bluuebunny/crossref_metadata_2025 huggingface dataset:
Sleep Neurophysiological Dynamics Through the Lens of Multitaper Spectral Analysis
Authors: Prerau Michael J. , Brown Ritchie E. , Bianchi Matt T. , Ellenbogen Jeffrey M. , Purdon Patrick L.
Published: December 2016

During sleep, cortical and subcortical structures within the brain engage in highly structured oscillatory dynamics that can be observed in the electroencephalogram (EEG). The ability to accurately describe changes in sleep state from these oscillations has thus been a major goal of sleep medicine. While numerous studies over the past 50 years have shown sleep to be a continuous, multifocal, dynamic process, long-standing clinical practice categorizes sleep EEG into discrete stages through visual inspection of 30-s epochs. By representing sleep as a coarsely discretized progression of stages, vital neurophysiological information on the dynamic interplay between sleep and arousal is lost. However, by using principled time-frequency spectral analysis methods, the rich dynamics of the sleep EEG are immediately visible—elegantly depicted and quantified at time scales ranging from a full night down to individual microevents. In this paper, we review the neurophysiology of sleep through this lens of dynamic spectral analysis. We begin by reviewing spectral estimation techniques traditionally used in sleep EEG analysis and introduce multitaper spectral analysis, a method that makes EEG spectral estimates clearer and more accurate than traditional approaches. Through the lens of the multitaper spectrogram, we review the oscillations and mechanisms underlying the traditional sleep stages. In doing so, we will demonstrate how multitaper spectral analysis makes the oscillatory structure of traditional sleep states instantaneously visible, closely paralleling the traditional hypnogram, but with a richness of information that suggests novel insights into the neural mechanisms of sleep, as well as novel clinical and research applications.
Antibacterial Properties of Calcium Fluoride-Based Composite Materials:In VitroStudy
Authors: Łukomska-Szymańska Monika , Zarzycka Beata , Grzegorczyk Janina , Sokołowski Krzysztof , Półtorak Konrad , Sokołowski Jerzy , Łapińska Barbara
Published: December 2016

The aim of the study was to evaluate antibacterial activity of composite materials modified with calcium fluoride against cariogenic bacteriaS. mutansandL. acidophilus. One commercially available conventional light-curing composite material containing fluoride ions (F2) and two commercially available flowable light-curing composite materials (Flow Art and X-Flow) modified with 1.5, 2.5, and 5.0 wt% anhydrous calcium fluoride addition were used in the study. Composite material samples were incubated in 0.95% NaCl at 35°C for 3 days; then dilution series ofS. mutansandL. acidophilusstrains were made from the eluates. Bacteria dilutions were cultivated on media afterwards. Colony-forming unit per 1 mL of solution (CFU/mL) was calculated. Composite materials modified with calcium fluoride highly reduced (p<0.001) bacteria growth compared to commercially available composite materials containing fluoride compounds. The greatest reduction in bacteria growth was observed for composite materials modified with 1.5% wt. CaF2. All three tested composite materials showed statistically greater antibacterial activity againstL. acidophilusthan againstS. mutans.
Centering Ability of ProTaper Next and WaveOne Classic in J-Shape Simulated Root Canals
Authors: Troiano Giuseppe , Dioguardi Mario , Cocco Armando , Giuliani Michele , Fabiani Cristiano , D’Alessandro Alfonso , Ciavarella Domenico , Lo Muzio Lorenzo
Published: December 2016

Introduction. The aim of this study was to evaluate and compare the shaping and centering ability of ProTaper Next (PTN; Dentsply Maillefer, Ballaigues, Switzerland) and WaveOne Classic systems (Dentsply Maillefer) in simulated root canals. Methods. Forty J-shaped canals in resin blocks were assigned to two groups (n=20 for each group). Photographic method was used to record pre- and postinstrumentation images. After superimposition, centering and shaping ability were recorded at 9 different levels from the apex using the software Autocad 2013 (Autodesk Inc., San Rafael, USA). Results. Shaping procedures with ProTaper Next resulted in a lower amount of resin removed at each reference point level. In addition, the pattern of centering ability improved after the use of ProTaper Next in 8 of 9 measurement points. Conclusions. Within the limitations of this study, shaping procedures with ProTaper Next instruments demonstrated a lower amount of resin removed and a better centering ability than WaveOne Classic system.
Report on the Medicinal Use of Eleven Lamiaceae Species in Lebanon and Rationalization of Their Antimicrobial Potential by Examination of the Chemical Composition and Antimicrobial Activity of Their Essential Oils
Authors: Khoury Madona , Stien Didier , Eparvier Véronique , Ouaini Naïm , El Beyrouthy Marc
Published: December 2016

Many Lamiaceae species are consumed in the Lebanese cuisine as food or condiment and are largely used in the traditional medicine of Lebanon to treat various diseases, including microbial infections. In this article we report the traditional medicinal uses of eleven Lamiaceae species: Coridothymus capitatus L., Lavandula stoechas L., Lavandula angustifolia Mill., Mentha spicata L. subsp. condensata, Origanum syriacum L., Rosmarinus officinalis, Salvia fruticosa Miller., Satureja cuneifolia Ten., Satureja thymbra L., Thymbra spicata L., and Vitex agnus-castus L. and study the chemical composition and antimicrobial activity of their essential oils (EOs). Our survey showed that Lamiaceae species are mainly used against gastrointestinal disorders and microbial infections. Chemical analysis of the EOs obtained from these plants allowed us to identify seventy‐five compounds describing more than 90% of the relative composition of each EO. Essential oils with high amounts of thymol and carvacrol possessed the strongest antimicrobial activity. As expected, these two compounds demonstrated an interesting antifungal efficacy against the filamentous fungus T. rubrum. Our results confirmed that some of the Lamiaceae species used in Lebanon ethnopharmacological practices as antimicrobial agents do possess antibacterial and antifungal potential consistent with their use in alternative or complementary medicine.
Differentiation Theory over Infinite-Dimensional Banach Spaces
Authors: Asci Claudio
Published: December 2016

We study, for any positive integerkand for any subsetIofN⁎, the Banach spaceEIof the bounded real sequencesxnn∈Iand a measure overRI,B(I)that generalizes thek-dimensional Lebesgue one. Moreover, we expose a differentiation theory for the functions defined over this space. The main result of our paper is a change of variables’ formula for the integration of the measurable real functions onRI,B(I). This change of variables is defined by some infinite-dimensional functions with properties that generalize the analogous ones of the standard finite-dimensional diffeomorphisms.
Exploring the Underlying Genetics of Craniofacial Morphology through Various Sources of Knowledge
Authors: Roosenboom Jasmien , Hens Greet , Mattern Brooke C. , Shriver Mark D. , Claes Peter
Published: December 2016

The craniofacial complex is the billboard of sorts containing information about sex, health, ancestry, kinship, genes, and environment. A thorough knowledge of the genes underlying craniofacial morphology is fundamental to understanding craniofacial biology and evolution. These genes can also provide an important foundation for practical efforts like predicting faces from DNA and phenotype-based facial diagnostics. In this work, we focus on the various sources of knowledge regarding the genes that affect patterns of craniofacial development. Although tremendous successes recently have been made using these sources in both methodology and biology, many challenges remain. Primary among these are precise phenotyping techniques and efficient modeling methods.
Role of CaMKII and PKA in Early Afterdepolarization of Human Ventricular Myocardium Cell: A Computational Model Study
Authors: Dai Ling , Zang Yunliang , Zheng Dingchang , Xia Ling , Gong Yinglan
Published: December 2016

Early afterdepolarization (EAD) plays an important role in arrhythmogenesis. Many experimental studies have reported that Ca2+/calmodulin-dependent protein kinase II (CaMKII) and β-adrenergic signaling pathway are two important regulators. In this study, we developed a modified computational model of human ventricular myocyte to investigate the combined role of CaMKII and β-adrenergic signaling pathway on the occurrence of EADs. Our simulation results showed that (1) CaMKII overexpression facilitates EADs through the prolongation of late sodium current’s (INaL) deactivation progress; (2) the combined effect of CaMKII overexpression and activation of β-adrenergic signaling pathway further increases the risk of EADs, where EADs could occur at shorter cycle length (2000 ms versus 4000 ms) and lower rapid delayed rectifier K+ current (IKr) blockage (77% versus 85%). In summary, this study computationally demonstrated the combined role of CaMKII and β-adrenergic signaling pathway on the occurrence of EADs, which could be useful for searching for therapy strategies to treat EADs related arrhythmogenesis.
Abdominal Massage for the Relief of Constipation in People with Parkinson’s: A Qualitative Study
Authors: McClurg D. , Walker K. , Aitchison P. , Jamieson K. , Dickinson L. , Paul L. , Hagen S. , Cunnington A.-L.
Published: December 2016

Objectives.To explore the experiences of people with Parkinson’s (PwP) who suffer from constipation, the impact this has on their lives, and the effect of using lifestyle changes and abdominal massage as a form of constipation management.Method.Fourteen semistructured interviews were completed (8 males and 6 females; mean age 72.2 years) at the end of a care programme, which consisted of either lifestyle advice and abdominal massage (intervention group;n=7) or lifestyle advice only (control group;n=7). Data were analysed using constant-comparison techniques and Framework methods. Themes and key quotes were identified to depict major findings.Findings.Four key themes were identified: (i) the adverse impact of bowel problems on quality of life; (ii) positive experience of behaviour adjustments: experimentation; (iii) abdominal massage as a dynamic and relaxing tool: experiential learning (intervention group only); (iv) abdominal massage as a contingency plan: hesitation (control group only). Constipation was reported as having a significant impact on quality of life. Participants in both groups perceived lifestyle advice to relieve symptoms. Specific improvements were described in those who also received the abdominal massage.Conclusions.Both lifestyle advice and abdominal massage were perceived to be beneficial in relieving symptoms of constipation for PwP.
Effects of Physical-Cognitive Dual Task Training on Executive Function and Gait Performance in Older Adults: A Randomized Controlled Trial
Authors: Falbo S. , Condello G. , Capranica L. , Forte R. , Pesce C.
Published: December 2016

Physical and cognitive training seem to counteract age-related decline in physical and mental function. Recently, the possibility of integrating cognitive demands into physical training has attracted attention. The purpose of this study was to evaluate the effects of twelve weeks of designed physical-cognitive training on executive cognitive function and gait performance in older adults. Thirty-six healthy, active individuals aged 72.30 ± 5.84 years were assigned to two types of physical training with major focus on physical single task (ST) training (n=16) and physical-cognitive dual task (DT) training (n=20), respectively. They were tested before and after the intervention for executive function (inhibition, working memory) through Random Number Generation and for gait (walking with/without negotiating hurdles) under both single and dual task (ST, DT) conditions. Gait performance improved in both groups, while inhibitory performance decreased after exercise training with ST focus but tended to increase after training with physical-cognitive DT focus. Changes in inhibition performance were correlated with changes in DT walking performance with group differences as a function of motor task complexity (with/without hurdling). The study supports the effectiveness of group exercise classes for older individuals to improve gait performance, with physical-cognitive DT training selectively counteracting the age-related decline in a core executive function essential for daily living.
The Optimization of Passengers’ Travel Time under Express-Slow Mode Based on Suburban Line
Authors: Ding Xiaobing , Yang Xuechen , Hu Hua , Liu Zhigang , Pan Hanchuan
Published: December 2016

The suburban line connects the suburbs and the city centre; it is of huge advantage to attempt the express-slow mode. The passengers’ average travel time is the key factor to reflect the level of rail transport services, especially under the express-slow mode. So it is important to study the passengers’ average travel time under express-slow, which can get benefit on the optimization of operation scheme. First analyze the main factor that affects passengers’ travel time and then mine the dynamic interactive relationship among the factors. Second, a new passengers’ travel time evolution algorithm is proposed after studying the stop schedule and the proportion of express/slow train, and then membrane computing theory algorithm is introduced to solve the model. Finally, Shanghai Metro Line 22 is set as an example to apply the optimization model to calculate the total passengers’ travel time; the result shows that the total average travel time under the express-slow mode can save 1 minute and 38 seconds; the social influence and value of it are very huge. The proposed calculation model is of great help for the decision of stop schedule and provides theoretical and methodological support to determine the proportion of express/slow trains, improves the service level, and enriches and complements the rail transit operation scheme optimization theory system.
Monitoring of Biological Changes in Electromechanical Reshaping of Cartilage Using Imaging Modalities
Authors: Hong Seok Jin , Lee Minseok , Oh Connie J. , Kim Sehwan
Published: December 2016

Electromechanical reshaping (EMR) is a promising surgical technique used to reshape cartilage by direct current and mechanical deformation. It causes local stress relaxation and permanent alterations in the shape of cartilage. The major advantages of EMR are its minimally invasive nature and nonthermal electrochemical mechanism of action. The purpose of this study is to validate that EMR does not cause thermal damage and to observe structural changes in post-EMR cartilage using several imaging modalities. Three imaging modality metrics were used to validate the performance of EMR by identifying structural deformation during cartilage reshaping: infrared thermography was used to sense the temperature of the flat cartilages (16.7°C at 6 V), optical coherence tomography (OCT) was used to examine the change in the cartilage by gauging deformation in the tissue matrix during EMR, and scanning electron microscopy (SEM) was used to show that EMR-treated cartilage is irregularly arranged and the thickness of collagen fibers varies, which affects the change in shape of the cartilage. In conclusion, the three imaging modalities reveal the nonthermal and electromechanical mechanisms of EMR and demonstrate that use of an EMR device is feasible for reshaping cartilage in a minimally invasive manner.
Effects of Active Components of Fuzi and Gancao Compatibility on Bax, Bcl‐2, and Caspase‐3 in Chronic Heart Failure Rats
Authors: Wang Liqin , He Yu , Zhang Yuyan , Zhou Huifen , Yu Li , Yang Jiehong , Wan Haitong
Published: December 2016

Hypaconitine (HA) and glycyrrhetinic acid (GA) are active components of Fuzi (Aconitum carmichaelii) and Gancao (Glycyrrhiza uralensis Fisch); they have been used in compatibility for chronic heart failure (CHF) from ancient times. The purpose of the present research was to explore whether apoptosis pathways were related with the protective effects of HA + GA against CHF rats or not. The rats were progressed with transverse‐aortic constriction (TAC) operation for 4 weeks to build the CHF state, and then the Digoxin (1 mg/kg), HA (2.07 mg/kg), GA (25 mg/kg), and HA (2.07 mg/kg) + GA (25 mg/kg) were orally administrated to rats for 1 week. The levels of BNP and cTnI in the plasma were decreased in the HA + GA group, and the heart/body weight ratio (H/B) and left ventricular (LV) parameters of transthoracic echocardiography were also declined; moreover, the expressions of Bax, Bcl‐2, and caspase‐3 were all improved in the HA + GA group than other groups in the immunohistochemistry and western blot methods. In general, the data suggested that Fuzi and Gancao compatibility could protect the CHF rats from apoptosis, which provided a strong evidence for further searching for mechanisms of them.
Histogenesis of the Oesophagus of Guinea Fowl (Numida meleagris) at Prehatch and Posthatch
Authors: Gosomji Innocent Jonah , Salami Sulaiman Olawoye , Nzalak James Oliver , Kawu Muhammed Umar , Tizhe Emmanuel Vandi , Gurumyen Yilzem George , Dung Edward Christopher
Published: December 2016

The histogenesis of the primordial oesophagus was studied to determine the period in which the tunics of the oesophagus developed and became functional in the helmeted guinea fowl (Numida meleagris). Eighteen embryos and nine keets were studied at prehatch and posthatch, respectively. Simple columnar epithelium surrounded by mesenchymal cells was obvious at the 8th day of embryonic development. By the 19th day of embryonic development, the four tunics, tunica mucosa, submucosa, tunica muscularis, and tunica adventitia/serosa, were beginning to differentiate from the mesenchymal cells and also the primordial oesophageal glands appeared as clusters of cells that invaginate from the epithelium. By the 27th day, the tunics were clearly differentiated and the primordial glands were fully developed as evident with positive reaction to Periodic Acid Schiff (PAS). The tunics of the muscularis were not well developed till at posthatch. This study therefore concludes that the primordial oesophagus is active at the late incubation due to mucin secretion by mucous glands but fully functional at posthatch since the tunica muscularis is completely developed at posthatch.
Low Positive Airway Pressure without Positive End-Expiratory Pressure Decreases Blood Loss during Hepatectomy in Living Liver Donors
Authors: Iguchi Tomohiro , Ikegami Toru , Fujiyoshi Tetsuhiro , Yoshizumi Tomoharu , Shirabe Ken , Maehara Yoshihiko
Published: December 2016

Background/Aims: Despite the development of strategies to minimize blood loss during hepatectomy challenges remain. Our aim was to determine whether low positive airway pressure (PAP) without positive end-expiratory pressure (PEEP) could minimize blood loss during hepatectomy. Methods: Forty-one living liver donors who underwent extended left lobectomy or right lobectomy between December 2012 and November 2013 were retrospectively analyzed. In the standard PAP group (n = 18), tidal volume was 8-10 ml/kg, respiratory rate was 10-12/min and PEEP was maintained at 5 cm H2O. In the low PAP group (n = 23), tidal volume was reduced to 5 ml/kg, respiratory rate was increased to 15/min and PEEP maintained at 0 cm H2O. Low central venous pressure (CVP) was maintained during surgery in all cases. Results: The low PAP group had significantly less blood loss (p = 0.0075) and shorter operation time (p = 0.0303) than the standard PAP group. In multiple regression analysis, ventilation mode and median CVP were found to be determining factors for blood loss. In no case did the ventilation mode affect perioperative management. Conclusions: Low PAP without PEEP is a safe mechanical ventilation mode that might help minimize blood loss along with CVP monitoring during hepatectomy.
Primary Carnitine Deficiency and Newborn Screening for Disorders of the Carnitine Cycle
Authors: Longo Nicola
Published: December 2016

Carnitine is needed for transfer of long-chain fatty acids across the inner mitochondrial membrane for subsequent β-oxidation. Carnitine can be synthesized by the body and is also obtained in the diet through consumption of meat and dairy products. Defects in carnitine transport such as those caused by defective activity of the OCTN2 transporter encoded by the SLC22A5 gene result in primary carnitine deficiency, and newborn screening programmes can identify patients at risk for this condition before irreversible damage. Initial biochemical diagnosis can be confirmed through molecular testing, although direct study of carnitine transport in fibroblasts is very useful to confirm or exclude primary carnitine deficiency in individuals with genetic variations of unknown clinical significance or who continue to have low levels of carnitine despite negative molecular analyses. Genetic defects in carnitine biosynthesis do not generally result in low plasma levels of carnitine. However, deletion of the trimethyllysine hydroxylase gene, a key gene in carnitine biosynthesis, has been associated with non-dysmorphic autism. Thus, new roles for carnitine are emerging that are unrelated to classic inborn errors of metabolism.
Anthracycline-Induced Cardiotoxicity in Young Cancer Patients: The Role of Carnitine
Authors: Armenian Saro H.
Published: December 2016

While the increased rates of survival in childhood cancers have increased progressively in recent decades, many childhood cancer survivors will have at least one chronic health condition within 40 years of age. In this regard, cardiovascular complications have emerged as a leading cause of long-term morbidity and mortality in long-term survivors of childhood cancer, likely due to exposure to anthracycline chemotherapy, and outcomes in patients with anthracycline-related cardiomyopathy remain poor. Some progress has been made in understanding the mechanisms at the basis of anthracycline-related cardiomyopathy, which appear to involve generation of reactive oxygen species, leading to mitochondrial dysfunction, followed by myocyte apoptosis and maladaptive left ventricular remodeling. Even if several guidelines currently exist for monitoring cancer patients treated with cardiotoxic therapies who are at high risk for heart failure, much work remains to be done in finding reliable markers for screening for cardiac dysfunction. Studies from our group have identified alterations in L-carnitine in cancer survivors. While additional investigations are needed, preliminary studies suggest a role for carnitine in primary prevention (during treatment) and secondary prevention (to improve function after treatment).
Round Table Discussion
Authors: Winter Susan , Buist Neil R.M. , Longo Nicola , Armenian Saro H. , Lopaschuk Gary , Wasilewska Anna
Published: December 2016

The 1st International Carnitine Working Group concluded with a round table discussion addressing several areas of relevance. These included the design of future studies that could increase the amount of evidence-based data about the role of carnitine in the treatment of fatty acid oxidation defects, for which substantial controversy still exists. There was general consensus that future trials on the effect of carnitine in disorders of fatty acid oxidation should be randomized, double-blinded, multicentered and minimally include the following diagnoses: medium-chain acyl coenzyme A (CoA) dehydrogenase deficiency, very long-chain acyl-CoA dehydrogenase deficiency, long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency and mitochondrial trifunctional protein deficiency. Another area that generated interest was trials of carnitine in cardiomyopathy and, especially, the use of biomarkers to identify patients at greater risk of cardiotoxicity following treatment with anthracyclines. The possibility that carnitine treatment may lead to improvements in autistic behaviors was also discussed, although the evidence is still not sufficient to make any firm conclusions in this regard. Preliminary data on carnitine levels in children and adolescents with primary hypertension, low birth weight and nephrotic syndrome was also presented. Lastly, the panelists stressed that there remains an objective need to harmonize the terminology used to describe carnitine deficiencies (e.g., primary, secondary and systemic deficiency).
Increased Need for Gastrointestinal Surgery and Increased Risk of Surgery-Related Complications in Patients with Ehlers-Danlos Syndrome: A Systematic Review
Authors: Kulas Søborg Marie-Louise , Leganger Julie , Rosenberg Jacob , Burcharth Jakob
Published: December 2016

Background/Aims: Ehlers-Danlos syndromes (EDSs) constitute a rare group of inherited connective tissue diseases, characterized by multisystemic manifestations and general tissue fragility. Most severe complications include vascular and gastrointestinal (GI) emergencies requiring acute surgery. The purpose of this systematic review was to assess the causes of GI-related surgery and related mortality and morbidity in patients with EDSs. Methods: A systematic search was conducted in PubMed, Embase, and Scopus to identify relevant studies. Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines for systematic reviews were followed. According to eligibility criteria, data were extracted and systematically screened by 2 authors. Results: Screening process identified 11 studies with a total of 1,567 patients. Findings indicated that patients with EDSs had a higher occurrence of surgery demanding GI manifestations, including perforation, hemorrhage, rupture of intra-abdominal organs, and rectal prolapse. Most affected was the vascular subtype, of which up to 33% underwent GI surgery and suffered from a lowered average life expectancy of 48 years (range 6-78). Secondary complications of surgery were common in all patients with EDSs. Conclusion: Studies suggested that patients with EDSs present an increased need for GI surgery, but also an increased risk of surgery-related complications, most predominantly seen in the vascular subtype.
Effects of Total Sleep Deprivation on Mouse Cytokine Levels
Authors: Yang Lin , Li Li , Xue Jianfeng
Published: December 2016

Objective: Cytokines play an integral role in sleep/wake regulation. The objective of this study was to identify how total sleep deprivation affects cytokine levels. Methods: Male C57BL/6 mice were subjected to 48 h of total sleep deprivation produced by brief rotation of activity wheels or 3 different controls: home cage, a sedentary wheel, or forced activity. In addition, the serum levels of cytokines were analyzed using a mouse magnetic bead-based multiplex immunoassay. Results: The concentrations of some cytokines (fibroblast growth factor-basic [FGF-basic], leukemia inhibitory factor [LIF], and monokine induced by interferon-γ [MIG]) decreased significantly after total sleep deprivation. However, other cytokines (macrophage colony-stimulating factor, macrophage inflammatory protein-2, platelet-derived growth factor-bb, vascular endothelial growth factor) did not show any significant difference. Serum corticosterone levels did not differ significantly among the groups. Conclusion: The biochemical mechanisms responsible for sleep regulation are very complex. These results suggest the involvement of 3 cytokines (FGF-basic, LIF, and MIG) in sleep/wake regulation.
Sustained Effects of Neonatal Systemic Lipopolysaccharide on IL-1β and Nrf2 in Adult Rat Substantia Nigra Are Partly Normalized by a Spirulina-Enriched Diet
Authors: Patil Jaspal , Matte Ashok , Nissbrandt Hans , Mallard Carina , Sandberg Mats
Published: December 2016

Background/Aim: Neonatal infection can sensitize the adult substantia nigra (SN) to secondary insults, causing a decrease in antioxidant capacity which may lead to Parkinson's disease in adults. We studied the prolonged effect of systemic infection by (i.p.) administration of lipopolysaccharide (LPS) on interleukin (IL)-1β, the antioxidant regulator nuclear factor-erythroid 2-related factor 2 (Nrf2), and the peroxisome proliferator-activated receptor γ coactivator (PGC)-1α in rat SN. Method and Results: Five-day-old rat pups were treated with LPS (i.p. 2 mg/kg). After 65 days, the mRNA level of IL-1β was significantly increased, in parallel with a decrease in that of the rate-limiting enzyme in glutathione synthesis, the γ-glutamylcysteine ligase catalytic subunit (γGCLc), Nrf2, and brain-derived neurotrophic factor (BDNF). Protein levels of γGCLc and Nrf2 were decreased while IL-1β protein was significantly increased. These LPS-induced long-term changes correlated with a decrease in phosphorylated (active) AKT (pAKT) and phosphorylated (inactive) GSK-3β (pGSK-3β). In another set of experiments, a 0.1% Spirulina-containing diet was given to lactating mothers 24 h before the LPS treatment of the pups. The Spirulina-supplemented diet decreased IL-1β protein expression in SN and elevated the mRNA level of γGCLc, Nrf2 protein, PGC-1α protein, and pAKT. Conclusion: Early-life infection can negatively affect Nrf2, pAKT, and pGSK-3β for a long time in SN. A diet enriched with antioxidant and anti-inflammatory phytochemicals can partly restore some, but not all, of the effects on the antioxidant defense, possibly via normalizing effects on pAKT.
Effectiveness of Vitamin D Supplementation for Cardiovascular Health Outcomes
Authors: Veloudi Panagiota , Jones Graeme , Sharman James E.
Published: December 2016

There is a plausible physiological theory, supported by many observational studies, that vitamin D supplementation should be effective for improving cardiovascular end points, such as blood pressure (BP), large artery stiffness, atherosclerosis, endothelial function and clinical events. However, results from randomised controlled trials (RCTs) have been inconsistent. In this review, we evaluated the evidence regarding the effectiveness of vitamin D supplementation for cardiovascular surrogate and hard clinical end points. RCTs were assessed in terms of sample size, duration of supplementation, baseline vitamin D level inclusion criteria (i.e., absence of vitamin D deficiency), dosage of vitamin D and population under investigation. Forty-five RCTs were identified. Eight RCTs with BP and 6 RCTs with large artery stiffness as the end points were found to comply with guidelines for the optimal design of clinical trials evaluating nutrient effects. Only 2 of the RCTs with an optimal design were effective in decreasing BP with vitamin D supplementation, although these were of moderate sample size (<150) and very short duration (8 weeks for both), whilst no RCT was effective in reducing large artery stiffness. Similar results were observed for atherosclerotic and endothelial function markers as end points. Only 1 RCT reported cardiovascular events as an end point and found neither increased nor decreased incident cardiovascular events over 7 years of follow-up. In conclusion, results from published RCTs indicate that vitamin D supplementation is ineffective in improving cardiovascular health among various patient populations, including in the presence or absence of vitamin D deficiency.
A Retrospective Analysis of Neonatal Encephalocele Predisposing Factors and Outcomes
Authors: Yucetas Seyho Cem , Uçler Necati
Published: December 2016

Objective: This study evaluates the predisposing factors and outcomes of surgical management of encephaloceles at our institution. Materials and Methods: A retrospective analysis of 32 occipital encephaloceles managed operatively at the Neurosurgery Department Clinics of the Faculty of Medicine, Adıyaman University, was performed between 2011 and 2015. Results: Among the study population, 19 mothers had been exposed to TORCH infections (toxoplasma, rubella, cytomegalovirus, herpes simplex virus), 18 were in consanguineous marriages, and 3 had regular prenatal screening. Associated congenital anomalies were common. Eight infants required reoperation, and 9 died during follow-up. Conclusions: The study identified key areas for prevention. Knowledge of the intracranial and associated anomalies can guide management.
HER2-Positive Neuroendocrine Breast Cancer: Case Report and Review of Literature
Authors: Gevorgyan Arpine , Bregni Giacomo , Galli Giulia , Zanardi Elisa , de Braud Filippo , Di Cosimo Serena
Published: December 2016

Background: Neuroendocrine carcinoma is an uncommon histology for breast cancer. Case Report: Our patient underwent right quadrantectomy for a neuroendocrine carcinoma in 1984 and had a bone relapse 30 years later. After thorough pathological and immunohistochemical analysis the diagnosis was confirmed and HER2 amplification was observed. Here we discuss the management, rationale and results of HER2-targeted therapy in advanced neuroendocrine breast carcinoma.
Real-time dose adjustment using point-of-care platelet reactivity testing in a double-blind study of prasugrel in children with sickle cell anaemia
Authors: Hoppe Carolyn C. , Zhou Chunmei , Smith Brendan E. , Brown Patricia B. , Heath Lori E. , Inusa Baba , Rees David C. , Small David S. , Gupta Neehar , Yao Suqin , Heeney Matthew M. , Kanter Julie , Jakubowski Joseph A.
Published: December 2016

Patients with sickle cell anaemia (SCA) have vaso-occlusive crises resulting from occlusive hypoxic-ischaemic injury. Prasugrel inhibits platelet activation and aggregation involved in SCA pathophysiology. Determining Effects of Platelet Inhibition on Vaso-Occlusive Events (DOVE) was a phase 3, double-blind, randomised, placebo-controlled trial assessing prasugrel efficacy. DOVE sought to bring patients’ P2Y12 reaction unit (PRU) value within a targeted range via prasugrel dose adjustments using encrypted VerifyNow P2Y12® (VN-P2Y12) point-of-care testing and an interactive voice-response system (IVRS). After PRU determination, randomised patients received 0.08 mg/kg/day prasugrel or placebo. Encrypted PRUs and IVRS provided double-blind dose adjustments to achieve a defined PRU target range of 136–231; placebo patients had mock titrations. Of 341 randomised patients, 166 placebo and 160 prasugrel patients reached the fully titrated dose (FTD). Most prasugrel patients (n=104, 65 %) remained on the initial 0.08 mg/kg dose; doses escalations occurred in 23 % of patients (n=36). Mean PRUs for the pharmacodynamic population at baseline were similar in the prasugrel (273 ± 44.9) and placebo groups (273 ± 51.7), with significant reductions in PRU (p<0.001) for prasugrel patients at the FTD and at 9 months. Concomitant use of hydroxyurea did not affect platelet reactivity at any time. The majority of prasugrel patients (n=135, 84.4 %) at the FTD were within the target range of 136–231 PRUs. Mean VN-P2Y12 percentage inhibition at baseline was similar in the prasugrel (2.8 ± 5.4 %) and placebo groups (2.0 ± 4.7 %); prasugrel patients had significant increases in inhibition (p<0.001) at FTD and at 9 months. Patients with higher PRU values at baseline required higher prasugrel doses to bring PRU within the prespecified range. DOVE is the first study to successfully employ double-blind, real-time, encrypted, point-of-care platelet testing and IVRS to dose-adjust antiplatelet therapy to a targeted range of platelet inhibition.
Scn2b
Deletion in Mice Results in Ventricular and Atrial Arrhythmias
Authors: Bao Yangyang , Willis B. Cicero , Frasier Chad R. , Lopez-Santiago Luis F. , Lin Xianming , Ramos-Mondragón Roberto , Auerbach David S. , Chen Chunling , Wang Zhenxun , Anumonwo Justus , Valdivia Héctor H. , Delmar Mario , Jalife José , Isom Lori L.
Published: December 2016

Background—

Mutations in
SCN2B
, encoding voltage-gated sodium channel β2-subunits, are associated with human cardiac arrhythmias, including atrial fibrillation and Brugada syndrome. Because of this, we propose that β2-subunits play critical roles in the establishment or maintenance of normal cardiac electric activity in vivo.

Methods and Results—

To understand the pathophysiological roles of β2 in the heart, we investigated the cardiac phenotype of
Scn2b
null mice. We observed reduced sodium and potassium current densities in ventricular myocytes, as well as conduction slowing in the right ventricular outflow tract region. Functional reentry, resulting from the interplay between slowed conduction, prolonged repolarization, and increased incidence of premature ventricular complexes, was found to underlie the mechanism of spontaneous polymorphic ventricular tachycardia.
Scn5a
transcript levels were similar in
Scn2b
null and wild-type ventricles, as were levels of Na
v
1.5 protein, suggesting that similar to the previous work in neurons, the major function of β2-subunits in the ventricle is to chaperone voltage-gated sodium channel α-subunits to the plasma membrane. Interestingly,
Scn2b
deletion resulted in region-specific effects in the heart.
Scn2b
null atria had normal levels of sodium current density compared with wild type.
Scn2b
null hearts were more susceptible to atrial fibrillation, had increased levels of fibrosis, and higher repolarization dispersion than wild-type littermates.

Conclusions—

Genetic deletion of
Scn2b
in mice results in ventricular and atrial arrhythmias, consistent with reported
SCN2B
mutations in human patients.
Extracorporeal Membrane Oxygenation for Hemodynamic Support of Ventricular Tachycardia Ablation
Authors: Baratto Francesca , Pappalardo Federico , Oloriz Teresa , Bisceglia Caterina , Vergara Pasquale , Silberbauer John , Albanese Nicolò , Cireddu Manuela , D’Angelo Giuseppe , Di Prima Ambra Licia , Monaco Fabrizio , Paglino Gabriele , Radinovic Andrea , Regazzoli Damiano , Silvetti Simona , Trevisi Nicola , Zangrillo Alberto , Della Bella Paolo
Published: December 2016

Background—

We report the experience in a cohort of consecutive patients receiving extracorporeal membrane oxygenation during catheter ablation of unstable ventricular tachycardia (VT) at our center.

Methods and Results—

From 2010 to 2015, extracorporeal membrane oxygenation was initiated in 64 patients (average age: 63±15 years; left ventricular ejection fraction in 27±9%; cardiogenic shock in 23%, and electrical storm in 62% of patients) undergoing 74 unstable VT catheter ablation procedures. At least one VT was terminated in 81% of procedures with baseline inducible VT, and VT noninducibility was achieved in 69%. Acute heart failure occurred in 5 patients: 3 underwent emergency heart transplantation, 1 had left ventricular assist device (LVAD) implantation, and 1 patient eventually died because of subsequent mesenteric ischemia. All other patients were discharged alive. After a median follow-up of 21 months (13–28 months), VT recurrence was 33%; overall survival was 56 out of 64 patients (88%). Extracorporeal membrane oxygenation–supported ablation was the bridge to LVAD in 6.9% and to heart transplantation in 3.5% of patients. VT recurrence was related to ablation success (after 180 days of follow up: 19% when VT was noninducible, 42% if nonclinical VT was inducible, 75% when clinical VT was inducible, and 75% in untested patients,
P
<0.001). Incidence of all-cause death, heart transplantation, and LVAD was independently related to ablation outcome (at 180 days of follow-up: 9% when noninducibility was achieved, 50% in case of inducible VT, and 75% in untested patients,
P
<0.001). At multivariable analyses, noninducibility (hazard ratio 0.198;
P
=0.001) and left ventricular ejection fraction (hazard ratio 0.916;
P
=0.008) correlated with all-cause death, LVAD, and heart transplantation.

Conclusions—

Ablation of unstable VTs can be safely supported by extracorporeal membrane oxygenation, which allows rhythm stabilization with low procedure mortality, bridging decompensated patients to permanent LVAD or heart transplantation. Successful ablation is associated with better outcomes than unsuccessful ablation.
Retrieval of the Leadless Cardiac Pacemaker
Authors: Reddy Vivek Y. , Miller Marc A. , Knops Reinoud E. , Neuzil Petr , Defaye Pascal , Jung Werner , Doshi Rahul , Castellani Mark , Strickberger Adam , Mead R. Hardwin , Doppalapudi Harish , Lakkireddy Dhanunjaya , Bennett Matthew , Sperzel Johannes
Published: December 2016

Background—

Leadless cardiac pacemakers have emerged as a safe and effective alternative to conventional transvenous single-chamber ventricular pacemakers. Herein, we report a multicenter experience on the feasibility and safety of acute retrieval (<6 weeks) and chronic retrieval (>6 weeks) of the leadless cardiac pacemaker in humans.

Methods and Results—

This study included patients enrolled in 3 multicenter trials, who received a leadless cardiac pacemaker implant and who subsequently underwent a device removal attempt. The overall leadless pacemaker retrieval success rate was 94%: for patients whose leadless cardiac pacemaker had been implanted for <6 weeks (acute retrieval cohort), complete retrieval was achieved in 100% (n=5/5); for those implanted for ≥ 6 weeks (chronic retrieval cohort), retrieval was achieved in 91% (n=10/11) of patients. The mean duration of time from implant to retrieval attempt was 346 days (range, 88–1188 days) in the chronic retrieval cohort, and nearly two thirds (n=7; 63%) had been implanted for >6 months before the retrieval attempt. There were no procedure-related adverse events at 30 days post retrieval procedure.

Conclusions—

This multicenter experience demonstrated the feasibility and safety of retrieving a chronically implanted single-chamber (right ventricle) active fixation leadless pacemaker.

Clinical Trial Registration—

URL:
https://www.clinicaltrials.gov
. Unique identifiers: NCT02051972, NCT02030418, and NCT01700244.
Pharmacokinetics and Pharmacodynamics of Inorganic Nitrate in Heart Failure With Preserved Ejection Fraction
Authors: Zamani Payman , Tan Victor , Soto-Calderon Haideliza , Beraun Melissa , Brandimarto Jeffrey A. , Trieu Lien , Varakantam Swapna , Doulias Paschalis-Thomas , Townsend Raymond R. , Chittams Jesse , Margulies Kenneth B. , Cappola Thomas P. , Poole David C. , Ischiropoulos Harry , Chirinos Julio A.
Published: December 2016

Rationale:

Nitrate-rich beetroot juice has been shown to improve exercise capacity in heart failure with preserved ejection fraction, but studies using pharmacological preparations of inorganic nitrate are lacking.

Objectives:

To determine (1) the dose–response effect of potassium nitrate (KNO
3
) on exercise capacity; (2) the population-specific pharmacokinetic and safety profile of KNO
3
in heart failure with preserved ejection fraction.

Methods and Results:

We randomized 12 subjects with heart failure with preserved ejection fraction to oral KNO
3
(n=9) or potassium chloride (n=3). Subjects received 6 mmol twice daily during week 1, followed by 6 mmol thrice daily during week 2. Supine cycle ergometry was performed at baseline (visit 1) and after each week (visits 2 and 3). Quality of life was assessed with the Kansas City Cardiomyopathy Questionnaire. The primary efficacy outcome, peak O
2
-uptake, did not significantly improve (
P
=0.13). Exploratory outcomes included exercise duration and quality of life. Exercise duration increased significantly with KNO
3
(visit 1: 9.87, 95% confidence interval [CI] 9.31–10.43 minutes; visit 2: 10.73, 95% CI 10.13–11.33 minute; visit 3: 11.61, 95% CI 11.05–12.17 minutes;
P
=0.002). Improvements in the Kansas City Cardiomyopathy Questionnaire total symptom (visit 1: 58.0, 95% CI 52.5–63.5; visit 2: 66.8, 95% CI 61.3–72.3; visit 3: 70.8, 95% CI 65.3–76.3;
P
=0.016) and functional status scores (visit 1: 62.2, 95% CI 58.5–66.0; visit 2: 68.6, 95% CI 64.9–72.3; visit 3: 71.1, 95% CI 67.3–74.8;
P
=0.01) were seen after KNO
3
. Pronounced elevations in trough levels of nitric oxide metabolites occurred with KNO
3
(visit 2: 199.5, 95% CI 98.7–300.2 μmol/L; visit 3: 471.8, 95% CI 377.8–565.8 μmol/L) versus baseline (visit 1: 38.0, 95% CI 0.00–132.0 μmol/L;
P
<0.001). KNO
3
did not lead to clinically significant hypotension or methemoglobinemia. After 6 mmol of KNO
3
, systolic blood pressure was reduced by a maximum of 17.9 (95% CI −28.3 to −7.6) mm Hg 3.75 hours later. Peak nitric oxide metabolites concentrations were 259.3 (95% CI 176.2–342.4) μmol/L 3.5 hours after ingestion, and the median half-life was 73.0 (interquartile range 33.4–232.0) minutes.

Conclusions:

KNO
3
is potentially well tolerated and improves exercise duration and quality of life in heart failure with preserved ejection fraction. This study reinforces the efficacy of KNO
3
and suggests that larger randomized trials are warranted.

Clinical Trial Registration
:

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT02256345
Associations Between Blood Pressure and Outcomes Among Blacks in the Jackson Heart Study
Authors: Randolph Tiffany C. , Greiner Melissa A. , Egwim Chidiebube , Hernandez Adrian F. , Thomas Kevin L. , Curtis Lesley H. , Muntner Paul , Wang Wei , Mentz Robert J. , O'Brien Emily C.
Published: December 2016

Background

In 2014, new hypertension guidelines liberalized blood pressure goals for persons 60 years and older. Little is known about the implications for blacks.

Methods and Results

Using data from 2000 through 2011 for 5280 participants in the Jackson Heart Study, a community‐based black cohort in Jackson, Mississippi, we examined whether higher blood pressure was associated with greater risk of mortality and heart failure hospitalization, and whether the risk was the same across age groups. We investigated associations between baseline blood pressure and both mortality and heart failure hospitalization. We also tested for interactions between age and blood pressure in the mortality model. Median systolic and diastolic blood pressures at baseline were 125 mm Hg (25th–75th percentile, 114–137 mm Hg) and 79 mm Hg (72–86 mm Hg), respectively. Median follow‐up was 9 years for mortality and 7 years for heart failure hospitalization. After multivariable adjustment, every 10 mm Hg increase in systolic blood pressure was associated with greater risks of mortality (hazard ratio, 1.12; 95%
CI
, 1.06–1.17) and heart failure hospitalization (1.07; 95%
CI
, 1.00–1.14). The mortality risk per 10 mm Hg increase in systolic blood pressure was greater in participants younger than 60 years (1.26; 95%
CI
, 1.13–1.42) than among participants 60 years and older (1.09; 95%
CI
, 1.03–1.15).

Conclusions

Adults in all age groups were at greater risk of mortality as systolic blood pressure increased. In the context of the 2014 hypertension guidelines, these findings should be considered when determining treatment goals in black patients.
Acute Coronary Syndrome and Suicide: A Case‐Referent Study
Authors: Liu Chao‐Han , Yeh Ming‐Kung , Wang Ji‐Hung , Weng Shu‐Chuan , Bai Meng‐Yi , Chang Jung‐Chen
Published: December 2016

Background

The high prevalence of acute coronary syndrome (
ACS
) represents a significant burden on healthcare resources. A robust association exists between depression and increased morbidity and mortality after
ACS
. This study examined the relationship between suicide and
ACS
after adjusting for depression and other comorbidities.

Methods and Results

In this case‐referent study conducted in Taiwan, the cases were people aged 35 years or older who died from suicide between 2000 and 2012 and 4 live referents, each matched by age, sex, and area of residence. The covariates adjusted for in the analysis were sociodemographic characteristics, physical comorbidities, and psychiatric disorders. We identified 41 050 persons who committed suicide and 164 200 referents. In the case and referent groups, 1027 (2.5%) and 2412 (1.5%) patients had
ACS
, respectively. After potential confounders were adjusted,
ACS
was significantly associated with increased odds of suicide (
aOR
=1.15, 95% confidence interval [
CI
]=1.05‐1.26). The odds of suicide were highest during the initial 6 months post‐
ACS
diagnosis (
OR
=3.05, 95%
CI
=2.55‐3.65) and remained high for at least 4 years after
ACS
diagnosis.

Conclusions

ACS
patients are at an increased risk of suicide compared with otherwise healthy people. The risk of suicide is particularly high in the 6 months after
ACS
diagnosis. Our results suggest that we need to identify efficacious methods to recognize those at risk for suicide and to develop effective interventions to prevent such deaths.