bluuebunny/crossref_metadata_2025 huggingface dataset:
Roles and Clinical Applications of OPG and TRAIL as Biomarkers in Cardiovascular Disease
Authors: Bernardi Stella , Bossi Fleur , Toffoli Barbara , Fabris Bruno
Published: April 2016

Cardiovascular diseases (CVD) remain the major cause of death and premature disability in Western societies. Assessing the risk of CVD is an important aspect in clinical decision-making. Among the growing number of molecules that are studied for their potential utility as CVD biomarkers, a lot of attention has been focused on osteoprotegerin (OPG) and its ligands, which are receptor activator of nuclear factorκB ligand (RANKL) and TNF-related apoptosis-inducing ligand. Based on the existing literature and on our experience in this field, here we review what the possible roles of OPG and TRAIL in CVD are and their potential utility as CVD biomarkers.
Chemical Characteristics of Rainwater in Sumatera, Indonesia, during 2001–2010
Authors: Budiwati Tuti , Setyawati Wiwiek , Aries Tanti Dyah
Published: April 2016

The chemical composition of acid deposition shows that ammonium and chloride concentrations as the indicators of forest fires were higher than sulfate and nitrate in Sumatera areas such as Medan, Lampung, Palembang, and Kototabang. Chloride had higher concentration than sodium (Na+ sea originated) with the ratio value of Cl−/Na+ > 1.16 found in Medan and Palembang. Ionic compositions from the lowest to the highest concentration in Kototabang were H+ > Cl− > Na+ > NH4+ > nss-Ca2+ > K+ > NO3- > nss-SO42- > Mg2+ > ss-SO42- > ss-Ca2+. Acid rain takes place if the acid compounds such as sulfates, nitrates, and chlorides dominate. If the ratio value of NO3-/(nss-SO42- + NO3-) < 0.5 then it indicates that nss-SO42- is higher than NO3-. Between 2001 and 2010 it was found that the frequency value of NO3-/(nss-SO42- + NO3-) < 0.5 was 97% from annual mean of 34 pieces of data in Medan, Kototabang, Lampung, and Palembang. Forest fires influence was more dominant than anthropogenic activities in Kototabang, Palembang and Lampung, except in Medan. It showed that ammonium was higher than NO3- content if the ratio value of NO3-/(NH4+ + NO3-) < 0.5 was 62%. For the period 2001–2010 the frequency value of NO3-/(NH4+ + NO3-) < 0.5 was 74% from total 34 annual mean pieces of data in four locations, that is, Medan, Kototabang, Palembang, and Lampung.
Appraisal of Chicken Production with Associated Biosecurity Practices in Commercial Poultry Farms Located in Jos, Nigeria
Authors: Maduka C. V. , Igbokwe I. O. , Atsanda N. N.
Published: April 2016

A questionnaire-based study of chicken production system with on-farm biosecurity practices was carried out in commercial poultry farms located in Jos, Nigeria. Commercial and semicommercial farms had 75.3% and 24.5% of 95,393 birds on 80 farms, respectively. Farms using deep litter and battery cage systems were 69 (86.3%) and 10 (12.5%), respectively. In our biosecurity scoring system, a correct practice of each indicator of an event scored 1.00 and biosecurity score (BS) of each farm was the average of the scores of biosecurity indicators for the farm, giving BS of zero and 1.00 as absence of biosecurity and optimal biosecurity, respectively. Semicommercial farms had higher BS than commercial farms. The flock size did not significantly (p>0.05) affect the mean BS. Disease outbreaks correlated (r=-0.97) with BS, showing a tendency of reduction of disease outbreaks with increasing BS. Outbreaks were significantly (p<0.05) associated with deep litter system. In conclusion, the chicken production system requires increased drive for excellent biosecurity practices and weak points in the biosecurity could be ameliorated by extension of information to farmers in order to support expansion of chicken production with robust biosecurity measures that drastically reduce risk of disease outbreak.
The Importance of CD44 as a Stem Cell Biomarker and Therapeutic Target in Cancer
Authors: Thapa Ranjeeta , Wilson George D.
Published: April 2016

CD44 is a cell surface HA‐binding glycoprotein that is overexpressed to some extent by almost all tumors of epithelial origin and plays an important role in tumor initiation and metastasis. CD44 is a compelling marker for cancer stem cells of many solid malignancies. In addition, interaction of HA and CD44 promotes EGFR‐mediated pathways, consequently leading to tumor cell growth, tumor cell migration, and chemotherapy resistance in solid cancers. Accumulating evidence indicates that major HA‐CD44 signaling pathways involve a specific variant of CD44 isoforms; however, the particular variant almost certainly depends on the type of tumor cell and the stage of the cancer progression. Research to date suggests use of monoclonal antibodies against different CD44 variant isoforms and targeted inhibition of HA/CD44‐mediated signaling combined with conventional radio/chemotherapy may be the most favorable therapeutic strategy for future treatments of advanced stage malignancies. Thus, this paper briefly focuses on the association of the major CD44 variant isoforms in cancer progression, the role of HA‐CD44 interaction in oncogenic pathways, and strategies to target CD44‐overexpressed tumor cells.
Gallbladder Tuberculosis Mimicking Gallbladder Carcinoma: A Case Report and Literature Review
Authors: Liu Yao , Wang Kai , Liu Heng
Published: April 2016

Gallbladder tuberculosis (GT) is extremely rare, and it is difficult to differentiate from other gallbladder diseases, such as gallbladder carcinoma and Xanthogranulomatous Cholecystitis. A correct preoperative diagnosis of GT is difficult. The final diagnosis is usually made postoperatively according to surgical biopsy. Here, we report a case of a patient who underwent surgery with the preoperative diagnosis of gallbladder carcinoma. We reviewed the literature and present the process of differential diagnosis between two or more conditions that share similar signs or symptoms.
Feature Extraction and Selection Scheme for Intelligent Engine Fault Diagnosis Based on 2DNMF, Mutual Information, and NSGA-II
Authors: Liu Peng-yuan , Li Bing , Han Cui-e , Wang Feng
Published: April 2016

A novel feature extraction and selection scheme is presented for intelligent engine fault diagnosis by utilizing two-dimensional nonnegative matrix factorization (2DNMF), mutual information, and nondominated sorting genetic algorithms II (NSGA-II). Experiments are conducted on an engine test rig, in which eight different engine operating conditions including one normal condition and seven fault conditions are simulated, to evaluate the presented feature extraction and selection scheme. In the phase of feature extraction, theStransform technique is firstly utilized to convert the engine vibration signals to time-frequency domain, which can provide richer information on engine operating conditions. Then a novel feature extraction technique, named two-dimensional nonnegative matrix factorization, is employed for characterizing the time-frequency representations. In the feature selection phase, a hybrid filter and wrapper scheme based on mutual information and NSGA-II is utilized to acquire a compact feature subset for engine fault diagnosis. Experimental results by adopted three different classifiers have demonstrated that the proposed feature extraction and selection scheme can achieve a very satisfying classification performance with fewer features for engine fault diagnosis.
An Unusual Cause of Subacute Headache in a Patient Undergoing Chemotherapy for Advanced Testicular Nonseminomatous Germ Cell Tumour
Authors: Clarke Helen M. , Rao Ankit R. , Porfiri Emilio
Published: April 2016

Testicular (germ cell) cancer is a model of a chemocurable malignancy and tends to have a favourable prognosis even in advanced stages due to exquisite sensitivity to platinum-based chemotherapy. However, both acute and longer-term toxicities of multiagent chemotherapy remain significant as causes of morbidity, very occasionally mortality, and impaired quality-of-life. Here, we report a case of acute cerebral venous sinus thrombosis occurring within 10 days of chemotherapy initiation in a young patient without comorbidities, whose only predisposing factors were malignancy, chemotherapy, and perhaps mild dehydration. The clinical presentation was also unusual with headache of moderate severity only without focal or global neurologic deficits. We suspect that cisplatin may have had direct vasculotoxic effects. The patient recovered fully after short-duration anticoagulation but oncologists must remain aware of unusual and unpredictable complications of cytotoxic treatment.
Brucella Septic Arthritis: Case Reports and Review of the Literature
Authors: Elzein Fatehi Elnour , Sherbeeni Nisreen
Published: April 2016

Brucellosis is one of the commonest zoonotic infections worldwide. The disease is endemic in Saudi Arabia, the Middle East, and the Mediterranean area. Osteoarticular involvement is a frequent manifestation of brucellosis. It tends to involve the sacroiliac joints more commonly; however, spondylitis and peripheral arthritis are increasingly reported. Brucellosis can be overlooked especially in the presence of companion bacteria. Hence, it should be suspected in all patients with septic arthritis in endemic areas or in patients visiting such areas.
Role of TFEB Mediated Autophagy, Oxidative Stress, Inflammation, and Cell Death in Endotoxin Induced Myocardial Toxicity of Young and Aged Mice
Authors: Li Fang , Lang Fangfang , Zhang Huilin , Xu Liangdong , Wang Yidan , Hao Enkui
Published: April 2016

Elderly patients are susceptible to sepsis. LPS induced myocardial injury is a widely used animal model to assess sepsis induced cardiac dysfunction. The age dependent mechanisms behind sepsis susceptibility were not studied. We analyzed age associated changes to cardiac function, cell death, inflammation, oxidative stress, and autophagy in LPS induced myocardial injury. Both young and aged C57BL/6 mice were used for LPS administration. The results demonstrated that LPS induced more cardiac injury (creatine kinase, lactate dehydrogenase, troponin I, and cardiac myosin‐light chains 1), cardiac dysfunction (left ventricular inner dimension, LVID, and ejection fraction (EF)), cell death, inflammation, and oxidative stress in aged mice compared to young mice. However, a significant age dependent decline in autophagy was observed. Translocation of Transcription Factor EB (TFEB) to nucleus and formation of LC3‐II were significantly reduced in LPS administered aged mice compared to young ones. In addition to that, downstream effector of TFEB, LAMP‐1, was induced in response to LPS challenge in young mice. The present study newly demonstrates that TFEB mediated autophagy is crucial for protection against LPS induced myocardial injury particularly in aging senescent heart. Targeting this autophagy‐oxidative stress‐inflammation‐cell death axis may provide a novel therapeutic strategy for cardioprotection in the elderly.
A Hierarchical Load Balancing Strategy Considering Communication Delay Overhead for Large Distributed Computing Systems
Authors: Yang Jixiang , Ling Ling , Liu Haibin
Published: April 2016

Load balancing technology can effectively exploit potential enormous compute power available on distributed systems and achieve scalability. Communication delay overhead on distributed system, which is time-varying and is usually ignored or assumed to be deterministic for traditional load balancing strategies, can greatly degrade the load balancing performance. Considering communication delay overhead and its time-varying feature, a hierarchical load balancing strategy based on generalized neural network (HLBSGNN) is presented for large distributed systems. The novelty of the HLBSGNN is threefold: (1) the hierarchy with optimized communication is employed to reduce load balancing overhead for large distributed computing systems, (2) node computation rate and communication delay randomness imposed by the communication medium are considered, and (3) communication and migration overheads are optimized via forecasting delay. Comparisons with traditional strategies, such as centralized, distributed, and random delay strategies, indicate that the HLBSGNN is more effective and efficient.
Vascular Anomalies in Pancreaticoduodenectomy: A Lesson Learned
Authors: Ochoa Joana E. , Pointer David T. , Hamner John B.
Published: April 2016

It is essential to identify any variant anatomy prior to surgery as this could have a drastic effect on surgical planning. We describe a case in which two vascular irregularities, an Arc of Buhler and celiac stenosis, were identified on angiogram after completion of a pancreaticoduodenectomy. While there could have been catastrophic results from his surgery in the setting of celiac stenosis, the presence of the aberrant Arc of Buhler allowed this patient to emerge without any permanent morbidity.
Magnetic Resonance Imaging of the Small Bowel in Crohn’s Disease: A Systematic Review and Meta-Analysis
Authors: Ahmed Osman , Rodrigues David Mario , Nguyen Geoffrey C.
Published: April 2016

Introduction. Crohn’s disease is most commonly found in the terminal ileum and colonic region. Magnetic resonance has become a useful modality for assessing small bowel activity. In this study, we performed a systematic review and meta-analysis on the use of MR in detecting small bowel activity as well as extramural complications in Crohn’s patients.Methods. Two independent reviewers sorted through articles until October 2, 2014. We included both studies providing raw data for pooling and studies without raw data. Sensitivity, specificity, likelihood ratios, and 95% confidence intervals were calculated for each study.Results. There were 27 included studies, of which 19 were included in the pooled analysis. Pooled analysis of the 19 studies (1020 patients) with raw data revealed a sensitivity of 0.88 (95% CI 0.86 to 0.91) and specificity was 0.88 (95% CI 0.84 to 0.91). In regard to detecting stenosis, pooled sensitivity was 0.65 (95% CI 0.53 to 0.76) and specificity was 0.93 (95% CI 0.89 to 0.96).Conclusion. MR imaging provides a reliable alternative in detecting small bowel activity in patients with Crohn’s disease. Its advantages include high diagnostic accuracy and no radiation exposure while its disadvantages include high cost and limited availability.
Oxidative Nanopatterning of Titanium Surface Influences mRNA and MicroRNA Expression in Human Alveolar Bone Osteoblastic Cells
Authors: Wimmers Ferreira Maidy Rehder , Rodrigo Fernandes Roger , Freire Assis Amanda , Dernowsek Janaína A. , Passos Geraldo A. , Variola Fabio , Fittipaldi Bombonato-Prado Karina
Published: April 2016

Titanium implants have been extensively used in orthopedic and dental applications. It is well known that micro- and nanoscale surface features of biomaterials affect cellular events that control implant-host tissue interactions. To improve our understanding of how multiscale surface features affect cell behavior, we used microarrays to evaluate the transcriptional profile of osteoblastic cells from human alveolar bone cultured on engineered titanium surfaces, exhibiting the following topographies: nanotexture (N), nano+submicrotexture (NS), and rough microtexture (MR), obtained by modulating experimental parameters (temperature and solution composition) of a simple yet efficient chemical treatment with a H2SO4/H2O2solution. Biochemical assays showed that cell culture proliferation augmented after 10 days, and cell viability increased gradually over 14 days. Among the treated surfaces, we observed an increase of alkaline phosphatase activity as a function of the surface texture, with higher activity shown by cells adhering onto nanotextured surfaces. Nevertheless, the rough microtexture group showed higher amounts of calcium than nanotextured group. Microarray data showed differential expression of 716 mRNAs and 32 microRNAs with functions associated with osteogenesis. Results suggest that oxidative nanopatterning of titanium surfaces induces changes in the metabolism of osteoblastic cells and contribute to the explanation of the mechanisms that control cell responses to micro- and nanoengineered surfaces.
BRD4 Connects Enhancer Remodeling to Senescence Immune Surveillance
Authors: Tasdemir Nilgun , Banito Ana , Roe Jae-Seok , Alonso-Curbelo Direna , Camiolo Matthew , Tschaharganeh Darjus F. , Huang Chun-Hao , Aksoy Ozlem , Bolden Jessica E. , Chen Chi-Chao , Fennell Myles , Thapar Vishal , Chicas Agustin , Vakoc Christopher R. , Lowe Scott W.
Published: April 2016

Oncogene-induced senescence is a potent barrier to tumorigenesis that limits cellular expansion following certain oncogenic events. Senescent cells display a repressive chromatin configuration thought to stably silence proliferation-promoting genes while simultaneously activating an unusual form of immune surveillance involving a secretory program referred to as the senescence-associated secretory phenotype (SASP). Here, we demonstrate that senescence also involves a global remodeling of the enhancer landscape with recruitment of the chromatin reader BRD4 to newly activated super-enhancers adjacent to key SASP genes. Transcriptional profiling and functional studies indicate that BRD4 is required for the SASP and downstream paracrine signaling. Consequently, BRD4 inhibition disrupts immune cell–mediated targeting and elimination of premalignant senescent cells in vitro and in vivo. Our results identify a critical role for BRD4-bound super-enhancers in senescence immune surveillance and in the proper execution of a tumor-suppressive program.

Significance: This study reveals how cells undergoing oncogene-induced senescence acquire a distinctive enhancer landscape that includes formation of super-enhancers adjacent to immune-modulatory genes required for paracrine immune activation. This process links BRD4 and super-enhancers to a tumor-suppressive immune surveillance program that can be disrupted by small molecule inhibitors of the bromo and extra terminal domain family of proteins. Cancer Discov; 6(6); 612–29. ©2016 AACR.

See related commentary by Vizioli and Adams, p. 576.

This article is highlighted in the In This Issue feature, p. 561
Who Needs More than 1,000 ppm? The Epidemiology of High-Risk Populations
Authors: Mascarenhas Ana Karina
Published: April 2016

Good oral health is necessary to overall health and well-being. Most oral diseases, and in particular dental caries, are entirely preventable. However, in 2010, 3.9 billion people were globally affected by oral conditions, and the global prevalence of untreated caries in permanent teeth was 35.3%. The contemporary thinking is that dental caries starts as an infectious disease which then becomes a chronic disease. Public health measures and other caries-preventive approaches have resulted in dramatic reductions in dental caries across populations. However, in a given population, not all individuals have experienced these successes uniformly. High-risk populations, defined as those with a ‘higher-than-expected risk', exist for most diseases and conditions including caries. The global scientific literature suggests that these are the following: (1) minorities, (2) individuals with low-socioeconomic status and (3) other vulnerable populations such as the very young and elderly who continue to battle with oral health disparities by experiencing higher oral disease levels including dental caries. As the science and resources exist to prevent caries, it is essential to identify and target these high-risk individuals and populations.
High Fluoride Concentration Toothpastes for Children and Adolescents
Authors: Pretty Iain A.
Published: April 2016

The purpose of this review is to present the available evidence to support the use of dentifrices with high (>1,500 ppm) concentrations of fluoride to help in the prevention and treatment of caries in high-risk children and adolescents. Recent evidence from high-quality systematic reviews supports the dose-response relationship between caries prevention and fluoride levels, and there is good evidence from randomised clinical trials to support the use of high fluoride dentifrices. Such products are typically prescribed oral pharmaceuticals that require thorough risk assessment by the clinician and restricting use in those less than 6 years old to cases where the risk of severe morbidity caused by caries is greater than that of aesthetically objectionable fluorosis and which should mitigate the risk of fluorosis. Further research is required on the use of population- or community-based interventions using such products and currently, the evidence for dentifrices containing more than 2,900 ppm is weaker than for those containing 2,800 ppm or less.
Using High Fluoride Concentration Products in Public Policy: A Rapid Review of Current Guidelines for High Fluoride Concentration Products
Authors: Douglas Gail V.A. , Ramsdale Martin P. , Vinall-Collier Karen , Csikar Julia I.
Published: April 2016

Despite improvements in dental caries levels since the widespread introduction of fluoride toothpastes, it is still a disease which is considered to be a priority in many countries around the world. Individuals at higher risk of caries can be targeted with products with a high fluoride concentration to help reduce the amount and severity of the disease. This paper compares guidance from around the world on the use of products with a high fluoride concentration and gives examples of how guidance has been translated into activity in primary care dental practice. A rapid review of electronic databases was conducted to identify the volume and variation of guidance from national or professional bodies on the use of products with a high fluoride concentration. Fifteen guidelines published within the past 10 years and in English were identified and compared. The majority of these guidelines included recommendations for fluoride varnish use as well as for fluoride gels, while a smaller number offered guidance on high fluoride strength toothpaste and other vehicles. Whilst there was good consistency in recommendations for fluoride varnish in particular, there was sometimes a lack of detail in other areas of recommendation for other vehicles with a high fluoride concentration. There are good examples within the UK, such as the Childsmile project and Delivering Better Oral Health, which highlight that the provision of evidence-based guidance can be influential in directing scarce resources towards oral health improvements. Policy can be influenced by evidence-based national recommendations and used to help encourage dental professionals and commissioners and third-party payers to adopt higher levels of practices aimed at oral health improvement.
Plasma Desphospho-Uncarboxylated Matrix Gla Protein as a Marker of Kidney Damage and Cardiovascular Risk in Advanced Stage of Chronic Kidney Disease
Authors: Kurnatowska Ilona , Grzelak Piotr , Masajtis-Zagajewska Anna , Kaczmarska Magdalena , Stefańczyk Ludomir , Vermeer Cees , Maresz Katarzyna , Nowicki Michał
Published: April 2016

Background/Aims: Desphospho-uncarboxylated matrix Gla protein (dp-ucMGP) is formed as a result of vitamin K insufficiency. The aim of this study was to investigate the association between plasma dp-ucMGP, kidney function and cardiovascular risk factors before and after 9-months substitution of vitamin K2 in non-dialysis patients with chronic kidney disease (CKD) stage 4 and 5. Methods: 38 CKD patients were supplemented for 270±12 days with 90 µg vitamin K2 and 10 µg cholecalciferol or 10 µg cholecalciferol alone. At baseline and at follow-up circulating calcium, phosphate, lipids, hemoglobin, albumin and total protein, dp-ucMGP, osteoprotegerin, fetuin A, osteocalcin and fibroblast grown factor 23 (FGF-23) were assessed. Proteinuria was assessed in the first morning void. Results: Baseline plasma dp-ucMGP was 1018.6±498.3 pmol/l and was significantly higher in patients at stage 5 CKD (1388.3 ±505.4 pmol/l) than at stage 4 (885.1±419.7 pmol/l), p=0.04. Vitamin K2 supplementation resulted in a decrease of dp-ucMGP level by 10.7%. Plasma dp-ucMGP was positively associated with proteinuria, serum creatinine, PTH and FGF-23; and inversely associated with glomerular filtration rate, serum hemoglobin and albumin. Conclusions: High dp-ucMGP level, reflecting a poor vitamin K status seems to be associated with kidney damage and may be also a marker of cardiovascular risk in CKD patients. Supplementation with vitamin K2 may improve the carboxylation status of MGP.
Fluoride Varnish for Caries Prevention: Efficacy and Implementation
Authors: Bonetti Debbie , Clarkson Jan E.
Published: April 2016

Many reviews support fluoride varnish (FV) as a caries-inhibitory agent. Evidence from 6 Cochrane systematic reviews involving 200 trials and more than 80,000 participants further confirms the effectiveness of FV, applied professionally 2-4 times a year, for preventing dental caries in both primary and permanent teeth. The relative benefit of FV application seems to occur irrespective of baseline caries risk, baseline caries severity, background exposure to fluorides, use of fluoride toothpaste and application features such as prior prophylaxis, concentration of fluoride or frequency of application. While the efficacy of FV is acknowledged in clinical practice guidelines globally, the implementation of this recommendation may still be an issue. Factors that may facilitate FV application in the USA include Medicaid eligibility, relationships with dentists/community centers and strong cooperation and communication between physicians and support staff. Barriers include insufficient time to integrate oral health services into well-child visits, difficulty in applying FV (lack of skills/training) and resistance among colleagues and staff. Research in the UK/Scotland also suggests encouraging clinicians in their motivation to perform this treatment and addressing professional and parental concerns relating to possible negative consequences may be influential. Further research targeting cost-effectiveness and how FV in routine care may fit in with political agendas relating to, for example, inequalities in health care provision and access will also play a key part in stakeholder decisions to put resources into this issue.
Association between the IFNA1 (-2C→T) Polymorphism and Increased IFNAR1 Gene Expression Levels in Chronic Hepatitis B Infection
Authors: Santos Joelma Carvalho , de Deus Dayse Maria Vasconcelos , de Moura Izolda Maria Fernandes , Lopes Edmundo Pessoa , Alves Maria Rosileide Bezerra , Coêlho Maria Rosângela Cunha Duarte
Published: April 2016

Background: Single nucleotide polymorphisms and variant expression of some interferon (IFN) genes in individuals with chronic hepatitis B virus (HBV) infection might be related to higher viral load and disease complications. Thereby, whole blood samples of 208 patients (94 chronic HBV-infected patients and 114 HBV immune subjects) were analyzed to investigate the association between IFNG (-5A→G), IFNA1 (-2C→T) and IFNAR1 (-97T→C) genes with their expression levels and HBV viral load. Methods: Genotyping was performed by high-resolution melting analysis with quantitative PCR (qPCR). Viral load quantification and gene expression were also carried out using qPCR. Results: Chronic HBV-infected subjects with IFNA1 CT genotype and T allele were more likely to develop protection against HBV when compared to immune subjects with wild-type genotype (IFNA1 CT/CC: OR = 0.45, p = 0.01, and T/C allele: OR = 0.55; p < 0.01). In patients with IFNAR1 wild-type TT genotype, the expression levels of this receptor may explain the lower viral load (r2 = 0.40; p = 0.04) and protection against chronic infection. Conclusions: These findings suggest that the polymorphic variant of IFNA1 (-2) gene is associated with chronic HBV infection, and high expression levels of the IFNAR1 gene and low levels of IFNA1 might contribute to the pathogenesis of chronic infection in these subjects.
Clinical Experience with Ivabradine in Acute Heart Failure
Authors: Pascual Izco Marina , Alonso Salinas Gonzalo Luis , Sanmartín Fernández Marcelo , Del Castillo Carnevalli Hugo , Jiménez Mena Manuel , Camino López Asunción , Zamorano Gómez José Luis
Published: April 2016

Objective: Ivabradine has been shown to improve symptoms and to reduce rehospitalization and mortality in patients with severe chronic heart failure (HF). Its indication in acute HF is not clear. Acute HF patients could also benefit from HR reduction, as myocardial consumption and oxidative stress are related to tachycardia. Moreover, beta-blockers are contraindicated in cardiogenic shock and should not be initiated with congestive signs. Accordingly, we evaluated the role of ivabradine in acute HF patients. Methods: This was a retrospective analysis of 29 consecutive patients treated for acute HF in the Cardiac ICU, and for whom ivabradine was initiated during hospitalization between January 2011 and January 2014. All patients were in sinus rhythm and had a heart rate (HR) >70 bpm. Catecholamine use was necessary in 16 patients (57.1%) during the hospitalization, in 14 (87.5%) of these before ivabradine treatment. Results: Systolic blood pressure showed no variation during the first 24 h of ivabradine administration or at discharge. HR showed an absolute reduction of 10 bpm at 6 h (p < 0.001), 11 bpm at 24 h (p = 0.004) and 19 bpm (p < 0.001) at discharge. No episodes of significant bradycardia or hypotension were recorded after starting the drug. Conclusions: HR reduction with ivabradine in acute HF is well tolerated. It represents an attractive option, especially when there is excessive catecholamine-related tachycardia; this should be appropriately evaluated in randomized trials.
Saliva Urea Nitrogen Continuously Reflects Blood Urea Nitrogen after Acute Kidney Injury Diagnosis and Management: Longitudinal Observational Data from a Collaborative, International, Prospective, Multicenter Study
Authors: Raimann Jochen G. , Calice-Silva Viviane , Thijssen Stephan , Nerbass Fabiana Baggio , Vieira Marcos A. , Dabel Pascal , Evans Rhys , Callegari John , Carter Mary , Levin Nathan W. , Winchester James F. , Kotanko Peter , Pecoits-Filho Roberto
Published: April 2016

Background: Acute kidney injury (AKI) is a growing global concern and often reversible. Saliva urea nitrogen (SUN) measured by a dipstick may allow rapid diagnosis. We studied longitudinal agreement between SUN and blood urea nitrogen (BUN) and the diagnostic performance of both. Methods: Agreement between SUN and BUN and diagnostic performance to diagnose AKI severity in AKI patients in the United States and Brazil were studied. Bland-Altman analysis and linear mixed effects models were employed to test the agreement between SUN and BUN. Receiver operating characteristics statistics were used to test the diagnostic performance to diagnose AKI severity. Results: We found an underestimation of BUN by SUN, decreasing with increasing BUN levels in 37 studied patients, consistent on all observation days. The diagnostic performance of SUN (AUC 0.81, 95% CI 0.63-0.98) was comparable to BUN (AUC 0.85, 95% CI 0.71-0.98). Conclusion: SUN reflects BUN especially in severe AKI. It also allows monitoring treatment responses. Video Journal Club ‘Cappuccino with Claudio Ronco' at http://www.karger.com/?doi=445041.
Antithrombin Dublin (p.Val30Glu): a relatively common variant with moderate thrombosis risk of causing transient antithrombin deficiency
Authors: Navarro-Fernández José , Morena-Barrio María , Padilla José , Miñano Antonia , Bohdan Nataliya , Águila Sonia , Martínez-Martínez Irene , Sevivas Teresa , de Cos Carmen , Fernández-Mosteirín Nuria , Llamas Pilar , Asenjo Susana , Medina Pilar , Souto Juan , Overvad Kim , Kristensen Søren R. , Corra Javier , Vicente Vicente
Published: April 2016

The key haemostatic role of antithrombin and the risk of thrombosis associated with its deficiency support that the low incidence of antithrombin deficiency among patients with thrombosis might be explained by underestimation of this disorder. It was our aim to identify mutations in SERPINC1 causing transient antithrombin deficiency. SERPINC1 was sequenced in 214 cases with a positive test for antithrombin deficiency, including 67 with no deficiency in the sample delivered to our laboratory. The p.Val30Glu mutation (Antithrombin Dublin) was identified in five out of these 67 cases, as well as in three out of 127 cases with other SERPINC1 mutations. Genotyping in 1593 patients with venous thrombosis and 2592 controls from two populations, revealed a low prevalent polymorphism (0.3 %) that moderately increased the risk of venous thrombosis (OR: 2.9; 95 % CI: 1.07–8.09; p= 0.03) and identified one homozygous patient with an early thrombotic event. Carriers had normal anti-FXa activity, and plasma antithrombin was not sensitive to heat stress or proteolytic cleavage. Analysis of one sample with transient deficit revealed a type I deficiency, without aberrant or increased latent forms. The recombinant variant, which lacked the two amino-terminal residues, had reduced secretion from HEK-EBNA cells, formed hyperstable disulphidelinked polymers, and had negligible activity. In conclusion, p.Val30Glu by affecting the cleavage of antithrombin’s signal peptide, results in a mature protein lacking the N-terminal dipeptide with no functional consequences in normal conditions, but that increases the sensitivity to be folded intracellularly into polymers, facilitating transient antithrombin deficiency and the subsequent risk of thrombosis.
Antiphospholipid antibodies in a large population-based cohort: genome-wide associations and effects on monocyte gene expression
Authors: Müller-Calleja Nadine , Rossmann Heidi , Müller Christian , Wild Philipp , Blankenberg Stefan , Pfeiffer Norbert , Binder Harald , Beutel Manfred , Manukyan Davit , Zeller Tanja , Lackner Karl
Published: April 2016

The antiphospholipid syndrome (APS) is characterised by venous and/ or arterial thrombosis and pregnancy morbidity in women combined with the persistent presence of antiphospholipid antibodies (aPL). We aimed to identify genetic factors associated with the presence of aPL in a population based cohort. Furthermore, we wanted to clarify if the presence of aPL affects gene expression in circulating monocytes. Titres of IgG and IgM against cardiolipin, D2glycoprotein 1 (antiD2GPI), and IgG against domain 1 of D2GPI (anti-domain 1) were determined in approx. 5,000 individuals from the Gutenberg Health Study (GHS) a population based cohort of German descent. Genotyping was conducted on Affymetrix Genome-Wide Human SNP 6.0 arrays. Monocyte gene expression was determined in a subgroup of 1,279 individuals by using the Illumina HT-12 v3 BeadChip. Gene expression data were confirmed in vitro and ex vivo by qRT-PCR. Genome wide analysis revealed significant associations of anti-D2GPI IgG and APOH on chromosome 17, which had been previously identified by candidate gene approaches, and of anti-domain1 and MACROD2 on chromosome 20 which has been listed in a previous GWAS as a suggestive locus associated with the occurrence of anti-D2GPI antibodies. Expression analysis confirmed increased expression of TNFD in monocytes and identified and confirmed neuron navigator 3 (NAV3) as a novel gene induced by aPL. In conclusion, MACROD2 represents a novel genetic locus associated with aPL. Furthermore, we show that aPL induce the expression of NAV3 in monocytes and endothelial cells. This will stimulate further research into the role of these genes in the APS.
Immunisation against αIIbβ3 and αvβ3 in a type 1 variant of Glanzmann’s thrombasthenia caused by a missense mutation Gly540Asp on β3
Authors: Wihadmadyatami Hevi , Röder Lida , Berghöfer Heike , Bein Gregor , Heidinger Kathrin , Sachs Ulrich J. , Santoso Sentot
Published: April 2016

Treatment of bleeding in patients with Glanzmann’s thrombasthenia (GT) can be hampered by iso-antibodies against the αIIbβ3 integrin, which cause rapid clearance of transfused donor platelets. Type 1 GT patients with a total absence of αIIbβ3 from the platelet surface are known to be susceptible to form such isoantibodies. In this study, we describe a type 1 GT patient with a missense mutation (Gly540Asn) located in the EGF3 domain of the β3 integrin subunit. Cotransfection analysis in CHO cells demonstrates total absence of αIIbβ3 from the surface, based on inappropriate αIIb maturation. The patient’s serum was reactive with αIIbβ3 and αvβ3 integrins in a capture assay, when platelets and endothelial cells were used. Two specificities could be isolated from the patient’s serum, anti-αIIbβ3 and anti-αvβ3 isoantibodies. Both specificities did not interfere with platelet aggregation. In contrast, isoantibodies against αvβ3, but not against αIIbβ3, were able to disturb endothelial cell adhesion onto vitronectin, triggered endothelial cell apoptosis and interfered with endothelial tube formation. This intriguing finding may explain more recently observed features of fetal/neonatal iso-immune thrombocytopenia in children from type 1 GT mothers with intracranial haemorrhage, which could be related to anti-endothelial activity of the maternal antibodies. In conclusion, we give evidence that two isoantibody entities exist in type 1 GT patients, which are unequivocally different, both in an immunological and functional sense. Further research on the clinical consequences of immunisation against αvβ3 is required, predominantly in GT patients of childbearing age.

Supplementary Material to this article is available online at www.thrombosis-online.com.
Saxagliptin and Tadalafil Differentially Alter Cyclic Guanosine Monophosphate (cGMP) Signaling and Left Ventricular Function in Aortic‐Banded Mini‐Swine
Authors: Hiemstra Jessica A. , Lee Dong I. , Chakir Khalid , Gutiérrez‐Aguilar Manuel , Marshall Kurt D. , Zgoda Pamela J. , Cruz Rivera Noelany , Dozier Daniel G. , Ferguson Brian S. , Heublein Denise M. , Burnett John C. , Scherf Carolin , Ivey Jan R. , Minervini Gianmaria , McDonald Kerry S. , Baines Christopher P. , Krenz Maike , Domeier Timothy L. , Emter Craig A.
Published: April 2016

Background

Cyclic guanosine monophosphate‐protein kinase G‐phosphodiesterase 5 signaling may be disturbed in heart failure (
HF
) with preserved ejection fraction, contributing to cardiac remodeling and dysfunction. The purpose of this study was to manipulate cyclic guanosine monophosphate signaling using the dipeptidyl‐peptidase 4 inhibitor saxagliptin and phosphodiesterase 5 inhibitor tadalafil. We hypothesized that preservation of cyclic guanosine monophosphate
cGMP
signaling would attenuate pathological cardiac remodeling and improve left ventricular (
LV
) function.

Methods and Results

We assessed
LV
hypertrophy and function at the organ and cellular level in aortic‐banded pigs. Concentric hypertrophy was equal in all groups, but
LV
collagen deposition was increased in only
HF
animals. Prevention of fibrotic remodeling by saxagliptin and tadalafil was correlated with neuropeptide Y plasma levels. Saxagliptin better preserved integrated
LV
systolic and diastolic function by maintaining normal
LV
chamber volumes and contractility (end‐systolic pressure‐volume relationship, preload recruitable
SW
) while preventing changes to early/late diastolic longitudinal strain rate. Function was similar to the
HF
group in tadalafil‐treated animals including increased
LV
contractility, reduced chamber volume, and decreased longitudinal, circumferential, and radial mechanics. Saxagliptin and tadalafil prevented a negative cardiomyocyte shortening‐frequency relationship observed in
HF
animals. Saxagliptin increased phosphodiesterase 5 activity while tadalafil increased cyclic guanosine monophosphate levels; however, neither drug increased downstream
PKG
activity. Early mitochondrial dysfunction, evident as decreased calcium‐retention capacity and Complex
II
‐dependent respiratory control, was present in both
HF
and tadalafil‐treated animals.

Conclusions

Both saxagliptin and tadalafil prevented increased
LV
collagen deposition in a manner related to the attenuation of increased plasma neuropeptide Y levels. Saxagliptin appears superior for treating heart failure with preserved ejection fraction, considering its comprehensive effects on integrated
LV
systolic and diastolic function.
Renewal Theology and the ‘Common Good’
Authors: Cartledge Mark J.
Published: April 2016

This study investigates how an account informed by sources from the Pentecostal and Charismatic Renewal tradition is able to address the domain of public theology and in particular the concept of ‘common good’. It uses the key Renewal topic of the charismata (spiritual gifts) as expressed by Paul in 1 Cor. 12.8–10 and reflects theologically on how these gifts may be used and expressed by the church for the benefit of wider society and the ‘common good’. It argues that because the mission of the church is for the benefit of the world there is an inevitable ‘spillover’ in the use of the charismata that is rooted in the concept of redemption. By means of these gifts the church both blesses society and resists evil. This argument is given a broader framework by being placed in relation to the concepts of creation, church and the kingdom of God.
The Soviet State and Lineage Societies: Doctrine, Local Interactions, and Political Hybridization in Kazakhstan and Kirghizia During the 1920s and 1930s
Authors: Ohayon Isabelle
Published: April 2016

The Soviet state, in the wake of colonial policy, manipulated the existing hierarchical social order of the Kazakh and Kirghiz ssrs, playing groups against one another to ensure loyalty. Lineages, like nomad pastoralism, were one of the traits of backwardness that Sovietization sought to eliminate. Newly discovered local party reports reveal how the Soviet authorities perceived the kinship relations, how they suggested and disseminated the lineage categories, and how these categories were actualized in the government on the local scale.
New species and records of Ischnosoma Stephens (Coleoptera, Staphylinidae, Tachyporinae) from China
Authors: KOCIAN MATÚŠ , SCHÜLKE MICHAEL
Published: April 2016

More than 1100 specimens of the genus Ischnosoma Stephens, 1829, from China and Taiwan are revised. In all, 29 species and one subspecies are recognized. Seven new species are described and illustrated: Ischnosoma zipapertum sp. n., I. vicinum sp. n., I. foedum sp. n., I. involutum sp. n., I. yunnanum sp. n., I. abstrusum sp. n., and I. gemellum sp. n. Additional records of previously described species are reported. The distributions of all the species are mapped. Four species, Ischnosoma dicoidale discoidale (Sharp, 1888), I. faciatocolle (Champion, 1922), I. hieroboam Kocian, 2003, and I. rosti (Bernhauer, 1923), are recorded from China for the first time. A revised key to the Ischnosoma species of China and Taiwan is presented.
A new genus of Entomobryinae (Collembola, Entomobryidae) from Brazilian Amazon with body scales and dental spines
Authors: CIPOLA NIKOLAS GIOIA , MORAIS JOSÉ WELLINGTON DE , BELLINI BRUNO CAVALCANTE
Published: April 2016

A new monotypic genus of Entomobryinae from Brazilian Amazon is described and illustrated. Amazhomidia gen. nov. is similar to other genera of the subfamily, especially to Sinhomidia Zhang, in presence of apically pointed scales on body dorsally and spines on dens. It differs from all other genera of Entomobryinae by the combination of: bifurcate prelabral chaetae, cephalic groove with scale-like chaetae and two transverse rows macrochaetae present on anterior central region of the abdominal IV segment. Amazhomidia ducke sp. nov., the type species of the new genus is described. An identification key to the genera of Entomobryidae with scales and dental spines is also provided.
The Pselaphinae (Coleoptera: Staphylinidae) of Madagascar. IV. Contribution to the knowledge of subtribes Hoplitoxenina and Dimerometopina with description of a new species of Hadrophorus Fairmaire, 1898
Authors: HLAVÁČ PETER , NAKLÁDAL OTO
Published: April 2016

The subtribe Dimerometopina Célis, 1970 is reestablished. A key and catalogue of the species of subtribes Hoplitoxenina and Dimerometopina is provided; a key to species of the genus Hadrophorus Fairmaire, 1898 is also given. Hadrophorus martinkae sp. n. from Madagascar, Montagne d’Ambre is described. New records for Hadrophorus spinipennis Célis, 1969 (Madagascar, Zombitse N.P.) and Hoplitoxenus joannae Jeannel, 1960 (Cameroon and Gabon, first record) are provided.
Grass-thrips of the genus Oelschlaegera (Thysanoptera: Thripidae), with the first description of a male
Authors: FEKRAT LIDA , HOSSEININEJAD MARZIYEH , DERAKHSHAN ALI , MINAEI KAMBIZ
Published: April 2016

The Chirothrips-like species are grass-living members of the Thysanoptera family Thripidae. All of these species were assigned to the genus Chirothrips Haliday (1836) until Hood (1954) erected Agrostothrips for a single species from South Africa, and Knechtel (1960) described a new monotypic genus Ereikethrips from Romania. An extensive identification key to the 52 species of Chirothrips then known was published by zur Strassen (1960), and the generic classification remained stable for the next 30 years. However, Bhatti (1990) erected five new genera for several species of this genus (Afrothripella, Arorathrips, Konothrips, Longothrips and Oelschlaegera). Bhatti also included three further species in Agrostothrips, but Minaei & Mound (2010) regarded Agrostothrips as a synonym, and returned all four species to Chirothrips. In the most recent study of the group, Nakahara & Foottit (2012) added one monobasic genus, Unilobothrips, and provided an identification system to the 36 Chirothrips-group species known from the Americas. Thus, eight genera are currently included in this genus group (Table 1).
The Mean Air Flow as Lagrangian Dynamics Approximation and Its Application to Moist Convection
Authors: Pauluis Olivier M.
Published: April 2016

This paper introduces the Mean Airflow as Lagrangian Dynamics Approximation (MAFALDA), a new method designed to extract thermodynamic cycles from numerical simulations of turbulent atmospheric flows. This approach relies on two key steps. First, mean trajectories are obtained by computing the mean circulation using height and equivalent potential temperature as coordinates. Second, thermodynamic properties along these trajectories are approximated by using their conditionally averaged values at the same height and θe. This yields a complete description of the properties of air parcels that undergo a set of idealized thermodynamic cycles.

MAFALDA is applied to analyze the behavior of an atmosphere in radiative–convective equilibrium. The convective overturning is decomposed into 20 thermodynamic cycles, each accounting for 5% of the total mass transport. The work done by each cycle can be expressed as the difference between the maximum work that would have been done by an equivalent Carnot cycle and a penalty that arises from the injection and removal of water at different values of its Gibbs free energy. The analysis indicates that the Gibbs penalty reduces the work done by all thermodynamic cycles by about 55%. The cycles are also compared with those obtained for doubling the atmospheric carbon dioxide, which in the model used here leads to an increase in surface temperature of about 3.4 K. It is shown that warming greatly increases both the energy transport and work done per unit mass of air circulated. As a result, the ratio of the kinetic energy generation to the convective mass flux increases by about 20% in the simulations.