bluuebunny/crossref_metadata_2025 huggingface dataset:
The Transcription Factor ATF4 Promotes Expression of Cell Stress Genes and Cardiomyocyte Death in a Cellular Model of Atrial Fibrillation
Authors: Freundt Johanna K. , Frommeyer Gerrit , Wötzel Fabian , Huge Andreas , Hoffmeier Andreas , Martens Sven , Eckardt Lars , Lange Philipp S.
Published: May 2018

Introduction. Cardiomyocyte remodelling in atrial fibrillation (AF) has been associated with both oxidative stress and endoplasmic reticulum (ER) stress and is accompanied by a complex transcriptional regulation. Here, we investigated the role the oxidative stress and ER stress responsive bZIP transcription factor ATF4 plays in atrial cardiomyocyte viability and AF induced gene expression. Methods. HL-1 cardiomyocytes were subjected to rapid field stimulation. Forced expression of ATF4 was achieved by adenoviral gene transfer. Using global gene expression analysis and chromatin immunoprecipitation, ATF4 dependent transcriptional regulation was studied, and tissue specimen of AF patients was analysed by immunohistochemistry. Results. Oxidative stress and ER stress caused a significant reduction in cardiomyocyte viability and were associated with an induction of ATF4. Accordingly, ATF4 was also induced by rapid field stimulation mimicking AF. Forced expression of wild type ATF4 promoted cardiomyocyte death. ATF4 was demonstrated to bind to the promoters of several cell stress genes and to induce the expression of a number of ATF4 dependent stress responsive genes. Moreover, immunohistochemical analyses showed that ATF4 is expressed in the nuclei of cardiomyocytes of tissue specimen obtained from AF patients. Conclusion. ATF4 is expressed in human atrial cardiomyocytes and is induced in response to different types of cell stress. High rate electrical field stimulation seems to result in ATF4 induction, and forced expression of ATF4 reduces cardiomyocyte viability.
Magnetic Resonance Imaging Findings in the Muscle Tissue of Patients with Limb Girdle Muscular Dystrophy Type 2I Harboring the Founder Mutation c.545A>G in the FKRP Gene
Authors: Xie Zhiying , Xiao Jiangxi , Zheng Yiming , Wang Zhaoxia , Yuan Yun
Published: May 2018

Limb girdle muscular dystrophy type 2I (LGMD2I) is an autosomal recessive muscular dystrophy that is rare in Asia and is caused by mutations in the fukutin-related protein gene (FKRP). The aim of this study was to determine if there are any characteristic features of muscle on magnetic resonance imaging (MRI) in patients with LGMD2I harboring the founder mutation c.545A>G in FKRP. Using MRI, we delineated changes in the thigh muscles of ten patients with genetically confirmed LGMD2I. The majority of muscle biopsy specimens showed reduced glycosylation of α-dystroglycan, decreased expression of laminin α2, and a dystrophic pattern. In our cohort, the muscles with the most severe fatty infiltration were adductor magnus and vastus intermedius, whereas the rectus femoris, sartorius, and gracilis muscles were relatively spared. In seven patients, we identified a concentric fatty infiltration pattern that was most pronounced in the vastus intermedius and vastus medialis muscles around the distal femoral diaphysis. In this disease, the initial fatty infiltration of the posterior thigh muscles gradually progresses anteriorly regardless of the founder mutation in FKRP. Muscle tissue in patients with LGMD2I who have the founder mutation c.545A>G in FKRP shows a distinctive concentric pattern of fatty infiltration and edema on MRI.
Could the Combined Administration of Bone Antiresorptive Drug, Taxanes, and Corticosteroids Worsen Medication Related Osteonecrosis of the Jaws in Cancer Patients?
Authors: Oteri Giacomo , Campisi Giuseppina , Panzarella Vera , Morreale Ilaria , Nucera Riccardo , Di Fede Olga , Picone Antonio , Marcianò Antonia
Published: May 2018

The study presents a report of 58 metastatic cancer patients who developed osteonecrosis of the jaws after being treated with zoledronic acid and taxanes, plus corticosteroids. A retrospective analysis of data registered in the archives of two Italian osteonecrosis of the jaws treatment centers, who are based at the University of Messina and at the University of Palermo, was performed in order to study, in these patients, demographic data and characteristics such as frequency of cancer location, lines of therapy, frequency of cancer drugs, presence/absence of oral trigger, number, location, and stage of jaw osteonecrosis. It was found that the majority of patients developed advanced stages of osteonecrosis, frequently complicated with infection. It was hypothesized that the concurrent administration of chemotherapeutic agents could be eventually considered as a factor able to allow a faster worsening of the clinical manifestation through the exacerbation of soft tissue defects, due to chemotherapy drugs.
Nonrelativistic Arbitrary l-States of Quarkonium through Asymptotic Iteration Method
Authors: Ciftci Hakan , Kisoglu Hasan Fatih
Published: May 2018

The energy eigenvalues with any l≠0 states and mass of heavy quark-antiquark system (quarkonium) are obtained by using Asymptotic Iteration Method in the view of nonrelativistic quantum chromodynamics, in which the quarks are considered as spinless for easiness and are bounded by Cornell potential. A semianalytical formula for energy eigenvalues and mass is achieved via the method in scope of the perturbation theory. The accuracy of this formula is checked by comparing the eigenvalues with the ones numerically obtained in this study and with exact ones in literature. Furthermore, semianalytical formula is applied to cc-, bb-, and cb- meson systems for comparing the masses with the experimental data.
The Antidiabetic Agent Sodium Tungstate Induces Abnormal Glycogen Accumulation in Renal Proximal Tubules from Diabetic IRS2-Knockout Mice
Authors: Bertinat Romina , Westermeier Francisco , Silva Pamela , Gatica Rodrigo , Oliveira Joana Moitinho , Nualart Francisco , Gomis Ramón , Yáñez Alejandro J.
Published: May 2018

The kidney is an insulin-sensitive organ involved in glucose homeostasis. One major effect of insulin is to induce glycogen storage in the liver and muscle. However, no significant glycogen stores are detected in normal kidneys, but diabetic subjects present a characteristic renal histopathological feature resulting from extensive glycogen deposition mostly in nonproximal tubules. The mechanism of renal glycogen accumulation is yet poorly understood. Here, we studied in situ glycogen accumulation in the kidney from diabetic IRS2-knockout mice and the effect of the insulin-mimetic agent sodium tungstate (NaW). IRS2-knockout mice displayed hyperglycemia and hyperinsulinemia. NaW only normalized glycemia. There was no evident morphological difference between kidneys from untreated wild-type (WT), NaW-treated WT, and untreated IRS2-knockout mice. However, NaW-treated IRS2-knockout mice showed tubular alterations resembling clear cells in the cortex, but not in the outer medulla, that were correlated with glycogen accumulation. Immunohistochemical detection of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase, mostly expressed by renal proximal tubules, showed that altered tubules were of proximal origin. Our preliminary study suggests that IRS2 differentially regulates glycogen accumulation in renal tubules and that NaW treatment in the context of IRS2 ablation induces abnormal glycogen accumulation in cortical proximal tubules.
Clinical and Epidemiological Status of Leptospirosis in a Tropical Caribbean Area of Colombia
Authors: Tique Vaneza , Mattar Salim , Miranda Jorge , Oviedo Misael , Noda Angel , Montes Eney , Rodriguez Virginia
Published: May 2018

Objective. To describe and analyze the clinical and epidemiological status in 28 confirmed cases of human leptospirosis at the main public hospital of Cordoba. Methods. Between 2012 and 2013, we conducted an active surveillance at the main hospital of Cordoba to establish the etiologic diagnosis of the undifferentiated tropical febrile illness (UTFI) cases. UTFI is defined as a fever without an infection focus in the initial physical examination or in basic laboratory tests. Patients in acute phase were accompanied by prodromal symptoms, including myalgia, arthralgia, headache, asthenia, chills, icterus, dyspnea, abdominal pain, rash, and nausea. Samples were collected on admission and at discharge. Clinical and epidemiological data were collected for each patient. Microscopic agglutination test (MAT) was performed. Results. The 28 leptospirosis cases presented the following gender distribution: male (n=24) and female (n=4). The duration of hospitalization was 10.39 days. The main symptoms and clinical manifestations were fever, headache and nausea, vomiting, and abdominal pain, all of which occurred in up to 60% of patients. Of the 28 cases studied, 4 were fatal. The most frequent infecting serogroups were Ballum and Canicola. Conclusion. Leptospirosis is a common cause of undifferentiated tropical febrile illness in Colombia; it is important to establish ongoing and accurate surveillance for acute febrile illness to facilitate the detection of cases of leptospirosis.
Successful Management of Teeth with Different Types of Endodontic-Periodontal Lesions
Authors: Alquthami Hind , Almalik Abdulaziz M. , Alzahrani Faisal F. , Badawi Lana
Published: May 2018

Endodontic-periodontal diseases often present great challenges to the clinician in their diagnosis, management, and prognosis. Understanding the disease process through cause-and-effect relationships between the pulp and supporting periodontal tissues with the aid of rational classifications leads to successful treatment outcomes. In this report, we present several treatment modalities in patients with different endodontic-periodontal lesions. A modification to the new endodontic-periodontic classification, Al-Fouzan’s classification, was also added. The first case was classified as retrograde periodontal disease (i.e., primary endodontic lesion with drainage through the periodontal ligament). The second case was diagnosed as an iatrogenic periodontal lesion caused by root perforation. The third case was diagnosed as an iatrogenic periodontal lesion caused by tooth trauma due to orthodontic treatment. The first two cases were managed with a nonsurgical approach, whereas the third case was managed with nonsurgical and surgical approaches. All patients showed complete healing of soft and hard tissue lesions. A thorough understanding of the disease history and the patient’s signs and symptoms, complete examination with full investigation, and the use of a systematic step-by-step approach in the management of such challenging endodontic-periodontal lesions with regular recall visits were very useful and successful.
Clinical and Etiological Aspects of Gynecomastia in Adult Males: A Multicenter Study
Authors: Costanzo Pablo René , Pacenza Néstor Antonio , Aszpis Sergio Mario , Suárez Sebastián Matías , Pragier Uriel Marcelo , Usher Jorge Guillermo Stewart , Vásquez Cayoja Miguel , Iturrieta Sergio , Gottlieb Silvia Elisa , Rey Rodolfo Alberto , Knoblovits Pablo
Published: May 2018

Objectives. To evaluate the characteristics of presentation, biochemical profile, and etiology of gynecomastia in adults. Methods. Medical records of 237 men aged 18-85 years with gynecomastia were evaluated. Results. Highest prevalence of gynecomastia was observed between 21 and 30 years (n = 74; 31.2%). The most common presenting complaints were aesthetic concerns (62.8%) and breast pain (51.2%). 25.3% of the subjects had a history of pubertal gynecomastia. 56.5% had bilateral gynecomastia. 39.9% were overweight and 22.8% were obese. The etiology could not be identified in 45.1% of the cases; the most frequent identified causes were anabolic steroids consumption (13.9%), hypogonadism (11.1%), and use of pharmaceutical drugs (7.8%). Patients with bilateral gynecomastia had a longer history of disease, higher BMI, and lower testosterone levels. Conclusions. Patients with gynecomastia presented more often with aesthetic concerns and secondarily with breast pain. The most frequent final diagnosis was idiopathic gynecomastia, whereas the most frequent identified etiologies were anabolic steroids consumption, hypogonadism, and use of pharmaceutical drugs. Despite the low frequency of etiologies such as thyroid dysfunction or adrenal carcinoma, we emphasize the importance of a thorough assessment of the patient, as gynecomastia may be the tip of the iceberg for the diagnosis of treatable diseases.
Arthroscopic Management and Radiographic Interpretation of an Everted Bony Bankart Lesion
Authors: Hron Alexander J. , Noonan Benjamin C.
Published: May 2018

Soft tissue injuries are prevalent after traumatic anterior shoulder dislocation. However, bony fractures, often referred to as bony Bankart injuries, are less common. The authors describe the case of a 16-year-old male who displayed a bony Bankart with a unique, everted presentation. The patient presented with left shoulder pain, restricted range of motion, and crepitus. Two weeks prior to physical examination, he sustained a traumatic anterior glenohumeral dislocation after a bicycle accident, which reduced spontaneously. Plain film imaging revealed a bony fragment off the anterior glenoid. Upon critical examination of magnetic resonance imaging axial cuts, the bony fragment was found to be flipped. Intraoperatively, this orientation was confirmed. The fragment was reduced and stabilized in an anatomic position using a double row technique with the capsule then advanced over the top of the fragment using three additional anchors. Imaging four months postoperatively revealed an anatomical reduction of the fragment. To the authors’ knowledge, this is the first reported case of bony fragment eversion following traumatic anterior shoulder dislocation. Although the incidence of everted bony fragments following traumatic dislocation is unknown, such a situation presents unique challenges to the orthopedic surgeon. The authors discuss potential eversion mechanisms, fragment identification by imaging, surgical indications, and operative techniques.
Elastic Tubing Resistance Training and Autonomic Modulation in Subjects with Chronic Obstructive Pulmonary Disease
Authors: Ricci-Vitor Ana Laura , Vanderlei Luiz Carlos M. , Pastre Carlos Marcelo , Ramos Dionei , Ramos Ercy Mara C. , Ferreira Filho Celso , Ferreira Celso
Published: May 2018

This study addresses evidence concerning elastic tubing resistance training (ET) on autonomic modulation in patients with chronic obstructive pulmonary disease (COPD). Autonomic dysfunction is common in COPD and contributes to the development of arrhythmias and sudden death. Along with autonomic dysfunction, muscle dysfunction is related to functional limitations and prognosis of the disease. This study investigated the effects of ET on autonomic modulation, muscle strength, and walking distance in COPD. Subjects were divided into two groups, ET (n=20; 66,5±8,9 y; 25,5±3,5 kg/m2; FEV1/FVC: 50,3±11,0) and conventional training (n=19; 66,0±6,9; 27,1±4,3; FEV1/FVC: 55,05±9,56). Both groups undertook 24 sessions for 60 minutes, 3 times in a week. The significance level was p ≤ 0,05. Autonomic modulation was evaluated using heart rate variability in the time (rMSSD, ms) and frequency domain (HF, ms). Strength for upper and lower limbs was measured using dynamometry and walking distance was measured using a 6-minute walking test. There were no significant differences in the outcomes between groups. There was an increment to rMSSD [(16,7±11,0 versus 20,8±14,9) versus (14,2±10,0 versus 17,4±12,1)], HF [(141,9±191,3 versus 234,9±335,7) versus (94,1±123,5 versus 177,6±275,5)], shoulder abduction [(50,1±19,6 versus 56,9±20,4) versus (50,5±19,0 versus 56,9±19,3)], knee flexion [(101,9±34,0 versus 116,8±43,3) versus (98,6±21,5 versus 115,1±30,8)], and walking test [(433,0±84,8 versus 468,9±90,8) versus (397,4±99,8 versus 426,3±101,6)] after training for ET and conventional training, respectively. In conclusion, ET improves autonomic modulation in COPD with additional benefits for strength and cardiorespiratory capacity similar to conventional training.
Notch-Induced Myeloid Reprogramming in Spontaneous Pancreatic Ductal Adenocarcinoma by Dual Genetic Targeting
Authors: Cheung Phyllis F. , Neff Florian , Neander Christian , Bazarna Anna , Savvatakis Konstantinos , Liffers Sven-Thorsten , Althoff Kristina , Lee Chang-Lung , Moding Everett J. , Kirsch David G , Saur Dieter , Bazhin Alexandr V. , Trajkovic-Arsic Marija , Heikenwalder Mathias F. , Siveke Jens T.
Published: May 2018

Despite advances in our understanding of the genetics of pancreatic ductal adenocarcinoma (PDAC), the efficacy of therapeutic regimens targeting aberrant signaling pathways remains highly limited. Therapeutic strategies are greatly hampered by the extensive desmoplasia that comprises heterogeneous cell populations. Notch signaling is a contentious pathway exerting opposite roles in tumorigenesis depending on cellular context. Advanced model systems are needed to gain more insights into complex signaling in the multilayered tumor microenvironment. In this study, we employed a dual recombinase-based in vivo strategy to modulate Notch signaling specifically in myeloid cells to dissect the tumorigenic role of Notch in PDAC stroma. Pancreas-specific KrasG12D activation and loss of Tp53 was induced using a Pdx1-Flp transgene, whereas Notch signaling was genetically targeted using a myeloid-targeting Lyz2-Cre strain for either activation of Notch2-IC or deletion of Rbpj. Myeloid-specific Notch activation significantly decreased tumor infiltration by protumorigenic M2 macrophages in spontaneous endogenous PDAC, which translated into significant survival benefit. Further characterization revealed upregulated antigen presentation and cytotoxic T effector phenotype upon Notch-induced M2 reduction. This approach is the first proof of concept for genetic targeting and reprogramming of myeloid cells in a complex disease model of PDAC and provides evidence for a regulatory role of Notch signaling in intratumoral immune phenotypes.

Significance: This study provides insight into the role of myeloid-dependent NOTCH signaling in PDAC and accentuates the need to dissect differential roles of signaling pathways in different cellular components within the tumor microenvironment. Cancer Res; 78(17); 4997–5010. ©2018 AACR.
Detection of Gastric Cancer with Novel Methylated DNA Markers: Discovery, Tissue Validation, and Pilot Testing in Plasma
Authors: Anderson Bradley W. , Suh Yun-Suhk , Choi Boram , Lee Hyuk-Joon , Yab Tracy C. , Taylor William R. , Dukek Brian A. , Berger Calise K. , Cao Xiaoming , Foote Patrick H. , Devens Mary E. , Boardman Lisa A. , Kisiel John B. , Mahoney Douglas W. , Slettedahl Seth W. , Allawi Hatim T. , Lidgard Graham P. , Smyrk Thomas C. , Yang Han-Kwang , Ahlquist David A.
Published: May 2018

Purpose: Gastric adenocarcinoma is the third most common cause of cancer mortality worldwide. Accurate and affordable noninvasive detection methods have potential value for screening and surveillance. Herein, we identify novel methylated DNA markers (MDM) for gastric adenocarcinoma, validate their discrimination for gastric adenocarcinoma in tissues from geographically separate cohorts, explore marker acquisition through the oncogenic cascade, and describe distributions of candidate MDMs in plasma from gastric adenocarcinoma cases and normal controls.

Experimental Design: Following discovery by unbiased whole-methylome sequencing, candidate MDMs were validated by blinded methylation-specific PCR in archival case–control tissues from U.S. and South Korean patients. Top MDMs were then assayed by an analytically sensitive method (quantitative real-time allele-specific target and signal amplification) in a blinded pilot study on archival plasma from gastric adenocarcinoma cases and normal controls.

Results: Whole-methylome discovery yielded novel and highly discriminant candidate MDMs. In tissue, a panel of candidate MDMs detected gastric adenocarcinoma in 92% to 100% of U.S. and South Korean cohorts at 100% specificity. Levels of most MDMs increased progressively from normal mucosa through metaplasia, adenoma, and gastric adenocarcinoma with variation in points of greatest marker acquisition. In plasma, a 3-marker panel (ELMO1, ZNF569, C13orf18) detected 86% (95% CI, 71–95) of gastric adenocarcinomas at 95% specificity.

Conclusions: Novel MDMs appear to accurately discriminate gastric adenocarcinoma from normal controls in both tissue and plasma. The point of aberrant methylation during oncogenesis varies by MDM, which may have relevance to marker selection in clinical applications. Further exploration of these MDMs for gastric adenocarcinoma screening and surveillance is warranted. Clin Cancer Res; 24(22); 5724–34. ©2018 AACR.
Phase Ib Study of Binimetinib with Paclitaxel in Patients with Platinum-Resistant Ovarian Cancer: Final Results, Potential Biomarkers, and Extreme Responders
Authors: Grisham Rachel N. , Moore Kathleen N. , Gordon Michael S. , Harb Wael , Cody Gwendolyn , Halpenny Darragh F. , Makker Vicky , Aghajanian Carol A.
Published: May 2018

Purpose: Epithelial ovarian cancer (EOC) is a molecularly diverse disease. MEK inhibition targets tumors harboring MAPK pathway alterations and enhances paclitaxel-induced apoptosis in EOC. This phase Ib study evaluated the MEK inhibitor binimetinib combined with paclitaxel in patients with platinum-resistant EOC.

Patients and Methods: Patients received intravenous weekly paclitaxel with oral binimetinib in three different administration schedules. Outcomes were assessed by RECIST and CGIC CA-125 response criteria. Tumor samples were analyzed using next-generation sequencing.

Results: Thirty-four patients received ≥1 binimetinib dose. A 30-mg twice-a-day continuous or 45-mg twice-a-day intermittent binimetinib dose was deemed the recommended phase II dose (RP2D) in combination with 80 mg/m2 i.v. weekly paclitaxel. Rate of grade 3/4 adverse events was 65%. The best overall response rate was 18%—one complete (CR) and four partial responses (PR)—among 28 patients with RECIST-measurable disease. Eleven patients achieved stable disease (SD), yielding a clinical benefit rate (CR+PR+SD) of 57%. Response rates, per both RECIST and CA-125 criteria, were highest in the 45-mg twice-a-day continuous cohort and lowest in the 45-mg twice-a-day intermittent cohort. All four evaluable patients with MAPK pathway–altered tumors experienced clinical benefit.

Conclusions: The combination of binimetinib and intravenous weekly paclitaxel was tolerable in this patient population. The RP2D of binimetinib in combination with paclitaxel was 30 mg twice a day as a continuous or 45 mg twice a day as an intermittent dose. Although response rates were modest, a higher clinical benefit rate was seen in patients harboring alterations affecting the MAPK pathway. Clin Cancer Res; 24(22); 5525–33. ©2018 AACR.
Alterations of Cortisol Metabolism in Human Disorders
Authors: White Perrin C.
Published: May 2018

The interconversion of active and inactive corticosteroids – cortisol and cortisone, respectively, in humans – is modulated by isozymes of 11β-hydroxysteroid dehydrogenase (11-HSD). Studies of this process have provided crucial insights into glucocorticoid effects in a wide variety of tissues. The 11-HSD1 isozyme functions mainly as an oxoreductase (cortisone to cortisol) and is expressed at high levels in the liver and other glucocorticoid target tissues. Because it is required for full physiological effects of cortisol, it has emerged as a drug target for metabolic syndrome and type 2 diabetes. Mutations in the corresponding HSD11B1 gene, or in the H6PD gene encoding hexose-6-phosphate dehydrogenase (which supplies the NADPH required for the oxoreductase activity of 11-HSD1), cause apparent cortisone reductase deficiency, a rare syndrome of adrenocortical hyperactivity and hyperandrogenism. In contrast, the 11-HSD2 isozyme functions as a dehydrogenase (cortisol to cortisone) and is expressed mainly in mineralocorticoid target tissues, where it bars access of cortisol to the mineralocorticoid receptor. Mutations in the HSD11B2 gene encoding 11-HSD2 cause the syndrome of apparent mineralocorticoid excess, a severe form of familial hypertension. The role of this enzyme in the pathogenesis of common forms of low-renin hypertension remains uncertain.
Effects of Progressive Additional Lenses on Binocular Vision in Children with Pseudophakia
Authors: Tanaka Minatsu , Matsumoto Fumiko , Kusaka Shunji
Published: May 2018

Binocular vision may be compromised in children after unilateral cataract surgery because the distances at which clear vision is present are different for the two eyes. We believe that wearing progressive additional lenses can be effective in improving the binocular vision in children with pseudophakia.
Experience of a Tertiary-Level Urology Center in the Clinical Urological Events of Rare and Very Rare Incidence. III. Psychourological Events: 1. Psychic Anuria
Authors: Gadelkareem Rabea A. , Moeen Ahmed M. , Reda Ahmed , Azoz Nashwa M. , Elhadad Ali F. , Taha Taha M. , Mohammed Nasreldin , Taha Mohammed I.
Published: May 2018

Introduction: Psychic anuria is an old term, referring to a very rare psycho-urological event that has scarcely been studied so far. Materials and Methods: A retrospective study of the patients with psychic anuria presented to Assiut Urology and Nephrology Hospital during the period July 1991–June 2016 was done. Psychic anuria was defined, and the demographic and clinical characteristics including the methods of diagnosis and management were studied. Results: Of more than 3,800 cases of anuria, 9 female patients (0.24%) experienced psychic anuria in the age range of 17–43 years. Cardinal clinical findings included anuria for 36–72 h with absence of organic causes and normal renal function tests. Psychosocial risk factors were reported in the 9 cases. Anuria was documented by reliable history (56%) or observable urine collection (44%). Diagnosis was done by exclusion, where the investigations revealed no organic causes. Seven cases responded to the placebo intervention and 2 cases were self-limiting and resolved spontaneously. Conclusions: Psychic anuria is an extremely rare urological emergency that presents, mainly, in young adult females with unknown mechanisms. Renal vasoconstriction following psychosocial stressors is suggested. It is diagnosed by exclusion and resolves spontaneously or responds to placebo intervention as a mental distraction technique.
Evaluation of the LC-1000 Flow Cytometry Screening System for Cervical Cancer Screening in Routine Health Checkups
Authors: Heo Ilyeong , Kwak Hyoung-Jung , Nah Eun-Hee , Cho Seon , Kim Suyoung , Cho Han-Ik
Published: May 2018

Objective: This study evaluated the performance of a flow cytometry system (LC-1000) in screening cervical precancerous lesions at routine health checkups. Study design: In total, 928 health examinees were enrolled at 16 health promotion centers in 13 Korean cities between 2016 and 2017. All participants underwent liquid-based cervical cytology and flow cytometry testing to determine the cell proliferation index (CPIx). Results: The positivity rate of the LC-1000 system increased with the severity of the cervical cytology findings (p for trend < 0.001). When low-grade squamous intraepithelial lesion (LSIL) or higher (including LSIL, high-grade squamous intraepithelial lesion [HSIL], and atypical squamous cells without excluding HSIL [ASC-H]) was defined as gold-standard positivity, the sensitivity, specificity, PPV, and NPV of LC-1000 were 75.3% (95% confidence interval [CI], 66.8–83.7), 58.5% (95% CI, 55.2–61.9), 18.1% (95% CI, 14.5–21.8), and 95.1% [95% CI, 93.2–97.0], respectively. The median CPIx increased significantly from normal cytology to HSIL (p < 0.001). The median CPIx was higher in high-risk human papillomavirus (HR-HPV)-positive cases than in HR-HPV-negative cases (0.23 vs. 0.17, p < 0.001), while it did not differ between HR-HPV-positive and HR-HPV-negative cases with normal cytology findings (0.16 vs. 0.16, p = 0.700). Conclusion: The LC-1000 system is potentially useful for screening cervical precancer and cancer, especially when excluding normal or ASC of undetermined significance cases in routinely screened populations.
Methotrexate-Associated Lymphoproliferative Disorder: Dermoscopic Features
Authors: Namiki Takeshi , Sone Yumiko , Miura Keiko , Tanaka Masaru , Yokozeki Hiroo
Published: May 2018

Methotrexate-related lymphoproliferative disorder (MTX-LPD) is a rare disorder caused by long-term MTX therapy for autoimmune diseases. There has been no report of the dermoscopic features of MTX-LPD to date. A 64-year-old female presented with a slightly elevated indurated erythematous plaque with scales on her right thigh. The patient had been treated for rheumatic arthritis with MTX and prednisolone for more than 15 years, and 18 mg/week MTX without prednisolone had been administered in the last year. Dermoscopy revealed dotted vessels and glomerular vessels on pink homogeneous areas and multiple surface scales. Enhanced computed tomography showed multiple nodules and lymphadenopathies at the mediastinum and axillae. Histopathological examination revealed telangiectasia in the superficial dermis. Atypical lymphoid cells were scattered in the whole dermis and subcutaneous tissue. A perivascular infiltrate of atypical lymphocytes and histiocytoid cells partially destroyed the vessel walls. Epstein-Barr virus in situ hybridization showed a positive result. The cessation of MTX reduced the erythematous plaque, and lymphadenopathies at the neck, mediastinum, and axillae were not palpable. We discuss the relevance of these dermoscopic and histopathological features. The accumulation of such cases will reveal the dermoscopic features of MTX-LPD and the utility of dermoscopy for the diagnosis of MTX-LPD.
Roles and Mechanisms of Human Cathelicidin LL-37 in Cancer
Authors: Chen Xi , Zou Xianqiong , Qi Guangying , Tang Ying , Guo Yong , Si Jia , Liang Lihua
Published: May 2018

LL-37, the C-terminal peptide of human cathelicidin antimicrobial peptide (CAMP, hCAP18), reportedly increases resistance to microbial invasion and exerts important physiological functions in chemotaxis, promotion of wound closure, and angiogenesis. Accumulating evidence indicates that LL-37 also plays a significant role in human cancer. LL-37 induces tumorigenic effects in cancers of the ovary, lung, breast, prostate, pancreas, as well as in malignant melanoma and skin squamous cell carcinoma. In contrast, LL-37 displays an anti-cancer effect in colon cancer, gastric cancer, hematologic malignancy and oral squamous cell carcinoma. Mechanistically, LL-37-induced activation of membrane receptors and subsequent signaling pathways lead to alteration of cellular functions. Different membrane receptors on various cancer cells appear to be responsible for the tissue-specific effects of LL-37. Meanwhile, the findings that vitamin D-dependent induction of cathelicidin in human macrophages activates the anti-cancer activity of tumor-associated macrophages (TAMs) and enhances antibody-dependent cellular cytotoxicity (ADCC) support critical roles of vitamin D-dependent induction of cathelicidin in cancer progression. This review describes novel advances involving the roles and mechanisms of human cathelicidin LL-37 in cancer.
Raddeanin a Suppresses Glioblastoma Growth by Inducing ROS Generation and Subsequent JNK Activation to Promote Cell Apoptosis
Authors: Peng Fei , Wang Xiaoxiong , Shu Mengting , Yang Mingfei , Wang Ligang , Ouyang Zhongrui , Shen Chen , Hou Xu , Zhao Boyan , Wang Xinzhuang , Zhang Linda Wei , Liu Yaohua , Zhao Shiguang
Published: May 2018

Background/Aims: Raddeanin A (RA), an active pharmacological ingredient from Anemone raddeana Regel, plays an important role in tumor suppression. In this study, we assessed the potentially therapeutic effect of RA on glioblastoma and its underlying mechanisms. Methods: Cell viability was examined using the MTT assay. Invasive and migratory capacities were examined using Transwell and wound healing assays. Apoptosis was determined by Hoechst staining, flow cytometry, DCFH-fluorescent probe and immunohistochemical staining. Autophagy was detected by transmission electron microscopy and western blotting. A U251 glioma xenograft model was established to evaluate the effect of RA in vivo. Results: The data demonstrated that RA inhibited viability, and abrogated the invasive/migratory abilities of glioblastoma cells. In addition, RA induced apoptosis by reactive oxygen species (ROS)/ Jun N-terminal kinase (JNK) signaling in glioblastoma. Conversely, the antioxidant N-Acetyl-L-cysteine (NAC) and pan-caspase inhibitor z-VAD-fmk attenuated RA-induced apoptosis by scavenging ROS and inactivating caspase-3. Furthermore, the inhibition of autophagy by 3-MA exacerbated apoptosis through ROS generation and JNK phosphorylation. In vivo, RA exhibited a curative effect on U251-derived xenografts in nude mice. Conclusions: The results of this study suggest that RA suppressed the growth of glioblastoma, thus serving as a promising and potential strategy for glioblastoma chemotherapy.
A souvenir from Nahur: a sample of “entanglement” in the reconstruction of the Mesopotamian past
Authors: Casero Chamorro María Dolores
Published: May 2018

A.0.76.25 não é uma inscrição de butim comum. O original ainda não foi encontrado, mas sua recordação foi integrada em um texto mais amplo, VAT 16381, gravado em uma tabueta de argila, onde é citado entre as linhas 21 e 24. As circustâncias e o contexto nos quais esta inscrição foi trasmitida apresentam algumas peculiaridades, que a faz um excelente exemplo de análise de uma perspectiva teórica de agência. O estudo buscará no modelo de "emaranhamento" proposto por Hodder (2012) em relação às interações e relações de dependência entre as esferas humana e dos objetos. Ele irá prover uma melhor compreensão dos objetos tomados como butim e seu papel na construção da identidade Assíria, por meio de sua vida e as camadas de significado que continham acerca de Adad-nirari I e Tukulti-Ninurta I, os reis Assírios que as possuía, as usava e as contemplava.
Musical choir as an anthropological place in the athenian society at the end of the sixth century BC. through the imagetical analysis of attic pottery
Authors: Araujo Felipe Nascimento de
Published: May 2018

Através de uma abordagem da antropologia social, baseada no conceito de lugar antropológico de Marc Augé, este artigo pretende estabelecer uma breve análise de como os coros musicais se relacionam com a ideia de cidadania ateniense que se construiu a partir da tirania até as reformas de Clístenes. Esse contexto histórico caracteriza-se pela instauração da isonomia – governo baseado na igualdade dos cidadãos perante a lei (nómos) – e tem como algumas de suas características principais a participação popular na boulé, nos festivais cívicos e na falange hoplita. A função dos coros musicais como componente de formação da cidadania ateniense teria se dado a partir de sua relação com a falange hoplita e de sua presença nos grandes festivais cívicos que ocorriam desde o período da tirania (560-510 a.C.). Encontramos evidências dessas relações na documentação imagética das cerâmicas áticas, exemplificadas neste artigo pelo skýphos de autoria de Heron
Geoprocessamento aplicado à história agrária: o vínculo da Jaguara
Authors: Carrara Angelo Alves , Zaidan Ricardo Tavares , Paula Lucas Pinheiro de
Published: May 2018

Apesar do crescimento da SIG histórica no mundo a partir dos anos 1990, no Brasil, as geotecnologias ainda são relativamente pouco conhecidas entre os historiadores e o número dos que a praticam, muito limitado. Este artigo tem por objetivo apresentar um exemplo de uso do geoprocessamento na criação de sistemas de informação geográfica – SIG em auxílio à pesquisa em história agrária. Especificamente, analisa, por meio da demarcação georreferenciada, um conjunto de grandes propriedades rurais de Minas Gerais no século XVIII conhecidas pelo nome de vínculo da Jaguara, com base em fontes documentais e cartográficas. Mais do que uma análise sobre um conjunto de propriedades rurais específicas, esperamos que a metodologia exposta neste estudo possa ser explorada em pesquisas bem mais abrangentes.
Energetics of Blood Flow in Cardiovascular Disease
Authors: Rijnberg Friso M. , Hazekamp Mark G. , Wentzel Jolanda J. , de Koning Patrick J.H. , Westenberg Jos J.M. , Jongbloed Monique R.M. , Blom Nico A. , Roest Arno A.W.
Published: May 2018

Visualization and quantification of the adverse effects of distorted blood flow are important emerging fields in cardiology. Abnormal blood flow patterns can be seen in various cardiovascular diseases and are associated with increased energy loss. These adverse energetics can be measured and quantified using 3-dimensional blood flow data, derived from computational fluid dynamics and 4-dimensional flow magnetic resonance imaging, and provide new, promising hemodynamic markers. In patients with palliated single-ventricular heart defects, the Fontan circulation passively directs systemic venous return to the pulmonary circulation in the absence of a functional subpulmonary ventricle. Therefore, the Fontan circulation is highly dependent on favorable flow and energetics, and minimal energy loss is of great importance. A focus on reducing energy loss led to the introduction of the total cavopulmonary connection (TCPC) as an alternative to the classical Fontan connection. Subsequently, many studies have investigated energy loss in the TCPC, and energy-saving geometric factors have been implemented in clinical care. Great advances have been made in computational fluid dynamics modeling and can now be done in 3-dimensional patient-specific models with increasingly accurate boundary conditions. Furthermore, the implementation of 4-dimensional flow magnetic resonance imaging is promising and can be of complementary value to these models. Recently, correlations between energy loss in the TCPC and cardiac parameters and exercise intolerance have been reported. Furthermore, efficiency of blood flow through the TCPC is highly variable, and inefficient blood flow is of clinical importance by reducing cardiac output and increasing central venous pressure, thereby increasing the risk of experiencing the well-known Fontan complications. Energy loss in the TCPC will be an important new hemodynamic parameter in addition to other well-known risk factors such as pulmonary vascular resistance and can possibly be improved by patient-specific surgical design. This article describes the theoretical background of mechanical energy of blood flow in the cardiovascular system and the methods of calculating energy loss, and it gives an overview of geometric factors associated with energy efficiency in the TCPC and its implications on clinical outcome. Furthermore, the role of 4-dimensional flow magnetic resonance imaging and areas of future research are discussed.
Low Serum Calcium and Magnesium Levels and Rupture of Intracranial Aneurysms
Authors: Can Anil , Rudy Robert F. , Castro Victor M. , Dligach Dmitriy , Finan Sean , Yu Sheng , Gainer Vivian , Shadick Nancy A. , Savova Guergana , Murphy Shawn , Cai Tianxi , Weiss Scott T. , Du Rose
Published: May 2018

Background and Purpose—

Both low serum calcium and magnesium levels have been associated with the extent of bleeding in patients with intracerebral hemorrhage, suggesting hypocalcemia- and hypomagnesemia-induced coagulopathy as a possible underlying mechanism. We hypothesized that serum albumin-corrected total calcium and magnesium levels are associated with ruptured intracranial aneurysms.

Methods—

The medical records of 4701 patients, including 1201 prospective patients, diagnosed at the Brigham and Women’s Hospital and Massachusetts General Hospital between 1990 and 2016 were reviewed and analyzed. One thousand two hundred seventy-five patients had available serum calcium, magnesium, and albumin values within 1 day of diagnosis. Individuals were divided into cases with ruptured aneurysms and controls with unruptured aneurysms. Univariable and multivariable logistic regression analyses were performed to determine the association between serum albumin-corrected total calcium and magnesium levels and ruptured aneurysms.

Results—

In multivariable analysis, both albumin-corrected calcium (odds ratio, 0.33; 95% confidence interval, 0.27–0.40) and magnesium (odds ratio, 0.40; 95% confidence interval, 0.28–0.55) were significantly and inversely associated with ruptured intracranial aneurysms.

Conclusions—

In this large case–control study, hypocalcemia and hypomagnesemia at diagnosis were significantly associated with ruptured aneurysms. Impaired hemostasis caused by hypocalcemia and hypomagnesemia may explain this association.
Multiscale examination of cytoarchitectonic similarity and human brain connectivity
Authors: Wei Yongbin , Scholtens Lianne H. , Turk Elise , van den Heuvel Martijn P.
Published: May 2018

The human brain comprises an efficient communication network, with its macroscale connectome organization argued to be directly associated with the underlying microscale organization of the cortex. Here, we further examine this link in the human brain cortex by using the ultrahigh-resolution BigBrain dataset; 11,660 BigBrain profiles of laminar cell structure were extracted from the BigBrain data and mapped to the MRI based Desikan–Killiany atlas used for macroscale connectome reconstruction. Macroscale brain connectivity was reconstructed based on the diffusion-weighted imaging dataset from the Human Connectome Project and cross-correlated to the similarity of laminar profiles. We showed that the BigBrain profile similarity between interconnected cortical regions was significantly higher than those between nonconnected regions. The pattern of BigBrain profile similarity across the entire cortex was also found to be strongly correlated with the pattern of cortico-cortical connectivity at the macroscale. Our findings suggest that cortical regions with higher similarity in the laminar cytoarchitectonic patterns have a higher chance of being connected, extending the evidence for the linkage between macroscale connectome organization and microscale cytoarchitecture.
Time-evolving dynamics in brain networks forecast responses to health messaging
Authors: Cooper Nicole , Garcia Javier O. , Tompson Steven H. , O’Donnell Matthew B. , Falk Emily B. , Vettel Jean M.
Published: May 2018

Neuroimaging measures have been used to forecast complex behaviors, including how individuals change decisions about their health in response to persuasive communications, but have rarely incorporated metrics of brain network dynamics. How do functional dynamics within and between brain networks relate to the processes of persuasion and behavior change? To address this question, we scanned 45 adult smokers by using functional magnetic resonance imaging while they viewed anti-smoking images. Participants reported their smoking behavior and intentions to quit smoking before the scan and 1 month later. We focused on regions within four atlas-defined networks and examined whether they formed consistent network communities during this task (measured as allegiance). Smokers who showed reduced allegiance among regions within the default mode and fronto-parietal networks also demonstrated larger increases in their intentions to quit smoking 1 month later. We further examined dynamics of the ventromedial prefrontal cortex (vmPFC), as activation in this region has been frequently related to behavior change. The degree to which vmPFC changed its community assignment over time (measured as flexibility) was positively associated with smoking reduction. These data highlight the value in considering brain network dynamics for understanding message effectiveness and social processes more broadly.
Nam June Paik's Etude 1 and the Indeterminate origins of Digital Media Art
Authors: Zinman Gregory
Published: May 2018

This essay describes the discovery and significance of Etude 1 (1967), a previously unknown work by media artist Nam June Paik. Composed at Bell Labs and written in an early version of the computer-programming language FORTRAN, Etude 1 stands as one of the earliest works of digital art—though whether Etude 1 was intended to be a film, the “computer opera” that Paik mentions elsewhere in his writings, or some other kind of art work altogether. By exploring Etude 1's uncertain status, as well as more conceptual indeterminacies concerning the relationship between image and code, music and media, and the analog and the digital, this essay demonstrates how such indefinite artifacts allow for a rethinking of cinema's digital past, film's place in computational media, and the nature of the archive.
Le témoignage d’Amīn Fikrī sur l’Exposition universelle de 1889 et la rue du Caire : petite polémique avec Timothy Mitchell
Authors: Sabry Randa
Published: May 2018

À la lumière de la biographie d’Amīn Fikrī et de la composition de son récit viatique en Europe, Iršād al-alibbā ilā maḥāsin Ūrūbbā (Le guide des esprits éclairés vers l’Europe et ses beautés), nous tentons d’expliquer, après avoir examiné les circonstances de sa visite à l’Exposition universelle de 1889, l’esprit qui anime sa description de la Rue du Caire. Cet épisode a fait l’objet d’un commentaire aussi célèbre que tendancieux dans le chapitre d’ouverture de Colonising Egypt. La lecture que nous proposons vise à souligner que, faites hors tout effort de contextualisation, les affirmations erronées, les fautes de traduction et les extrapolations de ce commentaire ont entraîné Timothy Mitchell à une interprétation abusive qui a cependant statut de vulgate depuis sa parution en 1991.
The genus Odontarrhena (Brassicaceae) in Albania: Taxonomy and Nickel accumulation in a critical group of metallophytes from a major serpentine hot-spot
Authors: CECCHI LORENZO , BETTARINI ISABELLA , COLZI ILARIA , COPPI ANDREA , ECHEVARRIA GUILLAUME , PAZZAGLI LUIGIA , BANI AIDA , GONNELLI CRISTINA , SELVI FEDERICO
Published: May 2018

Metal hyperaccumulator plants represent a unique biological resource for scientific research and practical applications. Though essential, however, an adequate knowledge of the systematics of these plants is often missing. This is the case of Odontarrhena, a large but taxonomically critical group of nickel hyperaccumulators from Eurasia. We present a study on this genus in Albania, to fill a gap in our knowledge of this group from a major centre of diversity of metallicolous flora, and to contribute updated information to the Global Hyperaccumulator Database. Morphological and karyological analyses of material from field collections across all major serpentine outcrops in the country, in different years and seasons, allowed to delimit seven taxa: O. albiflora, O. chalcidica, O. moravensis, O. sibirica, O. decipiens, O. smolikana subsp. glabra and O. rigida. The three latter taxa have been long neglected and were resurrected in view of their clear distinctness, while commonly accepted taxa such as O. bertolonii subsp. scutarina and O. markgrafii were reduced to synonymy of O. chalcidica due to the lack of consistent differentiation. Polyploidy was prevalent, while diploid complements were typical of the two vicariant endemics O. rigida and O. moravensis. Types are indicated or newly designated for each entity, and nomenclatural issues are addressed based on in-depth studies of literature and herbarium material. Revised descriptions, phenology, habitat and distribution data are given for each taxon, as well as original iconographies and chromosome counts. A revised identification key is provided. Shoot nickel concentrations were determined to assess accumulation levels of taxa and populations in natural conditions and their potential for phytoextraction of this metal from the soil. With ca. 23000 and 17000 µg of Ni g-1 of shoot dry weight, respectively, the tetraploids O. chalcidica and O. decipiens were the most promising candidates, especially the latter for its robust habit.