bluuebunny/crossref_metadata_2025 huggingface dataset:
A computational study of the role of the aortic arch in idiopathic unilateral vocal-fold paralysis
Authors: Williams Megan J. , Ayylasomayajula Avinash , Behkam Reza , Bierhals Andrew J. , Jacobs M. Eileen , Edgar Julia D. , Paniello Randal C. , Barkmeier-Kraemer Julie M. , Vande Geest Jonathan P.
Published: December 2014

Unilateral vocal-fold paralysis (UVP) occurs when one of the vocal folds becomes paralyzed due to damage to the recurrent laryngeal nerve (RLN). Individuals with UVP experience problems with speaking, swallowing, and breathing. Nearly two-thirds of all cases of UVP is associated with impaired function of the left RLN, which branches from the vagus nerve within the thoracic cavity and loops around the aorta before ascending to the larynx within the neck. We hypothesize that this path predisposes the left RLN to a supraphysiological, biomechanical environment, contributing to onset of UVP. Specifically, this research focuses on the identification of the contribution of the aorta to onset of left-sided UVP. Important to this goal is determining the relative influence of the material properties of the RLN and the aorta in controlling the biomechanical environment of the RLN. Finite element analysis was used to estimate the stress and strain imposed on the left RLN as a function of the material properties and loading conditions. The peak stress and strain in the RLN were quantified as a function of RLN and aortic material properties and aortic blood pressure using Spearman rank correlation coefficients. The material properties of the aortic arch showed the strongest correlation with peak stress [ρ = −0.63, 95% confidence interval (CI), −1.00 to −0.25] and strain (ρ = −0.62, 95% CI, −0.99 to −0.24) in the RLN. Our results suggest an important role for the aorta in controlling the biomechanical environment of the RLN and potentially in the onset of left-sided UVP that is idiopathic.
Neural responses in songbird forebrain reflect learning rates, acquired salience, and stimulus novelty after auditory discrimination training
Authors: Bell Brittany A. , Phan Mimi L. , Vicario David S.
Published: December 2014

How do social interactions form and modulate the neural representations of specific complex signals? This question can be addressed in the songbird auditory system. Like humans, songbirds learn to vocalize by imitating tutors heard during development. These learned vocalizations are important in reproductive and social interactions and in individual recognition. As a model for the social reinforcement of particular songs, male zebra finches were trained to peck for a food reward in response to one song stimulus (GO) and to withhold responding for another (NoGO). After performance reached criterion, single and multiunit neural responses to both trained and novel stimuli were obtained from multiple electrodes inserted bilaterally into two songbird auditory processing areas [caudomedial mesopallium (CMM) and caudomedial nidopallium (NCM)] of awake, restrained birds. Neurons in these areas undergo stimulus-specific adaptation to repeated song stimuli, and responses to familiar stimuli adapt more slowly than to novel stimuli. The results show that auditory responses differed in NCM and CMM for trained (GO and NoGO) stimuli vs. novel song stimuli. When subjects were grouped by the number of training days required to reach criterion, fast learners showed larger neural responses and faster stimulus-specific adaptation to all stimuli than slow learners in both areas. Furthermore, responses in NCM of fast learners were more strongly left-lateralized than in slow learners. Thus auditory responses in these sensory areas not only encode stimulus familiarity, but also reflect behavioral reinforcement in our paradigm, and can potentially be modulated by social interactions.
Task-related changes in intracortical inhibition assessed with paired- and triple-pulse transcranial magnetic stimulation
Authors: Opie George M. , Ridding Michael C. , Semmler John G.
Published: December 2014

Recent research has demonstrated a task-related modulation of postsynaptic intracortical inhibition within primary motor cortex for tasks requiring isolated (abduction) or synergistic (precision grip) muscle activation. The current study sought to investigate task-related changes in pre- and postsynaptic intracortical inhibition in motor cortex. In 13 young adults (22.5 ± 3.5 yr), paired-pulse transcranial magnetic stimulation (TMS) was used to measure short (SICI)- and long-interval intracortical inhibition (LICI) (i.e., postsynaptic motor cortex inhibition) in first dorsal interosseous muscle, and triple-pulse TMS was used to investigate changes in SICI-LICI interactions (i.e., presynaptic motor cortex inhibition). These measurements were obtained at rest and during muscle activation involving isolated abduction of the index finger and during a precision grip using the index finger and thumb. SICI was reduced during abduction and precision grip compared with rest, with greater reductions during precision grip. The modulation of LICI during muscle activation depended on the interstimulus interval (ISI; 100 and 150 ms) but was not different between abduction and precision grip. For triple-pulse TMS, SICI was reduced in the presence of LICI at both ISIs in resting muscle (reflecting presynaptic motor cortex inhibition) but was only modulated at the 150-ms ISI during index finger abduction. Results suggest that synergistic contractions are accompanied by greater reductions in postsynaptic motor cortex inhibition than isolated contractions, but the contribution of presynaptic mechanisms to this disinhibition is limited. Furthermore, timing-dependent variations in LICI provide additional evidence that measurements using different ISIs may not represent activation of the same cortical process.
Distinguishing intrinsic from extrinsic factors underlying firing rate saturation in human motor units
Authors: Fuglevand Andrew J. , Lester Rosemary A. , Johns Richard K.
Published: December 2014

During voluntary contraction, firing rates of individual motor units (MUs) increase modestly over a narrow force range beyond which little additional increase in firing rate is seen. Such saturation of MU discharge may be a consequence of extrinsic factors that limit net synaptic excitation acting on motor neurons (MNs) or may be due to intrinsic properties of the MNs. Two sets of experiments involving recording of human biceps brachii MUs were carried out to evaluate saturation. In the first set, the extent of saturation was quantified for 136 low-threshold MUs during isometric ramp contractions. Firing rate-force data were best fit by a saturating function for 90% of MUs recorded with a maximum rate of 14.8 ± 2.0 impulses/s. In the second set of experiments, to distinguish extrinsic from intrinsic factors underlying saturation, we artificially augmented descending excitatory drive to biceps MNs by activation of muscle spindle afferents through tendon vibration. We examined the change in firing rate caused by tendon vibration in 96 MUs that were voluntarily activated at rates below and at saturation. Vibration had little effect on the discharge of MUs that were firing at saturation frequencies but strongly increased firing rates of the same units when active at lower frequencies. These results indicate that saturation is likely caused by intrinsic mechanisms that prevent further increases in firing rate in the presence of increasing synaptic excitation. Possible intrinsic cellular mechanisms that limit firing rates of motor units during voluntary effort are discussed.
Enhanced Tumorigenic Potential of Colorectal Cancer Cells by Extracellular Sulfatases
Authors: Vicente Carolina M. , Lima Marcelo A. , Yates Edwin A. , Nader Helena B. , Toma Leny
Published: December 2014

Heparan sulfate endosulfatase-1 and -2 (SULF1 and SULF2) are two important extracellular 6-O-endosulfatases that remove 6-O sulfate groups of N-glucosamine along heparan sulfate (HS) proteoglycan chains often found in the extracellular matrix. The HS sulfation pattern influences signaling events at the cell surface, which are critical for interactions with growth factors and their receptors. SULFs are overexpressed in several types of human tumors, but their role in cancer is still unclear because their molecular mechanism has not been fully explored and understood. To further investigate the functions of these sulfatases in tumorigenesis, stable overexpression models of these genes were generated in the colorectal cancer cells, Caco-2 and HCT-116. Importantly, mimicking overexpression of these sulfatases resulted in increased viability and proliferation, and augmented cell migration. These effects were reverted by shRNA-mediated knockdown of SULF1 or SULF2 and by the addition of unfractionated heparin. Detailed structural analysis of HS from cells overexpressing SULFs showed reduction in the trisulfated disaccharide UA(2S)-GlcNS(6S) and corresponding increase in UA(2S)-GlcNS disaccharide, as well as an unexpected rise in less common disaccharides containing GlcNAc(6S) residues. Moreover, cancer cells transfected with SULFs demonstrated increased Wnt signaling. In summary, SULF1 or SULF2 overexpression contributes to colorectal cancer cell proliferation, migration, and invasion.

Implications: This study reveals that sulfatases have oncogenic effects in colon cancer cells, suggesting an important role for these enzymes in cancer progression. Mol Cancer Res; 13(3); 510–23. ©2014 AACR.
Oxidative Stress in Benign Prostatic Hyperplasia: A Systematic Review
Authors: Minciullo Paola Lucia , Inferrera Antonino , Navarra Michele , Calapai Gioacchino , Magno Carlo , Gangemi Sebastiano
Published: December 2014

Background: Several parameters including inflammatory mediators, hormones, dietary factors, inflammatory genes, and oxidative stress (OS) have been considered to play a role in the development of benign prostatic hyperplasia (BPH). Prostate tissue damage and OS may lead to compensatory cellular proliferation with resulting hyperplastic growth. Methods: We searched MEDLINE for articles in English published up to March 2014 using the key words ‘oxidative stress', ‘antioxidants' and ‘benign prostatic hyperplasia'. Results: Prostatic inflammation can cause the generation of free radicals. The extent of oxidative damage can be exacerbated by a decreased efficiency of antioxidant defense mechanisms. The balance between OS and the antioxidant component also has a role in developing prostate disease. Several works show the role of oxidant products and of depletion of antioxidant substances in BPH patients. It is accepted that free radicals play a role in carcinogenesis and that BPH should be considered a premalignant condition which may evolve into prostate cancer. High OS parameters and low antioxidant activity are more prominent in prostate cancer patients compared with BPH and controls. Conclusions: Further studies are needed to clarify the potential role of antioxidants in BPH also in view of preventing the progression to prostate cancer.
Microarray-Based Cell-Free DNA Analysis Improves Noninvasive Prenatal Testing
Authors: Juneau Kara , Bogard Patrick E. , Huang Stephanie , Mohseni Morassa , Wang Eric T. , Ryvkin Paul , Kingsley Christopher , Struble Craig A. , Oliphant Arnold , Zahn Jacob M.
Published: December 2014

Objective: To develop a microarray-based method for noninvasive prenatal testing (NIPT) and compare it with next-generation sequencing. Methods: Maternal plasma from 878 pregnant women, including 187 trisomy cases (18 trisomy 13, 37 trisomy 18, 132 trisomy 21), was evaluated for trisomy risk. Targeted chromosomes were analyzed using Digital Analysis of Selected Regions (DANSR™) assays. DANSR products were subsequently divided between two DNA quantification methods: microarrays and next-generation sequencing. For both microarray and sequencing methodologies, the Fetal-Fraction Optimized Risk of Trisomy Evaluation (FORTE™) algorithm was used to determine trisomy risk, assay variability across samples, and compute fetal fraction variability within samples. Results: NIPT using microarrays provided faster and more accurate cell-free DNA (cfDNA) measurements than sequencing. The assay variability, a measure of variance of chromosomal cfDNA counts, was lower for microarrays than for sequencing, 0.051 versus 0.099 (p < 0.0001). Analysis time using microarrays was faster, 7.5 versus 56 h for sequencing. Additionally, fetal fraction precision was improved 1.6-fold by assaying more polymorphic sites with microarrays (p < 0.0001). Microarrays correctly classified all trisomy and nontrisomy cases. Conclusions: NIPT using microarrays delivers more accurate cfDNA analysis than next-generation sequencing and can be performed in less time.
Nodular Melanoma Serendipitously Detected by Airport Full Body Scanners
Authors: Mayer Jonathan E. , Adams Brian B.
Published: December 2014

Background: Nodular melanoma is the most dangerous form of melanoma and often evades early detection. Methods: We present a frequently traveling businessman whose nodular melanoma was detected by airport full body scanners. Results: For about 20 flights over 2 months, the airport full body scanners singled out an area on his left lower leg for a pat-down. Dermatologic examination discovered a nodular melanoma in this area, and after surgical excision, the man traveled without incident. Conclusion: This case raises the possibility of using full body imaging in the detection of melanomas, especially of the nodular subtype. In its current form, full body scanning would most likely not be sensitive or specific enough to become a recommended screening tool. Nonetheless, for travelers with areas repeatedly singled out by the machines without a known justification, airport scanners could serve as incidental free screening for suspicious nodular lesions that should prompt dermatologist referral.
Functional Bronchoscopy: Development of a New Bronchoscopic Method for Real-Time Gas Exchange Assessment of Lobes and Lung Segments
Authors: Freitag Lutz , Lenkens Dierik , Zarogoulidis Paul , Karpf-Wissel Rüdiger , Hang Heiko , Darwiche Kaid
Published: December 2014

Background: There are various imaging methods in use designed to provide information on lung functional status, particularly gas exchange within specific lung segments. These complex imaging methods provide indirect information about volume and local lung function. Objectives: The objective of this research was to develop a simpler and more direct method for the functional assessment of gas exchange in lung segments. Method: We have developed a new bronchoscopic method to sample gas concentrations of oxygen and carbon dioxide at the orifices of segmental bronchi in a breathing patient. Endocapnometry and oximetry curves are displayed in real time and superimposed on the endoscopic video images. Results: The gas exchange mapping of a lung could be achieved in <5 min. We identified typical curve patterns of localized slow and fast clearance regions, and segments with higher or lower oxygen uptake. This method is simple and versatile and the data displayed can help to identify target zones for endoscopic emphysema treatments, e.g. for lowering the risk of resection surgery, or to improve ventilation strategies in ICU patients. Conclusion: This new method enables gas sampling at the lung segment level. The concomitant display of local endocapnometry and endooximetry curves allows for a better identification of target zones for endoscopic emphysema treatments or to improve ventilation strategies for patients on respiratory support.
Mineralocorticoid-Induced Sodium Appetite and Renal Salt Retention: Evidence for Common Signaling and Effector Mechanisms
Authors: Fu Yiling , Vallon Volker
Published: December 2014

An increase in renal sodium chloride (salt) retention and an increase in sodium appetite are the body's responses to salt restriction or depletion in order to restore salt balance. Renal salt retention and increased sodium appetite can also be maladaptive and sustain the pathophysiology in conditions like salt-sensitive hypertension and chronic heart failure. Here we review the central role of the mineralocorticoid aldosterone in both the increase in renal salt reabsorption and sodium appetite. We discuss the working hypothesis that aldosterone activates similar signaling and effector mechanisms in the kidney and brain, including the mineralocorticoid receptor, the serum- and glucocorticoid-induced kinase SGK1, the ubiquitin ligase NEDD4-2, and the epithelial sodium channel ENaC. The latter also mediates the gustatory salt sensing in the tongue, which is required for the manifestation of increased salt intake. Effects of aldosterone on both the brain and kidney synergize with the effects of angiotensin II. Thus, mineralocorticoids appear to induce similar molecular pathways in the kidney, brain, and possibly tongue, which could provide opportunities for more effective therapeutic interventions. Inhibition of renal salt reabsorption is compensated by stimulation of salt appetite and vice versa; targeting both mechanisms should be more effective. Inhibiting the arousal to consume salty food may improve a patient's compliance to reducing salt intake. While a better understanding of the molecular mechanisms is needed and will provide new therapeutic options, current pharmacological interventions that target both salt retention and sodium appetite include mineralocorticoid receptor antagonists and potentially inhibitors of angiotensin II and ENaC.
Extracorporeal Shock Wave Therapy for Injection Site Panniculitis in Multiple Sclerosis Patients
Authors: Stieger Marco , Schmid Jean-Paul , Yawalkar Nikhil , Hunziker Thomas
Published: December 2014

Background: Painful cutaneous injection site reactions may hamper treatment with interferon β (IFN-β) and glatiramer acetate (GA) in multiple sclerosis (MS) patients. Objective: To maintain therapy adherence, efficient therapeutic modalities for these subcutaneous inflammatory lesions are urgently needed. We tested the application of local extracorporeal shock wave therapy (ESWT). Methods: We applied 5 sessions of ESWT to 8 patients suffering from MS who had developed painful panniculitis at the injection sites of either IFN-β or GA. Clinical outcomes, i.e. pain reduction and regression of induration, were assessed 3 and 6 months after completion of the ESWT using a visual analogue score. Results: All patients showed both significant pain reduction and reduction of the skin induration in the treated lesions, while in untreated control lesions there was no improvement. Conclusion: ESWT proved to be a non-invasive, safe and efficient physical treatment modality for injection-induced painful cutaneous side effects of disease-modifying drugs in MS.
Relationships among Sex, Season and Testosterone in the Expression of Androgen Receptor mRNA and Protein in the Green Anole Forebrain
Authors: Kerver Halie N. , Wade Juli
Published: December 2014

Sexual behavior in male green anole lizards is regulated by a seasonal increase in testosterone (T). However, T is much more effective at activating behavioral, morphological and biochemical changes related to reproduction in the breeding season (BS; spring) compared to nonbreeding season (NBS; fall). An increase in androgen receptor (AR) during the BS is one potential mechanism for this differential responsiveness. AR expression has not been investigated in specific brain regions across seasons in anoles. The present studies were designed to determine relative AR expression in areas important for male (preoptic area, ventromedial amygdala) and female (ventromedial hypothalamus) sexual behavior, as well as whether T upregulates AR in the anole brain. In situ hybridization and Western blot analyses were performed in unmanipulated animals across sex and season, as well as in gonadectomized animals with and without T treatment. Among hormone-manipulated animals, more cells expressing AR mRNA were detected in females than males in the amygdala. T treatment increased the volume of the ventromedial hypothalamus of gonadectomized animals in the BS, but not the NBS. AR protein in dissections of the hypothalamus and preoptic area was increased in males compared to females specifically in the BS. Additionally, among females, it was increased in the NBS compared to the BS. Collectively, these results indicate that differences in central AR expression probably do not facilitate a seasonal responsiveness to T. However, they are consistent with a role for AR in regulating some differences between sexes in the display of reproductive behaviors.
Pathogenesis and Treatment of Chronic Kidney Disease: A Review of Our Recent Basic and Clinical Data
Authors: Tomino Yasuhiko
Published: December 2014

Chronic kidney disease (CKD) is a worldwide public health problem that affects millions of people from all racial and ethnic groups. At end of 2013, over 300,000 Japanese patients had maintenance dialysis therapy (JSDT). In Japan, the major causes of end stage kidney disease (ESKD) are chronic glomerulonephritis (particularly IgA nephropathy), type 2 diabetic nephropathy, and hypertensive nephrosclerosis. Hypertension is a major factor driving the progression of CKD to ESKD. Since many features of the pathogenesis of IgA nephropathy are still obscure, specific treatment is not yet available. However, efforts by investigators around the world have gradually clarified different aspects of the pathogenesis and treatment of IgA nephropathy. Today, around half of all diabetic patients in Japan receive medical treatment. Type 2 diabetic nephropathy is one of the major long-term microvascular complications occurring in nearly 40% of Japanese diabetic patients. The pathogenesis of diabetic nephropathy involves both genetic and environmental factors. However, the candidate genes related to the initiation and progression of the disorder are still obscure in patients with diabetic nephropathy. Regarding environmental factors, the toxicity of persistent hyperglycemia, reactive oxygen species, systemic and/or glomerular hypertension, dyslipidemia and complement are considered to play an important role. The first part of this review covers the pathogenesis of IgA nephropathy and type 2 diabetic nephropathy, and combines the clinicopathological findings in patients with our research on the ddY and KKA-y mouse models (spontaneous animal models for IgA nephropathy and diabetic nephropathy, respectively). In Japan, the major renal replacement therapies (RRT) are peritoneal dialysis (PD) and hemodialysis (HD). The second part of this review focuses on PD and HD. Based on our research findings from patients and as well as from animal models, we discuss strategies for the management of patients on PD and HD. i 2015 S. Karger AG, Basel
Retrospective, Observational Study in Patients Receiving a Dexamethasone Intravitreal Implant 0.7 mg for Macular Oedema Secondary to Retinal Vein Occlusion
Authors: Augustin Albert J. , Holz Frank G. , Haritoglou Christos , Mayer Wolfgang J. , Bopp Silvia , Scheuerle Alexander F. , Maier Matthias , Sekundo Walter , Sandner Dirk , Shirlaw Andrew , Hattenbach Lars-Olof
Published: December 2014

Purpose: To retrospectively evaluate the re-injection interval, efficacy and safety of dexamethasone (DEX) intravitreal implant 0.7 mg in the treatment of macular oedema (ME) due to retinal vein occlusion (RVO) in Germany in 2009-2012. Methods: Retrospective, multicentre, anonymised observational study of data collected from the first DEX implant 0.7 mg injection through 3-6 months following the last injection. Data were included if the patient was >18 years old, had a diagnosis of ME secondary to branch or central RVO, and received at least 2 DEX implant 0.7 mg injections during routine practice. Results: Data from 87 patients were analysed. Mean time to re-injection between first and second treatments was 5.03 months in the total RVO population, and 5.46 and 4.52 months for the branch and central RVO subpopulations, respectively. An intraocular pressure increase of >25 mm Hg was recorded in 20% of patients, and 34% of patients began treatment with anti-glaucoma medication, but surgery was not needed for this condition. Conclusions: DEX implant 0.7 mg was found to be well tolerated and effective with repeat treatments in clinical practice.
Inhaled Interventions in Cystic Fibrosis: Mucoactive and Antibiotic Therapies
Authors: Hurt Katharine , Bilton Diana
Published: December 2014

Treatment of cystic fibrosis lung disease has developed from an understanding of the abnormal airway surface liquid resulting from a lack of function of the cystic fibrosis transmembrane regulator protein. Mucus plugging resulting in infection and inflammation leads to airway wall destruction and bronchiectasis. Inhaled therapies have formed the backbone of treatments. In combination with antibiotics delivered direct to the airway, mucoactive drugs, including mucolytics and hyperosmolar agents, are utilised to improve mucociliary clearance to reduce infection and inflammation. Until recently, airway therapies were delivered as nebulisers, but we have now entered the era of dry powder inhalers for treatment of cystic fibrosis lung disease. The theory and practice of these therapies are discussed in this review.
Multifocal Adenomatous Oncocytic Hyperplasia of the Parotid Gland
Authors: Kinoshita Yuichi , Harada Hiroshi , Kobayashi Tadao K. , Yoshizawa Katsuhiko , Yuri Takashi , Takasu Kosho , Tsubura Airo , Shikata Nobuaki
Published: December 2014

Multifocal adenomatous oncocytic hyperplasia (MAOH) is a non-neoplastic lesion that is classified as oncocytosis. MAOH is a rare entity of the parotid gland and accounts for approximately 0.1% of salivary gland lesions. Here, we report a case of MAOH of the parotid gland. The patient was a 71-year-old woman who presented with discomfort at the left side of her neck. Fine-needle aspiration cytology of the parotid gland revealed a loose sheet-like cluster of round to polygonal cells with granular cytoplasm against a hemorrhagic background. The cells had round to oval, centrally located nuclei with granular chromatin and without distinct nucleoli. Histologically, the lesion was formed of many variable-sized nodules, comprising oncocyte-like cells with small round nuclei and eosinophilic granular cytoplasm that was positive for mitochondrial antibodies. The diagnosis of MAOH is difficult to make by cytology alone, because the findings overlap with those of other oncocytic lesions. In particular, the cytological findings of MAOH have not been sufficiently reported to date. A correlation of cytology and histology was expected.
Prevalence of Nonatheromatous Lesions in Peripheral Arterial Disease
Authors: O’Neill W. Charles , Han Kum Hyun , Schneider Thomas M. , Hennigar Randolph A.
Published: December 2014

Objective—

The histopathology of peripheral arterial disease and the accompanying calcification are poorly defined, and it is not known whether this varies according to different risk factors.

Approach and Results—

Sections from 176 upper and lower leg arteries were examined histologically in specimens from amputations of 60 patients with peripheral arterial disease, of whom 58% had diabetes mellitus, 35% had end-stage renal disease, and 48% had a history of smoking. The most common findings were calcification of the media (72% of arteries) and intimal thickening without lipid (68% of arteries), with the presence of atheromas in only 23% of arteries. Intimal calcification occurred in 43% and was generally much less extensive than medial calcification. Nonatheromatous intimal thickening was frequently severe, resulting in complete occlusion in some vessels. The absence of lipid and macrophages was confirmed by staining with oil red O and staining for CD68. Other than a greater prevalence and severity of medial calcification in end-stage renal disease, the findings did not differ between diabetics, patients with end-stage renal disease, or smokers.

Conclusions—

The results indicate that the majority of arteries in patients with peripheral arterial disease have a vascular lesion that is distinct from atherosclerosis, suggesting a different pathogenesis. This pattern does not differ substantially between patients with different risk factors for peripheral arterial disease. The bulk of vascular calcification in the lower extremities is medial rather than intimal.
Genome-Wide Meta-Analyses of Plasma Renin Activity and Concentration Reveal Association With the Kininogen 1 and Prekallikrein Genes
Authors: Lieb Wolfgang , Chen Ming-Huei , Teumer Alexander , de Boer Rudolf A. , Lin Honghuang , Fox Ervin R. , Musani Solomon K. , Wilson James G. , Wang Thomas J. , Völzke Henry , Petersen Ann-Kristin , Meisinger Christine , Nauck Matthias , Schlesinger Sabrina , Li Yong , Menard Jöel , Hercberg Serge , Wichmann H.-Erich , Völker Uwe , Rawal Rajesh , Bidlingmaier Martin , Hannemann Anke , Dörr Marcus , Rettig Rainer , van Gilst Wiek H. , van Veldhuisen Dirk J. , Bakker Stephan J.L. , Navis Gerjan , Wallaschofski Henri , Meneton Pierre , van der Harst Pim , Reincke Martin , Vasan Ramachandran S.
Published: December 2014

Background—

The renin–angiotensin–aldosterone system (RAAS) is critical for regulation of blood pressure and fluid balance and influences cardiovascular remodeling. Dysregulation of the RAAS contributes to cardiovascular and renal morbidity. The genetic architecture of circulating RAAS components is incompletely understood.

Methods and Results—

We meta-analyzed genome-wide association data for plasma renin activity (n=5275), plasma renin concentrations (n=8014), and circulating aldosterone (n=13289) from ≤4 population-based cohorts of European and European-American ancestry, and assessed replication of the top results in an independent sample (n=6487). Single-nucleotide polymorphisms (SNPs) in 2 independent loci displayed associations with plasma renin activity at genome-wide significance (
P
<5×10
−8
). A third locus was close to this threshold (rs4253311 in
kallikrein
B
[KLKB1],
P
=5.5×10
−8
). Two of these loci replicated in an independent sample for both plasma renin and aldosterone concentrations (SNP rs5030062 in
kininogen 1
[KNG1]:
P
=0.001 for plasma renin,
P
=0.024 for plasma aldosterone concentration; and rs4253311 with
P
<0.001 for both plasma renin and aldosterone concentration). SNPs in the
NEBL
gene reached genome-wide significance for plasma renin concentration in the discovery sample (top SNP rs3915911;
P
=8.81×10
−9
), but did not replicate (
P
=0.81). No locus reached genome-wide significance for aldosterone. SNPs rs5030062 and rs4253311 were not related to blood pressure or renal traits; in a companion study, variants in the
kallikrein B locus
were associated with B-type natriuretic peptide concentrations in blacks.

Conclusions—

We identified 2 genetic loci (
kininogen 1
and
kallikrein B
) influencing key components of the RAAS, consistent with the close interrelation between the kallikrein–kinin system and the RAAS.
Transcriptional Reversion of Cardiac Myocyte Fate During Mammalian Cardiac Regeneration
Authors: O’Meara Caitlin C. , Wamstad Joseph A. , Gladstone Rachel A. , Fomovsky Gregory M. , Butty Vincent L. , Shrikumar Avanti , Gannon Joseph B. , Boyer Laurie A. , Lee Richard T.
Published: December 2014

Rationale:

Neonatal mice have the capacity to regenerate their hearts in response to injury, but this potential is lost after the first week of life. The transcriptional changes that underpin mammalian cardiac regeneration have not been fully characterized at the molecular level.

Objective:

The objectives of our study were to determine whether myocytes revert the transcriptional phenotype to a less differentiated state during regeneration and to systematically interrogate the transcriptional data to identify and validate potential regulators of this process.

Methods and Results:

We derived a core transcriptional signature of injury-induced cardiac myocyte (CM) regeneration in mouse by comparing global transcriptional programs in a dynamic model of in vitro and in vivo CM differentiation, in vitro CM explant model, as well as a neonatal heart resection model. The regenerating mouse heart revealed a transcriptional reversion of CM differentiation processes, including reactivation of latent developmental programs similar to those observed during destabilization of a mature CM phenotype in the explant model. We identified potential upstream regulators of the core network, including interleukin 13, which induced CM cell cycle entry and STAT6/STAT3 signaling in vitro. We demonstrate that STAT3/periostin and STAT6 signaling are critical mediators of interleukin 13 signaling in CMs. These downstream signaling molecules are also modulated in the regenerating mouse heart.

Conclusions:

Our work reveals new insights into the transcriptional regulation of mammalian cardiac regeneration and provides the founding circuitry for identifying potential regulators for stimulating heart regeneration.
Symptomatic Carotid Atherosclerotic Disease
Authors: Howard Dominic P.J. , van Lammeren Guus W. , Rothwell Peter M. , Redgrave Jessica N. , Moll Frans L. , de Vries Jean-Paul P.M. , de Kleijn Dominique P.V. , den Ruijter Hester M. , de Borst Gert Jan , Pasterkamp Gerard
Published: December 2014

Background and Purpose—

For symptomatic patients with carotid artery stenosis, the risk benefit for surgical intervention may vary among patient groups. Various modalities of plaque imaging have been promoted as potential tools for additional risk stratification, particularly in patients with moderate stenosis. However, it remains uncertain to what extent carotid plaque components predict risk of future ipsilateral ischemic stroke.

Methods—

In 2 large atherosclerotic carotid plaque biobank studies, we related histological characteristics of 1640 carotid plaques with a validated risk model for the prediction of individual 1- and 5-year stroke risk.

Results—

No significant heterogeneity between the studies was found. Predicted 5-year stroke risk (top versus bottom quartile) was related to plaque thrombus (odds ratio, 1.42; 95% confidence interval, 1.11–1.89;
P
=0.02), fibrous content (0.65; 0.49–0.87;
P
=0.004), macrophage infiltration (1.41; 1.05–1.90;
P
=0.02), high microvessel density (1.49; 1.05–2.11;
P
=0.03), and overall plaque instability (1.40; 1.05–1.87;
P
=0.02). This association was not observed for cap thickness, calcification, intraplaque hemorrhage, or lymphocyte infiltration. Plaques removed within 30 days of most recent symptomatic event were most strongly correlated with predicted stroke risk.

Conclusions—

Features of the vulnerable carotid plaque, including plaque thrombus, low fibrous content, macrophage infiltration, and microvessel density, correlate with predicted stroke risk. This study provides a basis for plaque imaging studies focused on stroke risk stratification.
Two-Layered Susceptibility Vessel Sign on 3-Tesla T2*-Weighted Imaging Is a Predictive Biomarker of Stroke Subtype
Authors: Yamamoto Nobuaki , Satomi Junichiro , Tada Yoshiteru , Harada Masafumi , Izumi Yuishin , Nagahiro Shinji , Kaji Ryuji
Published: December 2014

Background and Purpose—

A susceptibility vessel sign (SVS) on 1.5-tesla (T)-T2*-weighted images may predict cardioembolism. It has also been detected in patients with large artery atherosclerosis. In patients with major vessel occlusion, the SVS was comprised 2 layers on 3T-T2*-weighted images. We assessed the efficacy of 2-layered SVS on 3T-T2*-weighted imaging scans for predicting cardioembolism.

Methods—

Our study included 132 patients who had ischemic stroke within the preceding 24 hours and presented with internal carotid artery or middle cerebral artery occlusion because of cardioembolism or large artery atherosclerosis. We compared 2-layered SVS and SVS on 3T-T2*-weighted imaging scans for their sensitivity, specificity, and diagnostic odds ratio for predicting cardioembolism.

Results—

We enrolled 132 patients (72 men; mean age, 74.5 years); of these, 63 (47.7%) were presented with cardioembolism. Although the sensitivity of SVS and 2-layered SVS for cardioembolism and large artery atherosclerosis was not statistically different (74.6% and 58.0%, respectively), the sensitivity of 2-layered SVS was significantly higher in patients with cardioembolism (42.9%) than those with large artery atherosclerosis (2.9%;
P
<0.001). The specificity and diagnostic odds ratio for 2-layered SVS for cardioembolism were 97.1% and 25.1; for SVS they were 42.0% and 2.1, respectively.

Conclusion—

The specificity of 2-layered SVS for cardioembolism was high. It may be useful for predicting cardioembolism and for the management of patients with acute ischemic stroke.
The Dynamics of Cumulative Step Size Adaptation on the Ellipsoid Model
Authors: Beyer Hans-Georg , Hellwig Michael
Published: December 2014

The behavior of the [Formula: see text]-Evolution Strategy (ES) with cumulative step size adaptation (CSA) on the ellipsoid model is investigated using dynamic systems analysis. At first a nonlinear system of difference equations is derived that describes the mean value evolution of the ES. This system is successively simplified to finally allow for deriving closed-form solutions of the steady state behavior in the asymptotic limit case of large search space dimensions. It is shown that the system exhibits linear convergence order. The steady state mutation strength is calculated, and it is shown that compared to standard settings in [Formula: see text] self-adaptive ESs, the CSA control rule allows for an approximately [Formula: see text]-fold larger mutation strength. This explains the superior performance of the CSA in non-noisy environments. The results are used to derive a formula for the expected running time. Conclusions regarding the choice of the cumulation parameter c and the damping constant D are drawn.
The Ruler’s Monologue: The Rhetoric of the Ottoman Penal Code of 1858
Authors: Heinzelmann Tobias
Published: December 2014

The penal code of 1858 was an important step in Ottoman legislation during the reform period (tanẓīmāt) and had a considerable impact on the concept of the state as the guardian of public order. Through the 20th century the penal code of 1858 was generally interpreted as a “(literal) translation” of the French Code Pénal of 1810 and as evidence for the “western influence” on Ottoman legislation. Recent research has started to question this interpretation, focussed more closely on the normative aspects of the Ottoman penal code and analysed the penal code of 1858 as an adaptation of French law within the context of the Ottoman legal concepts during the tanẓīmāt. In my article I analyse the text as a part of political communication, as a monologue by which the state adresses its subjects. Even if large parts of the Ottoman penal code are translations from the French, the rhetoric patterns and terminology have to be taken seriously. The amalgamation of traditional rhetorics and a new terminology turns out to be a successful strategy to legitimise new legal concepts, which include a new relation between ḳānūn and şerīʿat. In my article I will argue that the state’s traditional role as the guardian of public order is the starting point for the introduction of these new legal concepts.
Hesitation as a System Response to Children Exposed to Violence
Authors: Ellonen Noora , Pösö Tarja
Published: December 2014

The article aims to explore how certain social welfare, health and education institutions and the police respond to children exposed to violence. In particular, it focuses on how the institutions interact with each other in terms of informing one another about violence targeted at children or the suspicion of it, as suggested by present Finnish legislation. Based on interviews with 33 practitioners, the analysis highlights hesitation as a common response, especially in cases of mild violence and uncontested “evidence”. Hesitation is against the present legal norms and reflects some lack of knowledge of professional duties. However, the rationalities for hesitation relate, especially, to the agency and profession-based understanding of the principle of the best interests of the child, and they may include some practice-based understanding of the system. Thus, hesitation as a system response should not be ignored but explored in more detail.
The genus Leucophenga (Diptera, Drosophilidae), part IV: the ornata species group from the East Asia, with morphological and molecular evidence (II)
Authors: Huang Jia , Li Tong , Chen Hongwei
Published: December 2014

Twenty-one species of the Leucophenga ornata species group are surveyed (including 12 new species): L. atrinervis     Okada, 1968; L. digmasoma Lin & Wheeler, 1972; L. multipunctata Chen & Aotsuka, 2003; L. nigrinervis Duda, 1924; L. pectinata Okada, 1968; L. pentapunctata Panigrahy & Gupta, 1982; L. quadripunctata (de Meijere, 1908); L. regina Malloch, 1935; L. trivittata Okada, 1990; L. acutifoliacea sp. nov.; L. albiterga sp. nov.; L. angustifoliacea sp. nov.;          L. baculifoliacea sp. nov.; L. cornuta sp. nov.; L. hirticeps sp. nov.; L. latifascia sp. nov.; L. pinguifoliacea sp. nov.;          L. retihirta sp. nov. L. securis sp. nov.; L. sinupenis sp. nov.; L. villosa sp. nov.; these species (except for L. baculifoliacea sp. nov.) having pubescence on the distal portion of aedeagus. A key to all the examined species of the ornata group in this study is provided. We try to improve our species delimitation by integrating the DNA sequences data with morphological information. The intra- and interspecific pairwise K-2P (Kimura’s two-parameter) distances are summarized.
A review of the ectoparasitic mites (Acari: Dermanyssoidea) associated with birds and their nests in Slovakia, with notes on identification of some species
Authors: MAŠÁN PETER , FENĎA PETER , KRIŠTOFÍK JÁN , HALLIDAY BRUCE
Published: December 2014

We review the parasitic mites of the superfamily Dermanyssoidea found in the nests of Slovakian domestic and wild birds (and a few mammals), compiled from new data and literature sources. Three mite genera are included, namely Dermanyssus Dugès (Dermanyssidae), Ornithonyssus Sambon and Pellonyssus Clark & Yunker (Macronyssidae), in which we recognised nine reliably documented species. Pellonyssus is represented by one species, Dermanyssus by five species, and Ornithonyssus by three species. We compiled information on the ecological requirements and host preferences of these mite species, including data on geographic distribution, altitudinal distribution, and occurrence in different habitats and nest types. An identification key to the species occurring in Slovakia is provided, together with taxonomic remarks on the identification and external morphology of some selected species. Parasitic mites have been reported from 119 taxa of Slovakian vertebrates (including man), of which 108 belong to 17 orders of birds. Dermanyssus americanus Ewing and Ornithonyssus bursa (Berlese) are reported from Slovakia for the first time. Examination of older voucher material collected in Slovakia revealed many misidentified specimens: the name Dermanyssus hirundinis (Hermann) has been widely used for misidentified specimens of Dermanyssus carpathicus Zeman; D. americanus was confused with D. hirundinis; while O. bursa has been confused with Ornithonyssus sylviarum (Canestrini & Fanzago). Slovakia is the second country in Europe with known occurrence of the genus Pellonyssus.
Predicting Critical Transitions in ENSO Models. Part I: Methodology and Simple Models with Memory
Authors: Mukhin Dmitry , Loskutov Evgeny , Mukhina Anna , Feigin Alexander , Zaliapin Ilia , Ghil Michael
Published: December 2014

A new empirical approach is proposed for predicting critical transitions in the climate system based on a time series alone. This approach relies on nonlinear stochastic modeling of the system’s time-dependent evolution operator by the analysis of observed behavior. Empirical models that take the form of a discrete random dynamical system are constructed using artificial neural networks; these models include state-dependent stochastic components. To demonstrate the usefulness of such models in predicting critical climate transitions, they are applied here to time series generated by a number of delay-differential equation (DDE) models of sea surface temperature anomalies. These DDE models take into account the main conceptual elements responsible for the El Niño–Southern Oscillation phenomenon. The DDE models used here have been modified to include slow trends in the control parameters in such a way that critical transitions occur beyond the learning interval in the time series. Numerical results suggest that the empirical models proposed herein are able to forecast sequences of critical transitions that manifest themselves in future abrupt changes of the climate system’s statistics.
Parent Participation in a Childhood Immunization Pain Reduction Method
Authors: Franck Linda S. , Berberich F. Ralph , Taddio Anna
Published: December 2014

Objectives. This randomized controlled trial evaluated the effectiveness, feasibility, and acceptability of parent participation (PP) in an evidence-based method to reduce the pain of prekindergarten immunizations. Methods. Healthy children aged 4 to 6 years were randomized to a multimodal distraction method during administration of routine vaccines with PP and 1 medical assistant (experimental group) or 2 medical assistants (standard-of-care comparison group). Children and parents rated the pain after injections, and a blinded observer coded children’s pain from videotapes. Results. In all, 76 children participated. Despite group randomization, more children in the medical assistant–only group received a 3-injection series (25; 68%) than in the PP group (6 [15%], P = .001). After adjustment for this imbalance, child-reported pain was higher in the PP group compared with the medical assistant–only group (2.95 vs 1.75; F = 5.87; df = 1.66; d = 0.64; P < .02). There were no differences between groups for parent-reported and observer-rated measures of pain or in intervention fidelity, duration of procedure, or child or parent satisfaction. Conclusions. Although child-reported pain was higher for the PP group, the magnitude of the difference may not be clinically significant. PP was feasible and acceptable to both parents and children, did not take any longer, and reduced the need for additional medical personnel. Together, these data provide preliminary support for PP for prekindergarten immunization pain management.
Outcomes of Kawasaki Disease
Authors: Uysal Fahrettin , Bostan Ozlem Mehtap , Celebi Solmaz , Uysal Berfin , Hamitoglu Serif , Cil Ergun
Published: December 2014

Objectives: Kawasaki disease (KD) is an acute systemic vasculitis of unknown etiology. Coronary artery lesions (CAL) develop in 15% to 20% of untreated cases. Our objective was to evaluate demographic, clinical, and laboratory features and short-intermediate coronary artery outcomes of children with KD. Patients and Methods: Medical records of patients with KD were retrospectively identified. Clinical information and echocardiography, laboratory, and angiographic results were noted using a standardized form. Results: The study included 44 patients with a mean age of the 29.72 ± 21 months (ranging from 1 month to 9.5 years). There were 28 male and 16 female patients; 20 patients were diagnosed as having had incomplete KD. Four cases with atypical presentation were significantly older than children with complete and incomplete KD; 17 patients (38.6 %) had coronary artery aneurysm (CAA), which declined to 6.8% after intravenous immunoglobulin (IVIG) treatment. Time between fever and diagnosis and abnormal levels of hemoglobin and platelets were all associated with CAA. The children were followed up for a mean of 36.39 ± 19 months (with a maximum of 16 years). Angiographic evolution and regression of CALs have been observed in 14 (82.3%) patients. Three patients in whom CALs persisted did not receive IVIG therapy because of delayed diagnosis. Conclusions: Awareness of KD in children has led to an increase in the number of cases. Utility of IVIG treatment to reduce the coronary artery involvement in patients with delayed diagnoses should be discussed and considered. Long-term results are required to assess whether the KD represents a risk factor for coronary artery diseases seen during adulthood.