bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronic Kidney Disease and Albuminuria in Children with Sickle Cell Disease
Authors: McPherson Yee Marianne , Jabbar Shameem F. , Osunkwo Ifeyinwa , Clement Lisa , Lane Peter A. , Eckman James R. , Guasch Antonio 
Published: September 2011

Summary

Background and objectives
Sickle cell nephropathy begins in childhood and may progress to renal failure. Albuminuria is a sensitive marker of glomerular damage that may indicate early chronic kidney disease (CKD).

Design, setting, participants, & measurements
The aims of this study were to determine the cross-sectional prevalence and clinical correlates of albuminuria and CKD among children with sickle cell disease (SCD). Over a 10-year period (1995 to 2005) 410 pediatric SCD patients ages 2 to 21 years were enrolled: 261 with hemoglobin SS (HbSS) or HbSβ0 thalassemia (HbSβ0) and 149 with HbSC or HbSβ+ thalassemia (HbSβ+). The albumin/creatinine ratio (ACR) of spot-urine specimens and serum creatinine were measured; abnormal albuminuria was defined as urinary ACR ≥ 30 mg/g.

Results
The prevalence of abnormal albuminuria was 20.7% (23.0% in HbSS/HbSβ0, 16.8% in HbSC/HbSβ+). Among HbSS/HbSβ0, abnormal albuminuria was associated with increasing age and lower baseline hemoglobin. GFR, estimated in 189 patients using the updated Schwartz formula, correlated negatively with age (r = −0.27, P = 0.0002). CKD defined according to the Kidney Disease: Improving Global Outcomes study was present in 26.5% (50 of 189) of patients: stage 1 in 27 (14.8%) and stage 2 in 22 (11.6%). In multivariate analysis, age and HbSC/HbSβ+ genotype were associated with CKD.

Conclusions
This is the first study to stage CKD in children with SCD and highlights a high prevalence of albuminuria and glomerular injury early in life. Detecting CKD in childhood could allow for earlier intervention and prevention of renal failure in adulthood.
Sympathetic Nerve Traffic and Asymmetric Dimethylarginine in Chronic Kidney Disease
Authors: Grassi Guido , Seravalle Gino , Ghiadoni Lorenzo , Tripepi Giovanni , Bruno Rosa Maria , Mancia Giuseppe , Zoccali Carmine 
Published: September 2011

Summary

Background and objectives
Sympathetic overactivity and high levels of the endogenous inhibitor of NO synthase asymmetric dimethylarginine (ADMA) are prevalent risk factors in chronic kidney disease (CKD).

Design, setting, participants, & measurements
In 48 stage 2 to 4 CKD patients, we investigated the relationship between efferent postganglionic muscle sympathetic nerve traffic (microneurography) and circulating ADMA and analyzed the links between these risk factors and estimated GFR (eGFR), proteinuria, and different parameters of left ventricular (LV) geometry.

Results
CKD patients characterized by sympathetic nerve traffic values in the third tertile showed the highest ADMA levels, and this association was paralleled by a continuous, positive relationship between these two risk factors (r = 0.32, P = 0.03) independent of other confounders. Both sympathetic nerve traffic and ADMA were inversely related to eGFR and directly to proteinuria and LV geometry. Remarkably, the variance of eGFR, proteinuria, and LV geometry explained by sympathetic nerve traffic and ADMA largely overlapped because sympathetic nerve traffic but not ADMA was retained as a significant correlate of the eGFR (P < 0.001) and of the relative wall thickness or the left ventricular mass index/LV volume ratio (P = 0.05) in models including both risk factors. ADMA, but not sympathetic nerve traffic, emerged as an independent correlate of proteinuria (P = 0.003) in a model including the same covariates.

Conclusions
Sympathetic activity and ADMA may share a pathway leading to renal disease progression, proteinuria, and LV concentric remodeling in CKD patients.
Dose-finding Study of Peginesatide for Anemia Correction in Chronic Kidney Disease Patients
Authors: Macdougall Iain C. , Wiecek Andrzej , Tucker Beatriz , Yaqoob Magdi , Mikhail Ashraf , Nowicki Michal , MacPhee Iain , Mysliwiec Michal , Smolenski Olgierd , Sułowicz Władysław , Mayo Martha , Francisco Carol , Polu Krishna R. , Schatz Peter J. , Duliege Anne-Marie 
Published: September 2011

Summary

Background and objectives
Peginesatide is a synthetic, PEGylated, investigational, peptide-based erythropoiesis-stimulating agent. We report the first assessment of its efficacy and safety in correcting renal anemia in a population of 139 nondialysis chronic kidney disease patients.

Design, setting, participants, & measurements
Chronic kidney disease patients who were not on dialysis and not receiving treatment with erythropoiesis-stimulating agents in the 12 weeks before study drug administration were sequentially assigned to one of 10 cohorts; cohorts differed in starting peginesatide dose (different body weight-based or absolute doses), route of administration (intravenous or subcutaneous), and frequency of administration (every 4 or 2 weeks).

Results
Across all cohorts, 96% of patients achieved a hemoglobin response. A dose-response relationship was evident for hemoglobin increase. Comparable subcutaneous and intravenous peginesatide doses produced similar hemoglobin responses. Rapid rates of hemoglobin rise and hemoglobin excursions >13 g/dl tended to occur more frequently with every-2-weeks dosing than they did with every-4-weeks dosing. The range of final median doses in the every-4-weeks dosing groups was 0.019 to 0.043 mg/kg. Across all cohorts, 20% of patients reported serious adverse events (one patient had a possibly drug-related serious event) and 81% reported adverse events (11.5% reported possibly drug-related events); these events were consistent with those routinely observed in this patient population.

Conclusions
This study suggests that peginesatide administered every 4 weeks can increase and maintain hemoglobin in nondialysis chronic kidney disease patients. Additional long-term data in larger groups of patients are required to further elucidate the efficacy and safety of this peptide-based erythropoiesis-stimulating agent.
Nonthyrotoxic Prevention of Diet-Induced Insulin Resistance by 3,5-Diiodo-L-Thyronine in Rats
Authors: de Lange Pieter , Cioffi Federica , Senese Rosalba , Moreno Maria , Lombardi Assunta , Silvestri Elena , De Matteis Rita , Lionetti Lillà , Mollica Maria Pina , Goglia Fernando , Lanni Antonia 
Published: September 2011

OBJECTIVE
High-fat diets (HFDs) are known to induce insulin resistance. Previously, we showed that 3,5-diiodothyronine (T2), concomitantly administered to rats on a 4-week HFD, prevented gain in body weight and adipose mass. Here we investigated whether and how T2 prevented HFD-induced insulin resistance.

RESEARCH DESIGN AND METHODS
We investigated the biochemical targets of T2 related to lipid and glucose homeostasis over time using various techniques, including genomic and proteomic profiling, immunoblotting, transient transfection, and enzyme activity analysis.

RESULTS
Here we show that, in rats, HFD feeding induced insulin resistance (as expected), whereas T2 administration prevented its onset. T2 did so by rapidly stimulating hepatic fatty acid oxidation, decreasing hepatic triglyceride levels, and improving the serum lipid profile, while at the same time sparing skeletal muscle from fat accumulation. At the mechanistic level, 1) transfection studies show that T2 does not act via thyroid hormone receptor β; 2) AMP-activated protein kinase is not involved in triggering the effects of T2; 3) in HFD rats, T2 rapidly increases hepatic nuclear sirtuin 1 (SIRT1) activity; 4) in an in vitro assay, T2 directly activates SIRT1; and 5) the SIRT1 targets peroxisome proliferator–activated receptor (PPAR)-γ coactivator (PGC-1α) and sterol regulatory element–binding protein (SREBP)-1c are deacetylated with concomitant upregulation of genes involved in mitochondrial biogenesis and downregulation of lipogenic genes, and PPARα/δ-induced genes are upregulated, whereas genes involved in hepatic gluconeogenesis are downregulated. Proteomic analysis of the hepatic protein profile supported these changes.

CONCLUSIONS
T2, by activating SIRT1, triggers a cascade of events resulting in improvement of the serum lipid profile, prevention of fat accumulation, and, finally, prevention of diet-induced insulin resistance.
A Novel Cellular Defect in Diabetes
Authors: Howard Amber C. , McNeil Anna K. , Xiong Fei , Xiong Wen-Cheng , McNeil Paul L. 
Published: September 2011

OBJECTIVE
Skeletal muscle myopathy is a common diabetes complication. One possible cause of myopathy is myocyte failure to repair contraction-generated plasma membrane injuries. Here, we test the hypothesis that diabetes induces a repair defect in skeletal muscle myocytes.

RESEARCH DESIGN AND METHODS
Myocytes in intact muscle from type 1 (INS2Akita+/−) and type 2 (db/db) diabetic mice were injured with a laser and dye uptake imaged confocally to test repair efficiency. Membrane repair defects were also assessed in diabetic mice after downhill running, which induces myocyte plasma membrane disruption injuries in vivo. A cell culture model was used to investigate the role of advanced glycation end products (AGEs) and the receptor for AGE (RAGE) in development of this repair defect.

RESULTS
Diabetic myocytes displayed significantly more dye influx after laser injury than controls, indicating a repair deficiency. Downhill running also resulted in a higher level of repair failure in diabetic mice. This repair defect was mimicked in cultured cells by prolonged exposure to high glucose. Inhibition of the formation of AGE eliminated this glucose-induced repair defect. However, a repair defect could be induced, in the absence of high glucose, by enhancing AGE binding to RAGE, or simply by increasing cell exposure to AGE.

CONCLUSIONS
Because one consequence of repair failure is rapid cell death (via necrosis), our demonstration that repair fails in diabetes suggests a new mechanism by which myopathy develops in diabetes.
Routine Data Sources Challenge International Diabetes Federation Extrapolations of National Diabetes Prevalence in Switzerland
Authors: Bopp Matthias , Zellweger Ueli , Faeh David 
Published: September 2011

OBJECTIVE
Information on diabetes prevalence in the general population is scarce and often based on extrapolations. We evaluated whether prevalence could be estimated from routine data sources.

RESEARCH DESIGN AND METHODS
The sources were 1) hospital discharges (2008, n = 828,171), 2) death registry (2007/2008, n = 118,659), and 3) Swiss Health Survey (SHS; 2007, n = 18,665). Persons without diabetes as underlying cause of death (death registry) or principal diagnosis (hospital discharges) were regarded as surrogate for a general population random sample.

RESULTS
In those aged 20–84 years, 4.5% of men and 3% of women were expected to have diabetes. By source, estimations were 4.4 and 2.8% (hospital discharges), 3.8 and 3.1% (death registry), and 4.9 and 3.7% (SHS) for men and women, respectively. Among sources, age–sex patterns were similar.

CONCLUSIONS
In countries with adequate data quality, combination of routine data may provide valid and reliable estimations of diabetes prevalence. Our figures suggest that International Diabetes Federation extrapolations substantially overestimate diabetes prevalence in Switzerland.
Long-Term Metabolic and Immunological Follow-Up of Nonimmunosuppressed Patients With Type 1 Diabetes Treated With Microencapsulated Islet Allografts
Authors: Basta Giuseppe , Montanucci Pia , Luca Giovanni , Boselli Carlo , Noya Giuseppe , Barbaro Barbara , Qi Meirigeng , Kinzer Katie P. , Oberholzer José , Calafiore Riccardo 
Published: September 2011

OBJECTIVE
To assess long-term metabolic and immunological follow-up of microencapsulated human islet allografts in nonimmunosuppressed patients with type 1 diabetes (T1DM).

RESEARCH DESIGN AND METHODS
Four nonimmunosuppressed patients, with long-standing T1DM, received intraperitoneal transplant (TX) of microencapsulated human islets. Anti-major histocompatibility complex (MHC) class I–II, GAD65, and islet cell antibodies were measured before and long term after TX.

RESULTS
All patients turned positive for serum C-peptide response, both in basal and after stimulation, throughout 3 years of posttransplant follow-up. Daily mean blood glucose, as well as HbA1c levels, significantly improved after TX, with daily exogenous insulin consumption declining in all cases and being discontinued, just transiently, only in patient 4. Anti-MHC class I–II and GAD65 antibodies all tested negative at 3 years after TX.

CONCLUSIONS
The grafts did not elicit any immune response, even in the cases where more than one preparation was transplanted, as a unique finding, compatible with encapsulation-driven “bioinvisibility” of the grafted islets. This result had never been achieved with the recipient’s general immunosuppression.
Pretransplant Risk Score for New-Onset Diabetes After Kidney Transplantation
Authors: Chakkera Harini A. , Weil E. Jennifer , Swanson Christine M. , Dueck Amylou C. , Heilman Raymond L. , Reddy Kunam S. , Hamawi Khaled , Khamash Hasan , Moss Adyr A. , Mulligan David C. , Katariya Nitin , Knowler William C. 
Published: September 2011

OBJECTIVE
New-onset diabetes after kidney transplantation (NODAT) has adverse clinical and economic implications. A risk score for NODAT could help identify research subjects for intervention studies.

RESEARCH DESIGN AND METHODS
We conducted a single-center retrospective cohort study using pretransplant clinical and laboratory measurements to construct a risk score for NODAT. NODAT was defined by hemoglobin A1c (HbA1c) ≥6.5%, fasting serum glucose ≥126 mg/dL, or prescribed therapy for diabetes within 1 year posttransplant. Three multivariate logistic regression models were constructed: 1) standard model, with both continuous and discrete variables; 2) dichotomous model, with continuous variables dichotomized at clinically relevant cut points; and 3) summary score defined as the sum of the points accrued using the terms from the dichotomous model.

RESULTS
A total of 316 subjects had seven pretransplant variables with P &lt; 0.10 in univariate logistic regression analyses (age, planned corticosteroid therapy posttransplant, prescription for gout medicine, BMI, fasting glucose and triglycerides, and family history of type 2 diabetes) that were selected for multivariate models. Areas under receiver operating curves for all three models were similar (0.72, 0.71, and 0.70). A simple risk score calculated as the sum of points from the seven variables performed as well as the other two models in identifying risk of NODAT.

CONCLUSIONS
A risk score computed from seven simple pretransplant variables can identify risk of NODAT.
Insulin Sensitizers May Attenuate Lean Mass Loss in Older Men With Diabetes
Authors: Lee Christine G. , Boyko Edward J. , Barrett-Connor Elizabeth , Miljkovic Iva , Hoffman Andrew R. , Everson-Rose Susan A. , Lewis Cora E. , Cawthon Peggy Mannen , Strotmeyer Elsa S. , Orwoll Eric S. ,   for the Osteoporotic Fractures in Men (MrOS) Study Research Group
Published: September 2011

OBJECTIVE
To examine longitudinal changes in total and appendicular lean body mass in older men with impaired fasting glucose (IFG) or diabetes and to determine whether these changes differ by diabetes treatment.

RESEARCH DESIGN AND METHODS
A total of 3,752 ambulatory men aged ≥65 years at baseline participated in a multicenter longitudinal cohort study. Baseline glycemic status was categorized as normoglycemia, IFG, undiagnosed/untreated diabetes, or treated diabetes. Insulin sensitizer medication use (metformin and/or thiazolidinediones) was assessed by prescription medication inventory. The change in total lean and appendicular lean mass was derived from dual X-ray absorptiometry scans taken at baseline and 3.5 ± 0.7 years later.

RESULTS
This male cohort included 1,853 individuals with normoglycemia, 1,403 with IFG, 234 with untreated diabetes, 151 with diabetes treated with insulin sensitizers, and 111 with diabetes treated without insulin sensitizers. Men with untreated diabetes, diabetes treated without insulin sensitizers, or IFG had greater percentage loss in total or appendicular lean mass (P ≤ 0.05 in comparison to normoglycemic men). There remained a significantly greater percentage loss in appendicular lean mass for these groups even after adjustment for medical comorbidities or lifestyle factors. In contrast, the percentage loss in total or appendicular lean mass in men with diabetes treated with insulin sensitizers was significantly less than that in normoglycemic men in minimally and fully adjusted models.

CONCLUSIONS
Skeletal muscle loss was accelerated in men with IFG and diabetes, except when the latter was treated with insulin sensitizers. These findings suggest that insulin sensitizers may attenuate muscle loss.
Purkynĕ’s contributions to neuroscience and biology: Part I
Authors: Judaš Miloš , Sedmak Goran 
Published: September 2011

Abstract
Jan Evangelista Purkyně (or Purkinje, as he was spelled in his German publications prior to 1850) was one of giants in the XIXth century science. His contributions are numerous, and his research interests were wide-ranging. This study is divided into two parts. In the Part I, we provide a general overview of Purkyně’s life and work, focusing on his pioneering role in the rise of experimental physiology and microscopical anatomy. In the Part II, we will: (a) focus on his contributions to neuroanatomy, neurohistology and cell theory; (b) provide the first complete English translation of his relevant publications, and (c) provide a critical historical review of the importance of his contributions in comparison to his main contemporary competitors: Christian Gottfried Ehrenberg, Gabriel Gustav Valentin, Theodor Schwann, Robert Remak and Adolf Hannover.
A neural-network controlled dynamic evolutionary scheme for global molecular geometry optimization
Authors: Styrcz Anna , Mrozek Janusz , Mazur Grzegorz 
Published: September 2011

A neural-network controlled dynamic evolutionary scheme for global molecular geometry optimizationA novel, neural network controlled, dynamic evolutionary algorithm is proposed for the purposes of molecular geometry optimization. The approach is tested for selected model molecules and some molecular systems of importance in biochemistry. The new algorithm is shown to compare favorably with the standard, statically parametrized memetic algorithm.
Who Picks Psychiatry? Perceptions, Preferences and Personality of Medical Students
Authors: Malhi Gin S. , Coulston Carissa M. , Parker Gordon B. , Cashman Emma , Walter Garry , Lampe Lisa A. , Vollmer-Conna Ute 
Published: September 2011

Objectives: This study aimed to characterise the personality profiles of junior medical students most likely to choose psychiatry as a career, determine aspects of psychiatry that most attract potential recruits, and identify misperceptions about psychiatry that may dissuade students from pursuing this specialism. Method: A total of 580 second-year medical students from the University of New South Wales, Australia completed a set of questionnaires that measured the likelihood with which various medical specialties were being considered as careers, personality traits using the NEO Five-Factor Inventory (NEO-FFI), and the degree to which students perceived each specialty as attractive across a number of parameters. Results: Only 86 students (15%) indicated a strong likelihood of choosing psychiatry, compared to other specialties which attracted higher proportions of students (range 19–49%). These 86 students had significantly higher openness scores than those who indicated a lesser likelihood of pursuing psychiatry. Students who were highly interested in psychiatry ranked it as very attractive in respect to providing interesting and challenging subject matter, and relatively attractive in respect to financial reward, work enjoyment, good lifestyle, having a bright and interesting future, and association with colleagues. However, psychiatry remained less attractive with respect to prestige, perceived low effectiveness of treatments, degree to which it draws upon aspects of medical training, and lack of reliable scientific foundation. Within the entire sample, psychiatry was ranked most unattractive compared to the other specialties across eight of the 13 parameters assessed. Conclusions: Students interested in psychiatry are more likely to be ‘open’ and view the specialty as interesting and challenging. Such characteristics should be promoted more widely along with countering myths that as a specialty, psychiatry lacks a scientific foundation or is somehow different from mainstream medicine in terms of training and outcomes. Championing psychiatry in this manner may attract more recruits and enhance its prestige.
Impact of admission month and hospital teaching status on outcomes in subarachnoid hemorrhage: evidence against the July effect
Authors: McDonald Robert J. , Cloft Harry J. , Kallmes David F. 
Published: September 2011

Object
The authors sought to identify the presence of a “July effect,” a transient increase in adverse outcomes during July, among a cohort of spontaneous subarachnoid hemorrhage (SAH) admissions recorded in the National Inpatient Sample (NIS).

Methods
The discharge status, admission month, patient demographics, treatment parameters, and hospital characteristics among spontaneous SAH admissions were extracted from the 2001–2008 NIS. Multivariate regression was used to determine whether an unfavorable discharge status and/or in-hospital mortality significantly increased in summer months in a pattern suggestive of a July effect. Additional models were generated to assess the impact of hospital teaching status on these outcomes.

Results
Among 57,663,486 hospital admissions from the 2001–2008 NIS, 52,879 cases of spontaneous SAH (ICD-9-CM 430) were treated at teaching (36,914 cases [70%]) and nonteaching (15,965 cases [30%]) facilities. Regression models failed to reveal a July effect for in-hospital mortality (χ2 = 0.75, p = 1.000) or unfavorable discharges (χ2 = 1.69, p = 0.999) among monthly SAH admissions, although they did suggest a significant reduction in these outcomes (in-hospital mortality, OR = 0.89, p < 0.001; unfavorable discharges, OR = 0.88, p < 0.001) among teaching hospitals as compared with nonteaching hospitals after adjustment for disparities in demographic, treatment, and hospital characteristics.

Conclusions
The discharge disposition among SAH admissions within the NIS was not suggestive of a July effect but did reveal that teaching institutions have significantly lower rates of adverse outcomes when compared with nonteaching hospitals. Note, however, that the origins of this difference related to teaching status remain unclear.