bluuebunny/crossref_metadata_2025 huggingface dataset:
Polyfluorinated Alkyl Phosphate Ester Surfactants – Current Knowledge and Knowledge Gaps
Authors: Taxvig Camilla , Rosenmai Anna Kjerstine , Vinggaard Anne Marie
Published: February 2014

Fluorochemicals are a diverse group of synthetically produced compounds with the unique ability to repel water as well as oil. This property makes them ideal for multiple purposes in a variety of consumer and industrial products. Fluorochemicals have been detected in the environment, as well as in human blood, urine and milk. Due to their long half‐life in human beings, there is an increased risk that exposure to these compounds can cause adverse effects. However, except for perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS), there is a large data gap regarding toxicological information on fluorochemicals. Polyfluorinated alkyl phosphate ester surfactants (PAPs) belong to the group of polyfluorinated alkyl surfactants. They have been detected in indoor dust and are widely used in food‐contact materials, from which they have the ability to migrate into food. Toxicological data on PAPs are very limited, but current studies indicate that some PAPs have the potential to interfere with sex hormone synthesis in vitro. Disturbance of the sex hormone balance in foetal life has been suggested to be an important mechanism involved in adverse effects on, for example, male reproductive health and development. The current lack of toxicological data on PAPs impairs the risk assessment of this group of compounds. However, until more toxicological data on PAPs are available, the limited data currently accessible give reason to believe that these compounds might have the ability to cause potentially adverse effects, as seen for other perfluorinated chemicals, including some metabolic products of PAPs.
Response to androgen therapy in patients with dyskeratosis congenita
Authors: Khincha Payal P. , Wentzensen Ingrid M. , Giri Neelam , Alter Blanche P. , Savage Sharon A.
Published: February 2014

Dyskeratosis congenita (DC) is an inherited bone marrow failure syndrome and telomere biology disorder characterized by dysplastic nails, reticular skin pigmentation and oral leucoplakia. Androgens are a standard therapeutic option for bone marrow failure in those patients with DC who are unable to undergo haematopoietic stem cell transplantation, but there are no systematic data on its use in those patients. We evaluated haematological response and side effects of androgen therapy in 16 patients with DC in our observational cohort study. Untreated DC patients served as controls. Seventy percent of treated DC patients had a haematological response with red blood cell and/or platelet transfusion independence. The expected age‐related decline in telomere length was noted in androgen‐treated patients. All treated DC patients had at least one significant lipid abnormality. Additional treatment‐related findings included a significant decrease in thyroid binding globulin, accelerated growth in pre‐pubertal children and splenic peliosis in two patients. Liver enzymes were elevated in both androgen‐treated and untreated patients, suggesting underlying liver involvement in DC. This study suggests that androgen therapy can be effectively used to treat bone marrow failure in DC, but that side effects need to be closely monitored.
C‐reactive protein promotes atherosclerosis by increasing LDL transcytosis across endothelial cells
Authors: Bian Fang , Yang Xiaoyan , Zhou Fan , Wu Pin‐Hui , Xing Shasha , Xu Gao , Li Wenjing , Chi Jiangyang , Ouyang Changhan , Zhang Yonghui , Xiong Bin , Li Yongsheng , Zheng Tao , Wu Dan , Chen Xiaoqian , Jin Si
Published: February 2014

Background and Purpose

The retention of plasma low‐density lipoprotein (LDL) particles in subendothelial space following transcytosis across the endothelium is the initial step of atherosclerosis. Whether or not C‐reactive protein (CRP) can directly affect the transcytosis of LDL is not clear. Here we have examined the effect of CRP on transcytosis of LDL across endothelial cells and have explored the underlying mechanisms.

Experimental Approach

Effects of CRP on transcytosis of FITC‐labelled LDL were examined with human umbilical vein endothelial cells and venous rings in vitro and, in vivo, ApoE‐/‐ mice. Laser scanning confocal microscopy, immunohistochemistry and Oil Red O staining were used to assay LDL.

Key Results

CRP increased transcytosis of LDL. An NADPH oxidase inhibitor, diphenylene iodonium, and the reducing agent, dithiothreitol partly or completely blocked CRP‐stimulated increase of LDL transcytosis. The PKC inhibitor, bisindolylmaleimide I and the Src kinase inhibitor, PP2, blocked the trafficking of the molecules responsible for transcytosis. Confocal imaging analysis revealed that CRP stimulated LDL uptake by endothelial cells and vessel walls. In ApoE‐/‐ mice, CRP significantly promoted early changes of atherosclerosis, which were blocked by inhibitors of transcytosis.

Conclusions and Implications

CRP promoted atherosclerosis by directly increasing the transcytosis of LDL across endothelial cells and increasing LDL retention in vascular walls. These actions of CRP were associated with generation of reactive oxygen species, activation of PKC and Src, and translocation of caveolar or soluble forms of the N‐ethylmaleimide‐sensitive factor attachment protein.
GABAB receptors in the bladder and bowel: therapeutic potential for positive allosteric modulators?: Commentary on Kalinichev et al., Br J Pharmacol 171: 995–1006
Authors: Hyland Niall P , Golubeva Anna V
Published: February 2014

Linked Article

This article is a Commentary on Kalinichev M, Palea S, Haddouk H, Royer‐Urios I, Guilloteau V, Lluel P, Schneider M, Saporito M and Poli S (2014). ADX71441, a novel, potent and selective positive allosteric modulator of the GABAB receptor, shows efficacy in rodent models of overactive bladder. Br J Pharmacol 171: 995–1006. doi: 10.1111/bph.12517
Different mechanisms of homologous and heterologous μ‐opioid receptor phosphorylation
Authors: Mann Anika , Illing Susann , Miess Elke , Schulz Stefan
Published: February 2014

The efficiency of μ‐opioid receptor signalling is tightly regulated and ultimately limited by the coordinated phosphorylation of intracellular serine and threonine residues. Here, we review and discuss recent progress in the generation and application of phosphosite‐specific μ‐opioid receptor antibodies, which have proved to be excellent tools for monitoring the spatial and temporal dynamics of receptor phosphorylation and dephosphorylation. Agonist‐induced phosphorylation of μ‐opioid receptors occurs at a conserved 10 residue sequence 370TREHPSTANT379 in the receptor's carboxyl‐terminal cytoplasmic tail. Diverse opioids induce receptor phosphorylation at S375, present in the middle of this sequence, but only high‐efficacy opioids have the ability to drive higher order phosphorylation on flanking residues (T370, T376 and T379). S375 is the initiating residue in a hierarchical phosphorylation cascade. In contrast, agonist‐independent heterologous μ‐opioid receptor phosphorylation occurs primarily at T370. The combination of phosphosite‐specific antibodies and siRNA knockdown screening also facilitated the identification of relevant kinases and phosphatases. In fact, morphine induces a selective S375 phosphorylation that is predominantly catalysed by GPCR kinase 5 (GRK5), whereas multisite phosphorylation induced by high‐efficacy opioids specifically requires GRK2/3. By contrast, T370 phosphorylation stimulated by phorbol esters or heterologous activation of Gq‐coupled receptors is mediated by PKCα. Rapid μ‐opioid receptor dephosphorylation occurs at or near the plasma membrane and is catalysed by protein phosphatase 1γ (PP1γ). These findings suggest that there are distinct phosphorylation motifs for homologous and heterologous regulation of μ‐opioid receptor phosphorylation. However, it remains to be seen to what extent different μ‐opioid receptor phosphorylation patterns contribute to the development of tolerance and dependence in vivo.

Linked Articles

This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2
Involvement of substance P in the development of cisplatin‐induced acute and delayed pica in rats
Authors: Yamamoto Kouichi , Asano Keiko , Tasaka Ayana , Ogura Yuko , Kim Seikou , Ito Yui , Yamatodani Atsushi
Published: February 2014

Background and Purpose

Although substance P (SP) and neurokinin NK1 receptors have been reported to be involved in cisplatin‐induced acute and delayed emesis, their precise roles remain unclear. Pica, the consumption of non‐nutrient materials such as kaolin in rats, can be used as a model of nausea in humans. We investigated the time‐dependent changes in cisplatin‐induced pica and the involvement of SP and NK1 receptors in this behaviour.

Experimental Approach

Rats were administered cisplatin with or without a daily injection of a 5‐HT3 receptor antagonist (granisetron) or an NK1 receptor antagonist (aprepitant), and kaolin intake was then monitored for 5 days. The effects of granisetron on the cisplatin‐induced expression of preprotachykinin‐A (PPT‐A) mRNA, which encodes mainly for SP, and on SP release in the medulla, measured by in vivo brain microdialysis, were also investigated.

Key Results

Cisplatin induced pica within 8 h of its administration that continued for 5 days. Granisetron inhibited the acute phase (day 1), but not the delayed phase (days 2–5), of pica, whereas aprepitant abolished both phases. Within 24 h of the injection of cisplatin, PPT‐A mRNA expression and SP release in the medulla were significantly increased; these findings lasted during the observation period and were inhibited by granisetron for up to 24 h.

Conclusions and Implications

The profiles of cisplatin‐induced pica in rats are similar to clinical findings for cisplatin‐induced emesis in humans, and we showed that SP production in the medulla and activation of NK1 receptors are involved in this cisplatin‐induced pica.
Resource allocation to reproduction in animals
Authors: Kooijman Sebastiaan A. L. M. , Lika Konstadia
Published: February 2014

The standard Dynamic Energy Budget (DEB) model assumes that a fraction κ of mobilised reserve is allocated to somatic maintenance plus growth, while the rest is allocated to maturity maintenance plus maturation (in embryos and juveniles) or reproduction (in adults). All DEB parameters have been estimated for 276 animal species from most large phyla and all chordate classes. The goodness of fit is generally excellent. We compared the estimated values of κ with those that would maximise reproduction in fully grown adults with abundant food. Only 13% of these species show a reproduction rate close to the maximum possible (assuming that κ can be controlled), another 4% have κ lower than the optimal value, and 83% have κ higher than the optimal value. Strong empirical support hence exists for the conclusion that reproduction is generally not maximised. We also compared the parameters of the wild chicken with those of races selected for meat and egg production and found that the latter indeed maximise reproduction in terms of κ, while surface‐specific assimilation was not affected by selection. We suggest that small values of κ relate to the down‐regulation of maximum body size, and large values to the down‐regulation of reproduction. We briefly discuss the ecological context for these findings.
Japanese phase I study ofGC33, a humanized antibody against glypican‐3 for advanced hepatocellular carcinoma
Authors: Ikeda Masafumi , Ohkawa Shinichi , Okusaka Takuji , Mitsunaga Shuichi , Kobayashi Satoshi , Morizane Chigusa , Suzuki Ikue , Yamamoto Shunsuke , Furuse Junji
Published: February 2014

GC33 is a humanizedmAb against human glypican‐3 (GPC3). In the first‐in‐human study carried out in the USA, GC33 was well tolerated and showed preliminary antitumor activity in patients with advanced hepatocellular carcinoma. This study aimed to assess the safety, tolerability, and pharmacokinetic characteristics of GC33 in Japanese patients with advanced hepatocellular carcinoma. The study design was a conventional 3 + 3 dose‐escalation design to determine the maximum tolerated dose of GC33 given i.v. at 5, 10, or 20 mg/kg weekly. Immunohistochemistry was carried out on tumor biopsies to evaluate GPC3 expression. Thirteen patients were enrolled across the three dose levels, and no patients observed any dose‐limiting toxicity up to the highest planned dose of 20 mg/kg. The most common adverse events were decreased lymphocyte count, decreased natural killer cell count, increased C‐reactive protein, and pyrexia. Grade 3 adverse events (increased blood pressure, decreased lymphocyte count, and decreased platelet count) were observed in two or more patients. The AUCinfshowed a dose‐proportional increase from the 5 mg/kg dose group to the 20 mg/kg dose group. The trough concentrations of GC33 appeared to reach a steady state after the fourth to the sixth dose. Seven of the 13 patients showed stable disease, the other six showed progressive disease. Furthermore, three patients showed long‐term stable disease of more than 5 months. In conclusion, GC33 given at up to 20 mg/kg weekly was well tolerated in Japanese patients with advanced hepatocellular carcinoma.
The PedPAD study: boys predominate in the hypogammaglobulinaemia registry of the ESID online database
Authors: Schatorjé E J H , Gathmann B , van Hout R W N M , de Vries E , Alsina L , Baumann U , Belohradsky BH , Bienemann K , Boardman B , Borte M , Bredius RG , Brodszki N , Caracseghi F , Ciznar P , de Vries E , Driessen GJ , Dückers G , Duppenthaler A , Farmaki E , Galal N , Gennery A , Gonzalez-Granado LI , Hlavackova E , Hoernes M , Kilic SS , Krüger R , Kuijpers TW , Kütükcüler N , Llobet P , Marques L , van Montfrans JM , Papadopoulou-Alataki E , Paschenko O , Pasic S , Pietrogrande MC , Pignata C , Reda SM , Reisli I , Roesler J , Santos JL , Schölvinck EH , Schulze Ilka , Seidel MG , Shcherbina A , Sundin M , Szaflarska A , Velbri S , Warnatz K , Warris A
Published: February 2014

Hypogammaglobulinaemias are the most common primary immunodeficiency diseases. This group of diseases is very heterogeneous, and little is known about these diseases in children. In the Pediatric Predominantly Antibody Deficiencies (PedPAD) study, we analysed data from the European Society for Immunodeficiencies (ESID) online database to gain more insight into the characteristics of children with hypogammaglobulinaemia; 46 centres in 18 different countries agreed to participate. Data from 2076 of the 3191 children who were registered at the time of data extraction with a diagnosis of hypogammaglobulinaemia (this excludes agammaglobulinaemia and defects in class-switch recombination) were available for analysis. The data set showed several limitations. Because of country-related differences in diagnostic criteria used for the classification of different types of primary hypogammaglobulinaemia, further analysis of the data was performed in the combined data set. The most striking observation is the strong majority of male patients in the group of children with primary hypogammaglobulinaemia (n = 1292, 63%). This male predominance was observed in each of the 18 countries involved. The boys were younger at diagnosis (mean age males 5·3 years; mean age females 5·8 years). Moreover, one or more complications were more frequently reported in boys (12%) compared to girls (5%). The male predominance suggests that patients with an undetected or unknown X-linked genetic cause are included in this group of children registered as primary hypogammaglobulinaemia.
State‐of‐the‐Art in Compressed GPU‐Based Direct Volume Rendering
Authors: Balsa Rodríguez M. , Gobbetti E. , Iglesias Guitián J.A. , Makhinya M. , Marton F. , Pajarola R. , Suter S.K.
Published: February 2014

Great advancements in commodity graphics hardware have favoured graphics processing unit (GPU)‐based volume rendering as the main adopted solution for interactive exploration of rectilinear scalar volumes on commodity platforms. Nevertheless, long data transfer times and GPU memory size limitations are often the main limiting factors, especially for massive, time‐varying or multi‐volume visualization, as well as for networked visualization on the emerging mobile devices. To address this issue, a variety of level‐of‐detail (LOD) data representations and compression techniques have been introduced. In order to improve capabilities and performance over the entire storage, distribution and rendering pipeline, the encoding/decoding process is typically highly asymmetric, and systems should ideally compress at data production time and decompress on demand at rendering time. Compression and LOD pre‐computation does not have to adhere to real‐time constraints and can be performed off‐line for high‐quality results. In contrast, adaptive real‐time rendering from compressed representations requires fast, transient and spatially independent decompression. In this report, we review the existing compressed GPU volume rendering approaches, covering sampling grid layouts, compact representation models, compression techniques, GPU rendering architectures and fast decoding techniques.
Inexpensive Reconstruction and Rendering of Realistic Roadside Landscapes
Authors: Andújar C. , Chica A. , Vico M. A. , Moya S. , Brunet P.
Published: February 2014

In this paper, we present an inexpensive approach to create highly detailed reconstructions of the landscape surrounding a road. Our method is based on a space‐efficient semi‐procedural representation of the terrain and vegetation supporting high‐quality real‐time rendering not only for aerial views but also at road level. We can integrate photographs along selected road stretches. We merge the point clouds extracted from these photographs with a low‐resolution digital terrain model through a novel algorithm which is robust against noise and missing data. We pre‐compute plausible locations for trees through an algorithm which takes into account perceptual cues. At runtime we render the reconstructed terrain along with plants generated procedurally according to pre‐computed parameters. Our rendering algorithm ensures visual consistency with aerial imagery and thus it can be integrated seamlessly with current virtual globes.
Fresh‐Socket Implants of Different Collar Length: Clinical Evaluation in the Aesthetic Zone
Authors: Crespi Roberto , Capparè Paolo , Polizzi Elisabetta , Gherlone Enrico
Published: February 2014

Background

The aim of this clinical study was to compare clinical evaluations of implants in the aesthetic zone with smooth collars of different length.

Materials and Methods

Sixty‐six patients requiring extractions of one, two, or three teeth in the aesthetic zone of the maxilla were enrolled in this study. Ninety‐four implants were positioned and were loaded immediately after tooth extraction. Forty‐seven implants with a short smooth collar of 0.5 mm (SCI) and 47 implants with a long smooth collar of 1.8 mm (LCI) were utilized in this study and were placed using a nonsubmerged approach. Clinical (gingival index, modified plaque index, modified bleeding index, probing depth, gingival recession) and intraoral digital radiographic parameters were measured at baseline and after 6, 12, 24, and 36 months of healing to evaluate crestal bone loss levels over time.

Results

After a follow‐up period of 36 months, a survival rate of 100% was reported. The SCI group showed a mean bone loss of 1.07 ± 0.38 mm at 12 months and 1.09 ± 0.38 mm at 36 months. The LCI group showed a mean bone loss of 0.46 ± 0.14 mm at 12 months and 0.53 ± 0.12 mm at 36 months. After the 36‐month follow‐up period, both groups showed stable bone levels over time. Statistically significant differences were found between groups (p < .05).

No statistically significant differences were found between SCI and LCI groups with regard to clinical parameters over time.

Conclusions

This study revealed significant differences in radiographically observed marginal bone loss between the two types of implant with different smooth‐collar lengths, but no differences in gingival vestibular margin outcome were observed.
Evaluation of Zirconia‐Based All‐Ceramic Single Crowns and Fixed Dental Prosthesis on Zirconia Implants: 5‐Year Results of a Prospective Cohort Study
Authors: Spies Benedikt Christopher , Stampf Susanne , Kohal Ralf‐Joachim
Published: February 2014

Objective

The objective of this 5‐year cohort investigation was to determine the survival and success rate of all‐ceramic reconstructions on zirconia oral implants.

Material and Methods

Ninety‐three patients received 122 one‐piece zirconia implants. One hundred seventeen implants were restored with 63 single crowns (SCs) and 27 three‐unit bridges (fixed dental prostheses, FDPs) fabricated using zirconia frameworks (Procera® Zirconia, Nobel Biocare®, Göteborg, Sweden) hand‐layered with a silicate ceramic (NobelRondo™ Zirconia, Nobel Biocare®). With any occurrence of chipping regarded as an event, Kaplan‐Meier success curves were plotted. Covariates (gender, location, manufacturing date) were estimated by the use of log‐rank tests.

Results

Eighty‐nine patients received prosthetic reconstructions. Sixty‐three of them were seen at the 5‐year follow‐up, with a mean observation time of 58.2 months (47 patients with SCs, 16 patients with FDPs). Reasons for the decreasing number of patients at the follow‐up sessions included dropouts due to implant loss (n = 21), moving (n = 3), missed appointments (n = 1), and severe illness (n = 1). Over half of the SCs (57.2%) and 38% of the FDPs were successful after an observation time of 5 years (overall success rate of 51.7%). The performed log‐rank tests revealed no statistically significant differences for the success curves regarding the above‐mentioned covariates. Among the 63 restorations that completed the study, 11 of 47 SCs and one of 16 FDPs had to be replaced due to the severity of the observed chipping. This results in survival rates of 76.6% for the SCs and 93.8% for the FDPs. No framework fractures or decementations were observed in any group.

Conclusion

Hand‐layering of zirconia‐based SCs and FDPs with NobelRondo™ Zirconia restoring one‐piece zirconia implants did not show acceptable survival and success rates. Meanwhile, the material has been recalled from the market. It is advised that new materials should undergo adequate preclinical evaluation before coming to the market.
Network Analysis of Translocated Takahe Populations to Identify Disease Surveillance Targets
Authors: GRANGE ZOË L. , VAN ANDEL MARY , FRENCH NIGEL P. , GARTRELL BRETT D.
Published: February 2014

Social network analysis is being increasingly used in epidemiology and disease modeling in humans, domestic animals, and wildlife. We investigated this tool in describing a translocation network (area that allows movement of animals between geographically isolated locations) used for the conservation of an endangered flightless rail, the Takahe (Porphyrio hochstetteri). We collated records of Takahe translocations within New Zealand and used social network principles to describe the connectivity of the translocation network. That is, networks were constructed and analyzed using adjacency matrices with values based on the tie weights between nodes. Five annual network matrices were created using the Takahe data set, each incremental year included records of previous years. Weights of movements between connected locations were assigned by the number of Takahe moved. We calculated the number of nodes (itotal) and the number of ties (ttotal) between the nodes. To quantify the small‐world character of the networks, we compared the real networks to random graphs of the equivalent size, weighting, and node strength. Descriptive analysis of cumulative annual Takahe movement networks involved determination of node‐level characteristics, including centrality descriptors of relevance to disease modeling such as weighted measures of in degree (kiin), out degree (kiout), and betweenness (Bi). Key players were assigned according to the highest node measure of kiin, kiout, and Bi per network. Networks increased in size throughout the time frame considered. The network had some degree small‐world characteristics. Nodes with the highest cumulative tie weights connecting them were the captive breeding center, the Murchison Mountains and 2 offshore islands. The key player fluctuated between the captive breeding center and the Murchison Mountains. The cumulative networks identified the captive breeding center every year as the hub of the network until the final network in 2011. Likewise, the wild Murchison Mountains population was consistently the sink of the network. Other nodes, such as the offshore islands and the wildlife hospital, varied in importance over time. Common network descriptors and measures of centrality identified key locations for targeting disease surveillance. The visual representation of movements of animals in a population that this technique provides can aid decision makers when they evaluate translocation proposals or attempt to control a disease outbreak.

Análisis de Redes de Poblaciones de Takahe Translocadas para Identificar Objetivos de Supervivencia a Enfermedades
Kidney donor risk index is a good prognostic tool for graft outcomes in deceased donor kidney transplantation with short, cold ischemic time
Authors: Han Miyeun , Jeong Jong Cheol , Koo Tai Yeon , Jeon Hee Jung , Kwon Hyuk Yong , Kim Yoon Jung , Ryu Hyun Jin , Ahn Curie , Yang Jaeseok
Published: February 2014

Background

We performed a retrospective cohort study to determine the prognostic value of standard criteria donor/expanded criteria donor (SCD/ECD) designation, with regard to one‐yr GFR and graft survival rate, in a region with short, cold ischemic time (CIT), and how this designation compares with the kidney donor risk index (KDRI) and zero‐time kidney biopsies.

Methods

We reviewed 362 cases of deceased donor kidney transplantation (DDKT). Donor kidneys were classified as SCD or ECD. They were also assessed by the KDRI. Zero‐time kidney biopsy was performed in 196 patients, and histologic score was assessed.

Results

Median follow‐up duration was 46 months. Forty‐two cases (11.6%) used ECD kidneys. The mean CIT was only 4.9 ± 2.7 h. Graft survival rates were not significantly different between ECD and SCD groups. The KDRI showed the best correlation with one‐yr estimations of glomerular filtration rate (eGFR) (R2 = 0.230, p < 0.001), and higher KDRI was associated with a higher risk of graft failure (hazard ratio 2.63, 95% confidence interval 1.01–6.87). However, higher histologic score was not associated with a higher risk of graft failure.

Conclusion

KDRI has greater predictive value for short‐term outcomes in DDKT with short CIT than the SCD/ECD designation or pathology.
Characterization of Echocardiographic Measures of Cardiac Structure and Function in Healthy Octogenarians
Authors: Balcioğlu Akif Serhat , Durakoğlugil Murtaza Emre , Okyay Kaan , Tavil Yusuf , Abaci Adnan
Published: February 2014

Background

Currently, there is not enough echocardiographic information regarding aging‐associated changes in the octogenarian population. We aimed to characterize echocardiographic measures of structure and function among a group of healthy octogenarians.

Methods

Approximately 350 octogenarians, residing in nursing homes, were screened in Ankara, Turkey. According to inclusion criteria, 40 octogenarians were enrolled. These subjects underwent conventional and tissue Doppler echocardiography according to the guidelines of the American Society of Echocardiography (ASE). The population was also separated into various groups according to gender, body mass index (BMI, <25 vs. 25–29.9), and blood pressure (<80/120 mmHg vs. 80–89/120–139 mmHg). All measurements were indexed by dividing to body surface area (BSA) for standardization.

Results

Left ventricular mass (LVM), posterior wall thickness, right ventricular diameter, tricuspid E/A ratio, and septal e'‐wave velocity were significantly higher in men, which lost significance after adjusting for BSA. There was no significant difference between groups formed by BMI and blood pressure. Moreover, mild global left and right ventricular dysfunction including a prominent diastolic counterpart, however, with normal ejection fraction was revealed using conventional and tissue Doppler techniques. Finally, we checked our results with the current reference values of the ASE and observed the following differences: ventricular septum, relative wall thickness, LVM, and mass index values were above ASE reference range, posterior wall measurements were close to upper range. On the contrary, left ventricular diameters and volumes were below ASE reference range.

Conclusions

We described echocardiographic measures of structure and function in a group of healthy octogenarians.
Naïve subset develops the most important alloreactive response among human CD4+T lymphocytes in Human Leukocyte Antigen‐identical related setting
Authors: Chérel Mathilde , Choufi Bachra , Trauet Jacques , Cracco Pascale , Dessaint Jean‐Paul , Yakoub‐Agha Ibrahim , Labalette Myriam
Published: February 2014

In longitudinal clinical studies, receiving a high percentage of allogeneic donor‐derived CD4+CCR7+ T cells, which include naïve and central memory subsets have been correlated with increased incidence and severity of acute GVHD. Whether naïve and central memory CD4+ T‐cell subsets contribute more or equally to alloimmune responses are still unclear in human. The aim of this study was to investigate in vitro the alloreactive response of purified naïve, central memory, and effector memory CD4+ T‐cell subsets in HLA identical setting. By coculturing monocyte‐derived dendritic cells and purified CD4+ T‐cell subsets, from healthy HLA‐identical male and female sibling pairs, we found that naïve CD4+CCR7+CD45RA+ T cells developed the highest proliferative response upon stimulation by minor histocompatibility antigens and were progressively driven to produce high levels of interferon‐γ, tumor necrosis factor, and interleukin‐6. Comparatively, the central memory CD4+CCR7+CD45RAneg subset proliferated to a lower extent and produced very low amounts of pro‐inflammatory cytokines while the CCR7neg effector memory CD4+ subset was unresponsive. This study demonstrates the superior capacity of naïve CD4+ T cells to mount a primary alloreactive response as compared to central memory T cells. Their proliferative response associated with a pro‐inflammatory differentiation makes them potentially acute GVHD inducers. These in vitro results in line with what we have observed in clinical studies and may also lend support to approaches of partial selective T‐cell depletion for GVHD prevention.
Task‐dependent changes in late inhibitory and disinhibitory actions within the primary motor cortex in humans
Authors: Caux‐Dedeystère Alexandre , Rambour Mélanie , Duhamel Alain , Cassim François , Derambure Philippe , Devanne Hervé
Published: February 2014

The objective of the present study was to investigate the time course of long‐interval intracortical inhibition (LICI) and late cortical disinhibition (LCD) as a function of the motor task (index abduction, thumb–index precision grip). Motor‐evoked potentials were recorded from the first dorsal interosseus (FDI) muscle of the dominant limb in 13 healthy subjects. We used paired‐pulse transcranial magnetic stimulation (TMS) paradigms in which a test pulse was preceded by a suprathreshold priming pulse (130% of the resting motor threshold) with varying interstimulus intervals (ISIs). In each task, double pulses were delivered with ISIs ranging from 30% of the corresponding silent period (SP; ~ 45 ms) to 220% of the SP (~ 330 ms). In both tasks, we found that LICI was followed by LCD (namely a period of increased cortical excitability lasting until ~ 200% of the SP). The time‐dependent modulation of LICI and LCD differed in the two tasks; LICI was shorter (i.e. disinhibition occurred earlier) and LCD was more intense during precision grip than during index abduction. Long‐interval intracortical inhibition disappeared well before the end of the SP in the precision grip task, suggesting that the mechanisms underlying these two inhibitory phenomena are distinct. Our data suggest that disinhibition might reflect adaptation of neural circuit excitability to the functional requirements of the motor task.
Regulation of pigmentation by substrate elasticity in normal human melanocytes and melanotic MNT1 human melanoma cells
Authors: Choi Hyunjung , Kim Mina , Ahn Song Ih , Cho Eun‐Gyung , Lee Tae Ryong , Shin Jennifer H.
Published: February 2014

The elasticity of the cellular microenvironment is a key regulator of cellular physiology in many cell types. To investigate the effects of substrate stiffness on the pigmentation process, we cultured normal human melanocytes (NHM) and MNT1 melanoma cells on laminin‐coated polydimethylsiloxane (PDMS) substrates of different stiffness. The dendricity of NHM and MNT1 cells was reduced as the substrate stiffness decreased, and the degree of melanosome transfer from NHM or MNT1 cells to normal human keratinocytes was decreased on softer substrates with the reduced dendricity. Gene and protein expressions of MITF, tyrosinase, TRP2, and gp100/PMEL17 exhibited a consistent decreasing trend with the decreasing stiffness. Because the stiffness sensing is mediated by focal adhesion complex through integrin receptors, we checked laminin specific integrin alpha 6 and p‐FAK for MNT1 cells to observe that the substrate adhesion was weakened as the substrate stiffness decreased. Weaker adhesion on a softer substrate was accompanied by dynamic shape changes in MNT1 cells with higher speed and larger scattering. Dendritic MNT1 cells cultured on a stiffer substrate exhibited lower migration with smaller root mean squared displacement. These results demonstrate the possibility that skin pigmentation can be influenced by mechanical properties of the cellular microenvironment and can increase when the skin becomes stiff.
Acyl‐coenzyme A:cholesterol acyltransferase 1 – significance of single‐nucleotide polymorphism at residue 526 and the role of Pro347 near the fifth transmembrane domain
Authors: Huang Li‐Hao , Nishi Koji , Li Song , Ho Thomas , Dong Ruhong , Chang Catherine C. Y. , Chang Ta‐Yuan
Published: February 2014

Acyl‐coenzyme A:cholesterol acyltransferases (ACATs), which are members of the membrane‐bound O‐acyltransferase family, catalyze the conversion of cholesterol to cholesteryl esters. Mammals have two isoenzymes: ACAT1 and ACAT2. Both enzymes are drug targets for treating human diseases. ACAT1 is present in various cell types. It contains nine transmembrane domains (TMDs), with the active site His460 located within TMD7, and the active site Asn421 located within the fourth large cytoplasmic loop. In human ACAT1, a single‐nucleotide polymorphism exists for residue 526: the codon is either CAG for Gln, or CGG for Arg. Gln526/Arg526 is present within the C‐terminal loop. Its biochemical significance is unknown. In addition, within the C‐terminal half of ACAT1, numerous residues conserved with those of ACAT2 are present; the functions of these conserved residues are largely unknown. Here, we performed single‐substitution mutagenesis experiments to investigate the roles of individual residues present in the C‐terminal loop, including Gln526/Arg526, and the eight conserved Pro residues located near/in various TMDs. The results show that the enzyme activity of ACAT1 with Gln526 is less active than that of ACAT1 with Arg526 by 40%. In addition, several residues in the C‐terminal loop are important for maintaining proper ACAT1 protein stability. Other results show that Pro347 plays an important role in modulating enzyme catalysis. Overall, our results imply that the CAG/CGG polymorphism can be utilized to perform ACAT1 activity/human disease susceptibility studies, and that Pro347 located near TMD5 plays an important role in modulating enzyme catalysis.
Thermal acclimation of shoot respiration in an Arctic woody plant species subjected to 22 years of warming and altered nutrient supply
Authors: Heskel Mary A. , Greaves Heather E. , Turnbull Matthew H. , O'Sullivan Odhran S. , Shaver Gaius R. , Griffin Kevin L. , Atkin Owen K.
Published: February 2014

Despite concern about the status of carbon (C) in the Arctic tundra, there is currently little information on how plant respiration varies in response to environmental change in this region. We quantified the impact of long‐term nitrogen (N) and phosphorus (P) treatments and greenhouse warming on the short‐term temperature (T) response and sensitivity of leaf respiration (R), the high‐T threshold of R, and associated traits in shoots of the Arctic shrub Betula nana in experimental plots at Toolik Lake, Alaska. Respiration only acclimated to greenhouse warming in plots provided with both N and P (resulting in a ~30% reduction in carbon efflux in shoots measured at 10 and 20 °C), suggesting a nutrient dependence of metabolic adjustment. Neither greenhouse nor N+P treatments impacted on the respiratory sensitivity to T (Q10); overall, Q10 values decreased with increasing measuring T, from ~3.0 at 5 °C to ~1.5 at 35 °C. New high‐resolution measurements of R across a range of measuring Ts (25–70 °C) yielded insights into the T at which maximal rates of R occurred (Tmax). Although growth temperature did not affect Tmax, N+P fertilization increased Tmax values ~5 °C, from 53 to 58 °C. N+P fertilized shoots exhibited greater rates of R than nonfertilized shoots, with this effect diminishing under greenhouse warming. Collectively, our results highlight the nutrient dependence of thermal acclimation of leaf R in B. nana, suggesting that the metabolic efficiency allowed via thermal acclimation may be impaired at current levels of soil nutrient availability. This finding has important implications for predicting carbon fluxes in Arctic ecosystems, particularly if soil N and P become more abundant in the future as the tundra warms.
Better adherence to prescribed treatment regimen is related to less chronic pain among adolescents and young adults with moderate or severe haemophilia
Authors: McLaughlin J. M. , Witkop M. L. , Lambing A. , Anderson T. L. , Munn J. , Tortella B.
Published: February 2014

Little data exist, especially for adolescent and young adult (AYA) persons with haemophilia (PWH), about the relationship between adherence to prescribed treatment regimen and chronic pain. We examined this relationship among PWH (moderate or severe) aged 13–25 via cross‐sectional survey. Adherence was assessed using the Validated Hemophilia Regimen Treatment Adherence Scale (VERITAS)‐Pro and VERITAS‐PRN for prophylactic and on‐demand participants respectively. VERITAS scores range from 24 (most adherent) to 120 (least adherent). Chronic pain was measured using the FPS‐R and was dichotomized as high for FPS‐R scores ≥4 and low for <4. Logistic regression models were constructed to assess factors associated with having high (vs. low) chronic pain. Of 80 AYA respondents (79 men), most had severe disease (91%), infused prophylactically (86%) and had haemophilia A (91%). Fifty‐one per cent were aged 13–17 and most were white (76%), non‐Hispanic (88%) and never married (93%). Chronic pain was reported as high for 35% of respondents. Mean VERITAS‐Pro scores for those with high and low chronic pain were 53.6 ± 12.3 vs. 47.4 ± 12.9, P = 0.05. VERITAS‐PRN scores were similar across chronic pain status. Logistic regression revealed that for each 10‐point reduction (i.e. increase in adherence) in the combined VERITAS (Pro and PRN) and VERITAS‐Pro scores there was a 35% (OR = 0.65; 95%CI = 0.44, 0.96; P = 0.03) and 39% (OR = 0.61; 95%CI = 0.39, 0.96; P = 0.03) reduction in odds of having high chronic pain respectively. Among AYA PWHs, better adherence was associated with significantly lower odds of having high chronic pain. Moreover, non‐whites were >4 times as likely as whites to report high chronic pain.
Usefulness of evaluating hepatic elasticity using artificial acoustic radiation force ultrasonography before hepatectomy
Authors: Nanashima Atsushi , Sakamoto Ayami , Sakamoto Ichiro , Hayashi Hideyuki , Abo Takafumi , Wakata Kouki , Murakami Goushi , Arai Junichi , Wada Hideo , Takagi Katsunori , Takeshita Hiroaki , Hidaka Shigekazu , To Kazuo , Nagayasu Takeshi
Published: February 2014

Aim

To evaluate hepatic fibrosis and tumor diagnosis preoperatively, we investigated the elasticity calculated by the new parameter of ultrasonography, acoustic radiation force impulse (ARFI).

Methods

We examined ARFI of the non‐tumorous right and left lateral liver and in the tumor by push pulse of probe in 95 patients with hepatic malignancies undergoing hepatectomy. Measurement of ARFI as hepatic stiffness was indicated as the Vs (m/s).

Results

Measuring the Vs in the non‐tumor region was achieved in the right liver in 99% and at the left lateral liver in 94%. The Vs in the right liver was significantly lower than in the left lateral liver, and the Vs of the liver tumor was significantly higher than in the non‐tumorous liver. The Vs in the right and left lateral liver was correlated with the platelet count, aspartate aminotransferase, fibrotic indices and indocyanine green test. The Vs in the right liver was significantly correlated with the fibrotic marker or index. The Vs of liver cirrhosis and histological stage 4 in the right and left liver was significantly the highest compared to the others. The Vs in the right liver showed a high area under the receiver–operator curve value predicting histological fibrosis. The Vs in the right was significantly correlated with blood loss and postoperative complications, particularly uncontrolled ascites.

Conclusion

Non‐invasive ARFI imaging elastography is useful in evaluating impaired liver function or in the differential diagnosis of liver malignancies, highly hepatic fibrosis and in predicting posthepatectomy morbidity.
Diversity of Ichneumonidae (Insecta: Hymenoptera) in a protected area of Central Spain: What are we protecting?
Authors: Mazón Marina , Bordera Santiago
Published: February 2014

Invertebrates are rarely considered when designing protected areas, and their biodiversity patterns in these areas are almost always unknown.

We studied the spatial and temporal diversity of Ichneumonidae in five selected habitats of Cabañeros National Park: grazing pastureland, shrubland, and three types of woodland (Pyrenean oak, cork oak, and ash woodlands). We focused on 11 subfamilies, with species classified into trophic guilds.

The highest diversity and richness of Ichneumonidae were found in ash woodland and pastureland, each with similar structural habitat complexity. Species turnover between habitats was about 50% and it contributed more to the total species richness than the fauna inherent to the habitats, though less to the total species diversity.

Shrubland is transitional between pasture and woodland and Ichneumonidae assemblages in this habitat are rather different in their species composition from the others.

Parasitoids of phytophages are well represented in all habitats; other guilds are more related to specific habitats, e.g. parasitoids of xylophages in shrubland.

We suggest that shrub may be invading and isolating some of the woodlands. The mosaic landscape of the National Park, including open areas, is essential to ensure the conservation of parasitoids.
Effects of NaOCl, EDTA and MTAD when applied to dentine on stress distribution in post‐restored roots with flared canals
Authors: Belli S. , Eraslan O. , Eraslan O. , Eskitascioglu M. , Eskitascioglu G.
Published: February 2014

Aim

To evaluate the effect of NaOCl, EDTA and MTAD on the stress distribution and levels in roots with flared canals and three different aesthetic post systems using finite element stress analysis (FEA).

Methodology

Three‐dimensional (3D) FEA models simulating a maxillary incisor with excessive structural loss and flared root canals were created. The dentine of the first models of each post group was assumed as homogenous, whereas the others were deemed as having their elastic modulus affected up to 100 μm deep as a result of irrigation protocol (5.25 NaOCl, 17% EDTA and MTAD for 2 h). A sound incisor tooth model was used as the control. Restorations were created according to the post system used (pre‐fabricated fibre post (PFP)), polyethylene fibre (Ribbond) post and core build‐up (RBP), and one‐piece milled zirconia post and core (ZP). Ceramic crowns were added to the models. A 300‐N static load was applied at the centre of the palatal surface of the models to calculate the stress distributions. The SolidWorks/Cosmosworks structural analysis programmes were used for FEA analysis. Results were presented by considering von Mises criteria.

Results

The analysis of the von Mises stresses revealed that RBP created less stress in the remaining root dentine when compared to PFP and ZP. ZP maintained the stresses inside its body and reduced stress on the palatal surface of the root; however, it forwarded more stress towards the apical area. NaOCl‐, EDTA‐ and MTAD‐treated dentine increased the stresses within the root structure regardless of the effect of the post system used (11–15.4 MPa for PFP, 9.5–13.02 MPa for RBP and 14.2 MPa for ZP). Amongst the irrigation solutions used, EDTA and MTAD increased the stresses more than NaOCl in all models. All the irrigation solutions showed the same stress levels and distributions in the ZP model.

Conclusion

NaOCl‐, EDTA‐ and MTAD‐ treated dentine and a rigid post with high elastic modulus may increase fracture risk in roots with flared canals by increasing the stresses within root dentine. Therefore, solutions that alter the elastic modulus of dentine less (such as NaOCl) or an individually shaped post–core system constructed with a material that has an elastic modulus close to dentine (polyethylene fibre) should be used in weak roots.
In vitro biocompatibility of a dentine substitute cement on human MG63 osteoblasts cells: Biodentine™ versus MTA®
Authors: Attik G. N. , Villat C. , Hallay F. , Pradelle‐Plasse N. , Bonnet H. , Moreau K. , Colon P. , Grosgogeat B.
Published: February 2014

Aim

To compare the in vitro biocompatibility of Biodentine™ and White ProRoot® mineral trioxide aggregate (MTA®) with MG63 osteoblast‐like cells and to characterize the cement surface.

Methodology

A direct contact model for MG63 osteoblast‐like cells with cements was used for 1, 3 and 5 days. Four end‐points were investigated: (i) cement surface characterization by atomic force microscopy (AFM), (ii) cell viability by MTT assay, (iii) protein amount quantification by Bradford assay and (iv) cell morphology by SEM. Statistical analyses were performed by analysis of variance (anova) with a repetition test method.

Results

The roughness of the cements was comparable as revealed by AFM analysis. The MTT test for Biodentine™ was similar to that of MTA®. Biodentine™ and MTA® induced a similar but slight decrease in metabolic activity. The amount of total protein was significantly enhanced at day three (P < 0.05) but slightly decreased at day five for both tested samples. Biodentine™ was tolerated as well as MTA® in all cytotoxicity assays. SEM observations showed improvement of cell attachment and proliferation on both material surfaces following the three incubation periods.

Conclusion

The biocompatibility of Biodentine™ to bone cells was comparable to MTA®.