bluuebunny/crossref_metadata_2025 huggingface dataset:
Oxygen consumption, substrate oxidation, and blood pressure following sprint interval exercise
Authors: Chan Huan Hao , Burns Stephen Francis
Published: February 2013

This study examined the acute effect of sprint interval exercise (SIE) on postexercise oxygen consumption, substrate oxidation, and blood pressure. The participants were 10 healthy males aged 21–27 years. Following overnight fasts, each participant undertook 2 trials in a random balanced order: (i) four 30-s bouts of SIE on a cycle ergometer, separated by 4.5 min of recovery, and (ii) resting (control) in the laboratory for an equivalent period. Time-matched measurements of oxygen consumption, respiratory exchange ratio, and blood pressure were made for 2 h into recovery. Total 2-h oxygen consumption was significantly higher in the SIE than in the control trial (mean ± SD: Control: 31.9 ± 6.7 L vs Exercise: 45.5 ± 6.8 L, p < 0.001). The rate of fat oxidation was 75% higher 2 h after the exercise trial compared with the control trial (Control: 0.08 ± 0.05 g·min−1 vs Exercise: 0.14 ± 0.06 g·min−1, p = 0.035). Systolic blood pressure (Control: 117 ± 8 mm Hg vs Exercise: 109 ± 8 mm Hg, p < 0.05) and diastolic blood pressure (Control: 84 ± 6 mm Hg vs Exercise: 77 ± 5 mm Hg, p < 0.05) were significantly lower 2 h after the exercise trial compared with the control trial. These data showed a 42% increase in oxygen consumption (∼13.6 L) over 2 h after a single bout of SIE. Moreover, the rate of fat oxidation increased by 75%, whereas blood pressure was reduced by ∼8 mm Hg 2 h after SIE. Whether these acute benefits of SIE can translate into long-term changes in body composition and an improvement in vascular health needs investigation.
Variation in cougar (Puma concolor) predation habits during wolf (Canis lupus) recovery in the southern Greater Yellowstone Ecosystem
Authors: Bartnick T.D. , Van Deelen T.R. , Quigley H.B. , Craighead D.
Published: February 2013

We examined predation habits of cougars (Puma concolor (L., 1771)) following the recent recovery of gray wolves (Canis lupus L., 1758) in the southern Greater Yellowstone Ecosystem. With the extirpation of wolves in the early 20th century, cougars likely expanded their niche space to include space vacated by wolves, and increased use of habitat better suited to the foraging of a coursing predator, like wolves. We predicted that as wolves recolonized their former range, competitive exclusion would compel cougars to cede portions of niche space occupied in the absence of wolves. To examine this hypothesis, we radio-tracked cougars and examined their predation sites from winter 2000–2001 through summer 2009. Variation in foraging by cougars was associated with increasing wolf presence. As wolf numbers increased and the mean distance between wolf pack activity centers and cougar predation sites decreased, cougars made kills at higher elevations on more north-facing slopes during summer and in more rugged areas during winter. In addition, cougars preyed on a higher proportion of mule deer (Odocoileus hemionus (Rafinesque, 1817)), consistent with predictions of exploitative competition with wolves. Observed changes in predation characteristics reflect differences in predation strategy between cougars and wolves, given that wolves are coursing predators and cougars are ambush predators. These possible predation effects should be considered when developing management strategies in systems where the recolonization of wolves may occur.
HARVESTING IN A STAGE-STRUCTURED POPULATION WITH APPLICATIONS TO THE RED SNAPPER IN THE GULF OF MEXICO
Authors: STURGILL CASSANDRA , DIAMOND SANDRA L. , JANG SOPHIA R.-J.
Published: February 2013

We propose deterministic discrete-time, discrete stage-structured population models with harvesting to investigate population persistence and extinction. The mathematical analysis is centered around the inherent net reproductive number of the population. We apply data of the red snapper in the Gulf of Mexico to simulate the models. We use the models to test for a hypothesis proposed by marine biologists by adding a stochastic component to the deterministic systems that simulating pulses of early juveniles from other populations. We conclude that although pulses of early juveniles from other populations can contribute to the stock size of the early juveniles in the Gulf of Mexico, this contribution is insignificant for the adult population. Therefore, the population may still be in danger of extinction since the ocean environment is unpredictable. Other control strategies are needed in order for the population to be harvested annually.
ON THE POWER QUANTUM COMPUTATION OVER REAL HILBERT SPACES
Authors: McKAGUE MATTHEW
Published: February 2013

We consider the power of various quantum complexity classes with the restriction that states and operators are defined over a real, rather than complex, Hilbert space. It is well known that a quantum circuit over the complex numbers can be transformed into a quantum circuit over the real numbers with the addition of a single qubit. This implies that BQP retains its power when restricted to using states and operations over the reals. We show that the same is true for QMA (k), QIP (k), QMIP and QSZK.
ENTANGLEMENT OF CONVEX LINEAR COMBINATION AND CONSTRUCTION OF PPT ENTANGLED STATES
Authors: CHENG WEI , XU FANG , LI HUA , WANG GANG
Published: February 2013

Given two bipartite quantum states and the convex linear combination of them, we discuss the relation between the entanglement of the convex linear combination state and the entanglement of states being combined. This is achieved by characterizing quantum states quantitatively via the positive partial transpose (PPT) criterion and the computable cross-norm or realignment (CCNR) criterion. Inspired by the Horodecki's 3 ⊗ 3 quantum states, we also give explicit examples to illustrate all possible cases of convex linear combination. Finally, as an application of this method, we show how to construct new bipartite PPT entangled states from known PPT entangled states by convex linear combination.
GABAergic synaptic inputs of locus coeruleus neurons in wild-type and Mecp2-null mice
Authors: Jin Xin , Cui Ningren , Zhong Weiwei , Jin Xiao-Tao , Jiang Chun
Published: February 2013

Rett syndrome is an autism spectrum disorder resulting from defects in the gene encoding the methyl-CpG-binding protein 2 (MeCP2). Deficiency of the Mecp2 gene causes abnormalities in several systems in the brain, especially the norepinephrinergic and GABAergic systems. The norepinephrinergic neurons in the locus coeruleus (LC) modulate a variety of neurons and play an important role in multiple functions in the central nervous system. In Mecp2−/Y mice, defects in the intrinsic membrane properties of LC neurons have been identified, while how their synaptic inputs are affected remains unclear. Therefore, we performed these brain slice studies to demonstrate how LC neurons are regulated by GABAergic inputs and how such synaptic inputs are affected by Mecp2 knockout. In whole cell current clamp, the firing activity of LC neurons was strongly inhibited by the GABAA receptor agonist muscimol, accompanied by hyperpolarization and a decrease in input resistance. Such a postsynaptic inhibition was significantly reduced (by ∼30%) in Mecp2−/Y mice. Post- and presynaptic GABABergic inputs were found in LC neurons, which were likely mediated by the G protein-coupled, Ba2+-sensitive K+ channels. The postsynaptic GABABergic inhibition was deficient by ∼50% in Mecp2 knockout mice. Although the presynaptic GABABergic modulation appeared normal, both frequency and amplitude of the GABAAergic mIPSCs were drastically decreased (by 30–40%) in Mecp2-null mice. These results suggest that the Mecp2 disruption causes defects in both post- and presynaptic GABAergic systems in LC neurons, impairing GABAAergic and GABABergic postsynaptic inhibition and decreasing the GABA release from presynaptic terminals.
Prolonged reaction time during episodes of elevated β-band corticomuscular coupling and associated oscillatory muscle activity
Authors: Matsuya Ryosuke , Ushiyama Junichi , Ushiba Junichi
Published: February 2013

Oscillatory activity in the sensorimotor cortex is coherent with 15–35 Hz band (β-band) muscle activity during tonic isometric voluntary contractions. In human subjects with higher corticomuscular coherence, prominent grouped discharge associated with a significant silent period was observed in electromyographic (EMG) signals. We examined the potential effects of β-band corticomuscular coupling on new ballistic movement as assessed by reaction time (RT). First, we quantified the coherence between electroencephalographic (EEG) signals over the sensorimotor cortex and rectified EMG signals from the tibialis anterior muscle during tonic isometric voluntary dorsiflexion at 30% of maximal effort in 15 healthy subjects. Subjects were divided into 2 groups [i.e., those with significant EEG-EMG coherence (COH+, n = 8) and those with no significant coherence (COH−, n = 7)]. Next, subjects performed ballistic contractions from a preliminary state of sustained contractions in reaction to auditory signals. RT was defined as the interval between the signal and the response onset measured by force. There were no intersubject differences in RT between COH+ and COH−. However, when the trials performed by COH+ subjects were divided into 2 groups depending on whether clear grouped discharge in the β-band was observed in the EMG (GD+ or GD−) just prior to the reaction, RT was significantly longer in the GD+ than in the GD− trials. We found that the magnitude of EEG-EMG coherence just before the reaction was significantly greater in the GD+ than in the GD− trials. These results suggest that generation of a new movement is delayed when corticomuscular coupling is elevated.
Function of the canine inspiratory muscle pump in pleural effusion: influence of body position
Authors: Leduc Dimitri , De Troyer André
Published: February 2013

Pleural effusion, a complicating feature of many diseases of the lung and pleura, adversely affects the pressure-generating capacity of the diaphragm in supine dogs. The objective of the present study was to assess the impact of body position on this effect and to evaluate the adaptation to effusion of the inspiratory muscle pump during breathing. Two experiments were performed. In the first, progressively increasing effusion was induced in anesthetized animals, and the changes in pleural (ΔPpl) and abdominal (ΔPab) pressure were measured during isolated phrenic nerve stimulation while the animals were placed in both the supine and the 45° head-up posture. In the second experiment, graded pleural effusion was also performed, and ΔPpl, ΔPab, and the electromyogram of the parasternal intercostal muscles were measured while the vagotomized animals were breathing spontaneously in the same two postures. The data showed that with effusion 1) ΔPpl during phrenic nerve stimulation was substantially lower with the animals in the head-up than in the supine posture; 2) this postural effect was primarily the result of the decrease in muscle length in the head-up posture; 3) during spontaneous breathing, however, parasternal intercostal inspiratory activity increased and ΔPpl remained unaltered while ΔPab decreased; and 4) the decrease in ΔPab and in the ΔPab/ΔPpl ratio was much larger in the head-up than in the supine posture. It is concluded that in the presence of pleural effusion, the pressure contribution of the inspiratory intercostal muscles during breathing increases and compensates for the shortening of the diaphragm, particularly in the upright posture.
Dexamethasone mimics aspects of physiological acclimatization to 8 hours of hypoxia but suppresses plasma erythropoietin
Authors: Liu Chun , Croft Quentin P. P. , Kalidhar Swati , Brooks Jerome T. , Herigstad Mari , Smith Thomas G. , Dorrington Keith L. , Robbins Peter A.
Published: February 2013

Dexamethasone ameliorates the severity of acute mountain sickness (AMS) but it is unknown whether it obtunds normal physiological responses to hypoxia. We studied whether dexamethasone enhanced or inhibited the ventilatory, cardiovascular, and pulmonary vascular responses to sustained (8 h) hypoxia. Eight healthy volunteers were studied, each on four separate occasions, permitting four different protocols. These were: dexamethasone (20 mg orally) beginning 2 h before a control period of 8 h of air breathing; dexamethasone with 8 h of isocapnic hypoxia (end-tidal Po2 = 50 Torr); placebo with 8 h of air breathing; and placebo with 8 h of isocapnic hypoxia. Before and after each protocol, the following were determined under both euoxic and hypoxic conditions: ventilation; pulmonary artery pressure (estimated using echocardiography to assess maximum tricuspid pressure difference); heart rate; and cardiac output. Plasma concentrations of erythropoietin (EPO) were also determined. Dexamethasone had no early (2-h) effect on any variable. Both dexamethasone and 8 h of hypoxia increased euoxic values of ventilation, pulmonary artery pressure, and heart rate, together with the ventilatory sensitivity to acute hypoxia. These effects were independent and additive. Eight hours of hypoxia, but not dexamethasone, increased the sensitivity of pulmonary artery pressure to acute hypoxia. Dexamethasone, but not 8 h of hypoxia, increased both cardiac output and systemic arterial pressure. Dexamethasone abolished the rise in EPO induced by 8 h of hypoxia. In summary, dexamethasone enhances ventilatory acclimatization to hypoxia. Thus, dexamethasone in AMS may improve oxygenation and thereby indirectly lower pulmonary artery pressure.
The Model Muddle: In Search of Tumor Growth Laws
Authors: Gerlee Philip
Published: February 2013

In this article, we will trace the historical development of tumor growth laws, which in a quantitative fashion describe the increase in tumor mass/volume over time. These models are usually formulated in terms of differential equations that relate the growth rate of the tumor to its current state and range from the simple one-parameter exponential growth model to more advanced models that contain a large number of parameters. Understanding the assumptions and consequences of such models is important, as they often underpin more complex models of tumor growth. The conclusion of this brief survey is that although much improvement has occurred over the last century, more effort and new models are required if we are to understand the intricacies of tumor growth. Cancer Res; 73(8); 2407–11. ©2013 AACR.
Brain Natriuretic Peptide as a Predictor of Cardioembolism in Acute Ischemic Stroke Patients: Brain Natriuretic Peptide Stroke Prospective Study
Authors: Sakai Kenichiro , Shibazaki Kensaku , Kimura Kazumi , Aoki Junya , Kobayashi Kazuto , Fujii Shuichi , Okada Yoko
Published: February 2013

Background and Purpose: Our previous retrospective study demonstrated that a brain natriuretic peptide (BNP) level of >140 pg/ml on admission was useful to distinguish cardioembolism (CE) from non-CE. The aim of the present study was to prospectively investigate the utility of this predefined threshold. Method: Two hundred and twenty-one consecutive patients were prospectively enrolled. On admission, the BNP levels of the patients were measured and classified according to low BNP (≤140.0 pg/ml) or high BNP (>140.0 pg/ml) levels. Final diagnosis of stroke subtype on discharge was made using the TOAST criteria. Measured parameters included the sensitivity, specificity, positive predictive value, and negative predictive value for CE in the high BNP group. Results: There were 81 patients in the high BNP group and 140 patients in the low BNP group. A total of 76 (34.4%) patients were diagnosed with CE, including 59 (72.8%) patients in the high BNP group and 17 (12.1%) patients in the low BNP group (p < 0.001). A BNP level >140.0 pg/ml corresponded to a sensitivity of 77.6%, specificity of 84.8%, positive predictive value of 72.8%, and negative predictive value of 87.9% for a diagnosis of CE. Conclusion: A BNP level of >140.0 pg/ml on admission in patients with acute ischemic stroke is a strong biochemical predictor for CE.
Exfoliative Cytological Assessment of Apparently Normal Buccal Mucosa among Quid Chewers Using Argyrophilic Nucleolar Organizer Region Counts and Papanicolaou Staining
Authors: Mohan Bhavna C. , Angadi Punnya V.
Published: February 2013

Objective: Quid chewing is associated with an increased risk of oral cancer. This study aims to analyze argyrophilic nucleolar organizer region (AgNOR) counts along with Papanicolaou (PAP) staining in exfoliative smears of quid chewers and non-chewers to correlate quid chewing habits with possible early cytological changes in apparently normal buccal mucosa. Study Design: Exfoliative smears were obtained from normal buccal mucosa of 30 male quid chewers and non-chewers. The smears were stained using the AgNOR silver staining technique to evaluate the proliferative activity and PAP for cytological appearance. Results: Statistically higher AgNOR counts were observed in chewers as compared to non-chewers. The difference in the mean percentage of nuclei having ≥5 AgNORs in both groups was statistically significant (p = 0.001). In chewers, PAP showed 77% with class I and the remaining 23% were class II, while the non-chewers showed only class I cytology. AgNOR counts between chewers and non-chewers having class I cytological appearance demonstrated a greater mean AgNOR count in chewers (p = 0.0001). Conclusion: Quid chewing seems to have a definite role in promoting proliferative activity of apparently normal buccal mucosal cells. Exfoliative cytological assessment of a combination of AgNOR counts and PAP has the potential for prediction of early quid-associated cellular changes before the appearance of clinical premalignant and malignant lesions.
Cribriform Morular Variant of Papillary Thyroid Carcinoma: Clinical and Cytomorphological Features on Fine-Needle Aspiration
Authors: Boonyaarunnate Thiraphon , Olson Matthew T. , Bishop Justin A. , Yang Grace C.H. , Ali Syed Z.
Published: February 2013

Background: Cribriform-morular variant of papillary thyroid carcinoma (CMV-PTC) is a rare tumor that may arise in patients with familial adenomatous polyposis (FAP), although sporadic instances of this tumor have been reported. When it arises in FAP, CMV-PTC may present before colonic manifestations are apparent, so proper identification and classification are essential for prompt assessment of the colonic disease status and genetic and familial counseling. Methods: Nine cases of PTC with cribriform morular cytomorphology were identified at 2 large tertiary-care hospitals; 6 were true CMV-PTC with positive β-catenin and 3 were CMV-like PTC with negative β-catenin. A review of the cytomorphology and a cytology-histology correlation were performed. Results: Only 1 patient presented with a known history of FAP. Patients presented with a median age of 41 years (range 19–64 years). There was a clear female predilection; 8 of 9 patients (89%) were female. All cases demonstrated the classical nuclear and architectural features of PTC. In addition, the most salient features were large tissue fragments with cribriform architecture and dense cellular morules. The elongated cellular shape of the tumor cells led to the misclassification of one tumor as a tall-cell variant of PTC on the FNA material. Conclusion: CMV-PTC or CMV-like PTC demonstrate cytomorphological features that overlap with classic PTC. β-Catenin immunostaining plays an important role in making a definitive diagnosis.
Effects of Placental Protein 13 on the Cardiovascular System in Gravid and Non-Gravid Rodents
Authors: Gizurarson Sveinbjorn , Huppertz Berthold , Osol George , Skarphedinsson Jon Olafur , Mandala Maurizio , Meiri Hamutal
Published: February 2013

Objectives: Here, we performed a pathophysiological examination of the vascular function of rodent in the presence of placental protein 13 (PP13) and its implication to regulate the development of preeclampsia. Methods: Single i.v. injection and prolonged in vivo exposure to PP13 via osmotic pumps were performed in gravid and non-gravid rats to examine the influence of PP13 on blood pressure and heart rate in animals. The effect of PP13 was also examined in isolated uterine and mesenteric arteries, along with the examination of placental blood supply. Results: Human PP13 has a major impact on the maternal cardiovascular system of rodents by reducing blood pressure, either at single or prolonged exposure, and causing significant vasodilatation in isolated arteries. Prolonged exposure was followed by increased elaboration and angiogenesis of the uteroplacental arteries supplying the placenta. Conclusion: This is the first study describing effects of PP13 on vasodilatation and uterine artery remodeling. The results imply that PP13 may have a physiological role in improving uteroplacental blood flow. The findings of this study make it tempting to speculate that keeping PP13 levels within a certain ‘therapeutic window' during pregnancy may facilitate proper adaptation of the maternal vasculature to pregnancy.
European Stroke Organization Guidelines for the Management of Intracranial Aneurysms and Subarachnoid Haemorrhage
Authors: Steiner Thorsten , Juvela Seppo , Unterberg Andreas , Jung Carla , Forsting Michael , Rinkel Gabriel
Published: February 2013

Background: Intracranial aneurysm with and without subarachnoid haemorrhage (SAH) is a relevant health problem: The overall incidence is about 9 per 100,000 with a wide range, in some countries up to 20 per 100,000. Mortality rate with conservative treatment within the first months is 50–60%. About one third of patients left with an untreated aneurysm will die from recurrent bleeding within 6 months after recovering from the first bleeding. The prognosis is further influenced by vasospasm, hydrocephalus, delayed ischaemic deficit and other complications. The aim of these guidelines is to provide comprehensive recommendations on the management of SAH with and without aneurysm as well as on unruptured intracranial aneurysm. Methods: We performed an extensive literature search from 1960 to 2011 using Medline and Embase. Members of the writing group met in person and by teleconferences to discuss recommendations. Search results were graded according to the criteria of the European Federation of Neurological Societies. Members of the Guidelines Committee of the European Stroke Organization reviewed the guidelines. Results: These guidelines provide evidence-based information on epidemiology, risk factors and prognosis of SAH and recommendations on diagnostic and therapeutic methods of both ruptured and unruptured intracranial aneurysms. Several risk factors of aneurysm growth and rupture have been identified. We provide recommendations on diagnostic work up, monitoring and general management (blood pressure, blood glucose, temperature, thromboprophylaxis, antiepileptic treatment, use of steroids). Specific therapeutic interventions consider timing of procedures, clipping and coiling. Complications such as hydrocephalus, vasospasm and delayed ischaemic deficit were covered. We also thought to add recommendations on SAH without aneurysm and on unruptured aneurysms. Conclusion: Ruptured intracranial aneurysm with a high rate of subsequent complications is a serious disease needing prompt treatment in centres having high quality of experience of treatment for these patients. These guidelines provide practical, evidence-based advice for the management of patients with intracranial aneurysm with or without rupture. Applying these measures can improve the prognosis of SAH.
Exploring the Ticagrelor-Statin Interplay in the PLATO Trial
Authors: DiNicolantonio James J. , Serebruany Victor L.
Published: February 2013

Context: Much emphasis has been placed on a ticagrelor-aspirin (ASA) interaction in the Platelet Inhibition and Patient Outcomes (PLATO) trial, despite this particular interaction being inconclusive. However, a potential ticagrelor-statin interplay occurred and may be important in PLATO, especially considering the remarkable and yet unexplained mortality advantage. Objective: To explore the ticagrelor-statin interaction in the PLATO trial. Results: The background statin use in hospital or at discharge was similar between ticagrelor (89.7%) and clopidogrel (89.2%) PLATO arms, respectively. In patients on statins, ticagrelor significantly decreased all-cause mortality (30 day and through study end), vascular mortality (30 day and through study end) and exhibited a trend in benefit for 30-day major adverse cardiovascular events (MACE) compared to clopidogrel: hazard ratio, HR = 0.55, 95% confidence interval, CI = 0.36–0.84 (p = 0.005), and HR = 0.69, 95% CI = 0.52–0.92 (p = 0.012); HR = 0.70, 95% CI = 0.51–0.96 (p = 0.030), and HR = 0.68, 95% CI = 0.49–0.94 (p = 0.020), and HR = 0.75, 95% CI = 0.55–1.01 (p = 0.057), respectively. These results may be attributed to the fact that ticagrelor, in contrast to clopidogrel, significantly increases the potency of CYP3A4-metabolized statins, which in turn may increase the vascular benefit derived from the statin, giving an unfair advantage to ticagrelor. Moreover, inappropriate statin dosing restrictions (underdosing of simvastatin and lovastatin) were deliberately utilized in PLATO, potentially contributing to the beneficial effect of ticagrelor. Conclusions: In patients on statins, both vascular and all-cause mortality rates were significantly reduced with ticagrelor in the PLATO trial. However, this benefit may in part be driven by an increased efficacy of CYP3A4-metabolized statins on top of ticagrelor and/or from the inappropriate dose restriction of simvastatin and lovastatin in the clopidogrel arm.
Retinal Microenvironment Imbalance in Dry Age-Related Macular Degeneration: A Mini-Review
Authors: Barnett Brad P. , Handa James T.
Published: February 2013

Background: Age-related macular degeneration (AMD) is the leading cause of blindness in the western world. To prevent what will certainly be a tremendous health and economic burden, effective therapeutics for AMD are urgently needed. To develop these agents in a timely fashion, the molecular pathways that cause disease progression must be elucidated. Objective: To briefly describe the clinical features of AMD, and review the current understanding of the molecular basis of AMD. Methods: A literature review. Results: The discussion will primarily focus on the interplay of oxidative stress and complement dysregulation and the resulting chronic proinflammatory state thought to be central in AMD pathogenesis. Conclusions: Oxidative stress and complement dysregulation play a substantive role in the development of AMD.
Endoscopic Treatment of Interhemispheric Arachnoid Cysts
Authors: Giannetti Alexandre Varella , Ferreira Fraga Sílvia Maria , Silva Márcia Cristina , Gurgel-Giannetti Juliana
Published: February 2013

Background: To describe the neuroendoscopic treatment of interhemispheric arachnoid cysts. Methods: Five children (aged 1-9 months) harboring interhemispheric arachnoid cysts underwent the procedure. The neuroendoscopic technique included cystoventriculostomy and cystocisternostomy. Imaging exams were compared before and after surgery, and the differences in cyst diameters were calculated. Head circumference and neurological development were also evaluated. Results: The cystoventriculostomy was performed through the lateral ventricle in 4 cases and through the third ventricle in 4 cases. An added cystocisternostomy was performed in 1 case. Cyst diameters were reduced in the anterior-posterior, lateral-medial and superior-inferior planes in 22, 31 and 31% of the cases, respectively. The rate of increasing head circumference slowed; however, all the children continued to show slight macrocrania. There were complications in 2 cases: cerebrospinal fluid fistula was managed by lumbar puncture in 1 case and subdural collection was treated with a shunt in another single case. Conclusion: The neuroendoscopic approach to interhemispheric arachnoid cysts was effective with few complications.
Early Inhibition of Natriuresis Suppresses Symptomatic Cerebral Vasospasm in Patients with Aneurysmal Subarachnoid Hemorrhage
Authors: Nakagawa Ichiro , Hironaka Yasuo , Nishimura Fumihiko , Takeshima Yasuhiro , Matsuda Ryosuke , Yamada Shuichi , Motoyama Yasushi , Park Young-Su , Nakase Hiroyuki
Published: February 2013

Background: Hyponatremia is a common complication occurring in one third of patients after subarachnoid hemorrhage (SAH). One mechanism that likely mediates the development of hyponatremia in SAH is cerebral salt wasting syndrome (CSWS), which induces natriuresis and reduces total blood volume, resulting in a risk of symptomatic vasospasm (SVS). The mineral corticoid fludrocortisone acetate enhances sodium reabsorption in the renal distal tubules and may help prevent post-SAH hyponatremia. However, management with fludrocortisone acetate is ineffective if hyponatremia is advanced, because CSWS and subsequent SVS develop rapidly. Therefore, an additional earlier marker is required to predict the development of hyponatremia for the initiation of immediate treatment in select patients. However, no conclusive evidence exists showing that hyponatremia influences the risk of SVS, and no standard treatment protocol exists for treating hyponatremia in patients with SAH. This study was undertaken to evaluate whether selective early treatment of hyponatremia prevents SVS in patients with increased urinary sodium excretion in the early phase following SAH. Methods: A total of 103 patients with aneurysmal SAH were managed for a postoperative electrolyte disorder after aneurysmal clipping or coil embolization. Between 2004 and 2007 (period 1), 54 patients started treatment to correct the electrolyte disorder after hyponatremia had occurred. Between 2007 and 2011 (period 2), 49 patients were prospectively subjected to sodium replacement treatment according to their daily sodium balance, and inhibition of natriuresis with fludrocortisone acetate was initiated just after an increase in urinary sodium excretion >300 mEq/day. The occurrence of hyponatremia, SVS, and outcomes were compared between the two periods. Results: Hyponatremia was observed in 14 patients (26%) in period 1 and 7 patients (14%) in period 2. The incidence of fludrocortisone acetate administration was significantly higher, and initiation of electrolyte correction was significantly earlier, in period 2 patients. We observed a significant difference in the frequency of SVS, which occurred in 10 patients (18.5%) in period 1 and 3 patients (6.1%) in period 2. Both urinary sodium excretion and urine volume at day 7 were significantly different between the two periods. However, no significant difference was observed in overall outcome between the two periods. Conclusions: Early inhibition of natriuresis with fludrocortisone acetate before the occurrence of hyponatremia prevented SVS after aneurysmal SAH. Increased urinary sodium excretion in the early phase of SAH is a good indicator for the initiation of electrolyte correction with fludrocortisone acetate.
White Matter Hyperintensities and Functional Outcomes at 2 Weeks and 1 Year after Stroke
Authors: Kang Hee-Ju , Stewart Robert , Park Man-Seok , Bae Kyung-Yeol , Kim Sung-Wan , Kim Jae-Min , Shin Il-Seon , Cho Ki-Hyun , Yoon Jin-Sang
Published: February 2013

Background: Many stroke survivors remain at a functionally disabled state. Early prediction of functional outcome is an important step in the treatment and care of stroke patients. Brain imaging measures have received particular attention as one of the predictors of stroke outcomes. However, the associations between white matter hyperintensities (WMHs) and post-stroke recovery have been controversial. This study aimed to investigate whether deep and periventricular WMHs (DWMHs and PVWMHs, respectively) were associated with functional outcomes at 2 weeks and 1 year after stroke separately and interactively. Methods: A total of 408 patients were evaluated at the time of admission and 2 weeks after stroke, and 284 (78%) were followed 1 year later in order to evaluate consequences of stroke at both acute and chronic stages. Stroke outcomes were dichotomized into good and poor by applying a modified Rankin Scale (mRS) score cutoff of 1 (no significant disability)/2 (slight disability). Measures of stroke severity (National Institutes of Health Stroke Scale: NIHSS), physical disability (Barthel Index: BI), and cognitive function (Mini-Mental State Examination: MMSE) were administered. Brain magnetic resonance imaging (MRI) was performed at admission. DWMHs and PVWMHs were rated visually on axial FLAIR images using the 4-point modified Fazeka’s scale and categorized into mild (grades 0 and 1) or severe (grades 2 and 3). The demographic and clinical covariates of age, gender, years of education, previous history of stroke, depression, stroke location, and vascular risk factors were obtained. Associations of WMHs with stroke outcomes (mRS) and other measures (NIHSS, BI, and MMSE) at 2 weeks and at 1 year after stroke were investigated using logistic regression and repeated measures ANOVA after adjustment for the potential covariates. Results: Severe PVWMHs, but not severe DWMHs, were significantly associated with worse outcomes both at 2 weeks and at 1 year after stroke. Furthermore, significant interactive effects of PVWMHs and DWMHs on poor outcomes were found. Significant PVWMH group by time interactions on NIHSS and BI scores, and significant group effects of both DWMHs and PVWMHs on MMSE score were found. Conclusions: PVWMHs predicted poorer functional outcomes after stroke both in the acute and chronic phases, independently and interactively with DWMHs. In addition, PVWMHs were independently associated with worsening of stroke severity and physical disability. More careful evaluation and management of stroke patients with a high risk of functional dependence are indicated. Overall, PVWMH might be a prognostic marker of short- and long-term stroke outcomes.
Anti-Oxidative Effect of Vitamin D Analog on Incipient Vascular Lesion in Non-Obese Type 2 Diabetic Rats
Authors: Kono Keiji , Fujii Hideki , Nakai Kentaro , Goto Shunsuke , Kitazawa Riko , Kitazawa Sohei , Shinohara Masami , Hirata Michinori , Fukagawa Masafumi , Nishi Shinichi
Published: February 2013

Background/Aims: Vascular disease is one of the critical complications of diabetes. A growing body of evidence suggests that oxidative stress plays a key role for vascular disease progression. Recent studies have demonstrated a strong link between vitamin D and cardiovascular disease. Methods: We investigated the anti-oxidative effects of a vitamin D analog, 22-oxacalcitriol (maxacalcitol), on vascular lesions in type 2 diabetic rats. We used Spontaneously Diabetic Torii (SDT) rats, a model of non-obese type 2 diabetes. At 20 weeks of age, SDT rats were randomly divided into three groups: diabetes mellitus (DM, n = 10), DM + maxacalcitol (DM + D, n = 10), and DM + insulin (DM + I, n = 10). The rats were sacrificed at 30 weeks for the evaluation of blood and urine samples as well as histopathology and mRNA expression in the aorta. Results: Urinary 8-hydroxydeoxyguanosine (8-OHdG) excretion and the number of 8-OHdG-positive cells were significantly lower in the DM + I and DM + D groups than in the DM group. Real-time polymerase chain reaction analysis demonstrated that NADPH p22 phox and NADPH p47 phox mRNA levels were markedly decreased in the DM + I and DM + D groups compared with the DM group. Furthermore, the mRNA expression of MCP-1, ICAM-1 and VCAM-1 was significantly reduced in the DM + I and DM + D groups compared with the DM group. Conclusion: Our results suggest that the vasoprotective effects of vitamin D are mediated by reducing oxidative stress.
Membranoproliferative Glomerulonephritis and Inflammatory Pseudotumour of the Spleen
Authors: Hadimeri U. , Hultman P. , Larsson R. , Melander S. , Mölne J. , Hadimeri H.
Published: February 2013

Inflammatory pseudotumour is a rare condition that can affect various organs. The clinical and histologic appearance of the pseudotumour may mimic haematological, lymphoproliferative, paraneoplastic or malignant processes. A previously healthy 39-year-old man presented with nephrotic syndrome. He had a history of headaches, nausea and swollen ankles. Computed tomography of the abdomen revealed a 6-cm mass in the spleen. Following a renal biopsy, a diagnosis of membranoproliferative glomerulonephritis (MPGN) type I was made. Splenectomy was performed and the examination revealed a mixed population of lymphocytes with predominantly T-cells, B-cells and lymphoplasmacytoid cells. Immunostaining confirmed that the small cells were mostly T-cells positive for all T-cell markers including CD2, CD3, CD4, CD5, CD7 and CD8. A diagnosis of inflammatory pseudotumour was established. The removal of the spleen was followed by remission of glomerulonephritis, but it was complicated by a subphrenic abscess and pneumonia. This association between an inflammatory pseudotumour of the spleen and MPGN has not been previously described. Abnormal immune response due to the inflammation leading to secondary glomerulonephritis might be the main pathogenic mechanism.
Thioredoxin-Interacting Protein Mediates Sustained VEGFR2 Signaling in Endothelial Cells Required for Angiogenesis
Authors: Park Shin-Young , Shi Xi , Pang Jinjiang , Yan Chen , Berk Bradford C.
Published: February 2013

Objective—

Thioredoxin-interacting protein (TXNIP) is an α-arrestin protein whose function is important for the regulation of vascular endothelial growth factor receptor 2 (VEGFR2) signaling and endothelial cell survival. Because VEGFR2 is critical for angiogenesis, we explored the role of TXNIP in VEGF-induced angiogenesis.

Approach and Results—

TXNIP knockdown inhibited VEGF-induced endothelial cell tube formation and proliferation in cultured human umbilical vein endothelial cell. To elucidate the mechanism by which TXNIP altered VEGFR2 signaling in human umbilical vein endothelial cell, we studied phosphorylation of VEGFR2, phospholipase C gamma-1 (PLCγ1), endothelial NO synthase, and Akt (known as protein kinase B). TXNIP knockdown significantly decreased phosphorylation of VEGFR2 and PLCγ1 at times >5 minutes, but phosphorylation was unchanged at 2 minutes, as was Akt and endothelial NO synthase phosphorylation. Cell-surface biotinylation assay showed that TXNIP knockdown significantly attenuated VEGFR2 internalization. These results suggested that TXNIP was required for sustained VEGFR2 signaling, which is mediated largely by internalized VEGFR2. Rab5 knockdown to inhibit the trafficking and fusion of early endosomes significantly blocked VEGF-induced VEGFR2 internalization and phosphorylation of VEGFR2 and PLCγ1. Immunofluorescence and coimmunoprecipitation showed that TXNIP was part of a complex that included Rab5 and VEGFR2. Finally, TXNIP knockdown prevented the association of VEGFR2 and Rab5.

Conclusions—

Our results show that TXNIP is essential for VEGFR2 internalization in Rab5 positive endosomes, which is required for endothelial cell growth and angiogenesis.
Organ-Specific Protection Against Lipopolysaccharide-Induced Vascular Leak Is Dependent on the Endothelial Protein C Receptor
Authors: von Drygalski Annette , Furlan-Freguia Christian , Ruf Wolfram , Griffin John H. , Mosnier Laurent O.
Published: February 2013

Objective—

To study the role of the endothelial protein C receptor (EPCR) in the modulation of susceptibility to inflammation-induced vascular leak in vivo.

Approach and Results—

Genetically modified mice with low, <10% EPCR expression (EPCR
low
) and control mice were challenged with lipopolysaccharides in a mouse model of endotoxemia. Infrared fluorescence and quantification of albumin-bound Evans Blue in tissues and intravascular plasma volumes were used to assess plasma extravasation. Pair-wise analysis of EPCR
low
and control mice matched for sex, age, and weight allowed determination of EPCR-dependent vascular leak. Kidney, lung, and brain were the organs with highest discriminative increased Evans Blue accumulation in EPCR
low
versus control mice in response to lipopolysaccharides. Histology of kidney and lung confirmed the EPCR-specific pathology. In addition to severe kidney injury in response to lipopolysaccharides, EPCR
low
and anti-EPCR–treated wild-type mice suffered from enhanced albuminuria and profound renal hemorrhage versus controls. Intravascular volume loss at the same extent of weight loss in EPCR
low
mice compared with control mice provided proof that plasma leak was the predominant cause of Evans Blue tissue accumulation.

Conclusions—

This study demonstrates an important protective role for EPCR in vivo against vascular leakage during inflammation and suggests that EPCR-dependent vascular protection is organ-specific.
MicroRNA-145 Restores Contractile Vascular Smooth Muscle Phenotype and Coronary Collateral Growth in the Metabolic Syndrome
Authors: Hutcheson Rebecca , Terry Russell , Chaplin Jennifer , Smith Erika , Musiyenko Alla , Russell James C. , Lincoln Thomas , Rocic Petra
Published: February 2013

Objective—

Transient, repetitive occlusion stimulates coronary collateral growth (CCG) in normal animals. Vascular smooth muscle cells (VSMCs) switch to synthetic phenotype early in CCG, then return to contractile phenotype. CCG is impaired in the metabolic syndrome. We determined whether impaired CCG was attributable to aberrant VSMC phenotypic modulation by miR-145–mediated mechanisms, and whether restoration of physiological miR-145 levels in metabolic syndrome (JCR rat) improved CCG.

Approach and Results—

CCG was stimulated by transient, repetitive left anterior descending artery occlusion and evaluated after 9 days by coronary blood flow measurements (microspheres). miR-145 was delivered to JCR VSMCs via adenoviral vector (miR-145-Adv). In JCR rats, miR-145 was decreased late in CCG (≈2-fold day 6; ≈4-fold day 9 versus SD), which correlated with decreased expression of smooth muscle-specific contractile proteins (≈5-fold day 6; ≈10-fold day 9 versus SD), indicative of VSMCs’ failure to return to the contractile phenotype late in CCG. miR-145 expression in JCR rats (miR-145-Adv) on days 6 to 9 of CCG completely restored VSMCs contractile phenotype and CCG (collateral/normal zone flow ratio was 0.93±0.09 JCR+miR-145-Adv versus 0.12±0.02 JCR versus 0.87±0.02 SD).

Conclusions—

Restoration of VSMC contractile phenotype through miR-145 delivery is a highly promising intervention for restoration of CCG in the metabolic syndrome.
Mechanism-Based Facilitated Maturation of Human Pluripotent Stem Cell–Derived Cardiomyocytes
Authors: Lieu Deborah K. , Fu Ji-Dong , Chiamvimonvat Nipavan , Tung Kelvin Chan , McNerney Gregory P. , Huser Thomas , Keller Gordon , Kong Chi-Wing , Li Ronald A.
Published: February 2013

Background—

Human embryonic stem cells (hESCs) can be efficiently and reproducibly directed into cardiomyocytes (CMs) using stage-specific induction protocols. However, their functional properties and suitability for clinical and other applications have not been evaluated.

Methods and Results—

Here we showed that CMs derived from multiple pluripotent human stem cell lines (hESC: H1, HES2) and types (induced pluripotent stem cell) using different in vitro differentiation protocols (embryoid body formation, endodermal induction, directed differentiation) commonly displayed immature, proarrhythmic action potential properties such as high degree of automaticity, depolarized resting membrane potential, Phase 4- depolarization, and delayed after-depolarization. Among the panoply of sarcolemmal ionic currents investigated (
I
Na
+
/
I
CaL
+
/
I
Kr
+
/
I
NCX
+
/
I
f
+
/
I
to
+
/
I
K1
−
/
I
Ks
−
), we pinpointed the lack of the Kir2.1-encoded inwardly rectifying K
+
current (
I
K1
) as the single mechanistic contributor to the observed immature electrophysiological properties in hESC-CMs. Forced expression of Kir2.1 in hESC-CMs led to robust expression of Ba
2+
-sensitive
I
K1
and, more importantly, completely ablated all the proarrhythmic action potential traits, rendering the electrophysiological phenotype indistinguishable from the adult counterparts. These results provided the first link of a complex developmentally arrested phenotype to a major effector gene, and importantly, further led us to develop a bio-mimetic culturing strategy for enhancing maturation.

Conclusions—

By providing the environmental cues that are missing in conventional culturing method, this approach did not require any genetic or pharmacological interventions. Our findings can facilitate clinical applications, drug discovery, and cardiotoxicity screening by improving the yield, safety, and efficacy of derived CMs.
Microembolism and Catheter Ablation I
Authors: Haines David E. , Stewart Mark T. , Ahlberg Sarah , Barka Noah D. , Condie Cathy , Fiedler Gary R. , Kirchhof Nicole A. , Halimi Franck , Deneke Thomas
Published: February 2013

Background—

Cerebral diffusion-weighted MRI lesions have been observed after catheter ablation of atrial fibrillation. We hypothesized that conditions predisposing to microembolization could be identified using a porcine model of pulmonary vein ablation and an extracorporeal circulation loop.

Methods and Results—

Ablations of the pulmonary veins were performed in 18 swine with echo monitoring. The femoral artery and vein were cannulated and an extracorporeal circulation loop with 2 ultrasonic bubble detectors and a 73-μm filter were placed in series. Microemboli and microbubbles were compared between ablation with an irrigated radiofrequency system (Biosense-Webster) and a phased radiofrequency multielectrode system (pulmonary vein ablation catheter [PVAC], Medtronic, Inc, Carlsbad, CA) in unipolar and 3 blended unipolar/bipolar modes. Animal pathology was examined. The size and number of microbubbles observed during ablation ranged from 30 to 180 μm and 0 to 3253 bubbles per ablation. Microbubble volumes with PVAC (29.1 nL) were greater than with irrigated radiofrequency (0.4 nL;
P
=0.045), and greatest with type II or III microbubbles on transesophageal echocardiography. Ablation with the PVAC showed fewest microbubbles in the unipolar mode (
P
=0.012 versus bipolar). The most occurred during bipolar energy delivery with overlap of proximal and distal electrodes (median microbubble volume, 1744 nL; interquartile range, 737–4082 nL; maximum, 19 516 nL). No cerebral MRI lesions were seen, but 2 animals had renal embolization.

Conclusions—

Left atrial ablation with irrigated radiofrequency and PVAC catheters in swine is associated with microbubble and microembolus production. Avoiding overlap of electrodes 1 and 10 on PVAC should reduce the microembolic burden associated with this procedure.