bluuebunny/crossref_metadata_2025 huggingface dataset:
In VitroInhibitory and Cytotoxic Activity of MFM 501, a Novel Codonopsinine Derivative, against Methicillin-ResistantStaphylococcus aureusClinical Isolates
Authors: Johari Saiful Azmi , Mohtar Mastura , Syed Mohammad Sharifah Aminah , Sahdan Rohana , Shaameri Zurina , Hamzah Ahmad Sazali , Mohammat Mohd Fazli
Published: February 2015

28 new pyrrolidine types of compounds as analogues for natural polyhydroxy alkaloids of codonopsinine were evaluated for their anti-MRSA activity using MIC and MBC value determination assay against a panel ofS. aureusisolates. One pyrrolidine compound, MFM 501, exhibited good inhibitory activity with MIC value of 15.6 to 31.3 μg/mL against 55S. aureusisolates (43 MRSA and 12 MSSA isolates). The active compound also displayed MBC values between 250 and 500 μg/mL against 58S. aureusisolates (45 MRSA and 13 MSSA isolates) implying that MFM 501 has a bacteriostatic rather than bactericidal effect against both MRSA and MSSA isolates. In addition, MFM 501 showed no apparent cytotoxicity activity towards three normal cell lines (WRL-68, Vero, and 3T3) with IC50values of >625 µg/mL. Selectivity index (SI) of MFM 501 gave a value of >10 suggesting that MFM 501 is significant and suitable for furtherin vivoinvestigations. These results suggested that synthetically derived intermediate compounds based on natural products may play an important role in the discovery of new anti-infective agents against MRSA.
Accurate Maximum Power Tracking in Photovoltaic Systems Affected by Partial Shading
Authors: Guerriero Pierluigi , Di Napoli Fabio , d’Alessandro Vincenzo , Daliento Santolo
Published: February 2015

A maximum power tracking algorithm exploiting operating point information gained on individual solar panels is presented. The proposed algorithm recognizes the presence of multiple local maxima in the power voltage curve of a shaded solar field and evaluates the coordinated of the absolute maximum. The effectiveness of the proposed approach is evidenced by means of circuit level simulation and experimental results. Experiments evidenced that, in comparison with a standard perturb and observe algorithm, we achieve faster convergence in normal operating conditions (when the solar field is uniformly illuminated) and we accurately locate the absolute maximum power point in partial shading conditions, thus avoiding the convergence on local maxima.
Developing Interventions for Frailty
Authors: Cameron Ian D. , Fairhall Nicola , Gill Liz , Lockwood Keri , Langron Colleen , Aggar Christina , Monaghan Noeline , Kurrle Susan
Published: February 2015

Frailty is a well-recognised, complex syndrome, predominantly affecting older people. Currently, there are two main conceptualizations of frailty: the phenotypic and the accumulated deficit models, with the phenotypic model being more widely applied in clinical research. Based on these models, we contend that a number of the phenotypic frailty components (weakness, slowness, and low energy expenditure) are potentially reversible. This paper outlines the results of a frailty research program. It summarizes the initial frailty treatment model and reports its effectiveness. Briefly, the effect of a twelve-month individually tailored multifactorial, interdisciplinary intervention targeting frailty was compared with usual care. The intervention reduced phenotypically defined frailty and improved mobility. Further, it is contended that there is evidence of substantial unmet need due to treatment fragmentation and the absence of a comprehensive approach for this population. Our paper then outlines the current stage of our research in which the model is now being extended to prefrailty. Interventions aimed at reversing the frailty syndrome or its consequences are only in their early stages. There is significant scope for future research to identify optimal management programs for frail older people.
The Potential Role of Polymethyl Methacrylate as a New Packaging Material for the Implantable Medical Device in the Bladder
Authors: Kim Su Jin , Choi Bumkyoo , Kim Kang Sup , Bae Woong Jin , Hong Sung Hoo , Lee Ji Youl , Hwang Tae-Kon , Kim Sae Woong
Published: February 2015

Polydimethylsiloxane (PDMS) is used in implantable medical devices; however, PDMS is not a completely biocompatible material for electronic medical devices in the bladder. To identify novel biocompatible materials for intravesical implanted medical devices, we evaluated the biocompatibility of polymethyl methacrylate (PMMA) by analyzing changes in the levels of macrophages, macrophage migratory inhibitory factor (MIF), and inflammatory cytokines in the bladder. A ball-shaped metal coated with PMMA or PDMS was implanted into the bladders of rats, and after intravesical implantation, the inflammatory changes induced by the foreign body reaction were evaluated. In the early period after implantation, increased macrophage activity and MIF in the urothelium of the bladder were observed. However, significantly decreased macrophage activity and MIF in the bladder were observed after implantation with PMMA- or PDMS-coated metal in the later period. In addition, significantly decreased inflammatory cytokines such as IL-1β, IL-6, and TNF-αwere observed with time. Based on these results, we suggest that MIF plays a role in the foreign body reaction and in the biocompatible packaging with PMMA for the implanted medical devices in the bladder.
The Protective Effect of Melatonin on Neural Stem Cell against LPS-Induced Inflammation
Authors: Song Juhyun , Kang So Mang , Lee Kyoung Min , Lee Jong Eun
Published: February 2015

Stem cell therapy for tissue regeneration has several limitations in the fact that transplanted cells could not survive for a long time. For solving these limitations, many studies have focused on the antioxidants to increase survival rate of neural stem cells (NSCs). Melatonin, an antioxidant synthesized in the pineal gland, plays multiple roles in various physiological mechanisms. Melatonin exerts neuroprotective effects in the central nervous system. To determine the effect of melatonin on NSCs which is in LPS-induced inflammatory stress state, we first investigated nitric oxide (NO) production and cytotoxicity using Griess reagent assays, LDH assay, and neurosphere counting. Also, we investigated the effect of melatonin on NSCs by measuring the mRNA levels of SOX2, TLX, and FGFR-2. In addition, western blot analyses were performed to examine the activation of PI3K/Akt/Nrf2 signaling in LPS-treated NSCs. In the present study, we suggested that melatonin inhibits NO production and protects NSCs against LPS-induced inflammatory stress. In addition, melatonin promoted the expression of SOX2 and activated the PI3K/Akt/Nrf2 signaling under LPS-induced inflammation condition. Based on our results, we conclude that melatonin may be an important factor for the survival and proliferation of NSCs in neuroinflammatory diseases.
Intramyocardial Hemorrhage: An Enigma for Cardiac MRI?
Authors: Calvieri Camilla , Masselli Gabriele , Monti Riccardo , Spreca Matteo , Gualdi Gian Franco , Fedele Francesco
Published: February 2015

Cardiovascular magnetic resonance (CMR) is a useful noninvasive technique for determining the presence of microvascular obstruction (MVO) and intramyocardial hemorrhage (IMH), frequently occurring in patients after reperfused myocardial infarction (MI). MVO, or the so-called no-reflow phenomenon, is associated with adverse ventricular remodeling and a poor prognosis during follow-up. Similarly, IMH is considered a severe damage after revascularization by percutaneous primary coronary intervention (PPCI) or fibrinolysis, which represents a worse prognosis. However, the pathophysiology of IMH is not fully understood and imaging modalities might help to better understand that phenomenon. While, during the past decade, several studies examined the distribution patterns of late gadolinium enhancement with different CMR sequences, the standardized CMR protocol for assessment of IMH is not yet well established. The aim of this review is to evaluate the available literature on this issue, with particular regard to CMR sequences. New techniques, such as positron emission tomography/magnetic resonance imaging (PET/MRI), could be useful tools to explore molecular mechanisms of the myocardial infarction healing process.
De NovoSequences ofHaloquadratum walsbyifrom Lake Tyrrell, Australia, Reveal a Variable Genomic Landscape
Authors: Tully Benjamin J. , Emerson Joanne B. , Andrade Karen , Brocks Jochen J. , Allen Eric E. , Banfield Jillian F. , Heidelberg Karla B.
Published: February 2015

Hypersaline systems near salt saturation levels represent an extreme environment, in which organisms grow and survive near the limits of life. One of the abundant members of the microbial communities in hypersaline systems is the square archaeon,Haloquadratum walsbyi. Utilizing a short-read metagenome from Lake Tyrrell, a hypersaline ecosystem in Victoria, Australia, we performed a comparative genomic analysis ofH. walsbyito better understand the extent of variation between strains/subspecies. Results revealed that previously isolated strains/subspecies do not fully describe the complete repertoire of the genomic landscape present inH. walsbyi. Rearrangements, insertions, and deletions were observed for the Lake Tyrrell derivedHaloquadratumgenomes and were supported by environmentalde novosequences, including shifts in the dominant genomic landscape of the two most abundant strains. Analysis pertaining to halomucins indicated that homologs for this large protein are not a feature common for all species ofHaloquadratum. Further, we analyzed ATP-binding cassette transporters (ABC-type transporters) for evidence of niche partitioning between different strains/subspecies. We were able to identify unique and variable transporter subunits from all five genomes analyzed and thede novoenvironmental sequences, suggesting that differences in nutrient and carbon source acquisition may play a role in maintaining distinct strains/subspecies.
The Value of Cerebral CT Angiography with Low Tube Voltage in Detection of Intracranial Aneurysms
Authors: Tang Kun , Li Rui , Lin Jie , Zheng Xiangwu , Wang Ling , Yin Weiwei
Published: February 2015

Objective. The aim of this study is to investigate the value of cerebral CT angiography (CTA) with low tube voltage in detection of intracranial aneurysms.Materials and Methods. A total of 294 consecutive patients with spontaneous subarachnoid hemorrhage (SAH) were enrolled in this study and randomly assigned into conventional voltage CTA (C-CTA) group and low voltage CTA (L-CTA) group. The objective and subjective image qualities were analyzed and compared between C-CTA and L-CTA groups. With the results of 3D-DSA as “gold standard,” the sensitivity, specificity, and accuracy of C-CTA and L-CTA in diagnosis of aneurysms were calculated and compared with each other.Results. Compared with group C-CTA, the CT dose index volume (CTDIvol) of group L-CTA reduced by 35.65%. There were no significant differences between C-CTA and L-CTA groups regarding objective and subjective image qualities. The sensitivity, specificity, and accuracy of L-CTA in diagnosis of aneurysms were 95.16%, 99.72%, and 99.42%, respectively. There were no significant differences in sensitivity, specificity, and accuracy between the C-CTA and L-CTA groups.Conclusion. The value of cerebral CTA with 100 kV low tube voltage in detection of intracranial aneurysms is significant, and it should be recommended as a routine scan method.
Metastatic Malignant Melanoma of the Inguinal Lymph Node with Unknown Primary Lesion
Authors: Eltawansy Sherif Ali , Panasiti Ryane , Hasanien Samaa , Lourdusamy Dennis , Sharon David
Published: February 2015

Background. Malignant melanoma could present with metastasis with unknown primary (MUP) and this happens in 2-3% according to the studies. Around 90% of melanomas have cutaneous origin, but still there are melanomas that could be found in visceral organs or lymph nodes with unknown primary site. Spontaneous regression of the primary site could be an explanation.Case Report. We report a 58-year-old Caucasian male who presented with a right sided swelling in the inguinal region. Surgery was performed and biopsy showed metastatic malignant melanoma. No cutaneous lesions were identified by history or physical examination. Work up could not detect the primary lesion and patient was started on radiotherapy and immunotherapy.Conclusion. We present a case of malignant melanoma of unknown primary presenting in an unusual place which is the inguinal lymph node. Theories try to explain the pathway of development of such tumors and one of the theories mentions that it could be a spontaneous regression of the primary cutaneous lesion. Another theory is that it could be from transformation of aberrant melanocyte within the lymph node. Prognosis is postulated to be better in this case than in melanoma with a known primary.
The Gastrointestinal Irritation of Polygala Saponins and Its Potential Mechanism In Vitro and In Vivo
Authors: Wen Li , Xia Nan , Tang PeiPei , Hong Yi , Wang ZiZhen , Liu YaJie , Liu YanJu , Liu JianJun , Li XiangQiong
Published: February 2015

Processing alters the pharmacological activity and reduces the gastrointestinal toxicity of the polygalae. To investigate the effect of processing, different glycosyl substituent products were tested. Hypnotic and subhypnotic doses of pentobarbital-induced sleep tests on mice were used to evaluate the sedative activity of polygala saponins with different glycosyl substituents; isolated gut motility experiment was employed to study excitatory effects of different polygala saponins; the gastrointestinal irritation effects of different polygala saponins were compared by measuring the levels of gastric PGE2 and intestinal TNF-αon mice. When compared with control, Onjisaponin B (OJB) and tenuifolin (TEN), but not senegenin (SNG), significantly increased the number of sleeping mice and prolonged the sleeping time (P<0.05); 80, 40, and 20 mg/L of OJB and 80 mg/L of TEN, but not SNG, obviously changed the amplitude and frequency of isolated jejunum (P<0.05); all the three compounds significantly decreased the level of gastric PGE2 but had no obvious influences on the reduction of intestinal TNF-αlevel. For sedative and hypnotic effects, OJB > TEN > SNG; for the protection form gastrointestinal irritation and damages, OJB > TEN > SNG. Therefore, in processing Polygala, glycosyl breaking may be related to the decline of pharmacological activity and gastrointestinal toxicity of polygala saponins.
The Effect ofCrocus sativusL. and Its Constituents on Memory: Basic Studies and Clinical Applications
Authors: Pitsikas Nikolaos
Published: February 2015

Memory-related disorders are a common public health issue. Memory impairment is frequent in degenerative diseases (such as Alzheimer’s disease and Parkinson disease), cerebral injuries, and schizophrenia. The dried stigma of the plantCrocus sativusL. (C. sativus), commonly known as saffron, is used in folk medicine for various purposes. Several lines of evidence suggest thatC. sativusand its constituents are implicated in cognition. Here we critically review advances in research of these emerging molecular targets for the treatment of memory disorders, and discuss their advantages over currently used cognitive enhancers as well remaining challenges. Current analysis has shown thatC. sativusand its components might be a promising target for cognition impairments.
Review on the Antimicrobial Resistance of Pathogens from Tracheal and Endotracheal Aspirates of Patients with Clinical Manifestations of Pneumonia in Bacolod City in 2013
Authors: Juayang Alain C. , Maestral Dominador G. , de los Reyes Gemma B. , Acosido Michael Angelo D. , Gallega Christine T.
Published: February 2015

Microbiological content specifically bacterial and fungal etiologies from tracheal aspirates in a tertiary hospital in Bacolod City was reviewed for baseline information. A total of 130 tracheal aspirates were subjected for culture to isolate and identify the pathogen and determine their susceptibilities to various antibiotics. Productions of certain enzymes responsible for antibiotic resistance like ESBL (Extended Spectrum Beta-Lactamase), metallo-β-lactamase, and carbapenemase were also studied. Out of 130 specimens, 69.23% were found to be positive for the presence of microorganisms. Most infections were from male patients aging 60 years and above, confined at the Intensive Care Units (ICU). Pseudomonas aeruginosa and Klebsiella pneumoniae were found to be the most frequent bacterial isolates and non-Candida albicans for fungal isolates, respectively. Among the various antibiotics tested, most isolates were found to be resistant to third generation cephalosporins and penicillins, but susceptible to aminoglycoside Amikacin. On the other hand, production of ESBL and carbapenemase was found to be common among members of Enterobacteriaceae especially K. pneumoniae.
Patients’ Compliance with Tuberculosis Medication in Ghana: Evidence from a Periurban Community
Authors: Danso Evans , Addo Isaac Yeboah , Ampomah Irene Gyamfuah
Published: February 2015

Globally, an estimated 2 million deaths occur every year as a result of tuberculosis. Ghana records over 46,000 new cases annually despite numerous efforts to curb the disease. One major challenge associated with the control of the disease is patients’ noncompliance with medication. Despite the noncompliance setback, not much information is available on the issue. This paper, therefore, examines patients’ compliance with medication at the Suhum Kraboa Coaltar District in Ghana. A cross-sectional descriptive study was carried out using interview schedules. Data were primarily retrieved from 40 treatment supporters, in addition to 110 previously treated persons registered in 2010 and 2011 with cases of pulmonary tuberculosis. Evidence from the study indicates that 63 percent of the previously treated persons complied with medication which is below the expected national target of at least 85 percent. However, those with treatment supporters significantly complied with medication. Depression, substance abuse, financial problems, and long duration of treatment were other issues that discouraged patients’ adherence to medication. Some patients also attributed supernatural explanations to the source of the disease which negatively affected compliance. Conclusively, future approaches aimed at controlling/eradicating tuberculosis in the district should consider counselling, economic empowerment packages, and detailed education for patients.
The G Allele of CaSR R990G Polymorphism Increases Susceptibility to Urolithiasis and Hypercalciuria: Evidences from a Comprehensive Meta-Analysis
Authors: Liu Kang , Wang Xiaolan , Ye Jiaxin , Qin Chao , Shao Pengfei , Zhang Wei , Li Jie , Yin Changjun
Published: February 2015

Background. The calcium-sensing receptor gene (CaSR) is a candidate to explain urolithiasis. A number of case-control studies were conducted to investigate associations between CaSR polymorphisms with risks of hypercalciuria and urolithiasis in humans. But the results were still inconsistent.Methods. A meta-analysis was performed to address this issue. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate the strength of associations between CaSR polymorphisms and the risk of urolithiasis. The pooled standardized mean difference (SMD) with 95% CI was used for the meta-analysis of CaSR polymorphisms and urine calcium concentration.Results. For urolithiasis association, the SS genotype of A986S polymorphism was a risk factor for urolithiasis in Asians and PHPT patients, but a protective factor in Caucasians. The GG genotype of R990 polymorphism was associated with an increased risk of urolithiasis, especially in Caucasians and healthy population. Regarding urine calcium concentration association, individuals with the G allele had a higher level of urine calcium than the noncarriers.Conclusions. This meta-analysis revealed that the G allele of CaSR R990G polymorphism increases susceptibility to urolithiasis and hypercalciuria. The A986S and Q1011E polymorphisms were associated with urolithiasis and hypercalciuria in specific populations.
Design and Implementation of Streaming Media Server Cluster Based on FFMpeg
Authors: Zhao Hong , Zhou Chun-long , Jin Bao-zhao
Published: February 2015

Poor performance and network congestion are commonly observed in the streaming media single server system. This paper proposes a scheme to construct a streaming media server cluster system based on FFMpeg. In this scheme, different users are distributed to different servers according to their locations and the balance among servers is maintained by the dynamic load‐balancing algorithm based on active feedback. Furthermore, a service redirection algorithm is proposed to improve the transmission efficiency of streaming media data. The experiment results show that the server cluster system has significantly alleviated the network congestion and improved the performance in comparison with the single server system.
Influence of El Niño Wind Stress Anomalies on South Brazil Bight Ocean Volume Transports
Authors: Assad Luiz Paulo de Freitas , Böck Carina Stefoni , Candella Rogerio Neder , Landau Luiz
Published: February 2015

The knowledge of wind stress variability could represent an important contribution to understand the variability over upper layer ocean volume transports. The South Brazilian Bight (SBB) circulation had been studied by numerous researchers who predominantly attempted to estimate its meridional volume transport. The main objective and contribution of this study is to identify and quantify possible interannual variability in the ocean volume transport in the SBB induced by the sea surface wind stress field. A low resolution ocean global circulation model was implemented to investigate the volume transport variability. The results obtained indicate the occurrence of interannual variability in meridional ocean volume transports along three different zonal sections. These results also indicate the influence of a wind driven large-scale atmospheric process that alters locally the SBB and near-offshore region wind stress field and consequently causes interannual variability in the upper layer ocean volume transports. A strengthening of the southward flow in 25°S and 30°S was observed. The deep layer ocean volume transport in the three monitored sections indicates a potential dominance of other remote ocean processes. A small time lag between the integrated meridional volume transports changes in each monitored zonal section was observed.
Predictors of Mortality and Prehospital Monitoring Limitations in Blunt Trauma Patients
Authors: Strnad Matej , Borovnik Lesjak Vesna , Vujanović Vitka , Pelcl Tine , Križmarić Miljenko
Published: February 2015

This study aimed at determining predictors of in-hospital mortality and prehospital monitoring limitations in severely injured intubated blunt trauma patients. We retrospectively reviewed patients’ charts. Prehospital vital signs, Injury Severity Score (ISS), initial Glasgow Coma Scale (GCS), Revised Trauma Score (RTS), arterial blood gases, and lactate were compared in two study groups: survivors (n=40) and nonsurvivors (n=30). There were no significant differences in prehospital vital signs between compared groups. Nonsurvivors were older (P=0.006), with lower initial GCS (P<0.001) and higher ISS (P<0.001), along with higher lactate (P<0.001) and larger base deficit (BD;P=0.006), whereas RTS (P=0.001) was lower in nonsurvivors. For predicting mortality, area under the curve (AUC) was calculated: for lactate 0.82 (P<0.001), for ISS 0.82 (P<0.001), and for BD 0.69 (P=0.006). Lactate level of 3.4 mmol/L or more was 82% sensitive and 75% specific for predicting in-hospital death. In a multivariate logistic regression model, ISS (P=0.037), GCS (P=0.033), and age (P=0.002) were found to be independent predictors of in-hospital mortality. The AUC for regression model was 0.93 (P<0.001). Increased levels of lactate and BD on admission indicate more severe occult hypoperfusion in nonsurvivors whereas vital signs did not differ between the groups.
Zr(IV), La(III), and Ce(IV) Chelates with 2-[(4-[(Z)-1-(2-Hydroxyphenyl)ethylidene]aminobutyl)-ethanimidoyl]phenol: Synthesis, Spectroscopic Characterization, and Antimicrobial Studies
Authors: El-ajaily M. M. , Abdullah H. A. , Al-janga Ahmed , Saad E. E. , Maihub A. A.
Published: February 2015

La(III), Zr(IV), and Ce(IV) chelates of 2-[(4-[(Z)-1-(2-hydroxyphenyl)ethylidene]aminobutyl)-ethanimidoyl]phenol were synthesized and characterized by using several physical techniques. The Schiff base was obtained by refluxing of o-hydroxyacetophenone with 1,4-butanediamine in 2 : 1 molar ratio. The CHN elemental analysis results showed the formation of the Schiff base and the chelates has been found to be in 1 : 1 [M : L] ratio. The molar conductance measurements revealed that all the chelates are nonelectrolytes. Structural elucidations of the ligand and its chelates were based on compatible analytical and spectroscopic evidences. The infrared spectral data revealed that the Schiff base coordinates to the metal ions through active sites which are –OH and –C=N groups. According to the electronic spectral data, an octahedral geometry was proposed for the chelates. The synthesized ligand and its metal chelates were screened for their antimicrobial activity against two Gram negative (Escherichia coli, Salmonella kentucky) and two Gram positive (Lactobacillus fermentum, Streptococcus faecalis) bacterial strains, unicellular fungi (Fusarium solani), and filamentous fungi (Aspergillus niger). The activity data showed that the metal chelates have antibacterial and antifungal activity more than the parent Schiff base ligand against one or more bacterial or fungi species. The results also indicated that the metal chelates are higher sensitive antimicrobial agents as compared to the Schiff base ligand.
FDA Approval: Idelalisib Monotherapy for the Treatment of Patients with Follicular Lymphoma and Small Lymphocytic Lymphoma
Authors: Miller Barry W. , Przepiorka Donna , de Claro R. Angelo , Lee Kyung , Nie Lei , Simpson Natalie , Gudi Ramadevi , Saber Haleh , Shord Stacy , Bullock Julie , Marathe Dhananjay , Mehrotra Nitin , Hsieh Li Shan , Ghosh Debasis , Brown Janice , Kane Robert C. , Justice Robert , Kaminskas Edvardas , Farrell Ann T. , Pazdur Richard
Published: February 2015

On July 23, 2014, the FDA granted accelerated approval to idelalisib (Zydelig tablets; Gilead Sciences, Inc.) for the treatment of patients with relapsed follicular B-cell non–Hodgkin lymphoma or relapsed small lymphocytic lymphoma (SLL) who have received at least two prior systemic therapies. In a multicenter, single-arm trial, 123 patients with relapsed indolent non–Hodgkin lymphomas received idelalisib, 150 mg orally twice daily. In patients with follicular lymphoma, the overall response rate (ORR) was 54%, and the median duration of response (DOR) was not evaluable; median follow-up was 8.1 months. In patients with SLL, the ORR was 58% and the median DOR was 11.9 months. One-half of patients experienced a serious adverse reaction of pneumonia, pyrexia, sepsis, febrile neutropenia, diarrhea, or pneumonitis. Other common adverse reactions were abdominal pain, nausea, fatigue, cough, dyspnea, and rash. Common treatment-emergent laboratory abnormalities were elevations in alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase, absolute lymphocytes, and triglycerides. Continued approval may be contingent upon verification of clinical benefit in confirmatory trials. Clin Cancer Res; 21(7); 1525–9. ©2015 AACR.

See related article by Gandhi et al., p. 1537
Pancreatic Cancer–Associated Diabetes Is an “Exosomopathy”
Authors: Korc Murray
Published: February 2015

Diabetes may be a consequence of pancreatic cancer, preceding cancer diagnosis. The underlying mechanism is the release of exosomes delivering adrenomedullin to β cells, inducing endoplasmic reticulum stress and perturbations in the unfolded protein response, leading to β-cell dysfunction and death. This knowledge could lead to improved diagnostic strategies for pancreatic cancer. Clin Cancer Res; 21(7); 1508–10. ©2015 AACR.

See related article by Javeed et al. p. 1722
New Blocking Antibodies against Novel AGR2–C4.4A Pathway Reduce Growth and Metastasis of Pancreatic Tumors and Increase Survival in Mice
Authors: Arumugam Thiruvengadam , Deng Defeng , Bover Laura , Wang Huamin , Logsdon Craig D. , Ramachandran Vijaya
Published: February 2015

Anterior gradient 2 (AGR2) promotes cancer growth, metastasis, and resistance to therapy via unknown mechanisms. We investigated the effects of extracellular AGR2 signaling through the orphan glycosylphosphatidylinositol-linked receptor C4.4A in pancreatic ductal adenocarcinoma (PDAC). Proliferation, migration, invasion, and apoptosis were measured using colorimetric, Boyden chamber, and FACS analyses. We developed blocking mAbs against AGR2 and C4.4A and tested their effects, along with siRNAs, on cancer cell functions and on orthotopic tumors in nude mice. Extracellular AGR2 stimulated proliferation, migration, invasion, and chemoresistance of PDAC cell lines. AGR2 interacted with C4.4A in cell lysates and mixtures of recombinant proteins. Knockdown of C4.4A reduced migration and resistance to gemcitabine. PDAC tissues, but not adjacent healthy pancreatic tissues, expressed high levels of AGR2 and C4.4A. AGR2 signaling through C4.4A required laminins 1 or 5 and integrin β1. Administration of antibodies against AGR2 and C4.4A reduced growth and metastasis and caused regression of aggressive xenograft tumors, leading to increased survival of mice. These data support a model in which AGR2 binds and signals via C4.4A in an autocrine loop and promotes the growth of pancreas tumors in mice. Blocking mAbs against AGR2 and C4.4A may have therapeutic potential against PDAC. Mol Cancer Ther; 14(4); 941–51. ©2015 AACR.
Genetic Variants of DICE1/INTS6 in German Prostate Cancer Families with Linkage to 13q14
Authors: Böhm Malte , Maier Christiane , Küfer Rainer , Röpke Albrecht , Vogel Walther , Wieland Ilse
Published: February 2015

Introduction: Prostate cancer is the most frequent malignancy found to occur in Caucasian men, but its genetic basis remains elusive. A prostate cancer-susceptibility locus has been identified on chromosome 13q14. The tumour suppressor gene deleted in cancer cells 1 (DICE1/INTS6) is located within this interval on 13q14.3. Materials and Methods: We performed mutation analysis of the DICE1/INTS6 gene in thirteen German prostate cancer families. Results and Conclusion: None of the patients harboured DICE1 mutations, and similar frequencies of the previously identified 13 bp deletion polymorphism in the DICE1 promoter were observed in the familial prostate cancer patients as compared with sporadic prostate cancer patients and controls. However, in one family with three affected brothers, the variations c.1215A>C (p.T405T) in exon 10 and c.2568A>G (p.S856S) in exon 17 were detected in a heterozygous pattern. In sporadic prostate cancer patients, variant c.2568A>G (p.S856S) was detected in 10/325 (3.08%) compared with 5/207 (2.42%) control samples (p > 0.05). We conclude that DICE1 appears to be involved in prostate cancer progression rather than in the initiation of prostate cancer.
Thioredoxin-Interacting Protein: A Potential Therapeutic Target for Treatment of Progressive Fibrosis in Diabetic Nephropathy
Authors: Tan Christina Y.R. , Weier Qi , Zhang Yuan , Cox Alison J. , Kelly Darren J. , Langham Robyn G.
Published: February 2015

Thioredoxin-interacting protein (TXNIP) is an endogenous inhibitor of the antioxidant thioredoxin, and a critical agent in the in vivo regulation of glucose. The well-described induction of TXNIP by high glucose may represent an important pathogenic trigger of complications arising in the diabetic environment, with sustained overexpression of TXNIP triggering the increased production of reactive oxygen species and collagen, both major contributors to the development of diabetic nephropathy (DN). To examine a possible therapeutic role for targeted TXNIP inhibition in DN, transgenic (mRen-2)27 rats were rendered diabetic with streptozotocin and then treated with 20 μM TXNIP deoxyribozyme (DNAzyme) delivered continuously over 12 weeks by an implanted osmotic mini-pump. Renal injury was measured using biochemical parameters of kidney function along with histological markers of damage. Catalytic activity of TXNIP DNAzyme was determined by TXNIP gene and peptide expression in the rat kidneys. TXNIP DNAzyme localization was demonstrated with a fluorescent-labelled TXNIP DNAzyme. A panel of markers was used to assess the extent of oxidative stress and renal fibrosis including superoxide level, nitrotyrosine staining, TGF-β1, NLRP3 and collagen IV expression. Fluorescent-labelled TXNIP DNAzyme was localized to tubulo-epithelial cells, but was not identified in glomeruli or endothelial cells. Elevated renal cortical TXNIP gene and protein expression seen in kidneys of DN animals were significantly attenuated by TXNIP DNAzyme (p < 0.05). Downstream markers of TXNIP activity, particularly oxidative stress, inflammasome signalling, tubulo-interstitial fibrosis and collagen deposition, were also attenuated in the tubulo-interstitium of DN rats treated with TXNIP DNAzyme. Consistent with the identified site of action of the DNAzyme, the effects of the TXNIP inhibition were limited to the tubulo-interstitial compartment. This study supports the role of TXNIP as an important mediator of progressive tubulo-interstitial fibrosis in DN, and also supports the notion of TXNIP inhibition as a potential new therapeutic target for DN.
Combination Therapy with Telmisartan and Oxacalcitriol Suppresses the Progression of Murine Adriamycin Nephropathy
Authors: Jeong Kyung Hwan , Asanuma Katsuhiko , Lydia Aida , Takagi Miyuki , Asao Rin , Kodama Fumiko , Asanuma Etsuko , Tomino Yasuhiko
Published: February 2015

Background: Blockade of the renin-angiotensin system plays a key role in suppressing the progression of renal diseases. It has not been well established whether this therapy provides additional effects when combined with vitamin D or its analog in a model of adriamycin (ADR)-induced nephropathy. Methods: We evaluated the effect of an angiotensin II subtype 1 receptor blocker (telmisartan) combined with a vitamin D analog (oxacalcitriol) on mice ADR-induced nephropathy (9.5 mg/kg single intravenous injection). We also tested immortalized murine podocytes to examine the effects on podocyte apoptosis. Results: Mice with ADR-induced nephropathy developed progressive albuminuria and glomerulosclerosis within 30 days accompanied by decreased expression of slit diaphragm (SD)-associated proteins (nephrin and podocin), reduced numbers of podocytes, and increased systolic blood pressure. Treatment with telmisartan or oxacalcitriol alone moderately ameliorated kidney injury. The combined treatment most effectively reduced the albuminuria and glomerulosclerosis. These effects were accompanied by the restoration of SD-associated proteins, reduction of podocyte apoptosis, and prevention of podocyte depletion in the glomeruli. Treatment with telmisartan, oxacalcitriol, and the combination therapy resulted in similar reductions in systolic blood pressure. In cultured murine podocytes, ADR stimulated the expression of Bax/Bcl-2 and apoptosis as determined by Hoechst 33342 staining. These changes were effectively inhibited by telmisartan or oxacalcitriol, but the combination treatment most effectively reduced these effects. Conclusions: These data demonstrated that application of a renin-angiotensin system blocker plus a vitamin D analog effectively prevented renal injury in ADR-induced nephropathy. The observed amelioration of renal injury may be partly attributable to antiapoptotic effects in podocytes.
Associated Aneurysms in Supratentorial Arteriovenous Malformations: Impact of Aneurysm Size on Haemorrhage
Authors: Stein Klaus-Peter , Wanke Isabel , Forsting Michael , Zhu Yuan , Moldovan Alexia Sabine , Dammann Phillipp , Sandalcioglu I. Erol , Sure Ulrich
Published: February 2015

Background: Associated aneurysms (AAs) are presumed to represent an additional risk factor for intracranial haemorrhage from cerebral arterio-venous malformations (AVMs). To date, efforts to capture their natural history, as well as to identify aneurysms with the potential capability of regression after AVM treatment remain incomprehensive. As the aneurysm size represents an important aspect for the treatment indication of incidental saccular aneurysms, this factor has rarely been encountered for the treatment of AAs so far. The present study aims to determine the angiographic and clinical characteristics of AAs with special focus on aneurysm size and their consequences for treatment. Methods: Patients with cerebral AVMs, treated in our department between 1990 and 2013, were analyzed retrospectively. Only patients with supratentorial AVMs and flow-related AAs of the feeding arteries were evaluated. Thus, patients harboring AVMs of the cerebellum and the brain stem and patients with intranidal, venous or remote aneurysms were excluded. Treatment strategies were assessed with special attention on bleeding source and on AA size. Results: In 59 of 409 patients (14%) with supratentorial AVMs, a total of 85 AAs of the feeding arteries were identified. 14 of 59 individuals (24%) presented with multiple AAs. Of 85 AA, 58 aneurysms (68%) were classified as proximal and 27 aneurysms (32%) as distal. The most common location of AAs was the middle cerebral artery (MCA, 39%), followed by the internal carotid artery (ICA, 27%) and the anterior cerebral artery (ACA, 21%). The mean AA size was 4.4 mm ± 3.4 mm. Intracranial haemorrhage was found in 21 of 59 patients (36%) with coexisting AAs. Among these, 10 individuals (17%) suffered from rupture of an AA, accounting for nearly half of all bleedings in this subgroup. Among those patients bearing a single AA, the size of ruptured aneurysms differed significantly from those unruptured (6.6 mm vs. 4.4 mm, p = 0.0046). Nineteen patients (32%) received treatment of 22 AAs, whereas sole AVM treatment was adopted in 26 patients (44%) and conservative management in 14 patients (24%). The main reasons to leave AAs untreated were the small AA size (<5 mm), poor clinical state or treatment denial by the patients. Conclusions: The aneurysm size of AAs in AVM influences the risk of haemorrhage. Therefore, the treatment of larger (diameter ≥5 mm) AAs should be considered, even if a treatment indication of the associated AVM is not given.
Guideline for the Diagnostic Pathway in Patients with Acute Abdominal Pain
Authors: Gans Sarah L. , Pols Margreet A. , Stoker Jaap , Boermeester Marja A. ,   on behalf of the expert steering group
Published: February 2015

Introduction: Diagnostic practice for acute abdominal pain at the Emergency Department varies widely and is mostly based on doctor's preferences. We aimed at developing an evidence-based guideline for the diagnostic pathway of patients with abdominal pain of non-traumatic origin. Methods: All available international literature on patients with acute abdominal pain was identified and graded according to their methodological quality by members of the multidisciplinary steering group. A guideline was synthetized, providing evidence-based recommendations together with considerations based on expertise of group members, patient preferences, costs, availability of facilities, and organizational aspects. Conclusions and Recommendations: Definition: Uniform terminology is needed in patients with acute abdominal pain to avoid difficulty in interpretation and ease comparison of findings between studies. We propose the use of the following definition for acute abdominal pain: pain of nontraumatic origin with a maximum duration of 5 days. Clinical diagnosis: Clinical evaluation is advised to differentiate between urgent and nonurgent causes. The diagnostic accuracy of clinical assessment is insufficient to identify the correct diagnosis but can discriminate between urgent and nonurgent causes. Patients suspected of nonurgent diagnoses can safely be reevaluated the next day. Based on current literature, no conclusions can be drawn on the differences in accuracy between residents and specialists. No conclusions can be drawn on the influence of a gynecological consultation. In patients suspected of an urgent condition, additional imaging is justified. CRP and WBC count alone are insufficient to discriminate urgent from nonurgent diagnoses. Diagnostic imaging: There is no place for conventional radiography in the work-up of patients with acute abdominal pain due to the lack of added value on top of clinical assessment. Computed tomography leads to the highest sensitivity and specificity in patients with acute abdominal pain. Positive predictive value of ultrasound is comparable with CT and therefore preferred as the first imaging modality due to the downsides of computed tomography; negative or inconclusive ultrasound is followed by CT. Based on current literature, no conclusions can be drawn on the added value of a diagnostic laparoscopy in the work-up of patients with acute abdominal pain. Antibiotic treatment should be started within the first hour after recognition of sepsis. Administration of opioids (analgesics) decreases the intensity of the pain and does not affect the accuracy of physical examination.
How Early Can Pancreatic Cancer Be Recognized A Case Report and Review of the Literature
Authors: Nai Qiang , Luo Hongxiu , Zhang Ping , Hossain Mohammed Amzad , Gu Ping , Sidhom Ibrahim W. , Mathew Teena , Islam Mohammed , Yousif Abdalla M. , Sen Shuvendu
Published: February 2015

The early symptoms of pancreatic cancer are often very vague. They may precede the diagnosis by years and go unrecognized. This makes pancreatic cancer one of the cancers with the worst survival rates. The progression rate of the early phase might be slower than previously thought. Here, we report a case where symptoms, including thromboembolism and new-onset diabetes mellitus, preceded the diagnosis of pancreatic cancer by 6 years or longer. The awareness of the early symptoms of pancreatic cancer is required for being vigilant and further diagnostic tests. A simple clinical model utilizing certain risk factors and symptoms for pancreatic cancer will help stratify the patients for further screening tests.
¿Aliados o enemigos? Las representaciones de Brasil en el debate público argentino durante la Guerra del Paraguay, 1864-1870
Authors: Baratta Maria Victoria
Published: February 2015

La Guerra del Paraguay generó la alianza entre dos tradicionales y fuertes enemigos, la Republica Argentina y el Imperio del Brasil. En este artículo nos proponemos analizar los lineamientos que justificaron ese acuerdo en el discurso público argentino y los que por otra parte se opusieron al mismo. Procuramos demostrar la importancia de las representaciones de Brasil en la formación de la identidad nacional argentina durante la guerra.
Reflexões sobre a imagem como gesto: apontamentos a partir do manuscrito Paris, BNF, Latin 9449
Authors: Aubert Eduardo Henrik
Published: February 2015

Este artigo propõe que compreender a imagem como gesto pode ser um modo frutífero de incrementar sua inteligibilidade, libertando a imagem do paradigma da representação, entendendo-a antes como veículo de ação social. Para tanto, estrutura-se em duas partes: uma primeira destinada à discussão historiográfica e conceitual direta, e uma segunda dedicada a um estudo de caso centrado no manuscrito Paris, BnF, latin 9449, originário de Nevers nos meados do século XI. Analisando as imagens desse manuscrito, em sua relação com o contexto do livro em que se inserem e com uma série de outros testemunhos nivernenses coevos, pretendemos avançar a factibilidade e o interesse de tal abordagem. 
Resenha do livro 'Uma história do roubo na Idade Média.'
Authors: Coelho Maria Filomena
Published: February 2015

CÂNDIDO DA SILVA, Marcelo. Uma história do roubo na Idade Média. Bens, normas e construção social no mundo franco. São Paulo: Ed. Fino Traço, 2014, 152 p.
Imbricações entre o ordinário e o excêntrico: literatura, feminismo e política na África do Sul nascente
Authors: Dulley Iracema
Published: February 2015

Resenha do livro

GOMES, Raquel. Uma feminista na contramão do colonialismo: Olive Schreiner, literatura e a construção da nação sul-africana, 1880-1902. São Paulo: Annablume, 2013.
Dinâmicas históricas de um porto centro-africano: Ambriz e o Baixo Congo nos finais do tráfico atlântico de escravos (1840 a 1870)
Authors: Wissenbach Maria Cristina Cortez
Published: February 2015

O objetivo deste artigo é o de seguir a história de Ambriz entre as décadas de 1840 e 1870, a fim de iluminar as questões de ordem política e econômica que mediavam as relações com o poder colonial baseada em Luanda, bem como revelar as características do comércio feito pelas sociedades africanas, especialmente por aquelas articuladas ao porto e ao Baixo Congo. Para além de uma abordagem puramente economicista, procura-se entender as atividades comerciais numa relação dialógica em que os setores africanos impõem regras e normas, e estas por sua vez, revelam concepções e formas de associação cuja lógica extrapola uma perspectiva essencialmente eurocêntrica.
Resenha do livro "A revolução americana"
Authors: Pandolfi Fernanda Cláudia
Published: February 2015

(primeiro parágrafo do texto)

O livro A Revolução Americana de Gordon Wood é um exemplo da importância dos livros de divulgação científica para difusão do conhecimento histórico. Publicado originalmente em inglês em 2002, o livro refina e aplica interpretações desenvolvidas pelo autor em trabalhos anteriores, por exemplo, Wood (1991), que lhe deu o prêmio Pulitzer de 1991, e Wood (1969). Com linguagem acessível ao público não especializado e capítulos dispostos cronologicamente, o autor analisa os efeitos que a Revolução Americana produziu na vida cotidiana daquela sociedade. Sua principal contribuição neste e em outros trabalhos tem sido a de criticar ou, em alguns casos, qualificar tanto análises que tendem a criar uma aura de divindade sobre a geração dos líderes revolucionários como os estudos produzidos principalmente na primeira metade do século XX, que tendem a privilegiar os aspectos de conflitos de classes na revolução. Autor de reconhecida produção acadêmica, Gordon Wood concluiu o doutorado em Harvard e leciona atualmente na Universidade Brown. 

 