bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment with pirfenidone for two years decreases fibrosis, cytokine levels and enhances CB2 gene expression in patients with chronic hepatitis C
Authors: Flores-Contreras Lucia , Sandoval-Rodríguez Ana S , Mena-Enriquez Mayra G , Lucano-Landeros Silvia , Arellano-Olivera Inmaculada , Álvarez-Álvarez Arnulfo , Sanchez-Parada M Guadalupe , Armendáriz-Borunda Juan 
Published: July 2014

Abstract

Background
The aim of this study was to assess whether two-years treatment with Pirfenidone influences necroinflammation, fibrosis and steatosis, serum levels of TGF-β1, IL-6, TNF-α and CB1 and CB2 gene expression, in patients with chronic hepatitis C (CHC).

Methods
Twenty-eight patients out of 34 with CHC virus infection were enrolled in the study and received Pirfenidone (1200 mg/day) for 24 months. Six patients dropped out after 12 months of PFD. Liver biopsies and serum samples were obtained at the beginning and end of treatment. Modified HAI was calculated. CB1 and CB2 gene expression was correlated with fibrosis progression alongside with necroinflammation and steatosis. TGF-β1, IL-6, TNF-α and liver transaminases were measured in serum at two-months intervals. HCV genotype and viral load were also assessed. Quality of life was evaluated by SF36 questionnaires and the prognosis of disease was assessed with Child-Pugh score. The Wilcoxon test matched-pair signed ranks were used to analyze the outcomes.

Results
Intention to treat analyses were performed for biochemistry and clinical parameters. At the end of treatment, necroinflammation grading was reduced in an average of 3.2 points in 82% of patients (p < 0.05) and Ishak’s fibrosis stage decreased 2-points average in 67% of patients (p < 0.05). Steatosis decreased in 61% of patients. IL-6 and TGF-β1 serum levels decreased significantly in 93% and 67% of patients (p < 0.05), respectively, while TNF-α diminished in 47% of patients. ALT and AST tended to normalize in 81% of patients; CB2 mRNA levels increased in 86% and CB1 expression diminished in 29% of patients. Both, quality of life and Child-Pugh score improvements were reported in all patients.

Conclusions
Pirfenidone for two years benefits CHC patients and improves inflammation, fibrosis and steatosis in higher number of patients as previously shown for 12-months treatment with PFD. Additionally, PFD improved TGFβ1 and IL-6 levels and diminished liver expression of anti-fibrogenic receptor CB2.

Trial registration
ClinicalTrials.gov identifier: NCT02161952. Protocol Registration Date: 06/11/2014.
Pain, motor function and health-related quality of life in children with cerebral palsy as reported by their physiotherapists
Authors: Badia Marta , Riquelme Inmaculada , Orgaz Begoña , Acevedo Raquel , Longo Egmar , Montoya Pedro 
Published: July 2014

AbstractBackgroundChildren and adolescents with cerebral palsy suffer from higher levels of pain than their peers without disability. The aim of this study was to explore the impact of pain on health-related quality of life and motor function in individuals with cerebral palsy as reported by health professionals.MethodsCross-sectional study carried out in Associations for Care of Individuals with Cerebral Palsy and Related Disabilities (ASPACE) in Balearic Islands and Castile Leon (Spain). Thirty-five physiotherapists rated pain, health-related quality of life and motor function in 91 children and adolescents with cerebral palsy [8-19y]. A semi-structured interview was used to collect demographic and clinical data according with the Study of Participation of Children with Cerebral Palsy Living in Europe (SPARCLE).ResultsPhysiotherapists reported that 51% of individuals with cerebral palsy suffered from pain. Physiotherapists also perceived that pain in individuals with cerebral palsy was responsible for reductions of psychological but not physical domains of health-related quality of life. According with physiotherapists’ estimations, motor impairment scores were not correlated with pain scores in individuals with cerebral palsy, but they were significantly associated with physical and autonomy domains of health-related quality of life.ConclusionsThese findings highlighted the importance of assessing and providing interventions for pain relief in persons with cerebral palsy even at an early age.
Lung fibrotic tenascin-C upregulation is associated with other extracellular matrix proteins and induced by TGFβ1
Authors: Estany Susanna , Vicens-Zygmunt Vanesa , Llatjós Roger , Montes Ana , Penín Rosa , Escobar Ignacio , Xaubet Antoni , Santos Salud , Manresa Frederic , Dorca Jordi , Molina-Molina Maria 
Published: July 2014

Abstract

Background
Idiopathic pulmonary fibrosis (IPF) is a progressive parenchymal lung disease of unknown aetiology and poor prognosis, characterized by altered tissue repair and fibrosis. The extracellular matrix (ECM) is a critical component in regulating cellular homeostasis and appropriate wound healing. The aim of our study was to determine the expression profile of highlighted ECM proteins in IPF lungs.

Methods
ECM gene and protein expression was analyzed by cDNA microarrays, rt-PCR, immunohistochemistry and western-blot in lungs from idiopathic pulmonary fibrosis (IPF), hypersensitivity pneumonitis (HP), categorized as chronic (cHP) and subacute (saHP), and healthy lung tissue. Primary fibroblast cultures from normal subjects and fibrotic patients were studied to evaluate tenascin-C (TNC) synthesis.

Results
A total of 20 ECM proteins were upregulated and 6 proteins downregulated in IPF. TNC was almost undetected in normal lungs and significantly upregulated in fibrotic lungs (IPF and cHP) compared to saHP. Furthermore, it was located specifically in the fibroblastic foci areas of the fibrotic lung with a subepithelial gradient pattern. TNC levels were correlated with fibroblastic foci content in cHP lungs. Versican and fibronectin glycoproteins were associated with TNC, mainly in fibroblastic foci of fibrotic lungs. Fibroblasts from IPF patients constitutively synthesized higher levels of TNC than normal fibroblasts. TNC and α-sma was induced by TGF-β1 in both fibrotic and normal fibroblasts. TNC treatment of normal and fibrotic fibroblasts induced a non-significant increased α-sma mRNA.

Conclusions
The difference in ECM glycoprotein content in interstitial lung diseases could contribute to the development of lung fibrosis. The increase of TNC in interstitial areas of fibrotic activity could play a key role in the altered wound healing.
Essential pediatric hypertension: defining the educational needs of primary care pediatricians
Authors: Cha Stephen D , Chisolm Deena J , Mahan John D 
Published: July 2014

Abstract

Background
In order to better understand the educational needs regarding appropriate recognition, diagnosis and management of pediatric hypertension (HTN), we asked practicing pediatricians questions regarding their educational needs and comfort level on this topic.

Methods
We conducted 4 focus group sessions that included 27 participants representing pediatric residents, adolescent medicine physicians, clinic based pediatricians and office based pediatricians. Each focus group session lasted for approximately an hour and 90 pages of total transcriptions were produced verbatim from audio recordings.

Results
Four reviewers read each transcript and themes were elucidated from these transcripts. Overall, 5 major themes related to educational needs and clinical concerns were found: utilization of resources to define blood pressure (BP), correct BP measurement method(s), co-morbidities, barriers to care, and experience level with HTN. Six minor themes were also identified: differences in BP measurement, accuracy of BP, recognition of HTN, practice pattern of care, education of families and patients, and differences in level of training. The focus group participants were also questioned on their preferences regarding educational methods (i.e. e-learning, small group sessions, self-study, large group presentations) and revealed varied teaching and learning preferences.

Conclusions
There are multiple methods to approach education regarding pediatric HTN for primary care pediatricians based on provider preferences and multiple educational activities should be pursued to achieve best outcomes. Based on this data, the next direction will be to develop and deliver multiple educational methods and to evaluate the impact on practice patterns of care for children and adolescents with HTN.
Green synthesis of protein capped silver nanoparticles from phytopathogenic fungus Macrophomina phaseolina (Tassi) Goid with antimicrobial properties against multidrug-resistant bacteria
Authors: Chowdhury Supriyo , Basu Arpita , Kundu Surekha 
Published: July 2014

Abstract
In recent years, green synthesis of nanoparticles, i.e., synthesizing nanoparticles using biological sources like bacteria, algae, fungus, or plant extracts have attracted much attention due to its environment-friendly and economic aspects. The present study demonstrates an eco-friendly and low-cost method of biosynthesis of silver nanoparticles using cell-free filtrate of phytopathogenic fungus Macrophomina phaseolina. UV-visible spectrum showed a peak at 450 nm corresponding to the plasmon absorbance of silver nanoparticles. Scanning electron microscopy (SEM), atomic force microscopy (AFM), and transmission electron microscopy (TEM) revealed the presence of spherical silver nanoparticles of the size range 5 to 40 nm, most of these being 16 to 20 nm in diameter. X-ray diffraction (XRD) spectrum of the nanoparticles exhibited 2θ values corresponding to silver nanoparticles. These nanoparticles were found to be naturally protein coated. SDS-PAGE analysis showed the presence of an 85-kDa protein band responsible for capping and stabilization of the silver nanoparticles. Antimicrobial activities of the silver nanoparticles against human as well as plant pathogenic multidrug-resistant bacteria were assayed. The particles showed inhibitory effect on the growth kinetics of human and plant bacteria. Furthermore, the genotoxic potential of the silver nanoparticles with increasing concentrations was evaluated by DNA fragmentation studies using plasmid DNA.
The effectiveness of lasers in the treatment of onychomycosis: a systematic review
Authors: Bristow Ivan R 
Published: July 2014

AbstractBackgroundOnychomycosis is a common nail pathology which has proven to be a treatment challenge to healthcare professionals. Antifungal drugs have been the mainstay of therapy for many years. Recently, laser technologies have been introduced as a treatment for onychomycosis avoiding the disadvantages of systemic and topical drug therapies, offering a rapid treatment for an often persistent nail condition. The purpose of this study was to review published evidence regarding the effectiveness of laser technologies in the treatment of onychomycosis.MethodsThe primary question for this review was “what evidence is there for the use of lasers in the treatment of onychomycosis”? A systematic literature search of published papers indexed on Pubmed and Web of Science® was undertaken in June 2014 for original, published research. The primary outcome measures for efficacy were mycological cure and clearance of the affected nail (clinical cure).ResultsThis review returned a total of twelve eligible published studies evaluating the use of lasers in the treatment of onychomycosis. Two were randomised controlled trials, four were comparative design studies (with no placebo/control groups) and the remainder were case series. The level of evidence was generally low level reflecting predominantly small sample size and lack of control groups. The results from studies were conflicting and follow up periods for patients in studies were generally short. Many studies excluded patients with severe or dystrophic onychomycosis.ConclusionsThe evidence pertaining to the effectiveness of laser treatment of onychomycosis is limited and of poor methodological quality. Future studies using a randomised controlled trial designs with larger study populations and clear procedures are required to permit a full evaluation of this emerging technology.
Tonsillotomy versus tonsillectomy on young children: 2 year post surgery follow-up
Authors: Ericsson Elisabeth , Graf Jonas , Lundeborg-Hammarstrom Inger , Hultcrantz Elisabeth 
Published: July 2014

Objectives To study the long-term effect of tonsillotomy and tonsillectomy in young children after two years in comparison to the results after six months. Method Children, age 4-5 with Sleep Disordered Breathing (SDB) and tonsil hyperplasia, were randomized to TE (32) or TT (35). TT was performed ad modum Hultcrantz with radiofrequency technique (Ellman). An adenoidectomy with cold steel was performed in the same session for 80% of cases. The patients were assessed prior to surgery, at six and 24 months postoperatively. Effects of surgery were evaluated clinically, through questionnaire (general health/snoring/ENT-infections), Quality of Life (QoL), survey of pediatric obstructive sleep apnea with OSA-18, and children's behavior with the Child Behavior Checklist. Results After two years there was still no difference between the groups with respect to snoring and frequency or severity of upper airway infections. Both TT and TE had resulted in large improvement in short and long term QoL and behavior. Three TT-children and one TE child had been re-operated due to recurrence of obstructive problems, the TE-child and one of the TT-children with adenoidectomy and two of the TT-children with tonsillectomy. Three of the TT-children had tonsil tissue protruding slightly out of the tonsil pouch and twelve TE-children had small tonsil remnants within the tonsil pouches, but with no need for surgery. Conclusion Younger children have a small risk of symptom-recurrence requiring re-surgery within two years after TT. For the majority, the positive effect on snoring, infections, behavior and quality of life remain and is similar to TE.
Phosphodiesterase 2A is a major negative regulator of iNOS expression in lipopolysaccharide-treated mouse alveolar macrophages
Authors: Rentsendorj Otgonchimeg , D'Alessio Franco R , Pearse David B 
Published: July 2014

ABSTRACTPDE2A is a dual-function PDE that is stimulated by cGMP to hydrolyze cAMP preferentially. In a two-hit model of ALI, we found previously that PDE2A decreased lung cAMP, up-regulated lung iNOS, and exacerbated ALI. Recent data suggest that macrophage iNOS expression contributes to ALI but later, promotes lung-injury resolution. However, macrophage iNOS is increased by cAMP, suggesting that PDE2A could negatively regulate macrophage iNOS expression. To test this, we examined the effects of manipulating PDE2A expression and function on LPS-induced iNOS expression in a mouse AM cell line (MH-S) and primary mouse AMs. In MH-S cells, LPS (100 ng/ml) increased PDE2A expression by 15% at 15 min and 50% at 6 h before decreasing at 24 h and 48 h. iNOS expression appeared at 6 h and remained increased 48 h post-LPS. Compared with control Ad, Ad.PDE2A-shRNA enhanced LPS-induced iNOS expression further by fourfold, an effect mimicked by the PDE2A inhibitor BAY 60–7550. Adenoviral PDE2A overexpression or treatment with ANP decreased LPS-induced iNOS expression. ANP-induced inhibition of iNOS was lost by knocking down PDE2A and was not mimicked by 8-pCPT-cGMP, a cGMP analog that does not stimulate PDE2A activity. Finally, we found that in primary AMs from LPS-treated mice, PDE2A knockdown also increased iNOS expression, consistent with the MH-S cell data. We conclude that increased AM PDE2A is an important negative regulator of macrophage iNOS expression.
Bocmodifies the spectrum of holoprosencephaly in the absence ofGas1function
Authors: Seppala Maisa , Xavier Guilherme M. , Fan Chen-Ming , Cobourne Martyn T. 
Published: July 2014

ABSTRACTHoloprosencephaly is a heterogeneous developmental malformation of the central nervous system characterized by impaired forebrain cleavage, midline facial anomalies and wide phenotypic variation. Indeed, microforms represent the mildest manifestation, associated with facial anomalies but an intact central nervous system. In many cases, perturbations in sonic hedgehog signaling are responsible for holoprosencephaly. Here, we have elucidated the contribution of Gas1 and an additional hedgehog co-receptor, Boc during early development of the craniofacial midline, by generating single and compound mutant mice. Significantly, we find Boc has an essential role in the etiology of a unique form of lobar holoprosencephaly that only occurs in conjunction with combined loss of Gas1. Whilst Gas1−/− mice have microform holoprosencephaly characterized by a single median maxillary central incisor, cleft palate and pituitary anomalies, Boc−/− mice have a normal facial midline. However, Gas1−/−; Boc−/− mutants have lobar holoprosencephaly associated with clefting of the lip, palate and tongue, secondary to reduced sonic hedgehog transduction in the central nervous system and face. Moreover, maxillary incisor development is severely disrupted in these mice, arresting prior to cellular differentiation as a result of apoptosis in the odontogenic epithelium. Thus, Boc and Gas1 retain an essential function in these tooth germs, independent of their role in midline development of the central nervous system and face. Collectively, this phenotype demonstrates both redundancy and individual requirements for Gas1 and Boc during sonic hedgehog transduction in the craniofacial midline and suggests BOC as a potential digenic locus for lobar holoprosencephaly in human populations.
Molecular cloning of ion channels inFelis catusthat are related to periodic paralyses in man: a contribution to the understanding of the genetic susceptibility to feline neck ventroflexion and paralysis
Authors: Zapata Marlyn , Kunii Ilda S. , Paninka Rolf M. , Simões Denise M. N. , Castillo Víctor A. , Reche Archivaldo , Maciel Rui M. B. , Dias da Silva Magnus R. 
Published: July 2014

ABSTRACTNeck ventroflexion in cats has different causes; however, the most common is the hypokalemia associated with flaccid paralysis secondary to chronic renal failure. In humans, the most common causes of acute flaccid paralysis are hypokalemia precipitated by thyrotoxicosis and familial forms linked to mutations in sodium, potassium, and calcium channel genes. Here, we describe the sequencing and analysis of skeletal muscle ion channels in Felis catus that could be related to periodic paralyses in humans, contributing to the understanding of the genetic susceptibility to feline neck ventroflexion and paralysis. We studied genomic DNA from eleven cats, including five animals that were hyperthyroid with hypokalemia, although only one presented with muscle weakness, and six healthy control domestic cats. We identified the ion channel ortholog genes KCNJ2, KCNJ12, KCNJ14, CACNA1S and SCN4A in the Felis catus genome, together with several polymorphic variants. Upon comparative alignment with other genomes, we found that Felis catus provides evidence for a high genomic conservation of ion channel sequences. Although we hypothesized that neck ventroflexion in cats could be associated with a thyrotoxic or familial periodic paralysis channel mutation, we did not identify any previously detected human channel mutation in the hyperthyroid cat presenting hypokalemia. However, based on the small number of affected cats in this study, we cannot yet rule out this molecular mechanism. Notwithstanding, hyperthyroidism should still be considered as a differential diagnosis in hypokalemic feline paralysis.
Autocrine signaling is a key regulatory element during osteoclastogenesis
Authors: Kopesky Paul , Tiedemann Kerstin , Alkekhia Dahlia , Zechner Christoph , Millard Bjorn , Schoeberl Birgit , Komarova Svetlana V. 
Published: July 2014

ABSTRACT
Osteoclasts are responsible for bone destruction in degenerative, inflammatory and metastatic bone disorders. Although osteoclastogenesis has been well-characterized in mouse models, many questions remain regarding the regulation of osteoclast formation in human diseases. We examined the regulation of human precursors induced to differentiate and fuse into multinucleated osteoclasts by receptor activator of nuclear factor kappa-B ligand (RANKL). High-content single cell microscopy enabled the time-resolved quantification of both the population of monocytic precursors and the emerging osteoclasts. We observed that prior to induction of osteoclast fusion, RANKL stimulated precursor proliferation, acting in part through an autocrine mediator. Cytokines secreted during osteoclastogenesis were resolved using multiplexed quantification combined with a Partial Least Squares Regression model to identify the relative importance of specific cytokines for the osteoclastogenesis outcome. Interleukin 8 (IL-8) was identified as one of RANKL-induced cytokines and validated for its role in osteoclast formation using inhibitors of the IL-8 cognate receptors CXCR1 and CXCR2 or an IL-8 blocking antibody. These insights demonstrate that autocrine signaling induced by RANKL represents a key regulatory component of human osteoclastogenesis.
Increased oxidative metabolism and myoglobin expression in zebrafish muscle during chronic hypoxia
Authors: Jaspers Richard T. , Testerink Janwillem , Della Gaspera Bruno , Chanoine Christophe , Bagowski Christophe P. , van der Laarse Willem J. 
Published: July 2014

ABSTRACT
Fish may be extremely hypoxia resistant. We investigated how muscle fibre size and oxidative capacity in zebrafish (Danio rerio) adapt during severe chronic hypoxia. Zebrafish were kept for either 3 or 6 weeks under chronic constant hypoxia (CCH) (10% air/90%N2 saturated water). We analyzed cross-sectional area (CSA), succinate dehydrogenase (SDH) activity, capillarization, myonuclear density, myoglobin (Mb) concentration and Mb mRNA expression of high and low oxidative muscle fibres. After 3 weeks of CCH, CSA, SDH activity, Mb concentration, capillary and myonuclear density of both muscle fibre types were similar as under normoxia. In contrast, staining intensity for Mb mRNA of hypoxic high oxidative muscle fibres was 94% higher than that of normoxic controls (P&lt;0.001). Between 3 and 6 weeks of CCH, CSA of high and low oxidative muscle fibres increased by 25 and 30%, respectively. This was similar to normoxic controls. Capillary and myonuclear density were not changed by CCH. However, in high oxidative muscle fibres of fish maintained under CCH, SDH activity, Mb concentration as well as Mb mRNA content were higher by 86%, 138% and 90%, respectively, than in muscle fibres of fish kept under normoxia (P&lt;0.001). In low oxidative muscle fibres, SDH activity, Mb and Mb mRNA content were not significantly changed. Under normoxia, the calculated interstitial oxygen tension required to prevent anoxic cores in muscle fibres (PO2crit) of high oxidative muscle fibres was between 1.0 and 1.7 mmHg. These values were similar at 3 and 6 weeks CCH. We conclude that high oxidative skeletal muscle fibres of zebrafish continue to grow and increase oxidative capacity during CCH. Oxygen supply to mitochondria in these fibres may be facilitated by an increased Mb concentration, which is regulated by an increase in Mb mRNA content per myonucleus.