bluuebunny/crossref_metadata_2025_split huggingface dataset:
“Cardio‐Neuromodulation” With a Multielectrode Irrigated Catheter: A Potential New Approach for Patients With Cardio‐Inhibitory Syncope
Authors: DEBRUYNE PHILIPPE 
Published: June 2016

“Cardio‐Neuromodulation”: A New Syncope TreatmentSyncope is frequently neurally mediated and can seriously affect quality of life. Different ablation strategies have been successfully performed. These approaches have not gained wide acceptance and are quite extensive and complex, exposing patients to significant risks. This article reports the case of a 16‐year‐old girl who was severely affected by frequent and prolonged episodes of syncope and was treated by tailored ablation of the anterior right ganglionated plexus with a multielectrode irrigated catheter. She had fainted >30 times in the 5 years preceding treatment, experiencing approximately 10 severe episodes of syncope in the previous 12 months. After 3 minutes of ablation, the P‐P interval was reduced by >400 milliseconds. Syncope disappeared and the patient has remained completely asymptomatic over a follow‐up of 22 months. The “reset” basal P‐P interval has remained unchanged (follow‐up electrocardiogram at 16 months). At 6 months, there was no residual heart rate activity <50 bpm. On 24‐hour rhythm registration, P‐P intervals ≥1,000 milliseconds (corresponding to a heart rate of ≤60 bpm) were reduced by >16,000 beats. We believe that this case report is original for several reasons: the unusual clinical presentation; the unique structure targeted; the very limited ablation, implying much lower risks for the patient; the anatomical approach; and the different endpoint. This new “cardio‐neuromodulation” approach could be useful for the treatment of patients with neurally mediated syncope.
Methylglyoxal induces cell death through endoplasmic reticulum stress‐associated ROS production and mitochondrial dysfunction
Authors: Chan Chi‐Ming , Huang Duen‐Yi , Huang Yi‐Pin , Hsu Shu‐Hao , Kang Lan‐Ya , Shen Chung‐Min , Lin Wan‐Wan 
Published: June 2016

AbstractDiabetic retinopathy (DR) and age‐related macular degeneration (AMD) are two important leading causes of acquired blindness in developed countries. As accumulation of advanced glycation end products (AGEs) in retinal pigment epithelial (RPE) cells plays an important role in both DR and AMD, and the methylglyoxal (MGO) within the AGEs exerts irreversible effects on protein structure and function, it is crucial to understand the underlying mechanism of MGO‐induced RPE cell death. Using ARPE‐19 as the cell model, this study revealed that MGO induces RPE cell death through a caspase‐independent manner, which relying on reactive oxygen species (ROS) formation, mitochondrial membrane potential (MMP) loss, intracellular calcium elevation and endoplasmic reticulum (ER) stress response. Suppression of ROS generation can reverse the MGO‐induced ROS production, MMP loss, intracellular calcium increase and cell death. Moreover, store‐operated calcium channel inhibitors MRS1845 and YM‐58483, but not the inositol 1,4,5‐trisphosphate (IP3) receptor inhibitor xestospongin C, can block MGO‐induced ROS production, MMP loss and sustained intracellular calcium increase in ARPE‐19 cells. Lastly, inhibition of ER stress by salubrinal and 4‐PBA can reduce the MGO‐induced intracellular events and cell death. Therefore, our data indicate that MGO can decrease RPE cell viability, resulting from the ER stress‐dependent intracellular ROS production, MMP loss and increased intracellular calcium increase. As MGO is one of the components of drusen in AMD and is the AGEs adduct in DR, this study could provide a valuable insight into the molecular pathogenesis and therapeutic intervention of AMD and DR.
Aerobic exercise training rescues cardiac protein quality control and blunts endoplasmic reticulum stress in heart failure rats
Authors: Bozi Luiz H. M. , Jannig Paulo R. , Rolim Natale , Voltarelli Vanessa A. , Dourado Paulo M. M. , Wisløff Ulrik , Brum Patricia C. 
Published: June 2016

AbstractCardiac endoplasmic reticulum (ER) stress through accumulation of misfolded proteins plays a pivotal role in cardiovascular diseases. In an attempt to reestablish ER homoeostasis, the unfolded protein response (UPR) is activated. However, if ER stress persists, sustained UPR activation leads to apoptosis. There is no available therapy for ER stress relief. Considering that aerobic exercise training (AET) attenuates oxidative stress, mitochondrial dysfunction and calcium imbalance, it may be a potential strategy to reestablish cardiac ER homoeostasis. We test the hypothesis that AET would attenuate impaired cardiac ER stress after myocardial infarction (MI). Wistar rats underwent to either MI or sham surgeries. Four weeks later, rats underwent to 8 weeks of moderate‐intensity AET. Myocardial infarction rats displayed cardiac dysfunction and lung oedema, suggesting heart failure. Cardiac dysfunction in MI rats was paralleled by increased protein levels of UPR markers (GRP78, DERLIN‐1 and CHOP), accumulation of misfolded and polyubiquitinated proteins, and reduced chymotrypsin‐like proteasome activity. These results suggest an impaired cardiac protein quality control. Aerobic exercise training improved exercise capacity and cardiac function of MI animals. Interestingly, AET blunted MI‐induced ER stress by reducing protein levels of UPR markers, and accumulation of both misfolded and polyubiquinated proteins, which was associated with restored proteasome activity. Taken together, our study provide evidence for AET attenuation of ER stress through the reestablishment of cardiac protein quality control, which contributes to better cardiac function in post‐MI heart failure rats. These results reinforce the importance of AET as primary non‐pharmacological therapy to cardiovascular disease.
Fluorofenidone attenuates pulmonary inflammation and fibrosis via inhibiting the activation of NALP3 inflammasome and IL‐1β/IL‐1R1/MyD88/NF‐κB pathway
Authors: Song Cheng , He Lujuan , Zhang Jin , Ma Hong , Yuan Xiangning , Hu Gaoyun , Tao Lijian , Zhang Jian , Meng Jie 
Published: June 2016

AbstractInterleukin (IL)‐1β plays an important role in the pathogenesis of idiopathic pulmonary fibrosis. The production of IL‐1β is dependent upon caspase‐1‐containing multiprotein complexes called inflammasomes and IL‐1R1/MyD88/NF‐κB pathway. In this study, we explored whether a potential anti‐fibrotic agent fluorofenidone (FD) exerts its anti‐inflammatory and anti‐fibrotic effects through suppressing activation of NACHT, LRR and PYD domains‐containing protein 3 (NALP3) inflammasome and the IL‐1β/IL‐1R1/MyD88/NF‐κB pathway in vivo and in vitro. Male C57BL/6J mice were intratracheally injected with Bleomycin (BLM) or saline. Fluorofenidone was administered throughout the course of the experiment. Lung tissue sections were stained with haemotoxylin and eosin and Masson's trichrome. Cytokines were measured by ELISA, and α‐smooth muscle actin (α‐SMA), fibronectin, collagen I, caspase‐1, IL‐1R1, MyD88 were measured by Western blot and/or RT‐PCR. The human actue monocytic leukaemia cell line (THP‐1) were incubated with monosodium urate (MSU), with or without FD pre‐treatment. The expression of caspase‐1, IL‐1β, NALP3, apoptosis‐associated speck‐like protein containing (ASC) and pro‐caspase‐1 were measured by Western blot, the reactive oxygen species (ROS) generation was detected using the Flow Cytometry, and the interaction of NALP3 inflammasome‐associated molecules were measured by Co‐immunoprecipitation. RLE‐6TN (rat lung epithelial‐T‐antigen negative) cells were incubated with IL‐1β, with or without FD pre‐treatment. The expression of nuclear protein p65 was measured by Western blot. Results showed that FD markedly reduced the expressions of IL‐1β, IL‐6, monocyte chemotactic protein‐1 (MCP‐1), myeloperoxidase (MPO), α‐SMA, fibronectin, collagen I, caspase‐1, IL‐1R1 and MyD88 in mice lung tissues. And FD inhibited MSU‐induced the accumulation of ROS, blocked the interaction of NALP3 inflammasome‐associated molecules, decreased the level of caspase‐1 and IL‐1β in THP‐1 cells. Besides, FD inhibited IL‐1β‐induced the expression of nuclear protein p65. This study demonstrated that FD, attenuates BLM‐induced pulmonary inflammation and fibrosis in mice via inhibiting the activation of NALP3 inflammasome and the IL‐1β/IL‐1R1/MyD88/ NF‐κB pathway.
Mapping the structural organization of the brain in conduct disorder: replication of findings in two independent samples
Authors: Fairchild Graeme , Toschi Nicola , Sully Kate , Sonuga‐Barke Edmund J.S. , Hagan Cindy C. , Diciotti Stefano , Goodyer Ian M. , Calder Andrew J. , Passamonti Luca 
Published: June 2016

BackgroundNeuroimaging methods that allow researchers to investigate structural covariance between brain regions are increasingly being used to study psychiatric disorders. Structural covariance analyses are particularly well suited for studying disorders with putative neurodevelopmental origins as they appear sensitive to changes in the synchronized maturation of different brain regions. We assessed interregional correlations in cortical thickness as a measure of structural covariance, and applied this method to investigate the coordinated development of different brain regions in conduct disorder (CD). We also assessed whether structural covariance measures could differentiate between the childhood‐onset (CO‐CD) and adolescence‐onset (AO‐CD) subtypes of CD, which may differ in terms of etiology and adult outcomes.MethodsWe examined interregional correlations in cortical thickness in male youths with CO‐CD or AO‐CD relative to healthy controls (HCs) in two independent datasets. The age range in the Cambridge sample was 16–21 years (mean: 18.0), whereas the age range of the Southampton sample was 13–18 years (mean: 16.7). We used FreeSurfer to perform segmentations and applied structural covariance methods to the resulting parcellations.ResultsIn both samples, CO‐CD participants displayed a strikingly higher number of significant cross‐cortical correlations compared to HC or AO‐CD participants, whereas AO‐CD participants presented fewer significant correlations than HCs. Group differences in the strength of the interregional correlations were observed in both samples, and each set of results remained significant when controlling for IQ and comorbid attention‐deficit/hyperactivity disorder symptoms.ConclusionsThis study provides new evidence for quantitative differences in structural brain organization between the CO‐CD and AO‐CD subtypes, and supports the hypothesis that both subtypes of CD have neurodevelopmental origins.
PCR and real‐time PCR approaches to the identification of Arthroderma otae species Microsporum canis and Microsporum audouinii/Microsporum ferrugineum
Authors: Kobylak N. , Bykowska B. , Kurzyk E. , Nowicki R. , Brillowska‐Dąbrowska A. 
Published: June 2016

AbstractObjectivesThe identification of species in the Arthroderma otae complex is essential to determine the origin of infection and to eliminate the risk of transmission. Microsporum canis is a zoophilic species, whereas Microsporum audouinii and Microsporum ferrugineum are anthropophilic species. In this paper, we propose alternative methods that permit species‐specific identification of both anthropophilic and zoophilic members of the A. otae complexMethodsTwo PCR assays were designed based on differences in the DNA fragment encoding β‐tubulin and were applied in both traditional and real‐time PCR using DNA isolated by rapid method from culture.ResultThe two assays presented in this study enable the identification of M. canis and M. audouinii/M. ferrugineum with 100% sensitivity and specificity by both traditional and real‐time PCR.ConclusionWe developed a new diagnostic assay using specific primers and both traditional and real‐time PCR reactions that can be applied in routine laboratory praxis as well as in epidemiological studies to detect M. canis and M. audouinii/M. ferrugineum DNA from a pure culture.
Changes in neurosyphilis presentation: a survey on 286 patients
Authors: Drago F. , Merlo G. , Ciccarese G. , Agnoletti A.F. , Cozzani E. , Rebora A. , Parodi A. 
Published: June 2016

AbstractAlthough neurosyphilis (NS) keeps plaguing worldwide, often with oligosymptomatic and atypical manifestations, the most recent reports fail to provide useful information, like details of the clinical history and even of the previous early therapy. We conducted a survey of the literature of the last 5 years on the clinical presentation of NS, recording the aforementioned inaccuracies. One hundred and thirty‐seven articles were collected, reporting on 286 patients. General paresis was the commonest form (49%), often manifesting with cognitive impairment and psychiatric symptoms. Syphilitic meningitis was found in 63 patients (22%), mainly with ocular or auditory involvement. Meningovascular and tabetic form were both found in 12% of cases. Gummatous and epileptic manifestations were rare. Perusal of the literature confirms that NS prevalence is increasing, often with manifestations that are atypical for timing and type of lesions. Unfortunately, many articles are lacking of critical information, like an accurate clinical history and timing of the therapy making difficult to assess the effectiveness of penicillin in preventing NS.
Effects of Blanching and Hot Air Drying Conditions on the Physicochemical and Technological Properties of Yellow Passion Fruit (Passiflora edulis Var. Flavicarpa) by‐Products
Authors: Duarte Y. , Chaux A. , Lopez N. , Largo E. , Ramírez C. , Nuñez H. , Simpson R. , Vega O. 
Published: June 2016

AbstractPassion fruit peel constitutes 50% of the whole fruit; therefore, a method to transform it to an active ingredient would be useful. Hot air drying is the most common process applied to extend the shelf life by reducing water activity. However, the processing conditions must be carefully selected to retain bioactive compounds. The goal of this study was to investigate the effects of blanching, temperature and airflow rate during hot air drying on the physicochemical and technological properties of passion fruit peel. A 32 experimental design with replicates in the central point was used. Three temperatures (50–55–60°C) and three airflow rates (2.4–2.7–3.0 m/s) were used, and the drying curves were analyzed to estimate the effective diffusion (Deff) and drying time. The dried peels were milled and their physicochemical properties (total fiber content and total polyphenol content), and technological properties (water holding capacity, the swelling capacity and the oil holding capacity) were measured. The results showed that the shortest drying time (∼2.5 h) was obtained at 60°C and 2.7 m/s for both control and blanched fruits. The physicochemical and technological properties were not affected by the drying conditions, because the temperatures used were not high enough to be detrimental. In addition, Deff and the physicochemical and technological properties were not affected by blanching due to preserve the samples a slower freezing process (freezing rate <1 cm/h) was performed, which can produce severe damage at the cellular level facilitating water diffusion and therefore can be considered such as pretreatment.Practical ApplicationsConsidering that Passion fruit waste constitutes 50% of the whole fruit and that has a high potential, primarily because it is rich in bioactive compounds, such as vitamins, minerals, polyphenolic compounds with a high antioxidant capacity and dietary fiber it is important study an adequate process to allow stabilize and store the passion fruit by‐products. Therefore, the passion fruit by‐product can be used as active ingredient in the formulation of different kind of foods, specially bakery and pastry products.
Comparison of Frailty Phenotypes for Prediction of Mortality, Incident Falls, and Hip Fracture in Older Women
Authors: Zaslavsky Oleg , Zelber‐Sagi Shira , Gray Shelly L. , LaCroix Andrea Z. , Brunner Robert L. , Wallace Robert B. , O'Sullivan Mary J. , Cochrane Barbara , Woods Nancy F. 
Published: June 2016

ObjectivesTo compare the ability of the commonly used Women's Health Initiative (WHI) and Cardiovascular Health Study (CHS) frailty phenotypes to predict falls, hip fracture, and death in WHI Clinical Trial participants aged 65 and older.DesignLongitudinal cohort study.SettingWHI Clinical Trial.ParticipantsParticipants with data for WHI and CHS frailty phenotypes (N = 3,558).MeasurementsFrailty was operationally defined in the CHS as the presence of three or more of weight loss, poor energy, weakness, slowness, and low physical activity. WHI operationalized frailty similarly but with the RAND‐36 physical function scale substituted for slowness and weakness (RAND‐36 physical function scale score <13 = 2 points, 13–78 = 1 point, >78 = 0 points). Frailty was defined as a summary score of 3 or greater, prefrailty as a score of 2 or 1, and nonfrailty as a score of 0. Outcomes were modeled using Cox regression. Harrell C‐statistics were compared for models containing alternative instruments.ResultsApproximately 5% of participants were frail based on the CHS or WHI phenotype. The WHI frailty phenotype was associated with higher rates of falls (hazard ratio (HR) = 1.48, P = .003), hip fracture (HR = 1.87, P = .04), and death (HR = 2.32, P < .001). Comparable HRs in CHS‐phenotype frail women were 1.32 (P = .04), 1.08 (P = .83), and 1.91 (P < .001), respectively. Harrell C‐statistics revealed marked but insignificant differences in predicting abilities between CHS and WHI phenotype models (P > .50 for all).ConclusionThe WHI phenotype, which does not require direct measurements of physical performance, might offer a practical advantage for epidemiological and clinical needs.
Molecular neuropathology of frontotemporal dementia: insights into disease mechanisms from postmortem studies
Authors: Mackenzie Ian R. A. , Neumann Manuela 
Published: June 2016

AbstractFrontotemporal dementia (FTD) is a clinical syndrome with a heterogeneous molecular basis. The past decade has seen the discovery of several new FTD‐causing genetic mutations and the identification of many of the relevant pathological proteins. The current neuropathological classification is based on the predominant protein abnormality and allows most cases of FTD to be placed into one of three broad molecular subgroups; frontotemporal lobar degeneration with tau, TDP‐43 or FET protein accumulation. This review will describe our current understanding of the molecular basis of FTD, focusing on insights gained from the study of human postmortem tissue, as well as some of the current controversies.
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Most cases of FTD can be subclassified into one of three broad molecular subgroups based on the predominant protein that accumulates as pathological cellular inclusions. Understanding the associated pathogenic mechanisms and recognizing these FTD molecular subtypes in vivo will likely be crucial for the development and use of targeted therapies.
This article is part of the Frontotemporal Dementia special issue.
Absence of neonatal intensive care units in secondary medical care zones is an independent risk factor of high perinatal mortality in Japan
Authors: Matsumoto Yoko , Nakai Akihito , Nishijima Yasuhiro , Kishita Eisaku , Hakuno Haruhiko , Sakoi Masami , Kusuda Satoshi , Unno Nobuya , Tamura Masanori , Fujii Tomoyuki 
Published: June 2016

AbstractAimNational medical projects are carried out according to medical care plans directed by the Medical Care Act of Japan. In order to improve Japanese perinatal medical care, it is necessary to determine the factors that might influence perinatal outcome.MethodsStatistical data of births and perinatal deaths were obtained for all municipalities in Japan from 2008 to 2012 from the Portal Site of Official Statistics of Japan (e‐Stat). The perinatal mortality of all 349 Japanese secondary medical care zones was calculated. The number of neonatal intensive care units (NICUs), maternal‐fetal intensive care units (MFICUs), pediatricians and obstetricians in 2011 were also obtained from e‐Stat. Nine secondary medical care zones in two prefectures, Fukushima (7) and Miyagi (2) were excluded to eliminate the influence of the 2011 Great East Japan Earthquake.ResultsThe 340 secondary medical care zones were divided into three groups according to population size and density: metropolis, provincial city, and depopulation. The number of secondary medical care zones in each group were 52, 168, and 120, respectively. The secondary medical care zones in the depopulation group had fewer pediatricians and significantly fewer NICUs and MFICUs than the metropolis group, but there was no significant difference in perinatal mortality. The only independent risk factor for high perinatal mortality, determined by multivariable analysis, was the absence of an NICU (P = 0.011).ConclusionsTo consider directions in perinatal medical care, planned arrangement and appropriate access to NICUs is indispensable.
Generic medications for hepatitis C
Authors: Jensen Donald M. , Sebhatu Phoebe , Reau Nancy S. 
Published: June 2016

AbstractThe recent development and approval of expensive but highly effective oral agents against hepatitis C has led to restrictions and access limitations in many countries with limited healthcare budgets. Generic formulations of many of these agents are available at a fraction of the retail price in several countries because of generic licensure agreements. The discounted alternatives are only accessible in developing countries and require manufacturing and distribution regulations to ensure the quality and bioequivalence of the new drug formulations. The continued medication access limitations have driven great interest in the practice of personal drug importation of the generic formulations. This review and debate will address the medical and legal issues involved in the purchase and importation of these medicines.
Mutations in the N‐terminal kinase‐like domain of the repressor of photomorphogenesis SPA1 severely impair SPA1 function but not light responsiveness in Arabidopsis
Authors: Holtkotte Xu , Dieterle Stefan , Kokkelink Leonie , Artz Oliver , Leson Lisa , Fittinghoff Kirsten , Hayama Ryosuke , Ahmad Margaret , Hoecker Ute 
Published: June 2016

SummaryThe COP1/SPA complex is an E3 ubiquitin ligase that acts as a key repressor of photomorphogenesis in dark‐grown plants. While both COP1 and the four SPA proteins contain coiled‐coil and WD‐repeat domains, SPA proteins differ from COP1 in carrying an N‐terminal kinase‐like domain that is not present in COP1. Here, we have analyzed the effects of deletions and missense mutations in the N‐terminus of SPA1 when expressed in a spa quadruple mutant background devoid of any other SPA proteins. Deletion of the large N‐terminus of SPA1 severely impaired SPA1 activity in transgenic plants with respect to seedling etiolation, leaf expansion and flowering time. This ΔN SPA1 protein showed a strongly reduced affinity for COP1 in vitro and in vivo, indicating that the N‐terminus contributes to COP1/SPA complex formation. Deletion of only the highly conserved 95 amino acids of the kinase‐like domain did not severely affect SPA1 function nor interactions with COP1 or cryptochromes. In contrast, missense mutations in this part of the kinase‐like domain severely abrogated SPA1 function, suggesting an overriding negative effect of these mutations on SPA1 activity. We therefore hypothesize that the sequence of the kinase‐like domain has been conserved during evolution because it carries structural information important for the activity of SPA1 in darkness. The N‐terminus of SPA1 was not essential for light responsiveness of seedlings, suggesting that photoreceptors can inhibit the COP1/SPA complex in the absence of the SPA1 N‐terminal domain. Together, these results uncover an important, but complex role of the SPA1 N‐terminus in the suppression of photomorphogenesis.