbuminaemia and albumin infusion prescriptions on changing from a bromocresol green (BCG) to a bromocresol purple (BCP) serum albumin assay.

Methods

Passing-Bablok regression analysis and Bland-Altman plot were used to compare Abbott BCP and Roche BCG methods. Linear regression analysis was used to compare in-house and an external laboratory Abbott BCP serum albumin results. Reference intervals for Abbott BCP serum albumin were derived in two different laboratories using pathology data from adult patients in primary care. Prescriptions for 20% albumin infusions were compared one year before and one year after changing the albumin method.

Results

Abbott BCP assay had a negative bias of approximately 6 g/L compared with Roche BCG method. There was good agreement ( y = 1.04  x − 1.03; R2 = 0.9933) between in-house and external laboratory Abbott BCP results. Reference intervals for the serum albumin Abbott BCP assay were 31–45 g/L, different to those recommended by Pathology Harmony and the manufacturers (35–50 g/L). Following the change in method there was a large increase in the number of patients classified as hypoalbuminaemic using Pathology Harmony references intervals (32%) but not when retrospectively compared to locally derived reference intervals (16%) compared with the previous year (12%). The method change was associated with a 44.6% increase in albumin prescriptions. This equated to an annual increase in expenditure of £35,234.

Conclusions

We suggest that serum albumin reference intervals be method specific to prevent misclassification of albumin status in patients. Change in albumin methodology may have significant impact on hospital resources.
Recent development of propensity score methods in observational studies: Multi-categorical treatment, causal mediation, and heterogeneity
Authors: Hu Anning , Mustillo Sarah A
Published: July 2015

This article reviews and comments on three major expansions of propensity score methods in recent decades. First, how to use generalized propensity scores to tackle multi-categorical or continuous treatment variables is shown in procedures of propensity score regression adjustment and propensity score weighting. Second, the counterfactual framework of causal inference in the analysis of mediation mechanisms is reviewed and the decomposition of the causal relationship between variables into causal direct effects and causal indirect effects is illustrated. Third, the heterogeneous treatment effect across the distribution of propensity score values is discussed in the framework of the stratification-multilevel model. For each methodological breakthrough, this article comments on potential issues which deserve serious attention in the practical application of these methods.
The knowledge worker is dead: What about professions?
Authors: Švarc Jadranka
Published: July 2015

This article examines the uncertain and ambivalent position of professions and professionalism in the post-industrial service economy driven by the collapse of the concept of the knowledge worker with which professions have largely been identified since the 1990s. The poor definition of knowledge activities, which are uncritically identified with service activities and creativity of all types, including low-skilled/wage occupations, suggests that the service-dominated economy has significantly challenged the classical concept of professions. In order to understand directions of change in the concept of professionalism the article discusses the reasons for the rise and fall of the knowledge worker and the evolution of the technical-rational to ‘creatocratic’ model of profession. It critically examines the statistical measurement of ‘knowledge-intensive activities’ (KIAs), which is based on poor definition of ‘knowledge intensity’ and cannot serve as a proxy to measure the extent of knowledge occupations in the service economies. Although many concepts for new types of professions have been devised which follow either ‘idealistic’ or ‘realistic’ discourse, the theoretical and normative aspects of new professionalism have not been captured, which makes the idea of a profession a fluid and ephemeral concept. This calls for a more precise definition of occupations and professions in a service economy and their working conditions to understand structural changes and polarization of the labour market, particularly the aspects related to growing social inequalities among new type of professions with the aim to better value professional work and reduce disparities.
Alienation: The critique that refuses to disappear
Authors: Kalekin-Fishman Devorah , Langman Lauren
Published: July 2015

Although it is often condemned as an imprecise concept, alienation continues to flourish as critique in contemporary philosophy, theology, and psychology, as well as in sociology. Historically originating in Roman law, where it referred to the transfer of land ownership, alienation has since been applied extensively to analyses of labor relations, politics, and culture. In the 19th century, Marx showed that workers’ alienation, their dehumanization and estrangement, was a consequence of the structure of exploitation in capitalist industry. The concern was echoed in Weber’s metaphor of the ‘iron cage’ as an outcome of rationalized structures, as well as in Durkheim’s conceptualization of anomie as a variant of alienation causing socially induced psychological states. Today, while research in the structural tradition does not assume that people necessarily are aware of their condition, researchers who assume that alienation is a conscious experience have invented scales to measure its intensity. Continuing both the structural and the psychosocial traditions, researchers now study alienation in relation to uses of digital technologies and new forms of exploitation in work, as well as in politics and popular culture. Alienation is also studied in families, especially in investigations of parenthood.
‘Job opportunities for the youth’: Competing and overlapping discourses on youth unemployment and work informality in Egypt
Authors: Barsoum Ghada
Published: July 2015

Employment informality, or employment without access to work contracts and social insurance, is the norm for Egypt’s working youth, including educated youth. Despite the policy focus on youth as a demographic group, particularly after the country’s recent political developments, informality and precariousness remain largely absent from the policy discourse in Egypt. Youth unemployment rates continue to be the main yardstick for youth welfare in the country. Drawing on Bacchi’s ‘What is the Problem Represented to be?’ (WPR) approach, the analysis in this article seeks to elucidate the implicit assumptions in this policy approach. The article juxtaposes the policy discourse on youth unemployment and informality to that of interviewed educated youth working informally. The two discourses overlap in assigning the state a central role in providing jobs in the public service for youth and in marginalizing the potential to address issues of employment precariousness outside such jobs. They are in discord, however, when young people articulate strong feelings of injustice when these prized jobs are not made available.