bluuebunny/crossref_metadata_2025 huggingface dataset:
Graft stabilization with cyanoacrylate decreases shrinkage of free gingival grafts
Authors: Gümüş P , Buduneli E
Published: February 2014

Background

The aim of this study was to comparatively evaluate three different stabilization methods with regards to the amount of shrinkage in free gingival graft.

Methods

Forty‐five patients were included in three study groups: where stabilization was achieved with conventional technique, cyanoacrylate or microsurgery. In the conventional group standardized 5‐0 sutures were used. In the microsurgery group grafts were stabilized with 7‐0 sutures and loupe. In the third group, graft was stabilized with cyanoacrylate. Keratinized tissue width, graft area, gingival recession were calculated by a specific software on standard photographs at baseline, 1‐, 3‐, 6‐month follow‐ups. Duration of surgery was also recorded. Pain in recipient and donor sites was assessed using visual analogue scale within the first postoperative week.

Results

Change in keratinized tissue width was similar in the study groups at all times. Graft shrinkage was significantly less (p < 0.05) in the cyanoacrylate group than the other groups, whereas those in the conventional and microsurgery groups were similar. Significantly less pain in the recipient site was reported by the patients in the cyanoacrylate group (p < 0.05). Duration of surgery was significantly less in the cyanoacrylate group than the other groups (p < 0.05).

Conclusions

Less graft shrinkage in the free gingival graft, together with shorter surgery time and less pain in the recipient site obtained in the cyanoacrylate group, suggest that cyanoacrylate may be considered as an alternative for stabilization of free gingival grafts.
Genome‐wide detection of signatures of selection in Korean Hanwoo cattle
Authors: Porto‐Neto L. R. , Lee S. H. , Sonstegard T. S. , Van Tassell C. P. , Lee H. K. , Gibson J. P. , Gondro C.
Published: February 2014

The Korean Hanwoo cattle have been intensively selected for production traits, especially high intramuscular fat content. It is believed that ancient crossings between different breeds contributed to forming the Hanwoo, but little is known about the genomic differences and similarities between other cattle breeds and the Hanwoo. In this work, cattle breeds were grouped by origin into four types and used for comparisons: the Europeans (represented by six breeds), zebu (Nelore), African taurine (N'Dama) and Hanwoo. All animals had genotypes for around 680 000 SNPs after quality control of genotypes. Average heterozygosity was lower in Nelore and N'Dama (0.22 and 0.21 respectively) than in Europeans (0.26–0.31, with Shorthorn as outlier at 0.24) and Hanwoo (0.29). Pairwise FST analyses demonstrated that Hanwoo are more related to European cattle than to Nelore, with N'Dama in an intermediate position. This finding was corroborated by principal components and unsupervised hierarchical clustering. Using genome‐wide smoothed FST, 55 genomic regions potentially under positive selection in Hanwoo were identified. Among these, 29 were regions also detected in previous studies. Twenty‐four regions were exclusive to Hanwoo, and a number of other regions were shared with one or two of the other groups. These regions overlap a number of genes that are related to immune, reproduction and fatty acid metabolism pathways. Further analyses are needed to better characterize the ancestry of the Hanwoo cattle and to define the genes responsible to the identified selection peaks.
Down‐Regulation of TIMP3 Leads to Increase in TACE Expression and TNFα Production by Placental Trophoblast Cells
Authors: Ma Rong , Gu Baihan , Gu Yang , Groome Lynn J. , Wang Yuping
Published: February 2014

Problem

To determine whether down‐regulation of TIMP3 expression promotes TACE expression and increases in TNFα production by placental trophoblast cells.

Method of study

Placental expression of TIMP3 and TACE was examined by immunostaining and Western blot. Effects of TIMP3 on TACE expression and TNFα production were assessed by transfection of TIMP3 siRNA into trophoblasts isolated from normal placentas. Effects of oxidative stress on trophoblast TIMP3 expression and TNFα production were also determined. Trophoblast production of TIMP3, TACE and TNFα were measured by ELISA.

Results

TIMP3 expression was markedly reduced in preeclamptic placentas compared with normal placentas; oxidative stress down‐regulated trophoblast TIMP3 expression and production, P < 0.01. Down‐regulation of TIMP3 expression by TIMP3 siRNA resulted in significant increases in TACE expression and TNFα production, P < 0.01.

Conclusion

As TIMP3 is an endogenous TACE inhibitor, down‐regulation of trophoblast TIMP3 expression/activity could result in increased TACE expression and subsequently lead to increased TNFα production in preeclamptic placentas.
Extensive changes in the transcriptional profile of human adipose tissue including genes involved in oxidative phosphorylation after a 6‐month exercise intervention
Authors: Rönn T. , Volkov P. , Tornberg Å. , Elgzyri T. , Hansson O. , Eriksson K.‐F. , Groop L. , Ling C.
Published: February 2014

Aim

Adipose tissue has an important function in total energy homeostasis, and its dysregulation may contribute to lifestyle‐related diseases such as type 2 diabetes, cancer and cardiovascular diseases. The aim of this study was to investigate genome‐wide mRNA expression in adipose tissue in healthy men before and after an exercise intervention to identify genes or pathways that mediate the beneficial effect of regular exercise. We also investigated the difference in adipose tissue mRNA expression between individuals with or without a family history of type 2 diabetes.

Methods

The 6‐month supervised exercise intervention was conducted in 47 healthy men (age 37.8 ± 4.3 years, BMI 28.5 ± 3.6 kg m−2) with a previous low level of physical activity. RNA was analysed using GeneChip Human Gene 1.0 ST arrays (Affymetrix) before and after the exercise.

Results

We identified 2,560 significant transcripts differentially expressed before vs. after exercise with a false discovery rate (FDR) < 0.1%, including genes encoding the respiratory chain, histone subunits, small nucleolar RNAs and ribosomal proteins. Additionally, pathways enriched in response to exercise include the ribosome, oxidative phosphorylation, proteasome and many metabolic pathways, whereas the WNT and MAPK signalling pathways were down‐regulated (FDR < 5%) after exercise. There were no significant differences in mRNA expression between individuals with or without a family history of type 2 diabetes.

Conclusion

Exercise increased the expression of genes involved in oxidative phosphorylation, which is the opposite of what has been seen in adipose tissue from elderly or obese individuals with low physical fitness, and our study thereby demonstrates a mechanism for the beneficial effect of exercise.
Calibration using constrained smoothing with applications to mass spectrometry data
Authors: Feng Xingdong , Sedransk Nell , Xia Jessie Q.
Published: February 2014

Linear regressions are commonly used to calibrate the signal measurements in proteomic analysis by mass spectrometry. However, with or without a monotone (e.g., log) transformation, data from such functional proteomic experiments are not necessarily linear or even monotone functions of protein (or peptide) concentration except over a very restricted range. A computationally efficient spline procedure improves upon linear regression. However, mass spectrometry data are not necessarily homoscedastic; more often the variation of measured concentrations increases disproportionately near the boundaries of the instruments measurement capability (dynamic range), that is, the upper and lower limits of quantitation. These calibration difficulties exist with other applications of mass spectrometry as well as with other broad‐scale calibrations. Therefore the method proposed here uses a functional data approach to define the calibration curve and also the limits of quantitation under the two assumptions: (i) that the variance is a bounded, convex function of concentration; and (ii) that the calibration curve itself is monotone at least between the limits of quantitation, but not necessarily outside these limits. Within this paradigm, the limit of detection, where the signal is definitely present but not measurable with any accuracy, is also defined. An iterative approach draws on existing smoothing methods to account simultaneously for both restrictions and is shown to achieve the global optimal convergence rate under weak conditions. This approach can also be implemented when convexity is replaced by other (bounded) restrictions. Examples from Addona et al. (2009, Nature Biotechnology 27, 663–641) both motivate and illustrate the effectiveness of this functional data methodology when compared with the simpler linear regressions and spline techniques.
Current status of prognostication in classical Hodgkin lymphoma
Authors: Venkataraman Girish , Mirza M. Kamran , Eichenauer Dennis A. , Diehl Volker
Published: February 2014

Classical Hodgkin lymphoma (cHL) is characterized by a paucity of neoplastic Hodgkin/Reed Sternberg (HRS) cells within a complex cellular milieu that is rendered immunologically incapable of reacting against CD30+HRS cells due to a plethora of immune escape mechanisms initiated by the neoplastic cells. Accounting for 25% of all lymphomas and nearly 95% of all Hodgkin lymphomas, patients with cHL are typically young adults. Besides traditional prognostic factors, such as the International Prognostic Index (IPI), newer imaging and ancillary biomarkers (CD68, Galectin‐1 and plasma microRNA) have shown promise. Furthermore, the evolution of gene expression profiling (GEP) in recent years has enabled the development of several practically feasible GEP‐based predictors with prognostic relevance. This review discusses the current status of clinical prognostication in cHL, the critical role of histological evaluation in light of several mimicking entities, and the relevance of tissue as well as serum biomarkers pertaining to immune escape mechanisms and recent GEP studies.
Webster‐Stratton Incredible Years Basic Parent Programme (IY) in child care placements: residential staff carers' satisfaction results
Authors: Silva Isabel Simões , Gaspar Maria Filomena da Fonseca , Anglin James P.
Published: February 2014

The aim of the present study was to investigate residential child care staff satisfaction with their involvement in the Webster‐Stratton Incredible Years Basic Parent Programme (IY). In an exploratory, not randomized study, 27 professionals from two different short‐term Portuguese residential child care centres (IG1, n = 15; IG2; n = 12) completed weekly IY evaluations and an overall satisfaction questionnaire at the end of their participation in the IY intervention. The weekly level of satisfaction was assessed with regard to each of the programme's components (content, DVDs, group leaders, group discussion). At the last session, they filled out a questionnaire aimed to evaluate the levels of satisfaction regarding the programme overall, the teaching format, the group leader(s) and the usefulness of specific educational techniques they learned. Data indicated that residential staff carers were highly satisfied with the weekly sessions and with the overall usefulness of the intervention programme. Results are discussed in terms of implications and future research directions.
Board Independence, Ownership Structure and the Valuation of IPOs in Continental Europe
Authors: Bertoni Fabio , Meoli Michele , Vismara Silvio
Published: February 2014

Manuscript Type

Empirical

Research Question/Issue

We combine the value‐creation and value‐protection views of the board of directors to study the impact of board independence (BI) on the value of the firm at the time of its initial public offering (IPO).

Research Findings/Insights

We conduct our analysis on a sample of 969 firms that went public in France, Germany, and Italy between 1995 and 2011. We show that BI is a critical factor in the valuation of IPO firms. Our results support both the value‐creation and value‐protection roles of the board of directors. The relative importance of the two roles of the board varies over time, with value‐creation (value‐protection) dominating in IPOs of young (mature) companies.

Theoretical/Academic Implications

Our theoretical framework combines the agency and resource‐dependence theories. The impact of BI on IPO valuation depends on the importance of the value‐creation and value‐protection roles played by the board. The change in the relative importance of the two roles determines a U‐shaped relationship between BI and firm age. Corporate governance is particularly important for young and innovative firms (where the resource‐dependence theory applies, and governance acts as a value‐creation device), as well as for mature firms and for companies where ownership and control are separated (where the agency theory applies, and governance serves as a value‐protection mechanism for minority shareholders).

Practitioner/Policy Implications

We show that corporate governance is a significant factor affecting the valuation of an IPO company. The importance of BI varies substantially with the knowledge intensity of the industry, the separation between ownership and control, and the age of the listing company.
Large Shareholders, Shareholder Proposals, and Firm Performance: Evidence from Japan
Authors: Yeh Tsung‐ming
Published: February 2014

Manuscript Type

Empirical

Research Question/Issue

Previous studies, primarily based on evidence from the United States, fail to link shareholder activism to firm performance, with one explanatory factor being that the legal and regulatory system in the United States limits the anti‐director rights of shareholders. This study is motivated by the question of whether legally binding shareholder resolutions can pressure management to improve firm performance and to enhance firm value.

Research Findings/Insights

By investigating 135 publicly listed Japanese firms which received shareholder resolutions from 2004 to 2010, this study finds supportive evidence for shareholder proposals. Announcement‐associated abnormal returns are higher for firms receiving election‐related proposals by large sponsors, than those unrelated to board election. Furthermore, an improving trend begins to appear in the post‐resolution year, particularly significant for firms receiving proposals to remove board members.

Theoretical/Academic Implications

This study provides new evidence suggesting that large shareholder activism in Corporate Japan can perform roles that used to be played by main banks before the 1990s. It also suggests that in countries where there is no active takeover market, large shareholders can effectively discipline entrenched management through active engagement.

Practitioner/Policy Implications

This study offers insights to corporate managers on the importance of communicating with large shareholders and addressing their concerns.
Use of clinical targets in diabetes patient education: qualitative analysis of the expectations and impact of a structured self‐management programme in Type 1 diabetes
Authors: Snow R. , Sandall J. , Humphrey C.
Published: February 2014

Aims

To explore the impact of education and target‐setting on the life stories of patients with diabetes up to 10 years after they had participated in the Dose Adjustment for Normal Eating programme (DAFNE).

Methods

Qualitative, semi‐structured interviews were conducted before and after DAFNE courses to elicit narrative accounts from participants at three UK education centres. Observations of courses also took place. Data were gathered from 21 participants over 32 interviews and 146 h of observations, and analysed using a narrative approach.

Results

Findings suggest that patient education can create positive transformations in the lives of people with diabetes in ways that are not fully captured by simple quality‐of‐life scores. However, a review of evidence from other studies shows that DAFNE‐recommended blood glucose results are in fact out of reach of even these most motivated and well‐informed patients. This information was not shared with DAFNE attendees, who were expected to aim for near‐normal HbA1c levels. After the course, participants sometimes perceived themselves as failing in their efforts, even when they had better than average blood glucose results.

Conclusions

Specific and measurable low HbA1c targets may be desirable for reducing the risk of complications in diabetes, but they are not attainable or realistic even for most DAFNE graduates. It is suggested that setting goals without information about how achievable they really are could be counterproductive in terms of supporting and maintaining patient self‐efficacy long‐term.
Plateau of adiposity in Australian children diagnosed with Type 1 diabetes: a 20‐year study
Authors: Islam S. T. , Abraham A. , Donaghue K. C. , Chan A. K. , Lloyd M. , Srinivasan S. , Craig M. E.
Published: February 2014

Aims

To examine temporal trends in anthropometry in children with Type 1 diabetes from Sydney, Australia.

Methods

We conducted a retrospective study in a total of 1975 children with Type 1 diabetes, aged <16 years, between 1990 and 2009. Trends in height, weight and BMI standard deviation score after initial stabilization were examined by age group (<5 years, 5 to <10 years, 10 to 16 years) and time period of diagnosis (T1: 1990–1994, T2: 1995–1999; T3: 2000–2004 and T4: 2005–2009). Factors associated with BMI standard deviation score (time period, age group, gender and socio‐economic status) were examined using multivariable linear regression.

Results

The mean BMI standard deviation score (±sd) increased between T1 and T2 (0.54 ± 1.14 vs 0.81 ± 1.14, P = 0.002), but remained steady thereafter (T3: 0.85 ± 1.11, T4: 0.87 ± 1.09; T2 to T4: P = 0.40). Similarly, the prevalence of overweight and obesity increased from T1 to T2 (26 to 35%, P = 0.01), but was unchanged thereafter (T3: 34%, T4: 34%; T2 to T4: P = 0.90). On multivariable regression analysis, a higher BMI standard deviation score was associated with younger age (≥5 years vs <5 years, β=‐0.40, 95% CI ‐0.51 to ‐0.28, P < 0.001), later time period (T2 to T4 vs T1, β=0.30, 95% CI 0.16–0.45, P < 0.001) and male gender (β=0.25, 95% CI 0.15–0.34, P < 0.001).

Conclusion

The prevalence of overweight and obesity has remained unchanged in children at diagnosis of Type 1 diabetes over 15 years. These findings suggest that higher adiposity alone cannot account for the continued rising incidence of Type 1 diabetes in recent years.
Impact of baseline patient characteristics on interventions to reduce diabetes distress: the role of personal conscientiousness and diabetes self‐efficacy
Authors: Fisher L. , Hessler D. , Masharani U. , Strycker L.
Published: February 2014

Aims

To improve patient‐centred care by determining the impact of baseline levels of conscientiousness and diabetes self‐efficacy on the outcomes of efficacious interventions to reduce diabetes distress and improve disease management.

Methods

Adults with Type 2 diabetes with diabetes distress and self‐care problems (N = 392) were randomized to one of three distress reduction interventions: computer‐assisted self‐management; computer‐assisted self‐management plus problem‐solving therapy; and health education. The baseline assessment included conscientiousness and self‐efficacy, demographics, diabetes status, regimen distress, emotional burden, medication adherence, diet and physical activity. Changes in regimen distress, emotional burden and self‐care between baseline and 12 months were recorded and ancova models assessed how conscientiousness and self‐efficacy qualified the significant improvements in distress and management outcomes.

Results

Participants with high baseline conscientiousness displayed significantly larger improvements in medication adherence and emotional burden than participants with low baseline conscientiousness. Participants with high baseline self‐efficacy showed greater improvements in diet, physical activity and regimen distress than participants with low baseline self‐efficacy. The impact of conscientiousness and self‐efficacy were independent of each other and occurred across all three intervention groups. A significant interaction indicated that those with both high self‐efficacy and high conscientiousness at baseline had the biggest improvement in physical activity by 12 months.

Conclusions

Both broad personal traits and disease‐specific expectations qualify the outcomes of efficacious interventions. These findings reinforce the need to change from a one‐size‐fits‐all approach to diabetes interventions to an approach that crafts clinical interventions in ways that fit the personal traits and skills of individual people.
Health status and hypoglycaemia with insulin degludec versus insulin glargine: a 2‐year trial in insulin‐naïve patients with type 2 diabetes
Authors: Rodbard H. W. , Cariou B. , Zinman B. , Handelsman Y. , Wolden M. L. , Rana A. , Mathieu C.
Published: February 2014

Insulin degludec (IDeg) is a new basal insulin with an ultra‐long and stable glucose‐lowering effect. We compared once‐daily IDeg and insulin glargine (IGlar), both in combination with metformin ± dipeptidyl peptidase‐4 inhibitors, in a 52‐week, open‐label, treat‐to‐target trial in patients with type 2 diabetes followed by a 52‐week extension trial in which subjects [n = 725/1030 (70.4%)] maintained their initial randomised treatment. Health status was assessed at baseline and 105 weeks using the Short Form‐36 (SF‐36 v2) questionnaire. SF‐36 scores were analysed (ITT population) using anova, with adjustments for covariates. At 105 weeks, the overall physical component score was significantly better with IDeg versus IGlar [treatment contrast (TC): 1.1 (0.1; 2.1)95%CI, p < 0.05]. This was largely because of significantly better physical functioning [TC: 1.1 (0.0; 2.3)95%CI, p < 0.05] and bodily pain sub‐domain scores [TC: 1.5 (0.2; 2.9)95%CI, p < 0.05]. Improvements in health status with IDeg compared to IGlar were maintained after 2 years.
Which Technique Is Better for Detection of Right‐to‐Left Shunt in Patients with Patent Foramen Ovale: Comparing Contrast Transthoracic Echocardiography with Contrast Transesophageal Echocardiography
Authors: Li Yue , Ya‐nan Zhai , Li‐qun Wei
Published: February 2014

Background

At present there is no consensus on which technique is more suitable for the detection of right‐to‐left shunt (RLS) in patients with patent foramen ovale (PFO). The aim of study was to compare the efficacy of contrast transthoracic echocardiography (cTTE) and contrast transesophageal echocardiography (cTEE) in the detection of RLS.

Methods

A prospective study was undertaken in 29 patients with PFO. Both cTTE with harmonic imaging modality and cTEE with fundamental imaging modality were performed for all the patients. The severity of RLS were semiquantitatively assessed with a four‐level grade system by scaling the numbers of microbubbles (MBs) in the left atrium after complete opacification of the right atrium within the first 3 cardiac cycles. Level 1 represents no MBs, indicating no RLS. Level 2, ≤10 MBs, indicating mild RLS. Level 3, 11–30 MBs, indicating moderate RLS and Level 4, >30 MBs, indicating severe RLS.

Results

Contrast TTE demonstrated significantly higher sensitivity for detection of RLS than cTEE (86% vs. 56%, P < 0.05). For cTTE, there were 4, 1, 5, and 19 cases determined at levels 1, 2, 3, and 4, respectively, whereas for the same group of patients 13, 2, 6, and 7 cases were identified by cTEE at levels 1, 2, 3, and 4, respectively. The severity of RLS detected by cTTE was significantly greater than that by cTEE (P < 0.01).

Conclusions

Contrast TTE is more efficacious in the detection of RLS than cTEE. The former can be used as an alternative to the latter in clinical practice.
Effectiveness of training senior dental students on oral health care for disabled patients
Authors: Mohebbi S. Z. , Chinipardaz Z. , Batebi A.
Published: February 2014

Introduction

Studies in several countries have shown that dental students need an improved educational programme concerning management of disabled patients. We aimed to study the effect of providing a course entitled ‘Oral health care of disabled patients' on knowledge and attitudes of senior dental students at Tehran University.

Materials and methods

A total number of 70 students (n = 70) were asked to fill in a questionnaire regarding their background, knowledge and attitudes, before and after the programme. The intervention group of 36 students (n = 36) received a four‐session course consisting of lectures, group discussion, screening and fluoride varnish provision for disabled patients. Statistical analysis was performed using the Mann–Whitney U‐test, the chi‐square test and linear regression modelling.

Results

Amongst all the participants, 36% had previously treated a disabled patient and 58% believed that merely specialists should treat disabled patients. Twenty‐seven percentage of participants believed that hospital is the only proper facility for treating disabled patients. A considerable improvement in both knowledge and attitudes of students was observed following the intervention (P < 0.05).

Conclusions

Our findings indicate that a short‐term training programme on oral health care has an immense impact on students' adherence to treating disabled patients. These results provide evidence to support the necessity of enrichment of the dental curriculum regarding oral health care for disabled patients.
The molecular interplay between endocannabinoid and neurotrophin signals in the nervous system and beyond
Authors: Keimpema Erik , Hökfelt Tomas , Harkany Tibor , Doherty Patrick
Published: February 2014

Neurotrophins are traditionally known for their roles in neuronal development, function and survival. More recent data has highlighted the importance of neurotrophin signalling in adult signalling contexts, including the regulation of synaptic transmission. In addition, neurotrophin levels are increased in inflammatory and neuropathic pain leading to sensitization to painful stimuli. Endocannabinoid (eCB) signalling was initially studied in the context of synaptic transmission and pain alleviation whilst recently gaining attention due to its involvement in the development of the nervous system. Similar to neurotrophins, eCB levels also rise during pain perception but result in diminished pain sensations. The overlap of cellular functions between neurotrophins and eCB signalling leads to the hypothesis that these signalling systems are positioned to regulate each other and narrow the multitude of actions that both systems can promote to the specific need of the cell. Therefore, in this review, we examine to what extent the involvement of these two signalling systems is co‐ordinated as opposed to being coincidental, and causal to neuronal circuit modifications in pain. Available data point to numerous direct molecular interactions between the neurotrophin and eCB signalling systems in developmental and adult contexts, including receptor‐level interplay, transcriptional control and synergistic regulation of downstream signalling cascades. Although experimental observations specifically in pain circuits are limited, the universality of downstream signalling systems from both neurotrophin and endocannabinoid receptors suggest an interdependent relationship between these two diverse signalling systems.
Neurobiology of pain, interoception and emotional response: lessons from nerve growth factor‐dependent neurons
Authors: Indo Yasuhiro
Published: February 2014

Although nerve growth factor (NGF) is a well‐known neurotrophic factor, it also acts as a mediator of pain, itch and inflammation. Congenital insensitivity to pain with anhidrosis (CIPA) is an autosomal recessive genetic disorder caused by loss‐of‐function mutations inNTRK1, the gene encoding a receptor tyrosine kinase for NGF, TrkA. Mutations inNTRK1cause the selective loss of NGF‐dependent neurons in otherwise intact systems. NGF‐dependent primary afferents are thinly myelinated Aδ or unmyelinated C‐fibers that are dependent on the NGF–TrkA system during development. In CIPA, the lack of pain and the presence of anhidrosis (inability to sweat) are due to the absence of both NGF‐dependent primary afferents and sympathetic postganglionic neurons, respectively. These peripheral neurons form an interface between the nervous system and the ‘body‐proper’ and play essential roles in the interoception and sympathetic regulation of various tissues or organs. Patients with CIPA also show mental retardation and characteristic behaviors and are probably neuron‐deficient within the brain. However, the functions of NGF‐dependent neurons in the brain are controversial, both in animal and in human studies. This review focuses on various brain regions that express TrkAmRNA, based on data from theAllen Human Brain Atlas, and discusses putative neuronal networks related to these brain regions in humans. A better understanding the distribution of NGF‐dependent neurons in the brain will provide a framework for further studies to investigate pain, interoception and emotional responses. Furthermore, strategies targeting the molecular mechanisms through which the NGF–TrkA system functions may provide hope for the development of novel analgesics.
Neurotrophins, endocannabinoids and thermo‐transient receptor potential: a threesome in pain signalling
Authors: Devesa Isabel , Ferrer‐Montiel Antonio
Published: February 2014

Because of the social and economic costs of chronic pain, there is a growing interest in unveiling the cellular and molecular mechanisms underlying it with the aim of developing more effective medications. Pain signalling is a multicomponent process that involves the peripheral and central nervous systems. At the periphery, nociceptor sensitisation by pro‐inflammatory mediators is a primary step in pain transduction. Although pain is multifactorial at cellular and molecular levels, it is widely accepted that neurotrophin (TrkA, p75NTR, Ret and GFRs), cannabinoid (CB1 and CB2), and thermo‐transient receptor potential (TRPs; TRPV1, TRPA1 and TRPM8) receptors play a pivotal role. They form a threesome for which endocannabinoids appear to be a first line of defence against pain, while neurotrophins and thermoTRPs are the major generators of painful signals. However, endocannabinoids may exhibit nociceptive activity while some neurotrophins may display anti‐nociception. Accordingly, a clear‐cut knowledge of the modulation and context‐dependent function of these signalling cascades, along with the molecular and dynamic details of their crosstalk, is critical for understanding and controlling pain transduction. Here, the recent progress in this fascinating topic, as well as the tantalizing questions that remain unanswered, will be discussed. Furthermore, we will underline the need for using a systems biology approach (referred to as systems pain) to uncover the dynamics and interplay of these intricate signalling cascades, taking into consideration the molecular complexity and cellular heterogeneity of nociceptor populations. Nonetheless, the available information confirms that pharmacological modulation of this signalling triad is a highly valuable therapeutic strategy for effectively treating pain syndromes.
Pro‐neurotrophins, sortilin, and nociception
Authors: Lewin Gary R. , Nykjaer Anders
Published: February 2014

Nerve growth factor (NGF) signaling is important in the development and functional maintenance of nociceptors, but it also plays a central role in initiating and sustaining heat and mechanical hyperalgesia following inflammation. NGF signaling in pain has traditionally been thought of as primarily engaging the classic high‐affinity receptor tyrosine kinase receptor TrkA to initiate sensitization events. However, the discovery that secreted proforms of nerve NGF have biological functions distinct from the processed mature factors raised the possibility that these proneurotrophins (proNTs) may have distinct function in painful conditions. ProNTs engage a novel receptor system that is distinct from that of mature neurotrophins, consisting of sortilin, a type I membrane protein belonging to the VPS10p family, and its co‐receptor, the classic low‐affinity neurotrophin receptor p75NTR. Here, we review how this new receptor system may itself function with or independently of the classic TrkA system in regulating inflammatory or neuropathic pain.
Heterogeneous presynaptic distribution of monoacylglycerol lipase, a multipotent regulator of nociceptive circuits in the mouse spinal cord
Authors: Horváth Eszter , Woodhams Stephen G. , Nyilas Rita , Henstridge Christopher M. , Kano Masanobu , Sakimura Kenji , Watanabe Masahiko , Katona István
Published: February 2014

Monoacylglycerol lipase (MGL) is a multifunctional serine hydrolase, which terminates anti‐nociceptive endocannabinoid signaling and promotes pro‐nociceptive prostaglandin signaling. Accordingly, both acute nociception and its sensitization in chronic pain models are prevented by systemic or focal spinal inhibition of MGL activity. Despite its analgesic potential, the neurobiological substrates of beneficial MGL blockade have remained unexplored. Therefore, we examined the regional, cellular and subcellular distribution of MGL in spinal circuits involved in nociceptive processing. All immunohistochemical findings obtained with light, confocal or electron microscopy were validated in MGL‐knockout mice. Immunoperoxidase staining revealed a highly concentrated accumulation of MGL in the dorsal horn, especially in superficial layers. Further electron microscopic analysis uncovered that the majority of MGL‐immunolabeling is found in axon terminals forming either asymmetric glutamatergic or symmetric γ‐aminobutyric acid/glycinergic synapses in laminae I/IIo. In line with this presynaptic localization, analysis of double‐immunofluorescence staining by confocal microscopy showed that MGL colocalizes with neurochemical markers of peptidergic and non‐peptidergic nociceptive terminals, and also with markers of local excitatory or inhibitory interneurons. Interestingly, the ratio of MGL‐immunolabeling was highest in calcitonin gene‐related peptide‐positive peptidergic primary afferents, and the staining intensity of nociceptive terminals was significantly reduced in MGL‐knockout mice. These observations highlight the spinal nociceptor synapse as a potential anatomical site for the analgesic effects of MGL blockade. Moreover, the presence of MGL in additional terminal types raises the possibility that MGL may play distinct regulatory roles in synaptic endocannabinoid or prostaglandin signaling according to its different cellular locations in the dorsal horn pain circuitry.
No more pain upon Gq‐protein‐coupled receptor activation: role of endocannabinoids
Authors: Hu Sherry Shu‐Jung , Ho Yu‐Cheng , Chiou Lih‐Chu
Published: February 2014

Marijuana has been used to relieve pain for centuries. The analgesic mechanism of its constituents, the cannabinoids, was only revealed after the discovery of cannabinoid receptors (CB1 and CB2) two decades ago. The subsequent identification of the endocannabinoids, anandamide and 2‐arachidonoylglycerol (2‐AG), and their biosynthetic and degradation enzymes discloses the therapeutic potential of compounds targeting the endocannabinoid system for pain control. Inhibitors of the anandamide and 2‐AG degradation enzymes, fatty acid amide hydrolase and monoacylglycerol lipase, respectively, may be superior to direct cannabinoid receptor ligands as endocannabinoids are synthesized on demand and rapidly degraded, focusing action at generating sites. Recently, a promising strategy for pain relief was revealed in the periaqueductal gray (PAG). It is initiated by Gq‐protein‐coupled receptor (GqPCR) activation of the phospholipase C–diacylglycerol lipase enzymatic cascade, generating 2‐AG that produces inhibition of GABAergic transmission (disinhibition) in the PAG, thereby leading to analgesia. Here, we introduce the antinociceptive properties of exogenous cannabinoids and endocannabinoids, involving their biosynthesis and degradation processes, particularly in the PAG. We also review recent studies disclosing the GqPCR–phospholipase C–diacylglycerol lipase–2‐AG retrograde disinhibition mechanism in the PAG, induced by activating several GqPCRs, including metabotropic glutamatergic (type 5 metabotropic glutamate receptor), muscarinic acetylcholine (M1/M3), and orexin 1 receptors. Disinhibition mediated by type 5 metabotropic glutamate receptor can be initiated by glutamate transporter inhibitors or indirectly by substance P, neurotensin, cholecystokinin and capsaicin. Finally, the putative role of 2‐AG generated after activating the above neurotransmitter receptors in stress‐induced analgesia is discussed.
A Qualitative Approach to Evidence–Based Entrepreneurship: Theoretical Considerations and an Example Involving Business Clusters
Authors: Rauch Andreas , van Doorn Robert , Hulsink Willem
Published: February 2014

Most research in evidence–based entrepreneurship builds on quantitative designs, which is unfortunate because qualitative studies provide a unique contribution to the domain of entrepreneurship. They look at distinctive phenomena in their specific time period and context in one way or another, and can help generate and test new theories. We, therefore, suggest using a systematic synthesis of case studies to aggregate the findings of qualitative research. Moreover, as a first step, we developed an example to demonstrate how this approach can advance evidence–based entrepreneurship. Specifically, we synthesized 13 cases to examine how business clusters increase the performance of firms within clusters.
Do Male Activity Level And Territory Quality Affect Female Association Time in The Brown Anole, Anolis sagrei?
Authors: Flanagan Sarah P. , Bevier Catherine R.
Published: February 2014

Female mate preference is an important component of sexual selection because some male traits, such as physiology and proficiency in acquiring resources, are indicators of male quality. In lizards, the importance of female choice remains unclear as results reported from previous experiments are contradictory. Here, we investigated the influence of male activity level, its associated physiology, and territory quality on female preference, estimated as association time, for male brown anoles, Anolis sagrei. Male A. sagrei were first rated for endurance then used in mismatched‐pair female association trials. Preference was scored as the time a female spent near a male relative to the amount of time she was in his half of the trial arena, and both male and female behaviors were recorded. Levels of blood glucose were measured in males before and after the endurance tests, and before and after the association trials. Levels of stored glycogen were measured in leg muscle and liver samples collected from males after an association trial. A path analysis indicates that final blood glucose levels affect male activity and that female preference is influenced by male activity. In a second experiment, females were given a choice between a male in a territory supplemented with plants and a size‐matched male in a bare territory. Male activity levels were recorded when both males interacted with the female. In those cases, females spent more time with the more active of the two males, regardless of territory quality. Combined, these results suggest that female A. sagrei exhibit preference for male activity regardless of territory quality.
Anticoagulants for secondary prevention after acute myocardial infarction: lessons from the past decade
Authors: Atar Dan , Bode Christoph , Stuerzenbecher André , Verheugt Freek W. A.
Published: February 2014

The impact of an acute coronary syndrome (ACS) event, such as an acute myocardial infarction (MI), is not limited to the acute management phase; patients face an elevated risk of residual atherothrombotic events that commonly requires chronic management for months or even years. Significant advances have been made in both the acute and chronic management of patients with acuteMIover the past decade, resulting in improved prognoses. One of the hallmarks of modern treatment strategies is more aggressive antiplatelet treatment regimens. However, the risks of furtherACSevents, stroke and premature death remain elevated in these patients, and addressing this residual risk is challenging owing to interpatient variability, differences in management strategies between centres and countries, incomplete understanding of the specific pathophysiology of post‐ACSthrombosis and limitations of current therapeutic approaches. The recent approval inEurope of the direct oral anticoagulant rivaroxaban for use in this setting in combination with clopidogrel and acetylsalicylic acid offers another strategy to consider in the management of these patients, and clinical strategies in this area continue to evolve. In this review, we chart the progress made over the past decade in reducing the burden of secondary thromboembolic events after acuteMIand discuss the current position of and future perspectives on the inclusion of oral anticoagulants into care pathways in this setting.
Predictions of climate change infer increased environmental harshness and altered connectivity in a cluster of temporary pools
Authors: Tuytens Karen , Vanschoenwinkel Bram , Waterkeyn Aline , Brendonck Luc
Published: February 2014

Future moderate changes in evaporation and precipitation regimes could have pronounced effects on zooplankton populations in small and temporary aquatic habitats, by causing higher salinity and a shorter wet phase and by reducing passive dispersal via hydrological connections between pools and increasing it by exposing propagules to the wind.

Using a hydrological model, we simulated various climate change scenarios in a natural cluster of temporary rock pools in South Africa.

In our simulations, a shift towards a drier climate was associated with reduced permanence and increased conductivity, resulting in a lower percentage of inundations sufficient for the hatching, growth and reproduction of aquatic organisms (up to a 21% decline for a fairy shrimp). Connections between pools by overflowing occurred less frequently (by up to 28%). However, more frequent desiccation events (by up to 15%) led to increased exposure of dormant propagules to wind, possibly promoting dispersal within the pool cluster but also leading to losses from the propagule bank.

Our results suggest that environmental change might not only affect local (within‐pool) selection pressures but also regional dynamics in rock pool metapopulations and communities.
PPARγ gene polymorphism, C‐reactive protein level, BMI and periodontitis in post‐menopausal Japanese women
Authors: Wang Yangming , Sugita Noriko , Yoshihara Akihiro , Iwasaki Masanori , Miyazaki Hideo , Nakamura Kazutoshi , Yoshie Hiromasa
Published: February 2014

Background

Several studies have reported inconsistent results regarding the association between the PPARγPro12Ala polymorphism and obesity. Obese individuals had higher C‐reactive protein (CRP) levels compared with those of normal weight, and PPARγ activation could significantly reduce serum high‐sensitive CRP level. We have previously suggested that the Pro12Ala polymorphism represents a susceptibility factor for periodontitis, which is a known risk factor for increased CRP level.

Objectives

The aim was to investigate associations between PPARγ gene polymorphism, serum CRP level, BMI and/or periodontitis among post‐menopausal Japanese women.

Materials and methods

The final sample in this study comprised 359 post‐menopausal Japanese women. Periodontal parameters, including PD, CAL and BOP, were measured per tooth. PPARγPro12Ala genotype was determined by PCR‐RFLP. Hs‐CRP value was measured by a latex nephelometry assay.

Results

No significant differences in age, BMI or periodontal parameters were found between the genotypes. The percentages of sites with PD ≥ 4 mm were significantly higher among the hsCRP ≥ 1 mg/l group than the hsCRP < 1 mg/l group (p = 0.003). Positive correlations were found between serum hsCRP levels and the percentages of sites with PD ≥ 4 mm (p = 0.043) in PPARγ Ala allele carriers, and BMI (p = 0.033) in non‐carriers. After adjustment for model covariates, BMI was significantly associated with serum hsCRP level.

Conclusion

The PPARγPro12Ala polymorphism was not independently associated with periodontitis, serum CRP level or BMI in post‐menopausal Japanese women. However, serum hsCRP level correlated with periodontitis in Ala allele carriers, and with BMI in non‐carriers.
Human cell growth regulator Ly‐1 antibody reactive homologue accelerates processing of preribosomal RNA
Authors: Miyazawa Naoki , Yoshikawa Harunori , Magae Satomi , Ishikawa Hideaki , Izumikawa Keiichi , Terukina Goro , Suzuki Ai , Nakamura‐Fujiyama Sally , Miura Yutaka , Hayano Toshiya , Komatsu Wataru , Isobe Toshiaki , Takahashi Nobuhiro
Published: February 2014

Ribosome biogenesis is an essential process for cell growth and proliferation and is enhanced in cancer and embryonic stem cells. Mouse Ly‐1 antibody reactive clone product (Lyar) is expressed at very high levels in many tumor, leukemia or embryonic stem cells; is a novel nucleolar protein with zinc‐finger DNA‐binding motifs and is involved in cell growth regulation. However, cellular function of Lyar remains unexplored. Here, we show that human homologue of Lyar (LYAR) accelerates ribosome biogenesis at the level of processing of preribosomal RNA (pre‐rRNA). We show that LYAR is excluded from the nucleolus after actinomycin D treatment and is present in preribosomal fraction of the nuclear extract as well as in the fractions with 40S, 60S and 90S sedimentation coefficients. LYAR is required for processing of 47S/45S, 32S, 30S and 21S pre‐rRNAs. In addition, we show that over‐expression of LYAR increases cell proliferation without affecting the expression of c‐Myc or p53. Combined, these results suggest that some rapidly growing cells enhance ribosome biogenesis by increasing the expression of LYAR.
Review of findings in prophylactic gynaecological specimens in Lynch syndrome with literature review and recommendations for grossing
Authors: Downes Michelle R , Allo Ghassan , McCluggage W Glenn , Sy Keiyan , Ferguson Sarah E , Aronson Melyssa , Pollett Aaron , Gallinger Steve , Bilbily Elaine , Shaw Pat , Clarke Blaise A
Published: February 2014

Aims

Prophylactic hysterectomy with bilateral salpingo‐oophorectomy is being increasingly undertaken in patients with Lynch syndrome (LS). The pathological features in such specimens are not well described and, unlike the SEE‐FIM protocol for salpingo‐oophorectomy specimens in BRCA1/2 mutation carriers and the gastrectomy grossing protocols for patients with CDH1 (E‐cadherin) mutations, guidelines have not been devised for the grossing of prophylactic gynaecological specimens from LS patients. We aimed to review the pathological findings in a series of prophylactic gynaecological specimens from LS patients and develop guidelines for the grossing of these specimens.

Methods and results

We reviewed the pathological findings in 25 prophylactic gynaecological specimens from LS patients and audited the grossing protocols in different centres across Ontario, Canada. We found a 32% incidence of endometrial carcinoma or a precursor lesion; the two endometrial cancers identified were low‐grade, low‐stage endometrioid adenocarcinomas. To address the absence of guidelines for pathological examination, we undertook a literature review of gynaecological malignancies and incidental findings in prophylactic specimens in LS patients.

Conclusion

We provide recommendations regarding the grossing of such specimens which includes in‐toto examination of the lower uterine segment, endometrium, ovaries and fallopian tubes with representative sampling of the cervix.