bluuebunny/crossref_metadata_2025_split huggingface dataset:
Progesterone therapy increases free thyroxine levels—data from a randomized placebo‐controlled 12‐week hot flush trial
Authors: Sathi P. , Kalyan S. , Hitchcock C. L. , Pudek M. , Prior J. C. 
Published: December 2012

SummaryObjectiveThyroid hormones and progesterone both influence core temperature, metabolism and are crucial during pregnancy. Our objective was to discover whether progesterone therapy caused changes in thyroid physiology compared with placebo.DesignPost hoc analysis from a randomized (1:1) placebo‐controlled 12‐week trial of oral micronized progesterone (Progesterone, 300 mg/d at bedtime) for hot flushes (vasomotor symptoms, VMS) conducted in an academic medical centre.PatientsPostmenopausal euthyroid, healthy (without cardiovascular diseases or risks) women, 1–11 years since last flow on no thyroid or ovarian hormone therapy with VMS participated.MeasurementsPrimary outcomes were final and 12‐week changes in TSH, FreeT3 and FreeT4 on progesterone vs placebo.ResultsWomen with thyroid data (69 of 133 in original trial) were randomized to progesterone (n = 39) or placebo (n = 30)—baseline thyroid values were normal. There were no VMS‐thyroid interactions—VMS Score (number × intensity) did not correlate with TSH, FreeT3 or FreeT4 (Spearman's rank correlations: −0.03 to −0.19, respectively; all P > 0.15). At 12 weeks on progesterone, TSH levels tended to be lower (1.7 mU) than on placebo (2.2), P = 0.06; FreeT4 levels were higher (16.4 pmol/l) than on placebo (15.3), P = 0.02. FreeT3 was unchanged throughout. Analysis of covariance showed a significant increase in FreeT4 on progesterone (+2.5 pmol/l; 1.9–3.0) vs on placebo (+1.7; 1.1–2.4) with 95% CI of difference = 0.8 pmol/l [0.0, 1.6], P = 0.04.ConclusionsProgesterone caused a significant FreeT4 increase that was discovered during this randomized controlled VMS trial. The clinical importance of this increased FreeT4 level remains to be documented. Registered at ClinialTrials.gov#NCT00152438.
Triptolide with Potential Medicinal Value for Diseases of the Central Nervous System
Authors: Zheng Yan , Zhang Wen‐Jing , Wang Xiao‐Min 
Published: December 2012

SummaryTripterygium wilfordii Hook.f. (TWHF) has a long history as a Traditional Chinese Medicine (TCM) herb that aids in treating inflammatory and autoimmune diseases. The major bioactive component of TWHF is triptolide, which has been recognized to possess a broad spectrum of biological profiles including antiinflammatory, immunosuppressive, antifertility, and antitumor activities, as well as neurotrophic and neuroprotective effects. Limitation of triptolide, such as poor water solubility and severe systemic toxicity, has postponed clinical development and trials; however, the wide range of medicinal value of triptolide has been drawing intensive worldwide attention. In particular, triptolide has been shown to have significant effects on central nervous system (CNS) diseases, such as Parkinson's disease, Alzheimer's disease, spinal cord and brain injury, and multiple sclerosis. This review focuses on the potential therapeutic role of triptolide on CNS diseases, and discusses the structural features, potential modifications, and the other pharmacological activities of triptolide.
Pifithrin‐α Enhances the Survival of Transplanted Neural Stem Cells in Stroke Rats by Inhibiting p53 Nuclear Translocation
Authors: Lei Xu‐Hui , Zhao Dan , Li Yong‐Li , Li Xian‐Feng , Sun Xu , Du Wen‐Zhong , Sun Ying , Hao Zhong‐Fei , Xin Shi‐Yue , Liu Cong , Zhang Zhi‐Ren , Jiang Chuan‐Lu 
Published: December 2012

SummaryAimsTo examine a novel strategy to enhance the survival of grafted neural stem cells (NSCs) in stroke model.MethodsUsing a cell counting kit‐8 (CCK‐8) and TUNEL assay to test the protective effects of p53 inhibitor, pifithrin‐α (PFT‐α), on oxygen glucose deprivation (OGD) in NSCs. We compared the effects of vehicle + NSCs and FFT‐α + NSCs on the efficacy of transplantation in stroke rat model using behavioral analysis, immunohistochemistry, etc.ResultsPifithrin‐α increased viability and decreased apoptosis in NSCs after OGD in vitro. By in vivo studies, we showed that the best recovery of neurological function in the stroke rats and the maximum survival of grafted NSCs were found in the PFT‐α + NSCs group. Twelve hours after cell transplantation, p53 was localized to the nuclei of grafted NSCs in the vehicle + NSCs group but was primarily localized to the cytoplasm in the PFT‐α + NSCs group. The p53‐upregulated modulator of apoptosis (PUMA) was highly expressed among the grafted cells in the vehicle + NSCs group compared with that in the PFT‐α + NSCs group.ConclusionOur results indicate that PFT‐α enhances the survival of grafted NSCs through the inhibition of p53 translocation into the nucleus.
Research Management Team (RMT): A Model for Research Support ‐Services at Duke University
Authors: Snyder Denise C. , Epps Shelly , Beresford Henry F. , Ennis Cory , Levens Justin S. , Woody Stephen K. , Tcheng James E. , Stacy Mark A. , Nahm Meredith 
Published: December 2012

AbstractCollecting and managing data for clinical and translational research presents significant challenges for clinical and translational researchers, many of whom lack needed access to data management expertise, methods, and tools. At many institutions, funding constraints result in differential levels of research informatics support among investigators. In addition, the lack of widely shared models and ontologies for clinical research informatics and health information technology hampers the accurate assessment of investigators’ needs and complicates the efficient allocation of crucial resources for research projects, ultimately affecting the quality and reliability of research. In this paper, we present a model for providing flexible, cost‐efficient institutional support for clinical and translational research data management and informatics, the research management team, and describe our initial experiences with deploying this model at our institution. Clin Trans Sci 2012; Volume 5: 464–469
Atypical updating of face representations with experience in children with autism
Authors: Ewing Louise , Pellicano Elizabeth , Rhodes Gillian 
Published: December 2012

AbstractFace identity aftereffects are significantly diminished in children with autism relative to typical children, which may reflect reduced perceptual updating with experience. Here, we investigated whether this atypicality also extends to non‐face stimulus categories, which might signal a pervasive visual processing difference in individuals with autism. We used a figural aftereffect task to measure directly perceptual updating following exposure to distorted upright faces, inverted faces and cars, in typical children and children with autism. A size‐change between study and test stimuli limited the likelihood that any processing atypicalities reflected group differences in adaptation to low‐level features of the stimuli. Results indicated that, relative to typical children, figural aftereffects for upright faces, but not inverted faces or cars, were significantly attenuated in children with autism. Moreover, the group difference was amplified when we isolated the ‘face‐selective’ component of the aftereffect, by partialling out the mid‐level shape adaptation common to upright and inverted face stimuli. Notably, the aftereffects of typical children were disproportionately larger for upright faces than for inverted faces and cars, but the magnitude of aftereffects of autistic children was not similarly modulated according to stimulus category. These findings are inconsistent with a pervasive adaptive coding atypicality relative to typical children, and suggest that reduced perceptual updating may constitute a high‐level, and possibly face‐selective, visual processing difference in children with autism.
Screening for diabetic retinopathy in pregnancy using photographic review clinics
Authors: Hampshire R. , Wharton H. , Leigh R. , Wright A. , Dodson P. 
Published: December 2012

AbstractAimsTo assess the efficacy and value of the National Institute for Health and Clinical Excellence guidelines for digital photographic screening for diabetic retinopathy in pregnancy using photographic review clinics.MethodsPregnant patients (n = 186) with known diabetes were screened at first antenatal visit and at 28 weeks' gestation, if no retinopathy was noted at first visit, or at other intervals if retinopathy was present. Two 45° images (disc‐centred and macula‐centred views) were taken in both eyes and graded by trained graders and by an ophthalmologist.ResultsNinety‐three patients (50%) remained free of diabetic retinopathy throughout pregnancy. Eighteen (10%) presented with sight‐threatening retinopathy at their first antenatal screen and were referred to the hospital eye service. Fifty patients (27%) were shown to have relatively stable retinopathy throughout pregnancy, with only two patients deteriorating and requiring referral to hospital eye service. Twenty‐three (12%) failed to complete the screening protocol after their first screen.ConclusionsThe study showed that pregnant patients screened for retinopathy in an ophthalmic photographic diabetic review clinic achieved National Institute for Health and Clinical Excellence guidelines in the majority and were clinically safe. Only 1% of patients required referral to ophthalmology after their initial screen, thus avoiding unnecessary hospital eye service appointments.
Exercise‐Induced Pulmonary Hypertension in Scleroderma Patients: A Common Finding but with Elusive Pathophysiology
Authors: Baptista Rui , Serra Sara , Martins Rui , Salvador Maria João , Castro Graça , Gomes Manuel , Santos Lèlita , Monteiro Pedro , da Silva Jose A. Pereira , Pêgo Mariano 
Published: December 2012

Background: The etiology of exercise‐induced pulmonary hypertension (exPH) in systemic sclerosis (SSc) remains a complex task, as both left ventricle (LV) diastolic dysfunction and pulmonary vascular disease can contribute to its development. We determined the incidence of exPH in SSc and examined the association between pulmonary artery systolic pressure (PASP) and tissue Doppler‐derived indexes of pulmonary capillary wedge pressure (PCWP). Methods: Thirty‐eight patients with SSc were studied, using a cycloergometer protocol; 10 were excluded due to resting PH or absence of tricuspid regurgitation (TR); TR and mitral E‐wave velocities, LV outflow tract time‐velocity integral and LV septal E′‐wave were measured before and in peak exercise to calculate cardiac output (CO), PCWP and pulmonary vascular resistance (PVR). Results: Mean age of diagnosis was 57.9 ± 8.9 years. At a mean workload of 64 ± 29 Watts, 48% of patients increased PASP ≥ 50 mmHg. PCWP, assessed by the E/e′ ratio, did not change significantly during exercise (10.2 ± 3.1–10.0 ± 5.1; P = NS). Only 3 patients had elevations of the E/e′ ratio ≥ 13 during exercise; 2 of them had an exercise PASP ≥ 50 mmHg, yielding a proportion of exPH due to elevated LV filling pressures of 2/11 (18%). Patients with exPH had lower DLCO and had more frequently the diffuse SSc. Conclusion: The elevation of PASP during exercise in most patients of this cohort seems to be related to a reduced pulmonary vascular reserve, and not to an increase in PCWP. Further studies are warranted to determine the therapeutic, as well as prognostic implications of these findings.
Risk prediction of very early recurrence, death and progression after acute ischaemic stroke
Authors: Maier I. L. , Bauerle M. , Kermer P. , Helms H.‐J. , Buettner T. 
Published: December 2012

Background and purposeEarly recurrent strokes lead to extended hospitalization and high number of complications. We investigated three stroke scores, the Essen Stroke Risk Score (ESRS), the ABCD² and the Recurrence Risk Estimator at 90 days (RRE‐90) for their prognostic value to predict early recurrent stroke, death and progressive stroke.MethodsClinical and radiological data from 1727 consecutive patients with ischaemic stroke, being admitted to the stroke unit, were evaluated retrospectively. Predictive value of stroke scores was tested for early recurrence within 7 days, death and progressive stroke expressed as observational risk and area under the receiver operator curve (AUROC).ResultsEarly recurrent stroke occurred in 56 patients (3.2%), 40 patients (2.3%) died within the first 7 days and 125 patients (7.2%) had a progressive stroke. ESRS was not predictive for early recurrence, death or progressive stroke. ABCD² score was predictive for death (P < 0.01; χ²; AUROC, 0.65; 0.58–0.72), and progressive stroke (P < 0.001; χ²; AUROC, 0.70; 0.66–0.74). RRE‐90 predicted early recurrent stroke (P < 0.001; χ²; AUROC, 0.65; 0.58–0.73), early death (P < 0.001; χ²; AUROC, 0.72; 0.66–0.78) and progressive stroke (P < 0.001; χ²; AUROC, 0.66; 0.61–0.71).ConclusionsRRE‐90 bears high potential to not only predict early recurrence but also death and progression after ischaemic stroke. ABCD² appears to be useful to predict risk of death and progression. These findings have relevant clinical implications for early triage of patients being admitted to stroke units.
Genetic variation in the receptor for advanced glycation end‐products (RAGE) gene and ischaemic stroke
Authors: Olsson S. , Jood K. 
Published: December 2012

Background and purposeThe multi‐ligand receptor for advanced glycation end‐products (RAGE, alias AGER) is suggested to contribute to the pathogenesis of vascular disease, but its potential role in stroke is unclear. The aim of this study was to investigate whether genetic variation in RAGE gene is associated with ischaemic stroke (IS).MethodsThe Sahlgrenska Academy Study on Ischaemic Stroke comprises 844 Caucasian patients with first ever (n = 732) and recurrent (n = 112) IS, and 668 Caucasian controls. Three tagSNPs were selected to capture genetic variation in the RAGE gene. IS subtypes were determined using TOAST criteria.ResultsOne SNP, rs1035798, showed significant association with the subtype of small‐vessel disease (SVD) after correction for multiple testing (OR 1.56, 95% CI 1.16–2.09), adjusted P‐value < 0.05). This association was independent of hypertension, diabetes and smoking. None of the SNPs was associated with overall IS.ConclusionIn this sample of patients with IS, genetic variation in RAGE is associated with the IS subtype SVD, but not overall IS.
Six‐year follow‐up of a case series with non‐communicating syringomyelia in multiple sclerosis
Authors: Weier K. , Naegelin Y. , Amann M. , Magon S. , Mueller‐Lenke N. , Radue E.‐W. , Kappos L. , Stippich C. , Gass A. , Sprenger T. 
Published: December 2012

BackgroundNon‐communicating syringomyelia (NCS) has occasionally been described in case reports and small case series as an incidental finding of spinal cord (SC) pathology in patients with multiple sclerosis (MS), but only little is known on the clinical course and progression of NCS, and in more general terms on the prognosis of patients with MS and NCS.MethodsNine patients with MS with known NCS at baseline and a control group of 18 age‐, sex‐ and disease course‐matched patients with MS without NCS were recruited for a follow‐up visit after 6 years. All 27 patients underwent clinical examination and brain magnetic resonance imaging (MRI), and 8/9 patients with NCS were additionally studied with MRI of the SC. MRI data were analysed for changes in length and maximal cross‐sectional area of the NCS, lesion volumes of the brain and cord as well as for volumetric metrics of the whole brain (using SIENAX), the cerebellum and medulla oblongata (using ECCET).ResultsNCS did not significantly change in size when corrected for multiple comparisons. The clinical data (annual relapse rate, EDSS and disease duration) and MRI metrics (T2 and T1 lesion load; whole brain, cerebellar and medulla oblongata volumes as well as their percentage volume change per year) did not significantly differ between patients with MS with or without NCS.ConclusionThe stable findings regarding size and shape of the syrinx and lack of distinguishing MRI and clinical features support the assumption that NCS is not defining a prognostically or pathogenetically distinct subgroup of patients with MS.
Advanced age and liability to oxaliplatin‐induced peripheral neuropathy: post hoc analysis of a prospective study
Authors: Argyriou A. A. , Briani C. , Cavaletti G. , Bruna J. , Alberti P. , Velasco R. , Lonardi S. , Cortinovis D. , Cazzaniga M. , Campagnolo M. , Santos C. , Kalofonos H. P. 
Published: December 2012

Background and purposeThe aim of this post hoc analysis of data extracted from a prospective, multicenter study is to test in a large homogenous population of chemotherapy‐naïve patients with colorectal cancer (CRC) treated with oxaliplatin (OXA)‐based chemotherapy whether advanced age increases the risk of developing OXA‐induced peripheral neuropathy (OXAIPN).MethodsOne‐hundred and forty‐five patients with CRC, without other significant co‐morbidities predisposing to peripheral neuropathy, were divided according to their age into two groups: patients aged between 50 and 68 years (group I, n = 75); and patients aged ≥ 69 years (group II, n = 70). Patients were prospectively monitored at baseline and followed‐up during chemotherapy using the motor and neurosensory National Cancer Institute Common Toxicity criteria, the clinical version of the Total Neuropathy Score and neurophysiology. The incidence and severity of both the acute and cumulative OXAIPN was thoroughly determined and then compared between age groups.ResultsNo statistically significant difference was observed in the incidence of both the acute (n = 64/75 vs. 56/70; P = 0.510) and cumulative OXAIPN (n = 51/75 vs. 49/70; P = 0.858) between age groups. The severity of OXAIPN was also similar between age groups. In line with the clinical data, the neurophysiological results between age groups were also comparable.ConclusionThe results of this study indicate that advanced age does not seem to represent a significant risk factor of OXAIPN in patients with CRC without any other significant co‐morbidities.
An investigation of the relationship between hindlimb lameness and saddle slip
Authors: Greve L. , Dyson S. J. 
Published: December 2012

SummaryReasons for performing studyWe have observed saddle slip consistently to one side because of a crooked rider, an ill‐fitting saddle, asymmetry in a horse's thoracolumbar shape and lameness. Currently, there are no objective data to permit assessment of the relative importance of each factor.ObjectivesTo document the frequency of occurrence of saddle slip in horses with hindlimb lameness compared with other horses. To describe the effect of lameness characteristics and grade, the abolition of lameness by diagnostic analgesia, breed, size, thoracolumbar shape and symmetry and the rider's weight.MethodsOne hundred and twenty‐eight horses were assessed prospectively, and lameness and saddle slip were assigned a grade before and after diagnostic analgesia. The thoracolumbar shape and symmetry were measured objectively. In 3 horses, the force distribution and magnitude underneath the saddle were measured before and after diagnostic analgesia.ResultsThe saddle consistently slipped to one side in 38 of 71 horses (54%) with hindlimb lameness, compared with one of 26 horses (4%) with forelimb lameness, none of 20 (0%) with back pain and/or sacroiliac joint region pain and none of 11 sound horses (0%). The association between saddle slip and hindlimb lameness was significant (Spearman's rank correlation coefficient, ρ = 0.548, P<0.001). Diagnostic analgesia abolishing the hindlimb lameness eliminated the saddle slip in 37 of 38 horses (97%). In 2 horses, the saddle continued to slip after resolution of lameness; one horse had bilateral forelimb lameness and the other horse had concurrent hindlimb and forelimb lameness. The saddle of both these horses was asymmetrically flocked. The saddle slipped to the side of the lamer hindlimb in most horses (32 of 37 [86%]). No horse with saddle slip had significant left–right asymmetry of the back at 4 predetermined sites.Conclusions and clinical relevanceHindlimb lameness is an important factor in inducing saddle slip. Saddle slip may be an indicator of the presence of hindlimb lameness.
The six amino acid antimicrobial peptide bLFcin6 penetrates cells and delivers siRNA
Authors: Fang Bing , Guo Hui Y , Zhang Ming , Jiang Lu , Ren Fa Z 
Published: December 2012

Cell‐penetrating peptides (CPPs) are a new class of vectors with high pharmaceutical potential to deliver bioactive cargos into cells. Here, we characterized bLFcin6, a six amino acid peptide derived from bovine lactoferricin, as a CPP. Uptake of bLFcin6 was measured by flow cytometry. The ability to delivery siRNA was analyzed in HeLa cells. bLFcin6 exhibited concentration‐dependent uptake and intracellular distribution. Below 7.5 μm, uptake of bLFcin6 was significantly lower than uptake of TAT (P < 0.05) because bLFcin6 has fewer cationic amino acids. Compared to CPP5 (RLRWR) and CPP6 (PFVYLI), bLFcin6 had a significantly higher internalization ratio above 2.5 μm because it has two tryptophan residues. Uptake of bLFcin6 starts with an ionic cell‐surface interaction. It is then rapidly internalized by lipid raft‐dependent macropinocytosis, followed by release from macropinosomes into the cytosol and nucleus. Moreover, bLFcin6 formed stable electrostatic complexes with siRNA and delivered siRNA into cells, resulting in significant knockout activity at both the mRNA and protein levels. The knockout activity of siRNA delivered by bLFcin6 was similar to that mediated by TAT, although knockout by bLFcin6 required a higher molar ratio. In this study, bLFcin6 was tested for its ability to act as an siRNA‐delivering CPP.
Empirical analysis of the influence of forest extent on annual and seasonal surface temperatures for the continental United States
Authors: Wickham James D. , Wade Timothy G. , Riitters Kurt H. 
Published: December 2012

AbstractAimBecause of the low albedo of forests and other biophysical factors, most scenario‐based climate modelling studies indicate that removal of temperate forest will promote cooling, indicating that temperate forests are a source of heat relative to other classes of land cover. Our objective was to test the hypothesis that US temperate forests reduce surface temperatures.LocationThe continental United States.MethodsOrdinary least squares regression was used to develop relationships between forest extent and surface temperature. Forest extent was derived from the 900 m2 2001 National Land Cover Database (NLCD 2001) and surface temperature data were from the MODIS 1 km2 8‐day composite (MYD11A2). Forest–surface temperature relationships were developed for winter, spring, summer, autumn and annually using 5 years of MODIS land surface temperature data (2007–11) across six spatial scales (1, 4, 9, 16, 25 and 36 km2). Regression models controlled for the effects of elevation, aspect and latitude (by constraining the regressions within a 1° range).ResultsWe did not find any significant positive slopes in regressions of average annual surface temperatures versus the proportion of forest, indicating that forests are not a source of heat relative to other types of land cover. We found that surface temperatures declined as the proportion of forest increased for spring, summer, autumn and annually. The forest–surface temperature relationship was also scale dependent in that spatially extensive forests produced cooler surface temperatures than forests that were dominant only locally.Main conclusionsOur results are not consistent with most scenario‐based climate modelling studies. Because of their warming potential, the value of temperate afforestation as a potential climate change mitigation strategy is unclear. Our results indicate that temperate afforestation is a climate change mitigation strategy that should be implemented to promote spatially extensive forests.