bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimal Constant-Stress Accelerated Degradation Test Plans Using Nonlinear Generalized Wiener Process
Authors: Chen Zhen , Li Shuo , Pan Ershun
Published: August 2016

Accelerated degradation test (ADT) has been widely used to assess highly reliable products’ lifetime. To conduct an ADT, an appropriate degradation model and test plan should be determined in advance. Although many historical studies have proposed quite a few models, there is still room for improvement. Hence we propose a Nonlinear Generalized Wiener Process (NGWP) model with consideration of the effects of stress level, product-to-product variability, and measurement errors for a higher estimation accuracy and a wider range of use. Then under the constraints of sample size, test duration, and test cost, the plans of constant-stress ADT (CSADT) with multiple stress levels based on the NGWP are designed by minimizing the asymptotic variance of the reliability estimation of the products under normal operation conditions. An optimization algorithm is developed to determine the optimal stress levels, the number of units allocated to each level, inspection frequency, and measurement times simultaneously. In addition, a comparison based on degradation data of LEDs is made to show better goodness-of-fit of the NGWP than that of other models. Finally, optimal two-level and three-level CSADT plans under various constraints and a detailed sensitivity analysis are demonstrated through examples in this paper.
Myoinositol as a Safe and Alternative Approach in the Treatment of Infertile PCOS Women: A German Observational Study
Authors: Regidor Pedro-Antonio , Schindler Adolf Eduard
Published: August 2016

The use of2×2000 mg myoinositol +2×200 μg folic acid per day is a safe and promising tool in the effective improvement of symptoms and infertility for patients with a polycystic ovary syndrome (PCOS). Using a questionnaire an observational study was performed under German gynecologists to collect data on ovulation and pregnancy rates in PCOS patients with infertility. In this observational study, 3602 infertile women used myoinositol and folic acid between 2 and 3 months in a dosage of2×2000 mg myoinositol +2×200 μg folic acid per day. In a subgroup of 32 patients, hormonal values for testosterone, free testosterone, and progesterone were analyzed before and after 12 weeks of treatment. The mean time of use was 10.2 weeks. During this time 70% of these women had a restored ovulation, and 545 pregnancies were obtained. This means a pregnancy rate of 15.1% of all the myoinositol and folic acid users. In 19 cases a concomitant medication with clomiphene or dexamethasone was used. One twin pregnancy was documented. Testosterone levels changed from 96.6 ng/ml to 43.3 ng/ml and progesterone from 2.1 ng/ml to 12.3 ng/ml (p<0.05) after 12 weeks of treatment. No relevant side effects were present among the patients. This study could show that a new treatment option for patients with a PCOS and infertility is available. The achieved pregnancy rates are at least in an equivalent or even superior range than those reported by the use of metformin.
WWOX and p53 Dysregulation Synergize to Drive the Development of Osteosarcoma
Authors: Del Mare Sara , Husanie Hussam , Iancu Ortal , Abu-Odeh Mohammad , Evangelou Konstantinos , Lovat Francesca , Volinia Stefano , Gordon Jonathan , Amir Gail , Stein Janet , Stein Gary S. , Croce Carlo M. , Gorgoulis Vassilis , Lian Jane B. , Aqeilan Rami I.
Published: August 2016

Osteosarcoma is a highly metastatic form of bone cancer in adolescents and young adults that is resistant to existing treatments. Development of an effective therapy has been hindered by very limited understanding of the mechanisms of osteosarcomagenesis. Here, we used genetically engineered mice to investigate the effects of deleting the tumor suppressor Wwox selectively in either osteoblast progenitors or mature osteoblasts. Mice with conditional deletion of Wwox in preosteoblasts (WwoxΔosx1) displayed a severe inhibition of osteogenesis accompanied by p53 upregulation, effects that were not observed in mice lacking Wwox in mature osteoblasts. Deletion of p53 in WwoxΔosx1 mice rescued the osteogenic defect. In addition, the Wwox;p53Δosx1 double knockout mice developed poorly differentiated osteosarcomas that resemble human osteosarcoma in histology, location, metastatic behavior, and gene expression. Strikingly, the development of osteosarcomas in these mice was greatly accelerated compared with mice lacking p53 only. In contrast, combined WWOX and p53 inactivation in mature osteoblasts did not accelerate osteosarcomagenesis compared with p53 inactivation alone. These findings provide evidence that a WWOX–p53 network regulates normal bone formation and that disruption of this network in osteoprogenitors results in accelerated osteosarcoma. The Wwox;p53Δosx1 double knockout establishes a new osteosarcoma model with significant advancement over existing models. Cancer Res; 76(20); 6107–17. ©2016 AACR.
Chemotherapy-Induced IL34 Enhances Immunosuppression by Tumor-Associated Macrophages and Mediates Survival of Chemoresistant Lung Cancer Cells
Authors: Baghdadi Muhammad , Wada Haruka , Nakanishi Sayaka , Abe Hirotake , Han Nanumi , Putra Wira Eka , Endo Daisuke , Watari Hidemichi , Sakuragi Noriaki , Hida Yasuhiro , Kaga Kichizo , Miyagi Yohei , Yokose Tomoyuki , Takano Atsushi , Daigo Yataro , Seino Ken-ichiro
Published: August 2016

The ability of tumor cells to escape immune destruction and their acquired resistance to chemotherapy are major obstacles to effective cancer therapy. Although immune checkpoint therapies such as anti-PD-1 address these issues in part, clinical responses remain limited to a subpopulation of patients. In this report, we identified IL34 produced by cancer cells as a driver of chemoresistance. In particular, we found that IL34 modulated the functions of tumor-associated macrophages to enhance local immunosuppression and to promote the survival of chemoresistant cancer cells by activating AKT signaling. Targeting IL34 in chemoresistant tumors resulted in a remarkable inhibition of tumor growth when accompanied with chemotherapy. Our results define a pathogenic role for IL34 in mediating immunosuppression and chemoresistance and identify it as a tractable target for anticancer therapy. Cancer Res; 76(20); 6030–42. ©2016 AACR.
Biospecimen Complexity—the Next Challenge for Cancer Research Biobanks?
Authors: Watson Peter H.
Published: August 2016

Purpose: Biospecimens (e.g., tissues, bloods, fluids) are critical for translational cancer research to generate the necessary knowledge to guide implementation of precision medicine. Rising demand and the need for higher quality biospecimens are already evident.

Experimental Design: The recent increase in requirement for biospecimen complexity in terms of linked biospecimen types, multiple preservation formats, and longitudinal data was explored by assessing trends in cancer research publications from 2000 to 2014.

Results: A PubMed search shows that there has been an increase in both raw numbers and the relative proportion (adjusted for total numbers of articles in each period) of the subgroups of articles typically associated with the use of biospecimens and both dense treatment and/or outcomes data and multiple biospecimen formats.

Conclusions: Increasing biospecimen complexity is a largely unrecognized and new pressure on cancer research biobanks. New approaches to cancer biospecimen resources are needed such as the implementation of more efficient and dynamic consent mechanisms, stronger participant involvement in biobank governance, development of requirements for registration of collections, and models to establish stock targets for biobanks. In particular, the latter two approaches would enable funders to establish a better balance between biospecimen supply and research demand, reduce expenditure on duplicate collections, and encourage increased efficiency of biobanks to respond to the research need for more complex cases. This in turn would also enable biobanks to focus more on quality and standardization that are surely factors in the even more important arena of research reproducibility. Clin Cancer Res; 23(4); 894–8. ©2016 AACR.
The Discovery and Preclinical Development of ASG-5ME, an Antibody–Drug Conjugate Targeting SLC44A4-Positive Epithelial Tumors Including Pancreatic and Prostate Cancer
Authors: Mattie Michael , Raitano Arthur , Morrison Kendall , Morrison Karen , An Zili , Capo Linnette , Verlinsky Alla , Leavitt Monica , Ou Jimmy , Nadell Rossana , Aviña Hector , Guevara Claudia , Malik Faisal , Moser Ruth , Duniho Steven , Coleman Jeffrey , Li Ying , Pereira Daniel S. , Doñate Fernando , Joseph Ingrid B.J. , Challita-Eid Pia , Benjamin Dennis , Stover David R.
Published: August 2016

Here, we report the development of an antibody–drug conjugate, ASG-5ME, which targets the solute carrier receptor SLC44A4. SLC44A4 is a member of a family of putative choline transporters that we show to be markedly upregulated in a variety of epithelial tumors, most notably prostate and pancreatic cancer. SLC44A4 is normally expressed on the apical surface of secretory epithelial cells, but in cancer we show expression is not restricted to the luminal surface in advanced and undifferentiated tumors. ASG-5ME consists of a human IgG2 anti-SLC44A4 antibody conjugated through a cleavable linker to the microtubule-disrupting agent monomethylauristatin E. It has potent antitumor activity in both cell line – and patient-derived xenograft models of pancreatic and prostate cancers. Combination studies with ASG-5ME and nab-paclitaxel demonstrated combination effect in both pancreatic and prostate tumor models. Altogether, the data presented here suggest that ASG-5ME may have the potential to offer a new therapeutic option for the treatment of pancreatic and prostate cancers. Mol Cancer Ther; 15(11); 2679–87. ©2016 AACR.
Identification of Pharmacodynamic Transcript Biomarkers in Response toFGFRInhibition by AZD4547
Authors: Delpuech Oona , Rooney Claire , Mooney Lorraine , Baker Dawn , Shaw Robert , Dymond Michael , Wang Dennis , Zhang Pei , Cross Sarah , Veldman-Jones Margaret , Wilson Joanne , Davies Barry R. , Dry Jonathan R. , Kilgour Elaine , Smith Paul D.
Published: August 2016

The challenge of developing effective pharmacodynamic biomarkers for preclinical and clinical testing of FGFR signaling inhibition is significant. Assays that rely on the measurement of phospho-protein epitopes can be limited by the availability of effective antibody detection reagents. Transcript profiling enables accurate quantification of many biomarkers and provides a broader representation of pathway modulation. To identify dynamic transcript biomarkers of FGFR signaling inhibition by AZD4547, a potent inhibitor of FGF receptors 1, 2, and 3, a gene expression profiling study was performed in FGFR2-amplified, drug-sensitive tumor cell lines. Consistent with known signaling pathways activated by FGFR, we identified transcript biomarkers downstream of the RAS-MAPK and PI3K/AKT pathways. Using different tumor cell lines in vitro and xenografts in vivo, we confirmed that some of these transcript biomarkers (DUSP6, ETV5, YPEL2) were modulated downstream of oncogenic FGFR1, 2, 3, whereas others showed selective modulation only by FGFR2 signaling (EGR1). These transcripts showed consistent time-dependent modulation, corresponding to the plasma exposure of AZD4547 and inhibition of phosphorylation of the downstream signaling molecules FRS2 or ERK. Combination of FGFR and AKT inhibition in an FGFR2-mutated endometrial cancer xenograft model enhanced modulation of transcript biomarkers from the PI3K/AKT pathway and tumor growth inhibition. These biomarkers were detected on the clinically validated nanoString platform. Taken together, these data identified novel dynamic transcript biomarkers of FGFR inhibition that were validated in a number of in vivo models, and which are more robustly modulated by FGFR inhibition than some conventional downstream signaling protein biomarkers. Mol Cancer Ther; 15(11); 2802–13. ©2016 AACR.
TLR4-Dependent Claudin-1 Internalization and Secretagogue-Mediated Chloride Secretion Regulate Irinotecan-Induced Diarrhea
Authors: Wardill Hannah R. , Bowen Joanne M. , Van Sebille Ysabella Z.A. , Secombe Kate R. , Coller Janet K. , Ball Imogen A. , Logan Richard M. , Gibson Rachel J
Published: August 2016

We have previously shown increased intestinal permeability, to 4-kDa FITC-dextran, in BALB/c mice treated with irinotecan. Importantly, genetic deletion of Toll-like receptor 4 (TLR4; Tlr4−/−) protected against loss of barrier function, indicating that TLR4 is critical in tight junction regulation. The current study aimed (i) to determine the molecular characteristics of intestinal tight junctions in wild-type and Tlr4−/− BALB/c mice and (ii) to characterize the secretory profile of the distal colon. Forty-two female wild-type and 42 Tlr4−/− BALB/c mice weighing between 18 and 25 g received a single 270 mg/kg [intraperitoneal (i.p.)] dose of irinotecan hydrochloride or vehicle control and were killed at 6, 24, 48, 72, and 96 hours. The secretory profile of the distal colon, following carbachol and forksolin, was assessed using Ussing chambers at all time points. Tight junction integrity was assessed at 24 hours, when peak intestinal permeability and diarrhea were reported, using immunofluorescence, Western blotting, and RT-PCR. Irinotecan caused internalization of claudin-1 with focal lesions of ZO-1 and occludin proteolysis in the ileum and colon of wild-type mice. Tlr4−/− mice maintained phenotypically normal tight junctions. Baseline conductance, a measure of paracellular permeability, was increased in irinotecan-treated wild-type mice at 24 hours (53.19 ± 6.46 S/cm2; P = 0.0008). No change was seen in Tlr4−/− mice. Increased carbachol-induced chloride secretion was seen in irinotecan-treated wild-type and Tlr4−/− mice at 24 hours (wild-type: 100.35 ± 18.37 μA/cm2; P = 0.022; Tlr4−/−: 102.72 ± 18.80 μA/cm2; P = 0.023). Results suggest that TLR4-dependent claudin-1 internalization and secondary anion secretion contribute to irinotecan-induced diarrhea. Mol Cancer Ther; 15(11); 2767–79. ©2016 AACR.
Nivolumab-Induced Pericardial Tamponade: A Case Report and Discussion
Authors: Kushnir Igal , Wolf Ido
Published: August 2016

Nivolumab, a programmed death 1 (PD1) inhibitor, belongs to a family of drugs known as immune checkpoint inhibitors that share a similar toxicity profile, which includes rash, pruritus, colitis, hepatitis, pneumonitis and thyroid dysfunction. Nivolumab has a proven efficacy in the treatment of malignant melanoma, non-small cell lung cancer and renal cell carcinoma. We present the case of a 67-year-old male patient with metastatic squamous cell carcinoma of the lung who suffered from a massive pericardial effusion secondary to treatment with nivolumab, which he began in June 2015. After five cycles the patient was hospitalized due to acute respiratory failure requiring mechanical ventilation. An echocardiogram revealed a massive pericardial effusion with tamponade. After pericardiocentesis and corticosteroid treatment, the patient's condition improved rapidly. A CT scan revealed a response of the tumor. Although anti-PD1 treatment is usually regarded as less toxic than chemotherapy, a wide spectrum of life-threatening immune-related side effects may still occur and clinical vigilance is required.
Surgical Replacement of Implantable Pulse Generators in Deep Brain Stimulation: Adverse Events and Risk Factors in a Multicenter Cohort
Authors: Fytagoridis Anders , Heard Tomas , Samuelsson Jennifer , Zsigmond Peter , Jiltsova Elena , Skyrman Simon , Skoglund Thomas , Coyne Terry , Silburn Peter , Blomstedt Patric
Published: August 2016

Background: Deep brain stimulation (DBS) is a growing treatment modality, and most DBS systems require replacement of the implantable pulse generator (IPG) every few years. The literature regarding the potential impact of adverse events of IPG replacement on the longevity of DBS treatments is rather scarce. Objective: To investigate the incidence of adverse events, including postoperative infections, associated with IPG replacements in a multicenter cohort. Methods: The medical records of 808 patients from one Australian and five Swedish DBS centers with a total of 1,293 IPG replacements were audited. A logistic regression model was used to ascertain the influence of possible predictors on the incidence of adverse events. Results: The overall incidence of major infections was 2.3% per procedure, 3.7% per patient and 1.7% per replaced IPG. For 28 of 30 patients this resulted in partial or complete DBS system removal. There was an increased risk of infection for males (OR 3.6, p = 0.026), and the risk of infection increased with the number of prior IPG replacements (OR 1.6, p < 0.005). Conclusions: The risk of postoperative infection with DBS IPG replacement increases with the number of previous procedures. There is a need to reduce the frequency of IPG replacements.
Vitamin-K-Dependent Protection of the Renal Microvasculature: Histopathological Studies in Normal and Diseased Kidneys
Authors: Wei Fang-Fei , Drummen Nadja E.A. , Thijs Lutgarde , Jacobs Lotte , Herfs Marjolein , van''t Hoofd Cynthia , Vermeer Cees , Staessen Jan A.
Published: August 2016

Vitamin-K-dependent carboxylation of matrix Gla protein (MGP) protects the macrocirculation against calcification. We recently reported in a multiethnic population study that the estimated glomerular filtration rate, a microvascular trait, decreased and the risk of chronic kidney disease increased with higher circulating levels of inactive dephospho-uncarboxylated MGP, a marker of vitamin K deficiency. These findings highlighted the possibility that vitamin K might have a beneficial effect on the renal microcirculation. To substantiate these epidemiological findings, we undertook a pilot study, in which we stained renal tissue samples obtained by biopsy from 2 healthy kidney donors and 4 patients with nephropathy for carboxylated and uncarboxylated MGP and calcium deposits. Three patients had renal calcifications, which were consistently associated with carboxylated and uncarboxylated MGP. Normal renal tissue was devoid of microcalcifications and staining for carboxylated and uncarboxylated MGP. Pending confirmation in a larger study covering a wider range of renal pathologies, these histopathological findings suggest that MGP might inhibit calcification not only in large arteries, as was known before, but in renal tissue as well, thereby highlighting potentially new avenues for promoting renal health, for instance by vitamin K supplementation.
Analysis of 58 Families of Holins Using a Novel Program, PhyST
Authors: Kuppusamykrishnan Harikrishnan , Chau Larry M. , Moreno-Hagelsieb Gabriel , Saier Jr. Milton H.
Published: August 2016

We have designed a freely accessible program, PhyST, which allows the automated characterization of any family of homologous proteins within the Transporter Classification Database. The program performs an NCBI-PSI-BLAST search and reports (1) the average protein sequence length with standard deviations, (2) the average predicted number of transmembrane segments, (3) the total number of homologues retrieved, (4) a quantitative list of all source phyla, and (5) potential fusion proteins of sizes considerably exceeding the average size of the proteins retrieved. We have applied this program to 58 families of holins, and the results are presented. The results show that holins are very rarely fused to other protein domains, suggesting that holins form transmembrane pores as homooligomers without the participation of other proteins or protein domains.
Distribution of CGRP and TRPV2 in Human Paranasal Sinuses
Authors: Sato Tadasu , Sasahara Nobuyuki , Kanda Noriyuki , Sasaki Yu , Yamaguma Yu , Kokubun Souichi , Yajima Takehiro , Ichikawa Hiroyuki
Published: August 2016

Immunohistochemistry for protein gene product 9.5 (PGP 9.5), calcitonin gene-related peptide (CGRP) and the transient receptor potential cation channel subfamily V member 2 (TRPV2) was performed on human paranasal sinuses. It was found that in the paranasal sinuses, mucous membranes contain PGP 9.5-immunoreactive (PGP 9.5-IR) nerve fibers. Such nerve fibers terminated around large blood vessels as fine varicosities. Isolated PGP 9.5-IR nerve fibers were scattered beneath the epithelium. Glandular tissues were also innervated by PGP 9.5-IR nerve fibers. These fibers were numerous in the maxillary and ethmoid sinuses, and relatively rare in the frontal and sphenoid sinuses. CGRP-IR nerve fibers were common in the maxillary sinus whereas TRPV2-IR nerve fibers were abundant in the ethmoid sinus. They were located around large blood vessels in the lamina propria. Many subepithelial nerve fibers contained TRPV2 immunoreactivity in the ethmoid sinus. CGRP- and TRPV2-IR nerve fibers were very infrequent in the frontal and sphenoid sinuses. In the human trigeminal ganglion (TG), sensory neurons contained CGRP or TRPV2 immunoreactivity. CGRP-IR TG neurons were more common than TRPV2-IR TG neurons. CGRP-IR TG neurons were of various cell body sizes, whereas TRPV2-IR TG neurons were mostly medium-to-large. In addition, human spinal and principal trigeminal sensory nuclei contained abundant CGRP- and TRPV2-IR varicosities. This study indicates that CGRP- and TRPV2-containing TG neurons probably innervate the paranasal sinus mucosae, and project into spinal and principal trigeminal sensory nuclei.
Ultrastructural Changes and Methylation of Human Oocytes Vitrified at the Germinal Vesicle Stage and Matured in vitro after Thawing
Authors: Liu Ming-Hui , Zhou Wen-Hui , Chu Da-Peng , Fu Lei , Sha Wei , Li Yuan
Published: August 2016

Aim: The study aimed to assess the effect of in vitro vitrification and maturation on the nuclear configuration, cytoplasmic maturation and global DNA methylation pattern of human germinal vesicle (GV) stage oocytes. Methods: Human oocytes from infertile women were randomly assigned to one of 3 groups: (i) metaphase II (MII) oocytes matured in vivo (vivo-MII, n = 56) as controls; (ii) MII oocytes matured in vitro (vitro-MII, n = 106); and (iii) MII oocytes that were vitrified at the GV stage, warmed and matured in vitro (cryo-MII, n = 122). All MII oocytes were fixed and immunofluorescence staining for spindle, chromosome, mitochondrion and cortical granules (CGs) were performed; examination was done using immunofluorescence laser scanning confocal microscope. The expression of 5-methycytosine in these MII oocytes was also assessed. Results: No significant difference was observed between vitro-MII and cryo-MII groups with respect to oocyte maturation rate (72.4 vs. 78.3%). No significant differences were observed in the distribution of mitochondria, migration of CG and global DNA methylation pattern among the 3 study groups. However, the abnormal configuration of spindle and chromosome was significantly higher in cryo-MII group (78.9 and 84.2%) as compared to that in the vitro-MII (45.0 and 50.0%, p < 0.05) and vivo-MII groups (27.3 and 36.4%, p < 0.05). Conclusion: GV oocytes appeared to resist vitrification and retain their potential for maturation to MII stage oocytes after thawing. However, GV oocytes vitrification combined with in vitro maturation could affect the organization of spindle and chromosome.
Aortic Stiffness, Cerebrovascular Dysfunction, and Memory
Authors: Cooper Leroy L. , Mitchell Gary F.
Published: August 2016

Background: Aortic stiffness is associated with cardiovascular and cerebrovascular events and cognitive decline. This mini-review focuses on relations of aortic stiffness with microvascular dysfunction and discusses the contribution of abnormal pulsatile hemodynamics to cerebrovascular damage and cognitive decline. We also provide a rationale for considering aortic stiffness as a putative and important contributor to memory impairment in older individuals. Summary: Aging is associated with stiffening of the aorta but not the muscular arteries, which reduces wave reflection and increases the transmission of pulsatility into the periphery. Aortic stiffening thereby impairs a protective mechanism that shields the peripheral microcirculation from excessive pulsatility within downstream target organs. Beyond midlife, aortic stiffness increases rapidly and exposes the cerebral microcirculation to abnormal pulsatile mechanical forces that are associated with microvascular damage and remodeling in the brain. Aortic stiffening and high-flow pulsatility are associated with alterations in the microvasculature of the brain; however, a mechanistic link between aortic stiffness and memory has not been established. We showed that in a community-based sample of older individuals, cerebrovascular resistance and white matter hyperintensities - markers of cerebrovascular remodeling and damage - mediated the relation between higher aortic stiffness and lower performance on memory function tests. These data suggest that microvascular and white matter damage associated with excessive aortic stiffness contribute to impaired memory function with advancing age. Key Messages: Increasing evidence suggests that vascular etiologies - including aortic stiffness and microvascular damage - contribute to memory impairment and the pathogenesis of dementia, including Alzheimer's disease. Interventions that reduce aortic stiffness may delay memory decline among older individuals.
Views of Cohort Study Participants about Returning Research Results in the Context of Precision Medicine
Authors: Hyams Travis , Bowen Deborah J. , Condit Celeste , Grossman Jeremy , Fitzmaurice Megan , Goodman Deborah , Wenzel Lari , Edwards Karen L.
Published: August 2016

Background: The practice of biorepository-based genetics research raises questions related to what ethical obligations researchers have to their participants. It is important to explore and include the thoughts of current biorepository participants as we move forward with this type of research. Methods: Thirty participants (17 cancer patients, 7 cancer-free controls, and 6 relatives) were drawn from the Northwest Cancer Genetics Registry and participated in qualitative interviews lasting between 45 and 90 min. Topics explored in this study include which types of genetic test results participants of large biorepositories expect and would like to receive from research analyzing their samples, as well as thoughts on best practice for conducting this type of research. Results: Cancer cases, controls, and first-degree relatives have differing views on what results they would like to receive from biorepository-based research. Participants across all groups attempted to balance the costs and benefits of returning individual research results. Discussion: In the wake of precision medicine, it is important to describe the range of ways participants in large biorepositories both think and talk about the utilization of their specimens for genetics research.
The Role of Home Blood Pressure Telemonitoring for Blood Pressure Control
Authors: Lee Chan Joo , Park Sungha
Published: August 2016

Despite improvements in hypertension awareness and treatment, the blood pressure (BP) control rate still remains at around 50%. One of the major determinants of low BP control results from therapeutic inertia of the physician and suboptimal compliance of the patients. Home BP self-measurement and monitoring improves patients' awareness and helps the management of hypertension. Recent technological advances are allowing for accurate measurement and telemonitoring of home BP, with a number of randomized clinical trials demonstrating the efficacy of telemonitoring for BP control. Home BP telemonitoring combined with self-adjustment based on prespecified treatment algorithms has been shown to improve BP control. Additionally, telemonitoring with active intervention by medical professionals has been shown to improve drug compliance and increase the target BP achievement rate. Although nothing can replace the tried and tested doctor-patient relationship in the office, telemonitoring of home BP will be an important tool for treating hypertension in the future.
Beweggründe von Krebspatienten für und gegen die Inanspruchnahme der Misteltherapie
Authors: Gschwendtner Kathrin M. , Holmberg Christine , Weis Joachim
Published: August 2016

Einleitung: Die Misteltherapie ist im deutschsprachigen Raum ein häufig angewandtes komplementärmedizinisches Verfahren (KM) in der Onkologie. Diese Studie hatte das Ziel, die Beweggründe für oder gegen eine Inanspruchnahme der Misteltherapie zu untersuchen und Themenfeldern zuzuordnen. Patienten und Methoden: Es wurden qualitative leitfadengestützte Interviews mit Krebspatienten geführt. Der Interviewleitfaden fragte nach der Inanspruchnahme von KM, der Motivation zur Inanspruchnahme, Informationsverhalten und -bedürfnissen zu KM sowie nach der Krebserkrankung. Um die Beweggründe für die Inanspruchnahme oder Nichtinanspruchnahme der Misteltherapie zu verstehen, wurden die Interviews inhaltsanalytisch ausgewertet. Ergebnisse: Insgesamt wurden Interviews mit 88 Krebspatienten geführt, davon nutzen 18 (20,5%) die Misteltherapie. Die Beweggründe für oder gegen eine Inanspruchnahme der Misteltherapie ließen sich den 2 Themenfeldern «Wahrgenommene Indikation» und «Abwägungen bei der Entscheidungsfindung» zuordnen. Diskussion und Schlussfolgerungen: Mit der Misteltherapie wird sowohl ein Einfluss auf das Tumorwachstum als auch eine supportive Wirkung assoziiert. Anwender sehen die Misteltherapie als sicheres Verfahren; Nichtnutzer befürchten eher Neben- oder Wechselwirkungen. Die Empfehlung von Fachpersonal spielt eine wichtige Rolle bei der Inanspruchnahme. Zum Teil waren die Nichtnutzer interessiert an der Anwendung der Misteltherapie, befanden sich jedoch noch im Klärungsprozess.
Морфологічні зміни слизової оболонки порожнини рота експериментальних тварин при гастродуоденіті та вплив на них різних методів лікування
Authors: Sydliaruk N. I. , Avdieiev O. V.
Published: August 2016

The aim of our study was to compare the efficiency of rotokan, metrogyl-denta and xenoderm in treatment of oral mucosa diseases combined with experimental gastroduodenitis using morphological methods of investigation. All of the applied medications showed positive results, but their effectiveness and impact on the oral mucosa were different. The use of xenoderm in treatment of mucous membrane changes in animals with gastroduodenitis showed the best results.
Пародонтологічний статус наркозалежних хворих із гепатобіліарною патологією
Authors: Furdychko A. I. , Fedun I. R. , Dyba A. Ya.
Published: August 2016

In drug abusers with inflammatory disease periodontitis with hepatobiliary pathology clinical and instrumental study of oral cavity and determination of hepatic markers in serum was conducted. The research showed that inflammatory periodontal diseases including chronic generalized catarrhal gingivitis, chronic generalized periodontitis initial – І degree and severity occurs much more frequently in drug addicts who have a pathology of the hepatobiliary system than in patients who are addicted but have no comorbidities of this system. This is according to assessment of the index of periodontal tissue and laboratory studies of liver markers that confirm the pathology of the hepatobiliary system.
Тютюнокуріння: розповсюдженість та вплив на органи і тканини порожнини рота (огляд літератури)
Authors: Shcherba V. V. , Lavrin O. Ya.
Published: August 2016

Smoking is a global problem of humanity, and its impact on the organs and tissues of the oral cavity is a major health and social problem. Smoking is associated with significantly increased risk of the oral cavity diseases, especially with paradont pathology and cancer. Persons who have extensive experience of smoking, use tobacco products for oral use, except of smoking alcohol abuse belong to risk group of the oral cavity cancer. The severity of periodontal disease depends on the age of onset of smoking, duration of smoking and number of cigaretteswhich are smoked daily. In the literature many papers are devoted to research the impact of smoking on periodontal status. However, a number of aspects, including free radical oxidation state is left without proper attention, which is the aim of our further investigation.
Плеоморфна аденома піднижньощелепної слинної залози у мешканців Тернопільської області
Authors: Nahirnyi Ya. P.
Published: August 2016

Frequency and gender features of pleomorfna adenoma of submandibular salivary gland among residents of Ternopil region for the period 2010 to 2014 were studied. Pleomorfna adenoma was found in
 40 % of all detected tumors of submandibular salivary gland and occurs equally in both sexes.
Associations of Macro- and Microvascular Endothelial Dysfunction With Subclinical Ventricular Dysfunction in End-Stage Renal Disease
Authors: Dubin Ruth F. , Guajardo Isabella , Ayer Amrita , Mills Claire , Donovan Catherine , Beussink Lauren , Scherzer Rebecca , Ganz Peter , Shah Sanjiv J.
Published: August 2016

Patients with end-stage renal disease (ESRD) suffer high rates of heart failure and cardiovascular mortality, and we lack a thorough understanding of what, if any, modifiable factors contribute to cardiac dysfunction in these high-risk patients. To evaluate endothelial function as a potentially modifiable cause of cardiac dysfunction in ESRD, we investigated cross-sectional associations of macro- and microvascular dysfunction with left and right ventricular dysfunction in a well-controlled ESRD cohort. We performed comprehensive echocardiography, including tissue Doppler imaging and speckle-tracking echocardiography of the left and right ventricle, in 149 ESRD patients enrolled in an ongoing prospective, observational study. Of these participants, 123 also underwent endothelium-dependent flow-mediated dilation of the brachial artery (macrovascular function). Microvascular function was measured as the velocity time integral of hyperemic blood flow after cuff deflation. Impaired flow-mediated dilation was associated with higher left ventricular mass, independently of age and blood pressure: per 2-fold lower flow-mediated dilation, left ventricular mass was 4.1% higher (95% confidence interval, 0.49–7.7;
P
=0.03). After adjustment for demographics, blood pressure, comorbidities, and medications, a 2-fold lower velocity time integral was associated with 9.5% higher E/e′ ratio (95% confidence interval, 1.0–16;
P
=0.03) and 6.7% lower absolute right ventricular longitudinal strain (95% confidence interval, 2.0–12;
P
=0.003). Endothelial dysfunction is a major correlate of cardiac dysfunction in ESRD, particularly diastolic and right ventricular dysfunction, in patients whose volume status is well controlled. Future investigations are needed to determine whether therapies targeting the vascular endothelium could improve cardiac outcomes in ESRD.
Rapid Early Growth May Modulate the Association Between Birth Weight and Blood Pressure at 5 Years in the EDEN Cohort Study
Authors: Taine Marion , Stengel Bénédicte , Forhan Anne , Carles Sophie , Botton Jérémie , Charles Marie-Aline , Heude Barbara
Published: August 2016

Physiological evidence suggests that birth weight (BW) and postnatal growth affect blood pressure (BP) level, independently or in interaction. Their respective roles are difficult to disentangle in epidemiological studies, however, especially when adjusting for final weight. We assessed the portion of the effect of BW on BP at 5 years that was not attributable to postnatal growth and investigated potential interactions between BW and postnatal growth velocity at different time points in the EDEN mother–child study. Collecting a median of 19 weight measurements for each of the 1119 children who completed follow-up enabled us to model instantaneous growth velocity at any age. After computing a BP SD-score at 5 years, adjusted for age, sex, current body mass index, and height, we used multiple linear regression to study its association with age- and sex-specific BW
z
score, adjusting for several maternal and pregnancy risk factors. We tested interactions between BW categories (small-, appropriate-, and large-for-gestational-age) and weight growth velocities at different ages. The BW
z
score was negatively and significantly correlated with the systolic BP SD-score at the age of 5 years (
r
=−0.07,
P
=0.02). Interactions were found between BW categories and weight growth velocities from 1 to 4 months (
P
from 0.002 to 0.08) but not at older ages; specifically, children born small for gestational age with a fast weight growth velocity in their first few months of life had the highest absolute systolic BP and SD score values at 5 years. They may need monitoring for cardiovascular risks.
Natural Killer Cell Reduction and Uteroplacental Vasculopathy
Authors: Golic Michaela , Haase Nadine , Herse Florian , Wehner Anika , Vercruysse Lisbeth , Pijnenborg Robert , Balogh Andras , Saether Per Christian , Dissen Erik , Luft Friedrich C. , Przybyl Lukasz , Park Joon-Keun , Alnaes-Katjavivi Patji , Staff Anne Cathrine , Verlohren Stefan , Henrich Wolfgang , Muller Dominik N. , Dechend Ralf
Published: August 2016

Uterine natural killer cells are important for uteroplacental development and pregnancy maintenance. Their role in pregnancy disorders, such as preeclampsia, is unknown. We reduced the number of natural killer cells by administering rabbit anti-asialo GM1 antiserum in an established rat preeclamptic model (female human angiotensinogen×male human renin) and evaluated the effects at the end of pregnancy (day 21), compared with preeclamptic control rats receiving normal rabbit serum. In 100% of the antiserum-treated, preeclamptic rats (7/7), we observed highly degenerated vessel cross sections in the mesometrial triangle at the end of pregnancy. This maternal uterine vasculopathy was characterized by a total absence of nucleated/living cells in the vessel wall and perivascularly and prominent presence of fibrosis. Furthermore, there were no endovascular trophoblast cells within the vessel lumen. In the control, normal rabbit serum–treated, preeclamptic rats, only 20% (1/5) of the animals displayed such vasculopathy. We confirmed the results in healthy pregnant wild-type rats: after anti-asialo GM1 treatment, 67% of maternal rats displayed vasculopathy at the end of pregnancy compared with 0% in rabbit serum–treated control rats. This vasculopathy was associated with a significantly lower fetal weight in wild-type rats and deterioration of fetal brain/liver weight ratio in preeclamptic rats. Anti-asialo GM1 application had no influence on maternal hypertension and albuminuria during pregnancy. Our results show a new role of natural killer cells during hypertensive pregnancy in maintaining vascular integrity. In normotensive pregnancy, this integrity seems important for fetal growth.
Early Postmenopausal Phase Is Associated With Reduced Prostacyclin-Induced Vasodilation That Is Reversed by Exercise Training
Authors: Nyberg Michael , Egelund Jon , Mandrup Camilla M. , Nielsen Mads B. , Mogensen Alexander S. , Stallknecht Bente , Bangsbo Jens , Hellsten Ylva
Published: August 2016

The postmenopausal phase is associated with an accelerated rate of rise in the prevalence of vascular dysfunction and hypertension; however, the mechanisms underlying these adverse vascular changes and whether exercise training can reverse the decline in vascular function remains unclear. We examined the function of the vascular prostanoid system in matched pre- and postmenopausal women before and after 12 weeks of exercise training. Twenty premenopausal and 16 early postmenopausal (3.1±0.5 [mean±SE] years after final menstrual period) women only separated by 4 (50±0 versus 54±1) years of age were included. Before the training period, the vasodilator response to intra-arterial infusion of either the prostacyclin analog epoprostenol or acetylcholine was lower (≈13%–41%;
P
<0.05) in the postmenopausal compared with the premenopausal women. Acetylcholine infusion induced a similar release of prostacyclin (6-keto prostaglandin F
1a
). To elucidate the role of vasoconstrictor prostanoids, acetylcholine infusion was combined with the cyclooxygenase inhibitor ketorolac and here the vascular response to acetylcholine was reduced to a similar extent in pre- and postmenopausal women. Exercise training increased (
P
<0.05) the vasodilator response to epoprostenol (≈100%–150%) and acetylcholine (≈100%–120%) infusion in the postmenopausal group. These findings demonstrate that the early postmenopausal phase is associated with a marked reduction in vascular function. Despite of a reduced sensitivity to prostacyclin, the overall balance between vasodilator and vasoconstrictor prostanoids does not seem to be altered. Exercise training can reverse the decline in vascular sensitivity to epoprostenol and acetylcholine, suggesting that beneficial vascular adaptations with exercise training are preserved in recent postmenopausal women.
Heteromerization Between the Bradykinin B
2
Receptor and the Angiotensin-(1–7) Mas Receptor
Authors: Cerrato Bruno D. , Carretero Oscar A. , Janic Brana , Grecco Hernán E. , Gironacci Mariela M.
Published: August 2016

Bradykinin B
2
receptor (B
2
R) and angiotensin-(1–7) Mas receptor (MasR)–mediated effects are physiologically interconnected. The molecular basis for such cross talk is unknown. It is hypothesized that the cross talk occurs at the receptor level. We investigated B
2
R–MasR heteromerization and the functional consequences of such interaction. B
2
R fused to the cyan fluorescent protein and MasR fused to the yellow fluorescent protein were transiently coexpressed in human embryonic kidney293T cells. Fluorescence resonance energy transfer analysis showed that B
2
R and MasR formed a constitutive heteromer, which was not modified by their agonists. B
2
R or MasR antagonists decreased fluorescence resonance energy transfer efficiency, suggesting that the antagonist promoted heteromer dissociation. B
2
R–MasR heteromerization induced an 8-fold increase in the MasR ligand-binding affinity. On agonist stimulation, the heteromer was internalized into early endosomes with a slower sequestration rate from the plasma membrane, compared with single receptors. B
2
R–MasR heteromerization induced a greater increase in arachidonic acid release and extracellular signal–regulated kinase phosphorylation after angiotensin-(1–7) stimulation, and this effect was blocked by the B
2
R antagonist. Concerning serine/threonine kinase Akt activity, a significant bradykinin-promoted activation was detected in B
2
R–MasR but not in B
2
R-expressing cells. Angiotensin-(1–7) and bradykinin elicited antiproliferative effects only in cells expressing B
2
R–MasR heteromers, but not in cells expressing each receptor alone. Proximity ligation assay confirmed B
2
R–MasR interaction in human glomerular endothelial cells supporting the interaction between both receptors in vivo. Our findings provide an explanation for the cross talk between bradykinin B
2
R and angiotensin-(1–7) MasR–mediated effects. B
2
R–MasR heteromerization induces functional changes in the receptor that may lead to long-lasting protective properties.
New deep-sea Paratanaoidea (Crustacea: Peracarida: Tanaidacea) from the northeastern Gulf of Mexico
Authors: DRUMM DAVID T. , BIRD GRAHAM J.
Published: August 2016

One new genus is erected and four new species of paratanaoidean tanaidaceans are described from deep waters in the northeastern Gulf of Mexico: one in each of the genera Collettea, Tanaella, and Pseudomacrinella, and one as a new genus in the family Anarthruridae. Keys to species in the genera Collettea, Tanaella, and the genera of the Anarthruridae are provided.
New and little known species of Halolaelaps (Acari: Mesostigmata: Halolaelapidae) from Ukraine
Authors: TRACH VIACHESLAV A.
Published: August 2016

A new species of the family Halolaelapidae (Acari: Mesostigmata), Halolaelaps euxinus sp. nov. is described from Black Sea coast. Adult mites were found in seaweed, while deutonymphs were collected from the amphipod Talorchestia deshayesii and from seaweed. The adult female of Halolaelaps saproincisus Hirschmann & Götz, 1968 is recorded in new localities of Ukraine for the first time, in soil and bird faeces in chicken coops, and new morphological information is provided. The adult male (collected from chicken coops) and the deutonymph (collected from chicken coops and on dung-beetles) of H. saproincisus are described for the first time.
A new species of Munidopsis Whiteaves, 1874 (Crustacea: Decapoda: Anomura) from the Northwest Indian Ocean Ridge
Authors: DONG DONG , LI XINZHENG , ZHOU YADONG , WANG CHUNSHENG
Published: August 2016

A new species, Munidopsis militaris n. sp., from the Carlsberg Ridge, Northwest Indian Ocean Ridge is described herein. The species belongs to a group of species having a pair of epigastric spines, mesial and lateral eye-spines, abdominal tergites unarmed, five or six spines on the lateral margin of the carapace, and a denticulate carina on the distolateral margin of the P1 fixed finger. It can be distinguished from its relatives by the spinous lateral margin of the palm and dorsal carinae on the P2–4 propodus. The Munidopsis fauna of the Indian Ocean Ridge is seldom reported on; this new species is the sixth member of this genus found inhabiting the Indian Ocean Ridge.
Review of the genus Chrysoscota in Cambodia (Lepidoptera, Erebidae, Arctiinae), with description of a new species
Authors: BAYARSAIKHAN ULZIIJARGAL , BAE YANG-SEOP
Published: August 2016

The genus Chrysoscota Hampson, 1900 in Cambodia is reviewed, with description of a new species, Chrysoscota kimsuni Bayarsaikhan & Bae, sp. n. is described as new to sciences, and C. cotriangulata Holloway, 2001 is reported as new for the country. Illustrations of adults and male and female genitalia are provided for both species, with a checklist of the genus Chrysoscota.
The Draupner Event: The Large Wave and the Emerging View
Authors: Cavaleri L. , Benetazzo A. , Barbariol F. , Bidlot J.-R. , Janssen P. A. E. M.
Published: August 2016

In a parallel paper mainly focused on the meteorological and oceanographic aspects, the conditions were described for the storm during which the iconic Draupner wave was recorded. Because of increased spatial resolution and improved model physics, the results provided new and previously unrecognized features of the storm, in particular of the wave spectra, features relevant for assessing the wave’s conditions nearby the Draupner platform. Starting from these, and after briefly summarizing the relevant information, the focus of this paper is on the nonlinear analysis of the local situation, with the main purpose of assessing if and how the conditions existed for the possible appearance of very large waves. An intensive analysis of the related probability is carried out, attacking the problem with two different statistical approaches, both briefly described: a completely new one working from the point of view of envelope heights, and a recent, though established, one based on space–time extreme waves. It is remarkable, and certainly supports this line of work, that the two different approaches lead independently to consistent results, supporting the idea, already derived from the meteo-oceanographic hindcast, that the wave conditions were indeed special at the position of the Draupner platform. This is related to a general analysis of high waves showing, also on the basis of 3D (2D space + time) measured wave data at open sea, how, given the severe sea state, the Draupner wave features represent what is expected at certain times and positions as the natural documented temporal evolution of wave groups.