bluuebunny/crossref_metadata_2025 huggingface dataset:
Blood Levels of Oxidant/Antioxidant Parameters in Rats Infected with Toxoplasma gondii
Authors: Bahrami Somayeh , Shahriari Ali , Tavalla Mehdi , Azadmanesh Somayeh , Hamidinejat Hossein
Published: September 2016

Toxoplasmosis is a common parasitic infection in the world. Since increased free radicals and oxidative stress are reported in many parasitic diseases the purpose of the present study was to evaluate the oxidative stress in acute and chronic toxoplasmosis. RH strains of Toxoplasma tachyzoites were used in the present study. Twenty‐five female rats were infected with the parasite while 25 other rats were as the control group that received normal saline. Zero‐, 5‐, 7‐, 10‐, and 45‐day postinfection (DPI) blood samples were taken. Some parameters related to oxidant and antioxidants such as antioxidant enzymes, malondialdehyde, and total antioxidant capacity were measured. On day 7 after infection, GPX activity and GSH level were significantly increased and in the mentioned day the amount of total antioxidant capacity was significantly reduced. In other cases, there were no significant differences between the groups in different days. Overall, based on the results it seems that, on day 7 after infection, in infected rats responses to oxidative stress were triggered and led to decrease of total antioxidant capacity. Furthermore, glutathione was increased to cope with stress. It seems that probably antioxidant defense system entered the infection to the chronic phase and changed the parasites stage.
Myeloid Neoplasms with t(5;12) and ETV6-ACSL6 Gene Fusion, Potential Mimickers of Myeloid Neoplasm with PDGFRB Rearrangement: Case Report with Imatinib Therapy and Review of the Literature
Authors: De Luca-Johnson Javier , Ninfea Jose I. Ruades , Pearson Lauren , Conant Joanna , Bryant Ronald , Zakai Neil A. , Tang Mary E.
Published: September 2016

We report the second case of ETV6-ACSL6 associated myeloproliferative neoplasm that has received a full course of imatinib therapy. The patient was a 51-year-old previously healthy man who presented with three months of worsening dyspnea and was found to have a white count of 216,000/cmm, of which 84% were eosinophil lineage. Cytogenetic analysis revealed a t(5;12)(q31~33;p13). FISH was negative for PDGFRB rearrangement but additional FISH testing demonstrated an ACSL6 rearrangement. ETV6-ACSL6 gene fusion is a rare abnormality that most often presents as a myeloproliferative-type disorder with prominent eosinophilia or basophilia. Review of the literature yielded a total of 11 previous cases. This gene fusion results in a t(5;12)(q31~33;p13) that mimics the t(5;12) found in ETV6-PDGFRB neoplasms. Identification of the fusion genes involved in t(5;12) in eosinophilia-associated myeloproliferative disorders is crucial to direct an effective treatment plan. In particular, while tyrosine kinase inhibitor therapy is effective in patients with PDGFRB rearrangement, there is little information on imatinib efficacy in patients with ETV6-ACSL6 gene fusion. Our patient was found to be nonresponsive to imatinib therapy.
Estimation of Cyclic Shift with Delayed Correlation and Matched Filtering in Time Domain Cyclic-SLM for PAPR Reduction
Authors: Pamungkasari Panca Dewi , Sanada Yukitoshi
Published: September 2016

Time domain cyclic-selective mapping (TDC-SLM) reduces the peak-to-average power ratio (PAPR) in OFDM systems while the amounts of cyclic shifts are required to recover the transmitted signal in a receiver. One of the critical issues of the SLM scheme is sending the side information (SI) which reduces the throughputs in wireless OFDM systems. The proposed scheme implements delayed correlation and matched filtering (DC-MF) to estimate the amounts of the cyclic shifts in the receiver. In the proposed scheme, the DC-MF is placed after the frequency domain equalization (FDE) to improve the accuracy of cyclic shift estimation. The accuracy rate of the propose scheme reaches 100% at Eb/N0 = 5 dB and the bit error rate (BER) improves by 0.2 dB as compared with the conventional TDC-SLM. The BER performance of the proposed scheme is also better than that of the conventional TDC-SLM even though a nonlinear high power amplifier is assumed.
Possible Relation between Lack of Posterior Vitreous Detachment and Severe Endogenous Endophthalmitis
Authors: Umazume Kazuhiko , Suzuki Jun , Usui Yoshihiko , Wakabayashi Yoshihiro , Goto Hiroshi
Published: September 2016

Purpose. Endogenous endophthalmitis (EE) is a rare ocular disease caused by bacterial or fungal infection of intraocular spaces by hematogenous spread of pathogens from distant infectious loci in the body. We investigated the clinical characteristics and management of eyes with EE in ten consecutive patients. Methods. Ten patients (10 eyes) with EE treated at Tokyo Medical University Hospital in 2014 were reviewed. We retrospectively studied the causative organisms, systemic complications, pre/postoperative mean best-corrected visual acuity (BCVA), and status of posterior vitreous detachment (PVD). Results. The 10 patients comprised 8 males and 2 females, with mean age of 71.2 years. The causative organisms were bacteria in 6 eyes and fungi in 4 eyes. Systemic complications included septicemia or disseminated intravascular coagulation in 5 patients and diabetes mellitus in 4 patients. Postoperative BCVA was improved by 0.2log⁡MAR or greater in 4 eyes and decreased in 4 eyes. Vitrectomy was performed in all eyes, and 4 required multiple surgeries. During vitrectomy, PVD was absent in 8 eyes, 4 of which showed retinal necrosis. The mean age of patients with no PVD was 71.2 years. Conclusion. Despite an advanced age, PVD was absent in the majority of patients with EE. PVD may be related to the pathogenesis and aggravation of EE.
Effects of Hot Water Extracts from Polygonum multiflorum on Ovariectomy Induced Osteopenia in Mice
Authors: Hwang Yun-Ho , Kang Kyung-Yun , Kim Jong-Jin , Lee Sung-Ju , Son Young-Jin , Paik Soo-Heui , Yee Sung-Tae
Published: September 2016

Polygonum multiflorum (PM), a traditional Chinese medicine, is used to treat various diseases including nonalcoholic fatty liver disease and hyperlipidemia. However, the influence of PM on osteoporosis in animals is unclear. The present study investigated the antiosteoporotic effect of PM on bone mass in ovariectomized (OVX) mice and its possible mechanism of action. Twenty‐five female C3H/HeN mice were divided into five groups of five mice as follows. Sham‐operated control mice received daily oral gavage of an equal volume of water, and OVX mice received daily oral gavage of water or an injection of β‐estradiol or PM for 6 weeks. Administration of PM significantly suppressed body weight and organs weight and increased weight and length of bone compared with the OVX group. Treatment with PM reversed osteopenia in OVX mice, thereby improving the bone morphometric parameters. Moreover, histological analysis using hematoxylin and eosin staining showed that PM inhibited OVX‐induced bone loss. Serum estradiol and bone alkaline phosphatase levels were significantly decreased in the OVX group, with the levels increasing with PM treatment. In addition, tartrate‐resistant acid phosphatase activity was inhibited by PM in OVX mice. These results suggest that PM is effective in preventing bone loss in OVX mice.
Bacteriostatic Substrate by Conductivity Method and Electric Spark Discharge Method Combined with Electrospinning for Silver Dressing
Authors: Tseng Kuo-Hsiung , Chang Chaur-Yang , Chung Meng-Yun , Tang Ya-Lan
Published: September 2016

This study uses the conductivity method, Electric Spark Discharge Method, and the electrospinning technique to develop a better silver-based antibacterial agent. The preparation process is free of chemical substances and also conforms to the green energy-saving process. The silver iodide was prepared in an iodine agar medium by using the conductivity method. Multiple bacteriostasis experiments showed that the molds grew in the position with iodine of the culture medium after 6 days, as well as in the position with silver iodide after 10 days. The results prove that silver iodide has better bacteriostatic ability than povidone iodine. The nanosilver colloid was prepared in the PVA solution by using the Electric Spark Discharge Method. UV-Vis, Zetasizer, and SEM-EDX analyses proved that the PVA solution contained nanosilver colloid with good suspension stability. Finally, the electrospinning technique was used to spin the PVA solution with nanosilver colloid into the PVA nanofibrous membrane. According to UV-Vis analysis, the absorption peak of this nanofibrous membrane is about 415 nm, meaning this nanofibrous membrane contains nucleate nanosilver colloid, and is very suitable for antiseptic dressing.
A Study on Water Pollution Source Localization in Sensor Networks
Authors: Yang Jun , Luo Xu
Published: September 2016

The water pollution source localization is of great significance to water environment protection. In this paper, a study on water pollution source localization is presented. Firstly, the source detection is discussed. Then, the coarse localization methods and the localization methods based on diffusion models are introduced and analyzed, respectively. In addition, the localization method based on the contour is proposed. The detection and localization methods are compared in experiments finally. The results show that the detection method using hypotheses testing is more stable. The performance of the coarse localization algorithm depends on the nodes density. The localization based on the diffusion model can yield precise localization results; however, the results are not stable. The localization method based on the contour is better than the other two localization methods when the concentration contours are axisymmetric. Thus, in the water pollution source localization, the detection using hypotheses testing is more preferable in the source detection step. If concentration contours are axisymmetric, the localization method based on the contour is the first option. And, in case the nodes are dense and there is no explicit diffusion model, the coarse localization algorithm can be used, or else the localization based on diffusion models is a good choice.
A Review on Fatigue Life Prediction Methods for Metals
Authors: Santecchia E. , Hamouda A. M. S. , Musharavati F. , Zalnezhad E. , Cabibbo M. , El Mehtedi M. , Spigarelli S.
Published: September 2016

Metallic materials are extensively used in engineering structures and fatigue failure is one of the most common failure modes of metal structures. Fatigue phenomena occur when a material is subjected to fluctuating stresses and strains, which lead to failure due to damage accumulation. Different methods, including the Palmgren-Miner linear damage rule- (LDR-) based, multiaxial and variable amplitude loading, stochastic-based, energy-based, and continuum damage mechanics methods, forecast fatigue life. This paper reviews fatigue life prediction techniques for metallic materials. An ideal fatigue life prediction model should include the main features of those already established methods, and its implementation in simulation systems could help engineers and scientists in different applications. In conclusion, LDR-based, multiaxial and variable amplitude loading, stochastic-based, continuum damage mechanics, and energy-based methods are easy, realistic, microstructure dependent, well timed, and damage connected, respectively, for the ideal prediction model.
FGF2 from Marrow Microenvironment Promotes Resistance to FLT3 Inhibitors in Acute Myeloid Leukemia
Authors: Traer Elie , Martinez Jacqueline , Javidi-Sharifi Nathalie , Agarwal Anupriya , Dunlap Jennifer , English Isabel , Kovacsovics Tibor , Tyner Jeffrey W. , Wong Melissa , Druker Brian J.
Published: September 2016

Potent FLT3 inhibitors, such as quizartinib (AC220), have shown promise in treating acute myeloid leukemia (AML) containing FLT3 internal tandem duplication (ITD) mutations. However, responses are not durable and resistance develops within months. In this study, we outline a two-step model of resistance whereby extrinsic microenvironmental proteins FLT3 ligand (FL) and fibroblast growth factor 2 (FGF2) protect FLT3-ITD+ MOLM14 cells from AC220, providing time for subsequent accumulation of ligand-independent resistance mechanisms. FL directly attenuated AC220 inhibition of FLT3, consistent with previous reports. Conversely, FGF2 promoted resistance through activation of FGFR1 and downstream MAPK effectors; these resistant cells responded synergistically to combinatorial inhibition of FGFR1 and FLT3. Removing FL or FGF2 from ligand-dependent resistant cultures transiently restored sensitivity to AC220, but accelerated acquisition of secondary resistance via reactivation of FLT3 and RAS/MAPK signaling. FLT3-ITD AML patients treated with AC220 developed increased FGF2 expression in marrow stromal cells, which peaked prior to overt clinical relapse and detection of resistance mutations. Overall, these results support a strategy of early combination therapy to target early survival signals from the bone marrow microenvironment, in particular FGF2, to improve the depth of response in FLT3-ITD AML. Cancer Res; 76(22); 6471–82. ©2016 AACR.
Spatial Proximity to Fibroblasts Impacts Molecular Features and Therapeutic Sensitivity of Breast Cancer Cells Influencing Clinical Outcomes
Authors: Marusyk Andriy , Tabassum Doris P. , Janiszewska Michalina , Place Andrew E. , Trinh Anne , Rozhok Andrii I. , Pyne Saumyadipta , Guerriero Jennifer L. , Shu Shaokun , Ekram Muhammad , Ishkin Alexander , Cahill Daniel P. , Nikolsky Yuri , Chan Timothy A. , Rimawi Mothaffar F. , Hilsenbeck Susan , Schiff Rachel , Osborne Kent C. , Letai Antony , Polyak Kornelia
Published: September 2016

Using a three-dimensional coculture model, we identified significant subtype-specific changes in gene expression, metabolic, and therapeutic sensitivity profiles of breast cancer cells in contact with cancer-associated fibroblasts (CAF). CAF-induced gene expression signatures predicted clinical outcome and immune-related differences in the microenvironment. We found that fibroblasts strongly protect carcinoma cells from lapatinib, attributable to its reduced accumulation in carcinoma cells and an elevated apoptotic threshold. Fibroblasts from normal breast tissues and stromal cultures of brain metastases of breast cancer had similar effects as CAFs. Using synthetic lethality approaches, we identified molecular pathways whose inhibition sensitizes HER2+ breast cancer cells to lapatinib both in vitro and in vivo, including JAK2/STAT3 and hyaluronic acid. Neoadjuvant lapatinib therapy in HER2+ breast tumors lead to a significant increase of phospho-STAT3+ cancer cells and a decrease in the spatial proximity of proliferating (Ki67+) cells to CAFs impacting therapeutic responses. Our studies identify CAF-induced physiologically and clinically relevant changes in cancer cells and offer novel approaches for overcoming microenvironment-mediated therapeutic resistance. Cancer Res; 76(22); 6495–506. ©2016 AACR.
Shifts in the Fecal Microbiota Associated with Adenomatous Polyps
Authors: Hale Vanessa L. , Chen Jun , Johnson Stephen , Harrington Sean C. , Yab Tracy C. , Smyrk Thomas C. , Nelson Heidi , Boardman Lisa A. , Druliner Brooke R. , Levin Theodore R. , Rex Douglas K. , Ahnen Dennis J. , Lance Peter , Ahlquist David A. , Chia Nicholas
Published: September 2016

Background: Adenomatous polyps are the most common precursor to colorectal cancer, the second leading cause of cancer-related death in the United States. We sought to learn more about early events of carcinogenesis by investigating shifts in the gut microbiota of patients with adenomas.

Methods: We analyzed 16S rRNA gene sequences from the fecal microbiota of patients with adenomas (n = 233) and without (n = 547).

Results: Multiple taxa were significantly more abundant in patients with adenomas, including Bilophila, Desulfovibrio, proinflammatory bacteria in the genus Mogibacterium, and multiple Bacteroidetes species. Patients without adenomas had greater abundances of Veillonella, Firmicutes (Order Clostridia), and Actinobacteria (family Bifidobacteriales). Our findings were consistent with previously reported shifts in the gut microbiota of colorectal cancer patients. Importantly, the altered adenoma profile is predicted to increase primary and secondary bile acid production, as well as starch, sucrose, lipid, and phenylpropanoid metabolism.

Conclusions: These data hint that increased sugar, protein, and lipid metabolism along with increased bile acid production could promote a colonic environment that supports the growth of bile-tolerant microbes such as Bilophilia and Desulfovibrio. In turn, these microbes may produce genotoxic or inflammatory metabolites such as H2S and secondary bile acids, which could play a role in catalyzing adenoma development and eventually colorectal cancer.

Impact: This study suggests a plausible biological mechanism to explain the links between shifts in the microbiota and colorectal cancer. This represents a first step toward resolving the complex interactions that shape the adenoma–carcinoma sequence of colorectal cancer and may facilitate personalized therapeutics focused on the microbiota. Cancer Epidemiol Biomarkers Prev; 26(1); 85–94. ©2016 AACR.
The Association between Alcohol Consumption and Breast Density: A Systematic Review and Meta-analysis
Authors: Ziembicki Stephanie , Zhu Jie , Tse Elizabeth , Martin Lisa J. , Minkin Salomon , Boyd Norman F.
Published: September 2016

Background: Percent breast density (PBD) is a strong risk factor for breast cancer that is influenced by several other risk factors for the disease. Alcohol consumption is associated with an increased risk of breast cancer with an uncertain association with PBD. We have carried out a systematic review and meta-analysis to examine the association of alcohol consumption with PBD.

Methods: We searched nine databases to identify all relevant studies on the association between alcohol intake and breast density. Two independent investigators evaluated and selected 20 studies that were included in our analyses. We divided the studies into three groups according to the methods used to measure and analyze the association of breast density with alcohol consumption.

Results: Meta-analysis of the 11 studies that used quantitative methods to measure and analyze PBD as a continuous variable found a statistically significant difference in PBD when comparing the highest with the lowest alcohol level [β = 0.84; 95% confidence interval (CI), 0.12–1.56]. Three studies that used quantitative methods to measure PBD and categories of PBD for analysis had a summary OR = 1.81 (95% CI, 1.07–3.04). Five studies that used categories to classify PBD and analyze their association with alcohol intake had a summary OR = 1.78 (95% CI, 0.90–3.51).

Conclusions: These results suggest that there is a positive association between alcohol intake and PBD.

Impact: Alcohol may increase the risk of breast cancer associated with PBD. Cancer Epidemiol Biomarkers Prev; 26(2); 170–8. ©2016 AACR.
Development of a Novel Antibody–Drug Conjugate for the Potential Treatment of Ovarian, Lung, and Renal Cell Carcinoma Expressing TIM-1
Authors: Thomas Lawrence J. , Vitale Laura , O'Neill Thomas , Dolnick Ree Y. , Wallace Paul K. , Minderman Hans , Gergel Lauren E. , Forsberg Eric M. , Boyer James M. , Storey James R. , Pilsmaker Catherine D. , Hammond Russell A. , Widger Jenifer , Sundarapandiyan Karuna , Crocker Andrea , Marsh Henry C. , Keler Tibor
Published: September 2016

T-cell immunoglobulin and mucin domain 1 (TIM-1) is a type I transmembrane protein that was originally described as kidney injury molecule 1 (KIM-1) due to its elevated expression in kidney and urine after renal injury. TIM-1 expression is also upregulated in several human cancers, most notably in renal and ovarian carcinomas, but has very restricted expression in healthy tissues, thus representing a promising target for antibody-mediated therapy. To this end, we have developed a fully human monoclonal IgG1 antibody specific for the extracellular domain of TIM-1. This antibody was shown to bind purified recombinant chimeric TIM-1-Fc protein and TIM-1 expressed on a variety of transformed cell lines, including Caki-1 (human renal clear cell carcinoma), IGROV-1 (human ovarian adenocarcinoma), and A549 (human lung carcinoma). Internalization studies using confocal microscopy revealed the antibody was rapidly internalized by cells in vitro, and internalization was confirmed by quantitative imaging flow cytometry. An antibody–drug conjugate (ADC) was produced with the anti-TIM-1 antibody covalently linked to the potent cytotoxin, monomethyl auristatin E (MMAE), and designated CDX-014. The ADC was shown to exhibit in vitro cytostatic or cytotoxic activity against a variety of TIM-1–expressing cell lines, but not on TIM-1–negative cell lines. Using the Caki-1, IGROV-1, and A549 xenograft mouse models, CDX-014 showed significant antitumor activity in a clinically relevant dose range. Safety evaluation in nonhuman primates has demonstrated a good profile and led to the initiation of clinical studies of CDX-014 in renal cell carcinoma and potentially other TIM-1–expressing tumors. Mol Cancer Ther; 15(12); 2946–54. ©2016 AACR.
AXL Inhibition Suppresses the DNA Damage Response and Sensitizes Cells to PARP Inhibition in Multiple Cancers
Authors: Balaji Kavitha , Vijayaraghavan Smruthi , Diao Lixia , Tong Pan , Fan Youhong , Carey Jason P.W. , Bui Tuyen N. , Warner Steve , Heymach John V. , Hunt Kelly K. , Wang Jing , Byers Lauren Averett , Keyomarsi Khandan
Published: September 2016

Epithelial to mesenchymal transition (EMT) is associated with a wide range of changes in cancer cells, including stemness, chemo- and radio-resistance, and metastasis. The mechanistic role of upstream mediators of EMT has not yet been well characterized. Recently, we showed that non–small cell lung cancers (NSCLC) that have undergone EMT overexpress AXL, a receptor tyrosine kinase. AXL is also overexpressed in a subset of triple-negative breast cancers (TNBC) and head and neck squamous cell carcinomas (HNSCC), and its overexpression has been associated with more aggressive tumor behavior and linked to resistance to chemotherapy, radiotherapy, and targeted therapy. Because the DNA repair pathway is also altered in patient tumor specimens overexpressing AXL, it is hypothesized that modulation of AXL in cells that have undergone EMT will sensitize them to agents targeting the DNA repair pathway. Downregulation or inhibition of AXL directly reversed the EMT phenotype, led to decreased expression of DNA repair genes, and diminished efficiency of homologous recombination (HR) and RAD51 foci formation. As a result, AXL inhibition caused a state of HR deficiency in the cells, making them sensitive to inhibition of the DNA repair protein, PARP1. AXL inhibition synergized with PARP inhibition, leading to apoptotic cell death. AXL expression also associated positively with markers of DNA repair across TNBC, HNSCC, and NSCLC patient cohorts.

Implications: The novel role for AXL in DNA repair, linking it to EMT, suggests that AXL can be an effective therapeutic target in combination with targeted therapy such as PARP inhibitors in several different malignancies. Mol Cancer Res; 15(1); 45–58. ©2016 AACR.
Interplay between Cytoplasmic and Nuclear Androgen Receptor Splice Variants Mediates Castration Resistance
Authors: Zhan Yang , Zhang Guanyi , Wang Xiaojie , Qi Yanfeng , Bai Shanshan , Li Dongying , Ma Tianfang , Sartor Oliver , Flemington Erik K. , Zhang Haitao , Lee Peng , Dong Yan
Published: September 2016

Androgen receptor splice variants (AR-V) are implicated in resistance of prostate cancer to androgen-directed therapies. When expressed alone in cells, some AR-Vs (e.g., AR-V7) localize primarily to the nucleus, whereas others (e.g., AR-V1, AR-V4, and AR-V6) localize mainly to the cytoplasm. Significantly, the latter are often coexpressed with the nucleus-predominant AR-Vs and the full-length AR (AR-FL). An important question to be addressed is whether the cytoplasmic-localized AR-Vs play a role in castration-resistant prostate cancer (CRPC) through interaction with the nucleus-predominant AR-Vs and AR-FL. Here, it is demonstrated that AR-V1, -V4, and -V6 can dimerize with both AR-V7 and AR-FL. Consequently, AR-V7 and androgen-bound AR-FL induced nuclear localization of AR-V1, -V4, and -V6, and these variants, in turn, mitigated the ability of the antiandrogen enzalutamide to inhibit androgen-induced AR-FL nuclear localization. Interestingly, the impact of nuclear localization of AR-V4 and -V6 on AR transactivation differs from that of AR-V1. Nuclear localization leads to an increased ability of AR-V4 and -V6 to transactivate both canonical AR targets and AR-V–specific targets and to confer castration-resistant cell growth. However, although AR-V1, which lacks inherent transcriptional activity, appears to activate AR-FL in an androgen-independent manner, it significantly antagonizes AR-V7 transactivation. Together, these data demonstrate that the complex interactions among different AR-Vs and AR-FL play a significant role in castration-resistant disease.

Implications: This study suggests important consequences for clinical castration resistance due to simultaneous expression of AR-FL and AR-Vs in patient tumors and suggests that dissecting these interactions should help develop effective strategies to disrupt AR-V signaling. Mol Cancer Res; 15(1); 59–68. ©2016 AACR.
Surgical Treatment of Metabolic Syndrome
Authors: Runkel Norbert , Brydniak Rainer
Published: September 2016

Background: Bariatric surgery is gastrointestinal surgery for weight control, and metabolic surgery refers to the use of surgery to primarily and purposely treat type 2 diabetes mellitus (T2DM)/metabolic syndrome mellitus. Methods: The most recent literature was reviewed for surgery and T2DM in a non-systematic fashion. Results: Roux-Y gastric bypass, biliopancreatic diversion with duodenal switch, and sleeve gastrectomy (SG) are the dominant procedures today. SG is emerging as the most popular operation worldwide. Laparoscopy has made metabolic surgery as safe as other common abdominal procedures. A BMI > 60 kg/m2, however, exposes a significantly higher perioperative risk. Most patients experience a sustained improvement of glycemic control with subsequent reduction of cardiovascular events. The remission rates depend on the severity and duration of diabetes. Prevention of long-term nutritional deficits and monitoring of metabolism require lifelong medical surveillance of the patients. Conclusions: The profound impact of weight reduction surgery on glucose metabolism explains the growing interest in treating T2DM by surgical means. Metabolic surgery is a safe option for carefully selected patients with metabolic syndrome.
Test Pricing and Reimbursement in Genomic Medicine: Towards a General Strategy
Authors: Vozikis Athanassios , Cooper David N. , Mitropoulou Christina , Kambouris Manousos E. , Brand Angela , Dolzan Vita , Fortina Paolo , Innocenti Federico , Lee Ming Ta Michael , Leyens Lada , Macek Jr Milan , Al-Mulla Fahd , Prainsack Barbara , Squassina Alessio , Taruscio Domenica , van Schaik Ron H. , Vayena Effy , Williams Marc S. , Patrinos George P.
Published: September 2016

This paper aims to provide an overview of the rationale and basic principles guiding the governance of genomic testing services, to clarify their objectives, and allocate and define responsibilities among stakeholders in a health-care system, with a special focus on the EU countries. Particular attention is paid to issues pertaining to pricing and reimbursement policies, the availability of essential genomic tests which differs between various countries owing to differences in disease prevalence and public health relevance, the prescribing and use of genomic testing services according to existing or new guidelines, budgetary and fiscal control, the balance between price and access to innovative testing, monitoring and evaluation for cost-effectiveness and safety, and the development of research capacity. We conclude that addressing the specific items put forward in this article will help to create a robust policy in relation to pricing and reimbursement in genomic medicine. This will contribute to an effective and sustainable health-care system and will prove beneficial to the economy at large.
Suppressive Effect of Carvedilol on Na+/Ca2+ Exchange Current in Isolated Guinea-Pig Cardiac Ventricular Myocytes
Authors: Tashiro Miyuki , Watanabe Yasuhide , Yamakawa Tomomi , Yamashita Kanna , Kita Satomi , Iwamoto Takahiro , Kimura Junko
Published: September 2016

Background and Aims: Carvedilol ((+/-)-1-(carbazol-4-yloxy)-3-[[2-(o-methoxyphenoxy)ethyl]amino]-2-propanol), a β-adrenoceptor-blocker, has multi-channel blocking and vasodilator properties. This agent dose-dependently improves left ventricular function and reduces mortality in patients with arrhythmia and chronic heart failure. However, the effect of carvedilol on the cardiac Na+/Ca2+ exchanger (NCX1) has not been investigated. Methods and Results: We examined the effects of carvedilol and metoprolol, 2 β-blockers, on Na+/Ca2+ exchange current (INCX) in guinea-pig cardiac ventricular cells and fibroblasts expressing dog cardiac NCX1. Carvedilol suppressed INCX in a concentration-dependent manner but metoprolol did not. IC50 values for the Ca2+ influx (outward) and efflux (inward) components of INCX were 69.7 and 61.5 µmol/l, respectively. Carvedilol at 100 μmol/l inhibited INCX in CCL39 cells expressing wild type NCX1 similar to mutant NCX1 without the intracellular regulatory loop. Carvedilol at 30 µmol/l abolished ouabain-induced delayed afterdepolarizations. Conclusion: Carvedilol inhibited cardiac NCX in a concentration-dependent manner in isolated cardiac ventricles, but metoprolol did not. We conclude that carvedilol inhibits NCX1 at supratherapeutic concentrations.
Recommendation for ISTH/SSC Criterion 2015 for autoimmune acquired factor XIII/13 deficiency
Authors: Kohler Hans P. , Philippou Helen , Ichinose Akitada
Published: September 2016

Supplementary Material to this article is available online at www.thrombosis-online.com.
Guimarães, Clarice e antes
Authors: Bueno Luís
Published: September 2016

Guimarães Rosa e Clarice Lispector têm sido vistos como fenômenos isolados em nossa história literária, como se eles inaugurassem caminhos de todo inéditos em nossa literatura. Este trabalho procura mostrar que essa sensação se deve menos à obra desses dois autores do que à visão pouco abrangente que se cristalizou acerca da geração que os antecedeu. De fato, um olhar cuidadoso sobre o romance de 30 demonstra que o sistema literário brasileiro estava pronto para o surgimento de Guimarães e Clarice nos anos 40
Machado Maxixe: Ocaso Pestana
Authors: Wisnik José Miguel
Published: September 2016

O conto “Um homem célebre” é o núcleo de uma série de textos de Machado de Assis, entre crônicas, contos e romance, em que a música tem destaque. Por trás do descompasso evidente entre o erudito e o popular no Brasil, trata-se da emergência não nomeada do maxixe, que envolve cifradamente escravidão e mestiçagem. Abolição, Monarquia e República convertem-se, nesses textos, em elementos de uma interpretação musical da História. O conto prefigura, ainda, linhas problemáticas que vieram a marcar a música brasileira no século 20
O papel das cartas e das confissões na ficção de Fernando Sabino
Authors: Betella Gabriela Kvacek
Published: September 2016

Antes de sua morte em 2004, Fernando Sabino publicou muito da correspondência trocada com amigos desde os anos de 1940. O “balanço” trouxe também o romance iné­ dito Os movimentos simulados, além de re-edições de textos autobiográficos. Embora os eventos dos últimos dez anos da vida do escritor destaquem uma intersecção entre o passado reconstituído e o presente ficcional, no período de 1946 a 1956 já era possível detectar essa associação íntima, razão principal do movimento de sua obra
Do horror: a cena contemporânea
Authors: Favaretto Celso
Published: September 2016

Hoje a representação do horror não mais decorre, como se acreditou, da multiplicação dos teatros da memória e da perda de eficácia dos dispositivos da representação, efetuados pelo enfraquecimento do simbólico, com a contribuição das várias tecnologias da comunicação. Tal enfraquecimento resulta da potência das imagens que circulam, do excesso e da espetacularização que compõem o seu regime estético. Passados o tempo de circulação de teorias e as experiências de fechamento da representação, percebe-se que não temos ainda “uma linguagem que esteja à altura de traduzir o estado atual das coisas”
A arte postal/ arte-correo/ mail art como sistema
Authors: Jobim José Luis
Published: September 2016

O artigo aborda a natureza da arte postal/ arte-correo/mail art, focalizando predominantemente uma de suas manifestações: as chamadas revistas-coletâneas (assembling magazines). Busca refletir sobre a maneira como as comunidades artísticas reunidas em torno dessas publicações tinham certos conceitos compartilhados (dos quais nem sempre estavam autoconscientes). Muitas vezes não percebiam que suas próprias declarações sobre as práticas de edição que operavam contradiziam os princípios apregoados para elas
A forma e o infinito, de Diderot a Baudelaire
Authors: Moraes Marcelo Jacques de
Published: September 2016

A noção de infinito em Baudelaire remete à vocação de uma coisa para intensificar-se, isto é, para alterar-se e transformar-se em si mesma pela mediação de uma forma. A partir daí, pretendo discutir a importância do infinito baudelairiano para pensar como a forma estética encena sua própria historicidade. A questão é trabalhada em contraponto com a reflexão estética de Diderot.
Na fanfarra de Almáquio Dinis
Authors: Prado Antonio Arnoni
Published: September 2016

No presente artigo, analisa-se a produção do baiano Almáquio Dinis (1880-1937), crítico que escapa a qualquer juízo que se arrisque a explicá-lo. Trabalhou com uma imensa variedade de temas, vasculhando ângulos comuns a objetos inconciliáveis, que costumava desdobrar em livros simultâneos, como ocorreu com os esboços sobre a Preparação socialista do Brasil e com o ensaio sobre a Sociologia soviética, em 1934.
Lima Barreto e o romance: crítica e crise
Authors: Figueiredo Carmem Lúcia Negreiros de
Published: September 2016

O artigo analisa o romance Recordações do escrivão Isaías Caminha, de Lima Barreto (1881-1922), apontando princípios formais presentes na obra, indicadores de uma nova realização estética que não se coaduna, plenamente, com o romance realista do século XIX. Por isso, propõe nova abordagem, ou moldura, para a obra que, de partida, considera a crise da subjetividade e da capacidade de narrar, coerente com a atmosfera das primeiras décadas do século XX.
Jorge Amado, crônica e ativismo
Authors: Duarte Eduardo De Assis
Published: September 2016

Em Jorge Amado, política e literatura caminham juntas e fazem o romancista conviver intensamente com o homem de imprensa e o militante. Partindo das crônicas publicadas, entre 1942 e 1944, na seção “Hora da Guerra”, do jornal baiano O Imparcial, e reunidas em livro recentemente, o presente trabalho empreende uma reflexão sobre o escritor enquanto cronista e intelectual orgânico — compagnon de route da utopia maior de seu tempo
A sighting of Plastingia naga (de Nicéville, [1884]) (Lepidoptera: Hesperiidae: Hesperiinae) from central Assam, India
Authors: Das Gaurab Nandi , Payra Arajush , Boruah Bitupan
Published: September 2016

The species Plastingia naga, de Niceville 1884is a very rare butterfly, and it occurs widely from Assam to Myanmar, Malay Peninsula, Sumatra, Borneo and Philippines (Evans, 1932). Except India, recently this species was recorded from Singapore, Sumatra and Thailand. On 10 Oct 2014 around 10:00hr, a solitary individual of Plastingia naga was sighted in Panbari Reserve Forest, Central Assam. Apart from the fact that these records constitute existence of this species in North-East India, this is probably the first photographic record from North-East India.
Is High Blood Pressure Self-Protection for the Brain?
Authors: Warnert Esther A.H. , Rodrigues Jonathan C.L. , Burchell Amy E. , Neumann Sandra , Ratcliffe Laura E.K. , Manghat Nathan E. , Harris Ashley D. , Adams Zoe , Nightingale Angus K. , Wise Richard G. , Paton Julian F.R. , Hart Emma C.
Published: September 2016

Rationale:

Data from animal models of hypertension indicate that high blood pressure may develop as a vital mechanism to maintain adequate blood flow to the brain. We propose that congenital vascular variants of the posterior cerebral circulation and cerebral hypoperfusion could partially explain the pathogenesis of essential hypertension, which remains enigmatic in 95% of patients.

Objective:

To evaluate the role of the cerebral circulation in the pathophysiology of hypertension.

Methods and Results:

We completed a series of retrospective and mechanistic case-control magnetic resonance imaging and physiological studies in normotensive and hypertensive humans (n=259). Interestingly, in humans with hypertension, we report a higher prevalence of congenital cerebrovascular variants; vertebral artery hypoplasia, and an incomplete posterior circle of Willis, which were coupled with increased cerebral vascular resistance, reduced cerebral blood flow, and a higher incidence of lacunar type infarcts. Causally, cerebral vascular resistance was elevated before the onset of hypertension and elevated sympathetic nerve activity (n=126). Interestingly, untreated hypertensive patients (n=20) had a cerebral blood flow similar to age-matched controls (n=28). However, participants receiving antihypertensive therapy (with blood pressure controlled below target levels) had reduced cerebral perfusion (n=19). Finally, elevated cerebral vascular resistance was a predictor of hypertension, suggesting that it may be a novel prognostic or diagnostic marker (n=126).

Conclusions:

Our data indicate that congenital cerebrovascular variants in the posterior circulation and the associated cerebral hypoperfusion may be a factor in triggering hypertension. Therefore, lowering blood pressure may worsen cerebral perfusion in susceptible individuals.
Moderate Alcohol Consumption Is Associated With Left Ventricular Diastolic Dysfunction in Nonalcoholic Hypertensive Patients
Authors: Catena Cristiana , Colussi GianLuca , Verheyen Nicolas D. , Novello Marileda , Fagotto Valentina , Soardo Giorgio , Sechi Leonardo A.
Published: September 2016

Ethanol consumption is associated with left ventricular dysfunction in heavy ethanol drinkers. The effect of moderate ethanol intake on left ventricular function in hypertension, however, is unknown. We investigated the relationship between ethanol consumption and cardiac changes in nonalcoholic hypertensive patients. In 335 patients with primary hypertension, we assessed daily ethanol consumption by questionnaires that combined evaluation of recent and lifetime ethanol exposure and examined cardiac structure and function by echocardiography. Patients with abnormal liver tests, previous cardiovascular events, left ventricular ejection fraction <50%, and creatinine clearance <30 mL/min 1.72 m
2
were excluded. Left ventricular hypertrophy was found in 21% of hypertensive patients and diastolic dysfunction was detected in 50% by tissue-Doppler imaging. Ethanol consumption was comparable in hypertensive patients with and without left ventricular hypertrophy, whereas patients with left ventricular diastolic dysfunction had significantly greater consumption than patients with normal ventricular filling. Left atrial diameter, e′ wave velocity, e′/a′ ratio, and E/e′ ratio changed progressively with increasing levels of ethanol consumption, and prevalence of left ventricular diastolic dysfunction increased with a change that became statistically significant in patients consuming 20 g/d of ethanol or more. The e′ wave velocity was inversely correlated with ethanol consumption, and multivariate logistic regression indicated that ethanol consumption predicted diastolic dysfunction independently of age, body mass index, blood pressure, insulin sensitivity, and left ventricular mass index. In conclusion, ethanol consumption is independently associated with left ventricular diastolic dysfunction in nonalcoholic hypertensive patients and might contribute to development of diastolic heart failure.
Monocrotaline-Induced Pulmonary Hypertension Involves Downregulation of Antiaging Protein Klotho and eNOS Activity
Authors: Varshney Rohan , Ali Quaisar , Wu Chengxiang , Sun Zhongjie
Published: September 2016

The objective of this study is to investigate whether stem cell delivery of secreted Klotho (SKL), an aging-suppressor protein, attenuates monocrotaline-induced pulmonary vascular dysfunction and remodeling. Overexpression of SKL in mesenchymal stem cells (MSCs) was achieved by transfecting MSCs with lentiviral vectors expressing SKL-green fluorescent protein (GFP). Four groups of rats were treated with monocrotaline, whereas an additional group was given saline (control). Three days later, 4 monocrotaline-treated groups received intravenous delivery of nontransfected MSCs, MSC-GFP, MSC-SKL-GFP, and PBS, respectively. Ex vivo vascular relaxing responses to acetylcholine were diminished in small pulmonary arteries (PAs) in monocrotaline-treated rats, indicating pulmonary vascular endothelial dysfunction. Interestingly, delivery of MSCs overexpressing SKL (MSC-SKL-GFP) abolished monocrotaline-induced pulmonary vascular endothelial dysfunction and PA remodeling. Monocrotaline significantly increased right ventricular systolic blood pressure, which was attenuated significantly by MSC-SKL-GFP, indicating improved PA hypertension. MSC-SKL-GFP also attenuated right ventricular hypertrophy. Nontransfected MSCs slightly, but not significantly, improved PA hypertension and pulmonary vascular endothelial dysfunction. MSC-SKL-GFP attenuated monocrotaline-induced inflammation, as evidenced by decreased macrophage infiltration around PAs. MSC-SKL-GFP increased SKL levels, which rescued the downregulation of SIRT1 (Sirtuin 1) expression and endothelial NO synthase (eNOS) phosphorylation in the lungs of monocrotaline-treated rats. In cultured endothelial cells, SKL abolished monocrotaline-induced downregulation of eNOS activity and NO levels and enhanced cell viability. Therefore, stem cell delivery of SKL is an effective therapeutic strategy for pulmonary vascular endothelial dysfunction and PA remodeling. SKL attenuates monocrotaline-induced PA remodeling and PA smooth muscle cell proliferation, likely by reducing inflammation and restoring SIRT1 levels and eNOS activity.
Repetition Enhancement of Amygdala and Visual Cortex Functional Connectivity Reflects Nonconscious Memory for Negative Visual Stimuli
Authors: Kark Sarah M. , Slotnick Scott D. , Kensinger Elizabeth A.
Published: September 2016

Most studies using a recognition memory paradigm examine the neural processes that support the ability to consciously recognize past events. However, there can also be nonconscious influences from the prior study episode that reflect repetition suppression effects—a reduction in the magnitude of activity for repeated presentations of stimuli—that are revealed by comparing neural activity associated with forgotten items to correctly rejected novel items. The present fMRI study examined the effect of emotional valence (positive vs. negative) on repetition suppression effects. Using a standard recognition memory task, 24 participants viewed line drawings of previously studied negative, positive, and neutral photos intermixed with novel line drawings. For each item, participants made an old–new recognition judgment and a sure–unsure confidence rating. Collapsed across valence, repetition suppression effects were found in ventral occipital-temporal cortex and frontal regions. Activity levels in the majority of these regions were not modulated by valence. However, repetition enhancement of the amygdala and ventral occipital-temporal cortex functional connectivity reflected nonconscious memory for negative items. In this study, valence had little effect on activation patterns but had a larger effect on functional connectivity patterns that were markers of nonconscious memory. Beyond memory and emotion, these findings are relevant to other cognitive and social neuroscientists that utilize fMRI repetition effects to investigate perception, attention, social cognition, and other forms of learning and memory.
Reduced Cognitive Control Demands after Practice of Saccade Tasks in a Trial Type Probability Manipulation
Authors: Pierce Jordan E. , McDowell Jennifer E.
Published: September 2016

Cognitive control is engaged to facilitate stimulus–response mappings for novel, complex tasks and supervise performance in unfamiliar, challenging contexts—processes supported by pFC, ACC, and posterior parietal cortex. With repeated task practice, however, the appropriate task set can be selected in a more automatic fashion with less need for top–down cognitive control and weaker activation in these brain regions. One model system for investigating cognitive control is the ocular motor circuitry underlying saccade production, with basic prosaccade trials (look toward a stimulus) and complex antisaccade trials (look to the mirror image location) representing low and high levels of cognitive control, respectively. Previous studies have shown behavioral improvements on saccade tasks after practice with contradictory results regarding the direction of functional MRI BOLD signal change. The current study presented healthy young adults with prosaccade and antisaccade trials in five mixed blocks with varying probability of each trial type (0%, 25%, 50%, 75%, or 100% anti vs. pro) at baseline and posttest MRI sessions. Between the scans, participants practiced either the specific probability blocks used during testing or only a general 100% antisaccade block. Results indicated an overall reduction in BOLD activation within pFC, ACC, and posterior parietal cortex and across saccade circuitry for antisaccade trials. The specific practice group showed additional regions including ACC, insula, and thalamus with an activation decrease after practice, whereas the general practice group showed a little change from baseline in those clusters. These findings demonstrate that cognitive control regions recruited to support novel task behaviors were engaged less after practice, especially with exposure to mixed task contexts rather than a novel task in isolation.
Racial Psychiatry and the Russian Imperial Dilemma of the “Savage Within”
Authors: Mogilner Marina
Published: September 2016

The article tells the story of racial psychiatry in the Russian Empire. The context in which it has developed is analyzed in epistemological as well as political terms, and the discussion of such scholarly categories as “savagery,” “atavism”, or “survivals” and the language of race in ethnography, race science, and psychiatry is complemented with the discussion of rising mass politics. These two threads of analysis are connected within a broader context of the Russian imperial situation of the turn of the century, marked by human, cultural and administrative heterogeneity and the asynchronous social and cultural dynamics of different peoples, classes, and regions. The article explores in details how the Russian psychiatric profession made sense of the Russian imperial situation, and why a group of highly influential psychiatrists turned to the concept of race and the method of inter-imperial comparison as a solution to this situation’s complexities and ambiguities.