bluuebunny/crossref_metadata_2025 huggingface dataset:
High Tap Density SphericalLi[Ni0.5Mn0.3Co0.2]O2Cathode Material Synthesized via Continuous Hydroxide Coprecipitation Method for Advanced Lithium-Ion Batteries
Authors: Yang Shunyi , Wang Xianyou , Yang Xiukang , Liu Ziling , Wei Qiliang , Shu Hongbo
Published: March 2012

Spherical[Ni0.5Mn0.3Co0.2](OH)2precursor with narrow size distribution and high tap density has been successfully synthesized by a continuous hydroxide coprecipitation, andLi[Ni0.5Mn0.3Co0.2]O2is then prepared by mixing the precursor with 6% excessLi2CO3followed by calcinations. The tap density of the obtainedLi[Ni0.5Mn0.3Co0.2]O2powder is as high as 2.61 g cm−3. The powders are characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscope (SEM), particle size distribution (PSD), and charge/discharge cycling. The XRD studies show that the preparedLi[Ni0.5Mn0.3Co0.2]O2has a well-ordered layered structure without any impurity phases. Good packing properties of spherical secondary particles (about 12 μm) consisted of a large number of tiny-thin plate-shape primary particles (less than 1 μm), which can be identified from the SEM observations. In the voltage range of 3.0–4.3 V and 2.5–4.6 V,Li[Ni0.5Mn0.3Co0.2]O2delivers the initial discharge capacity of approximately 175 and 214 mAh g−1at a current density of 32 mA g−1, and the capacity retention after 50 cycles reaches 98.8% and 90.2%, respectively. Besides, it displays good high-temperature characteristics and excellent rate capability.
A Fast Interpretation Method for Inverse Modeling of Residual Gravity Anomalies Caused by Simple Geometry
Authors: Essa Khalid S.
Published: March 2012

An inversion technique using a fast method is developed to estimate, successively, the depth, the shape factor, and the amplitude coefficient of a buried structure using residual gravity anomalies. By defining the anomaly value at the origin and the anomaly value at different points on the profile, the problem of depth estimation is transformed into a problem of solving a nonlinear equation of the form . Knowing the depth, the shape factor can be estimated and finally the amplitude coefficient can be estimated. This technique is applicable for a class of geometrically simple anomalous bodies, including the semiinfinite vertical cylinder, the infinitely long horizontal cylinder, and the sphere. The efficiency of this technique is demonstrated with gravity anomaly due to a theoretical model, in each case with and without random errors. Finally, the applicability is illustrated using the residual gravity anomaly of Mobrun ore body, situated near Noranda, QC, Canada. The interpreted depth and the other model parameters are in good agreement with the known actual values.
Artificial Neural Network-Statistical Approach for PET Volume Analysis and Classification
Authors: Sharif Mhd Saeed , Abbod Maysam , Amira Abbes , Zaidi Habib
Published: March 2012

The increasing number of imaging studies and the prevailing application of positron emission tomography (PET) in clinical oncology have led to a real need for efficient PET volume handling and the development of new volume analysis approaches to aid the clinicians in the clinical diagnosis, planning of treatment, and assessment of response to therapy. A novel automated system for oncological PET volume analysis is proposed in this work. The proposed intelligent system deploys two types of artificial neural networks (ANNs) for classifying PET volumes. The first methodology is a competitive neural network (CNN), whereas the second one is based on learning vector quantisation neural network (LVQNN). Furthermore, Bayesian information criterion (BIC) is used in this system to assess the optimal number of classes for each PET data set and assist the ANN blocks to achieve accurate analysis by providing the best number of classes. The system evaluation was carried out using experimental phantom studies (NEMA IEC image quality body phantom), simulated PET studies using the Zubal phantom, and clinical studies representative of nonsmall cell lung cancer and pharyngolaryngeal squamous cell carcinoma. The proposed analysis methodology of clinical oncological PET data has shown promising results and can successfully classify and quantify malignant lesions.
Oxidative Stress and Microglial Cells in Parkinson's Disease
Authors: Peterson Lynda J. , Flood Patrick M.
Published: March 2012

Significant evidence has now been accumulated that microglial cells play a central role in the degeneration of DA neurons in animal models of PD. The oxidative stress response by microglial cells, most notably the activity of the enzyme NADPH oxidase, appears to play a central role in the pathology of PD. This oxidative stress response occurs in microglia through the activation of the ERK signaling pathway by proinflammatory stimuli, leading to the phosphorylation and translocation of the p47phoxand p67phoxcytosolic subunits, the activation of membrane-bound PHOX, and the production of ROS. Therapeutic anti-inflammatories which prevent DA neurodegeneration in PD, including anti-inflammatory cytokines, morphinan compounds, NADPH oxidase inhibitors, NF-κB inhibitors, andβ2-AR agonists, all function to inhibit the activation of the PHOX in microglial cells. These observations suggest a central role for the oxidative stress response in microglial cells as a mediator or regulator of DA neurodegeneration in PD.
Retention Behaviour in Micellar Liquid Chromatography
Authors: Rambla-Alegre Maria
Published: March 2012

Retention in micellar liquid chromatography is highly reproducible and can be modelled using empirical or mechanistic models with great accuracy to predict the retention changes when the mobile phase composition varies (surfactant and organic solvent concentrations), thus facilitating the optimisation of separation conditions. In addition, the different equilibria inside the column among the solute, the mobile phase, and the modified stationary phase by monomers of surfactant have been exhaustively studied.
In a sequential strategy, the retention of the solutes is not known a priori, and each set of mobile phases is designed by taking into account the retention observed with previous eluents. By contrast, in an interpretative strategy, the experiments are designed before the optimization process and used to fit a model that will allow the prediction of the retention of each solute. This strategy is more efficient and reliable. The sequential strategy will be inadequate when several local and/or secondary maxima exist, as frequently occurs in chromatography, and may not give the best maximum, that is to say, the optimum.
More often than not, the complexity of the mixtures of compounds studied and the relevant modification of their chromatographic behaviour when changing the mobile phase composition requires the use of computer-assisted simulations in MLC to follow the modifications in the chromatograms in detail. These simulations can be done with sound reliability thanks to the use of chemometrics tools.
Primary Leiomyosarcoma of Breast in an Adolescent Girl: A Case Report and Review of the Literature
Authors: Rane Swapnil Ulhas , Batra Charu , Saikia Uma Nahar
Published: March 2012

Leiomyosarcoma of the breast is a rare neoplasm, primarily reported in older women. Only 44 cases have been reported in world literature and to the best of our knowledge, no case has been reported from India till date. We report a case of primary breast leiomyosarcoma in an adolescent girl who underwent a lumpectomy for rapidly increasing lump in the left breast. Here we report the histological findings and immunohistochemical profile of this entity, along with a review of existing literature.
Toxoplasmaon the Brain: Understanding Host-Pathogen Interactions in Chronic CNS Infection
Authors: Kamerkar Sushrut , Davis Paul H.
Published: March 2012

Toxoplasma gondiiis a prevalent obligate intracellular parasite which chronically infects more than a third of the world’s population. Key to parasite prevalence is its ability to form chronic and nonimmunogenic bradyzoite cysts, which typically form in the brain and muscle cells of infected mammals, including humans. While acute clinical infection typically involves neurological and/or ocular damage, chronic infection has been more recently linked to behavioral changes. Establishment and maintenance of chronic infection involves a balance between the host immunity and parasite evasion of the immune response. Here, we outline the known cellular interplay betweenToxoplasma gondiiand cells of the central nervous system and review the reported effects ofToxoplasma gondiion behavior and neurological disease. Finally, we review new technologies which will allow us to more fully understand host-pathogen interactions.
Theory of Square-Wave Voltammetry of Two-Electron Reduction with the Adsorption of Intermediate
Authors: Lovrić Milivoj , Komorsky-Lovrić Šebojka
Published: March 2012

Thermodynamically unstable intermediate of fast and reversible two-electron electrode reaction can be stabilized by the adsorption to the electrode surface. In square-wave voltammetry of this reaction mechanism, the split response may appear if the electrode surface is not completely covered by the adsorbed intermediate. The dependence of the difference between the net peak potentials of the prepeak and postpeak on the square-wave frequency is analyzed theoretically. This relationship can be used for the estimation of adsorption constant.
Aggrephagy: Selective Disposal of Protein Aggregates by Macroautophagy
Authors: Lamark Trond , Johansen Terje
Published: March 2012

Protein aggregation is a continuous process in our cells. Some proteins aggregate in a regulated manner required for different vital functional processes in the cells whereas other protein aggregates result from misfolding caused by various stressors. The decision to form an aggregate is largely made by chaperones and chaperone-assisted proteins. Proteins that are damaged beyond repair are degraded either by the proteasome or by the lysosome via autophagy. The aggregates can be degraded by the proteasome and by chaperone-mediated autophagy only after dissolution into soluble single peptide species. Hence, protein aggregates as such are degraded by macroautophagy. The selective degradation of protein aggregates by macroautophagy is called aggrephagy. Here we review the processes of aggregate formation, recognition, transport, and sequestration into autophagosomes by autophagy receptors and the role of aggrephagy in different protein aggregation diseases.
Building the Clinical Bridge to Advance Education, Research, and Practice Excellence
Authors: Svejda Marilyn , Goldberg Janet , Belden Maureen , Potempa Kathleen , Calarco Margaret
Published: March 2012

The University of Michigan School of Nursing and the Health System partnered to develop an undergraduate clinical education model as part of a larger project to advance clinical education, practice, and scholarship with education serving as the clinical bridge that anchors all three areas. The clinical model includes clusters of clinical units as the clinical home for four years of a student's education, clinical instruction through team mentorship, clinical immersion, special skills preparation, and student portfolio. The model was examined during a one-year pilot with junior students. Stakeholders were largely positive. Findings showed that Clinical Faculty engaged in more role modeling of teaching strategies as Mentors assumed more direct teaching used more clinical reasoning strategies. Students reported increased confidence and competence in clinical care by being integrated into the team and the Mentor's assignment. Two new full time faculty roles in the Health System support education, practice, and research.
An Algorithm That Predicts CSI to Allocate Bandwidth for Healthcare Monitoring in Hospital's Waiting Rooms
Authors: Lin Di , Labeau Fabrice
Published: March 2012

In wireless healthcare monitoring systems, bandwidth allocation is an efficient solution to the problem of scarce wireless bandwidth for the monitoring of patients. However, when the central unit cannot access the exact channel state information (CSI), the efficiency of bandwidth allocation decreases, and the system performance also decreases. In this paper, we propose an algorithm to reduce the negative effects of imperfect CSI on system performance. In this algorithm, the central unit can predict the current CSI by previous CSI when the current CSI is not available. We analyze the reliability of the proposed algorithm by deducing the standard error of estimated CSI with this algorithm. In addition, we analyze the efficiency of the proposed algorithm by discussing the system performance with this algorithm.
Surgical Treatment Options for the Young and Active Middle-Aged Patient with Glenohumeral Arthritis
Authors: Bhatia Sanjeev , Hsu Andrew , Lin Emery C. , Chalmers Peter , Ellman Michael , Cole Brian J. , Verma Nikhil N.
Published: March 2012

The diagnosis and treatment of symptomatic chondral lesions in young and active middle-aged patients continues to be a challenging issue. Surgeons must differentiate between incidental chondral lesions from symptomatic pathology that is responsible for the patient's pain. A thorough history, physical examination, and imaging work up is necessary and often results in a diagnosis of exclusion that is verified on arthroscopy. Treatment of symptomatic glenohumeral chondral lesions depends on several factors including the patient's age, occupation, comorbidities, activity level, degree of injury and concomitant shoulder pathology. Furthermore, the size, depth, and location of symptomatic cartilaginous injury should be carefully considered. Patients with lower functional demands may experience success with nonoperative measures such as injection or anti-inflammatory pharmacotherapy. When conservative management fails, surgical options are broadly classified into palliative, reparative, restorative, and reconstructive techniques. Patients with lower functional demands and smaller lesions are best suited for simpler, lower morbidity palliative procedures such as debridement (chondroplasty) and cartilage reparative techniques (microfracture). Those with higher functional demands and large glenohumeral defects will usually benefit more from restorative techniques including autograft or allograft osteochondral transfers and autologous chondrocyte implantation (ACI). Reconstructive surgical options are best suited for patients with bipolar lesions.
Stability of Facial Affective Expressions in Schizophrenia
Authors: Fatouros-Bergman H. , Spang J. , Merten J. , Preisler G. , Werbart A.
Published: March 2012

Thirty-two videorecorded interviews were conducted by two interviewers with eight patients diagnosed with schizophrenia. Each patient was interviewed four times: three weekly interviews by the first interviewer and one additional interview by the second interviewer. 64 selected sequences where the patients were speaking about psychotic experiences were scored for facial affective behaviour with Emotion Facial Action Coding System (EMFACS). In accordance with previous research, the results show that patients diagnosed with schizophrenia express negative facial affectivity. Facial affective behaviour seems not to be dependent on temporality, since within-subjects ANOVA revealed no substantial changes in the amount of affects displayed across the weekly interview occasions. Whereas previous findings found contempt to be the most frequent affect in patients, in the present material disgust was as common, but depended on the interviewer. The results suggest that facial affectivity in these patients is primarily dominated by the negative emotions of disgust and, to a lesser extent, contempt and implies that this seems to be a fairly stable feature.
Fuzzy Modeling and Control of HIV Infection
Authors: Zarei Hassan , Kamyad Ali Vahidian , Heydari Ali Akbar
Published: March 2012

The present study proposes a fuzzy mathematical model of HIV infection consisting of a linear fuzzy differential equations (FDEs) system describing the ambiguous immune cells level and the viral load which are due to the intrinsic fuzziness of the immune system's strength in HIV-infected patients. The immune cells in question are considered CD4+ T-cells and cytotoxic T-lymphocytes (CTLs). The dynamic behavior of the immune cells level and the viral load within the three groups of patients with weak, moderate, and strong immune systems are analyzed and compared. Moreover, the approximate explicit solutions of the proposed model are derived using a fitting-based method. In particular, a fuzzy control function indicating the drug dosage is incorporated into the proposed model and a fuzzy optimal control problem (FOCP) minimizing both the viral load and the drug costs is constructed. An optimality condition is achieved as a fuzzy boundary value problem (FBVP). In addition, the optimal fuzzy control function is completely characterized and a numerical solution for the optimality system is computed.
Characterization of Forested Landscapes from Remotely Sensed Data Using Fractals and Spatial Autocorrelation
Authors: Al-Hamdan Mohammad Z. , Cruise James F. , Rickman Douglas L. , Quattrochi Dale A.
Published: March 2012

The characterization of forested landscapes is frequently required in civil engineering practice. In this study, some spatial analysis techniques are presented that might be employed with Landsat TM data to analyze forest structure characteristics. A case study is presented wherein fractal dimensions (FDs), along with a simple spatial autocorrelation technique (Moran’sI), were related to stand density parameters of the Oakmulgee National Forest located in the southeastern United States (Alabama). The results indicate that when smaller trees do not dominate the landscape (<50%), forested areas can be differentiated according to breast sizes and thus important flood plain characteristics such as ratio of obstructed area to total area can be estimated from remotely sensed data using the studied indices. This would facilitate the estimation of hydraulic roughness coefficients for computation of flood profiles needed for bridge design. FD and Moran’sIremained fairly constant around the values of 2.7 and 0.9 (resp.) for samples with either greater than 50% saplings or less than 50% sawtimber and with ranges of 2.7–2.9 and 0.6–0.9 as the saplings decreased or the sawtimber increased. Those indices can also distinguish hardwood and softwood species facilitating forested landscapes mapping for preliminary environmental impact analysis.
Neural Oscillators Programming Simplified
Authors: McDowell Patrick , Beaubouef Theresa
Published: March 2012

The neurological mechanism used for generating rhythmic patterns for functions such as swallowing, walking, and chewing has been modeled computationally by the neural oscillator. It has been widely studied by biologists to model various aspects of organisms and by computer scientists and robotics engineers as a method for controlling and coordinating the gaits of walking robots. Although there has been significant study in this area, it is difficult to find basic guidelines for programming neural oscillators. In this paper, the authors approach neural oscillators from a programmer’s point of view, providing background and examples for developing neural oscillators to generate rhythmic patterns that can be used in biological modeling and robotics applications.
Neuroprotective Effects of Meloxicam and Selegiline in Scopolamine-Induced Cognitive Impairment and Oxidative Stress
Authors: Goverdhan Puchchakayala , Sravanthi Akina , Mamatha Thati
Published: March 2012

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by a gradual decline in memory associated with shrinkage of brain tissue, with localized loss of neurons mainly in the hippocampus and basal forebrain, with diminished level of central cholinergic neurotransmitter-acetylcholine and also reported to be associated with accumulation of ubiquitinated proteins in neuronal inclusions and also with signs of inflammation. In these disorders, the abnormal protein aggregates may themselves trigger the expression of inflammatory mediators, such as cyclooxygenase 2 (COX-2). In the present study, the effects of Meloxicam, Selegiline, and coadministration of these drugs on scopolamine-induced learning and memory impairments in mice were investigated. Rectangular maze test, Morris water maze test, Locomotor activity, and Pole climbing test were conducted to evaluate the learning and memory parameters. Various biochemical parameters such as acetylcholinesterase(AChE), TBARS assay, catalase activity, and DPPH assay were also assessed. The present study demonstrates that Meloxicam, Selegiline, and co-administration of these test drugs had potential therapeutic effects on improving the antiamnesic activity in mice through inhibiting lipid peroxidation, augmenting endogenous antioxidant enzymes, and decreasing acetylcholinesterase activity in brain. The memory enhancing capacity of the drugs was very significant when compared to disease control (P<0.001).
Gender Influences the Class III and V β-Tubulin Ability to Predict Poor Outcome in Colorectal Cancer
Authors: Mariani Marisa , Zannoni Gian Franco , Sioletic Stefano , Sieber Steven , Martino Candice , Martinelli Enrica , Coco Claudio , Scambia Giovanni , Shahabi Shohreh , Ferlini Cristiano
Published: March 2012

Purpose: Colorectal cancer is one of the deadliest diseases in Western countries. To predict the outcome of therapy, we assessed the role of class III (TUBB3) and class V β-tubulin (TUBB6) as predictive biomarkers.

Experimental Design: Using immunohistochemistry and nanofluidics, the expression of TUBB3 and TUBB6 was assessed in two cohorts of 180 and 134 patients, respectively. The CYP17A1 RS743572 was genotyped to identify GG carriers with enhanced androgen levels. TUBB3 and TUBB6 were investigated in 22 colorectal cancer cell lines in basal conditions and after serum starvation, the latter serving as activator of this prosurvival pathway. To ascertain the role of androgen receptor (AR) in such regulation, we silenced AR and checked TUBB3 and TUBB6 expression and sensitivity to chemotherapy.

Results: There was a link between poor survival, the expression of TUBB3/TUBB6, and AR only in females. Conversely, only in males carriers of the GG phenotype exhibited the worst outcome. Importantly, male cell lines were resistant to serum starvation and exhibited higher levels of TUBB6, thereby suggesting that the pathway is activated by androgens. In female cells this phenomenon was absent. In both genders, AR was the main driver of TUBB3/TUBB6 expression, as constitutive silencing of AR was associated with downregulation of TUBB3/TUBB6 expression and increased sensitivity to oxaliplatin and SN-38.

Conclusions: The involvement of androgens in the TUBB3 pathway opens the way for clinical trials to assess the efficacy of antiandrogens for increasing the efficacy of chemotherapy in male colorectal cancer patients. Clin Cancer Res; 18(10); 2964–75. ©2012 AACR.
For Breast Cancer Prognosis, Immunoglobulin Kappa Chain Surfaces to the Top
Authors: Whiteside Theresa L. , Ferrone Soldano
Published: March 2012

The stromal immunoglobulin kappa chain (IGKC) has been validated as an immunologic biomarker of prognosis and response to therapy in human breast cancer and other cancers. This validation emphasizes the key role of humoral immunity in control of cancer progression and has major implications for determining prognosis of patients with cancer. Clin Cancer Res; 18(9); 2417–9. ©2012 AACR.
Functional Metabolic Screen Identifies 6-Phosphofructo-2-Kinase/Fructose-2,6-Biphosphatase 4 as an Important Regulator of Prostate Cancer Cell Survival
Authors: Ros Susana , Santos Claudio R. , Moco Sofia , Baenke Franziska , Kelly Gavin , Howell Michael , Zamboni Nicola , Schulze Almut
Published: March 2012

Alterations in metabolic activity contribute to the proliferation and survival of cancer cells. We investigated the effect of siRNA-mediated gene silencing of 222 metabolic enzymes, transporters, and regulators on the survival of 3 metastatic prostate cancer cell lines and a nonmalignant prostate epithelial cell line. This approach revealed significant complexity in the metabolic requirements of prostate cancer cells and identified several genes selectively required for their survival. Among these genes was 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 (PFKFB4), an isoform of phosphofructokinase 2 (PFK2). We show that PFKFB4 is required to balance glycolytic activity and antioxidant production to maintain cellular redox balance in prostate cancer cells. Depletion of PFKFB4 inhibited tumor growth in a xenograft model, indicating that it is required under physiologic nutrient levels. PFKFB4 mRNA expression was also found to be greater in metastatic prostate cancer compared with primary tumors. Taken together, these results indicate that PFKFB4 is a potential target for the development of antineoplastic agents.

Significance: Cancer cells undergo several changes in their metabolism that promote growth and survival. Using an unbiased functional screen, we found that the glycolytic enzyme PFKFB4 is essential for prostate cancer cell survival by maintaining the balance between the use of glucose for energy generation and the synthesis of antioxidants. Targeting PFKFB4 may therefore present new therapeutic opportunities. Cancer Discov; 2(4); 328–43. ©2012 AACR.

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The Clinical Effect of the Inhibitor of Apopotosis Protein Livin in Melanoma
Authors: Lazar Itay , Perlman Riki , Lotem Michal , Peretz Tamar , Ben-Yehuda Dina , Kadouri Luna
Published: March 2012

Objective: The inhibitor of apoptosis protein (IAP) livin is frequently overexpressed in melanoma. Livin binds caspases and thereby inhibits apoptosis. We found that caspases cleave livin to produce a truncated form with a paradoxical proapoptotic activity. Methods: We assessed the correlation of livin expression with survival among 114 melanoma patients treated with an autologous melanoma vaccine. In 52 patients, resection resulted in no evidence of disease (NED) and 62 remained with active disease (WAD). Protein levels were assessed using Western blot. Results: We found livin protein expression in 44/114 samples (38.4%). Median overall survival was 1.4 years in NED patients with high levels of livin protein, 8.4 years in those with low-intermediate levels and not reached in patients who did not express livin (p = 0.025). The corresponding overall survival was 2.3 years among WAD patients with high levels of livin protein, 11.3 years in those with low-intermediate levels and, paradoxically, only 4.0 years in patients who did not express livin (p = 0.012). Conclusion: Livin protein expression may play a role in the progression of melanoma and correlates with survival. A high level of the protein is associated with a poor prognosis. However, in WAD patients low to intermediate level of livin, rather than absence of the protein, is associated with a favorable prognosis. This is probably due to the paradoxical proapoptotic activity of this important regulator of apoptosis.
The Exon 3-Deleted/Full-Length Growth Hormone Receptor Polymorphism and Response to Growth Hormone Therapy in Growth Hormone Deficiency and Turner Syndrome: A Multicenter Study
Authors: Baş Firdevs , Darendeliler Feyza , Aycan Zehra , Çetinkaya Ergun , Berberoğlu Merih , Şıklar Zeynep , Öcal Gönül , Timirci Özlem , Çetinkaya Semra , Darcan Şükran , Gökşen Şimşek Damla , Bideci Aysun , Cinaz Peyami , Böber Ece , Demir Korcan , Bereket Abdullah , Turan Serap , Atabek M. Emre , Tütüncüler Filiz , İsbir Turgay , Bozkurt Nilüfer , Kabataş Eryılmaz Sema , Uzunhan Ozan , Küçükemre Aydın Banu , Bundak Rüveyde
Published: March 2012

Background/Aim: The exon 3-deleted/full-length (d3/fl) growth hormone (GH) receptor (GHR) polymorphism has been associated with responsiveness to GH therapy in some diagnostic groups. However, there are still controversies on this issue. To evaluate the effect of the GHR exon 3 polymorphism on growth after 1 and 2 years of GH therapy in Turkish patients with GH deficiency (GHD) and Turner’s syndrome (TS) and the distribution of GHR exon 3 isoforms. Materials and Methods: 218 patients with GHD (125 males/93 females) and 43 patients with TS were included in the study. The control group included 477 healthy adults aged from 18 to 57 years (54 females/423 males). Anthropometric parameters and insulin-like growth factor (IGF)-1 and IGF binding protein (IGFBP)-3 were evaluated annually. GHR isoforms were studied using simple multiplex PCR. Height and body mass index were expressed as standard deviation score (SDS). Results: There were no differences among TS, GHD and healthy adults regarding the distribution of GHR exon 3 isoforms (fl/fl, fl/d3 and d3/d3). There was a significant increase in height SDS in both diagnostic groups on GH therapy; however, there were neither differences in height SDS and Δheight velocity between fl/fl, fl/d3 and d3/d3 groups nor a correlation between the distribution of GHR exon 3 isoforms and change in IGF-1 SDS and IGFBP-3 SDS levels on GH therapy in either of the diagnostic groups. There was also no gender difference in GHR isoforms in healthy adults. Conclusion: The results suggest that responsiveness to GH therapy does not depend on the exon 3 GHR genotypes in GHD and TS patients.
Differential Profiles of Crack Users in Respondent-Driven and Institutional Samples: A Three-Site Comparison
Authors: Oteo Pérez Alberto , Benschop Annemieke , Korf Dirk J.
Published: March 2012

Background/Aim: Respondent-driven sampling (RDS) is increasingly applied in social epidemiological surveys among ‘hidden populations’ of hard drug users. The objective of the present study was to assess whether the profile of frequent crack users recruited through RDS differed from those surveyed in two random institutional samples, i.e. low-threshold opiate substitution treatment (ST) and user rooms (URs). Methods: A total of 1,039 crack users (mean age 45.1 ± 9.1 years; 81.5% males; 49.5% non-Western ethnicity) were interviewed in three Dutch cities, using each sampling strategy in each city. Characteristics of respondents in the three samples (per city and aggregated) were compared. Results: Crack users in the RDS sample were more likely to be younger and less likely to be poorly educated, have a long crack-using career (≥10 years), use opiates and attend ST than those in both of the other samples. The RDS and UR samples showed the most differences, with more female and Western crack users in the RDS group, and UR participants were more likely to have been arrested and to have entered inpatient drug treatment in the last year. Conclusion: RDS resulted in a different profile of crack users. It is a valuable methodology to achieve a more diverse representation of crack-using populations than institutional random samples.
The Relationship of Poor Linear Growth Velocity with Neonatal Illness and Two-Year Neurodevelopment in Preterm Infants
Authors: Ramel Sara E. , Demerath Ellen W. , Gray Heather L. , Younge Noelle , Boys Christopher , Georgieff Michael K.
Published: March 2012

Background: Poor postnatal weight gain in very low birth weight (VLBW) preterm infants has been shown to have a negative effect on neurodevelopment. However, the dose-dependent neurodevelopmental consequences of linear stunting in this population have not previously been assessed. Understanding this relationship is important because organ growth and differentiation are more tightly linked to lean body mass and thus linear growth. Objective: To assess the duration and clinical determinants of poor linear growth and its relationship to neurodevelopment in preterm infants. Methods: Weight, recumbent length and head circumference were recorded at birth, hospital discharge, and at 4, 12 and 24 months corrected age (CA) in 62 VLBW infants. Standardized Z-scores for weight (WZ), length (LZ) and head circumference (HCZ) were calculated and assessed as a function of inpatient clinical factors using linear regression models. Twenty-four-month neurodevelopmental function was analyzed as a function of growth status. Results: Mean LZ was lower than WZ (p = 0.004) at hospital discharge, was related in part to illness severity and remained lower than baseline LZ until 24 months CA. Controlling for WZ and HCZ at each age, lower LZ at 4 and 12 months CA was associated with lower cognitive function scores at 24 months CA (p ≤ 0.03). Conclusions: Nutritional and nonnutritional factors influenced the degree of pre- and postdischarge linear growth suppression in VLBW infants, which in turn was negatively associated with developmental outcomes at 24 months CA. Since linear growth correlates with brain growth and indexes a number of clinical factors, it is an important biomarker that can be used in VLBW infants to predict long-term developmental outcomes.
Osteoporosis-Pseudoglioma Syndrome: Three Novel Mutations in the LRP5 Gene and Response to Bisphosphonate Treatment
Authors: Tüysüz B. , Bursalı A. , Alp Z. , Suyugül N. , Laine C.M. , Mäkitie O.
Published: March 2012

Background/Aims: Osteoporosis-pseudoglioma (OPPG) syndrome is a rare disorder characterized by congenital or infancy-onset visual loss and severe juvenile osteoporosis. OPPG is caused by homozygous mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene. We present three novel homozygous LRP5 mutations found in 3 unrelated Turkish children with consanguineous parents, along with clinical phenotypes and response to treatment with bisphosphonates (bisP). Methods/Results: The LRP5 gene was analyzed by direct sequencing after PCR amplification. Mutation screening for LRP5 revealed homozygous nonsense R1002X mutation in the first patient and homozygous missense mutations V336M and G507S in the second and third patient, respectively. The parents were heterozygous for these mutations. The patients’ eye symptoms began during the first months of life but the OPPG diagnoses were made based on skeletal deformities and osteopenia after 4 years of age. The patients’ bone mineral density Z scores were very low and consistent with osteopenia. All patients were treated with bisP for 3.5–7 years. Conclusion: We report three novel LRP5 mutations in 3 Turkish patients with OPPG. We show that the response of bisP therapy has improved the lumbar spinal bone mineral density Z scores and the patients’ quality of life as the bone pains decreased.
Gallbladder Cancer in the Netherlands: Incidence, Treatment and Survival Patterns since 1989
Authors: Witjes Caroline D.M. , van den Akker Sanne A.W. , Visser Otto , Karim-Kos Henrike E. , de Vries Esther , IJzermans Jan N.M. , de Man Robert A. , Coebergh Jan Willem W. , Verhoef Cornelis
Published: March 2012

Background: To examine recent trends in gallbladder cancer (GBC) in the general population in the Western world, cancer registration data on GBC in the Netherlands were analyzed. Methods: Trends in incidence, treatment and survival, according to gender, age and stage of disease, between 1989 and 2008 for 3,917 patients were studied. Rates were age-standardized to the European standard population (European Standardized Rates – ESR). Results: The incidence rate for GBC in the Netherlands decreased rapidly during the period of 1989–2008, except for males younger than 60 years. Overall survival remained stable, short-term (3-month) and long-term (5-year) relative survival among surgically treated patients increased significantly. Treatment patterns for GBC changed. Surgery decreased from 55% in 1989 to 38% in 2008 (p < 0.001). Chemotherapy and/or irradiation increased from 1.0 to 5.8% (p < 0.001). Receiving best supportive care increased from 44% in 1989 to 57% in 2008 (p < 0.001). Conclusion: The incidence rate for GBC in the Netherlands has decreased rapidly. Treatment patterns for GBC have changed and survival among surgically treated patients has increased.
Fetal and Maternal Complications after Selective Fetoscopic Laser Surgery for Twin-to-Twin Transfusion Syndrome: A Single-Center Experience
Authors: Rustico M.A. , Lanna M.M. , Faiola S. , Schena V. , Dell’Avanzo M. , Mantegazza V. , Parazzini C. , Lista G. , Scelsa B. , Consonni D. , Ferrazzi E.
Published: March 2012

Objective: To report the incidence of fetal and maternal complications after selective fetoscopic laser surgery for twin-to-twin transfusion syndrome (TTTS). Methods: A total of 150 cases of TTTS were treated from January 2004 to June 2009 (period 1, 2004–2006, 62 cases; period 2, 2007 to June 2009, 88 cases). Fetal complications (double and single intrauterine fetal death, recurrence of TTTS, twin anemia-polycythemia sequence (TAPS), reversal of TTTS, cerebral lesions in one twin) and maternal complications were recorded, and retrospectively analyzed. Results: Nineteen (12.6%), 58 (38.7%), 61 (40.7%) and 12 cases (8.0%) were classified preoperatively as Quintero stage I, II, III and IV, respectively. The anterior placenta was described in 73 cases (48.6%). Double and single fetal death occurred overall in 7.3 and 36.0% of cases, respectively. The rate of recurrence was 11.3%, of TAPS 3.3%, and of reversal of TTTS 1.3%. Cerebral lesions were diagnosed in 3 donors (2.0%). Eighteen cases (12.0%) of fetal complications had a second procedure (6 repeat laser, 4 serial amnioreduction, 8 bipolar cord coagulation). Pregnancies undergoing a second procedure delivered at a median gestational age of 30.2 weeks compared to 32.1 weeks for those not repeating (p = 0.04). Perinatal survival of at least one twin improved from 66.1 to 79.5% (p = 0.06) in the two consecutive periods. For every 10 laser surgeries performed, there was an average improvement of 1.5% in the predicted percentage of survival of at least one twin (OR 1.09, 95% CI 1.00–1.19). Major maternal complications occurred in 9 cases (6.0%), 3 of which required admission to intensive care unit. Conclusions: Fetal complications are common after fetoscopic laser surgery. In this experience, an increasing number of procedures improved the performance of a new fetoscopic laser center.
Diabetes Insipidus – Diagnosis and Management
Authors: Di Iorgi Natascia , Napoli Flavia , Allegri Anna Elsa Maria , Olivieri Irene , Bertelli Enrica , Gallizia Annalisa , Rossi Andrea , Maghnie Mohamad
Published: March 2012

Central diabetes insipidus (CDI) is the end result of a number of conditions that affect the hypothalamic-neurohypophyseal system. The known causes include germinoma/craniopharyngioma, Langerhans cell histiocytosis (LCH), local inflammatory, autoimmune or vascular diseases, trauma resulting from surgery or an accident, sarcoidosis, metastases and midline cerebral and cranial malformations. In rare cases, the underlying cause can be genetic defects in vasopressin synthesis that are inherited as autosomal dominant, autosomal recessive or X-linked recessive traits. The diagnosis of the underlying condition is challenging and raises several concerns for patients and parents as it requires long-term follow-up. Proper etiological diagnosis can be achieved via a series of steps that start with clinical observations and then progress to more sophisticated tools. Specifically, MRI identification of pituitary hyperintensity in the posterior part of the sella, now considered a clear marker of neurohypophyseal functional integrity, together with the careful analysis of pituitary stalk shape and size, have provided the most striking findings contributing to the diagnosis and understanding of some forms of ‘idiopathic’ CDI. MRI STIR (short-inversion-time inversion recovery sequencing) is a promising technology for the early identification of LCH-dependent CDI.
On-Site Drugs of Abuse Urinary Screening Tests for the Management of Opiate-Addicted Patients: A Survey among French General Practitioners
Authors: Dupouy Julie , Bismuth Serge , Oustric Stéphane , Lapeyre-Mestre Maryse
Published: March 2012

In France, opiate-addicted patients are mainly managed by general practitioners (GPs). Because on-site abuse drugs urinary screening tests (ODUTs) are now on the market, we investigated French GPs’ knowledge and practices concerning drug tests with a focus on ODUTs. We conducted a descriptive cross-sectional study in ambulatory practice. Postal questionnaires were sent to a random sample of GPs in the Midi-Pyrénées area of France in December 2009. Of the 482 GPs in the sample, 116 (24.1%) regularly treated opiate- addicted patients. Only 31 of them (26.7%) used drug tests and 4 of them (3.4%) performed ODUTs in their consultation rooms. Most of the GPs did not perform ODUTs because they were unaware of whether such tests were reliable or available. Many French GPs treating opiate-addicted patients regularly did not perform ODUTs and lacked knowledge of them.
Gastric Autoimmunity in Children and Adolescents with Type 1 Diabetes: A Prospective Study
Authors: Kakleas K. , Kostaki M. , Critselis E. , Karayianni C. , Giannaki M. , Anyfantakis K. , Haramaras I. , Fotinou A. , Papathanasiou A. , Karavanaki K.
Published: March 2012

Background/Aims: Type 1 diabetes (T1DM) is associated with gastric autoimmunity, which is characterized by the presence of parietal cell antibodies (APCA). We investigated gastric autoimmunity prevalence in T1DM children, its manifestations, determinants and association with thyroid gland (anti-Tg, anti-TPO) and pancreatic β-cell autoimmunity (anti-GAD) at baseline and 4 years later. Methods: The initial cohort (D1) included 97 children with T1DM. At follow-up after 4 years (D2), 84.5% of participants were evaluated. We assessed APCA, anti-Tg, anti-TPO, and anti-GAD presence, as well as symptoms of gastritis. APCA-positive patients were evaluated with gastrin, B12, ferritin levels and were submitted to gastroscopy. Results: Thyroid antibody positivity was increased among the APCA-positive patients. Four years later, among initially APCA-positive patients, 2/6 became APCA negative, while 4/6 developed high titers of APCA. On gastroscopy, 2 patients had chronic hypertrophic gastritis and one Helicobacter pylori gastritis. Conclusions: Gastric autoimmunity was associated with thyroid autoimmunity and anti-GAD persistence. After 4 years, the majority of APCA-positive patients developed high titers of APCA and mild symptoms of gastritis. Thus, patients with T1DM, and in particular those with thyroid and/or pancreatic autoimmunity, should have periodic autoantibody screening for the early diagnosis and follow-up of gastric autoimmunity.
A Novel SRY Mutation Leads to Asymmetric SOX9 Activation and Is Responsible for Mixed 46,XY Gonadal Dysgenesis
Authors: Klee Philippe , Béna Frédérique , Birraux Jacques , Dahoun Sophie , Dirlewanger Mirjam , Girardin Céline , Plotton Ingrid , Rougemont Anne-Laure , Morel Yves , Schwitzgebel Valérie M.
Published: March 2012

Background: SRY, located on the Y chromosome, is one of the key genes involved in human sex determination. SRY mutations are responsible for 10–15% of all cases of 46,XY gonadal dysgenesis (GD) but are rarely implicated in the pathogenesis of mixed GD. Methods: SRY was analyzed by sequence analysis of DNA extracted from blood leukocytes. SRY activity was evaluated by SOX9 immunostaining, one of the targets of SRY. Results: We report a case of mixed GD due to a novel SRY point mutation in a patient with a 46,XY karyotype, without mosaicism or submicroscopic genomic imbalances. Hormonal studies showed low anti-müllerian hormone and histological examination of the gonads showed a streak gonad on the right side and a left dysgenetic testis, thus permitting the diagnosis of mixed GD. Immunostaining for SOX9, a target of SRY, was positive in nuclei of Sertoli and epididymal cells in the left gonad and negative on the right, thus indicating asymmetric activation of SRY. Conclusion: Mixed GD can result from SRY mutations without mosaicism, neither in peripheral blood, nor within the gonads. The asymmetric effect of the point mutation implies the presence of local factors modulating SRY expression or action.
Structural Analysis of the Leptospiral Sphingomyelinases: in silico and Experimental Evaluation of Sph2 as an Mg++-Dependent Sphingomyelinase
Authors: Narayanavari Suneel A. , Kishore Nanda M. , Sritharan M.
Published: March 2012

Background: Leptospiral sphingomyelinases are candidate virulence factors present only in pathogenic Leptospira spp. Leptospira interrogans serovar Lai encodes Sph1, Sph2, Sph3, Sph4 and SphH. Except for Sph4, they all possess the exo-endo-phosphatase domain that groups them under the DNase I superfamily. Methods, Results and Conclusions: Modeling of exo-endo-phosphatase domains reveals high-level structural similarity of Sph2 with the crystal structure of SmcL and BC SMase sphingomyelinases from Listeria ivanovii and Bacillus cereus, respectively. A β-hairpin loop, essential for host cell membrane interaction, is absent in leptospiral sphingomyelinases. Instead, several aromatic amino acids were oriented outward from the surface of these molecules and formed clusters of hydrophobic regions that possibly enables the anchoring of these molecules into the host cell membrane, as demonstrated in Sph2 and Sph3. Sph2 is unique and possesses the Mg++-binding Glu53 residue in the metal-binding site and two His residues (His151 and His286) in the catalytic site. We demonstrate experimentally the Mg++-dependent hemolysis of erythrocytes by rSph2 and its ability to cleave sphingomyelin to ceramide. Anti-Sph2 antibodies neutralized the hemolytic activity of Sph2. In conclusion, we provide evidence showing that Sph2 is a Mg++-dependent hemolysin with both sphingomyelinase and hemolytic activities.
Tacrolimus Improves the Proteinuria Remission in Patients with Refractory IgA Nephropathy
Authors: Zhang Qingxian , Shi Su-fang , Zhu Li , Lv Ji-cheng , Liu Li-jun , Chen Yu-qing , Zhang Hong , Wang Hai-yan
Published: March 2012

Background: Tacrolimus has been reported to be effective in refractory nephrotic syndrome, such as focal segmental glomerulosclerosis and membranous nephropathy. Some IgA nephropathy (IgAN) patients with massive proteinuria showed resistance to steroids and/or cytotoxic immunosuppressants based on the supportive therapy with renin- angiotensin system blockade. The efficacy and safety of tacrolimus in such refractory IgAN patients are extremely ambiguous, and the mechanism of tacrolimus improving proteinuria remission needs to be investigated. Methods: 14 refractory IgAN patients were enrolled. The patients received tacrolimus (0.05–0.1 mg/kg/day) and prednisone (0.5 mg/kg/day) for at least 6 months. Synaptopodin and calcineurin expression were detected in renal tissues of patients who received re-biopsy. A puromycin aminonucleoside (PAN)-induced human podocyte injury model was applied to investigate the possible role of tacrolimus in proteinuria remission. Results: Of the 14 patients enrolled, 3 were withdrawn because serum creatinine increased over 30% baseline. In 11 patients treated with tacrolimus over 6 months, 9 showed complete or partial remission and 7 achieved remission within 1 month. In renal tissues, the expression of calcineurin increased while synaptopodin decreased and recovered partially after tacrolimus therapy. In an in vitro study, F-actin disrupted in human podocytes after stimulation of PAN, while calcineurin increased and synaptopodin decreased. After co-treatment with tacrolimus the reorganization of F-actin and the expression of calcineurin and synaptopodin recovered. Conclusions: Tacrolimus showed a rapid proteinuria remission in refractory IgAN patients. The possible mechanism of tacrolimus to proteinuria remission might be podocyte cytoskeleton stabilization through inhibition of calcineurin expression.