bluuebunny/crossref_metadata_2025 huggingface dataset:
Interruption of CD40 Pathway Improves Efficacy of Transplanted Endothelial Progenitor Cells in Monocrotaline Induced Pulmonary Arterial Hypertension
Authors: Pan YanYun , Wang Shuai , Yang JinXiu , Chen Bin , Sun ZeWei , Ye LiFang , Zhu JianHua , Wang XingXiang
Published: June 2015

Background/Aims: Transplantation of endothelial progenitor cells (EPCs) plays a therapeutic role in pulmonary arterial hypertension (PAH). Meanwhile, recruitment of progenitors has potential inflammatory effects and exaggerates vascular injury. CD40 pathway is identified as a major player in vascular inflammatory events. In this study, we investigated the role of CD40 pathway in regulating early outgrowth EPC functions, and searched for improvements in PAH cell therapy. Methods: EPCs were isolated from rat bone marrow and cultured for 7 days. After treatment with soluble CD40 ligand (sCD40L) for 24 hours, EPC migration, adhesion, proliferation, paracrine and vasculogenesis functions were tested. Rat PAH model was founded by subcutaneous injection of monocrotaline (MCT). Control EPCs or lentivirus vectors (Lv)-shRNA-CD40 EPCs were infused via tail vein at day 7, 14, and 21 after MCT injection. Therapeutic effects were evaluated at day 28. Results: sCD40L dose-dependently impaired EPC migration, adhesion, proliferation, and vasculogenesis functions. However, paracrine effects of soluble intercellular adhesion molecule-1, vascular endothelial growth factor and interleukin-6 were dose-dependently improved by sCD40L. Control EPC-derived conditioned medium protected endothelial cell in vitro vasculogenesis, while sCD40L-pretreated ones showed detrimental effects. After MCT injection, sCD40L levels in rat serum increased gradually. Other than in vitro results, benefits of both two EPC treatments were obvious, even taken at day 21. Benefits of control EPCs wore off over time, but those of Lv-shRNA-CD40 EPCs were more effective and enduring, as characterized by both ameliorated rat hemodynamic and reversed vascular remodeling. Furthermore, Lv-shRNA-CD40 EPCs integrated into endothelium better, rather than into adventitia and media. Conclusion: sCD40L impaired protective effects of EPCs. Traditional EPC treatments were limited in PAH, while interruption of CD40 pathway of transplanted cells could apparently improve the therapeutic efficacy.
Lipocalin 2 Upregulation Protects Hepatocytes from IL1-β-Induced Stress
Authors: Hu Ying , Xue Jihua , Yang Ying , Zhou Xiaotang , Qin Chaochao , Zheng Min , Zhu Haihong , Liu Yanning , Liu Weixia , Lou Guohua , Wang Jing , Wu Shanshan , Chen Zhi , Chen Feng
Published: June 2015

Background: Lipocalin 2 (LCN2), a protein primarily produced by hepatocytes, is highly upregulated under various conditions that induce cellular stress, such as intoxication, infection or inflammation. However, the precise biological functions and underlying mechanisms of LCN2 in hepatocytes remains unknown. Methods: Hepatocyte stress was successfully induced by treating Huh7 cells with interleukin-1β (IL-1β). Interleukin-6 (IL-6), Tumor Necrosis Factor-α (TNF-α) and LCN2 levels were measured in IL-1β treated Huh7 cells and supernatant. Additionally, microarray analysis was conducted to identify genes differentially expressed in LCN2-silenced and control Huh7 cells. Results: TNF-α, IL-6 and LCN2 were significantly elevated in Huh7 cells after IL-1β) treatment. In LCN2-silenced Huh7 cells, expression of IL-6 and TNF-α was significantly increased when compared with the expression levels of control Huh7 cells. Furthermore, differentially expressed genes were observed between the LCN2-silenced and control cells. Microarray analysis indicated that LCN2 acted by influencing genes involved in protein metabolism, stress response, cell cycle and proliferation. Conclusions: Our results suggest that LCN2 upregulation protects hepatocytes from IL-1β-induced stress. Additionally, our microarray analysis of LCN2-silenced and control cells provides a better understanding of the mechanisms that may be influenced by LCN2 induction.
The Functional Variant in the 3'UTR of IGF1 with the Risk of Gastric Cancer in a Chinese Population
Authors: Jiang Haiqiang , Wang Huiyun , Ge Fengyuan , Wu Lamei , Wang Xiao , Chen Shengxia
Published: June 2015

Background/Aims: IGF-1 can act as an endocrine hormone and its signaling server as essential roles in regulating tumorigenesis. Polymorphisms in IGF-1 have been reported associated bad prognosis of with human cancer, but their association with the risk of human gastric cancer (GC) has not been found so far. In this study rs6218 located in the 3'UTR of IGF-1 was selected to evaluate its relationship with the risk of GC among Chinese population. Methods: Questionnaire, SNaPshot genotype assay, real time PCR assay, cell transfection and the dual luciferase reporter assay were used in our study. Results: SNP rs6218 in IGF-1 3'-UTR was involved in the occurrence of GC by acting as a tumor promotion factor while rs6128 acting as a risk factor. SNP rs6128 was also could be regulated by miR-603 which caused an up-regulation of IGF-1 in patients with UC and CC genotype. Furthermore, the carriers of UC and CC genotype presented a big tumor size as well as the high probability of metastasis. Conclusion: In conclusion, our findings have shown that the SNP rs6218 in IGF-1 3'-UTR, through disrupting the regulatory role of miR-603 in IGF-1 expression, rs16128 in IGF-1 might act as a promotion factor in the pathogenesis of GC.
The Addition of Inhaled Budesonide to Standard Therapy Shortens the Length of Stay in Hospital for Asthmatic Preschool Children: A Randomized, Double-Blind, Placebo-Controlled Trial
Authors: Razi Cem Hasan , Akelma Ahmet Zulfikar , Harmanci Koray , Kocak Mesut , Kuras Can Yasemin
Published: June 2015

Background: Asthma exacerbations lead to frequent emergency visits and hospitalizations, and are associated with high morbidity and occasionally mortality. New therapeutic strategies are needed. We sought to investigate whether the addition of high-dose inhaled budesonide to standard therapy would shorten the length of stay (LOS) in hospital of children admitted for asthma exacerbations. Methods: The study was designed as a single-center, double-blind, placebo-controlled and parallel-group trial. Children aged 7-72 months and admitted with an asthma exacerbation clinical asthma score (CAS) of between 3 and 9 were allocated to either the budesonide (n = 50) or the placebo (n = 50) group. Hospital LOS was compared between children who received 2 mg/day of budesonide versus placebo in addition to standard management of asthma exacerbation involving oxygen inhalation and β2-agonist, anticholinergic and oral corticosteroid therapy. All patients were assessed every 4 h. Children with a CAS <3, a peripheral oxygen saturation >95% and normal pulmonary function, and those with a symptom-free period of at least 4 h after salbutamol treatment were discharged. Results: Total hospital LOS was significantly shorter in the budesonide group than in the placebo group (median: 44 vs. 80 h, respectively; p = 0.01). When compared with placebo, the number of inpatients was significantly less in the budesonide group at all the assessed end points (Kaplan-Meier; p = 0.022). Additionally, nebulized budesonide was found to reduce the overall cost of treatment. Conclusion: We demonstrated that, for children hospitalized for asthma exacerbations, an additional 2 mg/day of nebulized budesonide significantly reduced hospital LOS as well as the overall cost of treatment.
Doubtful Role of IL28B Polymorphism in Occult Hepatitis B Infection
Authors: Bes Marta , Vargas Victor , Piron Maria , Casamitjana Natalia , Esteban Juan Ignacio , Campos-Varela Isabel , Puig Lluís , Sauleda Silvia
Published: June 2015

Aims: To investigate the influence of IL28B polymorphism in occult hepatitis B infection (OBI) and whether IL28B genetic variants are associated with hepatitis B virus (HBV)-specific T-cell responses. Patients and Methods: The rs12979860 IL28B genotype was determined in 34 OBI blood donors, 22 spontaneous HBV resolvers, 36 inactive HBV carriers and 25 seronegative donors. T-cell responses to HBV recombinant proteins were assessed by interferon-γ enzyme-linked immunospot assay. Results: The frequency of the IL28B CC genotype among OBI patients was similar to that of inactive carriers [41 vs. 39%, respectively, p = 0.961; odds ratio (OR) = 1.10; 95% confidence interval (CI) = 0.42-2.86; p = 0.845]. The IL28B CC genotype was found more frequently in spontaneous resolvers, although the differences were not significant (45 vs. 39%, spontaneous resolvers and inactive carriers, respectively; p = 0.828; OR = 1.31; 95% CI = 0.45-3.83; p = 0.622). HBV-specific T-cell responses were detected in OBIs, and significantly stronger T-cell responses towards hepatitis B envelope antigen were observed in those with the IL28B CC genotype. In spontaneous resolvers and inactive carriers, IL28B CC did not correlate with the magnitude of T-cell responses. Conclusions: In OBI donors, IL28B CC correlates with the intensity of HBV-specific T-cell responses. In this study, IL28B CC is not statistically associated with OBI or with HBV clearance, but a larger number of cases is needed before completely ruling out its role in HBV infection.
Systemic Cyclosporine Therapy for Scleritis: A Proposal of a Novel System to Assess the Activity of Scleritis
Authors: Aoki Haruka , Hiraoka Miki , Hashimoto Masato , Ohguro Hiroshi
Published: June 2015

In the present study, two female patients with unilateral scleritis without systemic complications were examined. Both patients were suffering from ocular pain and received corticosteroid therapy. The first patient, a 45-year-old woman, was diagnosed with scleritis and iritis in her right eye. Topical corticosteroid treatment could eradicate the iritis but not the scleritis. Oral corticosteroid administration and corticosteroid pulse therapy were applied with little effect. The application of systemic cyclosporine had a satisfactory effect in controlling the scleritis. The other patient, a 60-year-old woman, was suffering from scleritis and lid swelling in her right eye. Not only did topical and systemic corticosteroid therapy prove insufficient, they also resulted in the elevation of her intraocular pressure. After termination of corticosteroid therapy, the systemic cyclosporine was applied orally. Subsequently, the patient's scleritis improved without any severe side effects. Scleritis is a painful and destructive inflammatory disease of the sclera that causes congestion of the scleral venous plexus. In this study, we have established a new grading system for assessing activity in scleritis that can score the extent of ocular pain and the area of congestion. This system provides a practical method for following the clinical course and monitoring the outcome of therapy. We report two cases of unilateral scleritis that were resistant to corticosteroid therapy but responsive to systemic administration of cyclosporine. Findings from these cases indicate that cyclosporine is an effective drug for controlling severe scleritis.
Mild to Moderate, but Not Minimal or Severe, Acute Histologic Chorioamnionitis or Intra-Amniotic Inflammation Is Associated with a Decrease in Respiratory Distress Syndrome of Preterm Newborns without Fetal Growth Restriction
Authors: Park Chan-Wook , Park Joong Shin , Jun Jong Kwan , Yoon Bo Hyun
Published: June 2015

Background: Acute histologic chorioamnionitis (acute-HCA) is known to be associated with a decreased risk of respiratory distress syndrome (RDS) in newborns. However, there is no information about whether the severity of acute-HCA or intra-amniotic inflammation (IAI) is associated with the development of RDS. Objectives: To assess the relationship between the severity of acute-HCA or IAI and the development of RDS in preterm newborns due to preterm labor and intact membranes (PTL) or preterm premature rupture of membranes (preterm-PROM) without fetal growth restriction (FGR). Methods: The frequency of RDS was examined in 378 singleton preterm neonates (24.5-34 weeks' gestation) due to PTL or preterm-PROM without FGR. Patients were divided into 4 groups according to the severity of acute-HCA (i.e. total grade: minimal, 1; mild, 2; moderate, 3-4; severe, 5-6) or IAI (i.e. amniotic fluid MMP-8: minimal, 23-100 ng/ml; mild, 100-400 ng/ml; moderate, 400-800 ng/ml; severe, ≥800 ng/ml). Amniotic fluid MMP-8 was measured in 196 patients delivered within 7 days of amniocentesis. Results: Mild to moderate, but not minimal or severe, acute-HCA (minimal, 24%; mild, 13%; moderate, 19%; severe, 41%; preterm-reference group, 26%) or IAI (minimal, 24%; mild, 11%; moderate, 17%; severe, 25%; preterm reference group, 23%) was associated with a significant decrease in RDS as compared with the preterm reference group (each for p < 0.05 after the adjustment of gestational age at delivery, antenatal corticosteroid use, newborn gender, cesarean delivery and preterm-PROM as a cause of preterm birth). Conclusions: Mild to moderate, but not minimal or severe, acute-HCA or IAI is associated with a significant decrease in RDS among preterm neonates due to PTL or preterm-PROM without FGR.
Late Recurrent Testicular Seminoma: Histological Evidence Is Required
Authors: Lebacle Cedric , Gizzi Marco , Michot Jean-Marie , Lambotte Olivier , Ackermann Felix , Lazure Thierry , Massard Christophe
Published: June 2015

Introduction: Over the past 3 decades, the appropriate management of metastatic germ cell tumours (GCT) has been defined by several phase III trials. Many follow-up recommendations have been published based on expert consensus. However, common clinical scenarios can still be vexing for clinicians who are less experienced at managing patients with testicular cancer. Case Report: We highlight the arduous diagnostic work-up of a suspected late relapsing metastatic GCT in a patient suffering from fatigue, weight loss and prominent retroperitoneal lymph nodes, 4 years after first-line chemotherapy for metastatic seminoma. The various explorations finally led to the diagnosis of Whipple's disease. Conclusion: This unusual clinical case strongly highlights the need to perform an exhaustive evaluation, with a biopsy, if a late recurrent GCT is suspected to avoid pointless and potentially harmful treatment.
Lifestyle Factors and Indices of Kidney Function in the Framingham Heart Study
Authors: Foster Meredith C. , Hwang Shih-Jen , Massaro Joseph M. , Jacques Paul F. , Fox Caroline S. , Chu Audrey Y.
Published: June 2015

Background and Objectives: Lifestyle characteristics are modifiable factors that could be targeted as part of chronic kidney disease (CKD) prevention. We sought to determine the association of lifestyle characteristics with incident estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 and rapid eGFR decline in older adults in the United States. Methods: Prospective cohort study of Framingham Offspring participants with baseline eGFR <60 ml/min/1.73 m2 (n = 1,802) who attended the seventh (1998-2001; baseline) and eighth (2005-2008; follow-up) examinations (mean age = 59 years, 54.8% women). Predictors included measures of diet quality, physical activity, alcohol intake, and current smoking status assessed during baseline. Outcomes were based on creatinine-based eGFR at baseline and follow-up and included incident eGFR <60 ml/min/1.73 m2 (at follow-up) and rapid eGFR decline (annual eGFR decrease ≥3 ml/min/1.73 m2). Results: Over an average follow-up of 6.6 years, 9.5% (n = 171) of participants developed incident eGFR <60. A trend was observed across quartiles of diet quality, with higher levels of diet quality associated with a decreased odds ratio (OR) of incident eGFR <60 (p trend = 0.045). Higher diet quality was associated with decreased odds of rapid eGFR decline (p trend = 0.03) and was attenuated with additional adjustment (p trend = 0.07). In sensitivity analysis for rapid eGFR decline using a secondary definition (annual eGFR decrease ≥3 and incident eGFR <60), diet associations remained significant with additional adjustment (p trend = 0.04). No associations were observed with physical activity, smoking status, or alcohol intake with incident eGFR <60 or rapid eGFR decline (all p > 0.19). Conclusions: Higher diet quality may be associated with a decreased risk of incident eGFR <60 ml/min/1.73 m2, and rapid eGFR decline. Whether adherence to a healthy diet can prevent reduction in kidney function warrants further study.
Effects of Endurance and Endurance Strength Training on Body Composition and Physical Capacity in Women with Abdominal Obesity
Authors: Skrypnik Damian , Bogdański Paweł , Mądry Edyta , Karolkiewicz Joanna , Ratajczak Marzena , Kryściak Jakub , Pupek-Musialik Danuta , Walkowiak Jarosław
Published: June 2015

Aims: To compare the effects of endurance training with endurance strength training on the anthropometric, body composition, physical capacity, and circulatory parameters in obese women. Methods: 44 women with abdominal obesity were randomized into groups A and B, and asked to perform endurance (A) and endurance strength training (B) for 3 months, 3 times/week, for 60 min. Dual-energy X-ray absorptiometry and Graded Exercise Test were performed before and after training. Results: Significant decreases in body mass, BMI, total body fat, total body fat mass, and waist and hip circumference were observed after both types of intervention. Marked increases in total body lean and total body fat-free mass were documented in group B. In both groups, significant increases in peak oxygen uptake, time to exhaustion, maximal work rate, and work rate at ventilatory threshold were accompanied by noticeably decreased resting heart rate, resting systolic blood pressure, and resting and exercise diastolic blood pressure. No significant differences were noticed between groups for the investigated parameters. Conclusion: Our findings demonstrate evidence for a favorable and comparable effect of 3-month endurance and endurance strength training on anthropometric parameters, body composition, physical capacity, and circulatory system function in women with abdominal obesity.
Long-Term Normal Renal Function after Drastic Weight Reduction in Patients with Obesity-Related Glomerulopathy
Authors: Serra Assumpta , Esteve Anna , Navarro-Díaz Maruja , López Dolores , Bancu Ioana , Romero Ramón
Published: June 2015

Aims: No long-term studies of renal function evolution in morbidly obese (MO) patients after weight loss are available. The aim of our work was to ascertain the long-term influence of drastic weight reduction on renal function in MO patients with obesity-related glomerular lesions. Methods: 92 MO patients with normal renal function and biopsy evidence of mild obesity-related glomerulopathy underwent bariatric surgery (BS) and subsequent drastic weight loss. A long-term prospective follow-up (mean duration: 76 ± 42 months) was carried out. Basal renal biopsies and basal and long-term metabolic and renal function studies were performed in all cases. Linear mixed models were applied. Results: Blood pressure dropped early after BS and remained stable thereafter. Creatinine clearance and BMI fell in the first 2 years, rose slightly after 5 years and then remained stable. Serum creatinine and albuminuria decreased throughout the follow-up period. Renal function and albuminuria evolution showed non-significant differences in relation to the number of glomerular lesions. Conclusions: Drastic weight loss in BS-treated MO patients with pre-surgical normal renal function and mild obesity-related glomerular lesions is associated with short- and long-term maintenance of normal renal function and improvement in both arterial hypertension and albuminuria.
Calcium Homeostasis Disruption - a Bridge Connecting Cadmium-Induced Apoptosis, Autophagy and Tumorigenesis
Authors: Zhou Xuehai , Hao Weiming , Shi Haifeng , Hou Yongzhong , Xu Qinggang
Published: June 2015

Calcium and cadmium are divalent metals and have similar chemical properties. Both can enter cells through, albeit different, channels, or through protein-dependent permeation. However, cadmium disturbs the calcium homeostasis by inhibiting calcium channels and/or related proteins. Cadmium can also alter membrane phospholipid concentrations, and so induce a calcium homeostasis disorder. The altered calcium homeostasis induced by cadmium results in cell apoptosis, autophagy or tumorigenesis. In this review, calcium homeostasis disruption is summarized as a bridge connecting cadmium-induced apoptosis, autophagy, and tumorigenesis.
Multiple Sclerosis Epidemiology in Middle East and North Africa: A Systematic Review and Meta-Analysis
Authors: Heydarpour Pouria , Khoshkish Shayan , Abtahi Shabnam , Moradi-Lakeh Maziar , Sahraian Mohammad Ali
Published: June 2015

Background: Multiple sclerosis (MS) is one of the most common neurological disorders and a leading cause of nontraumatic disability in young adults in many countries. Recent reports from the Middle East and North Africa have suggested a moderate to high risk of MS in these countries. Methods: A literature search was performed in August 2014 in MEDLINE, EMBASE, and IMEMR to retrieve original population-based studies on MS epidemiology in the Middle East and North African countries published between 1st January 1985 and 1st August 2014. We designed search strategies using the key words: MS, prevalence, incidence, and epidemiology. According to the inclusion criteria, 52 studies were included in this systematic review. Results: McDonald's criteria were the most widely used diagnostic criteria in the studies. Most studies were conducted in single hospital-based centers with a defined catchment area. The female/male ratio ranged from 0.8 in Oman to 4.3 in Saudi Arabia. MS prevalence ranged from 14.77/100,000 population in Kuwait (2000) to 101.4/100,000 in Turkey (2006). The overall MS prevalence in the region was 51.52/100,000. The mean age at disease onset ranged from 25.2 years in Kuwait to 32.5 years in Northeastern Iran, with an overall estimate of 28.54 years. Conclusions: Recent advances in MS registries will allow nation-wide studies and temporal comparisons between countries, provided that age- and sex-standardized estimates are available.
Primary Adenoid Cystic Carcinoma of the Skin with Multiple Local Recurrences
Authors: Tonev Ivan Dimitrov , Pirgova Yana Stoeva , Conev Nikolay Vladimirov
Published: June 2015

Primary adenoid cystic carcinoma (PACC) of the skin is a rare tumor with fewer than 70 cases studied in detail in the English literature. This type of tumor shows a prolonged course and a growth pattern usually manifested by multiple local recurrences and has a low potential for distant metastases. The most important modality for primary treatment is surgical resection followed by radiotherapy. We report a woman aged 43 years at the time of diagnosis, who presented with a slow-growing nodule in the right axilla without lymph node enlargement. A wide local excision was performed, and the histology revealed an adenoid cystic carcinoma. During the next 24 years, another four local recurrences were excised (the last one in 2015) and confirmed histologically to be adenoid cystic carcinoma. The patient was given 44 Gy of radiotherapy after the second surgery in 1996. PACC of the skin is a rare tumor with insufficient data concerning the efficacy of the surgical technique and chemotherapy and radiotherapy treatment, even more so in the case of multiple recurrences. After the last recurrence, the patient was offered an active follow-up based on the long tumor-free intervals in the past and because the site of the primary tumor allowed further surgical excisions in future recurrences.
Cardiopulmonary Exercise Test in Patients with Hypertension: Focused on Hypertensive Response to Exercise
Authors: Youn Jong-Chan , Kang Seok-Min
Published: June 2015

The cardiopulmonary exercise test (CPET) provides integrative exercise responses including the cardiovascular, pulmonary and skeletal muscle systems. It can be used for the identification of myocardial ischemia, evaluation of exercise capacity and tolerance, and the assessment of chronotropic competence or arrhythmias with the addition of ventilatory and gas exchange measurement information. Among them, hypertensive response to exercise (HRE) is known to be related with higher risk of future heart failure and cardiovascular events in patients with hypertension. Proposed underlying mechanisms of HRE can be found in ventricular-vascular uncoupling including decreased aortic distensibility, increased left ventricular mass, endothelial dysfunction, and diastolic dysfunction. The CPET might be useful in the identification of masked hypertension and the assessment of antihypertensive treatment efficacy in patients with hypertension.
Ginsenoside Rb2 Attenuates UV-B Radiation-Induced Reactive Oxygen Species and Matrix Metalloproteinase-2 through Upregulation of Antioxidant Components in Human Dermal Fibroblasts
Authors: Oh Sun-Joo , Kim Kyunghoon , Lim Chang-Jin
Published: June 2015

Aims: The antiphotoaging activities of ginsenoside Rb2 on the skin, one of the predominant protopanaxadiol-type ginsenosides, were evaluated in cultured human dermal fibroblasts. Methods: The antiphotoaging activity was examined by analyzing the levels of reactive oxygen species (ROS), matrix metalloproteinase-2 (MMP-2), total glutathione (GSH) and superoxide dismutase (SOD) activity as well as cell viability for fibroblasts under UV-B irradiation. Results: When cultured fibroblasts were exposed to Rb2 prior to UV-B irradiation, Rb2 displayed suppressive activities on UV-B-induced ROS elevation and MMP-2 on both activity and protein levels, while it exhibited an enhancing activity on total GSH level and SOD activity diminished by UV-B irradiation. However, Rb2 could not interfere with cell viabilities in UV-B-irradiated fibroblasts. Conclusion: Ginsenoside Rb2 plays a photoprotective role against UV-B-induced oxidative stress in human dermal fibroblasts, which implies its skin antiphotoaging potential.
Metastatic Breast Cancer with Extensive Osseous Metastasis Presenting with Symptomatic Immune Thrombocytopenic Purpura and Anemia: A Case Report and Review of the Literature
Authors: Niu Jiaxin , Goldin Teresa , Markman Maurie , Kundranda Madappa N.
Published: June 2015

Background: Immune thrombocytopenic purpura (ITP) is a rare acquired bleeding disorder with an estimated incidence of 1 in 10,000 people in the general population. The association of ITP with breast cancer is an even rarer entity with very limited reports in the English literature. Case Presentation: We report a case of a 51-year-old female with no significant past medical history who presented with sudden onset of malaise, syncope, gingival bleed and epistaxis. She was found to have severe thrombocytopenia (platelet count 6,000/μl) and anemia (hemoglobin 7.2 g/dl). Her workup led to the diagnosis of metastatic ductal breast cancer with extensive bone metastasis. Bone marrow biopsy demonstrated myelophthisis which was initially thought to be consistent with her presentation of thrombocytopenia and anemia. Therefore, the patient was started on hormonal therapy for the treatment of her metastatic breast cancer. After 3 months of therapy, she did not improve and developed severe mucosal bleeding. Her clinical presentation was suspicious for ITP and immune-mediated anemia, and hence she was started on steroids and intravenous immunoglobulin. The patient had a dramatic response to therapy with normalization of her platelet count and hemoglobin within 2 weeks. Conclusion: To our knowledge, this is the first reported case of metastatic breast cancer presenting with symptomatic ITP and anemia, and both symptoms are postulated to be immune-mediated.
Allergen Levels in the Hair of Different Cattle Breeds
Authors: Zahradnik Eva , Sander Ingrid , Brüning Thomas , Raulf Monika
Published: June 2015

Background: Cattle are well-known sources of respiratory allergens in agricultural environments. Breed-specific differences in Bos d 2 (a major bovine allergen) levels in cattle hair have been previously suggested but not fully characterized. Therefore, the aim of the current study was to determine whether hair from common cattle breeds differs in protein and allergen content. Methods: In total, 80 hair samples from 16 different cattle breeds were analyzed. The protein concentration was determined using the Bradford assay. The allergen content was measured using a sandwich ELISA based on polyclonal antibodies against a bovine hair protein extract and a commercial immunoassay based on monoclonal antibodies against Bos d 2. Results are given in micrograms per gram of hair. Statistical analysis was performed using the Kruskal-Wallis test and Spearman's rank correlation. Results: A wide variability in all 3 tested parameters was observed between the individual samples. The protein content differed by about 35-fold (0.3-12 mg/g), the bovine hair allergen content differed by about 500-fold (37-18,553 µg/g), and the Bos d 2 content differed by about 1,200-fold (5-6,323 µg/g). Protein, bovine hair allergen, and Bod d 2 values correlated strongly and significantly with one another. The median Bos d 2/bovine hair allergen ratio was 0.28. No significant differences were found between the most common breeds in Germany (Simmental, Holstein, and Braunvieh) and a group of rare breeds or between female and male animals. Conclusions: The results confirm a high variability in allergen levels between individual animals but also indicate that allergen production is related neither to the breed nor to gender.
Wilkie's Syndrome or Superior Mesenteric Artery Syndrome: Fact or Fantasy
Authors: Zaraket Vera , Deeb Liliane
Published: June 2015

Superior mesenteric artery (SMA) syndrome (known as Wilkie's syndrome) is a rare cause of upper gastrointestinal obstruction. It is an acquired disorder in which acute angulation of the SMA causes compression of the third part of the duodenum between the SMA and the aorta. This is commonly due to loss of fatty tissue as a result of a variety of debilitating conditions. We report a 17-year-old female who presented with intermittent abdominal pain and intractable vomiting following significant weight loss after hospitalization for pneumonia. Symptoms persisted for 2 years and the patient underwent extensive invasive and non-invasive tests, but to no avail. Thereafter she developed acute high intestinal obstruction, which unraveled her diagnosis. This case emphasizes the challenges in the diagnosis of SMA syndrome and the need for increased awareness of this entity. This will improve early recognition in order to reduce irrelevant tests and unnecessary treatments.
Serenoa repens as an Endocrine Disruptor in a 10-Year-Old Young Girl: A New Case Report
Authors: Morabito Paolo , Miroddi Marco , Giovinazzo Salvatore , Spina Edoardo , Calapai Gioacchino
Published: June 2015

Serenoa repens, commonly known as saw palmetto, is the sole species currently classified in the genus Serenoa. The plant is a low shrubby palm that is native of West Indies, and it grows in the coastal lands of North America and other European mediterranean countries. Its fruits contain high concentrations of fatty acids and phytosterols. S. repens extracts have been studied for the symptomatic treatment of benign prostatic hyperplasia. Recently, they have been proposed to treat androgenic alopecia and other hair disorders. We report a new case of hot flashes in a 10-year-old girl using a food supplement containing the extract of S. repens for the treatment of hirsutism. When the girl discontinued the treatment, the hot flashes stopped. A ‘rechallenge' of the supplement was tried and symptoms reappeared. About 4 months after starting therapy, the girl experienced menarche. Exposure to the plant-derived product could be responsible for the appearance of menarche. In our opinion, use of phytotherapeutic agents in pediatric patients should be associated to a better evaluation of benefit/risk profile taking in account the physiological changes that occurs at different ages in this subgroup of population.
Cholangiocarcinoma Derived from Remnant Intrapancreatic Bile Duct Arising 32 Years after Congenital Choledochal Cyst Excision: A Case Report
Authors: Ishikawa Kentaro , Ogasawar Sadahisa , Chiba Tetsuhiro , Sakamoto Dai , Kanogawa Naoya , Saito Tomoko , Motoyama Tenyu , Suzuki Eiichiro , Ooka Yoshihiko , Sugiyama Harutoshi , Tawada Akinobu , Sakai Yuji , Tsuyuguchi Toshio , Kishimoto Takashi , Yokosuka Osamu
Published: June 2015

We report a rare case of a 46-year-old woman with cholangiocarcinoma derived from remnant intrapancreatic bile duct arising 32 years after the excision of a congenital choledochal cyst. She had undergone anastomosis of the choledochal cyst and duodenum at birth, excision of the choledochal cyst and hepaticoduodenostomy with jejunal interposition at 14 years of age as well as the excision of an infectious cyst around the anastomosis site at 21 years of age. At 29 years of age, she was diagnosed with a chronic hepatitis C virus (HCV) infection and was referred to our hospital for treatment. She did not consent to interferon-based therapy against the HCV infection. At 46 years of age, she experienced epigastric discomfort. A dynamic CT revealed multiple tumors in the liver, a tumor in the head of the pancreas as well as lymph node metastases in the mediastinum and abdominal cavity. A liver tumor biopsy revealed adenocarcinoma, and she was clinically diagnosed with cholangiocarcinoma derived from remnant intrapancreatic bile duct with multiple metastasis in the liver and lymph node metastasis. She requested palliative therapy and eventually died during the treatment course. The autopsy specimen revealed a tumor in the head of the pancreas, and on the basis of local existence and the pattern of metastasis, it was confirmed as cholangiocarcinoma derived from remnant intrapancreatic bile duct. A microscopic examination revealed a poorly differentiated adenocarcinoma. This report provides information on a case of cholangiocarcinoma derived from remnant intrapancreatic bile duct arising after the excision of congenital choledochal cyst that was assessed pathologically.
Molecular Pharmacology of the Incretin Receptors
Authors: Al-Sabah Suleiman
Published: June 2015

The incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are important regulators of insulin and glucagon secretion as well as lipid metabolism and appetite. These biological functions make their respective receptors (GIPR and GLP-1R) attractive targets in the treatment of both type 2 diabetes mellitus (T2DM) and obesity. The use of these native peptides in the treatment of these conditions is limited by their short half-lives. However, long-acting GLP-1R agonists and inhibitors of the enzyme that rapidly inactivates GIP and GLP-1 (dipeptidyl peptidase IV) are in clinical use. Although there is a loss of response to both hormones in T2DM, this effect appears to be more pronounced for GIP. This has made targeting GIPR less successful than GLP-1R. Furthermore, results demonstrating that GIPR knockout mice were resistant to diet-induced obesity suggested that GIPR antagonists may prove to be useful therapeutics. More recently, molecules that activate both receptors have shown promise in terms of glycemic and body weight control. This review focused on recent advances in the understanding of the signaling mechanisms and regulation of these two clinically important receptors.
Computational Analysis of Missense Variants of G Protein-Coupled Receptors Involved in the Neuroendocrine Regulation of Reproduction
Authors: Min Le , Nie Min , Zhang Anna , Wen Junping , Noel Sekoni D. , Lee Vivian , Carroll Rona S. , Kaiser Ursula B.
Published: June 2015

Introduction: Many missense variants in G protein-coupled receptors (GPCRs) involved in the neuroendocrine regulation of reproduction have been identified by phenotype-driven or large-scale exome sequencing. Computational functional prediction analysis is commonly performed to evaluate their impact on receptor function. Methods: To assess the performance and outcome of functional prediction analyses for these GPCRs, we performed a statistical analysis of the prediction performance of SIFT and PolyPhen-2 for variants with documented biological function as well as variants retrieved from Ensembl. We obtained missense variants with documented biological function testing from patients with reproductive disorders from a comprehensive literature search. Missense variants from individuals with known reproductive disorders were retrieved from the Human Gene Mutation Database. Missense variants from the general population were retrieved from the Ensembl genome database. Results: The accuracies of SIFT and PolyPhen-2 were 83 and 85%, respectively. The performance of both prediction tools was greater in predicting loss-of-function variants (SIFT: 92%; PolyPhen-2: 95%) than in predicting variants that did not affect function (SIFT: 54%; PolyPhen-2: 57%). Concordance between SIFT and PolyPhen-2 did not improve accuracy. Surprisingly, approximately half of the variants retrieved from Ensembl were predicted as loss-of-function variants by SIFT (47%) and PolyPhen-2 (54%). Conclusion: Our findings provide new guidance for interpreting the results and limitations of computational functional prediction analyses for GPCRs and will help to determine which variants require biological function testing. In addition, our findings raise important questions regarding the link between genotype and phenotype in the general population.
САМОСВІДОМІСТЬ ЯК СКЛАДНИК МОВНОЇ КОМПЕТЕНЦІЇ ОСОБИСТОСТІ
Authors: Бобак М. І. , Бондаренко С. В. , Кульчицький В. Й. , Кушик М. Л. , Паласюк Г. Б. , Попадинець Г. О. , Прокоп І. А. , Пришляк А. М. , Саварин Т. В. , Юкало В. Я.
Published: June 2015

У статті розглянута проблема самосвідомості як складника мовної компетенції особистості. Аналізується значення
самосвідомості як центрального утворення, без якого людина не може стати особистістю. Висвітлюється громадянська
свідомість та самосвідомість, щоє однією із найважливіших складових психологічної структури особистості. Зосереджена
увага на питанні зв’язку мови з мисленням людини, її внутрiшнiм світом та культурними цінностями. Обговорюються
основнішляхиформування мовної компетенції особистості. Визначено головні ознаки мовної особистості. Окреслюється
мета формування гармонійної, високо розвиненої свідомості й самосвідомості мовної особистості.
B-1b Cells Secrete Atheroprotective IgM and Attenuate Atherosclerosis
Authors: Rosenfeld Sam M. , Perry Heather M. , Gonen Ayelet , Prohaska Thomas A. , Srikakulapu Prasad , Grewal Sukhdeep , Das Deepanjana , McSkimming Chantel , Taylor Angela M. , Tsimikas Sotirios , Bender Timothy P. , Witztum Joseph L. , McNamara Coleen A.
Published: June 2015

Rationale:

B cells contribute to atherosclerosis through subset-specific mechanisms. Whereas some controversy exists about the role of B-2 cells, B-1a cells are atheroprotective because of secretion of atheroprotective IgM antibodies independent of antigen. B-1b cells, a unique subset of B-1 cells that respond specifically to T-cell–independent antigens, have not been studied within the context of atherosclerosis.

Objective:

To determine whether B-1b cells produce atheroprotective IgM antibodies and function to protect against diet-induced atherosclerosis.

Methods and Results:

We demonstrate that B-1b cells are sufficient to produce IgM antibodies against oxidation-specific epitopes on low-density lipoprotein both in vitro and in vivo. In addition, we demonstrate that B-1b cells provide atheroprotection after adoptive transfer into B- and T-cell deficient (
Rag1
−/−
Apoe
−/−
) hosts. We implicate inhibitor of differentiation 3 (Id3) in the regulation of B-1b cells as B-cell–specific Id3 knockout mice (Id3
BKO
Apoe
−/−
) have increased numbers of B-1b cells systemically, increased titers of oxidation-specific epitope–reactive IgM antibodies, and significantly reduced diet-induced atherosclerosis when compared with Id3
WT
Apoe
−/−
controls. Finally, we report that the presence of a homozygous single nucleotide polymorphism in
ID3
in humans that attenuates Id3 function is associated with an increased percentage of circulating B-1 cells and anti–malondialdehyde-low-density lipoprotein IgM suggesting clinical relevance.

Conclusions:

These results provide novel evidence that B-1b cells produce atheroprotective oxidation-specific epitope–reactive IgM antibodies and protect against atherosclerosis in mice and suggest that similar mechanisms may occur in humans.
Cerebral Microbleeds Predict Intracerebral Hemorrhage in Hemodialysis Patients
Authors: Naganuma Toshihide , Takemoto Yoshiaki , Shoji Tetsuo , Ishimura Eiji , Okamura Mikio , Nakatani Tatsuya
Published: June 2015

Background and Purpose—

In hemodialysis patients, previous reports have described a high prevalence of cerebral microbleeds (CMBs), but no longitudinal studies have been performed to determine the clinical significance of CMBs in these patients. In this study, we investigated whether the presence of CMBs was a predictor of future strokes in hemodialysis patients.

Methods—

Cranial MRI, including T2*-weighted magnetic resonance imaging, was performed on 179 hemodialysis patients with no past history of cerebrovascular events. The patients were followed prospectively until death or renal transplantation. We used the Cox proportional hazards model with inverse probability of treatment weighting using the propensity score to compare the event-free survivals of patients with/without CMBs. For sensitivity analyses, stratification by propensity score quintile and regression adjustment were used.

Results—

CMBs were detected in 45 of the 179 patients. During a median follow-up period of 5.0 years, stroke occurred in 24 patients, including 12 with intracerebral hemorrhage and 12 with cerebral infarctions. Cox proportional hazards analysis with inverse probability of treatment weighting using the propensity score revealed that the presence of CMBs was a strong and significant predictor of intracerebral hemorrhage (hazard ratio, 26.53; 95% confidence interval, 2.88–244.90) but not cerebral infarction (hazard ratio, 0.91; 95% confidence interval, 0.25–3.34). Sensitivity analyses yielded similar results.

Conclusions—

This study showed that the presence of CMBs was an independent and strong predictor of intracerebral hemorrhage in stroke-free hemodialysis patients, indicating that hemodialysis patients with CMBs should be carefully monitored for future onset of intracerebral hemorrhage.
Pediatric Idiopathic Intracranial Hypertension Presenting With Sensorineural Hearing Loss
Authors: Reitsma Sietze , Stokroos Robert , Weber Jacobiene W. , van Tongeren Joost
Published: June 2015

Objective:

To present the rare case of a young boy with idiopathic intracranial hypertension presenting with bilateral sensorineural hearing loss developing over several months. This was accompanied by headaches, otalgia, tinnitus, and vertigo. Furthermore, we aim to provide a concise review on this matter, as this report represents the second case in literature of pediatric idiopathic intracranial hypertension presenting with hearing loss.

Methods:

Workup of a 9-year-old boy with bilateral sensorineural hearing loss, including (among others) physical examination, audiometry, diagnostic imaging, and lumbar puncture.

Results:

Physical examination including fundoscopy as well as imaging showed no abnormalities. At presentation, pure tone audiometry revealed bone conduction thresholds of about 30 dB HL in both ears. Two months later, this declined to about 35 dB HL in both ears. Lumbar puncture revealed an increased intracranial pressure. The boy was thus diagnosed with idiopathic intracranial hypertension. After the lumbar puncture, the otological complaints gradually resolved, and the hearing normalized (bone conduction thresholds of 0-5 dB HL).

Conclusion:

Although rare, sensorineural hearing loss in the pediatric population together with otalgia, tinnitus, and vertigo can be due to idiopathic intracranial hypertension and as such can be reversible.
Decisional Conflict in Parents Considering Bone-Anchored Hearing Devices in Children With Unilateral Aural Atresia
Authors: Graham M. Elise , Haworth Rebecca , Chorney Jill , Bance Manohar , Hong Paul
Published: June 2015

Objective:

The benefits of bone-anchored hearing devices (BAHD) in children with unilateral aural atresia are controversial. We sought to determine whether there is parental decisional conflict surrounding elective placement of BAHD for this indication.

Methods:

Caregivers of pediatric patients with unilateral aural atresia and normal contralateral ear undergoing percutaneous BAHD consultation were enrolled. All consultations were carried out by one pediatric otolaryngologist in a consistent manner. After consultation, the participants completed a demographics form and the Decisional Conflict Scale (DCS) questionnaire.

Results:

Twenty-three caregivers of 15 male (65.2%) and 8 female (34.8%) children (mean age 5.65 years) participated. The overall median DCS score was 15.63 (standard error = 4.21). Significant decisional conflict (DCS score ≥ 25) was found in 10 participants (43.5%). The median DCS score in the group choosing surgery was 5.47, and it was 23.44 in those who did not choose surgery (Mann–Whitney U = 39, Z = −1.391, P = .164). The median DCS score for mothers and fathers was 25 and 3.91, respectively.

Conclusion:

Many parents experienced significant decisional conflict when considering percutaneous BAHD surgery in children with unilateral aural atresia in our study population. Future research should explore the impact of decisional conflict on health outcomes.
Verdi: Il brutto, il grottesco e la parola
Authors: Scaramuzza Gabriele
Published: June 2015

Nell’ambito del passaggio, nel corso del XIX secolo, dall’estetica del tragico e del bello a un’estetica del grottesco e del brutto, Giuseppe Verdi è un importante rappresentante e promotore di quest’ultima. Dal Rigoletto al Falstaff, dai Masnadieri alla Traviata, l’estetica del brutto domina a quasi tutti i livelli nelle sue diverse modalità. C’è un brutto psicologico che inerisce all’insistita morbosità dei personaggi (a volte accompagnata, come in Rigoletto, da deformità fisica), all'irrazionalità, crudeltà o dismisura delle loro azioni e passioni. C’è il brutto di un urgente realismo sociale, visibile nell’attenzione rivolta a emarginati e reietti, colti nel loro sottomondo, oppure alla banalità di situazioni piccolo-borghesi, e in generale allo squallore della morte (drastico correttivo alla “bella” morte privilegiata nel secolo precedente). Stilisticamente, alla categoria del brutto appartengono la trasgressione dei generi (per esempio la compresenza di comico e tragico), l’alternanza di registri alti e bassi, e la promiscuità degli stili (del volgare e del sublime, del terribile e dell’ironico) – tutti elementi costanti nell’opera verdiana. Lungi dall’essere gratuito esercizio o esaltazione fine a sé stessa, la frequentazione del brutto è in Verdi sempre funzionale alla verità del dramma – al perseguimento della quale egli non esita a sacrificare i tradizionali ideali di bellezza, decoro e armonia.
A System for Recording the Dynamics of the Water Drop’s Impact on a Surface
Authors: Korbiel Tomasz , Ryżak Magdalena , Przech Dariusz , Lamorski Krzysztof , Bieganowski Andrzej
Published: June 2015

The splash phenomenon is the first stage of water erosion on the soil. It occurs when the water drops of the rain strike the surface. The impact of the water drop is fast. But if one has a fast enough measuring system, it can be considered as a temporally extended phenomenon. The aim of this paper is to describe a system for the measurement of the dynamic of the changing forces when a water drop interacts with the surface during impact. The constructive assumptions and validation of the measurement system, which has been based on piezoelectric sensors, are also presented. The system allows one to measure the changes of the force with the frequency of 150 kHz. The maximum force is 200 N, which is quite sufficient for all sizes of water drops which occur in nature and their maximum speeds. The results of test measurements, that is, the changes of the force obtained from water drops falling on the sensors, are also shown.