bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fabry disease: polymorphic haplotypes and a novel missense mutation in the GLA gene
Authors: Ferri L , Guido C , la Marca G , Malvagia S , Cavicchi C , Fiumara A , Barone R , Parini R , Antuzzi D , Feliciani C , Zampetti A , Manna R , Giglio S , Della Valle CM , Wu X , Valenzano KJ , Benjamin ER , Donati MA , Guerrini R , Genuardi M , Morrone A 
Published: April 2011

Ferri L, Guido C, la Marca G, Malvagia S, Cavicchi C, Fiumara A, Barone R, Parini R, Antuzzi D, Feliciani C, Zampetti A, Manna R, Giglio S, Della Valle CM, Wu X, Valenzano KJ, Benjamin ER, Donati MA, Guerrini R, Genuardi M, Morrone A. Fabry disease: polymorphic haplotypes and a novel missense mutation in the GLA gene.Fabry disease (FD) is an X‐linked lysosomal storage disorder with a heterogeneous spectrum of clinical manifestations that are caused by the deficiency of α‐galactosidase A (α‐Gal‐A) activity. Although useful for diagnosis in males, enzyme activity is not a reliable biochemical marker in heterozygous females due to random X‐chromosome inactivation, thus rendering DNA sequencing of the α‐Gal‐A gene, alpha‐galactosidase gene (GLA), the most reliable test for the confirmation of diagnosis in females. The spectrum of GLA mutations is highly heterogeneous. Many polymorphic GLA variants have been described, but it is unclear if haplotypes formed by combinations of such variants correlate with FD, thus complicating molecular diagnosis in females with normal α‐Gal‐A activity. We tested 67 female probands with clinical manifestations that may be associated with FD and 110 control males with normal α‐Gal‐A activity. Five different combinations of GLA polymorphic variants were identified in 14 of the 67 females, whereas clearcut pathogenetic alterations, p.Met51Ile and p.Met290Leu, were identified in two cases. The latter has not been reported so far, and both mutant forms were found to be responsive to the pharmacological chaperone deoxygalactonojirimycin (DGJ; migalastat hydrochloride). Analysis of the male control population, as well as male relatives of a suspected FD female proband, permitted the identification of seven different GLA gene haplotypes in strong linkage disequilibrium. The identification of haplotypes in control males provides evidence against their involvement in the development of FD phenotypic manifestations.
In vitro susceptibility of 188 clinical and environmental isolates of Aspergillus flavus for the new triazole isavuconazole and seven other antifungal drugs
Authors: Shivaprakash M. R. , Geertsen Erik , Chakrabarti Arunaloke , Mouton Johan W. , Meis Jacques F. 
Published: April 2011

SummaryRecently isavuconazole, an experimental triazole agent, was found to be active against Aspergillus species. As Aspergillus flavus is the second‐most common Aspergillus species isolated from human infection and the fungus has not been widely tested against the drug, we studied a large collection of clinical (n = 178) and environmental (n = 10) strains of A. flavus against isavuconazole and compared the results with seven other Aspergillus‐active antifungal agents (some of them triazoles, others echinocandins or polyene antifungals: voriconazole, posaconazole, itraconazole, caspofungin, anidulafungin, micafungin and amphotericin B) using Clinical and Laboratory Standards Institute methods. Strains with high minimal inhibitory concentrations (MICs) were tested by E‐test as well. The strains were collected from two different geographical locations (India and the Netherlands). Three isolates (1.6%) had high MIC (2 mg l−1 by microbroth dilution and 8 mg l−1 by E‐test) for amphotericin B. Isavuconazole showed good activity against A. flavus strains with MIC50 and MIC90 values of 1 mg l−1. As compared with voriconazole (the drug recommended for primary therapy of aspergillosis), isavuconazole had better activity (99.5% of strains had MIC of ≤1 mg l−1 for isavuconazole, compared to 74% of strains with same MIC for voriconazole). All strains were, following recently proposed clinical breakpoints, susceptible for the triazoles tested except three strains, which had MICs of 4 mg l−1 for voriconazole. Testing these strains with high MIC by E‐test, gave results of 0.5–2 mg l−1. Posaconazole had the lowest MIC50 and MIC90 of 0.125 mg l−1 and 0.25 mg l−1, respectively. Among echinocandins, 97% of strains had a minimum effective concentration (MEC) of ≤0.5 mg l−1 for caspofungin, and all strains had a MEC of ≤0.016 mg l−1 and ≤0.125 mg l−1 for anidulafungin and micafungin, respectively.
Pivotal role of pericytes in kidney fibrosis
Authors: Kida Yujiro , Duffield Jeremy S 
Published: April 2011

Summary1. Kidney pericytes were recently identified as collagen Iα1‐producing cells in healthy kidney, but the developmental, physiological and pathological roles of kidney pericytes remain poorly understood. Pericytes are stromal‐derived cells that envelop and have intimate connections with adjacent capillary endothelial cells (EC). Recent studies in the eye and brain have revealed that pericytes are crucial for angiogenesis, vascular stability and vessel integrity.2. In response to kidney injury, pericytes promptly migrate away from the capillary wall into the interstitial space. Here, pericytes are activated and differentiate into scar‐forming myofibroblasts. In the absence of pericytes, peritubular capillaries are destabilized, leading to vascular regression. Consequently, capillary loss and fibrosis following kidney injury are intimately linked and hinge centrally around pericyte detachment from EC.3. Kinetic mathematical modelling has demonstrated that pericytes are the major source of myofibroblasts in the fibrotic kidney. Comprehensive genetic fate mapping studies of nephron epithelia or kidney stroma has demonstrated that epithelial cells do not migrate outside of the epithelial compartment to become myofibroblasts; rather, interstitial pericytes are progenitors of scar‐forming myofibroblasts. Bidirectional signalling between pericytes and EC is necessary for pericyte detachment from peritubular capillaries.4. In the present review, we summarize the pathologically vital roles of kidney pericytes in fibrosis, including our new findings. The study of kidney pericytes and endothelial–pericyte cross‐talk will identify novel therapeutic targets for currently incurable chronic kidney diseases.
Sticking to the facts: a systematic review of fibrin glue for pilonidal disease
Authors: Handmer Marcus 
Published: April 2011

AbstractBackground:  Pilonidal disease occurs when hair invading the natal cleft causes inflammation and abscess formation. Opinions vary on best practice, and most procedures have considerable morbidity and high recurrence rates of 6–40%.Objectives:  This study systematically reviews the use of fibrin glue in the treatment of pilonidal disease. Outcomes measured were healing time and recurrence rate.Data source:  ScienceDirect and PubMed databases were searched for relevant literature, yielding seven papers including five small trials. The total number of patients receiving fibrin glue treatments across all trials was 85. There were no exclusion criteria in this review.Results:  Fibrin glue treatments had equivalent or better reported healing times than conventional therapies at an average of 2–6 weeks, and low recurrence rates between 0 and 17% at follow‐up periods between 4 and 28 months. Considerable heterogeneity in study methodologies and surgical techniques prevented statistical significance or aggregate figures from being determined.Conclusions:  There appears to be early promise for the use of fibrin glue in the treatment of pilonidal disease and an impetus for definitive research.
Inguinal hernia: aetiology, diagnosis, post‐repair pain and compensation
Authors: O'Rourke Michael G. E. , O'Rourke Thomas R. 
Published: April 2011

AbstractBackground:  Inguinal hernia compensation depends on aetiology, diagnosis and complications, particularly post‐hernia pain. New studies in these three areas bring confusion to claims.Methods:  A comprehensive research of the literature using Medline: in aetiology, in diagnoses, the use of ultrasound and/or other investigations, in chronic post‐hernia pain and the understanding of the pathogenesis of hernia and post‐hernia pain. Using the above data, a creation of a protocol for acceptance of compensation claim.Results:  Although intra‐abdominal pressure has been accepted for 200 years as a significant aetiological factor in inguinal hernia, tissue studies and prospective studies suggest an inevitability. In diagnosis, the clinical detection of a lump is the gold standard; investigations are not required. An ultrasonic detection of a hernia without clinical correlation does not require surgery. Post‐hernia chronic pain is not singular to hernia, is now considered neuropathic pain and treatment is conservative.Conclusions:  The work scene is possibly an aggravating factor but not a prime aetiological factor. The diagnosis does not require ultrasound. Chronic pain is neuropathic. A protocol for claim acceptance is presented.
Prospective evaluation of the self‐pressurized air‐Q intubating laryngeal airway in children
Authors: Jagannathan Narasimhan , Sohn Lisa E. , Mankoo Ravinder , Langen Kenneth E. , Roth Andrew G. , Hall Steven C. 
Published: April 2011

SummaryObjectives:  To assess the clinical efficacy of the self‐pressurized air‐Q ILA™ (ILA‐SP).Aim:  The purpose of this prospective audit was to evaluate the feasibility of the ILA‐SP in clinical practice and generate data for future comparison trials.Background:  The ILA‐SP is a new first‐generation supraglottic airway for children with a self‐adjusting cuff and lack of a pilot balloon.Methods:  Over a 4‐month period, 352 children with an ASA physical status of I–III, newborn to 18 years of age, undergoing various procedures were studied. Data points assessed included insertion success rates, airway leak pressures, quality of ventilation, and perioperative complications associated with the use of this device.Results:  In 349 of the 352 patients in this study, the ILA‐SP was used successfully as a primary supraglottic airway device in a variety of patients. Three patients required conversion to a standard laryngeal mask airway or a tracheal tube. The mean initial airway leak pressure for all patients was 17.8 ± 5.4 cm H2O, and 20.4 ± 5.5 cm H2O when re‐checked at 10 min, which was statistically significant (P < 0.001). Complications were limited to 14 patients and related to reflex activation of the airway (coughing, laryngospasm, and bronchospasm) (n = 10), sore throat (n = 3), and blood staining on removal of the device (n = 1). There were no episodes of regurgitation, aspiration, or hoarseness.Conclusions:  Acceptable clinical performance was demonstrated with the ILA‐SP for a variety of procedures in infants and children with spontaneous and positive pressure ventilation. Future studies comparing this device to other supraglottic airways may provide useful information regarding the safety of the ILA‐SP in pediatric clinical practice.
Medication errors – new approaches to prevention
Authors: Merry Alan F. , Anderson Brian J. 
Published: April 2011

SummaryMedication errors in pediatric anesthesia represent an important risk to children. Concerted action to reduce harm from this cause is overdue. An understanding of the genesis of avoidable adverse drug events may facilitate the development of effective countermeasures to the events or their effects. Errors include those involving the automatic system of cognition and those involving the reflective system. Errors and violations are distinct, but violations often predispose to error. The system of medication administration is complex, and many aspects of it are conducive to error. Evidence‐based practices to reduce the risk of medication error in general include those encompassed by the following recommendations: systematic countermeasures should be used to decrease the number of drug administration errors in anesthesia; the label on any drug ampoule or syringe should be read carefully before a drug is drawn up or injected; the legibility and contents of labels on ampoules and syringes should be optimized according to agreed standards; syringes should always be labeled; formal organization of drug drawers and workspaces should be used; labels should be checked with a second person or a device before a drug is drawn up or administered. Dosage errors are particularly common in pediatric patients. Causes that should be addressed include a lack of pediatric formulations and/or presentations of medication that necessitates dilution before administration or the use of intravenous formulations for oral administration in children, a frequent failure to obtain accurate weights for patients and a paucity of pharmacokinetic and pharmacodynamic data. Technological innovations, including the use of bar codes and various cognitive aids, may facilitate compliance with these recommendations. Improved medication safety requires a system‐wide strategy standardized at least to the level of the institution; it is the responsibility of institutional leadership to introduce such strategies and of individual practitioners to engage in them.
Sacral nerve modulation in the treatment of chronic pain after pelvic surgery
Authors: Martellucci J. , Naldini G. , Del Popolo G. , Carriero A. 
Published: April 2011

AbstractAim  The aim of the study was to evaluate the efficacy of sacral nerve modulation for chronic pelvic pain after pelvic or anal surgery for benign disease.Method  From January 2004 to December 2009, 17 (14 female; age 56 years) consecutive patients suffering from chronic pelvic pain underwent evaluation for sacral nerve modulation in three pelvic floor units.Results  The previous surgery included stapled transanal rectal resection (five), hysterectomy (four), haemorrhoidectomy (two), stapled haemorrhoidopexy (one), fistulectomy (one), urethral sphincterotomy (one), appendicectomy (one), discectomy (one) and laparoscopy for endometriosis (one). Eight (47%) patients fulfilled the criteria for definitive implantation and were followed for a mean of 39 months. Using a visual analog pain score, pain levels fell from 8.2 preoperatively to 1.9, 2.1, 2.0 and 1.8 at 6, 12, 24 and 36 months, respectively. Age < 60 years and duration of symptoms of < 24 months were good predictors and stapling was a poor predictor of success.Conclusion  Sacral nerve modulation seems to be effective over time in some patients with chronic pain related to previous surgery.
Spermatogenesis and changes in testicular structure during the reproductive cycle in Cichlasoma dimerus (Teleostei, Perciformes)
Authors: Vázquez Graciela Rey , Cuña Rodrigo H. Da , Meijide Fernando J. , Guerrero Graciela A. 
Published: April 2011

AbstractRey Vázquez, G., Da Cuña, R.H., Meijide, F.J., and Guerrero, G.A. 2012. Spermatogenesis and changes in testicular structure during the reproductive cycle in Cichlasoma dimerus (Teleostei, Perciformes). —Acta Zoologica (Stockholm) 93: 338–350.The present study aimed at analyzing spermatogenesis and the changes occurring in the testis throughout the reproductive cycle in the South American perciform fish Cichlasoma dimerus. Testes were studied using light and electron microscopy techniques. This species has an unrestricted lobular testis composed of two compartments: germinal, containing Sertoli and germ cells, exhibiting a cystic mode of spermatogenesis; and interstitial, composed of Leydig cells and connective tissue elements. Spermatozoa belong to the anacrosomal type I aquasperm and possess two flagella, this being the first report of an externally fertilizing cichlid exhibiting biflagellate sperm. Under laboratory conditions, C. dimerus proved to be a multiple spawner throughout the year, with a season of higher reproductive activity extending from September to March, during which fish spawned on average every 29.4 days. Changes in the germinal epithelium and the germ cell stages present allowed the description of five reproductive classes: regressed, early, mid‐, and late maturation, and regression. During the high reproductive season, each cycle went through the first four classes. The regressed class overlapped with the late maturation class, because sperm was being released while spermatogonia were proliferating. The regression class occurred solely in sexually inactive males during the period of low reproductive activity.
Meal‐induced increases in C‐reactive protein, interleukin‐6 and tumour necrosis factor α are attenuated by prandial + basal insulin in patients with Type 2 diabetes
Authors: Beisswenger P. J. , Brown W. V. , Ceriello A. , Le N. A. , Goldberg R. B. , Cooke J. P. , Robbins D. C. , Sarwat S. , Yuan H. , Jones C. A. , Tan M. H. ,   for the IOOI Study Investigators
Published: April 2011

Diabet. Med. 28, 1088–1095 (2011)AbstractAim  To determine if a regimen with prandial + basal insulin compared with basal insulin attenuates post‐meal inflammatory and glycative biomarkers in patients with Type 2 diabetes.Methods  This test‐meal sub‐study in the USA is from a previously reported clinical trial comparing the effect on glycaemic control of 24 weeks of thrice‐daily pre‐meal insulin lispro mix 50 (50% insulin lispro, 50% insulin lispro protamine suspension) or bedtime insulin glargine, both plus metformin. In the sub‐study, glucose, insulin, triglycerides, high‐sensitivity C‐reactive protein, tumour necrosis factor α, interleukin‐6, methylglyoxal and 3‐deoxyglucosone were measured during the post‐meal period of a mixed‐meal breakfast at the final visit. Prandial + basal (n = 25) and basal (n = 21) insulin were administered at the same times as during the previous 24 weeks.Results  Post‐meal, the prandial + basal insulin group had significantly higher insulin, lower glucose and triglycerides, as well as lower high‐sensitivity C‐reactive protein, tumour necrosis factor α and interleukin‐6, than the basal insulin group. Glucose incremental area under the concentration curve significantly correlated with high‐sensitivity C‐reactive protein, tumour necrosis factor α, interleukin‐6, methylglyoxal and 3‐deoxyglucosone incremental area under the concentration curve. Insulin incremental area under the concentration curve correlated inversely with high‐sensitivity C‐reactive protein and tumour necrosis factor α incremental area under the concentration curve. However, after adjusting for glucose incremental area under the concentration curve, these inverse correlations were no longer significant. Triglyceride incremental area under the concentration curve was not correlated with any biomarker incremental area under the concentration curve.Conclusions  Controlling post‐meal hyperglycaemia with prandial + basal insulin in patients with Type 2 diabetes attenuates meal‐induced increases in high‐sensitivity C‐reactive protein, interleukin‐6 and tumour necrosis factor α compared with basal insulin. The rise in post‐meal glucose, but not triglycerides, significantly correlated with the rise in post‐meal inflammatory and glycative biomarkers.
High prevalence of capillary abnormalities in patients with diabetes and association with retinopathy
Authors: Barchetta I. , Riccieri V. , Vasile M. , Stefanantoni K. , Comberiati P. , Taverniti L. , Cavallo M. G. 
Published: April 2011

Diabet. Med. 28, 1039–1044 (2011)AbstractAims  To investigate the presence of capillary abnormalities in patients with Type 1 and Type 2 diabetes using nailfold videocapillaroscopy and to evaluate the possible correlation with the typical diabetes mellitus microangiopathic lesions detectable in retinal blood vessels.Methods  Forty‐nine patients with diabetes mellitus (21 with Type 1 and 28 with Type 2 diabetes) and 39 subjects without diabetes were enrolled. Ophthalmoscopy was performed on all patients and was followed by retinal fluorangiography when indicated. Subjects underwent nailfold videocapillaroscopy to evaluate density, length, morphology and distribution of capillary loops, presence of ectasia, microbleedings and blood flow modifications. A score (0–3) was applied to quantify features of nailfold videocapillaroscopy.Results  Subjects with diabetes showed a significantly increased (P = 0.0001) nailfold videocapillaroscopy score and significantly greater alterations of capillary length (P = 0.004), distribution (P = 0.02), morphology (P = 0.0001), density (P = 0.02) and flux (P = 0.004), as well as presence of ectasic loops (P = 0.009) and of oedema/exudates (P = 0.03) compared with control subjects. In addition, patients with Type 1 diabetes had a significantly higher score (P = 0.01) and greater morphologic alterations (P = 0.03) compared with subjects with Type 2 diabetes. Nailfold videocapillaroscopy score also showed a positive correlation with retinopathy, detected by both ophthalmoscopy (P = 0.0001) and fluorangiography (P = 0.02), independently from sex, age, type of diabetes and all potential confounders. Moreover, nailfold videocapillaroscopy was capable of identifying alterations in almost 50% of patients with diabetes without retinopathy.Conclusions  A high prevalence of nailfold capillary changes is detected in patients with diabetes using nailfold videocapillaroscopy. These abnormalities tightly correlate with retinal damage and may be expression of a generalized microvessel involvement in both Type 1 and Type 2 diabetes.
Solving the Entrepreneurial Puzzle: The Role of Entrepreneurial Interpretation in Opportunity Formation and Related Processes
Authors: Barreto Ilídio 
Published: April 2011

abstractOpportunity formation plays a central role in the entrepreneurship literature. The two dominant perspectives on this topic (discovery view and creation view) tended to consider search and action as the main mechanisms. Drawing on strategic issue interpretation view and managerial cognition perspective, we argue for the inclusion of a third mechanism (entrepreneurial interpretation). Specifically, we develop the boundary assumptions and testable propositions of an entrepreneurial interpretation model. Then, we show how entrepreneurial interpretation informs both discovery and creation processes. Overall, our theory provides an expanded understanding of how individuals form and decide to exploit opportunities.
Metallothionein expression in chloroplasts enhances mercury accumulation and phytoremediation capability
Authors: Ruiz Oscar N. , Alvarez Derry , Torres Cesar , Roman Laura , Daniell Henry 
Published: April 2011

SummaryGenetic engineering to enhance mercury phytoremediation has been accomplished by expression of the merAB genes that protects the cell by converting Hg[II] into Hg[0] which volatilizes from the cell. A drawback of this approach is that toxic Hg is released back into the environment. A better phytoremediation strategy would be to accumulate mercury inside plants for subsequent retrieval. We report here the development of a transplastomic approach to express the mouse metallothionein gene (mt1) and accumulate mercury in high concentrations within plant cells. Real‐time PCR analysis showed that up to 1284 copies of the mt1 gene were found per cell when compared with 1326 copies of the 16S rrn gene, thereby attaining homoplasmy. Past studies in chloroplast transformation used qualitative Southern blots to evaluate indirectly transgene copy number, whereas we used real‐time PCR for the first time to establish homoplasmy and estimate transgene copy number and transcript levels. The mt1 transcript levels were very high with 183 000 copies per ng of RNA or 41% the abundance of the 16S rrn transcripts. The transplastomic lines were resistant up to 20 μm mercury and maintained high chlorophyll content and biomass. Although the transgenic plants accumulated high concentrations of mercury in all tissues, leaves accumulated up to 106 ng, indicating active phytoremediation and translocation of mercury. Such accumulation of mercury in plant tissues facilitates proper disposal or recycling. This study reports, for the first time, the use of metallothioniens in plants for mercury phytoremediation. Chloroplast genetic engineering approach is useful to express metal‐scavenging proteins for phytoremediation.