bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypereosinophilic syndromes
Authors: Civardi Giuseppe , Zanlari Luca , Bassi Emanuele , Bonassi Roberta , Ajolfi Corrado
Published: April 2013

Background: The last few years have seen a complete change in the etiopathogenetic features, classification and therapeutic approach of the hypereosinophilic syndrome (HES), a multiorgan targeted blood disease. The discovery of a genetic mutation and the occurrence of a new fusion gene, named FIP1L1-PDGFRA (FIP gene), in some patients allowed the identification of a new myeloproliferative disorder, M-HES: thereafter, the pivotal therapeutic role of the tyrosine kinase inhibitors, particularly, imatinib mesylate, was clearly detected. In the same period a new pathogenetic mechanism has been detected: some authors described the presence of a CD3-CD4 +Tcell clone correlating with the overproduction of IL5, a potent eosinophilic cell line stimulating cytokine. As a consequence an international consensus committee proposed a new classification for these syndromes, in accordance with these new pathogenetic features. The disease is characterized by an extensive tissue and organ damage due to an eosinophilic cell infiltration and leading to the release of toxic cytokines and subsequent organ dysfunction. The heart, lungs, gastrointestinal apparatus, skin and central nervous system are affected. Moreover the released cytokines can induce a thrombophilic status and thromboembolic events can occur throughout the body. Aim of the study: We describe the diagnostic procedures that are necessary in order to obtain a correct diagnosis and classification of the disease and to evaluate the presence of an organ and tissue damage. In particular, bone marrow biopsy and cytogenetic examination of blood and marrow are necessary for detecting M-HES cases that are positive for the FIP gene. In these patients, imatinib mesylate has a leading role for obtaining complete remission of the disease in a high percentage of cases. We also examine the therapeutic options for the other forms of the disease: prednisone, interferon, hydroxiurea are effective therapeutic tools in these patients. Finally, the new therapeutic perspectives, such as monoclonal antibodies directed against IL 5 or IL 5 receptor and novel tyrosine kinase inhibiting drugs, are examined.
Hypertriglyceridemia, a common dyslipidemia of complex definition
Authors: Trenti Chiara , Negri Emanuele A. , Iori Ido , Favali Davide
Published: April 2013

Background: Hypertriglyceridemia is a common biochemical finding. Depending on the triglyceride levels it can be associated with increased risk of acute pancreatitis and of cardiovascular disease. The most severe forms have a genetic basis. Clinical case: We report a case of a 60-year-old woman with very high triglycerides (800- 3,000 mg/dL) and normal cholesterol levels. The patient is a non smoker, on hypolipemic diet, non alcoholic consumer, and on regular physical exercise. Her blood pressure is normal, BMI is 20, waist circumference is 78 cm. Thyroid, renal and hepatic function are normal. She has never had acute pancreatitis or cardiovascular disease. Discussion: The diagnostic and therapeutic management of this case is discussed. Causes of primary (genetic) and secondary hypertriglyceridemia are also reviewed, together with clinical features and management on every day practice. We focused on severe hypertriglyceridemia.
HCV carriers with normal aminotransferase levels: “normal” does not always mean “healthy”
Authors: Puoti Claudio
Published: April 2013

BACKGROUND Approximately 30% of patients with chronic HCV infection show persistently normal ALT levels (PNALT), and another 40% have minimally raised ALT values. Although formerly referred to as “healthy” or “asymptomatic” HCV carriers, it has now become clear that the majority of these patients have some degree of histological liver damage. Controversies still exist regarding the definition of “persistent” ALT normality, the virological and histological features of these subjects, and the natural history and optimal management of chronic hepatitis C (CHC) with normal ALT. Most patients with normal ALT have histologically proven liver damage that may be significant (> F2) in up to 20% of patients, and might progress toward more severe degree of liver fibrosis. A significant proportion of patients (≥ 20%) experiences periods of increased serum ALT (flare) associated with disease progression. AIM OF THE STUDY The introduction of the new combination therapy of PEG-IFN plus ribavirin allowed response rates higher than 50%, with a favourable risk-benefit ratio also in patients with benign or slow progressive disease. Given the efficacy of the new treatments, which soon became the standard of care for CHC, it has been suggested that the issue of whether or not to treat subjects with PNALT should be re-evaluated. ALT levels may have less importance in deciding who should be treated. Many other factors might influence the decision to treat, such as the age of the patient, HCV genotype, liver histology, patient’s motivation, symptoms, extrahepatic manifestations, comorbid illness. The role of non-invasive tools for the assessment of liver fibrosis (transient hepatic elastography) remains to be further validated.
Clinical Research and Internal Medicine: between Science and Bioethics
Authors: Cataldi Amatriain Roberto M.
Published: April 2013

Not available
Psychiatric disorders in systemic lupus erythematosus (SLE): a serious SLE-related crime
Authors: Nicolosi Gabriele , Donia Maria G. , Tripi Ettore , Rinollo Carmelina
Published: April 2013

Introduction: Systemic lupus erythematosus (SLE) is associated with CNS disorders in 50-90% of all cases. Thus far 19 neuropsychiatric syndromes have been reported in association with SLE, and many others will be added to this list in the future. Long-term observation and use of the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (Text Revision) is the solution for a correct diagnosis. Case report: The patient was an 18-year-old woman who had been charged with the attempted murder of an elderly woman in the latter’s home. According to the victim’s testimony, the young woman had entered the victim’s home under pretence and suddently attacked her with a hammer. The young woman denied all knowledge of the event. A few days after her arrest the patient was hospitalized for attempted suicide. The work-up that began with this hospitalization led to the diagnosis of an intermittent explosive disorder secondary to SLE. The authors analyze this case from the psychiatric, medical, and legal points of view. Conclusions: This is the first report of this type of disorder is a patient with SLE. The authors suggest that intermittent explosive disorder should be added to the list of neuropsychiatric syndromes associated with this disease.
Can we eradicate gastric MALT-lymphoma?
Authors: Zullo Angelo , Hassan Cesare , Cristofari Francesca , Iegri Claudia , Villiva Nicoletta , Andriani Alessandro , Morini Sergio
Published: April 2013

The incidence of primary gastric lymphoma in Italy is considerably higher than that observed in the rest of Europe. It is widely accepted that gastric B-cell, low-grade mucosalassociated lymphoid tissue (MALT) lymphoma is caused by specific host-bacterial interactions that occur during Helicobacter pylori infection. This review examines recent findings on the origins, diagnosis, treatment, and follow-up of gastric MALT lymphomas. Clinical and endoscopic findings at diagnosis vary widely. In a substantial number of cases, the patient presents only vague dyspeptic symptoms or poorly defined abdominal pain with no macroscopic lesions on the gastric mucosa. Review of data from 32 trials in which a total of 1,387 MALT-lymphoma patients of the stomach were treated solely with H. pylori eradication revealed high remission rates when the disease is treated early (stage I-II1). Neoplasia confined to the submucosa, antral localization of tumors, and negativity for the API2-MALT1 translocation were associated with a high probability of remission following H. pylori eradication. When the latter approach is not sufficient, radiotherapy, chemotherapy and, in selected cases, surgery are associated with high success rates; data on the efficacy of monoclonal antibody therapy (rituximab) are still limited. Five-year survival rates are higher than 90%. Patients whose tumors have been eliminated require close, long-term endoscopic follow-up since recurrence has been reported in some cases. Broader clinical follow-up is also advisable because the incidence of other solid tumors and of cardiovascular events is reportedly increased in these patients.
Destructive, multifocal squamous-cell carcinoma nodules on the cheecks and neck of an elderly woman with a dementia syndrome
Authors: Marigliano Norma , Colosimo Manuela , Flocco Marcella , Mazzei Francesca , Sirianni Maria V. , Galasso Domenico , Tucci Luigi , Abbonante Francesco , Ruotolo Giovanni
Published: April 2013

Introduction: Squamous-cell carcinoma is the second most common form of skin cancer. It can develop on normal skin, actinic keratoses, leukoplakia, and burn scars. The tumor is characterized by remarkable variability at the macroscopic and histopathologic levels. Case report: A 93-year-old woman was admitted to nursing home with a diagnosis of dementia syndrome and squamous cell nodular carcinoma on cheeks and neck region. The physical examination revealed firm, black excrescences with irregular surfaces over both cheekbones, which were roughly the size of hazelnuts. Similar nodules were present with ulcers on other areas of the face. The patient was admitted to the day hospital twice for wide excision of the tumors in the zygomatic region. Later, the neck tumors were removed, and the wound was repaired with a rotation flap after careful control of bleeding. For the latter surgery, the patient was hospitalized for a few days in a geriatric ward to ensure optimal medical care and psychological support. The histological examination revealed ulcerated, well-differentiated squamous-cell carcinoma that extended down to the subcutaneous layer. Shortly after surgery, she returned to the nursing home to resume rehabilitation and group therapy.
The Italian charter for quality assurance in internal medicine
Authors: Berti Franco
Published: April 2013

The Italian Charter for Quality Assurance in Internal Medicine is a response to the European Charter of Patients’ Rights presented in Brussels in 2002. It is the product of collaborative efforts by Cittadinanza Attiva (a nonprofit citizens’ rights group), the National Association of Hospital Nurses (ANIMO), and the Federation of Associations of Executive-Level Hospital Internists (FADOI). Its objectives are to enhance respect for patients’ rights and promote uniformity in the quality of care delivered in Italy’s health-care facilities, which is currently characterized by marked inter-regional and inter-hospital variability. This article describes the reasons and principles that have guided the Charter’s elaboration and the benefits of partnership between citizens and health-care providers.
The malaise of medicine
Authors: Cagli Vito
Published: April 2013

Not available
Noninvasive ventilation for acute respiratory failure: state of the art (II part)
Authors: Lari Federico , Giostra Fabrizio , Bragagni Gianpaolo , Di Battista Nicola
Published: April 2013

Background: In the last years Non-Invasive Ventilation (NIV) has been playing an important role in the treatment of Acute Respiratory Failure (ARF). Prospective randomised controlled trials have shown improvements in clinical features (respiratory rate, neurological score), pH and arterial blood gases and in particular clinical conditions (Acute Cardiogenic Pulmonary Edema, ACPE, and acute exacerbation of Chronic Obstructive Pulmonary Disease, COPD) systematic reviews and metha-analysis confirm a reduction in the need for intubation and in-hospital mortality compared to standard medical treatment. Methods: The most important techniques of ventilation in spontaneous breathing are: Continuous Positive Airway Pression (CPAP), usually performed with Venturi-like flow generators, and bi-level positive pressure ventilation (an high inspiratory pressure and a low expiratory pressure), performed with ventilators. Facial mask rather than nasal mask is used in ARF: the helmet is useful for prolonged treatments. Results: NIV’s success seems to be determined by early application, correct selection of patients and staff training. Controindications to NIV are: cardiac or respiratory arrest, a respiratory rate < 12 per minute, upper airway obstruction, hemodynamic instability or unstable cardiac arrhythmia, encephalopathy (Kelly score > 3), facial surgery trauma or deformity, inability to cooperate or protect the airway, high risk of aspiration and an inability to clear respiratory secretions. Conclusions: Bi-level ventilation for ARF due to COPD and CPAP or bi-level bentilation for ARF due to ACPE are feasible, safe and effective also in a General Medical ward if the selection of patients, the staff’s training and the monitoring are appropriate: they improve clinical parameters, arterial blood gases, prevent ETI, decrease mortality and hospitalisation. This should encourage the diffusion of NIV in this specific setting.
Artificial nutrition and bioethics issues: medical therapy or basic assistance?
Authors: Lesi Carlo , Fabozzi Maria T. , Valeriani Luca , Zoni Luisa
Published: April 2013

Background: Artificial nutrition provides nutrients artificially to those patients who cannot take food by mouth because of their pathological condition. Artificial nutrition is the therapeutical approach in case of protein-energy malnutrition, which is secondary to many conditions which do not allow to take food by mouth. In the last years the use of artificial nutrition has increased, both in hospitals and in the territory, because of the improvement of techniques and of the increasing knowledge of doctors and people and an increasing number of conditions benefit from it. In a temporary or permanent way, artificial nutrition sets important bioethical issues, as it substitutes the function deficit of the gastroenteric system, which is in charge of natural food intake. It is understandable that in human conscience and culture, food and drinking are very strictly related to life more than any other vital function. This concept is stressed by the phrase: ‘‘Give drink to the thirsty and food to the starving’’, that influences the Christian western culture we live in. Materials and methods: The main documents produced by laymen, Italian Catholic Religion institutions, and scientific societies and the medical ethical code have been analyzed with particular attention to whether artificial nutrition should be considered as a medical therapy or as basic assistance, together with the different ethical consequences on its suspension. Conclusions: Even if the doctor is not a specialist of the field and he has to deal with patients subject to artificial nutrition, he must be aware of the bioethical issues that this technique involves, in order to use it in the best way and to develop his own opinion towards it. The review of the documents presented here cannot be considered to be exhaustive, as this topic continuously evolves.
Approche méthodologique d'inventaire de bâtiments pour les études de risque sismique en milieu urbain : Ville de Québec, Arrondissement La Cité - Limoilou
Authors: Nollet M -J , Désilets C , Abo-El-Ezz A , Nastev M
Published: April 2013

This document presents a methodological approach to perform specific building inventory in view of detailed urban seismic risk studies. This study makes part of the Quantitative Risk Assessment project carried out by the Geological Survey of Canada - Earth
Sciences Sector of Natural Resources Canada to adapt and develop risk assessment tools and promote their use in Canada. Hazus was selected as the best practice GIS-based risk assessment methodology. To adapt Hazus for the Canadian settings, detailed inventories representing typical Canadian cities
have to be performed together with more robust inventories for regional studies. These inventories typically consider building classes representative of a group of buildings with similar structural properties such as construction material, structural type, number of stories, lateral resisting
system, etc. Structural type and other building parameters are generally collected by traditional sidewalk surveys considering first of all visual building characteristics. This approach has its merits, however, it is time consuming, expensive, difficult to update and the reliability of the assigned
building class is often dependent on the surveyormp;gt;'s expertise. The methodological approach for rapid building inventory proposed in this document has for objective to increase the efficiency and reduce subjectivity in inventory data collection. The approach considers the gradual evolution with
time of the typical construction systems used in Quebec City and in the province of Quebec in general. It is based on typical building parameters usually found in the municipal databases. An inference matrix associates the most probable structural type with common building parameters such as year of
construction, number of stories, floor area, building use, and geographical location. La Cité - Limoilou, a district within the central part of Quebec City, was selected as a study area to validate the developed methodological approach. First, two samples of 200 and 2000 buildings were
considered to corroborate the inference matrix. The procedure was then applied for the inventory of a set of 16,421 buildings in the district La Cité - Limoilou and assign building and occupancy classes to each building. The second objective of this study was to identify structural
characteristics of the typical stone masonry buildings found in the Old Quebec City in view of defining a prototype and propose a specific building class for Hazus application. The proposed inference matrix will be useful to perform similar inventory for application in seismic risk studies with
Hazus or other similar risk assessment tools. A seismic risk assessment study of the district La Cité - Limoilou in Quebec City is currently underway at École de technologie supérieure.
Kazanistan: John Rawls's Oriental Utopia
Authors: Hatzenberger Antoine
Published: April 2013

In The Law of Peoples (1999), John Rawls develops the concept of realistic utopia within the framework of a philosophy of international relations. In order to illustrate his definition of “decent peoples” he imagines an “idealized Islamic people named Kazanistan.” What are the context and status of the imaginary construct of a society of peoples? How are the people of Kazanistan described? In what sense, and to what extent, is this “idealized Islamic people” imagined by Rawls really a utopia?
Does Size Matter? Short and Tall Officers Policing the Streets
Authors: Lagestad Pål
Published: April 2013

The importance of physical characteristics is rarely addressed in the literature on professional competence and authority. In police work it is almost taken for granted that height is advantageous in police work, despite a lack of research on the topic. This study examines how height may affect police inter-actions with the public and how short and tall men and women experience the importance of their height in patrol work. Results show that being tall was perceived as beneficial in patrol work. Furthermore, the authority of short police officers is challenged more often by the public, and short female police may have a particular focus on verbal communication. Tallness will probably be perceived as beneficial in fields in which physical conflicts arises.
Low Electron Scattering Potentials in High Performance Mg2Si0.45Sn0.55 Based Thermoelectric Solid Solutions with Band Convergence
Authors: Liu Xiaohua , Zhu Tiejun , Wang Heng , Hu Lipeng , Xie Hanhui , Jiang Guangyu , Snyder G. Jeffrey , Zhao Xinbing
Published: April 2013

Understanding the electron and phonon transport characteristics is crucial for designing and developing high performance thermoelectric materials. Weak scattering effects on charge carriers, characterized by deformation potential and alloy scattering potential, are favorable for thermoelectric solid solutions to enable high carrier mobility and thereby promising thermoelectric performance. Mg2(Si,Sn) solid solutions have attracted much attention due to their low cost and environmental compatibility. Usually, their high thermoelectric performance with ZT ∼ 1 is ascribed to the band convergence and reduced lattice thermal conductivity caused by alloying. In this work, both a low deformation potential Ξ = 13 eV and a low alloy scattering potential U = 0.7 eV are found for the thermoelectric alloys by characterizing and modeling of thermoelectric transport properties. The band convergence is also verified by the increased density‐of‐states effective mass. It is proposed that, in addition to band convergence and reduced lattice thermal conductivity, the low deformation potential and alloy scattering potential are additional intrinsic features that contribute to the high thermoelectric performance of the solid solutions.
A new single gene deletion on 2q34: ERBB4 is associated with intellectual disability
Authors: Kasnauskiene Jurate , Ciuladaite Zivile , Preiksaitiene Egle , Utkus Algirdas , Peciulyte Agnė , Kučinskas Vaidutis
Published: April 2013

We report on a 15‐year‐old patient with hyperactivity, intellectual disability and severe speech developmental delay. An array CGH analysis revealed de novo 2q34 deletion, 958 kb in size, involving a single protein coding gene ERBB4 (position 212,505,294–213,463,152; NCBI build 36). The ERBB4 gene is important in numerous neurobiological processes in both the developing and the adult brain. The NRG1–ERBB4 signaling pathway has been recently implicated in the pathophysiology of schizophrenia and epilepsy. Many risk haplotypes were identified in several studies across different populations. The severe clinical consequences in our patient demonstrate that the haploinsufficiency of ERBB4 is crucial for intellectual and cognitive function. These observations are compatible with previously reported results. © 2013 Wiley Periodicals, Inc.
Technical Note: Comparing von Luschan skin color tiles and modern spectrophotometry for measuring human skin pigmentation
Authors: Swiatoniowski Anna K. , Quillen Ellen E. , Shriver Mark D. , Jablonski Nina G.
Published: April 2013

Prior to the introduction of reflectance spectrophotometry into anthropological field research during the 1950s, human skin color was most commonly classified by visual skin color matching using the von Luschan tiles, a set of 36 standardized, opaque glass tiles arranged in a chromatic scale. Our goal was to establish a conversion formula between the tile‐based color matching method and modern reflectance spectrophotometry to make historical and contemporary data comparable. Skin pigmentation measurements were taken on the forehead, inner upper arms, and backs of the hands using both the tiles and a spectrophotometer on 246 participants showing a broad range of skin pigmentation. From these data, a second‐order polynomial conversion formula was derived by jackknife analysis to estimate melanin index (M‐index) based on tile values. This conversion formula provides a means for comparing modern data to von Luschan tile measurements recorded in historical reports. This is particularly important for populations now extinct, extirpated, or admixed for which tile‐based measures of skin pigmentation are the only data available. Am J Phys Anthropol 151:325–330, 2013. © 2013 Wiley Periodicals, Inc.
Evidence That CXCL16 Is a Potent Mediator of Angiogenesis and Is Involved in Endothelial Progenitor Cell Chemotaxis: Studies in Mice With K/BxN Serum–Induced Arthritis
Authors: Isozaki Takeo , Arbab Ali S. , Haas Christian S. , Amin M. Asif , Arendt Monica D. , Koch Alisa E. , Ruth Jeffrey H.
Published: April 2013

Objective

To examine the possibility that CXCL16 recruits endothelial cells (ECs) to developing neovasculature in rheumatoid arthritis (RA) synovium.

Methods

We utilized the RA synovial tissue SCID mouse chimera system to examine human microvascular EC (HMVEC) and human endothelial progenitor cell (EPC) recruitment into engrafted human synovium that was injected intragraft with CXCL16‐immunodepleted RA synovial fluid (SF). CXCR6‐deficient and wild‐type (WT) C57BL/6 mice were primed to develop K/BxN serum–induced arthritis and evaluated for angiogenesis. HMVECs and EPCs from human cord blood were also examined for CXCR6 expression, by immunofluorescence and assessment of CXCL16 signaling activity.

Results

CXCR6 was prominently expressed on human EPCs and HMVECs, and its expression on HMVECs could be up‐regulated by interleukin‐1β. SCID mice injected with CXCL16‐depleted RA SF exhibited a significant reduction in EPC recruitment. In experiments using the K/BxN serum–induced inflammatory arthritis model, CXCR6−/− mice showed profound reductions in hemoglobin levels, which correlated with reductions in monocyte and T cell recruitment to arthritic joint tissue compared to that observed in WT mice. Additionally, HMVECs and EPCs responded to CXCL16 stimulation, but exhibited unique signal transduction pathways and homing properties.

Conclusion

These results indicate that CXCL16 and its receptor CXCR6 may be a central ligand/receptor pair that is closely associated with EPC recruitment and blood vessel formation in the RA joint.
Comparison of two functional kappa light‐chain transcripts amplified from a hybridoma
Authors: Yang Juan , Zhu Huifen , Tan Zheng , He Fengrong , Sun Xiaoxu , Hong Yi , Hu Heyu , Bian Jing , Lin Yu , Lei Ping , Shen Guanxin
Published: April 2013

Three heavy‐chain and three kappa (κ)‐chain transcripts were amplified from hybridoma cells secreting a monoclonal antibody (mAb) against transferrin receptor. Sequence analysis via IMGT/V‐QUEST yielded the functional/aberrant prediction. Two functional κ‐chain transcripts, Vκ2 and Vκ3, and one functional VH1 were revealed. Comprehensive bioinformatics analyses including sequence alignment, phylogenetic tree, somatic hypermutation prediction, and three‐dimensional‐molecular structure modeling were used to predict the origin of the two κ‐chain transcripts. The results of bioinformatics analysis suggest that Vκ3 is derived from the myeloma partner of the hybridoma; Vκ2 is derived from B‐cell. Functional transcripts VH1 and Vκ2 and Vκ3 were then used to construct two chimeric antibodies chi‐C2 (Vκ2–VH1) and chi‐C3 (Vκ3–VH1), respectively. Antigen‐binding experiments showed that only chi‐C2 remained the same affinity as its parental mAb. Possible explanations for the coexistence of two functional κ‐chain transcripts and the different affinity of the two chimeric antibodies are discussed.
B cell lymphoma, unclassifiable, with features intermediate between diffuse large B cell lymphoma and classical hodgkin lymphoma: Diagnosis by fine‐needle aspiration cytology
Authors: Lynnhtun Kyaw , Varikatt Winny , Pathmanathan Nirmala
Published: April 2013

A 58‐year‐old lady presented with mediastinal lymphadenopathy. A thoracoscopic ultrasound‐guided fine‐needle aspiration showed large atypical epithelioid cells arranged in cohesive sheets and dispersed as single cells with intact cytoplasm amid a background of lymphocytes and histiocytes. A cytological diagnosis of “a malignant neoplasm” was made, raising a broad list of differential diagnoses. A broad panel of immunocytochemical stains performed on the cell block was indicative of a lymphoproliferative disorder, but the immunophenotype was intermediate between diffuse large B cell lymphoma (DLBCL) and classical Hodgkin lymphoma (cHL). Diffuse and strong reactivity to CD20, CD79a, and PAX‐5, and weak reactivity to CD30, was in favor of a DLBCL, or more precisely mediastinal (thymic) large B cell lymphoma (MLBL). However, there were negative staining for LCA, OCT‐2, and BOB‐1 as well as positive staining for EBV‐encoded RNA, which were against a diagnosis of MLBL and raised the possibility of cHL. The absence of RS cells and the typical mileu, the negativity for CD15 and the strong positivity of CD20 and PAX‐5 were against a diagnosis of cHL. On this basis, the diagnosis of “B‐cell lymphoproliferative disorder with features intermediate between DLBCL and cHL” was rendered. The diagnosis was subsequently confirmed on excisional biopsy. This case report demonstrates broad differential diagnoses raised by this diagnostic entity and the importance of an adequate cell block for accurate designation. Diagn. Cytopathol. 2014;42:690–693. © 2013 Wiley Periodicals, Inc.
Defects of leukocyte migration in primary immunodeficiencies
Authors: Badolato Raffaele
Published: April 2013

This Viewpoint gives an overview of the inherited disorders that are characterized by defects of leukocyte trafficking. Three paradigmatic diseases have been selected: warts, hypogammaglobulinemia, infections, and myelokathexis; Wiskott–Aldrich; and leukocyte adhesion deficiency syndromes. These conditions encompass defects in the steps that are required for leukocyte motility: from the response to chemokines, which is altered in warts, hypogammaglobulinemia, infections, and myelokathexis syndrome, to the impairment of leukocyte adhesion and migration found in leukocyte adhesion deficiency syndrome, and finally to abnormal actin filament formation, which is affected in leukocytes of Wiskott–Aldrich syndrome patients.
Dinuclear Cobalt(II) Complexes as Metallo‐β‐lactamase Mimics
Authors: Daumann Lena J. , Larrabee James A. , Comba Peter , Schenk Gerhard , Gahan Lawrence R.
Published: April 2013

The β‐lactamase activity of two previously reported dinuclear cobalt(II) complexes is described. The two complexes, [Co2(CO2EtH2L1)(CH3COO)2](PF6) (CO2EtH3L1 = ethyl 4‐hydroxy‐3,5‐bis{[(2‐hydroxyethyl)(pyridin‐2‐ylmethyl)amino]methyl}benzoate) and [Co2(CO2EtL2)(CH3COO)2](PF6) (CO2EtHL2 = ethyl 4‐hydroxy‐3,5‐bis{[(2‐methoxyethyl)(pyridin‐2‐ylmethyl)amino]methyl}benzoate), differ in that the latter has methyl ether donors in contrast to potentially nucleophilic alkoxide donors in the former. They thus offer a direct comparison of potential ligand‐centered nucleophiles. The complexes were treated with the antibiotic penicillin G and the commonly used lactamase substrate nitrocefin. On the basis of mass spectrometry, UV/Vis, and infrared spectroscopy measurements in solution, it was shown that only [Co2(CO2EtH2L1)(CH3COO)2](PF6) was capable of hydrolyzing both penicillin and nitrocefin, and that the hydrolysis‐initiating nucleophile was an alkoxide donor. Analysis of kinetic data showed that nitrocefin binding occurs more rapidly {k1 = [(2.5 × 103) ± (1.9 × 101)] M–1 min–1} than its subsequent hydrolysis {k2 = [(1.6 × 10–1) ± (8.1 × 10–4)] min–1}. The pH dependence of nitrocefin hydrolysis by [Co2(CO2EtH2L1)(CH3COO)2]+ displays two pKa values (6.88 ± 0.74; 8.45 ± 0.68), the first of which is attributed to the deprotonation of a CoII alcohol, and the second of which is proposed to arise from CoII–OH2. For [Co2(CO2EtL2)(CH3COO)2]+, only one relevant pKa1 (8.47 ± 0.14) is evident, assigned to a terminal water molecule. By using variable‐temperature/variable‐field magnetic circular dichroism (VTVH MCD), it was demonstrated that the sign of the magnetic exchange coupling parameter (J) for the parent dinuclear cobalt(II) complexes changes upon binding of the substrate. This work presents one of the few cobalt(II) β‐lactamase model complexes that is capable of facile hydrolysis of β‐lactam substrates, an outcome that provides a good benchmark to investigate the reaction mechanism(s) applicable to the enzyme systems.
Influence of heavy metals on glyceraldehyde-3-phosphate dehydrogenase interactions in Chironomus riparius larvae
Authors: Wai Isaac , Chong King , Ho Wing Shing
Published: April 2013

Some aquatic organisms can live in contaminated environment due to their adaptable defense mechanism related to their inducible detoxification and excretion. A recent study showed glyceraldehyde-3-phosphate dehydrogenase (GAPDH) can modulate different cellular activities including transcription activation and detoxification. In the present study, the authors report on experiments to test the GAPDH activity of Chironomus riparius toward heavy metals. Glyceraldehyde-3-phosphate dehydrogenase was isolated and purified from C. riparius. The kinetics of the enzyme was measured. The results showed that GAPDH was inhibited by heavy metals including Co2+, Cu2+, Fe2+, Ni2+, Pb2+, but was activated by zinc ions. The kinetics study of the enzyme showed maximum initial velocity (Vmax) of GAPDH increased by 50%. In addition, the substrate and cofactor affinity increased in the presence of zinc. The GAPDH from C. riparius had maximum activities at pH 8.5 and 37 °C. The protein sequence analysis shows that there are 2 additional cysteine and histidine residues in the conserved region of GAPDH from C. riparius, which is believed to play an important role in the interactions with heavy metals. The results suggest that exposure to zinc could modulate GAPDH, which could be related to response of antioxidant defense to other heavy metals. Environ Toxicol Chem 2013;32:1882–1887. © 2013 SETAC
Computational Studies for the Evaluation of Fuel Flexibility in Solid Oxide Fuel Cells: A Case with Biosyngas
Authors: Fan L. , Qu Z. , Pourquie M. J. B. M. , Verkooijen A. H. M. , Aravind P. V.
Published: April 2013

The fuel flexibility of solid oxide fuel cells (SOFCs) is one of the advantages of this technology, and biosyngas produced from biomass is emerging as a new fuel. The fuelling of SOFCs with different fuels is always challenging because of the associated risks. Mathematical modeling tools are useful for predicting the operational safety constraints and designs of SOFCs that are suitable for different fuels. Using a single channel model that incorporates direct internal reforming (DIR), this work investigates the fuel flexibility of an anode‐supported intermediate temperature planar solid oxide fuel under co‐flow operation. The DIR reaction of methane, the water‐gas shift reaction (WGS) and the electrochemical reaction of hydrogen are the three reactions taken into account in this simulation work. Detailed comparisons of the gas concentrations, the current density distributions and the temperature change profiles are presented and discussed. These simulation results provide the initial data for performance analyses and safety predictions, which will be helpful for our future experimental investigations. The thermodynamic predictions of both nickel oxidation and carbon deposition are employed to check the operational safety of SOFCs fuelled with biosyngas.
Fabrication and Performance of Tubular, Electrode‐Supported BaCe0.2Zr0.7Y0.1O3–δ Fuel Cells
Authors: Robinson S. , Manerbino A. , Grover Coors W. , Sullivan N. P.
Published: April 2013

In this report, we describe fabrication and electrochemical‐performance testing of tubular, anode‐supported fuel cells based on the protonic ceramic BaCe0.2Zr0.7Y0.1O3–δ (BCZY27). These devices are comprised of a 20‐μm‐thick BCZY27 electrolyte spray‐coated and co‐fired onto an extruded, tubular 9.8‐mm‐diameter, 1.25‐mm‐thick 65 wt.% NiO/35 wt.% BCZY27 anode support. Reactive sintering with NiO forms the BCZY27 material from parent oxides. An La0.6Sr0.4 Co0.2Fe0.8O3–δ (LSCF) cathode is applied following co‐sintering. While anode supports can be extruded to 3‐m lengths, the active area of the cells tested here is 7.5 cm2. Performance is quantified through polarization measurements across a range of temperatures with hydrogen‐air reactants. Peak power ranges from 78 to 189 mW cm–2 over the 700–850 °C temperature range. Open‐circuit voltage decreases with increasing operating temperature due to the co‐diffusion of the multiple charge carriers present. The ionic transference number is determined over a range operating temperatures and anode‐gas compositions, and is found to range from 0.77 to 0.88. Finally, an external power supply is used to drive hydrogen across the BCZY27 membrane. At an applied current density of 1 A cm–2 and 700 °C operating temperature, hydrogen flux is measured at 7.5 smL min–1 cm–2 active area.
Chemical Compatibility and Electrical Contact of LaNi0.6Co0.4O3–δ (LNC) between Crofer22APU Interconnect and La0.6Sr0.4FeO3 (LSF) Cathode for IT‐SOFC
Authors: Morán‐Ruiz A. , Vidal K. , Larrañaga A. , Arriortua M. I.
Published: April 2013

In order to simulate the contact situation of interconnect/contact layer/cathode in SOFC stacks, contact resistance and chemical compatibility of LaNi0.6Co0.4O3–δ (LNC) as contact layer between Crofer22APU interconnect and La0.6Sr0.4FeO3 (LSF) cathode was investigated at 800 °C in air for more than 1300 h using X‐ray diffraction (XRD), scanning electron microscopy (SEM) set‐up equipped with an energy dispersive X‐ray analyser (EDX) and area specific resistance (ASR) measurements. The XRD analysis reveals that multiple phases were formed during ASR test. The point microanalysis on cross‐section of Fe–Cr/LNC/LSF system, after ASR measurements, shows chromium within the porous contact material mainly concentrated close to interconnect, but no Cr, Ni, or Co was detected in the cathode. It was found between LNC and LSF cathode, a thin and uniform layer which contains Sr, La, Cr, Co, Ni, and Fe. The contact between layers could act as a physical barrier for element migration and thus can suppress degradation of the cathode for these systems. The area specific resistance slope depends on the interactions between the contact material and/or cathode and the interconnect. Co‐containing spinels formed during ASR test can be responsible of the resistance decrease of the system, related to the low degradation of the cell.
Short‐Form CDYLb but not long‐form CDYLa functions cooperatively with histone methyltransferase G9a in hepatocellular carcinomas
Authors: Wu Hui , Zhang Haihong , Wang Peng , Mao Zhuo , Feng Li , Wang Yuqian , Liu Chenlu , Xia Qiu , Li Bo , Zhao Heya , Chen Yan , Wu Jiaxin , Kong Wei , Yu Xianghui
Published: April 2013

In hepatocellular carcinomas (HCCs), the levels of histone H3 dimethylation at lysine 9 (H3K9me2) and its corresponding histone methyltransferase G9a are significantly elevated. Recently, G9a was reported to form a complex with the H3K9 methylation effector protein CDYL, but little is known about the expression of CDYL in HCC patients. The human CDYL gene produces two transcripts, a long form (CDYLa) and a short form (CDYLb), but it is unclear whether the protein products have different functions. The aim of this study was to investigate the distinctions between CDYLa and CDYLb and their expression levels in HCC tissues. We first examined binding abilities of the different CDYL forms with methylated H3 peptides by a pull‐down assay. Human CDYLb (h‐CDYLb) specifically recognized H3Kc9me2 and H3Kc9me3 modifications, whereas human CDYLa (h‐CDYLa) did not interact with any methylated H3 peptides. Similarly, mouse CDYLb (m‐CDYLb) specifically bound with di‐ and tri‐methylated H3Kc9 peptides, while mouse CDYLa (m‐CDYLa) lacked that ability. Affinity purification also was used to identify the distinct composition of the h‐CDYLa or h‐CDYLb protein complex. h‐CDYLb was found in a multiprotein complex with G9a and GLP, while the h‐CDYLa complex did not contain these two enzymes. Consistent with the protein complex composition, h‐CDYLb and G9a were both upregulated in HCC tissues, compared with adjacent non‐cancerous liver tissues. Furthermore, the positive correlation between expression levels of h‐CDYLb and G9a was statistically significant. In contrast, h‐CDYLa showed no enrichment in HCC tissues. These findings suggest that h‐CDYLb and G9a are cooperatively involved in HCC. © 2013 Wiley Periodicals, Inc.
How stem cells speak with host immune cells in inflammatory brain diseases
Authors: Pluchino Stefano , Cossetti Chiara
Published: April 2013

Advances in stem cell biology have raised great expectations that diseases and injuries of the central nervous system (CNS) may be ameliorated by the development of non‐hematopoietic stem cell medicines. Yet, the application of adult stem cells as CNS therapeutics is challenging and the interpretation of some of the outcomes ambiguous. In fact, the initial idea that stem cell transplants work only via structural cell replacement has been challenged by the observation of consistent cellular signaling between the graft and the host. Cellular signaling is the foundation of coordinated actions and flexible responses, and arises via networks of exchanging and interacting molecules that transmit patterns of information between cells. Sustained stem cell graft‐to‐host communication leads to remarkable trophic effects on endogenous brain cells and beneficial modulatory actions on innate and adaptive immune responses in vivo, ultimately promoting the healing of the injured CNS. Among a number of adult stem cell types, mesenchymal stem cells (MSCs) and neural stem/precursor cells (NPCs) are being extensively investigated for their ability to signal to the immune system upon transplantation in experimental CNS diseases. Here, we focus on the main cellular signaling pathways that grafted MSCs and NPCs use to establish a therapeutically relevant cross talk with host immune cells, while examining the role of inflammation in regulating some of the bidirectionality of these communications. We propose that the identification of the players involved in stem cell signaling might contribute to the development of innovative, high clinical impact therapeutics for inflammatory CNS diseases.
Relationship between observable emotional expression and wandering behavior of people with dementia
Authors: Lee Kyung Hee , Algase Donna L. , McConnell Eleanor S.
Published: April 2013

Objective

This study explored the relationship between observable emotional expression and wandering behaviors of people with dementia (PWD).

Methods

A secondary data analysis was conducted of a multi‐site study that used a cross‐sectional design with repeated measures nested within subjects. Participants included 142 PWD residing in 17 nursing homes and six assisted‐living facilities in Michigan and Pennsylvania who were randomly assigned to six 20‐min videotaped observation periods, conducted on two non‐consecutive days. Poisson hierarchical linear modeling was used to examine associations between emotional expression and wandering.

Results

Participants exhibited an average of 13.5 (standard deviation [SD] ± 12.4) episodes of positive emotional expression per observation; only 1.5 (SD ± 2.3) episodes of negative emotional expression per observation were noted. The mean wandering rate was 2.9 episodes (SD ± 6.9) per hour. Positive emotional expression was positively related to wandering rates, whereas negative emotional expression and higher cognitive status were negatively related to wandering rates after controlling for other predictors (age, education, gender, facility type, mobility, and time of day).

Conclusions

Both positive and negative emotional expressions, along with cognitive status, should be considered when developing interventions to improve wandering behaviors of PWD. Copyright © 2013 John Wiley & Sons, Ltd.
Available potential energy gain from mixing due to the nonlinearity of the equation of state in a global ocean model
Authors: Urakawa L. S. , Saenz J. A. , Hogg A. M.
Published: April 2013

Densification in the ocean interior upon mixing at high latitudes, due to the nonlinear equation of state (EoS) of seawater, enhances the meridional overturning circulation (MOC). However, recent calculations using numerical simulations of global ocean circulation have shown that the nonlinearity of the EoS leads to a sink of gravitational potential energy (PE), from which one might infer that there is less energy available to be released to the MOC. Here the available PE (APE) budget of the global ocean is investigated using a numerical model with a nonlinear EoS under a realistic configuration. The results show that, while the nonlinearity of the EoS leads to a loss of gravitational PE, it is a source of APE. For the model used in this study, nonlinearity of the EoS is as significant as surface buoyancy forcing in generating APE.
Expertise modulates local regional homogeneity of spontaneous brain activity in the resting brain: An fMRI study using the model of skilled acupuncturists
Authors: Dong Minghao , Qin Wei , Zhao Ling , Yang Xuejuan , Yuan Kai , Zeng Fang , Sun Jinbo , Yu Dahua , von Deneen Karen M. , Liang Fanrong , Tian Jie
Published: April 2013

Studies on training/expertise‐related effects on human brain in context of neuroplasticity have revealed that plastic changes modulate not only task activations but also patterns and strength of internetworks and intranetworks functional connectivity in the resting state. Much has known about plastic changes in resting state on global level; however, how training/expertise‐related effect affects patterns of local spontaneous activity in resting brain remains elusive. We investigated the homogeneity of local blood oxygen level‐dependent fluctuations in the resting state using a regional homogeneity (ReHo) analysis among 16 acupuncturists and 16 matched nonacupuncturists (NA). To prove acupuncturists' expertise, we used a series of psychophysical tests. Our results demonstrated that, acupuncturists significantly outperformed NA in tactile‐motor and emotional regulation domain and the acupuncturist group showed increased coherence in local BOLD signal fluctuations in the left primary motor cortex (MI), the left primary somatosensory cortex (SI) and the left ventral medial prefrontal cortex/orbitofrontal cortex (VMPFC/OFC). Regression analysis displayed that, in the acupuncturists group, ReHo of VMPFC/OFC could predict behavioral outcomes, evidenced by negative correlation between unpleasantness ratings and ReHo of VMPFC/OFC and ReHo of SI and MI positively correlated with the duration of acupuncture practice. We suggest that expertise could modulate patterns of local resting state activity by increasing regional clustering strength, which is likely to contribute to advanced local information processing efficiency. Our study completes the understanding of neuroplasticity changes by adding the evidence of local resting state activity alterations, which is helpful for elucidating in what manner training effect extends beyond resting state. Hum Brain Mapp 35:1074–1084, 2014. © 2013 Wiley Periodicals, Inc.
Cardiac toxicity in breast cancer patients treated with dual HER2 blockade
Authors: Valachis Antonis , Nearchou Andreas , Polyzos Nikolaos P. , Lind Pehr
Published: April 2013

Although dual HER2 blockade shows promising results in patients with HER2‐positive breast cancer it is unclear whether this treatment strategy increases the risk for cardiac adverse events. We conducted a meta‐analysis of randomized trials to investigate the risk of cardiac adverse events when a combination of anti‐HER2 therapies compared to anti‐HER2 monotherapy. We searched Medline, the Cochrane library, as well as the electronic abstract databases of the major international congresses' proceedings to identify randomized trials that evaluated the administration of anti‐HER2 monotherapy (lapatinib or trastuzumab or pertuzumab) versus anti‐HER2 combination (pertuzumab plus trastuzumab or trastuzumab plus lapatinib) therapy in breast cancer. The trials were considered eligible if the only systematic difference between the study arms was the type of anti‐HER2 therapy used. Study outcomes were the congestive heart failure (CHF) grade ≥3 and left ventricular ejection fraction (LVEF) decline <50% or more than 10% from baseline. Six trials were considered eligible. Overall incidence results for CHF in the combined anti‐HER2 therapy and the anti‐HER2 monotherapy were 0.88% (95% CI: 0.47–1.64%) and 1.49% (95% CI: 0.98–2.23%). The incidence of LVEF decline was 3.1% (95% CI: 2.2–4.4%) and 2.9% (95% CI: 2.1–4.1%), respectively. The OR of CHF between anti‐HER2 combination and monotherapy was 0.58 (95% CI: 0.26–1.27, p‐value= 0.17) while the OR of LVEF decline was 0.88 (95% CI: 0.53–1.48, p‐value= 0.64). This meta‐analysis provides evidence supporting comparable cardiac toxicity between anti‐HER2 combination therapy and anti‐HER2 monotherapy.