bluuebunny/crossref_metadata_2025 huggingface dataset:
AMPK Causes Cell Cycle Arrest in LKB1-Deficient Cells via Activation of CAMKK2
Authors: Fogarty Sarah , Ross Fiona A. , Vara Ciruelos Diana , Gray Alexander , Gowans Graeme J. , Hardie D. Grahame
Published: May 2016

The AMP-activated protein kinase (AMPK) is activated by phosphorylation at Thr172, either by the tumor suppressor kinase LKB1 or by an alternate pathway involving the Ca2+/calmodulin-dependent kinase, CAMKK2. Increases in AMP:ATP and ADP:ATP ratios, signifying energy deficit, promote allosteric activation and net Thr172 phosphorylation mediated by LKB1, so that the LKB1–AMPK pathway acts as an energy sensor. Many tumor cells carry loss-of-function mutations in the STK11 gene encoding LKB1, but LKB1 reexpression in these cells causes cell-cycle arrest. Therefore, it was investigated as to whether arrest by LKB1 is caused by activation of AMPK or of one of the AMPK-related kinases, which are also dependent on LKB1 but are not activated by CAMKK2. In three LKB1-null tumor cell lines, treatment with the Ca2+ ionophore A23187 caused a G1 arrest that correlated with AMPK activation and Thr172 phosphorylation. In G361 cells, expression of a truncated, Ca2+/calmodulin-independent CAMKK2 mutant also caused G1 arrest similar to that caused by expression of LKB1, while expression of a dominant-negative AMPK mutant, or a double knockout of both AMPK-α subunits, also prevented the cell-cycle arrest caused by A23187. These mechanistic findings confirm that AMPK activation triggers cell-cycle arrest, and also suggest that the rapid proliferation of LKB1-null tumor cells is due to lack of the restraining influence of AMPK. However, cell-cycle arrest can be restored by reexpressing LKB1 or a constitutively active CAMKK2, or by pharmacologic agents that increase intracellular Ca2+ and thus activate endogenous CAMKK2.

Implications: Evidence here reveals that the rapid growth and proliferation of cancer cells lacking the tumor suppressor LKB1 is due to reduced activity of AMPK, and suggests a therapeutic approach by which this block might be circumvented. Mol Cancer Res; 14(8); 683–95. ©2016 AACR.
Association between Circulating Vitamin D Metabolites and Fecal Bile Acid Concentrations
Authors: Jacobs Elizabeth T. , Haussler Mark R. , Alberts David S. , Kohler Lindsay N. , Lance Peter , Martínez María Elena , Roe Denise J. , Jurutka Peter W.
Published: May 2016

Although hydrophobic bile acids have been demonstrated to exhibit cytotoxic and carcinogenic effects in the colorectum, ursodeoxycholic acid (UDCA) has been investigated as a potential chemopreventive agent. Vitamin D has been shown to play a role in both bile acid metabolism and in the development of colorectal neoplasia. Using a cross-sectional design, we sought to determine whether baseline circulating concentrations of the vitamin D metabolites 25(OH)D and 1,25(OH)2D were associated with baseline fecal bile acid concentrations in a trial of UDCA for the prevention of colorectal adenoma recurrence. We also prospectively evaluated whether vitamin D metabolite concentrations modified the effect of UDCA on adenoma recurrence. After adjustment for age, sex, BMI, physical activity, and calcium intake, adequate concentrations of 25(OH)D (≥30 ng/mL) were statistically significantly associated with reduced odds for high levels of total [OR, 0.61; 95% confidence interval (CI), 0.38–0.97], and primary (OR, 0.61; 95% CI, 0.38–0.96) bile acids, as well as individually with chenodeoxycholic acid (OR, 0.39; 95% CI, 0.24–0.63) and cholic acid (OR, 0.56; 95% CI, 0.36–0.90). No significant associations were observed for 1,25(OH)2D and high versus low fecal bile acid concentrations. In addition, neither 25(OH)D nor 1,25(OH)2D modified the effect of UDCA on colorectal adenoma recurrence. In conclusion, this is the first study to demonstrate an inverse relationship between circulating levels of 25(OH)D and primary fecal bile acid concentrations. These results support prior data demonstrating that vitamin D plays a key role in bile acid metabolism, and suggest a potential mechanism of action for 25(OH)D in colorectal cancer prevention. Cancer Prev Res; 9(7); 589–97. ©2016 AACR.
Surrogate Markers: Lessons from the Next Gen?
Authors: Reid Brian J.
Published: May 2016

The article by Banerjee and colleagues published in this issue of the journal involving a randomized control prevention trial of ursodeoxycholic acid (UDCA) in Barrett esophagus reported a null outcome despite being well designed and executed. Possible reasons for this null outcome are discussed focusing on use of surrogate endpoints in the trial. The trial is especially topical because it comes at a time when there are calls for a Pre-Cancer Genome Atlas (PCGA) for “understanding the earliest molecular and cellular events associated with cancer initiation…” This commentary discusses current concepts in prevention research including branched evolution that leads to therapeutic resistance. Length bias sampling postulates underdiagnosis is due to rapidly progressing disease that is difficult to detect by screening because it progresses to cancer too rapidly and that overdiagnosis is the result of very slowly or nonprogressing disease that is easy to detect by screening because it persists for a lifetime and the patient dies of unrelated causes. Finally, it also explores study designs, including surrogate endpoints in Barrett esophagus trials, and opportunities and pitfalls for a PCGA in the context of high levels of over and underdiagnosis of Barrett esophagus as well as many other cancers and their precursors. Cancer Prev Res; 9(7); 512–7. ©2016 AACR.

See related article by Banerjee, et al., p. 528
The Influence of Chitin on the Immune Response to the House Dust Mite Allergen Blo t 12
Authors: Zakzuk Josefina , Benedetti Inés , Fernández-Caldas Enrique , Caraballo Luis
Published: May 2016

Background: Information about the biological properties of Blomia tropicalis allergens is scarce. It is predicted that Blo t 12, an allergen with two described isoforms, contains a chitin-binding domain, similar to that found in peritrophins. Th2 adjuvant properties have been described for chitin. Therefore, it is feasible that binding to this carbohydrate influences its allergenicity. We aimed to evaluate the chitin-binding activity of Blo t 12 isoallergens and its effect on airway inflammation and antibody responses in a murine model of allergen sensitization. Methods: Chitin-binding assays were conducted with the recombinant isoallergens Blo t 12.0101 and Blo t 12.0102. BALB/c mice were sensitized via i.p. with any of the two isoforms (alone, with chitin or alum) and then challenged intranasally. Methacholine-induced bronchial hyperreactivity was tested by whole-body plethysmography and lung sections were stained with hematoxylin and eosin and periodic-acid Schiff. Total IgE and allergen-specific IgE, IgG1 and IgG2 levels were measured by ELISA. Results: The two isoforms bound chitin, but Blo t 12.0101 showed a stronger binding capacity. Both isoforms induced total and allergen-specific IgE, airway hyperreactivity, bronchial inflammation and mucus secretion without any adjuvant; however, when administered with chitin, Blo t 12.0101 induced higher total IgE levels. The IgG1/IgG2a ratio was significantly higher in mice immunized with Blo t 12.0101 than those immunized with Blo t 12.0102. As peritrophins, Blo t 12 was detected in mite feces. Conclusions: Blo t 12 isoforms are chitin-binding proteins that induce airway inflammation and bronchial hyperreactivity. However, for Blo t 12.0101, chitin reinforces its effects on total IgE production.
Symptomatic Central Venous Stenosis in a Hemodialysis Patient Leading to Loss of Arteriovenous Access: A Case Report and Literature Review
Authors: Tatapudi Vasishta S. , Spinowitz Noam , Goldfarb David S.
Published: May 2016

Central venous stenosis is a well-described sequel to the placement of hemodialysis catheters in the central venous system. The presence of an ipsilateral arteriovenous fistula or graft often leads to severe venous dilatation, arm edema and recurrent infections. Vascular access thrombosis, compromised blood flow and inadequate dialysis delivery are dreaded complications that eventually render the access unusable. We report the case of a 58-year-old male hemodialysis patient who developed symptomatic central venous stenosis to illustrate the problem and review the pertinent literature. This patient developed severe enlargement of upper extremity veins due to central venous stenosis. The symptoms were refractory to multiple endovascular interventions and eventually necessitated ligation of his arteriovenous fistula. Central venous stenosis remains a pervasive problem despite advances in our understanding of its etiology and recognition of the enormity of its consequences. Due to the lack of effective therapeutic options, prevention is better than cure.
Corneal and Scleral Dellen after an Uneventful Pterygium Surgery and a Febrile Episode
Authors: Accorinti Massimo , Gilardi Marta , Giubilei Marco , De Geronimo Daniele , Iannetti Ludovico
Published: May 2016

Introduction: We describe a patient with corneal and scleral dellen, which occurred after an uneventful pterygium excision without adjunctive therapy and a subsequent febrile episode. Case Report: A 43-year-old woman presented with a history of recurrent irritation in her right eye and a diagnosis of pterygium. The pterygium was excised under local anesthesia with the bare scleral technique and without the use of antimetabolites. No complications occurred until 14 days after surgery when corneal and sclera dellen appeared; this was 2 days after a concomitant febrile episode (39°C). Tobramycin and dexamethasone eye drops given after surgery were withdrawn and topical lubricants and antibiotic ointment, in combination with oral L-amino acids, were administered along with eye patching. One week later, the corneal dellen had completely healed and, 4 weeks later, the thinned sclera appeared regularly thick and white in color. Three months after surgery, a small recurrent pterygium was diagnosed, which remained stable without signs of inflammation for additional 18 months. Conclusions: Corneal and scleral dellen might be a late complication of uneventful pterygium surgery without antimetabolites and a subsequent febrile episode.
Predictors of Weight Loss in Obese Older Adults: Findings from the USA and the UK
Authors: Jackson Sarah E. , Beeken Rebecca J. , Wardle Jane
Published: May 2016

Objective: To examine the prevalence and demographic predictors of clinically meaningful weight loss in community samples of obese older adults in the USA and the UK. Methods: Data were from obese older adults (BMI ≥ 30 kg/m2; age ≥ 52 years), free of a cancer diagnosis, from the Health and Retirement Study (HRS; n = 3398) and the English Longitudinal Study of Ageing (ELSA; n = 998). Weight change was assessed from 2004 to 2008. Multivariable logistic regression tested whether age, sex, ethnicity, marital status, education, or BMI predicted ≥ 5% weight loss. Results: Over a quarter (28.7%) of obese participants from HRS and 16.6% from ELSA lost ≥ 5% weight. Being female (odds ratio (OR) = 1.31, 95% confidence interval (CI) = 1.11-1.54) and heavier (BMI ≥ 35 kg/m2) (OR = 1.60, 95% CI = 1.37-1.87) predicted weight loss in HRS. Trends were similar in ELSA (female: OR = 1.18, 95% CI = 0.83-1.69; BMI ≥ 35 kg/m2: OR = 1.24, 95% CI = 0.85-1.82). ORs were increased in ≥ 65-year-olds in HRS (OR = 1.55, 95% CI = 1.33-1.81), and reduced in married people in ELSA (OR = 0.69, 95% CI = 0.48-1.00). Neither education nor ethnicity predicted weight loss in either cohort. Conclusion: A high proportion of obese older adults experience clinically meaningful weight loss, but few demographic variables consistently predict weight loss in this population.
A Differential Diagnosis for Left Atrial Mass on Transthoracic Echocardiography: Hiatus Hernia
Authors: Dhutia Harshil , Gill Felix , Vinnicombe Z.
Published: May 2016

Hiatus hernia is a common medical condition. An elderly woman being investigated for dyspnoea of unknown aetiology had a transthoracic echocardiogram as part of her investigations. This alarmingly demonstrated a large left atrial mass. Further assessment with cardiac magnetic resonance imaging revealed a large hiatus hernia compressing the left atrium and no intra-cardiac mass. The case succinctly highlights gastrointestinal pathology simulating cardiac symptoms and masses.
Influence of Socioeconomic Status on Survival and Clinical Outcomes in Patients with Advanced Gastric Cancer after Chemotherapy
Authors: Choi In Keun , Hyun Jong Jin , Kim Seung Young , Jung Sung Woo , Koo Ja Seol , Kim Jong Han , Yim Hyung Joon , Lee Sang Woo
Published: May 2016

Background: Socioeconomic inequalities are known to influence the survival of cancer patients due to differences in treatment modalities and disease extent at diagnosis. However, there are few studies regarding the influence of socioeconomic status on patient survival, especially after palliative chemotherapy for advanced gastric cancer. Patients and Methods: This retrospective study was performed on 138 advanced gastric cancer patients who received palliative chemotherapy. Demographic, socioeconomic, and cancer-related variables were analyzed according to education level. Effects of socioeconomic factors and cancer-related variables on patient survival were also evaluated. Results: In our study, higher education level (> 6 years of schooling; p = 0.01), disease control (p < 0.01), and a greater number of chemotherapeutic agents (≥ 5 drugs; p < 0.01) were associated with a significant increase in median survival. Multivariate analysis showed that a higher education level (hazard ratio (HR) 0.53; 95% confidence interval (CI) 0.35-0.82; p < 0.01), disease control (HR 0.21; 95% CI 0.13-0.34), and total number of chemotherapeutic agents used (HR 0.44; 95% CI 0.26-0.73) were significantly associated with prolonged survival. Conclusions: Among socioeconomic factors, only higher education level was associated with better survival. Increase in survival was also associated with clinical outcomes, including total number of chemotherapeutic agents used and disease control after chemotherapy.
Receptor Expression Discrepancy between Primary and Metastatic Breast Cancer Lesions
Authors: Karagöz Özen Düriye S. , Ozturk Mehmet A. , Aydin Övgü , Turna Zeynep H. , Ilvan Sennur , Özgüroglu Mustafa
Published: May 2016

SummaryBackground: Recent studies have shown that the expression status of hormone receptors and human epidermal growth factor receptor 2 (HER2) in breast cancer may change during disease progression. The aim of this study was to determine and compare the estrogen receptor (ER), progesterone receptor (PR), and HER2 expression status in primary breast cancer and metastatic lesions. Methods: 58 patients with registered biopsy reports or available samples of the primary tumor and distant metastases were included in the final analysis. Biopsy samples were re-stained using immunohistochemical methods to determine receptor status (if not already recorded in previous reports) and re-examined by 2 independent pathologists. Results: Discordance rates for receptor expression status of the primary tumor and distant metastases for ER, PR, and HER2 were 17.4, 45.4, and 13.3%, respectively. No statistically significant difference in overall survival due to receptor expression discordance between the primary tumor and metastatic sites (p > 0.05) was found, although a tendency toward worse survival time was observed in patients with HER2 expression discrepancies. Conclusion: This study showed receptor discordance rates between primary and metastatic breast cancer sites for ER, PR, and HER2 of 17.8, 45.4, and 13.3%, respectively. Re-biopsy and IHC evaluation of metastatic sites for receptor status may change treatment decisions in patients with relapsed/progressed BC.
A Case of Gastrointestinal Stromal Tumor That Underwent Endoscopic Ultrasound-Guided Aspiration with a 25-Gauge Biopsy Needle
Authors: Tomizawa Minoru , Shinozaki Fuminobu , Motoyoshi Yasufumi , Sugiyama Takao , Yamamoto Shigenori , Ishige Naoki
Published: May 2016

Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is performed to obtain specimens for pathological analysis. For this procedure, 19-gauge (19G), 22-guage (22G), and 25-guage (25G) needles are available. The needles are classified into aspiration type and biopsy type. A 56-year-old woman underwent upper gastrointestinal endoscopy that showed a 38-mm-diameter submucosal tumor. The elevated lesion was diagnosed as a submucosal tumor of the stomach. Contrast-enhanced computed tomography showed a low-density area on the luminal surface of the gastric wall, which was covered with a thin layer of gastric mucosa. EUS showed a hypoechoic lesion in the submucosal layer. Color Doppler image showed a pulsating vascular signal extending into the center of the hypoechoic lesion from the periphery. EUS-FNA was performed with a 25G biopsy needle. The specimen tissue consisted of spindle-shaped cells. The cells were positive for CD117 and CD34. The submucosal tumor was diagnosed as a gastrointestinal stromal tumor.
Icosabutate, a Structurally Engineered Fatty Acid, Improves the Cardiovascular Risk Profile in Statin-Treated Patients with Residual Hypertriglyceridemia
Authors: Kastelein John J.P. , Hallén Jonas , Vige Runar , Fraser David A. , Zhou Rong , Hustvedt Svein Olaf , Orloff David G. , Bays Harold E.
Published: May 2016

Objectives: To evaluate the efficacy and safety of icosabutate, an oral, once-daily, first-in-class medication, in reducing non-high-density lipoprotein cholesterol (non-HDL-C) in patients with persistent hypertriglyceridemia despite statin therapy. Methods: The study was designed to randomly assign 140 patients with fasting triglyceride levels ≥200 but <500 mg/dl on a stable dose of statin therapy to receive either masked icosabutate 600 mg once daily or a control for 12 weeks. The primary end point was a percentage change in non-HDL-C from baseline to 12 weeks. Results: With icosabutate, non-HDL-C levels were reduced (-9.2%) when compared with the control (-0.4%) for a between-group difference of -7.4% (p = 0.02). Compared with the control, icosabutate reduced triglycerides (-27.0%, p < 0.001), very- low-density lipoprotein (VLDL) cholesterol (-31.5%, p < 0.001) and apolipoprotein C-III (-22.5%, p < 0.001). LDL-C levels did not change (0.5%, p = 0.87). HDL-C (10.2%, p < 0.001) was increased. After 113 subjects had been randomized, the study was terminated due to a partial clinical hold imposed by US regulators after observing QT prolongation at supratherapeutic doses of icosabutate in a dog study. In this study, adverse events were balanced between treatment arms, and there were no discontinuations due to adverse events. Conclusions: Icosabutate was efficacious in lowering non-HDL-C and other biomarkers of cardiovascular risk and was generally well tolerated.
Increased Levels of Total p-Cresylsulfate Are Associated with Pruritus in Patients with Chronic Kidney Disease
Authors: Wang Chao-Ping , Lu Yung-Chuan , Tsai I-Ting , Tang Wei-Hua , Hsu Chia-Chang , Hung Wei-Chin , Yu Teng-Hung , Chen Shih-Chieh , Chung Fu-Mei , Lee Yau-Jiunn , Houng Jer-Yiing
Published: May 2016

Background: Pruritus is a common and distressing symptom that affects patients with chronic kidney disease (CKD). Indoxyl sulfate (IS) and p-cresylsulfate (PCS) are uremic toxins with similar protein binding, dialytic clearance, and proinflammatory features. Pruritus in CKD may correlate better with uremic toxins than the glomerular filtration rate (GFR), suggesting that uremic toxins either in the central nervous system or peripherally may play an important role in the pathophysiology. Objective: We sought to investigate the potential contribution of serum total IS and PCS to the pathogenesis of pruritus. Methods: The serum levels of total IS and PCS concentrations were measured in all patients by using the Ultra Performance LC System. The characteristics of pruritus were assessed using a visual analog scale score and an interview questionnaire. Results: Among the 320 CKD patients, 35% had pruritus. The patients with pruritus were older and had a higher frequency of diabetes mellitus, higher uric acid, calcium, phosphorus, creatinine, high-sensitivity C-reactive protein, and total IS and PCS levels, and lower albumin concentrations and estimated GFR (eGFR) than those without pruritus. Increasing concentrations of total PCS were independently and significantly associated with pruritus. Multiple logistic regression analysis revealed total PCS as an independent association factor for pruritus, even after full adjustment of known biomarkers. Furthermore, serum total PCS levels were positively associated with calcium, phosphorus, blood urea nitrogen, creatinine, and white blood cell count, and negatively associated with eGFR, hemoglobin, and hematocrit. Conclusion: Our results indicate that total PCS may play a role in the pathogenesis of pruritus.
Tryptophan Metabolism in Allergic Disorders
Authors: Gostner Johanna M. , Becker Katrin , Kofler Heinz , Strasser Barbara , Fuchs Dietmar
Published: May 2016

Allergic diseases such as asthma and rhinitis, as well the early phase of atopic dermatitis, are characterized by a Th2-skewed immune environment. Th2-type cytokines are upregulated in allergic inflammation, whereas there is downregulation of the Th1-type immune response and related cytokines, such as interferon-γ (IFN-γ). The latter is a strong inducer of indoleamine 2,3-dioxygenase-1 (IDO-1), which degrades the essential amino acid tryptophan, as part of an antiproliferative strategy of immunocompetent cells to halt the growth of infected and malignant cells, and also of T cells - an immunoregulatory intervention to avoid overactivation of the immune system. Raised serum tryptophan concentrations have been reported in patients with pollen allergy compared to healthy blood donors. Moreover, higher baseline tryptophan concentrations have been associated with a poor response to specific immunotherapy. It has been shown that the increase in tryptophan concentrations in patients with pollen allergy only exists outside the pollen season, and not during the season. Interestingly, there is only a minor alteration of the kynurenine to tryptophan ratio (Kyn/Trp, an index of tryptophan breakdown). The reason for the higher tryptophan concentrations in patients with pollen allergy outside the season remains a matter of discussion. To this regard, the specific interaction of nitric oxide (NO∙) with the tryptophan-degrading enzyme IDO-1 could be important, because an enhanced formation of NO∙ has been reported in patients with asthma and allergic rhinitis. Importantly, NO∙ suppresses the activity of the heme enzyme IDO-1, which could explain the higher tryptophan levels. Thus, inhibitors of inducible NO∙ synthase should be reconsidered as candidates for antiallergic therapy out of season that may abrogate the arrest of IDO-1 by decreasing the production of NO∙. Considering its association with the pathophysiology of atopic disease, tryptophan metabolism may play a relevant role in the pathophysiology of allergic disorders.
Cord Blood Soluble CD14 Predicts Wheeze and Prolonged Cough in Young Children: The PATCH Study
Authors: Su Kuan-Wen , Tu Yu-Ling , Chiu Chih-Yung , Huang Yu-Ling , Liao Sui-Lin , Chen Li-Chen , Yao Tsung-Chieh , Ou Liang-Shiou , Lee Wen-I , Huang Jing-Long , Yeh Kuo-Wei ,   for the PATCH Study Group
Published: May 2016

Background: Soluble cluster of differentiation 14 (sCD14) plays a role in the development and manifestation of atopic symptoms, although the results of previous studies have been inconclusive. The aim of this study is to evaluate the practical use of sCD14 as a predictive biomarker of allergy in young children. Methods: Children aged 0-1 year from a birth cohort in the Prediction of Allergies in Taiwanese Children (PATCH) study were enrolled. Cord blood sCD14 concentrations were measured. Pediatrician evaluation and questionnaire interviews were performed periodically until 1 year of age to determine the children's allergic and respiratory symptoms. Results: Two hundred and six 1-year-old subjects were enrolled. Wheeze was positively associated with cord blood sCD14, a family member with asthma and parental smoking. Prolonged cough was associated with cord blood sCD14, older maternal age and more siblings. In the multivariate logistic regression analysis, cord blood sCD14 was the only independent predictive biomarker for wheeze and prolonged cough by 1 year of age. Every 100-ng/ml increase in cord blood sCD14 resulted in a 1.56-fold higher risk of developing wheeze and a 1.62-fold higher risk of prolonged cough in children by 1 year of age. Conclusions: Cord blood sCD14 may be a useful biomarker for predicting infant wheeze and prolonged cough by 1 year of age.
Preoperative Risk Factors for Conversion of Laparoscopic Cholecystectomy to Open Surgery - A Systematic Review and Meta-Analysis of Observational Studies
Authors: Philip Rothman Josephine , Burcharth Jakob , Pommergaard Hans-Christian , Viereck Søren , Rosenberg Jacob
Published: May 2016

Background: Preoperative risk factors for the conversion of laparoscopic cholecystectomy to open surgery have been identified, but never been explored systematically. Our objective was to systematically present the evidence of preoperative risk factors for conversion of laparoscopic cholecystectomy to open surgery. Methods: PubMed and Embase were searched systematically in March 2014. Observational studies evaluating preoperative risk factors for conversion of laparoscopic cholecystectomy to open surgery in patients with gallstone disease were included. The outcome variables extracted were patient demographics, medical history, severity of gallstone disease, and preoperative laboratory values. Results: A total of 1,393 studies were screened for eligibility. We found 32 studies, including 460,995 patients operated with laparoscopic cholecystectomy, eligible for the systematic review. Of these, 10 studies were suitable for 7 meta-analyses on age, gender, body mass index, previous abdominal surgery, severity of disease, white blood cell count, and gallbladder wall thickness. Conclusions: A gallbladder wall thicker than 4-5 mm, a contracted gallbladder, age above 60 or 65, male gender, and acute cholecystitis were risk factors for the conversion of laparoscopic cholecystectomy to open surgery. Furthermore, there was no association between diabetes mellitus or white blood cell count and conversion to open surgery.
Recovery from Choriocarcinoma Syndrome Associated with a Metastatic Extragonadal Germ Cell Tumor Hemorrhage
Authors: Komori Koji , Takahari Daisuke  , Kimura Kenya , Kinoshita Takashi , Ito Seiji , Abe Tetsuya , Senda Yoshiki , Misawa  Kazunari  , Ito Yuichi , Uemura Norihisa , Natsume Seiji , Kawakami Jiro , Iwata Yoshinori  , Tsutsuyama Masayuki  , Shigeyoshi Itaru  , Akazawa Tomoyuki , Hayashi Daisuke , Ouchi Akira , Shimizu Yasuhiro
Published: May 2016

A germ cell tumor is the most common form of malignancy in early male life, and can be classified as either seminomatous or nonseminomatous. Choriocarcinoma, comprised of nonseminomatous germ cells, is the most aggressive type of germ cell tumor and characteristically metastasizes to the retroperitoneal lymph nodes and less frequently to the lungs, liver, bone or brain [Shibuya et al., 2009;48: 551–554]. A 56-year-old man was admitted to another hospital complaining of abdominal distension. Symptoms included anorexia, vomiting, and diarrhea. The patient was diagnosed with an extragonadal germ cell tumor and referred to our hospital to receive chemotherapy. The day after admission, the patient’s abdominal distension gradually worsened. An emergency operation revealed venous hemorrhage from the surface of a metastatic extragonadal germ cell tumor between the ligament of Treitz and the inferior mesenteric vein in a horizontal position. Hemostatic treatment was performed with 4-0 proline thread attached to a medicated cotton sponge, rather than using a simple proline thread, and the closure area was manually compressed. Chemotherapy was initiated on postoperative day 10. A metastatic extragonadal germ cell tumor that causes massive hemorrhage and gastrointestinal hemorrhage is very rare, and represents a life-threatening emergency. If the patient’s condition carries a substantial risk of bleeding to death, it may be worthwhile to attempt abdominal operations.
Novel Genetic Loci Associated with the Plasma Triglyceride Response to an Omega-3 Fatty Acid Supplementation
Authors: Vallée Marcotte Bastien , Cormier Hubert , Guénard Frédéric , Rudkowska Iwona , Lemieux Simone , Couture Patrick , Vohl Marie-Claude
Published: May 2016

Background: A recent genome-wide association study (GWAS) by our group identified 13 loci associated with the plasma triglyceride (TG) response to omega-3 (n-3) fatty acid (FA) supplementation. This study aimed to test whether single-nucleotide polymorphisms (SNPs) within the IQCJ, NXPH1, PHF17 and MYB genes are associated with the plasma TG response to an n-3 FA supplementation. Methods: A total of 208 subjects followed a 6-week n-3 FA supplementation of 5 g/day of fish oil (1.9-2.2 g of eicosapentaenoic acid and 1.1 g of docosahexaenoic acid). Measurements of plasma lipids were made before and after the supplementation. Sixty-seven tagged SNPs were selected to increase the density of markers near GWAS hits. Results: In a repeated model, independent effects of the genotype and the gene-supplementation interaction were associated with plasma TG. Genotype effects were observed with two SNPs of NXPH1, and gene-diet interactions were observed with ten SNPs of IQCJ, four SNPs of NXPH1 and three SNPs of MYB. Positive and negative responders showed different genotype frequencies with nine SNPs of IQCJ, two SNPs of NXPH1 and two SNPs of MYB. Conclusion: Fine mapping in GWAS-associated loci allowed the identification of SNPs partly explaining the large interindividual variability observed in plasma TG levels in response to an n-3 FA supplementation.
Visceral Adiposity Index Is Associated with Pre-Diabetes and Type 2 Diabetes Mellitus in Chinese Adults Aged 20-50
Authors: Liu Peng Ju , Ma Fang , Lou Hui Ping , Chen Yu
Published: May 2016

Background/Aims: Diabetes mellitus and pre-diabetes are closely associated with visceral obesity. Visceral adiposity index (VAI) is a novel sex-specific index, indirectly expressing visceral adipose function. Our aim was to determine the associations of VAI with dysglycemia (the combination of diabetes and pre-diabetes) and to compare the predictive ability for dysglycemia between VAI and traditional obesity indices. Methods: We performed a cross-sectional analysis of the data of 2,754 Chinese community-dwelling people who participated in the health checkup. Sex-specific VAI tertile cut-off points were used as follows: 1.70, 2.77 in males and 0.98, 1.75 in females. Binary logistic regression models were performed to estimate the association of the higher values of all the obesity indices with pre-diabetes and diabetes. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was applied to compare the predictive potential for dysglycemia among the obesity indices. Results: VAI was the only index significantly associated with both pre-diabetes and diabetes in both sexes after adjusting for potential confounders. The results of ROC analysis and AUC showed that VAI possessed the largest AUC, followed by other obesity indices. Conclusions: Higher VAI values are positively associated with the presence of pre-diabetes and diabetes in Chinese adults.
Editorial Vol. 27 N. 1
Authors: Braga Debora Cordeiro
Published: May 2016

Trata-se de sucinto descritivo dos artigos e de uma resenha publicados no Vol. N. 1 2016.
Urbanização, globalização e saúde
Authors: Ribeiro Helena , Vargas Heliana Comin
Published: May 2016

The article probes the interfaces between the concepts of urban health and environmental quality by presenting conceptual frameworks and focusing on elements that make urban environment qualit y a determinant of health. T hen, it addresses the relations between globalization and world urbanization; and presents the example case of Brazilian urbanization and some of its most striking features with a significant impact on urban health: urban sprawl, agglomeration diseconomies , and the effects of globalized virtual communication
Left Atrial Appendage and Closure
Authors: Holmes David R. , Reddy Vivek Y.
Published: May 2016

Patients with nonvalvular atrial fibrillation have a 4- to 5-fold increase in strokes and that rhythm may be responsible for 15% to 20% of all strokes, particularly in the elderly. In this setting, thrombus in the left atrial appendage has been found to be the source of stroke in 90% of cases. Although oral anticoagulants have been found effective in reducing stroke rates, for a variety of issues, they may only be used in 40% to 50% of patients at increased risk for stroke. Given pathophysiology of stroke, site-specific therapy directed at left atrial appendage occlusion has been now studied for stroke prevention, and one device is FDA approved (Watchman). A meta-analysis of 2 randomized clinical trials and 2 registries with this device documented the following: (1) patients receiving the device had significantly fewer hemorrhagic strokes (hazard ratio 0.22,
P
=0.004); (2) a significant reduction in cardiovascular or unexplained death (hazard ratio 0.48,
P
=0.004); (3) more ischemic strokes in the device group; however, when periprocedural events were excluded, the difference was not significant; and (4) a significant reduction in nonprocedural bleeding with the device (hazard ratio 0.51,
P
=0.006) versus control. At present, the only device approved in the United States is indicated in patients with nonvalvular atrial fibrillation with acceptable anatomy who are at increased risk for stroke and would be candidates for anticoagulation in whom there is concern about the risk/benefit ratio for chronic anticoagulation. Unresolved issues include optimal patient selection criteria, the role of devices in patients in whom anticoagulation is contraindicated, and the relative role of novel oral anticoagulants versus the device which has not been tested in randomized trials.
Sustained Endocrine Gland–Derived Vascular Endothelial Growth Factor Levels Beyond the First Trimester of Pregnancy Display Phenotypic and Functional Changes Associated With the Pathogenesis of Pregnancy-Induced Hypertension
Authors: Sergent Frédéric , Hoffmann Pascale , Brouillet Sophie , Garnier Vanessa , Salomon Aude , Murthi Padma , Benharouga Mohamed , Feige Jean-Jacques , Alfaidy Nadia
Published: May 2016

Pregnancy-induced hypertension diseases are classified as gestational hypertension, preeclampsia, or eclampsia. The mechanisms of their development and prediction are still to be discovered. Endocrine gland–derived vascular endothelial growth factor (EG-VEGF) is an angiogenic factor secreted by the placenta during the first trimester of human pregnancy that was shown to control trophoblast invasion, to be upregulated by hypoxia, and to be abnormally elevated in pathological pregnancies complicated with preeclampsia and intrauterine growth restriction. These findings suggested that sustaining EG-VEGF levels beyond the first trimester of pregnancy may contribute to pregnancy-induced hypertension. To test this hypothesis, osmotic minipumps delivering EG-VEGF were implanted subcutaneously into gravid OF1 (Oncins France 1) mice on day 11.5 post coitus, which is equivalent to the end of the first trimester of human pregnancy. Mice were euthanized at 15.5 and 18.5 days post coitus to assess (1) litter size, placental, and fetal weights; (2) placental histology and function; (3) maternal blood pressure; (4) renal histology and function; and (5) circulating soluble fms-like tyrosine kinase 1 and soluble endoglin. Increased EG-VEGF levels caused significant defects in placental organization and function. Both increased hypoxia and decreased trophoblast invasion were observed. Treated mice had elevated circulating soluble fms-like tyrosine kinase 1 and soluble endoglin and developed gestational hypertension with dysregulated maternal kidney function. EG-VEGF effect on the kidney function was secondary to its effects on the placenta as similarly treated male mice had normal kidney functions. Altogether, these data provide a strong evidence to confirm that sustained EG-VEGF beyond the first trimester of pregnancy contributes to the development of pregnancy-induced hypertension.
Interleukin-17A Regulates Renal Sodium Transporters and Renal Injury in Angiotensin II–Induced Hypertension
Authors: Norlander Allison E. , Saleh Mohamed A. , Kamat Nikhil V. , Ko Benjamin , Gnecco Juan , Zhu Linjue , Dale Bethany L. , Iwakura Yoichiro , Hoover Robert S. , McDonough Alicia A. , Madhur Meena S.
Published: May 2016

Angiotensin II–induced hypertension is associated with an increase in T-cell production of interleukin-17A (IL-17A). Recently, we reported that IL-17A
−/−
mice exhibit blunted hypertension, preserved natriuresis in response to a saline challenge, and decreased renal sodium hydrogen exchanger 3 expression after 2 weeks of angiotensin II infusion compared with wild-type mice. In the current study, we performed renal transporter profiling in mice deficient in IL-17A or the related isoform, IL-17F, after 4 weeks of Ang II infusion, the time when the blood pressure reduction in IL-17A
−/−
mice is most prominent. Deficiency of IL-17A abolished the activation of distal tubule transporters, specifically the sodium–chloride cotransporter and the epithelial sodium channel and protected mice from glomerular and tubular injury. In human proximal tubule (HK-2) cells, IL-17A increased sodium hydrogen exchanger 3 expression through a serum and glucocorticoid-regulated kinase 1–dependent pathway. In mouse distal convoluted tubule cells, IL-17A increased sodium–chloride cotransporter activity in a serum and glucocorticoid-regulated kinase 1/Nedd4-2–dependent pathway. In both cell types, acute treatment with IL-17A induced phosphorylation of serum and glucocorticoid-regulated kinase 1 at serine 78, and treatment with a serum and glucocorticoid-regulated kinase 1 inhibitor blocked the effects of IL-17A on sodium hydrogen exchanger 3 and sodium–chloride cotransporter. Interestingly, both HK-2 and mouse distal convoluted tubule 15 cells produce endogenous IL-17A. IL17F had little or no effect on blood pressure or renal sodium transporter abundance. These studies provide a mechanistic link by which IL-17A modulates renal sodium transport and suggest that IL-17A inhibition may improve renal function in hypertension and other autoimmune disorders.
Clinical Implications and Determinants of Left Atrial Mechanical Dysfunction in Patients With Stroke
Authors: Kim Darae , Shim Chi Young , Hong Geu-Ru , Kim Mi-Hyun , Seo Jiwon , Cho In Jeong , Kim Young Dae , Chang Hyuk-Jae , Ha Jong-Won , Heo Ji Hoe , Chung Namsik
Published: May 2016

Background and Purpose—

The evaluation of sources of cardioembolism with transesophageal echocardiography (TEE) in patients with stroke is crucial but semi-invasive. We hypothesized that the size and mechanical function of the left atrium (LA) assessed by transthoracic echocardiography (TTE) could provide useful information on high risk of cardioembolism on TEE in patients with stroke. Furthermore, we sought to define the determinants of LA mechanical dysfunction in these patients.

Methods—

A total of 248 patients with acute ischemic stroke (147 men; 64±13 years) who underwent 2-dimensional and speckle tracking TTE followed by TEE were analyzed.

Results—

LA appendage emptying velocity, prevalence of LA or LA appendage thrombus, prevalence of aortic plaques, and incidence of embolic stroke showed significant differences among the 4 groups classified according to the median values of the LA volume index and global LA longitudinal strain (LALS). Patients at high risk of cardioembolism evidenced by TEE revealed significantly larger LA volume index and lower global LALS than those without. Global LALS (cutoff, 11.5%; area under the curve, 0.947; sensitivity, 100%; specificity, 91%;
P
<0.001) revealed a significantly better diagnostic power (
P
=0.04) for LA or LA appendage thrombus than LA volume index (cutoff, 36.2 mL/m
2
; area under the curve, 0.823; sensitivity, 88%; specificity, 75%;
P
=0.002). Age, left ventricular systolic function, LA volume index, and pulse wave velocity were independent determinants for global LALS.

Conclusions—

LA mechanical dysfunction is closely associated with high risks of cardioembolism. Global LALS assessed by speckle tracking TTE well discriminates the presence of LA or LA appendage thrombus on TEE in patients with acute ischemic stroke.
Emergence of Signal-Based Self-Replication without Manual Design
Authors: Ripps David
Published: May 2016

In the realm of cellular-automata-based artificial life, configurations that self-reproduce employing signals are a more advanced form than those that reproduce holistically by simple fission. One might view those signals as a very rudimentary genetic code, since they guide the formation of the “child” from its “parent.” In principle, the signals could mutate to deliver a child better suited to reproduction in this artificial world. But even the simplest signal-based replicator discovered so far requires 58 specific CA transition rules that have been carefully hand-crafted to exactly meet the requirement of self-replication. Could such a system emerge without human design? This article considers how that might occur. Specifically, it demonstrates that the application of two heuristics can increase the probability that self-replication will emerge when needed transition rules are completed at random. The heuristics are using minimum total resources (parsimony) and maintaining structural continuity. Finally, the article suggests why parsimony is effective in catalyzing the emergence of self-replication.
Artificial Metamorphosis: Evolutionary Design of Transforming, Soft-Bodied Robots
Authors: Joachimczak Michał , Suzuki Reiji , Arita Takaya
Published: May 2016

We show how the concept of metamorphosis, together with a biologically inspired model of multicellular development, can be used to evolve soft-bodied robots that are adapted to two very different tasks, such as being able to move in an aquatic and in a terrestrial environment. Each evolved solution defines two pairs of morphologies and controllers, together with a process of transforming one pair into the other. Animats develop from a single cell and grow through cellular divisions and deaths until they reach an initial larval form adapted to a first environment. To obtain the adult form adapted to a second environment, the larva undergoes metamorphosis, during which new cells are added or removed and its controller is modified. Importantly, our approach assumes nothing about what morphologies or methods of locomotion are preferred. Instead, it successfully searches the vast space of possible designs and comes up with complex, surprising, lifelike solutions that are reminiscent of amphibian metamorphosis. We analyze obtained solutions and investigate whether the morphological changes during metamorphosis are indeed adaptive. We then compare the effectiveness of three different types of selective pressures used to evolve metamorphic individuals. Finally, we investigate potential advantages of using metamorphosis to automatically produce soft-bodied designs by comparing the performance of metamorphic individuals with their specialized counterparts and designs that are robust to both environments.
Electroencephalographic Motor Imagery Brain Connectivity Analysis for BCI: A Review
Authors: Hamedi Mahyar , Salleh Sh-Hussain , Noor Alias Mohd
Published: May 2016

Recent research has reached a consensus on the feasibility of motor imagery brain-computer interface (MI-BCI) for different applications, especially in stroke rehabilitation. Most MI-BCI systems rely on temporal, spectral, and spatial features of single channels to distinguish different MI patterns. However, no successful communication has been established for a completely locked-in subject. To provide more useful and informative features, it has been recommended to take into account the relationships among electroencephalographic (EEG) sensor/source signals in the form of brain connectivity as an efficient tool of neuroscience. In this review, we briefly report the challenges and limitations of conventional MI-BCIs. Brain connectivity analysis, particularly functional and effective, has been described as one of the most promising approaches for improving MI-BCI performance. An extensive literature on EEG-based MI brain connectivity analysis of healthy subjects is reviewed. We subsequently discuss the brain connectomes during left and right hand, feet, and tongue MI movements. Moreover, key components involved in brain connectivity analysis that considerably affect the results are explained. Finally, possible technical shortcomings that may have influenced the results in previous research are addressed and suggestions are provided.
Predictors of Interest in Participation in an Animal-Assisted Activity Program among Elderly Citizens
Authors: Strickland Oriel J. , Davidson Stacie
Published: May 2016

Animal-Assisted Activity Programs have been shown to improve physiological and mental health outcomes among program participants. The purpose of this study was to assess the significance of gender, depression, and companion animal attitudes as predictors of interest in participation in an animal-assisted activity program. The participants were 62 residents (average age 82 years) at assisted-living centers who responded to survey measures including the Pet Attitude Scale (pas), Center for Epidemiological Studies Depression Scale (ces-d), and a newly developed scale to measure interest in an animal assisted activity program. Pet attitudes and gender significantly predicted willingness to participate in the program. These results provide a contribution to the literature, which has not yet documented predictors of interest in participation in such a program among elderly citizens.
Humanism, Anti-Humanism, and Nonhuman Animals
Authors: Coghlan Simon
Published: May 2016

Many attacks against the anthropocentric prejudice that nonhuman animals have a slight or impoverished ethical subjecthood are also attacks on the humanistic idea of human moral uniqueness. This essay examines a way of overturning that anthropocentric prejudice by deploying certain conceptual resources of an expansive ethical humanism. Although this may appear to be a strange route to that destination, the suggestion is raised that this approach might significantly enrich our conception of nonhumans as ethical subjects.
William of Ockham’s Ontology of Arithmetic
Authors: Roques Magali
Published: May 2016

Ockham’s ontology of arithmetic, specifically his position on the ontological status of natural numbers, has not yet attracted the attention of scholars. Yet it occupies a central role in his nominalism; specifically, Ockham’s position on numbers constitutes a third part of his ontological reductionism, alongside his doctrines of universals and the categories, which have long been recognized to constitute the first two parts. That is, the first part of this program claims that the very idea of a universal thing is self-contradictory, while the second part asserts that it is more rational to accept only two distinct types of singular things, namely substance and quality. These two elements are incomplete, however, for they do not fully encompass Ockham’s position on what realists take to be abstract objects. For this, one needs the third part of Ockham’s program of ontological reductionism, dealing with numbers, among the most paradigmatic abstract objects for realists.