bluuebunny/crossref_metadata_2025 huggingface dataset:
Epidemiology of Diabetic Foot Ulcers and Amputations in Romania: Results of a Cross-Sectional Quality of Life Questionnaire Based Survey
Authors: Bondor Cosmina I. , Veresiu Ioan A. , Florea Bogdan , Vinik Etta J. , Vinik Aaron I. , Gavan Norina A.
Published: February 2016

This is a post hoc analysis of quality of life in diabetic neuropathy patients in a cross-sectional survey performed in 2012 in Romania, using the Norfolk QOL-DN in which 21,756 patients with self-reported diabetes were enrolled. This current analysis aims to expand research on the diabetic foot and to provide an update on the number of foot ulcers found in Romania. Of the 21,174 patients included in this analysis, 14.85% reported a history of foot ulcers and 3.60% reported an amputation. The percentage of neuropathy patients with foot ulcers increased with age; the lowest percentage was observed in the 20–29-year age group (6.62%) and the highest in the 80–89-year age group (17.68%). The highest number of amputations was reported in the 70–79-year age group (largest group). Compared to patients without foot ulcers, those with foot ulcers had significantly higher scores for total DN and all its subdomains translating to worse QOL (p<0.001). This analysis showed a high rate of foot ulcers and amputations in Romanian diabetic patients. It underscores the need for implementation of effective screening and educational programs.
Unexplained Neonatal Cardiorespiratory Collapse at Five Minutes of Age
Authors: Zaleta Sona , Miller Sarah , Kumar Prashant
Published: February 2016

We report a case in which a term neonate suffered cardiorespiratory collapse at five minutes of age following an uncomplicated delivery and Apgar score of eight at one minute. Following prolonged cardiopulmonary resuscitation, the infant recovered well with no neurological deficit. Although sudden and unexpected postnatal collapse has been extensively described, this case does not fulfil its definition criteria. It provides a diagnostic challenge for clinicians and to the best of our knowledge is the first report of unexplained cardiorespiratory collapse at five minutes of age. The case serves as a timely reminder that cord gas analysis is recommended in all cases of potential fetal compromise and that Apgar scores should be used with caution as a predictor of neurological sequelae.
Emerging Link between Alzheimer’s Disease and Homeostatic Synaptic Plasticity
Authors: Jang Sung-Soo , Chung Hee Jung
Published: February 2016

Alzheimer’s disease (AD) is an irreversible brain disorder characterized by progressive cognitive decline and neurodegeneration of brain regions that are crucial for learning and memory. Although intracellular neurofibrillary tangles and extracellular senile plaques, composed of insoluble amyloid-β(Aβ) peptides, have been the hallmarks of postmortem AD brains, memory impairment in early AD correlates better with pathological accumulation of soluble Aβoligomers and persistent weakening of excitatory synaptic strength, which is demonstrated by inhibition of long-term potentiation, enhancement of long-term depression, and loss of synapses. However, current, approved interventions aiming to reduce Aβlevels have failed to retard disease progression; this has led to a pressing need to identify and target alternative pathogenic mechanisms of AD. Recently, it has been suggested that the disruption of Hebbian synaptic plasticity in AD is due to aberrant metaplasticity, which is a form of homeostatic plasticity that tunes the magnitude and direction of future synaptic plasticity based on previous neuronal or synaptic activity. This review examines emerging evidence for aberrant metaplasticity in AD. Putative mechanisms underlying aberrant metaplasticity in AD will also be discussed. We hope this review inspires future studies to test the extent to which these mechanisms contribute to the etiology of AD and offer therapeutic targets.
Hydrogen Sulfide Signaling Axis as a Target for Prostate Cancer Therapeutics
Authors: Liu Mingzhe , Wu Lingyun , Montaut Sabine , Yang Guangdong
Published: February 2016

Hydrogen sulfide (H2S) was originally considered toxic at elevated levels; however just in the past decade H2S has been proposed to be an important gasotransmitter with various physiological and pathophysiological roles in the body. H2S can be generated endogenously from L-cysteine by multiple enzymes, including cystathionine gamma-lyase, cystathionine beta-synthase, and 3-mercaptopyruvate sulfurtransferase in combination with cysteine aminotransferase. Prostate cancer is a major health concern and no effective treatment for prostate cancers is available. H2S has been shown to inhibit cell survival of androgen-independent, androgen-dependent, and antiandrogen-resistant prostate cancer cells through different mechanisms. Various H2S-releasing compounds, including sulfide salts, diallyl disulfide, diallyl trisulfide, sulforaphane, and other polysulfides, also have been shown to inhibit prostate cancer growth and metastasis. The expression of H2S-producing enzyme was reduced in both human prostate cancer tissues and prostate cancer cells. Androgen receptor (AR) signaling is indispensable for the development of castration resistant prostate cancer, and H2S was shown to inhibit AR transactivation and contributes to antiandrogen-resistant status. In this review, we summarized the current knowledge of H2S signaling in prostate cancer and described the molecular alterations, which may bring this gasotransmitter into the clinic in the near future for developing novel pharmacological and therapeutic interventions for prostate cancer.
Antimutagenic Compounds of White Shrimp (Litopenaeus vannamei): Isolation and Structural Elucidation
Authors: López-Saiz Carmen-María , Hernández Javier , Cinco-Moroyoqui Francisco-Javier , Velázquez Carlos , Ocaño-Higuera Víctor-Manuel , Plascencia-Jatomea Maribel , Robles-Sánchez Maribel , Machi-Lara Lorena , Burgos-Hernández Armando
Published: February 2016

According to the World Health Organization, cancer is the main cause of mortality worldwide; thus, the search of chemopreventive compounds to prevent the disease has become a priority. White shrimp (Litopenaeus vannamei) has been reported as a source of compounds with chemopreventive activities. In this study, shrimp lipids were extracted and then fractionated in order to isolate those compounds responsible for the antimutagenic activity. The antimutagenic activity was assessed by the inhibition of the mutagenic effect of aflatoxin B1 on TA98 and TA100 Salmonella tester strains using the Ames test. Methanolic fraction was responsible for the highest antimutagenic activity (95.6 and 95.9% for TA98 and TA100, resp.) and was further separated into fifteen different subfractions (M1–M15). Fraction M8 exerted the highest inhibition of AFB1 mutation (96.5 and 101.6% for TA98 and TA100, resp.) and, after further fractionation, four subfractions M8a, M8b, M8c, and M8d were obtained. Data from 1H and 13C NMR, and mass spectrometry analysis of fraction M8a (the one with the highest antimutagenic activity), suggest that the compound responsible for its antimutagenicity is an apocarotenoid.
The Possible Role of Mast Cells in the Odontogenic Cyst’s Pathogenesis: A Comparative Study between Dentigerous Cyst and Keratocystic Odontogenic Tumor
Authors: Farhadi Sareh , Shahsavari Fatemeh , Davardan MirMahdi
Published: February 2016

Background. Recently, mast cells were recognized in the pathogenesis of more aggressive pathologic lesions. This study was aimed to evaluate and compare the density of mast cells in Dentigerous cyst (DC) and Keratocystic odontogenic tumor (KCOT) regarding their different clinical behavior.Method. This study was conducted on 23 and 26 cases of DC and KCOT, respectively. Four-micron sections were prepared for Toluidine blue staining and mast cell densities in two desired cysts were studied. Final data was analyzed viat-test and Mann-WhitneyUtest method regarding the significant level lower than 0.05.Results. Mast cell densities were significantly higher in KCOTs for deep and superficial layers and both layers (P<0.05). The density of degranulated mast cells in the deeper layers and both layers was significantly higher in KCOTs (P<0.05). However, the density of degranulated mast cells in the superficial layer had no significant difference (P>0.05).Conclusion. It seems that mast cells may be involved in the pathogenesis of KCOT, but, regarding wide range of mast cell’s biologic activities, further investigations are recommended to confirm the issue and prepare the details.
A Robust Service Selection Method Based on Uncertain QoS
Authors: Chen Yanping , Jiang Lu , Zhang Jianke , Dong Xiaoxiao
Published: February 2016

Nowadays, the number of Web services on the Internet is quickly increasing. Meanwhile, different service providers offer numerous services with the similar functions. Quality of Service (QoS) has become an important factor used to select the most appropriate service for users. The most prominent QoS-based service selection models only take the certain attributes into account, which is an ideal assumption. In the real world, there are a large number of uncertain factors. In particular, at the runtime, QoS may become very poor or unacceptable. In order to solve the problem, a global service selection model based on uncertain QoS was proposed, including the corresponding normalization and aggregation functions, and then a robust optimization model adopted to transform the model. Experiment results show that the proposed method can effectively select services with high robustness and optimality.
Adrenergic Inhibition with Dexmedetomidine to Treat Stress Cardiomyopathy during Alcohol Withdrawal: A Case Report and Literature Review
Authors: Harris Zachary M. , Alonso Alvaro , Kennedy Thomas P.
Published: February 2016

Stress (Takotsubo) cardiomyopathy is a form of reversible left ventricular dysfunction with a heightened risk of ventricular arrhythmia thought to be caused by high circulating catecholamines. We report a case of stress cardiomyopathy that developed during severe alcohol withdrawal successfully treated with dexmedetomidine. The case involves a 53-year-old man with a significant history of alcohol abuse who presented to a teaching hospital with new-onset seizures. His symptoms of acute alcohol withdrawal were initially treated with benzodiazepines, but the patient later developed hypotension, and stress cardiomyopathy was suspected based on ECG and echocardiographic findings. Adjunctive treatment with the alpha-2-adrenergic agonist, dexmedetomidine, was initiated to curtail excessive sympathetic outflow of the withdrawal syndrome, thereby targeting the presumed pathophysiology of the cardiomyopathy. Significant clinical improvement was observed within one day of initiation of dexmedetomidine. These findings are consistent with other reports suggesting that sympathetic dysregulation during alcohol withdrawal produces ideal pathobiology for stress cardiomyopathy and leads to ventricular arrhythmogenicity. Stress cardiomyopathy should be recognized as a complication of alcohol withdrawal that significantly increases cardiac-related mortality. By helping to correct autonomic dysregulation of the withdrawal syndrome, dexmedetomidine may be useful in the treatment of stress-induced cardiomyopathy.
Sulforaphane Attenuates Contrast‐Induced Nephropathy in Rats via Nrf2/HO‐1 Pathway
Authors: Zhao Zhihong , Liao Guixiang , Zhou Qin , Lv Daoyuan , Holthfer Harry , Zou Hequn
Published: February 2016

Background. Oxidative stress plays an important role in the pathogenesis of contrast‐induced nephropathy (CIN). The aim of this study was to investigate the antioxidant effects of sulforaphane (SFN) in a rat model of CIN and a cell model of oxidative stress in HK2 cells. Methods. Rats were randomized into four groups (n = 6 per group): control group, Ioversol group (Ioversol‐induced CIN), Ioversol + SFN group (CIN rats pretreated with SFN), and SFN group (rats treated with SFN). Renal function tests, malondialdehyde (MDA), and reactive oxygen species (ROS) were measured. Western blot, real‐time polymerase chain reaction analysis, and immunohistochemical analysis were performed for nuclear factor erythroid‐derived 2‐like 2 (Nrf2) and heme oxygenase‐1 (HO‐1) detection. Results. Serum blood urea nitrogen (BUN), creatinine, and renal tissue MDA were increased after contrast exposure. Serum BUN, creatinine, and renal tissue MDA were decreased in the Ioversol + SFN group as compared with those in the Ioversol group. SFN increased the expression of Nrf2 and HO‐1 in CIN rats and in Ioversol‐induced injury HK2 cells. SFN increased cell viability and attenuated ROS level in vitro. Conclusions. SFN attenuates experimental CIN in vitro and in vivo. This effect is suggested to activate the Nrf2 antioxidant defenses pathway.
Co-Existence of Thyroid Nodule and Thyroid Cancer in Children and Adolescents with Hashimoto Thyroiditis: A Single-Center Study
Authors: Keskin Meliksah , Savas-Erdeve Senay , Aycan Zehra
Published: February 2016

Background: Currently, there is an inadequate number of studies on nodule and malignancy development in children and adolescents with Hashimoto thyroiditis (HT). Material and Methods: Patients who were diagnosed with HT between 2004 and 2013 were included in the study. The HT diagnosis was made with a heterogeneous appearance on thyroid ultrasonography and the elevation of antithyroid peroxidase and/or anti-thyroglobulin antibodies. Fine-needle aspiration biopsy (FNAB) was performed in cases with a nodule size >1 cm or who had ultrasonography findings indicating malignancy. Results: A total of 39 (13%) thyroid nodules were detected in 300 patients with a diagnosis of HT. Papillary thyroid carcinoma (PTC) was diagnosed in 2 of the 12 cases in whom FNAB was performed. The thyroid nodule was detected at the same time as HT in the 2 cases with malignancy. The PTC diagnosis was made 2 years after the HT diagnosis in the first case and 3 years later in the second case. The largest diameter of the thyroid nodule was 5 mm in both cases. Conclusion: The thyroid nodule rate on an HT background was found to be 13%, and the thyroid malignancy rate was 0.67% in our study.
Safety of Regular-Dose Imatinib Therapy in Patients with Gastrointestinal Stromal Tumors Undergoing Dialysis
Authors: Niikura Ryota , Serizawa Takako , Yamada Atsuo , Yoshida Shuntaro , Tanaka Mariko , Hirata Yoshihiro , Koike Kazuhiko
Published: February 2016

The number of cancer patients undergoing dialysis has been increasing, and the number of these patients on chemotherapy is also increasing. Imatinib is an effective and safe therapy for KIT-positive gastrointestinal stromal tumors (GIST), but the efficacy and safety of imatinib in dialysis patients remain unclear. Because clinical trials have not been conducted in this population, more investigations are required. We report on a 75-year-old Japanese man undergoing dialysis who presented with massive tarry stool from a duodenal GIST. The duodenal GIST was 14 cm in diameter with multiple liver and bone metastases. The patient underwent an urgent pancreaticoduodenectomy to achieve hemostasis. After surgery, he was administered imatinib 400 mg/day. No severe adverse event including myelosuppression, congestive heart failure, liver functional impairment, intestinal pneumonia, or Steven-Johnson syndrome occurred, and the liver metastasis remained stable for 4 months. During chemotherapy, hemodialysis continued three times per week without adverse events. We suggest that regular-dose imatinib is an effective and safe treatment in patients with GIST undergoing dialysis. In addition, we present a literature review of the effectiveness and safety of imatinib treatment in dialysis patients.
The Clinical Significance of Uric Acid and Complement Activation in the Progression of IgA Nephropathy
Authors: Caliskan Yasar , Ozluk Yasemin , Celik Dilara , Oztop Nida , Aksoy Aysun , Ucar Ayse Serra , Yazici Halil , Kilicaslan Isin , Sever Mehmet Sukru
Published: February 2016

Background/Aims: The aim of this study is to investigate the utility of clinical [age, gender, mean arterial pressure (MAP)] and laboratory parameters [eGFR, hemoglobin (Hgb), serum levels of creatinine, uric acid, albumin, proteinuria, hematuria] and also histopathological lesions (Oxford classification parameters, crescents, intensity and pattern of staining for C3, C1Q, IgA, IgG, IgM) as progression markers in patients with IgA Nephropathy (IgAN). Methods: A total of 111 IgAN patients with a follow-up period >1 year or who reached kidney failure [GFR category G5 chronic kidney disease (CKD)] <1 year were investigated. Primary endpoint was the development of kidney failure or eGFR decline ≥50% from the baseline. Kaplan-Meier and Cox proportional hazards analyses were performed. Results: Mean follow-up period was 33±29 months. Thirty-seven (33.3%) patients progressed to kidney failure and 4 (3.6%) patients developed eGFR decline ≥50% from the baseline after a median of 23 and 65 months, respectively. In multivariate Cox regression analysis, baseline levels of Hgb (HR:0.782, 95% CI 0.559-0.973, p=0.037), serum uric acid (HR:1.293, 95% CI 1.023-1.621, p=0.046), eGFR (HR:0.966, 95% CI 0.947-0.984, p=0.004) and intensity of C3 staining (HR:1.550, 95% CI 1.198-1.976, p=0.049) predicted primary endpoint. Serum uric acid level was associated independently with T score (β=0.303, p=0.005) in patients with eGFR>30 ml/min/m2. Conclusions: Hyperuricemia and the deposition of C3 are independent risk factors for IgAN progression.
The Use of Echocardiography in Certified Chest Pain Units: Results from the German Chest Pain Unit Registry
Authors: Breuckmann Frank , Hochadel Matthias , Voigtländer Thomas , Haude Michael , Schmitt Claus , Münzel Thomas , Giannitsis Evangelos , Mudra Harald , Heusch Gerd , Schumacher Burghard , Barth Sebastian , Schuler Gerhard , Hailer Birgit , Walther Dirk , Senges Jochen
Published: February 2016

Objectives: To analyze the current usage of transthoracic echocardiography (TTE) as a rapid, noninvasive tool in the early stratification of acute chest pain in certified German chest pain units (CPUs). Methods: A total of 23,997 patients were enrolled. Analyses comprised TTE evaluation rates in relation to clinical presentation, risk profile, left ventricular impairment, final diagnosis and invasive management. Critical times were assessed. Multivariable analyses for independent determinants for the use of TTE were performed. Results: TTE evaluation was available in CPUs in 70.1% of cases. It was associated with lower rates of invasive management in unstable angina pectoris (UAP) and with higher rates in patients with initially suspected non-cardiac origin of symptoms and/or reduced systolic function (p < 0.05). Non-ST-segment elevation acute coronary syndrome (NSTE-ACS) was an independent determinant favoring TTE evaluation [NSTE-myocardial infarction: odds ratio (OR) 1.62; UAP: OR 1.34; p < 0.001 for both]. Clinical signs of heart failure (OR 1.31; p < 0.001), referral by emergency medical service (OR 1.18; p < 0.001) and kidney failure (OR 1.16; p < 0.05) were independently associated with higher TTE rates. TTE did not delay door-to-balloon times. Conclusions: About two thirds of the patients admitted to certified CPUs received TTE evaluation, with the highest rates being in ACS patients, and thereby providing diagnostic information supporting or refuting further invasive management.
Prevalence and Outcomes of Head and Neck versus Non-Head and Neck Second Primary Malignancies in Head and Neck Squamous Cell Carcinoma: An Analysis of the Surveillance, Epidemiology, and End Results Database
Authors: Birkeland Andrew C. , Rosko Andrew J. , Chinn Steven B. , Prince Mark E. , Sun Gordon H. , Spector Matthew E.
Published: February 2016

Background/Aims: Patients with head and neck squamous cell carcinoma (HNSCC) are at risk for second primary malignancies (SPMs). The prevalence, distribution, and patient survival in head and neck versus non-head and neck SPMs are not fully elucidated. The objective of this study was to quantify the rate of SPMs in patients with HNSCC. Methods: This is a population-based cohort study using the Surveillance, Epidemiology, and End Results (SEER) database. Prevalence and location of SPMs, and survival data were analyzed. Results: There were 58,363 HNSCC patients, and the prevalence of HNSCC and non-HNSCC SPMs was 3.0% (1,746) and 8.8% (5,109), respectively. Overall survival (OS) was higher in patients with HNSCC SPMs compared to non-HNSCC SPMs (p < 0.001), with no difference in disease-specific survival. Patients with SPMs in the lung and esophagus had a worse OS (p < 0.001), and patients with SPMs in the prostate and breast had a better OS (p < 0.001). Conclusion: In HNSCC patients who develop SPMs, nearly 75% are non-HNSCC SPMs. Patients with non-HNSCC SPMs have a lower OS. Future clinical practice guidelines should take the risks and locations of SPM development into consideration for screening.
Psychosocioeconomic Precariousness, Cognitive Decline and Risk of Developing Dementia: A 25-Year Study
Authors: Ouvrard Camille , Meillon Céline , Dartigues Jean-François , Ávila-Funes José Alberto , Amieva Hélène
Published: February 2016

Background: This study investigates the relationship between psychosocioeconomic precariousness, cognitive decline and risk of developing dementia. Methods: The sample consisted of 3,710 subjects aged ≥65 years. Psychosocioeconomic precariousness was assessed with a ratio consisting of 8 self-reported items of poor socioeconomic status and psychosocial vulnerability. Results: Participants who were considered as precarious (n = 1,444) presented greater cognitive decline (β = -0.07; p = 0.0067) after adjusting for various confounders. They also had a 36% increased risk of developing dementia (hazard ratio 1.36, 95% confidence interval 1.17-1.57; p < 0.0001) over the 25-year follow-up period. Conclusion: Psychosocioeconomic precariousness is associated with greater cognitive decline and increased risk of developing dementia. This relationship can be explained in light of the concept of cognitive reserve and strengthens the need to consider psychosocioeconomic precariousness of elderly individuals in the definition of successful ageing policies.
Programmed Cell Death Genes Are Linked to Elevated Creatine Kinase Levels in Unhealthy Male Nonagenarians
Authors: Kim Sangkyu , Simon Eric , Myers Leann , Hamm L. Lee , Jazwinski S. Michal
Published: February 2016

Declining health in the oldest-old takes an energy toll for the simple maintenance of body functions. The underlying mechanisms, however, differ in males and females. In females, the declines are explained by loss of muscle mass; but this is not the case in males, in whom they are associated with increased levels of circulating creatine kinase. This relationship raises the possibility that muscle damage rather than muscle loss is the cause of the increased energy demands of unhealthy aging in males. We have now examined factors that contribute to the increase in creatine kinase. Much of it (60%) can be explained by a history of cardiac problems and lower kidney function, while being mitigated by moderate physical activity, reinforcing the notion that tissue damage is a likely source. In a search for genetic risk factors associated with elevated creatine kinase, the Ku70 gene XRCC6 and the ceramide synthase gene LASS1 were investigated because of their roles in telomere length and longevity and healthy aging, respectively. Single nucleotide polymorphisms in these two genes were independently associated with creatine kinase levels. The XRCC6 variant was epistatic to one of the LASS1 variants but not to the other. These gene variants have potential regulatory activity. Ku70 is an inhibitor of the proapoptotic Bax, while the product of Lass1, ceramide, operates in both caspase-dependent and -independent pathways of programmed cell death, providing a potential cellular mechanism for the effects of these genes on tissue damage and circulating creatine kinase.
Calreticulin Regulates Neointima Formation and Collagen Deposition following Carotid Artery Ligation
Authors: Zimmerman Kurt A. , Xing Dongqi , Pallero Manuel A. , Lu Ailing , Ikawa Masahito , Black Leland , Hoyt Kenneth L. , Kabarowski Janusz H. , Michalak Marek , Murphy-Ullrich Joanne E.
Published: February 2016

Background/Aims: The endoplasmic reticulum (ER) stress protein, calreticulin (CRT), is required for the production of TGF-β-stimulated extracellular matrix (ECM) by fibroblasts. Since TGF-β regulates vascular fibroproliferative responses and collagen deposition, we investigated the effects of CRT knockdown on vascular smooth-muscle cell (VSMC) fibroproliferative responses and collagen deposition. Methods: Using a carotid artery ligation model of vascular injury, Cre-recombinase-IRES-GFP plasmid was delivered with microbubbles (MB) to CRT-floxed mice using ultrasound (US) to specifically reduce CRT expression in the carotid artery. Results: In vitro, Cre-recombinase-mediated CRT knockdown in isolated, floxed VSMCs decreased the CRT transcript and protein, and attenuated the induction of collagen I protein in response to TGF-β. TGF-β stimulation of collagen I was partly blocked by the NFAT inhibitor 11R-VIVIT. Following carotid artery ligation, CRT staining was upregulated with enhanced expression in the neointima 14-21 days after injury. Furthermore, Cre-recombinase-IRES-GFP plasmid delivered by targeted US reduced CRT expression in the neointima of CRT-floxed mice and led to a significant reduction in neointima formation and collagen deposition. The neointimal cell number was also reduced in mice, with a local, tissue-specific knockdown of CRT. Conclusions: This work establishes a novel role for CRT in mediating VSMC responses to injury through the regulation of collagen deposition and neointima formation.
Effects of Obesity on Perivascular Adipose Tissue Vasorelaxant Function: Nitric Oxide, Inflammation and Elevated Systemic Blood Pressure
Authors: Aghamohammadzadeh Reza , Unwin Richard D. , Greenstein Adam S. , Heagerty Anthony M.
Published: February 2016

Introduction: Perivascular adipose tissue (PVAT) surrounds most vessels in the human body. Healthy PVAT has a vasorelaxant effect which is not observed in obesity. We assessed the contribution of nitric oxide (NO), inflammation and endothelium to obesity-induced PVAT damage. Methods: Rats were fed a high-fat diet or normal chow. PVAT function was assessed using wire myography. Skeletonised and PVAT-intact mesenteric vessels were prepared with and without endothelium. Vessels were incubated with L-NNA or superoxide dismutase (SOD) and catalase. Gluteal fat biopsies were performed on 10 obese and 10 control individuals, and adipose tissue was assessed using proteomic analysis. Results: In the animals, there were significant correlations between weight and blood pressure (BP; r = 0.5, p = 0.02), weight and PVAT function (r = 0.51, p = 0.02), and PVAT function and BP (r = 0.53, p = 0.01). PVAT-intact vessel segments from healthy animals constricted significantly less than segments from obese animals (p < 0.05). In a healthy state, there was preservation of the PVAT vasorelaxant function after endothelium removal (p < 0.05). In endothelium-denuded vessels, L-NNA attenuated the PVAT vasorelaxant function in control vessels (p < 0.0001). In obesity, incubation with SOD and catalase attenuated PVAT-intact vessel contractility in the presence and absence of endothelium (p < 0.001). In obese humans, SOD [Cu-Zn] (SOD1; fold change -2.4), peroxiredoxin-1 (fold change -2.15) and adiponectin (fold change -2.1) were present in lower abundances than in healthy controls. Conclusions: Incubation with SOD and catalase restores PVAT vasorelaxant function in animal obesity. In the rodent model, obesity-induced PVAT damage is independent of endothelium and is in part due to reduced NO bioavailability within PVAT. Loss of PVAT function correlates with rising BP in our animal obesity model. In keeping with our hypothesis of inflammation-induced damage to PVAT function in obesity, there are lower levels of SOD1, peroxiredoxin-1 and adiponectin in obese human PVAT.
Protection on Skin Aging Mediated by Antiapoptosis Effects of the Water Lily (Nymphaea Tetragona Georgi) via Reactive Oxygen Species Scavenging in Human Epidermal Keratinocytes
Authors: Park Gunhyuk , Sim Yeomoon , Lee Wonil , Sung Sang Hyun , Oh Myung Sook
Published: February 2016

Aims: The water lily (WL) is found in Europe, Asia, and North America. WL reportedly has various pharmacological activities that improve the activities of daily life in humans. To our knowledge, no previous study has investigated about the aspect of protection on skin aging due to the mitochondria-mediated antiapoptosis effects of WL rhizome extract (WLRE) on human epidermal keratinocytes. Methods: Human epidermal keratinocytes cells were treated with WLRE (100, 200, and 400 μg/ml) for 1 h and then with ultraviolet radiation B (UVB) (50 mJ/cm2) for another 23 h. The levels of lactate dehydrogenase, reactive oxygen species (ROS), MitoTracker, caspase-3, and glutathione were analyzed spectrophotometrically. Also, the levels of B-cell lymphoma 2 (Bcl-2) family proteins were determined with immunohistochemistry or western blotting. Results: We investigated the protective effects of WLRE against UVB-induced mitochondria-mediated apoptosis. WLRE significantly and concentrations-dependently reduced UVB-induced apoptotic cytotoxicity. Furthermore, WLRE decreased ROS generation, mitochondrial dysfunction, Bcl-2-associated X protein levels, and cytochrome c release from mitochondria while increasing Bcl-2 protein levels as assessed. Moreover, WLRE inhibited caspase-3 activity and expression, indicating the inhibition of the apoptotic cascade, and induced increased levels of total glutathione, heme oxygenase 1, and radical-scavenging activity. Conclusion: Together, these results demonstrate that WLRE can protect human epidermal keratinocytes against UVB-induced mitochondria-mediated apoptosis by regulating ROS-eliminating pathways.
The Clinical Presentation and Management of Systemic Light-Chain Amyloidosis in China
Authors: Huang Xiang-Hua , Liu Zhi-Hong
Published: February 2016

Background: Amyloidosis includes a group of diseases characterized by the extracellular deposition of various fibrillary proteins that can autoaggregate in a highly abnormal fibrillary conformation. The amyloid precursor protein of systemic light-chain (AL) amyloidosis is comprised of monoclonal light chains that are due to plasma cell dyscrasia. The clinical presentation of patients with AL amyloidosis varies from patient to patient. Current treatment strategies target the clone in order to decrease the production of the pathologic light chains. Recent advances in therapy have helped many patients with AL amyloidosis achieve hematologic and organ responses. Summary: AL amyloidosis is the most common type of systemic amyloidosis in China with increasing morbidity and a high mortality rate. The clinical presentation of AL amyloidosis is variable, and the median overall survival was found to be 36.3 months. The disease prognosis and risk stratification are linked to serialized measurement of cardiac biomarkers and free light chains. The treatment of AL amyloidosis is mainly based on chemotherapy and autologous hematopoietic stem cell transplantation (ASCT). The use of novel agents (thalidomide, lenalidomide, and bortezomib) alone and in combination with steroids and alkylating agents has shown efficacy and continues to be explored. Key Messages: AL amyloidosis is the most common type of systemic amyloidosis in China with increasing morbidity and a high mortality rate. The lack of prospective clinical trials using the current therapies is a challenge for evidence-based decision making concerning the treatment of AL amyloidosis. Facts from East and West: (1) AL amyloidosis is the most prevalent type of amyloidosis accounting for 65% of the amyloidosis-diagnosed patients in the UK and for 93% of the amyloidosis-diagnosed patients in China. The predisposition of men over women to develop AL amyloidosis might be higher in China than in Western countries (2:1 vs. 1.3:1). Both in the East and West, incidence increases with age. At the time of diagnosis, edema is twice as frequent and the proportion of renal involvement is higher in Chinese compared to Western patients. (2) Melphalan followed by ASCT is the current standard therapy but is restricted to eligible patients. The efficacy and safety of bortezomib combined with dexamethasone were proven in Western patients and recently confirmed in a Chinese cohort. Recent studies in China and the US indicate that bortezomib induction prior to ASCT increases the response rate. Thalidomide and lenalidomide have shown benefit, but toxicity and lack of clinical evidence exclude these agents from first-line therapy. The green tea extract epigallocatechin-3-gallate is under investigation as an inhibitor of AL amyloid formation and a compound that might dissolve amyloid.
Pitavastatin Exhibits Protective Effects on Podocytes Accompanied by BMP-7 Up-Regulation and Rho Suppression
Authors: Ohigashi Makoto , Imai Nobuyoshi , Toba Hiroe , Kobara Miyuki , Nakata Tetsuo
Published: February 2016

Background/Aims: Podocytes injury is involved in the development of diabetic nephropathy. This study was designed to confirm the reno- and podocyte-protective effects of pitavastatin in diabetic rats and clarify its mechanisms. Methods: Wistar rats were divided into 4 treatment groups: control, streptozotocin (STZ; 55 mg/kg)-induced diabetes, STZ with pitavastatin (10 mg/kg/day), and STZ with tempol (1 mmol/l). Results: STZ-induced diabetic rats exhibited increases in urinary protein excretion and plasma creatinine, and a decrease in creatinine clearance. Pitavastatin significantly improved these parameters without reducing cholesterol levels, whereas tempol did not. The treatment with STZ-enhanced renal fibrosis, mesangial proliferation, transforming growth factor (TGF)-β, MCP-1 and suppressed Rho in association with decrement of bone morphogenetic protein (BMP)-7 expression in renal cortex. Moreover, STZ decreased podocyte related factors, podocin and nephrin, and BMP-7 in podocytes. Pitavastatin significantly ameliorated all these indices. On the other hand, improvement by tempol was found only in TGF-β, MCP-1 and histological changes. Conclusion: Pitavastatin exhibited reno- and podocyte-protective effects accompanied by BMP-7 preservation and Rho suppression.
Isobolographic Analysis of Interaction for Three-Drug Combination of Carbamazepine, Phenobarbital and Topiramate in the Mouse Maximal Electroshock-Induced Seizure Model
Authors: Luszczki Jarogniew J.
Published: February 2016

Background/Aims: To characterize the anticonvulsant effects of a combination of 3 antiepileptic drugs (AEDs; i.e. carbamazepine (CBZ), phenobarbital (PB) and topiramate (TPM)) at the fixed-ratio of 1:1:1 in the mouse maximal electroshock (MES)-induced seizure model. Methods: Tonic hind limb extension (seizure activity) was evoked in adult male albino Swiss mice by a current (sine-wave, 25 mA, 500 V, 50 Hz, 0.2 s stimulus duration) delivered via auricular electrodes. Type I isobolographic analysis for parallel dose-response relationship curves (DRRCs) was used to analyze the 3-drug combination. Results: In the mouse MES model, all the studied AEDs (i.e. CBZ, PB and TPM) administered singly had their DRRCs parallel to each other. With type I isobolography for parallel DRRCs, a combination of CBZ, PB and TPM at the fixed-ratio of 1:1:1 exerted supra-additive (synergistic) interaction in the mouse MES model. Conclusions: Synergistic interaction among CBZ, PB and TPM at the fixed-ratio of 1:1:1 against MES-induced seizures is worthy of consideration in further clinical settings. All detailed calculations required to perform type I isobolographic analysis for the 3-drug combination were presented.
Interaction of αβ-Methylene ATP with the Cholinergic Twitch Response in the Guinea-Pig Ileum
Authors: Donnerer Josef , Liebmann Ingrid
Published: February 2016

In this study, direct effects of the P2X purinoceptor agonist αβ-methylene ATP (αβ-meATP) and effects on the cholinergic twitch response of the electrically stimulated longitudinal muscle-myenteric plexus (LMMP) strip of the guinea-pig ileum, were investigated. αβ-meATP (1, 3, and 10 µmol/l) induced short-lasting contractions on its own, followed by an inhibition of the twitch response during its presence in the organ bath. The inhibitor of small conductance Ca2+-activated K+ (SK) channels, apamin (100 nmol/l), prevented the inhibitory effect of αβ-meATP on the twitch response, whereas tetraethylammonium (300 µmol/l), a blocker of voltage-gated K+ channels and an inhibitor at nicotinic acetylcholine receptors, augmented the inhibitory effect of αβ-meATP on the twitch response. It is concluded, that there is a functional interaction between P2X receptors and nicotinic receptors in the LMMP strip, and that a major part of the excitatory input to the cholinergic motor neuron evoking the twitch response is purinergic and not nicotinergic.
Idiopathic Membranous Nephropathy: Diagnostic and Therapeutic Challenges
Authors: El-Husseini Amr , Saxon David , Jennings Stuart , Cornea Virgilius , Beck Laurence , Sawaya B. Peter
Published: February 2016

Background: In adults, membranous nephropathy (MN) is a major cause of nephrotic syndrome. While a majority of cases of MN are idiopathic, secondary forms can be seen in the setting of autoimmune disease, neoplasia, infection, and after being exposed to certain therapeutic agents. Both human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections could cause MN. However, the effect of coexisting HIV and HCV infection on the spectrum and progression of kidney disease as well as the effect of MN treatment on HIV and HCV infection are not well known. Methods: In this study, we describe a patient with hemophilia A and acquired HIV and HCV infections, a patient who developed severe nephrotic syndrome and for whom renal biopsy showed MN. Results: Patient responded well to adrenocorticotropic hormone gel without adversely affecting HIV or HCV infections. Conclusion: Adrenocorticotropic hormone gel might be useful in the management of complex cases of idiopathic MN.
Four Neuroendocrine Tumor Types and Neuroendocrine Carcinoma of the Duodenum: Analysis of 203 Cases
Authors: Vanoli Alessandro , La Rosa Stefano , Klersy Catherine , Grillo Federica , Albarello Luca , Inzani Frediano , Maragliano Roberta , Manca Rachele , Luinetti Ombretta , Milione Massimo , Doglioni Claudio , Rindi Guido , Capella Carlo , Solcia Enrico
Published: February 2016

Background: Several types of neuroendocrine neoplasms (NENs) have been described in the duodenal tract, from low-grade tumors (NETs) to high-grade neuroendocrine carcinomas (NECs). A comprehensive analysis of histology, hormonal profile and prognostic parameters of a sufficiently large duodenal NEN series to cover all main kinds of neoplasms is however lacking. Methods: We collected a retrospective series of 203 duodenal wall and ampullary region NENs, from six specialized endocrine pathology centers. All were characterized histopathologically and histochemically, and 190 were followed for a median of 9 years. Results: Twenty-seven poorly differentiated NECs, mostly from the ampullary region, were identified and shown to lead to patient demise in a median of 10 months. Among 176 NETs, four subtypes were characterized, including 20 gastrinomas, 37 ampullary-type somatostatin-producing NETs (ASTs), 12 gangliocytic paragangliomas (GPs) and 106 nonfunctioning NETs (nfNETs). ASTs and GPs were mostly localized in the ampullary/periampullary region, while gastrinomas and nfNETs were mainly from the proximal duodenum. ASTs and gastrinomas showed high rates of local infiltration (especially lymphoinvasion and deep duodenal wall/pancreatic tissue invasion) and lymph node metastasis, while nfNETs had significantly lower and more size-dependent local invasive potential. Disease-specific survival differed significantly between NETs and NECs, though not among NET subtypes. NET cases with distant metastases (n = 23) were significantly associated with larger size, higher proliferative grade, lymphovascular invasion, deep invasion and local lymph node metastasis. Conclusion: Our careful analysis of a large series of duodenal NENs identified five histologically and prognostically different histotypes of potential clinical relevance.
Cemitérios verticais, espaço urbano e meio ambiente: O novo discurso científico universitário de incentivo a verticalização do cemitério e cremação.
Authors: Thompson Barbara
Published: February 2016

􀀈􀂕􀂖􀂇􀀃􀂇􀂕􀂖􀂗􀂆􀂑􀀃􀂘􀂋􀂕􀂃􀀃􀂝􀀃􀂃􀂐􀂞􀂎􀂋􀂕􀂇􀀃􀂆􀂑􀀃􀂆􀂋􀂕􀂅􀂗􀂔􀂕􀂑􀀃􀂅􀂋􀂇􀂐􀂖Este estudo visa à análise do discurso científico que, nos últimos tempos, vem difundindo e incentivando a implantação de cemintérios verticais e de crematórios no Brasil. Entre 2000 e 2014, diversos artigos acadêmicos abordaram a contaminação das águas subterrâneas devido ao necrochorume produzido pela decomposição dos corpos. Assim, esta análise se apresenta como uma ponderação favorável à reestruturação dos cemitérios, enquanto parte da solução do problema de degradação ambiental. De antemão, faz-se necessário esclarecer a inviabilidade de conclusões categóricas, dada a atualidade do estudo – ainda em andamento. Visa-se, então, a fim de corroborar para a literatura específica de um estudo tão recente, a comparação entre o discurso higienista dos séculos XVIII e XIX, e o discurso científico hodierno da sustentabilidade ambiental. A relevância dessa comparação reside na configuração do espaço urbano, que leva em conta a forma como a sociedade concebe a morte. O discurso mais antigo, por exemplo, foi responsável pelo afastamento dos cemitérios da Igreja Católica em relação à cidade.  No atual contexto, por outro lado, a verticalização dos cemitérios é cientificamenete favorecida pelo fator meio ambiente. Tais investigações convergem para um desenredo que, embora aponte para valorização da sustentabilidade, apresenta-se ainda dicotômico: a defesa do meio ambiente é tão válida quanto necessária, todavia consiste num discurso científico que oculta a negação da morte, presente em nossa sociedade. O cemitério vertical extingue símbolos que promovem a memória dos mortos e dos grupos. Com a decadência do objeto material da memória, isto é, do túmulo monumental, os grupos que se relacionam com essa memória poderão ser enfraquecidos.
Figuras da Cisão – judaísmo e unificação no jovem Hegel
Authors: Eichenberger Hernandez Vivan
Published: February 2016

No presente texto reconstruiremos os escritos do jovem Hegel a respeito do judaísmo a fim de demonstrar o vínculo entre essa reflexão e a filosofia da unificação (Vereinigungsphilosophie). Os escritos a respeito do judaísmo se legitimam como um exemplar da estruturação da noção de cisão, conceito central do debate em torno da unificação, e servem como preparação e pressuposto dos escritos acerca do cristianismo em vista do correto posicionamento da figura de Jesus.
Steinernema beitlechemi n. sp., a new entomopathogenic nematode (Nematoda: Steinernematidae) from South Africa
Authors: Çimen Harun , Půža Vladimír , Nermuť Jiří , Hatting Justin , Ramakuwela Tshima , Faktorová Lucie , Hazir Selcuk
Published: February 2016

Steinernema beitlechemin. sp. is a new species of entomopathogenic nematode isolated from soil samples collected in Bethlehem, Free State province, South Africa. The infective juveniles ofS. beitlechemin. sp. are characterised by a body length of 696 (606-768) μm, position of nerve ring of 96 (86-105) μm from the head and lateral fields with six ridges (i.e., seven lines) in mid-body. First-generation males ofS. beitlechemin. sp. can be distinguished by a spicule length of 93 (88-100) μm and 12 pairs of genital papillae. First-generation females have a moderately protruding vulva and a rounded tail tip bearing one spine-like projection. The new species is further characterised by sequences of the ITS and partial 28S regions of the ribosomal DNA. Phylogenetic analyses showS. beitlechemin. sp. as a member of a strongly supported monophyletic clade with three other African species:S. sacchari,S. cameroonenseandS. nyetense.
Family Background and Education: China in Comparative Perspective
Authors: Evans M.D.R. , Kelley Jonathan , Yang Juhua
Published: February 2016

This paper investigates how the drastic educational reforms during the Communist period changed the effects of family background on education in China, in comparison to other nations. Data are from the Life Histories and Social Change in Contemporary China survey and the World Inequality Study; N=130,109 in 28 societies. Since World Warii, the mean number of years of education in China paralleled, at a lower level, the rises in Eastern European Communist countries and in Western market economies. Multi-level regression analysis shows that China’s educational level is not higher than would be predicted on the basis of worldwide patterns linking education togdpand family background. Overall, the drastic educational reforms of the Communist period do not seem to have raised educational attainments, contrary to the Rousseau/Marx understanding of the primacy of private property as a generator of social inequality.
Heidegger’s Breakdown: Health and Healing Under the Care of Dr. V.E. von Gebsattel
Authors: Mitchell Andrew J.
Published: February 2016

In 1946 Heidegger suffered a mental breakdown and received treatment by Dr. Viktor Emil Freiherr von Gebsattel. I explore the themes of health and help in Heidegger’s work before and after his treatment. I begin with Heidegger’s views on health while Rector in 1933–34 (1) and his abandonment of these views by war’s end (2). A short while later, Heidegger’s breakdown occurs and the treatment under Gebsattel begins (3). Soon after his treatment, Heidegger lauds what he terms a “broken-down” thinking, and I examine his contribution to a 1958 Festschrift for Gebsattel to better articulate such a thinking (4). Lastly, I take up Heidegger’s remarks on the role of the medical profession in a technological age from a 1962 speech (5). In presenting this material, I hope to shed new light on a little known aspect of Heidegger’s career and biography and to situate philosophically his relationship with Dr. Gebsattel.
Against the Sartrean Background: Ricoeur’s Lectures on Imagination
Authors: Geniusas Saulias
Published: February 2016

The paper addresses Ricoeur’s critique of Sartre in light of Ricoeur’s unpublished Lectures on Imagination. I argue that Ricoeur’s critique is twofold: hermeneutical and phenomenological. The hermeneutical critique relies on two central claims, namely, that Sartre fails to distinguish productive and reproductive imagination and that this distinction is language-based. I argue that neither claim is justified. The phenomenological critique casts doubts on Sartre’s sharp distinction between the real and the imaginary. It relies on Ricoeur’s phenomenology of painting, which offers an alternative way to distinguish productive and reproductive imagination. In place of a conclusion, I inquire into the reasons why Ricoeur, who considers imagination a theme of central philosophical importance, never wrote a separate book on imagination. I maintain that the reasons are methodological: the phenomenological and hermeneutical approaches to imagination are irreconcilable since the first one relies on the primacy of pre-predicative experience, while the second one is based on the primacy of language.