bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Ponesimod, a Selective S1P1 Receptor Modulator, on the QT Interval in Healthy Individuals
Authors: Hoch Matthias , Darpo Borje , Brossard Patrick , Zhou Meijian , Stoltz Randall , Dingemanse Jasper
Published: October 2014

Ponesimod is an orally active selective sphingosine‐1‐phosphate receptor 1 modulator under investigation for the treatment of multiple sclerosis. This was a single‐centre, double‐blind, randomized, placebo‐ and positive‐controlled parallel‐group study investigating the effects of ponesimod on the QTc interval in healthy individuals. A nested cross‐over comparison between moxifloxacin and placebo was included in the combined moxifloxacin/placebo treatment group. Subjects in group A received multiple doses of 10–100 mg ponesimod according to an uptitration regimen on days 2–23 and moxifloxacin‐matching placebo on days 1 and 24. Subjects in group B received ponesimod‐matching placebo on days 2–23 and were randomized to receive either a single dose of 400 mg moxifloxacin or matching placebo on days 1 and 24. The primary end‐point was the baseline‐adjusted, placebo‐corrected effect on the individually corrected QT interval (QTcI) on days 12 (after 5 days of 40 mg ponesimod) and 23 (after 5 days of 100 mg ponesimod). Ponesimod caused a mild QTcI prolongation with a largest effect of 6.9 ms (90% two‐sided confidence interval (CI): 2.5–11.3) and 9.1 ms (90% CI: 4.1–14.0) for doses of 40 mg and 100 mg, respectively. A concentration–effect analysis confirmed the QTcI‐prolonging effect of ponesimod with a shallow slope of 0.0053 ms per ng/mL. Using the concentration–effect analysis, the QTc prolongation caused by 20 mg ponesimod and the current highest therapeutic dose was predicted to be below the level of clinical concern (i.e. an upper bound of the two‐sided 90% CI of ≥10 ms).
On the Selection of Ordinary Differential Equation Models with Application to Predator-Prey Dynamical Models
Authors: Zhang Xinyu , Cao Jiguo , Carroll Raymond J.
Published: October 2014

We consider model selection and estimation in a context where there are competing ordinary differential equation (ODE) models, and all the models are special cases of a “full” model. We propose a computationally inexpensive approach that employs statistical estimation of the full model, followed by a combination of a least squares approximation (LSA) and the adaptive Lasso. We show the resulting method, here called the LSA method, to be an (asymptotically) oracle model selection method. The finite sample performance of the proposed LSA method is investigated with Monte Carlo simulations, in which we examine the percentage of selecting true ODE models, the efficiency of the parameter estimation compared to simply using the full and true models, and coverage probabilities of the estimated confidence intervals for ODE parameters, all of which have satisfactory performances. Our method is also demonstrated by selecting the best predator-prey ODE to model a lynx and hare population dynamical system among some well-known and biologically interpretable ODE models.
Cycloamylose‐nanogel drug delivery system‐mediated intratumor silencing of the vascular endothelial growth factor regulates neovascularization in tumor microenvironment
Authors: Fujii Hidetaka , Shin‐Ya Masaharu , Takeda Shigeo , Hashimoto Yoshihide , Mukai Sada‐atsu , Sawada Shin‐ichi , Adachi Tetsuya , Akiyoshi Kazunari , Miki Tsuneharu , Mazda Osam
Published: October 2014

RNAi enables potent and specific gene silencing, potentially offering useful means for treatment of cancers. However, safe and efficient drug delivery systems (DDS) that are appropriate for intra‐tumor delivery of siRNA or shRNA have rarely been established, hindering clinical application of RNAi technology to cancer therapy. We have devised hydrogel polymer nanoparticles, or nanogel, and shown its validity as a novel DDS for various molecules. Here we examined the potential of self‐assembled nanogel of cholesterol‐bearing cycloamylose with spermine group (CH‐CA‐Spe) to deliver vascular endothelial growth factor (VEGF)‐specific short interfering RNA (siVEGF) into tumor cells. The siVEGF/nanogel complex was engulfed by renal cell carcinoma (RCC) cells through the endocytotic pathway, resulting in efficient knockdown of VEGF. Intra‐tumor injections of the complex significantly suppressed neovascularization and growth of RCC in mice. The treatment also inhibited induction of myeloid‐derived suppressor cells, while it decreased interleukin‐17A production. Therefore, the CH‐CA‐Spe nanogel may be a feasible DDS for intra‐tumor delivery of therapeutic siRNA. The results also suggest that local suppression of VEGF may have a positive impact on systemic immune responses against malignancies.
Examining Change in Cortisol Patterns During the 10‐Week Transition to a New Child‐Care Setting
Authors: Bernard Kristin , Peloso Elizabeth , Laurenceau Jean‐Philippe , Zhang Zhiyong , Dozier Mary
Published: October 2014

The transition to out‐of‐home child care brings a number of challenges for children, including complex peer interactions and extended separations from parents. Children often show a midmorning to afternoon rise in cortisol on child‐care days, compared to the typical diurnal decline seen at home. Changes in cortisol were examined in a wide age range of children (N = 168; 1.2 months to 8 years, M = 3.27 years) during the 10‐week transition to a new child‐care setting. Structural equation modeling using latent change scores showed that children experienced an increase in the cortisol rise at child care across the 10‐week transition. Furthermore, child age moderated the difference between home‐ and child‐care cortisol patterns. Findings are placed in a developmental context, and potential implications and future directions are discussed.
Bound by Laws, or by Values? A Multi‐Level and Cross‐National Approach to Understanding the Protection of Minority Owners in Family Firms
Authors: Stevens Charles E. , Kidwell Roland E. , Sprague Robert
Published: October 2014

Manuscript Type

Conceptual

Research Question/Issue

How do firm‐level attributes and country‐level institutions affect cross‐national and firm‐level differences in how minority owner rights in family firms are protected?

Research Insights

We consider differences in family dynamics, stewardship‐oriented organizational culture, and countries' legal and cultural dimensions to develop theory predicting differences in minority owner protection in family firms. We advance propositions and a model delineating the role of these key firm‐level and country‐level constructs.

Theoretical/Academic Implications

We contribute to the literature in three ways: (1) We illustrate the importance of family dynamics for predicting the likelihood of a stewardship‐oriented culture to emerge in a family firm; (2) our multi‐level and cross‐national approach extends earlier explanations of agency and stewardship that are centered at the firm, family, and individual levels of analysis; and (3) we consider the impact of cross‐cultural dimensions on family firms, an area that has received limited attention in the literature.

Practitioner/Policy Implications

Our research implies that individuals considering becoming a minority owner in a family firm should take into account not only the legal institutions of that country (which might not be as strong as they first seem) but also intra‐firm family dynamics and the prevalent norms and values of the firm's national culture to get a more complete picture of the protections available to them.
Esophageal carcinoid tumor treated by endoscopic resection
Authors: Yagi Makoto , Abe Yasuhiko , Sasaki Yu , Nomura Eiki , Sato Takeshi , Iwano Daisuke , Yoshizawa Kazuya , Sakuta Kazuhiro , Kanno Nana , Nishise Syouichi , Ueno Yoshiyuki
Published: October 2014

The present report describes a rare case of esophageal carcinoid tumor that was treated by endoscopic resection. A 43‐year‐old woman underwent esophagogastroduodenoscopy at her family clinic for screening of the upper digestive tract and a small lesion resembling a submucosal tumor was detected in the lower esophagus. A biopsy sample from the lesion was diagnosed as esophageal carcinoid tumor and the patient visited our hospital for detailed examination. The tumor was approximately 3 mm in diameter and its surface appeared to be covered with normal squamous epithelium. The tumor had a shiny reddish surface without ulceration or erosion. Magnifying endoscopy with narrow‐band imaging showed structures resembling reticular vessels under the epithelium. Endoscopic ultrasonography depicted the tumor as a low‐echoic mass within the lamina propria. Computed tomography did not detect the tumor and no metastatic lesions were evident in other organs. With the patient's informed consent, the tumor was resected using endoscopic submucosal dissection, with a sufficient free margin in both the vertical and horizontal directions. Magnifying endoscopic examination showed the resected tumor to have abundant reticular vessels. Finally, the tumor was diagnosed immunopathologically as an esophageal carcinoid tumor (neuroendocrine cell tumor, grade 1), without lymphatic or vascular invasion.
Endoscopic ultrasonography‐guided gallbladder drainage for acute cholecystitis: From evidence to practice
Authors: Choi Jun‐Ho , Lee Sang Soo
Published: October 2014

With the evolution of the linear echoendoscope and the improved ability to direct a needle within the field of interest, the therapeutic potential of endoscopic ultrasonography (EUS) has greatly expanded. Endoscopic ultrasonography‐guided transmural gallbladder drainage (EUS‐GBD) may be the next frontier for therapeutic EUS. Since EUS‐GBD was first described in 2007, recent reports have suggested it as an alternative to external gallbladder drainage for acute cholecystitis. EUS‐GBD includes EUS‐guided transmural nasogallbladder drainage, EUS‐guided gallbladder aspiration, and EUS‐guided transmural gallbladder stenting. Indications for the EUS‐GBD technique as currently practiced, including equipment, technical details, complications, and efficacy are herein reviewed.
Comparison between double‐guidewire technique and transpancreatic sphincterotomy technique for difficult biliary cannulation
Authors: Huang Long , Yu Qing‐sheng , Zhang Qi , Liu Ju‐da , Wang Zhen
Published: October 2014

Background and Aim

The aim of the present study was to compare the effectiveness and complications of the double‐guidewire technique (DWT) with the transpancreatic sphincterotomy (TPS) technique.

Methods

From January 2013 to December 2014, 366 consecutive endoscopic retrograde cholangiopancreatography (ERCP) procedures were carried out. Of 366 procedures, 354 procedures were carried out in patients with native major papilla biliary cannulation. A total of 279 consecutive therapeutic ERCP were included in the study and data of included patients were collected retrospectively. One hundred and thirty‐seven procedures (49.1%) were done with DWT and 142 procedures (50.9%) were done with TPS for patients with difficult cannulation. The results and complications of ERCP were compared.

Results

Success rate of first‐attempt cannulation was 62.0% in the DWT group and 81.0% in the TPS group (P = 0.00). Final rate of successful cannulation of the two biliary cannulation techniques was 86.9% and 90.8%, respectively (P = 0.09). Cannulation time in the DWT group was 7.8 ± 1.7 min compared with 3.7 ± 2.3 min in the TPS group (P = 0.00). Overall incidence of post‐ERCP pancreatitis (PEP), hemorrhage, perforation and cholangitis was 1.8%, 1.1%, 0.4% and 1.1%, respectively. Adverse event rate was 2.19% in the DWT group and 7.04% in the TPS group (P = 0.04).

Conclusions

DWT and TPS procedures were safe and effective. Overall cannulation rate was similar between the groups. Although DWT had a longer cannulation time, it could be considered the preferred technique in patients with failed standard cannulation for lower adverse event rate.
Individuation training with other‐race faces reduces preschoolers’ implicit racial bias: a link between perceptual and social representation of faces in children
Authors: Xiao Wen S. , Fu Genyue , Quinn Paul C. , Qin Jinliang , Tanaka James W. , Pascalis Olivier , Lee Kang
Published: October 2014

The present study examined whether perceptual individuation training with other‐race faces could reduce preschool children's implicit racial bias. We used an ‘angry = outgroup’ paradigm to measure Chinese children's implicit racial bias against African individuals before and after training. In Experiment 1, children between 4 and 6 years were presented with angry or happy racially ambiguous faces that were morphed between Chinese and African faces. Initially, Chinese children demonstrated implicit racial bias: they categorized happy racially ambiguous faces as own‐race (Chinese) and angry racially ambiguous faces as other‐race (African). Then, the children participated in a training session where they learned to individuate African faces. Children's implicit racial bias was significantly reduced after training relative to that before training. Experiment 2 used the same procedure as Experiment 1, except that Chinese children were trained with own‐race Chinese faces. These children did not display a significant reduction in implicit racial bias. Our results demonstrate that early implicit racial bias can be reduced by presenting children with other‐race face individuation training, and support a linkage between perceptual and social representations of face information in children.
Regulation of later neurogenic stages of adult‐derived neural stem/progenitor cells byL‐typeCa2+channels
Authors: Teh Daniel B. L. , Ishizuka Toru , Yawo Hiromu
Published: October 2014

In the adult hippocampus, new neurons are continuously generated and incorporated into the local circuitry in a manner dependent on the network activity. Depolarization evoked by neurotransmitters has been assumed to activateL‐typeCa2+channels (LTCC) which regulate the intracellularCa2+‐dependent signaling cascades. The process of neurogenesis contains several stages such as proliferation, fate determination, selective death/survival and maturation. Here, we investigated which stage of neurogenesis is under the regulation ofLTCCusing a clonal line of neural stem/progenitor cells,PZ5, which was derived from adult rat hippocampus. Although undifferentiatedPZ5 cells were type 1‐like cells expressing both nestin and glial fibrillary acidic protein, they generated neuronal, astrocytic and oligodendrocytic populations in differentiation medium containing retinoic acid. Proliferation of undifferentiatedPZ5 cells was dependent on neither theLTCCantagonist, nimodipine (Nimo) nor theLTCCagonists, Bay K 8644 (BayK) orFPL64176 (FPL), whereas the fraction of neuronal population that expressed both βIII‐tubulin andMAP2 was reduced by Nimo but increased by BayK orFPL. At an earlier period of differentiation (e.g. day 4), the fraction ofPZ5 cells expressing HuC/D, pan‐neuronal marker, was not affected either by theLTCCactivation or inhibition. At a later period of differentiation (e.g. day 9), the fraction of dying neurons was decreased byLTCCactivation and increased byLTCCinhibition. It is suggested that theLTCCactivation facilitates the survival and maturation of immature neurons, and that its inhibition facilitates the neuronal death.
Drivers of freshwater fish colonisations and extirpations under climate change
Authors: Conti Lorenza , Comte Lise , Hugueny Bernard , Grenouillet Gaël
Published: October 2014

Climate change is expected to bring about profound rearrangement of ecological communities by affecting individual species distributions. The resulting communities arise from the idiosyncratic responses of species to future changes, which ultimately relate to both shrinking and expanding species ranges. While spatial patterns of colonisation and extirpation events have received great attention, the identification of specific drivers remains poorly explored. This study aims to investigate the relative contribution of species gain and loss to the turnover of fish assemblages in French rivers under future climate change, and to identify their principal drivers. Future projections of potential habitat suitability in 2080 derived from species distribution models for 40 fish species showed that colonisations and extirpations could play counterbalancing roles in the reshuffling of communities. Simultaneously, these two processes exhibited patchy spatial patterns, segregated along the longitudinal and altitudinal gradients, resulting in dramatic species turnover of ∼ 60% of the current composition of species assemblages. Beyond the effect of topographic location, colonisations were found to be driven by temperature seasonality while extirpations were affected by modifications in both thermal and precipitation regimes.

These results generate the possibility of developing ecosystem‐based management tools focused on the early identification of areas where particular species may be sensitive to climate changes. Disentangling the drivers of colonisation and extirpation processes provides ready‐to‐use information that may be easily integrated into conservation planning. This information could be used to identify potential hotspots of species gain and loss and to then compare these hotspots with newly favourable areas so as to consider their actual accessibility in order to facilitate future range shifts.
Increasing temperature may compensate for lower amounts of dead wood in driving richness of saproxylic beetles
Authors: Müller Jörg , Brustel Herve , Brin Antoine , Bussler Heinz , Bouget Christophe , Obermaier Elisabeth , Heidinger Ina M. M. , Lachat Thibault , Förster Bernhard , Horak Jakub , Procházka Jiří , Köhler Frank , Larrieu Laurent , Bense Ulrich , Isacsson Gunnar , Zapponi Livia , Gossner Martin M.
Published: October 2014

Global warming and land‐use change are expected to be additive threats to global diversity, to which insects contribute the highest proportion. Insects are strongly influenced by temperature but also require specific habitat resources, and thus interaction between the two factors is likely. We selected saproxylic beetles as a model group because their life cycle depends on dead wood, which is highly threatened by land use. We tested the extent to which higher temperatures compensate for the negative effects of low amounts of dead wood on saproxylic beetle species richness (Temperature–Dead wood compensation hypothesis) on both a macroclimate and a topoclimate scale (north‐ and south‐facing slopes). We analyzed 1404 flight‐interception trap catches across Europe to test for interaction effects of temperature and dead‐wood amount on species richness. To experimentally test our findings from the activity trap data, we additionally reared beetles from 80 bundles of dead wood initially exposed at high and low elevations. At the topoclimate scale, we analyzed trap catches and reared beetles from dead wood exposed in 20 forest stands on south‐facing and north‐facing slopes in one region. On the macroscale, both temperature and dead‐wood amount positively affected total and threatened species richness independently, but their interaction was significantly negative, indicating compensation. On both scales and irrespective of the method, species richness decreased with temperature decline. Our observation that increasing temperature compensates for lower amounts of dead wood has two important implications. First, managers of production forests should adapt their dead‐wood enrichment strategy to site‐specific temperature conditions. Second, an increase in temperature will compensate at least partially for poor habitat conditions in production forests. Such a perspective contrasts the general assumption of reinforcing impacts of global warming and habitat loss on biodiversity, but it is corroborated by recent range expansions of threatened beetle species.
The association between traumatic dental injuries and atypical external root resorption in maxillary primary incisors
Authors: Holan Gideon , Yodko Elizabeth , Sheinvald‐Shusterman Kineret
Published: October 2014

Atypical root resorption (ARR), which is observed on radiographs of primary incisors, has been reported in the dental literature to result from digit sucking; thus ignoring any association between ARR and traumatic dental injuries (TDI). The purpose of this study was to evaluate and compare the contributions of sucking habits and TDI to external ARR in primary incisors. A history of dental trauma was assessed based on clinical and radiographic findings. Periapical radiographs of the premaxilla were evaluated for the presence of ARR. The presence or history of sucking habits was based on parents' report. Data were collected from files of 727 patients with a mean age of 52 months. Sixty‐four children (8.8%) presented ARR in one or both central incisors. All 64 had experienced some type of TDI. Five hundred and forty‐nine (76%) of the children had sucking habits; of them, 501 were pacifier‐suckers and 48 digit suckers. Digit sucking was found in only 4 (6%) of the 64 children presenting ARR. These findings support the association of traumatic dental injury, and not of digit sucking, with ARR in primary incisors.
Suitable design of mouthguard for sports‐active person with spaced dentition
Authors: Chowdhury Ruman U. , Churei Hiroshi , Takahashi Hidekazu , Shahrin Sharika , Fukasawa Shintaro , Shrestha Abhishekhi , Takashino Nami , Negoro Takefumi , Ueno Toshiaki
Published: October 2014

Aim

Custom‐made mouthguard (MG) is popularly used by sports‐active persons or athletes having either normo‐occlussion or malocclusion to prevent dental injury. For sports‐active person with malocclusion, specially designed mouthguard is often required. The purpose of this study was to make a suitable design custom‐made mouthguard for sports‐active person with spaced dentition by the shock absorption capability.

Materials and methods

Two different types of double layered mouthguards were made from a model of a sports‐active person having spaced dentition with polyolefin sheets. One type was made by filling the interproximal spaces of the spaced dentition and the other type, which was devoid of interproximal space covering, without mouthguard materials (keeping space). The impact tests were carried out by a free‐falling object via testing machine and a vertical rod. The strains of the dentition with mouthguard were measured by means of strain gage system to compare between two different designs of mouthguard. Unpaired t‐test was carried out as statistical analysis.

Result

The strains of the dentition with mouthguard by filling the interproximal spaces were significantly low compared with the mouthguard by keeping spaces (P < 0.05).

Conclusion

For sports‐active person with spaced dentition, it is important for reducing injury risks that the mouthguard covered the teeth and filled or embedded interproximal space certainly.
Advanced glycation end products‐induced chondrocyte apoptosis through mitochondrial dysfunction in cultured rabbit chondrocyte
Authors: Yang Qingshan , Guo Shifang , Wang Song , Qian Yaowen , Tai Huiping , Chen Zhixin
Published: October 2014

Advanced glycation end products (AGEs) are an important mediator in osteoarthritis (OA) and cause apoptosis in articular chondrocytes. Mitochondrial function is involved in modulating apoptosis of articular chondrocytes. This study was performed to investigate the mechanism of AGEs‐induced chondrocyte apoptosis. The ratio of apoptotic cell and cell viability was surveyed by TUNEL, MTT,LDH release assay. The reactive oxygen species was determined by the fluorescent probe 2’, 7’‐dichlorofluorescein diacetate. The expression of caspase‐3 and cytochrome c was detected by Western blot. The mitochondrial membrane potential (▵Ψm) was evaluated by rhodamine‐123 fluorescence. We found that AGEs induced apoptosis in primary rabbit chondrocytes, upregulation of ROS production, cytochrome c, and caspase‐3 levels. Simultaneously, AGEs decreases the levels of ▵Ψm and ATP production; however, the antibody of AGEs (sRAGE) and antioxidant‐N‐acetylcys‐teine (NAC) significantly reversed AGEs‐induced the above damage thus to protect the cells from apoptosis. These observations suggested that the mechanism of AGEs‐induced chondrocyte apoptosis was primarily via ROS production and mitochondria‐mediated caspase‐3 activation.
Auditory stimulation with music intensifies cardiac autonomic responses to a mental task
Authors: Gomes Fontes Anne M , Guida Heraldo L , Barbosa Juliana C , dos Antônio Ana MS , Cardoso Marco A , Garner David M , de Abreu Luiz C , Vanderlei Luiz CM , Raimundo Rodrigo D , Valenti Vitor E
Published: October 2014

Background

The literature is ambiguous as to whether exposure to relaxing classical music before mental arithmetic overload tests can affect cardiac autonomic regulation.

Objectives

To evaluate the effects of musical auditory stimulation on cardiac autonomic regulation after a mental arithmetic test.

Methods

This prospective study was conducted with 28 healthy male students aged 18–25 years. In the first evaluation protocol, participants rested for 10 min with the earphone turned off. After this period, participants had 5 min to perform the mental arithmetic overload test and 5 min of rest post test. In the second protocol, the participant was exposed to musical auditory stimuli for 10 min before completing the mental arithmetic overload test. Geometric indices [triangular interpolation of RR intervals (TINN); triangular index of RR intervals (RRtri); and Poincaré plot ratios SD1, SD2 and SD1/SD2] of heart‐rate variability (HRV) were evaluated before, during and after the mental arithmetic test. The Shapiro–Wilk test was used to verify data normality. For parametric variables, repeated measures ANOVA was used followed by the Bonferroni test. For non‐parametric distributions, Friedman's test was used followed by the Dunn's post‐test.

Results

The mental task did not change HRV under control conditions. Following exposure to musical stimuli, there was significant (P<0.05) cardiac autonomic changes, derived from RRtri, TINN and SD2 indices, which decreased during and after the mental arithmetic test.

Conclusions

We evaluated the acute effects of classic baroque musical auditory stimulation on cardiac autonomic regulation after a mental task in 28 male volunteers. The findings suggest auditory stimulation increases cardiac autonomic sensitivity induced by mental tasks.
(–)‐Epicatechin improves mitochondrial‐related protein levels and ameliorates oxidative stress in dystrophic δ‐sarcoglycan null mouse striated muscle
Authors: Ramirez‐Sanchez Israel , De los Santos Sergio , Gonzalez‐Basurto Silvia , Canto Patricia , Mendoza‐Lorenzo Patricia , Palma‐Flores Carlos , Ceballos‐Reyes Guillermo , Villarreal Francisco , Zentella‐Dehesa Alejandro , Coral‐Vazquez Ramon
Published: October 2014

Muscular dystrophies (MDs) are a group of heterogeneous genetic disorders characterized by progressive striated muscle wasting and degeneration. Although the genetic basis for many of these disorders has been identified, the exact mechanism of disease pathogenesis remains unclear. The presence of oxidative stress (OS) is known to contribute to the pathophysiology and severity of the MD. Mitochondrial dysfunction is observed in MD, and probably represents an important determinant of increased OS. Experimental antioxidant therapies have been implemented with the aim of protecting against disease progression, but results from clinical trials have been disappointing. In this study, we explored the capacity of the cacao flavonoid (–)‐epicatechin (Epi) to mitigate OS by acting as a positive regulator of mitochondrial structure/function endpoints and redox balance control systems in skeletal and cardiac muscles of dystrophic, δ‐sarcoglycan (δ‐SG) null mice. Wild‐type or δ‐SG null 2.5‐month‐old male mice were treated via oral gavage with either water (controls) or Epi (1 mg·kg−1, twice daily) for 2 weeks. The results showed significant normalization of total protein carbonylation, recovery of the glutathione/oxidized glutathione ratio and enhanced superoxide dismutase 2, catalase and citrate synthase activities with Epi treatment. These effects were accompanied by increases in the protein levels of thioredoxin, glutathione peroxidase, superoxide dismutase 2, catalase, and mitochondrial endpoints. Furthermore, we found decreases in heart and skeletal muscle fibrosis, accompanied by an improvement in skeletal muscle function, with treatment. These results warrant further investigation of Epi as a potential therapeutic agent to mitigate MD‐associated muscle degeneration.
Emerging role of HMGB1 in fibrotic diseases
Authors: Li Liu‐Cheng , Gao Jian , Li Jun
Published: October 2014

High‐mobility group box 1 (HMGB1) is originally identified as a DNA‐binding protein that functions as a structural co‐factor critical for proper transcriptional regulation in somatic cells. Recent studies indicate that HMGB1 can be passively released from necrotic cells or actively secreted into the extracellular milieu under appropriate signal stimulation. Extracellular HMGB1 is a multifunctional cytokine that contributes to the process of infection, injury, inflammation, apoptosis, and immune responses by binding to specific cell‐surface receptors. Recently, emerging studies indicate that HMGB1 is closely involved in fibrotic disorders including cystic fibrosis, liver fibrosis and pulmonary fibrosis, while HMGB1 signal inhibitions protect against the experimental models of fibrotic diseases. From a clinical perspective, HMGB1 represents a current challenge that can be exploited orchestrate reparative responses. This review focuses on the crucial role of HMGB1 in the pathogenesis of fibrotic diseases and inhibition of which may represent a promising clinical approach for treating tissue fibrosis.
Extending the time window of mammalian heart regeneration by thymosin beta 4
Authors: Rui Liu , Yu Nie , Hong Lian , Feng He , Chunyong Han , Jian Meng , Zhe Zheng , Shengshou Hu
Published: October 2014

Recent studies demonstrated that the heart of 1‐day‐old neonatal mice could regenerate, with Wt1+ EPDCs migrating into myocardial regions after partial surgical resection, but this capacity was lost by 7 days of age. By treatment with Tβ4 to maintain Wt1 expression and retain the migrating feature of EPDCs in neonatal mice, we explored the possibility of restoring the cardiac regeneration potential of mice. We intraperitoneally injected Tβ4 into 1‐day‐old mice on daily basis and then apical resection was performed on the mice 7 days later. Twenty one days after the resection, morphological analysis revealed that the Tβ4‐treated mice regenerated the resected ventricular apex, while the mice in PBS control group developed significant fibrosis without apical regeneration. The Tβ4‐treated mice had significantly better ventricular ejection fraction and fractional shortening than controls. During the process of regeneration, Wt1+ EPDCs migrated into myocardial region and some of them expressed Islet1 and the markers for mature cardiomyocytes, such as cTnT and SαA. These characteristics of Wt1+ EPDCs were also seen in the heart regeneration of mice subjected to apical resection 1 day after birth. Tβ4 has no essential effect on cell cycle activity as no disruption of actin filaments was observed in Tβ4‐treated hearts. These results revealed that the cardiac regeneration potential of neonatal mice could be extended to the 7th post‐natal day by Tβ4 and Wt1+ EPDCs mobilization might play an important role in the extension.
Endometrial stem cell transplantation in MPTP‐ exposed primates: an alternative cell source for treatment of Parkinson's disease
Authors: Wolff Erin F. , Mutlu Levent , Massasa Efi E. , Elsworth John D. , Eugene Redmond D. , Taylor Hugh S.
Published: October 2014

Parkinson's disease (PD) is a neurodegenerative disease caused by the loss of dopaminergic neurons in the substantia nigra. Cell‐replacement therapies have emerged as a promising strategy to slow down or replace neuronal loss. Compared to other stem cell types, endometrium‐derived stem cells (EDSCs) are an attractive source of stem cells for cellular therapies because of their ease of collection and vast differentiation potential. Here we demonstrate that endometrium‐derived stem cells may be transplanted into an MPTP exposed monkey model of PD. After injection into the striatum, endometrium‐derived stem cells engrafted, exhibited neuron‐like morphology, expressed tyrosine hydroxylase (TH) and increased the numbers of TH positive cells on the transplanted side and dopamine metabolite concentrations in vivo. Our results suggest that endometrium‐derived stem cells may provide a therapeutic benefit in the primate model of PD and may be used in stem cell based therapies.
Telocytes are reduced during fibrotic remodelling of the colonic wall in ulcerative colitis
Authors: Manetti Mirko , Rosa Irene , Messerini Luca , Ibba‐Manneschi Lidia
Published: October 2014

Ulcerative colitis (UC) is characterized by chronic relapsing intestinal inflammation finally leading to extensive tissue fibrosis and resulting in a stiff colon unable to carry out peristalsis or to resorb fluids. Telocytes, a peculiar type of stromal cells, have been recently identified in the human gastrointestinal tract. Several roles have been proposed for telocytes, including mechanical support, intercellular signalling and modulation of intestinal motility. The aim of the present work was to investigate the presence and distribution of telocytes in colonic specimens from UC patients compared with controls. Archival paraffin‐embedded samples of the left colon from UC patients who underwent elective bowel resection and controls were collected. Tissue sections were stained with Masson's trichrome to detect fibrosis. Telocytes were identified by CD34 immunohistochemistry. In early fibrotic UC cases, fibrosis affected the muscularis mucosae and submucosa, while the muscularis propria was spared. In advanced fibrotic UC cases, fibrosis extended to affect the muscle layers and the myenteric plexus. Few telocytes were found in the muscularis mucosae and submucosa of both early and advanced fibrotic UC colonic wall. In the muscle layers and myenteric plexus of early fibrotic UC, telocytes were preserved in their distribution. In the muscularis propria of advanced fibrotic UC, the network of telocytes was reduced or even completely absent around smooth muscle bundles and myenteric plexus ganglia, paralleling the loss of the network of interstitial cells of Cajal. In UC, a loss of telocytes accompanies the fibrotic remodelling of the colonic wall and might contribute to colonic dysmotility.
Occlusion on oral implants: current clinical guidelines
Authors: Koyano K. , Esaki D.
Published: October 2014

Proper implant occlusion is essential for adequate oral function and the prevention of adverse consequences, such as implant overloading. Dental implants are thought to be more prone to occlusal overloading than natural teeth because of the loss of the periodontal ligament, which provides shock absorption and periodontal mechanoreceptors, which provide tactile sensitivity and proprioceptive motion feedback. Although many guidelines and theories on implant occlusion have been proposed, few have provided strong supportive evidence. Thus, we performed a narrative literature review to ascertain the influence of implant occlusion on the occurrence of complications of implant treatment and discuss the clinical considerations focused on the overloading factors at present. The search terms were ‘dental implant’, ‘dental implantation’, ‘dental occlusion’ and ‘dental prosthesis’. The inclusion criteria were literature published in English up to September 2013. Randomised controlled trials (RCTs), prospective cohort studies and case–control studies with at least 20 cases and 12 months follow‐up interval were included. Based on the selected literature, this review explores factors related to the implant prosthesis (cantilever, crown/implant ratio, premature contact, occlusal scheme, implant–abutment connection, splinting implants and tooth–implant connection) and other considerations, such as the number, diameter, length and angulation of implants. Over 700 abstracts were reviewed, from which more than 30 manuscripts were included. We found insufficient evidence to establish firm clinical guidelines for implant occlusion. To discuss the ideal occlusion for implants, further well‐designed RCTs are required in the future.
Prevalence and geographic distribution of edentulism among older Ghanaians
Authors: Hewlett Sandra A. , Calys‐Tagoe Benedict N.L. , Yawson Alfred E. , Dako‐Gyeke Phyllis , Nakua Emmanuel , Folson Gloria , Baddo Akosua N. , Mensah George , Minicuci Nadia , Kowal Paul , Biritwum Richard B.
Published: October 2014

Objectives

Edentulism has important health implications for aging individuals and is used as an indicator of the oral health of a population. Its distribution is unequal within populations, with the greatest burden on disadvantaged and socially marginalized populations. With an increasing older adult population in Ghana, its burden may increase; however, there is no nationwide information on edentulism in Ghana. Focusing on adults 50 years and older, this study assessed the prevalence of edentulism among older Ghanaians and its distribution across the country.

Methods

Secondary analysis of WHO's Study on global AGEing and adult health (SAGE) Wave 1 in Ghana was conducted using self‐reported edentulism as the dependent variable.

Results

The overall prevalence was 2.8%, varying by sex (men had lower rates; OR = 0.67, 95% CI = 0.47‐0.97); by location, being more prevalent in urban areas (3.6%) and the Western Region (4.7%); by education levels (rates were higher among those with no formal education; OR = 1.626, 95% CI = 1.111‐2.380); and by marital status (those living without a partner had higher rates; OR = 1.980, 95% CI =1.366‐2.870). On multivariate logistic regression, the variables positively associated with edentulism were older age (OR = 0.945) and urban residence (OR = 0.582). Living in the Brong Ahafo (OR = 3.138), Central (OR = 2.172), Eastern (OR = 2.257), or Volta regions (OR = 3.333) was negatively associated with edentulism.

Conclusion

Edentulism is unequally distributed across Ghana. Future aged cohorts are likely to follow the same patterns of geographic and social disadvantage if needed interventions are not carried out. This study provides nationwide data to assist service planning.
Penile Prostheses and the Litigious Patient: A Legal Database Review
Authors: Sunaryo Peter L. , Colaco Marc , Terlecki Ryan
Published: October 2014

Introduction

Erectile dysfunction (ED) is a common problem with significant impact on patient quality of life. Penile prosthesis implantation provides an effective treatment for ED but as an invasive procedure carries with it an increased risk of medicolegal liability.

Aim

To investigate factors associated with malpractice litigation surrounding penile prosthesis implantation.

Methods

The Westlaw legal database was used to perform an advanced search for case reports using the term “medical malpractice” in combination with “penile” or “penis” and “prosthesis” or “implant” with dates between the January 1990 and December 2013.

Main Outcome Measures

Each report was examined for trial information including patient demographics, device model and indications, alleged breach of duty, alleged damages, progression to trial, case outcome, and plaintiff award(s).

Results

The initial search yielded 76 cases that were narrowed to 40 after exclusions. There were 23 (57.5%) cases that were found in favor of the defendant, while 17 (42.5%) cases led to indemnity payment to the plaintiff including two cases (5.0%) that were settled out of court and 15 (37.5%) favoring the plaintiff in front of a jury. The mean settlement received was $335,500 compared with the mean indemnity award of $831,050 for verdicts decided in favor of the plaintiff (P = 0.68). The most common breach of duty was error in surgical decision making, present in 20 cases (48.8%). Informed consent was an issue in 13 filings (31.7%), and postoperative infection was seen in 13 cases (31.7%). In cases that identified the type of implant used, 58.3% were malleable implants, and 41.7% were inflatable devices.

Conclusions

The main issues involved in malpractice litigation for penile prosthesis implants included surgical performance, informed consent, and postoperative management. Urologists must be aware of these potential issues in order to minimize their malpractice liability.
A Review of the Current State of the Male Circumcision Literature
Authors: Bossio Jennifer A. , Pukall Caroline F. , Steele Stephen
Published: October 2014

Introduction

Male circumcision is one of the most commonly performed surgical procedures worldwide and a subject that has been the center of considerable debate. Recently, the American Association of Pediatrics released a statement affirming that the medical benefits of neonatal circumcision outweigh the risks. At present, however, the majority of the literature on circumcision is based on research that is not necessarily applicable to North American populations, as it fails to take into account factors likely to influence the interpretability and applicability of the results.

Aims

The purpose of this review is to draw attention to the gaps within the circumcision literature that need to be addressed before significant changes to public policy regarding neonatal circumcision are made within North America.

Methods

A literature review of peer-reviewed journal articles was performed.

Main Outcome Measures

The main outcome measure was the state of circumcision research, especially with regard to new developments in the field, as it applies to North American populations.

Results

This review highlights considerable gaps within the current literature on circumcision. The emphasis is on factors that should be addressed in order to influence research in becoming more applicable to North American populations. Such gaps include a need for rigorous, empirically based methodologies to address questions about circumcision and sexual functioning, penile sensitivity, the effect of circumcision on men's sexual partners, and reasons for circumcision. Additional factors that should be addressed in future research include the effects of age at circumcision (with an emphasis on neonatal circumcision) and the need for objective research outcomes.

Conclusion

Further research is needed to inform policy makers, health-care professionals, and stakeholders (parents and individuals invested in this debate) with regard to the decision to perform routine circumcision on male neonates in North America.
OnabotulinumtoxinA (Botox) Nerve Blocks Provide Durable Pain Relief for Men with Chronic Scrotal Pain: A Pilot Open-Label Trial
Authors: Khambati Aziz , Lau Susan , Gordon Allan , Jarvi Keith A.
Published: October 2014

Introduction

Chronic scrotal pain (CSP) is a common, often debilitating, condition affecting approximately 4.75% of men. While nerve blocks using local anesthetics usually provide temporary pain relief, there are no publications on the use of longer acting nerve blocks to provide more durable pain relief for men with CSP.

Aim

The aim of this study was to determine if onabotulinumtoxinA (Botox) cord blocks provide durable pain relief for men with CSP.

Methods

In this pilot open-label study, men with CSP who had failed medical management but experienced temporary pain relief from a standard cord block underwent a cord block with 100U Botox.

Main Outcome Measures

The outcomes measured were changes 1, 3, and 6 months post-Botox injection in (i) a 10-point visual analog scale (VAS) pain score; (ii) scrotal tenderness on a three-point scale as rated by physical examination; and (iii) the Chronic Epididymitis Symptom Index (CESI) to measure the severity and impact of scrotal pain on men. Paired t-tests were used to compare groups.

Results

Eighteen patients with CSP seen between April and September 2013 had Botox injected as a cord block. At the 1-month follow-up, pain reduction was reported by 72% of patients (mean VAS score: 7.36 vs. 5.61, P < 0.003), while by physical examination 44 and 34% of the men had either complete or partial resolution of scrotal tenderness. In addition, there was also a significant reduction in CESI scores (22.19 vs. 19.25, P < 0.04). At 3 months, 56% had both sustained pain reduction and reduced tenderness based on the VAS score (mean: 7.36 vs. 6.02, P < 0.05) and physical exam. The CESI score continued to be significantly lower. Unfortunately, by 6 months, most men had a return to their baseline levels of pain and tenderness.

Conclusions

Our pilot study found that Botox cord blocks provide pain reduction for 3 months or more for most men with CSP.
Ant Colony Optimization Model for Tsunamis Evacuation Routes
Authors: Forcael Eric , González Vicente , Orozco Francisco , Vargas Sergio , Pantoja Alejandro , Moscoso Pablo
Published: October 2014

Natural disasters such as earthquakes and tsunamis foster the creation of effective evacuation strategies to prevent the loss of human lives. This article proposes a simulation model to find out optimum evacuation routes, during a tsunami using Ant Colony Optimization (ACO) algorithms. ACO is a discrete optimization algorithm inspired by the ability of ants to establish the shortest path from their nest to a food source, and vice versa, using pheromones. The validation of the model was carried out through two drills, which were conducted in the coastal town of Penco, Chile. This town was strongly affected by an 8.8 Mw earthquake and tsunami over February 2010. The first drill was held with minimum information, leaving the population to act randomly and intuitively. The second drill was carried out with information provided by the model, inducing people to use the optimized routes generated by the ACO algorithm. The results showed that, in case of an emergency, conventional evacuation routes showed longer escape times compared to those produced by the model developed in this research.
The importance of lipid modified proteins in plants
Authors: Hemsley Piers A.
Published: October 2014

Membranes have long been known to act as more than physical barriers within and between plant cells. Trafficking of membrane proteins, signalling from and across membranes, organisation of membranes and transport through membranes are all essential processes for plant cellular function. These processes rely on a myriad array of proteins regulated in a variety of manners and are frequently required to be directly associated with membranes. For integral membrane proteins, the mode of membrane association is readily apparent, but many peripherally associated membrane proteins are outwardly soluble proteins. In these cases the proteins are frequently modified by the addition of lipids allowing direct interaction with the hydrophobic core of membranes. These modifications include N‐myristoylation, S‐acylation (palmitoylation), prenylation and GPI anchors but until recently little was truly known about their function in plants. New data suggest that these modifications are able to act as more than just membrane anchors, and dynamic S‐acylation in particular is emerging as a means of regulating protein function in a similar manner to phosphorylation. This review discusses how these modifications occur, their impact on protein function, how they are regulated, recent advances in the field and technical approaches for studying these modifications.

Contents

Summary
476

I.
Introduction
476

II.
Types of lipid modification
477

III.
Effects of lipid modifications on proteins in plants
481

IV.
Strategies for study
485

V.
Outlook
487

Acknowledgements
487

References
487