bluuebunny/crossref_metadata_2025 huggingface dataset:
Purkinje cell intrinsic excitability increases after synaptic long term depression
Authors: Yang Zhen , Santamaria Fidel
Published: June 2016

Coding in cerebellar Purkinje cells not only depends on synaptic plasticity but also on their intrinsic membrane excitability. We performed whole cell patch-clamp recordings of Purkinje cells in sagittal cerebellar slices in mice. We found that inducing long-term depression (LTD) in the parallel fiber to Purkinje cell synapses results in an increase in the gain of the firing rate response. This increase in excitability is accompanied by an increase in the input resistance and a decrease in the amplitude of the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel-mediated voltage sag. Application of a HCN channel blocker prevents the increase in input resistance and excitability without blocking the expression of synaptic LTD. We conclude that the induction of parallel fiber-Purkinje cell LTD is accompanied by an increase in excitability of Purkinje cells through downregulation of the HCN-mediated h current. We suggest that HCN downregulation is linked to the biochemical pathway that sustains synaptic LTD. Given the diversity of information carried by the parallel fiber system, we suggest that changes in intrinsic excitability enhance the coding capacity of the Purkinje cell to specific input sources.
Human parietal cortex lesions impact the precision of spatial working memory
Authors: Mackey Wayne E. , Devinsky Orrin , Doyle Werner K. , Golfinos John G. , Curtis Clayton E.
Published: June 2016

The neural mechanisms that support working memory (WM) depend on persistent neural activity. Within topographically organized maps of space in dorsal parietal cortex, spatially selective neural activity persists during WM for location. However, to date, the necessity of these topographic subregions of human parietal cortex for WM remains unknown. To test the causal relationship of these areas to WM, we compared the performance of patients with lesions to topographically organized parietal cortex with those of controls on a memory-guided saccade (MGS) task as well as a visually guided saccade (VGS) task. The MGS task allowed us to measure WM precision continuously with great sensitivity, whereas the VGS task allowed us to control for any deficits in general spatial or visuomotor processing. Compared with controls, patients generated memory-guided saccades that were significantly slower and less accurate, whereas visually guided saccades were unaffected. These results provide key missing evidence for the causal role of topographic areas in human parietal cortex for WM, as well as the neural mechanisms supporting WM.
Using melanopsin to study G protein signaling in cortical neurons
Authors: McGregor K. M. , Bécamel C. , Marin P. , Andrade R.
Published: June 2016

Our understanding of G protein-coupled receptors (GPCRs) in the central nervous system (CNS) has been hampered by the limited availability of tools allowing for the study of their signaling with precise temporal control. To overcome this, we tested the utility of the bistable mammalian opsin melanopsin to examine G protein signaling in CNS neurons. Specifically, we used biolistic (gene gun) approaches to transfect melanopsin into cortical pyramidal cells maintained in organotypic slice culture. Whole cell recordings from transfected neurons indicated that application of blue light effectively activated the transfected melanopsin to elicit the canonical biphasic modulation of membrane excitability previously associated with the activation of GPCRs coupling to Gαq-11. Remarkably, full mimicry of exogenous agonist concentration could be obtained with pulses as short as a few milliseconds, suggesting that their triggering required a single melanopsin activation-deactivation cycle. The resulting temporal control over melanopsin activation allowed us to compare the activation kinetics of different components of the electrophysiological response. We also replaced the intracellular loops of melanopsin with those of the 5-HT2A receptor to create a light-activated GPCR capable of interacting with the 5-HT2A receptor interacting proteins. The resulting chimera expressed weak activity but validated the potential usefulness of melanopsin as a tool for the study of G protein signaling in CNS neurons.
Looking for symmetry: fixational eye movements are biased by image mirror symmetry
Authors: Meso Andrew Isaac , Montagnini Anna , Bell Jason , Masson Guillaume S.
Published: June 2016

Humans are highly sensitive to symmetry. During scene exploration, the area of the retina with dense light receptor coverage acquires most information from relevant locations determined by gaze fixation. We characterized patterns of fixational eye movements made by observers staring at synthetic scenes either freely (i.e., free exploration) or during a symmetry orientation discrimination task (i.e., active exploration). Stimuli could be mirror-symmetric or not. Both free and active exploration generated more saccades parallel to the axis of symmetry than along other orientations. Most saccades were small (<2°), leaving the fovea within a 4° radius of fixation. Analysis of saccade dynamics showed that the observed parallel orientation selectivity emerged within 500 ms of stimulus onset and persisted throughout the trials under both viewing conditions. Symmetry strongly distorted existing anisotropies in gaze direction in a seemingly automatic process. We argue that this bias serves a functional role in which adjusted scene sampling enhances and maintains sustained sensitivity to local spatial correlations arising from symmetry.
Activation of GPR119 Stimulates Humanβ-Cell Replication and Neogenesis in Humanized Mice with Functional Human Islets
Authors: Ansarullah  , Free Colette , Christopherson Jenica , Chen Quanhai , Gao Jie , Liu Chengyang , Naji Ali , Rabinovitch Alex , Guo Zhiguang
Published: June 2016

Using humanized mice with functional human islets, we investigated whether activating GPR119 by PSN632408, a small molecular agonist, can stimulate humanβ-cell regenerationin vivo. Human islets were transplanted under the left kidney capsule of immunodeficient mice with streptozotocin- (STZ-) induced diabetes. The recipient mice were treated with PSN632408 or vehicle and BrdU daily. Human islet graft function in the mice was evaluated by nonfasting glucose levels, oral glucose tolerance, and removal of the grafts. Immunostaining for insulin, glucagon, and BrdU or Ki67 was performed in islet grafts to evaluateα- andβ-cell replication. Insulin and CK19 immunostaining was performed to evaluateβ-cell neogenesis. Four weeks after human islet transplantation, 71% of PSN632408-treated mice achieved normoglycaemia compared with 24% of vehicle-treated mice. Also, oral glucose tolerance was significantly improved in the PSN632408-treated mice. PSN632408 treatment significantly increased both humanα- andβ-cell areas in islet grafts and stimulatedα- andβ-cell replication. In addition,β-cell neogenesis was induced from pancreatic duct cells in the islet grafts. Our results demonstrated that activation of GPR119 increasesβ-cell mass by stimulating humanβ-cell replication and neogenesis. Therefore, GPR119 activators may qualify as therapeutic agents to increase humanβ-cell mass in patients with diabetes.
The Need for Pediatric Formulations to Treat Children with HIV
Authors: Schlatter Adrienne F. , Deathe Andrew R. , Vreeman Rachel C.
Published: June 2016

Over 3.2 million children worldwide are infected with HIV, but only 24% of these children receive antiretroviral therapy (ART). ART adherence among children is a crucial part of managing human-immunodeficiency virus (HIV) infection and extending the life and health of infected children. Important causes of poor adherence are formulation- and regimen-specific properties, including poor palatability, large pill burden, short dosing intervals, and the complex storage and transportation of drugs. This review aims to summarize the various regimen- and formulation-based barriers to ART adherence among children to support the need for new and innovative pediatric formulations for antiretroviral therapy (ART). Detailing the arguments both for and against investing in the development of pediatric HIV medications, as well as highlighting recent advances in pediatric ART formulation research, provides a synopsis of the current data related to pediatric ART formulations and adherence.
Diagnostic Accuracy of Five Different Fecal Markers for the Detection of Precancerous and Cancerous Lesions of the Colorectum
Authors: Rutka Mariann , Bor Renáta , Bálint Anita , Fábián Anna , Milassin Ágnes , Nagy Ferenc , Szepes Zoltán , Szűcs Mónika , Tiszlavicz László , Farkas Klaudia , Molnár Tamás
Published: June 2016

Background.Colorectal cancer (CRC) is the second deadliest malignancy worldwide. This study aimed to compare the diagnostic accuracy of different fecal markers in the detection of colorectal adenomas and cancer.Methods.Stool samples of patients referred to colonoscopy were collected for the analysis of tumor M2pyruvate kinase (M2PK), human hemoglobin (Hb), hemoglobin/haptoglobin (Hb/Hp) complex, fecal calprotectin (FC), and matrix metalloproteinase-9 (MMP-9).Results.Sensitivity and specificity of M2PK for adenomas sized > 1 cm were 60% and 67.5% and for CRC were 94.7% and 67.5%. Sensitivity and specificity of iFOBT for adenomas sized ≥ 1 cm were 80% and 72.5% and for CRC were 94.7% and 72.5%. Sensitivity and specificity of Hb/Hp complex for adenomas sized ≥ 1 cm were 80% and 52.9% and for CRC were 100% and 52.9%. Sensitivity of FC and MMP-9 for CRC was 77.8% and 72.2%. Combined use of M2PK, iFOBT, and FC resulted in a sensitivity and specificity of 95% and 47.5% for the detection of adenomas sized ≥ 1 cm.Discussion.In CRC, sensitivity of M2PK, iFOBT, and Hb/Hp complex proved to be high. Combined use of M2PK, iFOBT, and FC may be valuable in the detection of large adenomas.
Urinary Biomarkers in the Assessment of Early Diabetic Nephropathy
Authors: Gluhovschi Cristina , Gluhovschi Gheorghe , Petrica Ligia , Timar Romulus , Velciov Silvia , Ionita Ioana , Kaycsa Adriana , Timar Bogdan
Published: June 2016

Diabetic nephropathy (DN) is a frequent and severe complication of diabetes mellitus (DM). Its diagnosis in incipient stages may allow prompt interventions and an improved prognosis. Towards this aim, biomarkers for detecting early DN can be used. Microalbuminuria has been proven a remarkably useful biomarker, being used for diagnosis of DN, for assessing its associated condition—mainly cardiovascular ones—and for monitoring its progression. New researches are pointing that some of these biomarkers (i.e., glomerular, tubular, inflammation markers, and biomarkers of oxidative stress) precede albuminuria in some patients. However, their usefulness is widely debated in the literature and has not yet led to the validation of a new “gold standard” biomarker for the early diagnosis of DN. Currently, microalbuminuria is an important biomarker for both glomerular and tubular injury. Other glomerular biomarkers (transferrin and ceruloplasmin) are under evaluation. Tubular biomarkers in DN seem to be of a paramount importance in the early diagnosis of DN since tubular lesions occur early. Additionally, biomarkers of inflammation, oxidative stress, podocyte biomarkers, and vascular biomarkers have been employed for assessing early DN. The purpose of this review is to provide an overview of the current biomarkers used for the diagnosis of early DN.
Optical Coherence Tomography Parameters in Morbidly Obese Patients Who Underwent Laparoscopic Sleeve Gastrectomy
Authors: Dogan Berna , Dogan Ugur , Erol Muhammet Kazim , Habibi Mani , Bulbuller Nurullah
Published: June 2016

Purpose. To investigate changes in optical coherence tomography parameters in morbidly obese patients who had undergone laparoscopic sleeve gastrectomy (LSG).Methods. A total of 41 eyes of 41 morbidly obese patients (BMI ≥ 40) who had undergone LSG were included in study. The topographic optic disc parameters, central macular thickness (CMT), total macular volume (TMV), and retinal ganglion cell layer (RGCL) were measured by spectral-domain optical coherence tomography (SD-OCT). Subfoveal choroidal thickness (SFCT) was measured by enhanced deep imaging-optical coherence tomography (EDI-OCT).Results. The mean CMT was237.4±24.5 μm,239.3±24.1 μm, and240.4±24.5 μm preoperatively, 3 months postoperatively, and 6 months postoperatively, respectively (p<0.01). The mean TMV was9.88±0.52 mm3,9.96±0.56 mm3, and9.99±0.56 mm3preoperatively, 3 months postoperatively, and 6 months postoperatively, respectively (p<0.01). The mean RGCL was81.2±6.5 μm,82.7±6.6 μm, and82.9±6.5 μm preoperatively, 3 months postoperatively, and 6 months postoperatively, respectively (p<0.01). The mean SFCT was309.8±71.8 μm,331.0±81.4 μm, and352.7±81.4 μm preoperatively, 3 months postoperatively, and 6 months postoperatively, respectively (p<0.01). No statistically significant differences were found between the preoperative values and 3- and 6-month postoperative values in rim area (p=0.34), disc area (p=0.64), vertical cup/disc ratio (p=0.39), cup volume (p=0.08), or retinal nerve fiber layer (p=0.90).Conclusions. Morbidly obese patients who undergo LSG experience a statistically significant increase in CMT, TMV, SFCT, and RGCL at 3 months and 6 months after surgery.
Identification of Novel Vaccine Candidates againstCampylobacterthrough Reverse Vaccinology
Authors: Meunier Marine , Guyard-Nicodème Muriel , Hirchaud Edouard , Parra Alberto , Chemaly Marianne , Dory Daniel
Published: June 2016

Campylobacteriosis is the most prevalent bacterial foodborne gastroenteritis affecting humans in the European Union. Human cases are mainly due toCampylobacter jejuniorCampylobacter coli, and contamination is associated with the handling and/or consumption of poultry meat. In fact, poultry constitutes the bacteria’s main reservoir. A promising way of decreasing the incidence of campylobacteriosis in humans would be to decrease avian colonization. Poultry vaccination is of potential for this purpose. However, despite many studies, there is currently no vaccine available on the market to reduce the intestinalCampylobacterload in chickens. It is essential to identify and characterize new vaccine antigens. This study applied the reverse vaccinology approach to detect new vaccine candidates. The main criteria used to select immune proteins were localization, antigenicity, and number of B-epitopes. Fourteen proteins were identified as potential vaccine antigens.In vitroandin vivoexperiments now need to be performed to validate the immune and protective power of these newly identified antigens.
A Quantitative Analysis of Cold Water for Human Consumption in Hospitals in Spain
Authors: González A. G. , García-Sanz-Calcedo J. , Salgado D. R. , Mena A.
Published: June 2016

An estimation of the water used for human consumption in hospitals is essential to determine possible savings and to fix criteria to improve the design of new water consumption models. The present work reports on cold water for human consumption (CWHC) in hospitals in Spain and determines the possible savings. In the period of 2005–2012, 80 Eco-Management and Audit Schemes (EMAS) from 20 hospitals were analysed. The results conclude that the average annual consumption of CWHC is 1.59 m3/m2(with a standard deviation of 0.48 m3/m2), 195.85 m3/bed (standard deviation 70.07 m3/bed), or 53.69 m3/worker (standard deviation 16.64 m3/worker). The results demonstrate the possibility of saving 5,600,000 m3of water per year. Assuming the cost of water as approximately 1.22 €/m3, annual savings are estimated as 6,832,000 €. Furthermore, 2,912 MWh of energy could be saved, and the emission of 22,400 annual tonnes of CO2into the atmosphere could be avoided.
A Multimethod Approach towards Assessing Urban Flood Patterns and Its Associated Vulnerabilities in Singapore
Authors: Chow Winston T. L. , Cheong Brendan D. , Ho Beatrice H.
Published: June 2016

We investigated flooding patterns in the urbanised city-state of Singapore through a multimethod approach combining station precipitation data with archival newspaper and governmental records; changes in flash floods frequencies or reported impacts of floods towards Singapore society were documented. We subsequently discussed potential flooding impacts in the context of urban vulnerability, based on future urbanisation and forecasted precipitation projections for Singapore. We find that, despite effective flood management, (i) significant increases in reported flash flood frequency occurred in contemporary (post-2000) relative to preceding (1984–1999) periods, (ii) these flash floods coincide with more localised, “patchy” storm events, (iii) storms in recent years are also more intense and frequent, and (iv) floods result in low human casualties but have high economic costs via insurance damage claims. We assess that Singapore presently has low vulnerability to floods vis-à-vis other regional cities largely due to holistic flood management via consistent and successful infrastructural development, widespread flood monitoring, and effective advisory platforms. We conclude, however, that future vulnerabilities may increase from stresses arising from physical exposure to climate change and from demographic sensitivity via rapid population growth. Anticipating these changes is potentially useful in maintaining the high resilience of Singapore towards this hydrometeorological hazard.
Development of a Stable TiO2Nanocomposite Self-Cleaning Coating for Outdoor Applications
Authors: Madidi F. , Momen G. , Farzaneh M.
Published: June 2016

A convenient and low-cost approach for the elaboration of a stable superhydrophobic coating is reported, involving the use of TiO2nanoparticles via the spray coating method. This method can be used for preparing self-cleaning superhydrophobic coatings on large areas for different kinds of substrates. The synergistic effect of the micro/nanobinary scale roughness was produced by a multilayer RTV SR/TiO2composite. The influence of the nanofiller concentration in a specific frequency range (40 Hz to 2 MHz) on the dielectric behavior was analyzed as well. It was found that the real relative permittivity (εr′) increases as the nanofiller concentration increases. Superhydrophobic behavior is analyzed by contact angle measurements, scanning electron microscopy (SEM), and profilometer. The stability of the developed coating also has been evaluated in terms of immersion in various aqueous solutions, heating, adhesion, and exposure to UV irradiation, and the results showed good stability against these factors. The coating retained its superhydrophobicity after several days of immersion in solutions of different pH levels (2, 4, 6, and 12) and different conductivities. In addition, they also exhibited exceptional stability against UV radiation and heating, as well as good mechanical stability.
Ulcerated Scrotal Hemangioma in an 18-Month-Old Male Patient: A Case Report and Review of the Literature
Authors: Patoulias Ioannis , Farmakis Konstantinos , Kaselas Christos , Patoulias Dimitrios
Published: June 2016

Deep scrotal hemangiomas are rare. Less than 50 case reports have been published. After systematic research of the literature, we found less than 5 cases of ulcerated scrotal hemangioma. The aim of this case report is to illustrate the challenges of scrotal hemangiomas pose and their potential therapies based on the successful surgical treatment of an ulcerated scrotal hemangioma in an 18-month-old male patient.
Reproductive Factors and Risk of Luminal, HER2-Overexpressing, and Triple-Negative Breast Cancer Among Multiethnic Women
Authors: Chen Lu , Li Christopher I. , Tang Mei-Tzu C. , Porter Peggy , Hill Deirdre A. , Wiggins Charles L. , Cook Linda S.
Published: June 2016

Background: Reproductive factors are among the most well-established risk factors for breast cancer. However, their associations with different breast cancer subtypes defined by joint estrogen receptor (ER)/progesterone receptor (PR)/HER2 status remain unclear.

Methods: We assessed relationships between reproductive factors and risks of luminal A (ER+/HER2−), luminal B (ER+/HER2+), triple-negative (TN; ER−/PR−/HER2−), and HER2-overexpressing (H2E; ER−/HER2+) breast cancers in a population-based case–case study consisting of 2,710 women ages 20–69 years diagnosed between 2004 and 2012. ORs and 95% confidence intervals (CI) were estimated with luminal A cases serving as the reference group using polytomous logistic regression.

Results: Earlier age at first full-term pregnancy and age at menopause were positively associated with odds of TN breast cancer (Ptrend: 0.003 and 0.024, respectively). Parity was associated with a 43% (95% CI, 1.08–1.89) elevated odds of H2E breast cancer, and women who had ≥3 full-term pregnancies had a 63% (95% CI, 1.16–2.29, Ptrend = 0.013) increased odds of this subtype compared with nulliparous women. Breast feeding for ≥36 months was associated with a 49% (OR 0.51; 95% CI, 0.27–0.99) lower odds of TN breast cancer.

Conclusion: Our results suggest that reproductive factors contribute differently to risks of the major molecular subtypes of breast cancer.

Impact: African American and Hispanic women have higher incidence rates of the more aggressive TN and H2E breast cancers and their younger average age at first pregnancy, higher parity, and less frequent breast feeding could in part contribute to this disparity. Cancer Epidemiol Biomarkers Prev; 25(9); 1297–304. ©2016 AACR.
Dysregulation of c-Myb Pathway by Aberrant Expression of Proto-oncogene MYB Provides the Basis for Malignancy in Adult T-cell Leukemia/lymphoma Cells
Authors: Nakano Kazumi , Uchimaru Kaoru , Utsunomiya Atae , Yamaguchi Kazunari , Watanabe Toshiki
Published: June 2016

Purpose: Adult T-cell leukemia/lymphoma (ATLL) is an aggressive human T-cell malignancy induced by human T-lymphotrophic virus-1 (HTLV-1) infection. The genetic alterations in infected cells that lead to transformation have not been completely elucidated, thus hindering the identification of effective therapeutic targets for ATL. Here, we present the first assessment of MYB proto-oncogene dysregulation in ATL and an exploration of its role in the onset of ATL.

Experimental Design: We investigated the expression patterns of MYB splicing variants in ATL. The molecular characteristics of the c-Myb-9A isoform, which was overexpressed in ATL cells, were examined using chromatin immunoprecipitation and promoter assays. We further examined the biologic impacts of abnormal c-Myb overexpression in ATL using overall c-Myb knockdown with shRNA or c-Myb-9A knockdown with morpholino oligomers.

Results: Both total c-Myb and c-Myb-9A, which exhibited strong transforming activity, were overexpressed in ATL cells in a leukemogenesis- and progression-dependent manner. Knockdown of either total c-Myb or c-Myb-9A induced ATL cell death. c-Myb transactivates nine genes that encode essential regulators of cell proliferation and NF-κB signaling. c-Myb-9A induced significantly stronger transactivation of all tested genes and stronger NF-κB activation compared with wild-type c-Myb.

Conclusions: Our data demonstrate that c-Myb pathway overactivation caused by unbalanced c-Myb-9A overexpression is associated with disorders in cellular homeostasis and consequently, accelerated transformation, cell proliferation, and malignancy in ATL cells. These data support the notion of the c-Myb pathway as a promising new therapeutic target for ATL. Clin Cancer Res; 22(23); 5915–28. ©2016 AACR.
Prognostic Significance of Major Histocompatibility Complex Class II Expression in Pediatric Adrenocortical Tumors: A St. Jude and Children's Oncology Group Study
Authors: Pinto Emilia Modolo , Rodriguez-Galindo Carlos , Choi John Kim , Pounds Stanley , Liu Zhifa , Neale Geoffrey , Finkelstein David , Hicks John M. , Pappo Alberto S. , Figueiredo Bonald C. , Ribeiro Raul C. , Zambetti Gerard P.
Published: June 2016

Purpose: Histologic markers that differentiate benign and malignant pediatric adrenocortical tumors are lacking. Previous studies have implicated an association of MHC class II expression with adrenocortical tumor prognosis. Here, we determined the expression of MHC class II as well as the cell of origin of these immunologic markers in pediatric adrenocortical tumor. The impact of MHC class II gene expression on outcome was determined in a cohort of uniformly treated children with adrenocortical carcinomas.

Experimental Design: We analyzed the expression of MHC class II and a selected cluster of differentiation genes in 63 pediatric adrenocortical tumors by Affymetrix Human U133 Plus 2.0 or HT HG-U133+PM gene chip analyses. Cells expressing MHC class II were identified by morphologic and immunohistochemical assays.

Results: MHC class II expression was significantly greater in adrenocortical adenomas than in carcinomas (P = 4.8 ×10−6) and was associated with a higher progression-free survival (PFS) estimate (P = 0.003). Specifically, HLA-DPA1 expression was most significantly associated with PFS after adjustment for tumor weight and stage. HLA-DPA1 was predominantly expressed by hematopoietic infiltrating cells and undetectable in tumor cells in 23 of 26 cases (88%).

Conclusions: MHC class II expression, which is produced by tumor-infiltrating immune cells, is an indicator of disease aggressiveness in pediatric adrenocortical tumor. Our results suggest that immune responses modulate adrenocortical tumorigenesis and may allow the refinement of risk stratification and treatment for this disease. Clin Cancer Res; 22(24); 6247–55. ©2016 AACR.
Periostin (POSTN) Regulates Tumor Resistance to Antiangiogenic Therapy in Glioma Models
Authors: Park Soon Young , Piao Yuji , Jeong Kang Jin , Dong Jianwen , de Groot John F.
Published: June 2016

Periostin (POSTN) interacts with multiple integrins to coordinate a variety of cellular processes, including epithelial-to-mesenchymal transition (EMT) and cell migration. In our previous study, anti-VEGF-A therapy was associated with resistance and EMT. This study sought to determine the role of POSTN in the resistance of glioma stem cells (GSC) to antiangiogenic therapy. In mouse xenograft models of human glioma, POSTN expression was associated with acquired resistance to anti-VEGF-A therapy and had a synergistic effect with bevacizumab in prolonging survival and decreasing tumor volume. Resistance to anti-VEGF-A therapy regulated by POSTN was associated with increased expression of TGFβ1 and hypoxia-inducible factor-1α (HIF1α) in GSCs. At the molecular level, POSTN regulated invasion and expression of EMT (caveolin-1) and angiogenesis-related genes (HIF1α and VEGF-A) through activation of STAT3. Moreover, recombinant POSTN increased GSC invasion. Collectively, our findings suggest that POSTN plays an important role in glioma invasion and resistance to antiangiogenic therapy. Mol Cancer Ther; 15(9); 2187–97. ©2016 AACR.
High-Resolution Mapping of Ventricular Scar
Authors: Tschabrunn Cory M. , Roujol Sebastien , Dorman Nicole C. , Nezafat Reza , Josephson Mark E. , Anter Elad
Published: June 2016

Background—

Mapping resolution is influenced by electrode size and interelectrode spacing. The aims of this study were to establish normal electrogram criteria for 1-mm multielectrode-mapping catheters (Pentaray) in the ventricle and to compare its mapping resolution within scar to standard 3.5-mm catheters (Smart-Touch Thermocool).

Methods and Results—

Three healthy swine and 11 swine with healed myocardial infarction underwent sequential mapping of the left ventricle with both catheters. Bipolar voltage amplitude in healthy tissue was similar between 3.5- and 1-mm multielectrode catheters with a 5th percentile of 1.61 and 1.48 mV, respectively. In swine with healed infarction, the total area of low bipolar voltage amplitude (defined as <1.5 mV) was 22.5% smaller using 1-mm multielectrode catheters (21.7 versus 28.0 cm2;
P
=0.003). This was more evident in the area of dense scar (bipolar amplitude <0.5 mV) with a 47% smaller very low–voltage area identified using 1-mm electrode catheters (7.1 versus 15.2 cm
2
;
P
=0.003). In this region, 1-mm multielectrode catheters recorded higher voltage amplitude (0.72±0.81 mV versus 0.30±0.12 mV;
P
<0.001). Importantly, 27% of these dense scar electrograms showed distinct triphasic electrograms when mapped using a 1-mm multielectrode catheter compared with fractionated multicomponent electrogram recorded with the 3.5-mm electrode catheter. In 8 mapped reentrant ventricular tachycardias, the circuits included regions of preserved myocardial tissue channels identified with 1-mm multielectrode catheters but not 3.5-mm electrode catheters. Pacing threshold within the area of low voltage was lower with 1-mm electrode catheters (0.9±1.3 mV versus 3.8±3.7 mV;
P
=0.001).

Conclusions—

Mapping with small closely spaced electrode catheters can improve mapping resolution within areas of low voltage.
Association of Central Adiposity With Adverse Cardiac Mechanics
Authors: Selvaraj Senthil , Martinez Eva E. , Aguilar Frank G. , Kim Kwang-Youn A. , Peng Jie , Sha Jin , Irvin Marguerite R. , Lewis Cora E. , Hunt Steven C. , Arnett Donna K. , Shah Sanjiv J.
Published: June 2016

Background—

Central obesity, defined by increased waist circumference or waist:hip ratio (WHR), is associated with increased cardiovascular events, including heart failure. However, the pathophysiological link between central obesity and adverse cardiovascular outcomes remains poorly understood. We hypothesized that central obesity and larger WHR are independently associated with worse cardiac mechanics (reduced left ventricular strain and systolic [s′] and early diastolic [e′] tissue velocities).

Methods and Results—

We performed speckle-tracking analysis of echocardiograms from participants in the Hypertension Genetic Epidemiology Network (HyperGEN) study, a population- and family-based epidemiological study (n=2181). Multiple indices of systolic and diastolic cardiac mechanics were measured. We evaluated the association between central obesity and cardiac mechanics using multivariable-adjusted linear mixed-effects models to account for relatedness among participants. The mean age of the cohort was 51±14 years, 58% were women, and 47% were black. Mean body mass index was 30.8±7.1 kg/m
2
, waist circumference was 102±17 cm, WHR was 0.91±0.08, and 80% had central obesity based on waist circumference and WHR criteria. After adjusting for multiple potential confounders (including age, sex, race, physical activity, body mass index, heart rate, smoking status, systolic blood pressure, fasting glucose, total cholesterol, antihypertensive medication use, glomerular filtration rate, left ventricular mass index, wall motion abnormalities, and ejection fraction), central obesity and WHR remained associated with worse global longitudinal strain, early diastolic strain rate, s′ velocity, and e′ velocity (
P
<0.05 for all comparisons). There were no significant statistical interactions between WHR and obesity status.

Conclusions—

In this cross-sectional study of participants with multiple comorbidities, central obesity was found to be associated with adverse cardiac mechanics.
Cardiac Remodeling in Patients With Primary and Secondary Aldosteronism
Authors: Cesari Maurizio , Letizia Claudio , Angeli Paolo , Sciomer Susanna , Rosi Silvia , Rossi Gian Paolo
Published: June 2016

Background—

Primary aldosteronism (PA) causes excess left ventricular (LV) hypertrophy and diastolic dysfunction; whether this occurs also in secondary aldosteronism (SA) without hypertension is unknown. We investigated the cardiac modifications in patients with preserved LV ejection fraction who had PA or SA.

Methods and Results—

We measured several Doppler echocardiography–derived variables, including tissue Doppler imaging (TDI) parameters and strain rate analysis, in 262 patients with PA, 117 with SA because of liver cirrhosis, and in 61 control healthy subjects. SA and PA patients showed markedly elevated aldosterone levels (67 versus 39 ng/dL, respectively; normal values <15 ng/dL) but contrasting values of plasma renin activity (15.00 versus 0.56 ng/mL/h;
P
<0.001). Compared with PA, SA patients showed higher heart rate, and lower blood pressure and vascular resistance values. Both PA and SA showed increased LV diameters, LV volumes, stroke volume, stroke work, and septal peak systolic tissue velocity, and had more LV hypertrophy (61% and 39%, respectively) and diastolic dysfunction (35% and 36%, respectively) than healthy subjects. Peak systolic septal strain (20% versus 23%;
P
=<0.001) and midwall fractional shortening (15.9% versus 16.7%;
P
=0.001) were lower in PA than in SA patients.

Conclusions—

Primary and secondary hyperaldosteronism correlate with LV enlargement and high prevalence of LV hypertrophy and diastolic dysfunction; a subclinical systolic dysfunction is evident only in PA. In SA, the high rate of LV hypertrophy, in spite of low peripheral resistances and low-to-normal blood pressure, could be accounted for the high renin and aldosterone values, and the work overload associated with a hyperdynamic circulatory state.
Data Protection Compliance in the Age of Digital Health
Authors: Hordern Victoria
Published: June 2016

Advances in technology are transforming the way that health data is collected and used. This includes improvements in existing technology as well as innovations in mobile technology such as smartphone apps and wearables. Health data is strictly regulated under the eu Data Protection Directive 95/46/ec. Under current data protection rules, health data is broadly interpreted and will, in most circumstances not connected to the provision of healthcare, require organisations to obtain explicit consent from individuals for its collection and use. Further data protection compliance issues arise such as identifying who is a controller, ensuring transparency, using health data for research purposes and keeping health data secure. As the eu data protection landscape is due to change in the next few years and will affect the collection and use of health data, the forthcoming Data Protection Regulation also deserves attention.
Electronic Health Record in Italy and Personal Data Protection
Authors: Bologna Silvio , Bellavista Alessandro , Corso Pietro Paolo , Zangara Gianluca
Published: June 2016

The present article deals with the Italian Electronic Health Record (hereinafter ehr), recently introduced by Act 221/2012, with a specific focus on personal data protection. Privacy issues — e.g., informed consent, data processing, patients’ rights and minors’ will — are discussed within the framework of recent e-Health legislation, national Data Protection Code, the related Data Protection Authority pronouncements and eu law. The paper is aimed at discussing the problems arising from a complex, fragmentary and sometimes uncertain legal framework on e-Health.
Les lois romaines définissant des parentèles (IIIe s. av. J.-C. ‒ Ier s. apr. J.-C.)
Authors: Moreau Philippe
Published: June 2016

The aim of this paper is to study specific clauses of certain Roman laws, namely leges rogatae and municipal statutes, written between 204 a.C. and the Augustan period and exempting one’s kindred (cognates and affins) from the prescriptions that they made (personae exceptae). The first section of this analysis reviews the epigraphic evidence, which is supposed to provide us with the most reliable phrasing of the laws; the paper then proceeds with studying texts of jurists and historians as transmitted by the manuscripts, and thus more doubtful formulations that require a thorough philological examination. On the basis of this twofold analysis, it is argued that Roman lawgivers repeatedly endeavoured to protect a nucleus consisting of a wide circle of cognates (generally going as far as the sobrinus, viz. at the 6th Roman degree) and of some close affins.
Hypothekarische Sukzession
Authors: Schanbacher Dietmar
Published: June 2016

What does ‘hypothekarische Sukzession’ mean? One pledgee is replaced by another, who paid the sum owed by the debtor. The Roman sources use the word succedere. But the cases are different. Not all of them should be spoken of as ‘hypothekarische Sukzession’.
The status of ambassadors in Lucas de Penna’s Commentary on the Tres Libri
Authors: Fedele Dante
Published: June 2016

Lucas de Penna’s commentary on the Tres Libri Codicis – and, in particular, that commentary’s section on the part de legationibus – documents how late-Medieval civil law scholarship contributed to work out the status of ambassadors. Although De Penna’s text has been overlooked in legal historiography and studies on Medieval diplomacy, the author’s specific approach was at the time unique in late-Medieval legal scholarship, both in terms of method and content, and anticipated in many ways essential themes of early-modern scholarship on the status of diplomats.
Recent research in the history of international law
Authors: Dhondt Frederik
Published: June 2016

This review article treats the booming scholarship on the history of international law over the past decade. Works with a broader view (1), including the recent big-book syntheses and collective works, are contrasted with monographs (2), from studies of treaties and doctrine, over diplomatic practice to scholarship by historians and, finally, interdisciplinary scholarship. This texts provides a personal panorama of the wide array of scholarly perspectives on a common object: rules recognised in the community or society of states. New insights from history and social sciences, especially the turn to global history, open fresh prospects for ‘traditional’ legal historical research. Studying the encounter between ‘European’ international law and other continents rises our indispensable intercultural awareness. Yet, it should also serve to better understand the specificity of European legal thinking or diplomatic practice, and does not render research on the latter obsolete or redundant.
Fraternalism as a Limitation on Religious Freedom: The Case of S.A.S. v. France
Authors: Daly Eoin
Published: June 2016

In upholding France’s ban on public face coverings, the European Court of Human Rights accepted that the manifestation of religious beliefs could legitimately be restricted in the interests of ‘vivre ensemble’—literally, ‘living together’—or what I label ‘fraternalism’. I will argue that fraternalism, in the French setting, is closely linked to the idea of a duty of civility in political theory: it is understood as a duty to practice a certain kind of fraternal sociability. This paper relates the Court’s judgment to France’s justificatory, ‘republican’ discourse. It argues that civility must be understood as a habitus—a set of learned orientations and bodily techniques—rather than as a set of discursive or speech constraints. In turn, this demonstrates the danger in the idea of civility (or fraternalism) as limiting religious liberties: far from simply fostering republican virtues, it will reinforce cultural and social power dynamics.
Lepeostegeres cebuensis (Loranthaceae), a new mistletoe species from Cebu, Philippines
Authors: PELSER PIETER B. , NICKRENT DANIEL L. , REINTAR ANDREW R. T. , BARCELONA JULIE F.
Published: June 2016

Lepeostegeres cebuensis is described as a new species from Cebu Island, Philippines. It is unique among currently known species in the genus by having peculiar ridges of orange-brown scales on the young leaves and internodes. This discovery brings the total number of Philippine Lepeostegeres species to three. We consider Lepeostegeres cebuensis to be Data Deficient (DD) following the Red List Criteria of the International Union for the Conservation of Nature (IUCN).
Notes on the genus Conocephalus (Orthoptera: Tettigoniidae; Conocephalinae; Conocephalini) from India and description of two new species
Authors: NAGAR RAJENDRA , SWAMINATHAN R.
Published: June 2016

The present paper describes two new species of Conocephalus: Conocephalus decaspinosus sp. nov. and C. kwasiphaiensis sp. nov., as additions to the previously known species of the genus; among these, two species have been reported for the first time from India, viz., C. concolor peneri and C. vaginalis. The key morphological characters of the head, pronotum, cerci, spines on the fore tibiae, hind femora, stridulatory file and the ovipositor have been illustrated with suitable line drawings to distinguish the reported new species. The distribution map of the species in India has been provided with a key to the subgenera.
Review of the genus Stigmaporus S. Zonstein, 2001 (Hymenoptera: Pompilidae), with description of new species
Authors: LOKTIONOV VALERY M. , LELEJ ARKADY S. , MOKROUSOV MIKHAIL V.
Published: June 2016

The genus Stigmaporus S. Zonstein, 2001 is newly recorded from Russia. Four species are reviewed. Stigmaporus volgadon Loktionov & Lelej, sp. nov. from South of European part of Russia (Volgograd Prov. and Astrakhan Prov.) is described and illustrated. Stigmaporus centralasiaticus Wolf, 1990 is distributed in Xinjiang (China) not in Afghanistan, Pakistan or former USSR as was recorded earlier. Key to species is provided.
First record of the sicklefin devilray Mobula tarapacana (Myliobatiformes: Mobulidae) from Australian waters
Authors: DUFFY CLINTON A.J. , VOGIATZIS ANTON
Published: June 2016

The sicklefin devilray Mobula tarapacana (Philippi, 1892) is one of the largest and least known mobulids (Compagno & Last 1999; Couturier et al. 2012). Collections, fisheries bycatch data and visual records suggest it is primarily oceanic, with a circumglobal tropical and warm temperate distribution (Notarbartolo-di-Sciara 1987; Compagno & Last 1999; Gadig & Sampaio 2002; White et al. 2006a, b; Weir et al. 2012; Sobral 2013; Tomita et al. 2013). In the Pacific Ocean it has been recorded from Chile, Gulf of California, Japan, Taiwan, South China Sea and Indonesia (Compagno & Last 1999; White et al. 2006b; Couturier et al. 2012; Tomita et al. 2013).
Image-Guided Placement of Osseointegrated Implants for Challenging Auricular, Orbital, and Rhinectomy Defects
Authors: Choi Kevin J. , Sajisevi Mirabelle B. , McClennen Jay , Kaylie David M.
Published: June 2016

Objectives:

Prosthetic reconstruction can restore the preoperative form and function after surgery for head and neck malignancies. We demonstrate the use of preoperative planning and intraoperative image guidance for placement of osseointegrated implants to restore craniofacial defects.

Methods:

A retrospective review of patients with craniofacial defects treated with image-guided placement of osseointegrated prosthetic implants was performed.

Results:

Case 1: 55-year-old male who underwent total auriculectomy with anterolateral thigh reconstruction. Case 2: 64-year-old male who required orbital exenteration and total auriculectomy with latissimus dorsi reconstruction. Case 3: 74-year-old male presented after a total rhinectomy. Cases 1 and 3 received adjuvant radiation prior to implantation. Case 2 underwent simultaneous placement of osseointegrated hearing and prosthetic implants. Computed tomography scans were used to perform preoperative planning to determine the optimal implant trajectories and sites. Complications included tissue overgrowth, delayed nonunion of implant, wound infection, and dehiscence.

Conclusions:

Defects following oncologic resection of head and neck malignancies can be difficult to achieve with native tissue alone. Osseointegrated implants offer an excellent means for reconstruction but can be challenging due to limited bone stock and anatomic landmarks. This can be overcome using intraoperative image guidance techniques for prosthetic reconstruction.
ATS-PD: An Adaptive Testing System for Psychological Disorders
Authors: Donadello Ivan , Spoto Andrea , Sambo Francesco , Badaloni Silvana , Granziol Umberto , Vidotto Giulio
Published: June 2016

The clinical assessment of mental disorders can be a time-consuming and error-prone procedure, consisting of a sequence of diagnostic hypothesis formulation and testing aimed at restricting the set of plausible diagnoses for the patient. In this article, we propose a novel computerized system for the adaptive testing of psychological disorders. The proposed system combines a mathematical representation of psychological disorders, known as the “formal psychological assessment,” with an algorithm designed for the adaptive assessment of an individual’s knowledge. The assessment algorithm is extended and adapted to the new application domain. Testing the system on a real sample of 4,324 healthy individuals, screened for obsessive-compulsive disorder, we demonstrate the system’s ability to support clinical testing, both by identifying the correct critical areas for each individual and by reducing the number of posed questions with respect to a standard written questionnaire.
Il futuro ha un cuore antico
Authors: Naccarella István
Published: June 2016

Carlo Levi riporta in questo libro l’esperienza del suo viaggio in Unione Sovietica nel 1955. Con la prospettiva del pittore e gli strumenti dello scrittore Levi propone un quadro a tinte neutre della società sovietica. I toni della rappresentazione si accendono nella descrizione dei singoli individui e ogni qual volta ritrova nella realtà sovietica delle analogie con la realtà delle sue esperienze passate. I motivi ricorrenti lungo le linee narrative che compongono l’intreccio sono il paesaggio e la visione d’insieme, l’evocazione del passato e la descrizione allegorica dell’incombere del tempo, il legame tra realtà lontane, il raggiungimento di una nuova dimensione e la compressione dello spazio.
Growth Factor Liberation and DPSC Response Following Dentine Conditioning
Authors: Sadaghiani L. , Gleeson H.B. , Youde S. , Waddington R.J. , Lynch C.D. , Sloan A.J.
Published: June 2016

Liberation of the sequestrated bioactive molecules from dentine by the action of applied dental materials has been proposed as an important mechanism in inducing a dentinogenic response in teeth with viable pulps. Although adhesive restorations and dentine-bonding procedures are routinely practiced, clinical protocols to improve pulp protection and dentine regeneration are not currently driven by biological knowledge. This study investigated the effect of dentine (powder and slice) conditioning by etchants/conditioners relevant to adhesive restorative systems on growth factor solubilization and odontoblast-like cell differentiation of human dental pulp progenitor cells (DPSCs). The agents included ethylenediaminetetraacetic acid (EDTA; 10%, pH 7.2), phosphoric acid (37%, pH <1), citric acid (10%, pH 1.5), and polyacrylic acid (25%, pH 3.9). Growth factors were detected in dentine matrix extracts drawn by EDTA, phosphoric acid, and citric acid from powdered dentine. The dentine matrix extracts were shown to be bioactive, capable of stimulating odontogenic/osteogenic differentiation as observed by gene expression and phenotypic changes in DPSCs cultured in monolayer on plastic. Polyacrylic acid failed to solubilize proteins from powdered dentine and was therefore considered ineffective in triggering a growth factor–mediated response in cells. The study went on to investigate the effect of conditioning dentine slices on growth factor liberation and DPSC behavior. Conditioning by EDTA, phosphoric acid, and citric acid exposed growth factors on dentine and triggered an upregulation in genes associated with mineralized differentiation, osteopontin, and alkaline phosphatase in DPSCs cultured on dentine. The cells demonstrated odontoblast-like appearances with elongated bodies and long extracellular processes extending on dentine surface. However, phosphoric acid–treated dentine appeared strikingly less populated with cells, suggesting a detrimental impact on cell attachment and growth when conditioning by this agent. These findings take crucial steps in informing clinical practice on dentine-conditioning protocols as far as treatment of operatively exposed dentine in teeth with vital pulps is concerned.