bluuebunny/crossref_metadata_2025 huggingface dataset:
PRAME Expression and Its Clinical Relevance in Hodgkin's Lymphoma
Authors: Ercolak Vehbi , Paydas Semra , Bagir Emine , Ergin Melek , Seydaoglu Gulsah , Celik Hikmet , Yavuz Basak , Tanriverdi Kahraman , Gunaldi Meral , Afsar Cigdem U. , Duman Berna B.
Published: June 2015

Objectives: Although Hodgkin's lymphoma (HL) is one of the most curable cancers in adult patients, new targets have to be defined in cases resistant to traditional chemotherapy. The preferentially expressed antigen of melanoma (PRAME) is a cancer testis antigen and its expression is very scarce or absent in normal tissues. For this reason PRAME is a promising candidate for tumor immunotherapy. The aim of this study is to understand the correlation of PRAME expression with prognostic factors in HL, to determine the utility of PRAME as a targeted molecule for immunotherapy and to compare real-time polymerase chain reaction (real-time PCR) and immunohistochemistry (IHC) for the detection of PRAME. Methods: In 82 patients, PRAME was studied using real-time PCR and IHC. Data analyses were performed using statistical methods such as t test, Mann-Whitney U test, χ2 test, Kaplan-Meier method, log-rank test and Cox regression analysis. Results: PRAME was detected in 15 (18.3%) patients using IHC and in 8 (9.8%) patients using real-time PCR. A correlation was found between PRAME positivity and higher International Prognostic Score (p = 0.039). PRAME positivity detected using real-time PCR was found to be correlated with shorter disease-free survival (DFS) and overall survival (OS, p = 0.0005). Discussion: The demonstration of PRAME especially in histiocytes and Reed-Sternberg cells may provide guidance for immunotherapy. Although PRAME positivity increases the risk for death (3.56), independent risk factors that affected DFS and OS occurred in advanced age and high-risk groups. Conclusion: Although real-time PCR is sensitive in the detection of PRAME, IHC can be another useful method. Despite the need for studies conducted on larger patient samples, PRAME expression is considered as a poor prognostic parameter in HL.
The Phonetic Realization of Devoiced Vowels in the Southern Ute Language
Authors: Oberly Stacey , Kharlamov Viktor
Published: June 2015

In this article, we analyze the phonetic realizations of devoiced vowels from 8 fluent speakers of Southern Ute, a severely endangered Southern Numic Uto-Aztecan language spoken in Southwestern Colorado. Devoiced vowels are considered to be an important aspect of the phonology of Southern Ute, yet very little is known about the pronunciation of such segments. Our findings indicate that devoiced vowels are realized phonetically in three ways: (i) fully voiceless, (ii) partially devoiced, and (iii) fully reduced with concurrent lengthening, lower intensity and greater voicelessness of the preceding consonant. Such variable and noncategorical devoicing is seen for both high and nonhigh vowels and all consonants regardless of their manner of articulation.
Improved Visual Perception in Very Low Birth Weight Infants on Enhanced Nutrient Supply
Authors: Blakstad Elin W. , Strømmen Kenneth , Moltu Sissel J. , Wattam-Bell John , Nordheim Trond , Almaas Astrid N. , Grønn Morten , Rønnestad Arild E. , Brække Kristin , Iversen Per Ole , von Hofsten Claes , Veierød Marit B. , Westerberg Ane C. , Drevon Christian A. , Nakstad Britt
Published: June 2015

Background: Optimal nutrient supply to very low birth weight (VLBW: BW <1,500 g) infants is important for growth and neurodevelopment. Growth restriction is common among these infants and may be associated with neurocognitive impairments. Objectives: To compare an enhanced nutrient supply to a routine supply given to VLBW infants and to evaluate the effects on visual perception of global form and motion measured by visual event-related potentials (VERP). Methods: A total of 50 VLBW infants were randomized to an intervention group that received an increased supply of energy, protein, fat, essential fatty acids, and vitamin A or a control group that received standard nutritional care. At 5 months' corrected age the infants were examined using VERP to investigate the responses to global form and motion. VERP were analysed at the first (f1) and third (f3) harmonics of the stimulus frequency. Results: Data from 31 subjects were eligible for analysis. The motion VERP responses for the f1 and f3 components were stronger in the area near the posterior midline region in the intervention group compared to the controls in the group analyses (p = 0.02 and p = 0.001, respectively). Conclusion: The results showed a more consistent response to global motion among infants receiving enhanced nutrition. The intervention may have improved visual perception of global motion.
Preoperative Thromboelastometry as a Predictor of Transfusion Requirements during Adult Living Donor Liver Transplantation
Authors: Fayed Nirmeen , Mourad Wessam , Yassen Khaled , Görlinger Klaus
Published: June 2015

Background: The ability to predict transfusion requirements may improve perioperative bleeding management as an integral part of a patient blood management program. Therefore, the aim of our study was to evaluate preoperative thromboelastometry as a predictor of transfusion requirements for adult living donor liver transplant recipients. Methods: The correlation between preoperative thromboelastometry variables in 100 adult living donor liver transplant recipients and intraoperative blood transfusion requirements was examined by univariate and multivariate linear regression analysis. Thresholds of thromboelastometric parameters for prediction of packed red blood cells (PRBCs), fresh frozen plasma (FFP), platelets, and cryoprecipitate transfusion requirements were determined with receiver operating characteristics analysis. The attending anesthetists were blinded to the preoperative thromboelastometric analysis. However, a thromboelastometry-guided transfusion algorithm with predefined trigger values was used intraoperatively. The transfusion triggers in this algorithm did not change during the study period. Results: Univariate analysis confirmed significant correlations between PRBCs, FFP, platelets or cryoprecipitate transfusion requirements and most thromboelastometric variables. Backward stepwise logistic regression indicated that EXTEM coagulation time (CT), maximum clot firmness (MCF) and INTEM CT, clot formation time (CFT) and MCF are independent predictors for PRBC transfusion. EXTEM CT, CFT and FIBTEM MCF are independent predictors for FFP transfusion. Only EXTEM and INTEM MCF were independent predictors of platelet transfusion. EXTEM CFT and MCF, INTEM CT, CFT and MCF as well as FIBTEM MCF are independent predictors for cryoprecipitate transfusion. Thromboelastometry-based regression equation accounted for 63% of PRBC, 83% of FFP, 61% of cryoprecipitate, and 44% of platelet transfusion requirements. Conclusion: Preoperative thromboelastometric analysis is helpful to predict transfusion requirements in adult living donor liver transplant recipients. This may allow for better preparation and less cross-matching prior to surgery. The findings of our study need to be re-validated in a second prospective patient population.
Does Physical Activity Improve Quality of Life in Cancer Patients Undergoing Chemotherapy?
Authors: Kripp Melanie , Heußer Anna-Lena , Belle Sebastian , Gerhardt Axel , Merx Kirsten , Hofmann Wolf-Karsten , Hofheinz Ralf-Dieter
Published: June 2015

Background: Improved cancer treatments have resulted in prolonged survival. Nevertheless, tumor symptoms and side effects still compromise physical activity and quality of life (QoL). Patients and Methods: We conducted an anonymous survey among cancer patients undergoing chemotherapy using standardized questionnaires: the ‘Freiburger Fragebogen zur körperlichen Aktivität' (Freiburg Questionnaire on Physical Activity) and European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30. Two main questions were addressed: were there differences (1) in physical activity and QoL between patients who do not believe that sport could improve their QoL and those who believe it could (group A vs. B); and (2) in QoL between patients with a total activity (TA) < 18 metabolic equivalent of task (MET) h/week and those with a TA of ≥ 18 MET h/week (group C vs. D)? Results: 276 of 400 questionnaires were completed. Groups A and B were balanced in terms of baseline characteristics. Group A suffered significantly more from fatigue and pain; group B reported higher levels of global health status (GHS) and TA. Groups C and D differed in gender distribution, age, and educational background. Group D had significantly higher levels of GHS, group C suffered more from fatigue, pain, and appetite loss. Conclusion: Physical activity correlates with a better QoL of cancer patients undergoing chemotherapy.
Relationship between Dementia Severity and Behavioral and Psychological Symptoms of Dementia in Dementia with Lewy Bodies and Alzheimer's Disease Patients
Authors: Hashimoto Mamoru , Yatabe Yusuke , Ishikawa Tomohisa , Fukuhara Ryuji , Kaneda Keiichiro , Honda Kazuki , Yuki Seiji , Ogawa Yusuke , Imamura Toru , Kazui Hiroaki , Kamimura Naoto , Shinagawa Syunichiro , Mizukami Katsuyoshi , Mori Etsuro , Ikeda Manabu
Published: June 2015

Background/Aims: Behavioral and psychological symptoms of dementia (BPSD) are common in the clinical manifestation of dementia. Although most patients with dementia exhibit some BPSD during the course of the illness, the association of BPSD with the stage of dementia remains unclear. It was the aim of this study to evaluate the impact of severity of dementia on the expression of BPSD in patients with dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). Methods: Ninety-seven patients with DLB and 393 patients with AD were recruited from 8 dementia clinics across Japan. BPSD were assessed by the Neuropsychiatric Inventory (NPI). A relationship between BPSD and dementia stage classified by the Clinical Dementia Rating (CDR) in each type of dementia was assessed. Results: No significant difference was seen in NPI total score across CDR staging in the DLB group. On the other hand, the NPI total score significantly increased with dementia stage in the AD group. Conclusion: The relationship of dementia stage with the expression of BPSD was different according to the type of dementia. BPSD and dementia stage were correlated in AD subjects, in whom psychiatric symptoms increase as the disease progresses, but not in DLB subjects.
Eosinophilic Fasciitis Associated with Myositis
Authors: Adachi Yuko , Mizutani Yoko , Shu En , Kanoh Hiroyuki , Miyazaki Tatsuhiko , Seishima Mariko
Published: June 2015

Eosinophilic fasciitis is clinically characterized by symmetrical scleroderma-like indurations of the skin with pain. The histological features are fascial inflammation with lymphocytes and eosinophils as well as thickened and fibrotic fascia. Lymphocytic infiltration and degeneration of the underlying muscle are rarely observed. We report a 69-year-old Japanese woman who presented with multiple areas of glossy induration and painful peau d'orange-like lesions on the chest and four extremities. T2-weighted magnetic resonance imaging showed significant hyperintense thickening of the fascia of the lower extremities. Histopathological examination of a biopsy specimen from the induration showed marked fibrinoid degeneration of the fascia and the neighboring muscle with mixed cellular infiltration of lymphocytes and eosinophils. The predominant CD8+ lymphocytic infiltrates were observed by immunohistological study. A diagnosis of eosinophilic fasciitis with myositis was made. Oral administration of prednisolone and discontinuation of exercise significantly improved the lesions and pain.
Population Growth and Allergen Content of Cultured Euroglyphus maynei House Dust Mites
Authors: Morgan Marjorie S. , Vyszenski-Moher DiAnn L. , Arlian Larry G.
Published: June 2015

Background: The house dust mite, Euroglyphus maynei, occurs in homes worldwide and is an important source of many allergens. Many patients sensitive to Dermatophagoides farinae and D. pteronyssinus are also sensitive to E. maynei. Extracts to detect sensitivity to E. maynei and reagents to detect E. maynei allergens in the environment or in cultures are not readily available. Information for the culture of E. maynei and for the determination of allergen and endotoxin levels in cultures is limited. Method: We mass cultured E. maynei at 23 and 30°C and determined the population growth profiles from inoculation until cultures could be harvested for the production of extracts. We also developed an ELISA to measure Eur m 1 and Eur m 2 allergens using mouse monoclonal antibodies directed at cross-reacting epitopes of group 1 and group 2 allergens of D. farinae and D. pteronyssinus. Results: The E. maynei populations grew exponentially at both 23 and 30°C; however, the cultures matured more rapidly at 23°C. The Eur m 1 and Eur m 2 allergen concentrations in culture extracts changed independently as the cultures grew and matured. At both temperatures, the Eur m 1 concentrations increased as the cultures matured, while the Eur m 2 concentrations did not. The endotoxin levels in these cultures were low. Conclusion: We report here that E. maynei can be cultured at 23 and 30°C. Monoclonal antibodies directed at cross-reacting epitopes on Dermatophagoides allergens can be used to measure the associated E. maynei allergen levels in these cultures.
Risk Factors for Diverticulosis, Diverticulitis, Diverticular Perforation, and Bleeding: A Plea for More Subtle History Taking
Authors: Böhm Stephan K.
Published: June 2015

Background: Diverticulosis is a very common condition. Around 20% of diverticula carriers are believed to suffer from diverticular disease during their lifetime. This makes diverticular disease one of the clinically and economically most significant conditions in gastroenterology. The etiopathogenesis of diverticulosis and diverticular disease is not well understood. Epidemiological studies allowed to define risk factors for the development of diverticulosis and the different disease entities associated with it, in particular diverticulitis, perforation, and diverticular bleeding. Methods: A comprehensive literature search was performed, and the current knowledge about risk factors for diverticulosis and associated conditions reviewed. Results: Non-controllable risk factors like age, sex, and genetics, and controllable risk factors like foods, drinks, and physical activity were identified, as well as comorbidities and drugs which increase or decrease the risk of developing diverticula or of suffering from complications. In naming risk factors, it is of utmost importance to differentiate between diverticulosis and the different disease entities. Conclusion: Risk factors for diverticulosis and diverticular disease may give a clue towards the possible etiopathogenesis of the conditions. More importantly, knowledge of comorbidities and particularly drugs conferring a risk for development of complicated disease is crucial for patient management.
Impact of Neoadjuvant Chemotherapy on Postoperative Morbidity after Gastrectomy for Gastric Cancer
Authors: Téoule Patrick , Trojan Jörg , Bechstein Wolf , Woeste Guido
Published: June 2015

Background/Aims: Patients with locally advanced gastric cancer benefit from neoadjuvant chemotherapy. Potential disadvantages of neoadjuvant chemotherapy include increased surgical complications, leading to increased postoperative morbidity. Methods: We retrospectively studied medical records of 135 patients with resectable cancer of the stomach who underwent gastrectomy between 2002 and 2009. The impact of neoadjuvant chemotherapy on postoperative morbidity was investigated. We compared demographic, clinical and operative data, morbidity and mortality from 105 patients who received surgical treatment immediately after diagnosis (SURG group), versus 30 patients who first received neoadjuvant chemotherapy (CHEMO group). Results: Demographic, clinical and surgical procedure parameters did not differ significantly between both groups. Postoperative morbidity was 46.7% in CHEMO- and 41.9% in SURG-patients (p = 0.680). There were eight cases of death, 2/30 (6.7%) in CHEMO and 6/105 (5.7%) in the SURG group (p = 1). The overall complications according to Clavien-classification did not differ significantly (p = 0.455). The wound infection rate (23.3 vs. 3.8%; p = 0.002) and insufficiency of the duodenal stump (13.3 vs. 1.9%; p = 0.022) were significantly higher in the CHEMO group. Conclusion: This study showed no significant impact of neoadjuvant chemotherapy on postoperative morbidity after gastrectomy using the Clavien-classification. Only an increase in wound infections in CHEMO compared with the SURG group were noted. Therefore, neoadjuvant chemotherapy can be considered safe and feasible.
Intestinal Surgery for Crohn's Disease: Role of Preoperative Therapy in Postoperative Outcome
Authors: Scarpa Marco , Martinato Matteo , Bertin Eugenia , Da Roit Anna , Pozza Anna , Ruffolo Cesare , D''Incà Renata , Bardini Romeo , Castoro Carlo , Sturniolo Giacomo C. , Angriman Imerio
Published: June 2015

Purposes: Patients affected by Crohn's disease (CD) require lifelong medical therapy, but they can also often require abdominal surgery. The effect of CD therapy on postoperative course is still unclear. The aim of this study was to evaluate the effect of preoperative medical therapy on the outcome of intestinal surgery in these patients. Methods: Data from a consecutive series of 167 patients with CD operated on at the University of Padova Hospital from 2000 to 2013 were retrieved. Data of preoperative therapy during the 6 months before surgery were available for 146 patients who were enrolled in this retrospective study. Clinical data and surgical details were retrieved and postoperative complications and reoperation were considered outcome measures. Univariate and multivariate analysis were performed. Results: No significant difference was observed between patients without data about their preoperative therapy and those with them. Eight patients underwent reoperation in the first 30 postoperative days: two of them for anastomotic leak, three for bleeding, one for obstruction and two for abdominal wound dehiscence. At multivariate analysis, preoperative adalimumab and budesonide resulted to be an independent predictor of reoperation (OR = 7.67 (95% CI = 1.49-39.20), p = 0.01 and OR = 6.7749 (95% CI = 0.98-46.48), p = 0.05, respectively). At multivariate analysis neither pharmacological nor clinical variables resulted to predict anastomotic leak. Conclusions: In our series, adalimumab seemed to be associated to early reoperation after intestinal surgery. This may be due to a worst disease severity in patients who needed surgery in spite of biological therapy. Preoperative tapering of budesonide dose seems a safe option before elective abdominal surgery for CD.
Aerobic and Anaerobic Bacteriology of Hidradenitis Suppurativa: A Study of 22 Cases
Authors: Katoulis Alexandros C. , Koumaki Dimitra , Liakou Aikaterini I. , Vrioni Georgia , Koumaki Vasiliki , Kontogiorgi Dimitra , Tzima Korina , Tsakris Athanasios , Rigopoulos Dimitris
Published: June 2015

Introduction: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease of unclear etiology. The role of bacteria in the pathogenesis of disease remains controversial. Materials and Methods: Specimens were obtained from 22 HS patients by direct percutaneous needle aspiration. The collected material was cultured in aerobic and anaerobic conditions, and sensitivity tests were performed. Results: Of the 22 patients, 32% were culture negative and 68% were culture positive. A total of 16 isolates was obtained, 14 aerobic and 2 anaerobic. Aerobic bacteria were present in 86% of the specimens, whereas only anaerobic bacteria were isolated in 7%. The predominant aerobic species were Proteus mirabilis, Staphylococcus haemolyticus and Staphylococcus lugdunensis. The isolated anaerobic bacteria were Dermacoccus nishinomiyaensis and Propionibacteriumgranulosum. Conclusion: A variety of aerobic and anaerobic bacteria was isolated from the HS lesions of our patients. In contrast to previous studies, fewer patients were found to be culture positive, and Staphylococcus aureus was isolated in only 1 of them. More studies are necessary to elucidate the controversial role of bacteria in the pathogenesis of HS.
Podocyte Structural Parameters Do Not Predict Progression to Diabetic Nephropathy in Normoalbuminuric Type 1 Diabetic Patients
Authors: Harindhanavudhi Tasma , Parks Alicia , Mauer Michael , Caramori M. Luiza
Published: June 2015

Background: Podocyte injury has been implicated in diabetic nephropathy (DN) ranging from normoalbuminuria to proteinuria in both type 1 and type 2 diabetes. Methods: To determine whether podocyte structural parameters predict DN risk in initially normoalbuminuric long-standing type 1 diabetic patients, we performed a nested case-control study in sex and diabetes duration-matched progressors (progression to proteinuria or ESRD, n = 10), non-progressors (normoalbuminuric at follow-up, n = 10), and non-diabetic controls (n = 10). Results: HbA1c and diastolic blood pressure were higher in progressors versus non-progressors. Podocyte number per glomerulus, numerical density of podocyte per glomerulus, and foot process width were not different among groups. The glomerular basement membrane width was greater in progressors versus non-progressors or controls, and in non-progressors versus controls. As expected, the mesangial fractional volume was greater in progressors and non-progressors versus controls, with no differences between progressors and non-progressors. Conclusion: This study does not indicate that podocyte structural changes are preconditions for later DN progression in initially normoalbuminuric type 1 diabetic patients. However, this does not preclude an important role for podocyte injury at a later stage of DN.
Multiple Sclerosis Relapses: Epidemiology, Outcomes and Management. A Systematic Review
Authors: Kalincik Tomas
Published: June 2015

Relapses (episodic exacerbations of neurological signs or symptoms) are a defining feature of relapsing-remitting multiple sclerosis (MS), the most prevalent MS phenotype. While their diagnostic value relates predominantly to the definition of clinically definite MS, their prognostic value is determined by their relatively high associated risk of incomplete remission resulting in residual disability. The mechanisms governing a relapse incidence are unknown, but numerous modifiers of relapse risk have been described, including demographic and clinical characteristics, many of which represent opportunities for improved disease management. Also relapse phenotypes have been associated with patient and disease characteristics and an individual predisposition to certain phenotypic presentations may imply individual neuroanatomical disease patterns. While immunomodulatory therapies and corticosteroids represent the mainstay of relapse prevention and acute management, respectively, their effect has only been partial and further search for more efficient relapse therapies is warranted. Other areas of research include pathophysiology and determinants of relapse incidence, recurrence and phenotypes, including the characteristics of the relapsing and non-relapsing multiple sclerosis variants and their responsiveness to therapies.
Characteristic miR-24 Expression in Gastric Cancers among Atomic Bomb Survivors
Authors: Naito Yutaka , Oue Naohide , Pham Trang T.B. , Yamamoto Manabu , Fujihara Megumu , Ishida Teruyoshi , Mukai Shoichiro , Sentani Kazuhiro , Sakamoto Naoya , Hida Eisuke , Sasaki Hiroki , Yasui Wataru
Published: June 2015

Objective: To elucidate the mechanism of radiation-induced cancers, we analyzed the expression profiles of microRNAs extracted from formalin-fixed paraffin-embedded (FFPE) gastric cancer (GC) tissue samples from atomic bomb survivors. Methods: The expression levels of miR-21, miR-24, miR-34a, miR-106a, miR-143, and miR-145 were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Results: The expression of microRNAs was measured by qRT-PCR in a Hiroshima University Hospital cohort comprising 32 patients in the high-dose-exposed group and 18 patients in the low-dose-exposed group who developed GC after the bombing. The GC cases showing high expression of miR-24, miR-143, and miR-145 were more frequently found in the high-dose-exposed group than in the low-dose-exposed group. We next performed qRT-PCR of miR-24, miR-143, and miR-145 in a cohort from the Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital comprising 122 patients in the high-dose-exposed group and 48 patients in the low-dose-exposed group who developed GC after the bombing. High expressions of miR-24 and miR-143 were more frequently found in the high-dose-exposed group than in the low-dose-exposed group. Multivariate analysis demonstrated that only high expression of miR-24 was an independent predictor for the exposure status. Conclusion: These results suggest that the measurement of miR-24 expression from FFPE samples is useful to identify radiation-associated GC.
Development of the Cognitive Test for Severe Dementia
Authors: Tanaka Hiroyuki , Nagata Yuma , Uematsu Masayasu , Takebayashi Takashi , Hanada Keisuke , Inokawa Maki , Fukuhara Keita , Ogawa Yasuhiro , Haga Daisuke , Kakegawa Yasuro , Nishikawa Takashi
Published: June 2015

Background/Aims: Existing cognitive measures for moderate-to-severe dementia have shown floor effects and an inability to assess the remaining cognitive function, especially for profound dementia. Methods: We constructed the Cognitive Test for Severe Dementia (CTSD), which consists of 13 items covering 7 cognitive domains, and examined its reliability and validity. Results: Cronbach's α in severe dementia participants was 0.896. Interrater and test-retest reliability were 0.961 and 0.969, respectively. The CTSD showed a significant correlation with 3 other measures of cognitive function (Mini-Mental State Examination, Severe Cognitive Impairment Rating Scale, and Hasegawa Dementia Scale-Revised: r values = 0.870-0.922, p values <0.001). While the other measures showed floor effects, the CTSD did not. Conclusion: The CTSD was able to sensitively capture the remaining cognitive function in severe dementia patients when compared with other cognitive tests.
Protomyofibroblast Pathway in Early Thermal Burn Healing
Authors: Hermanns-Lê Trinh , Piérard Gérald E. , Jennes Serge , Piérard-Franchimont Claudine
Published: June 2015

Wound healing following partial thickness thermal burns is commonly hampered by the risk of hypertrophic scarring. Skin myofibroblast (MF) density is commonly increased in postburn healing. The transition between fibroblast-like cells and α-smooth muscle actin (SMA)+ MF possibly begins with CD14+ monocytes, evolving to CD14+ CD34+ fibrocytes, followed by β-SMA+ protomyofibroblast (PMF) maturation. Skin biopsies from 25 burn patients were collected about 1 and 4 weeks after injury. Immunohistochemistry was performed using monoclonal antibodies to α-SMA, β-SMA, factor XIIIa, lysozyme, Mac 387, CD14, CD117 and Ulex europaeus agglutinin-1 (UEA-1). The set of Mac 387+ and CD14+ monocytes was accompanied by both CD34+ fibrocytes and factor XIIIa+ dendrocytes. By contrast, β-SMA+ PMF were rare. Of note, α-SMA+ MF were more abundant at week 4 than at week 1 (p < 0.01). The UEA-1+ endothelial cells showed marked variations in their dermal distribution, irrespective of the densities in the other scrutinized cells. In conclusion, healing of partial thickness thermal burns involves a diversity of cell types including PMF. In the present samples, the PMF density remained low.
Nesfatin-1 Suppresses Cardiac L-type Ca2+ Channels Through Melanocortin Type 4 Receptor and the Novel Protein Kinase C Theta Isoform Pathway
Authors: Ying Jiaoqian , Zhang Yuan , Gong Shan , Chang Zhigang , Zhou Xiaofeng , Li Hua , Tao Jin , Zhang Guoqiang
Published: June 2015

Background/Aims: Nesfatin-1 (NF-1), an anorexic nucleobindin-2 (NUCB2)-derived hypothalamic peptide, acts as a peripheral cardiac modulator and it can induce negative inotropic effects. However, the mechanisms underlying these effects in cardiomyocytes remain unclear. Methods: Using patch clamp, protein kinase assays, and western blot analysis, we studied the effect of NF-1 on L-type Ca2+ currents (ICa,L) and to explore the regulatory mechanisms of this effect in adult ventricular myocytes. Results: NF-1 reversibly decreased ICa,L in a dose-dependent manner. This effect was mediated by melanocortin 4 receptor (MC4-R) and was associated with a hyperpolarizing shift in the voltage-dependence of inactivation. Dialysis of cells with GDP-β-S or anti-Gβ antibody as well as pertussis toxin pretreatment abolished the inhibitory effects of NF-1 on ICa,L. Protein kinase C (PKC) antagonists abolished NF-1-induced responses, whereas inhibition of PKA activity or intracellular application of the fast Ca2+-chelator BAPTA elicited no such effects. Application of NF-1 increased membrane abundance of PKC theta isoform (PKCθ), and PKCθ inhibition abolished the decrease in ICa,L induced by NF-1. Conclusion: These data suggest that NF-1 suppresses L-type Ca2+ channels via the MC4-R that couples sequentially to the βγ subunits of Gi/o-protein and the novel PKCθ isoform in adult ventricular myocytes.
A Case Report of Listeria monocytogenes Abscesses Presenting as Cortically Predominant Ring-Enhancing Lesions
Authors: De Jesus-Alvelo Indira , Merenda Amedeo
Published: June 2015

Introduction:Listeria monocytogenes, a common cause of bacterial meningitis, rarely involves the central nervous system (CNS) in the form of multiple cerebral ring-enhancing lesions. Methods: An 81-year-old woman with rapidly progressive decline in her mental status in the setting of multiple cortically predominant ring-enhancing lesions was transferred to our institution. A mild upper respiratory tract infection and diarrhea symptoms preceded the mental status deterioration. Her past medical history is significant for type 2 diabetes mellitus. In light of the patient's age, the presence of hyponatremia and the history of diabetes mellitus, the empiric antimicrobial treatment was modified to include ampicillin, meropenem, vancomycin, voriconazole and pyrimethamine/sulfadiazine to prevent opportunistic infections. Intravenous dexamethasone was added due to significant perilesional vasogenic edema. Results: The patient presented with stupor, but neither fever nor leukocytosis. CSF results were significant only for a mildly elevated protein level. The report of a repeat brain MRI was as follows: large areas of high FLAIR signals and tubular/lobulated/ring enhacement in bifrontal regions with a smaller focus in the left anterior midbrain, indicating for underlying multicentric glioma or multicentric primary CNS lymphoma. A brain biopsy, however, revealed an early abscess formation caused by a L. monocytogenes infection. Conclusion: A high index of suspicion in patients with risk factors for this infection is key to ensure the timely initiation of appropriate empirical antibiotic therapy in the setting of cerebral ring-enhancing lesions. Intravenous ampicillin is the treatment of choice, but meropenem represents a valid alternative.
An Observational Study of the Diagnosis and Management of Chronic Urticaria in the UK
Authors: Wu Cheng-Han , Ardern-Jones Michael Roger , Eren Efrem , Venter Carina
Published: June 2015

Background: Patients with chronic urticaria (CU) in the UK could be referred to health care professionals (HCPs) with diverse specialties using different guidelines. The aims of the present study were to determine which CU guidelines HCPs in the UK use, which tests they use for the diagnosis of CU, and how they manage CU. Methods: In this UK-wide survey, we designed a questionnaire covering the diagnosis and management of CU based on current guidelines. The link to the questionnaire was sent to the British Society for Allergy and Clinical Immunology (BSACI), the British Association of Dermatologists (BAD), the British Society of Immunology (BSI), and the Food Allergy and Intolerance Specialist Group (FAISG) of the British Dietetic Association (BDA), who distributed the link to their members. Results: The questionnaire was completed by 55 allergists/immunologists, 64 dermatologists, and 43 dietitians. More dermatologists used the BAD guidelines in comparison with allergists and immunologists (93.6 vs. 12.5%; p < 0.001). On the other hand, the BSACI guidelines (83.3 vs. 14.9%; p < 0.001) and the European Academy of Allergy and Clinical Immunology (EAACI)/Global Allergy and Asthma European Network (GA2LEN)/European Dermatology Forum (EDF)/World Allergy Organization (WAO) guidelines (2013) (52.1 vs. 10.6%; p < 0.001) were used by more allergists and immunologists compared to dermatologists. Differences were found between allergists/immunologists and dermatologists with regard to guidelines used, investigations performed, preference of first-line antihistamine, and prescription of alternative treatment methods. Conclusion: In conclusion, differences in the diagnosis and management of CU between HCPs of diverse specialties were identified, which reflected differences among the guidelines used.
Interpreting CD56+ and CD163+ Infiltrates in Early versus Late Renal Transplant Biopsies
Authors: Shin Sung , Kim Young Hoon , Cho Yong Mee , Park Yangsoon , Han Seungbong , Choi Byung Hyun , Choi Ji Yoon , Han Duck Jong
Published: June 2015

Background: CD56+ and CD163+ cell infiltration in human kidney transplant biopsies have not been fully evaluated. Methods: We investigated the association of CD56+ and CD163+ cell infiltration with human kidney transplant biopsies with antibody- or T-cell-mediated rejection (TCMR) and other histologic lesions. One hundred and seventy four clinically indicated transplant biopsies were included in this analysis. Immunohistochemical staining for C4d, CD56 and CD163 was performed. Results: One hundred and seventy four indication biopsies were divided into early (≤1 year posttransplant; n = 49) and late (>1 year posttransplant; n = 125) biopsies. High numbers of CD56+ cells were uncommon in early biopsies except for those with antibody-mediated rejection (AMR) only. On the other hand, high numbers of CD56+ cells were observed in late biopsies diagnosed as TCMR only, AMR only, and TCMR combined with AMR. In early biopsies, both CD56+ and CD163+ infiltrates correlated strongly with interstitial inflammation, tubulitis, and peritubular capillaritis (ptc) scores. The ci and ct scores, however, were correlated only with the number of CD56+ cells. In late biopsies, on the other hand, the number of CD56+ infiltrates was correlated only with ptc, while the number of CD163+ infiltrates was weakly correlated with any histologic lesion. Multivariable analyses showed that chronic active AMR and the number of CD56+ cells/10 HPF were independently associated with death-censored graft failure post-biopsy. The number of CD163+ cells was not correlated with any pathologic lesion and post-biopsy graft failure. CD56+ infiltrates were also associated with interstitial fibrosis and tubular atrophy. Conclusions: Intragraft CD56+ cell infiltrates were significantly associated with AMR and subsequent poor clinical outcomes.
White Rice Intake Varies in Its Association with Metabolic Markers of Diabetes and Dyslipidemia Across Region among Chinese Adults
Authors: Dong Fei , Howard Annie-Green , Herring Amy H. , Popkin Barry M. , Gordon-Larsen Penny
Published: June 2015

Background/Aims: There are inconsistent associations between white rice consumption and diabetes and dyslipidemia, perhaps due to the nature of samples studied and quality of diet data. Methods: Using regionally diverse data from adults enrolled in the China Health and Nutrition Survey (n = 7,878) with diet data from three repeated 24-hour recalls and fasting blood to derive diabetes and dyslipidemia, we examined the odds of diabetes and dyslipidemia in participants across region-specific tertiles of percent energy from white rice consumption. Results: The prevalence of undiagnosed diabetes, high triglycerides, high low-density lipoprotein (LDL), low high-density lipoprotein (HDL), and atherogenic dyslipidemia (AD) was 4.7%, 31.8%, 31.3%, 25.9%, and 14.6%, respectively. We found an inverse association between the highest (versus lowest) tertile of rice intake and diabetes in Central China (odds ratio (OR): 0.59, 95% confidence interval (CI): 0.36-0.99). The highest rice consumption was also associated with high triglycerides (OR: 1.46, 95% CI: 1.09-1.95), low HDL (OR: 1.38, 95% CI: 1.03-1.85), and AD (OR: 1.63, 95% CI: 1.15-2.31) in North China, and low LDL (OR: 0.54, 95% CI: 0.42-0.69) in Central China. Conclusions: The association between white rice consumption and diabetes and dyslipidemia markers varied across regions of China, suggesting a role of other dietary and health-related exposures, beyond rice.
Olanzapine Reversed Brain Gene Expression Changes Induced by Phencyclidine Treatment in Non-Human Primates
Authors: Martin Maureen V. , Mirnics Karoly , Nisenbaum Laura K. , Vawter Marquis P.
Published: June 2015

The NMDA receptor antagonist phencyclidine (PCP) creates schizophrenia-like symptoms in normal controls. The effect of PCP on non-human primate brain gene expression was examined and compared to changes induced by olanzapine treatment. Experimental studies of PCP and antipsychotic drugs have direct relevance to understanding the pathophysiology and treatment of schizophrenia. Genome-wide changes in prefrontal cortex gene expression revealed alterations of 146 transcripts in the PCP treatment group compared to vehicle controls. Dysregulated genes were enriched in identified classes implicated in neurological and genetic disorders, including schizophrenia genes from the Psychiatric Genomics Consortium 108 loci as well as cell death in PCP-treated primates. Canonical pathway analysis revealed a significant overrepresentation of several groups including synaptic long-term potentiation and calcium signaling. Olanzapine coadministered with PCP normalized 34% of the 146 PCP-induced probe set expression changes, and a network of 17 olanzapine-normalized genes was identified enriched in schizophrenia candidate genes containing RGS4, SYN1 and AKT as nodes. The results of this study support the use of PCP administration in non-human primates as a glutamatergic model of schizophrenia and suggest that a large number of PCP-induced expression differences can be reversed by olanzapine. The results of this study may be informative for identification of potential candidates for pharmacogenetics and biomarker research related to the treatment of schizophrenia.
Synergistic Interaction of Retigabine with Levetiracetam in the Mouse Maximal Electroshock-Induced Seizure Model: A Type II Isobolographic Analysis
Authors: Luszczki Jarogniew J. , Zagaja Mirosław , Miziak Barbara , Florek-Luszczki Magdalena , Czuczwar Stanislaw J.
Published: June 2015

Background/Aims: To assess interactions between retigabine and levetiracetam in suppressing maximal electroshock-induced tonic seizures in Albino Swiss mice, type II isobolographic analysis was used. Total brain antiepileptic drug concentrations were measured with high pressure liquid chromatography. Results: The combinations of retigabine with levetiracetam at the fixed-ratios of 1:5 and 1:10 were supra-additive (synergistic; p < 0.05) in terms of seizure suppression, while the combinations at the fixed-ratios of 1:1 and 1:2 were additive. No pharmacokinetic changes in total brain concentrations of levetiracetam and retigabine were documented, indicating the pharmacodynamic nature of interaction between these antiepileptic drugs in the mouse maximal electroshock-induced tonic seizure model. Conclusion: The combination of retigabine with levetiracetam at the fixed-ratios of 1:5 and 1:10 appears to be particularly beneficial combination exerting supra-additive interaction in suppressing maximal electroshock-induced tonic seizures.
The Risk of Ovarian Malignancy Algorithm (ROMA) as a Predictive Marker of Peritoneal Dissemination in Epithelial Ovarian Cancer Patients
Authors: Ikeda Yuji , Hasegawa Kosei , Kurosaki Akira , Miyara Akiko , Hanaoka Tatsuya , Shintani Daisuke , Imai Yuichi , Nishikawa Tadaaki , Oda Katsutoshi , Fujiwara Keiichi
Published: June 2015

Background: This study aimed to determine the efficacy of the risk of ovarian malignancy algorithm (ROMA), calculated using the carbohydrate antigen 125 (CA125) and human epididymis protein 4 (HE4) levels and the menopausal status, as a predictor of peritoneal dissemination in ovarian cancer. Methods: The CA125 and HE4 levels and the ROMA were compared between ovarian cancer patients (n = 122) with or without peritoneal dissemination. The sensitivity, specificity, positive predictive value, and negative predictive value were calculated, and the results were compared with those of computed tomography (CT). Results: The CA125, HE4, and ROMA values differed significantly depending on the presence of peritoneal dissemination (p < 0.0001). The cut-off values were 181 U/ml for CA125, 161 pmol/ml for HE4, 44% for the ROMA (premenopausal), and 86% for the ROMA (postmenopausal). Among these markers, the ROMA (premenopausal) was the strongest predictor of peritoneal dissemination, with a specificity of 85.0% and a positive predictive value of 81.3%. In addition, the detection rates of small disseminations with less than 2 cm in diameter for the ROMA (93%) and HE4 (60%) were superior to that of CT (53%). Conclusions: The ROMA was a significant predictor of peritoneal dissemination and may be superior to CT for the detection of patients with small disseminations.
Multiple-Dose Study to Evaluate Pharmacokinetics, Pharmacodynamics, and Safety in Healthy Subjects: A Comparison of Controlled-Release Sarpogrelate and Immediate-Release Sarpogrelate
Authors: Lee Soo-Yun , Kim Jung-Ryul , Jung Jin Ah , Kim Tae-Eun , Lee Soo-Youn , Huh Wooseong , Lee Jae-Won , Jun Hun , Ko Jae-Wook
Published: June 2015

Aims: To compare the pharmacokinetics, pharmacodynamics, and safety of sarpogrelate between controlled-release (CR) and immediate-release (IR) formulations after multiple-dose administration. Methods: This study was a randomized, open-label, 2-period, 2-treatment, crossover study in healthy subjects. All subjects received CR sarpogrelate 300 mg once daily and IR sarpogrelate 100 mg three times daily by random order each for 3 days with a 7-day washout period. Serial blood sampling was performed over 24 h. Pharmacokinetic parameters were determined by noncompartmental methods. Platelet aggregation to collagen, measured by light transmission aggregometry, was reported as maximal platelet aggregation. Results: Thirty-two subjects completed the study. CR sarpogrelate increased rapidly, reaching Cmax in 1.25 h (vs. 1.00 h in IR sarpogrelate) and declined with a t1/2 of 3.59 h (vs. 1.12 h in IR sarpogrelate). The 90% CIs for the geometric mean ratio of AUCτ and Cmax,ss between IR and CR formulations were 1.18 to 1.40 and 0.99 to 1.29, respectively. The degree of inhibition of platelet aggregation was similar between two formulations. Conclusions: CR sarpogrelate showed slightly higher systemic exposure and similar peak concentration compared with IR sarpogrelate. The profiles of pharmacodynamics and safety were comparable between two formulations.
Renal Function and Long-Term Decline in Cognitive Function: The Baltimore Longitudinal Study of Aging
Authors: Seliger Stephen L. , Wendell Carrington R. , Waldstein Shari R. , Ferrucci Luigi , Zonderman Alan B.
Published: June 2015

Background: Renal disease has been associated with greater risk of dementia and greater cognitive impairment. However, the relationship of lower renal function with long-term decline in specific domains of cognitive function remains unclear among community-dwelling, non-demented individuals. Methods: Stroke- and dementia-free participants (n = 2,116) were enrolled in the Baltimore Longitudinal Study of Aging, a community-based, prospective, longitudinal study. Renal function was estimated by the inverse of serum creatinine adjusted for age, sex and race and (in sensitivity analyses) estimated glomerular filtration rate (eGFR) using the MDRD formula. Outcome measures were changes in scores on 6 cognitive tests encompassing a range of cognitive functions, measured at 2-year intervals. Mixed-effects regression models examined the longitudinal relations of renal function with cognitive functions after adjusting for demographics, comorbidity and other potential confounders. Results: Mean age at initial testing was 53.9 years (SD 17.1), and 94 participants (4.4%) had an eGFR <60 ml/min/1.73 m2 and 18.5% had at least one comorbidity. With increasing age, longitudinal increases in creatinine concentrations were associated with more rapid decline in performance on several cognitive measures, including the learning slope of the California Verbal Learning Test, a test of verbal learning (p < 0.01), and the Benton Visual Retention Test, a test of visual memory (p < 0.01). Associations were similar for changes in eGFRMDRD, which was also associated with the rate of decline in verbal memory. Conclusion: In a community-based adult population, declines in renal function independently associated with greater long-term declines in visual memory and verbal memory and learning.
Expression of Methylthioadenosine Phosphorylase (MTAP) in Pilocytic Astrocytomas
Authors: Becker Aline Paixão , Scapulatempo-Neto Cristovam , Menezes Weder P. , Clara Carlos , Machado Hélio R. , Oliveira Ricardo S. , Neder Luciano , Reis Rui Manuel
Published: June 2015

Background/Objectives: Pilocytic astrocytomas (PAs) are the most frequent astrocytomas in children and adolescents. Methilthioadenosine phosphorylase(MTAP) is a tumor-suppressor gene, the loss of expression of which is associated with a poor prognosis and better response to specific chemotherapy in leukemia and non-small-cell lung cancer. The expression of MTAP in brain tumors remains largely unknown and its biological role in PA is still unexplored. Our aims were to describe the immunohistochemical MTAP expression in a series of PAs and relate it to the clinicopathological features of the patients. Methods: We assessed MTAP expression on immunohistochemistry in 69 pediatric and adult patients with PA in a tissue microarray platform. Results: Retained expression of MTAP was seen in >85% of the tumors compared to in the nonneoplastic adjacent tissue. Only 3 supratentorial tumors showed a complete loss of MTAP expression. No significant association with clinicopathological features or overall survival of the patients was found. Conclusions: MTAP expression is retained in PAs and is not an outcome predictor for these tumors. Nevertheless, a subset of patients with PAs exhibiting a loss of MTAP could potentially benefit from treatment with specific chemotherapy, especially when lesions are recurrent or surgical resection is not recommended.