bluuebunny/crossref_metadata_2025_split huggingface dataset:
There is no relation between the occurrence of proliferative vitreoretinopathy and the location of the donor site after transplantation of a free autologous retinal pigment epithelium–choroid graft
Authors: van Zeeburg Elsbeth J. T. , Maaijwee Kristel , van Meurs Jan C. 
Published: July 2013

Abstract.Purpose:  A free autologous retinal pigment epithelium (RPE)–choroid graft can be harvested during transplantation surgery from a 6 or 12 o’clock site in the midperiphery. This study evaluated whether proliferative vitreoretinopathy (PVR) occurs more frequently in patients with an inferior donor site retinotomy, which is not closed by the tamponade and is in contact with the hydrophilic, pro‐inflammatory and fibrotic environment, than in patients with a superior donor site retinotomy.Methods:  Retrospective analysis of a prospective cohort of 246 patients with exudative age‐related macular degeneration treated with an RPE–choroid graft transplantation and a lighter‐than‐water, 5000 centistoke silicone oil endotamponade. The location of the donor site, the presence or absence of PVR development and the location of PVR were noted. The two‐tailed Fisher’s exact test was used for statistical analysis.Results:  Thirty‐nine of 246 (15.9%) patients developed PVR, of whom 35 had a superior donor site and four an inferior donor site. Of the 209 patients without PVR, 155 had a superior donor site and 25 had an inferior one. For 27 patients, no donor site location was explicitly documented in the patient files. We found no difference between the groups with a superior or inferior donor site and the occurrence of PVR (p = 0.8).Conclusion:  Shifting the inflammatory aqueous milieu away from the graft donor site does not prevent the occurrence of PVR.
Diagnosis and complications of Cushing's disease: gender‐related differences
Authors: Zilio Marialuisa , Barbot Mattia , Ceccato Filippo , Camozzi Valentina , Bilora Franca , Casonato Alessandra , Frigo Anna Chiara , Albiger Nora , Daidone Viviana , Mazzai Linda , Mantero Franco , Scaroni Carla 
Published: July 2013

AbstractObjectiveCushing's disease (CD) presents a remarkable preponderance in female gender, with a female‐to‐male ratio of 3–8:1. The aim of this study was to evaluate gender‐related differences in the presentation of CD, as regards: biochemical indices of hypercortisolism; sensitivity of diagnostic tests; clinical features and complications of disease.MethodsWe retrospectively studied 84 adult patients with CD, 67 women and 17 men, evaluated at diagnosis. We compared the features of the disease between the sexes and analysed the effect of gender on CD complications, adjusted for potential confounders (age, gonadal status, BMI, urinary free cortisol values).ResultsWe observed no differences between males and females as regards age at diagnosis, disease duration and BMI. Men, compared with women, presented higher urinary free cortisol values (P < 0·001) and ACTH values (P < 0·05). As regards diagnostic tests, men presented a lower ACTH response to DDAVP stimulation (P < 0·05). The pituitary tumour itself was less easily visualized by pituitary MRI in males compared with females (P < 0·05). Furthermore, some complications of disease were more frequent or more severe in men, in particular hypokalaemia (P < 0·05), hypercoagulable state and osteoporosis at lumbar spine (P < 0·01), with consequent higher risk of vertebral fractures. Male gender was found to be an independent risk factor for dyslipidaemia, severity of hypertension, lumbar osteoporosis and fractures.ConclusionsAlthough CD is less frequent in male patients, in this gender, it presents with more florid clinical manifestations and may imply more diagnostic difficulties.
Reliability and validity of short‐term performance tests for wheelchair‐using children and adolescents with cerebral palsy
Authors: Verschuren Olaf , Zwinkels Maremka , Obeid Joyce , Kerkhof Nicky , Ketelaar Marjolijn , Takken Tim 
Published: July 2013

AimTo investigate the test–retest reproducibility of the Muscle Power Sprint Test (MPST), the 10 × 5‐m sprint test, and the arm‐cranking Wingate Anaerobic Test (WAnT) in children and adolescents with cerebral palsy (CP). A secondary objective was to assess the construct validity of the MPST.MethodTwenty‐three participants with spastic CP (mean age 13y 3mo, range 7‐18y, SD 3.6y; 18 males, five females, two classified as having spastic unilateral CP, 21 as having spastic bilateral CP) using a manual wheelchair for at least part of the day were recruited and tested in different rehabilitation settings in the Netherlands. Participants were classified as in Gross Motor Function Classification System Expanded and Revised (GMFCS‐E&R) levels III and IV.ResultsIntraclass correlation coefficients (range 0.93–0.99; 95% confidence interval 0.82–1.0) for all variables indicated highly acceptable reproducibility. Limits of agreement analysis revealed satisfactory levels of agreement. The MPST variables demonstrated very strong significant positive correlations for peak power and mean power from both tests (peak power: r=0.91, p<0.001; mean power: r=0.88, p<0.001).InterpretationThe MPST, the 10 × 5‐m sprint test, and the arm‐cranking WAnT are reproducible tests for measuring anaerobic performance and agility in adolescents with spastic CP who self‐propel a manual wheelchair. The MPST has been shown to be a valid test to measure anaerobic performance in this population.
Pneumopericardium Secondary to Esophago‐Pericardial Fistula
Authors: Caselli Stefano , Serdoz Andrea , Palumbo Barbara , Todi Fiammetta , Palma Mario Di , Serdoz Roberto 
Published: July 2013

Mini‐AbstractWe report the clinical case of a 63‐year‐old woman with a squamous cell carcinoma in the distal esophagus complicated by an esophago‐pericardial fistula and pneumopericardium. This is a rarely observed condition usually associated with a high mortality because may result in cardiac tamponade. However, as the esophago‐pericardial fistula was open and the air was free to enter and exit throughout the cardiac and respiratory cycle without significantly increasing pericardial pressure, our patient showed only a mild hemodynamic impairment without overt clinical signs of cardiac tamponade.
Multimerization of anti‐(epidermal growth factor receptor) IgG fragments induces an antitumor effect: the case for humanized 528 scFv multimers
Authors: Asano Ryutaro , Hagiwara Yasuyo , Koyama Noriaki , Masakari Yosuke , Orimo Ryota , Arai Kyoko , Ogata Hiromi , Furumoto Shozo , Umetsu Mitsuo , Kumagai Izumi 
Published: July 2013

The construction of antibody fragments has the potential to reduce the high cost of therapeutic antibody production, but the structures of these fragments, with monovalency and the lack of an Fc region, can lead to reduced function. Multimerization is one strategy for recovering function that also yields better tumor‐to‐blood ratios than IgGs or monomeric antibody fragments because of rapid tumor uptake and clearance. Here, we constructed single‐chain variable fragment (scFv) multimers by modifying the linker length and domain order of humanized anti‐(epidermal growth factor receptor) IgG 528 (h528) and tested their ability to inhibit tumor growth. h528 scFv multimers, expressed using a bacterial expression system, were successfully fractionated and inhibited cancer growth in a multimerization‐dependent manner, whereas the h528 scFv monomer showed no inhibition. h528 scFv trimers with variable heavy–light domain order and no linkers showed the highest in vitro and in vivo antitumor effects, which were comparable with those of the approved anti‐(epidermal growth factor receptor) therapeutic IgG Cetuximab and Panitumumab. The trimers were also structurally stable in vitro and in vivo, which may be attributable to a strong interaction between the variable heavy and variable light domains of h528 Fv. Thus, h528 scFv multimers, especially trimers, are attractive as the next generation of anti‐(epidermal growth factor receptor) therapeutic IgG and offer the possibility of low‐cost production.
Phosphoproteomic analysis of anaplastic lymphoma kinase (ALK) downstream signaling pathways identifies signal transducer and activator of transcription 3 as a functional target of activated ALK in neuroblastoma cells
Authors: Sattu Kamaraj , Hochgräfe Falko , Wu Jianmin , Umapathy Ganesh , Schönherr Christina , Ruuth Kristina , Chand Damini , Witek Barbara , Fuchs James , Li Pui‐Kai , Hugosson Fredrik , Daly Roger J. , Palmer Ruth H. , Hallberg Bengt 
Published: July 2013

Activation of the anaplastic lymphoma kinase (ALK) receptor tyrosine kinase is a key oncogenic mechanism in a growing number of tumor types. In the majority of cases, ALK is activated by fusion with a dimerizing partner protein as a result of chromosomal translocation events, most studied in the case of the nucleophosmin–ALK and echinoderm microtubule‐associated protein‐like 4–ALK oncoproteins. It is now also appreciated that the full‐length ALK receptor can be activated by point mutations and by deletions within the extracellular domain, such as those observed in neuroblastoma. Several studies have employed phosphoproteomics approaches to find substrates of ALK fusion proteins. In this study, we used MS‐based phosphotyrosine profiling to characterize phosphotyrosine signaling events associated with the full‐length ALK receptor. A number of previously identified and novel targets were identified. One of these, signal transducer and activator of transcription 3 (STAT3), has previously been observed to be activated in response to oncogenic ALK signaling, but the significance of this in signaling from the full‐length ALK receptor has not been explored further. We show here that activated ALK robustly activates STAT3 on Tyr705 in a number of independent neuroblastoma cell lines. Furthermore, knockdown of STAT3 by RNA interference resulted in a reduction in myelocytomatosis neuroblastom (MYCN) protein levels downstream of ALK signaling. These observations, together with a decreased level of MYCN and inhibition of neuroblastoma cell growth in the presence of STAT3 inhibitors, suggest that activation of STAT3 is important for ALK signaling activity in neuroblastoma.
Microbial mat controls on infaunal abundance and diversity in modern marine microbialites
Authors: Tarhan L. G. , Planavsky N. J. , Laumer C. E. , Stolz J. F. , Reid R. P. 
Published: July 2013

AbstractMicrobialites are the most abundant macrofossils of the Precambrian. Decline in microbialite abundance and diversity during the terminal Proterozoic and early Phanerozoic has historically been attributed to the concurrent radiation of complex metazoans. Similarly, the apparent resurgence of microbialites in the wake of Paleozoic and Mesozoic mass extinctions is frequently linked to drastic declines in metazoan diversity and abundance. However, it has become increasing clear that microbialites are relatively common in certain modern shallow, normal marine carbonate environments—foremost the Bahamas. For the first time, we present data, collected from the Exuma Cays, the Bahamas, systematically characterizing the relationship between framework‐building cyanobacteria, microbialite fabrics, and microbialite‐associated metazoan abundance and diversity. We document the coexistence of diverse microbialite and infaunal metazoan communities and demonstrate that the predominant control upon both microbialite fabric and metazoan community structure is microbial mat type. These findings necessitate that we rethink prevalent interpretations of microbialite–metazoan interactions and imply that microbialites are not passive recipients of metazoan‐mediated alteration. Additionally, this work provides support for the theory that certain Precambrian microbialites may have been havens of early complex metazoan life, rather than bereft of metazoans, as has been traditionally envisaged.
Deregulation of PAX2 expression in renal cell tumours: mechanisms and potential use in differential diagnosis
Authors: Patrício Patrícia , Ramalho‐Carvalho João , Costa‐Pinheiro Pedro , Almeida Mafalda , Barros‐Silva João Diogo , Vieira Joana , Dias Paula Cristina , Lobo Francisco , Oliveira Jorge , Teixeira Manuel R. , Henrique Rui , Jeronimo Carmen 
Published: July 2013

AbstractExpression of PAX2 (Paired‐box 2) is suppressed through promoter methylation at the later stages of embryonic development, but eventually reactivated during carcinogenesis. Pax‐2 is commonly expressed in the most prevalent renal cell tumour (RCT) subtypes—clear cell RCC (ccRCC), papillary RCC (pRCC) and oncocytoma—but not in chromophobe RCC (chrRCC), which frequently displays chromosome 10 loss (to which PAX2 is mapped). Herein, we assessed the epigenetic and/or genetic alterations affecting PAX2 expression in RCTs and evaluated its potential as biomarker. We tested 120 RCTs (30 of each main subtype) and four normal kidney tissues. Pax‐2 expression was assessed by immunohistochemistry and PAX2 mRNA expression levels were determined by quantitative RT‐PCR. PAX2 promoter methylation status was assessed by methylation‐specific PCR and bisulfite sequencing. Chromosome 10 and PAX2 copy number alterations were determined by FISH. Pax‐2 immunoexpression was significantly lower in chrRCC compared to other RCT subtypes. Using a 10% immunoexpression cut‐off, Pax‐2 immunoreactivity discriminated chrRCC from oncocytoma with 67% sensitivity and 90% specificity. PAX2 mRNA expression was significantly lower in chrRCC, compared to ccRCC, pRCC and oncocytoma, and transcript levels correlated with immunoexpression. Whereas no promoter methylation was found in RCTs or normal kidney, 69% of chrRCC displayed chromosome 10 monosomy, correlating with Pax‐2 immunoexpression. We concluded that Pax‐2 expression might be used as an ancillary tool to discriminate chrRCC from oncocytomas with overlapping morphological features. The biological rationale lies on the causal relation between Pax‐2 expression and chromosome 10 monosomy, but not PAX2 promoter methylation, in chrRCC.
Safety Assessment of Enterococcus faecium and Enterococcus faecalis Strains Isolated from Turkish Tulum Cheese
Authors: Inoğlu Zehra Nur , Tuncer Yasin 
Published: July 2013

AbstractThe aim of this study was to evaluate several genetic and phenotypic traits of clinical significance in 21 Enterococcus faecium and seven E. faecalis strains previously isolated from Turkish Tulum Cheese. Enterococcus strains were tested for the presence of 14 virulence genes and two vancomycin resistance genes by polymerase chain reaction (PCR). Biogenic amine production was also investigated by decarboxylase medium and PCR. Investigation of virulence factors by PCR amplification revealed the presence of genes encoding for gelatinase (gelE), cell wall adhesin (efaAfm and efaAfs), sex pheromone (ccf), cell wall‐associated protein (espfm and espfs) and aggregation substance (agg). Other presumed virulence genes (cpd, cob, cad, ace, cylM, cylB and cylA) were not detected. At least one virulence gene was detected in all strains. The ccf (85.7%), efaAfm (75.0%) and gelE (32.1%) were detected most frequently present virulence genes in enterococcal strains. Phenotypic gelatinase testing revealed the existence of apparently silent gelE gene. None of the strains carried the vanA and vanB genes. Enterococcus strains did not decarboxylate histidine, lysine or ornithine, but the majority of strains (92.9%) produced tyramine from tyrosine. The tyrosine decarboxylase gene (tdc) was detected in all tyraminogenic strains.Practical ApplicationEnterococci are lactic acid bacteria that are important both in food and clinical microbiology. Enterococci species especially E. faecium and E. faecalis play an important role in the development of sensory characteristics of different traditional fermented foods such as dairy and meat products. On the other hand, E. faecium and E. faecalis are recognized as nosocomial pathogens. Results of this study indicated that E. faecium and E. faecalis strains isolated from Turkish Tulum Cheese carried some virulence genes and most of them produce tyramine. The findings of our study suggest that E. faecium and E. faecalis strains isolated from Turkish Tulum Cheese may be potential risk factors for consumer health. For this reason, use of Enterococcus strains as starter cultures requires thorough safety evaluation.
Association Between a Geriatric Trauma Resuscitation Protocol Using Venous Lactate Measurements and Early Trauma Surgeon Involvement and Mortality Risk
Authors: Bar‐Or David , Salottolo Kristin M. , Orlando Alessandro , Mains Charles W. , Bourg Pamela , Offner Patrick J. 
Published: July 2013

ObjectivesTo investigate whether implementing a geriatric resuscitation protocol that uses lactate‐guided therapy with early trauma surgeon involvement is associated with lower mortality through the early recognition of occult hypoperfusion (OH).DesignProspective cohort study.SettingLevel I trauma center.ParticipantsAll hemodynamically stable individuals with blunt trauma aged 65 and older admitted to the Level I trauma center from October 1, 2008, through December 31, 2011 (n = 1,998).MeasurementsMortality over time (according to quarter) was analyzed using an adjusted logarithmic regression model stratified according to the presence of OH. OH was defined as lactate of 2.5 mM or greater.ResultsOverall mortality was 3.9% (n = 78). Admission venous lactate was collected in 73.5% of participants, of whom 20.5% had OH (n = 301). In participants with OH, a significant decrease in mortality was observed over time (adjusted coefficient of determination (R2) = 0.66, P = .002). A smaller yet significant decrease in mortality rates in participants with normal perfusion status was also observed (adjusted R2 = 0.55, P = .01).ConclusionEarly identification and treatment of OH in elderly adults with trauma using venous lactate‐guided therapy coupled with early trauma surgeon involvement was associated with significantly lower mortality. A protocol that uses lactate‐guided therapy with early trauma surgeon involvement should be followed to improve the care of elderly adults with trauma.
Variations in Self‐Reported Practice of Physicians Providing Clinical Care to Individuals with Dementia: A Systematic Review
Authors: Sivananthan Saskia N. , Puyat Joseph H. , McGrail Kimberlyn M. 
Published: July 2013

ObjectivesTo determine to what extent actual practice as reported in the literature is consistent with clinical guidelines for dementia care.DesignA systematic review of empirical studies of clinical services provided by physicians to older adults with a diagnosis of dementia.SettingAll settings involving primary care physicians in which a diagnosis of dementia is provided.ParticipantsPhysicians providing care to individuals aged 60 and older with a primary or secondary diagnosis of dementia.InterventionSeven dementia care processes recommended by guidelines: formal memory testing, imaging, laboratory testing, interventions, counseling, community service, and specialist referrals.MeasurementsWeb of Knowledge, PubMed, Science Direct, MedLine, PsychINFO, EMBASE, and Google Scholar databases were searched for articles in English published before March 1, 2012.ResultsTwelve studies met the final inclusion criteria, all of which were self‐reported cross‐sectional surveys. There was broad variation in the proportion of physicians who reported conducting each dementia care process, with the widest variation in formal memory testing (4–96%). Recently published studies reflected a shift in scope of care, reporting that high proportions of physicians provided interventions, counseling, and referrals to specialist.ConclusionDespite the availability and dissemination of established best practice guidelines, there is still wide variation in physician practice patterns in dementia care. The quality of currently available studies limits the ability to draw strong conclusions. Better information on practice patterns and their relationship to outcomes for individuals with dementia and their caregivers using more‐robust study designs is needed to address the needs of the increasing number of individuals who will require dementia care.
Age, Renal Dysfunction, Cardiovascular Disease, and Antihyperglycemic Treatment in Type 2 Diabetes Mellitus: Findings from the Renal Insufficiency and Cardiovascular Events Italian Multicenter Study
Authors: Solini Anna , Penno Giuseppe , Bonora Enzo , Fondelli Cecilia , Orsi Emanuela , Trevisan Roberto , Vedovato Monica , Cavalot Franco , Cignarelli Mauro , Morano Susanna , Ferrannini Ele , Pugliese Giuseppe ,   Renal Insufficiency and Cardiovascular Events Study Group
Published: July 2013

ObjectivesTo assess the distribution of antihyperglycemic treatments according to age and renal function and its relationship with cardiovascular disease in type 2 diabetes mellitus (T2DM).DesignCross‐sectional analysis.SettingNineteen hospital‐based diabetes mellitus clinics in 2007 and 2008.ParticipantsFifteen thousand seven hundred thirty‐three individuals with T2DM from the Renal Insufficiency and Cardiovascular Events (RIACE) Italian Multicenter Study.MeasurementsCurrent antihyperglycemic treatments were recorded. Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. Albuminuria was measured using immunonephelometry or immunoturbidimetry. Prevalence of major acute cardiovascular events was calculated according to age quartiles, treatments, and categories of eGFR (1 = ≥90; 2 = 60–89; 3 = 30–59; and 4 = <30 mL/min per 1.73 m2).ResultsAcross age quartiles, eGFR declined progressively at a time‐linear rate, with an acceleration in older adults, whereas albuminuria increased; age and eGFR were associated with cardiovascular events independently of other confounders. With increasing age, percentage of participants using lifestyle treatments for their T2DM and taking metformin or glitazones fell; percentage taking sulphonylureas and repaglinide rose, and percentage taking insulin remained stable. In eGFR categories 3 and 4, use of metformin was 41.4% and 14.5%, respectively, and that of sulphonylureas was 34.2% and 18.1%, respectively. Inappropriate prescription of these agents, especially sulphonylureas, increased with age. Metformin was independently associated with lower prevalence of cardiovascular disease for any age quartile and eGFR category than all other treatments.ConclusionIn real‐life conditions, use of agents that are not recommended in elderly adults with diabetes mellitus with moderate to severe renal impairment is frequent, but metformin is associated with lower cardiovascular event rates even in these individuals.