bluuebunny/crossref_metadata_2025 huggingface dataset:
Reelin and the Cdc42/Rac1 guanine nucleotide exchange factor αPIX/Arhgef6 promote dendritic Golgi translocation in hippocampal neurons
Authors: Meseke Maurice , Rosenberger Georg , Förster Eckart
Published: February 2013

In the cerebral cortex of reeler mutant mice lacking reelin expression, neurons are malpositioned and display misoriented apical dendrites. Neuronal migration defects in reeler have been studied in great detail, but how misorientation of apical dendrites is related to reelin deficiency is poorly understood. In wild‐type mice, the Golgi apparatus transiently translocates into the developing apical dendrite of radially migrating neurons. This dendritic Golgi translocation has recently been shown to be promoted by reelin. However, the underlying signalling mechanisms are largely unknown. Here, we show that the Cdc42/Rac1 guanine nucleotide exchange factor αPIX/Arhgef6 promoted translocation of Golgi cisternae into developing dendrites of hippocampal neurons. Reelin treatment further increased the αPIX‐dependent effect. In turn, overexpression of exchange activity‐deficient αPIX or dominant‐negative (dn) Cdc42 or dn‐Rac1 impaired dendritic Golgi positioning, an effect that was not compensated by reelin treatment. Together, these data suggest that αPIX may promote dendritic Golgi translocation, as a downstream component of a reelin‐modulated signalling pathway. Finally, we found that reelin promoted the translocation of the Golgi apparatus into the dendrite that was most proximal to the reelin source. The distribution of reelin may thus contribute to the selection of the process that becomes the apical dendrite.
Lack of galectin‐3 speeds Wallerian degeneration by altering TLR and pro‐inflammatory cytokine expressions in injured sciatic nerve
Authors: Mietto Bruno Siqueira , Jurgensen Sofia , Alves Lucinéia , Pecli Cyntia , Narciso Marcelo Sampaio , Assunção‐Miranda Iranaia , Villa‐Verde Dea Maria Serra , de Souza Lima Flávia Regina , de Menezes João Ricardo Lacerda , Benjamim Cláudia Farias , Bozza Marcelo Torres , Martinez Ana Maria Blanco
Published: February 2013

Wallerian degeneration (WD) comprises a series of events that includes activation of non‐neuronal cells and recruitment of immune cells, creating an inflammatory milieu that leads to extensive nerve fragmentation and subsequent clearance of the myelin debris, both of which are necessary prerequisites for effective nerve regeneration. Previously, we documented accelerated axon regeneration in animals lacking galectin‐3 (Gal‐3), a molecule associated with myelin clearance. To clarify the mechanisms underlying this enhanced regeneration, we focus here on the early steps of WD following sciatic nerve crush in Gal‐3−/− mice. Using an in vivo model of nerve degeneration, we observed that removal of myelin debris is more efficient in Gal‐3−/− than in wild‐type (WT) mice; we next used an in vitro phagocytosis assay to document that the phagocytic potential of macrophages and Schwann cells was enhanced in the Gal‐3−/− mice. Moreover, both RNA and protein levels for the pro‐inflammatory cytokines IL‐1β and TNF‐α, as well as for Toll‐like receptor (TLR)‐2 and ‐4, show robust increases in injured nerves from Gal‐3−/−mice compared to those from WT mice. Collectively, these data indicate that the lack of Gal‐3 results in an augmented inflammatory profile that involves the TLR–cytokine pathway, and increases the phagocytic capacity of Schwann cells and macrophages, which ultimately contributes to speeding the course of WD.
Working with Identity and Self‐soothing in Emotion‐Focused Therapy for Couples
Authors: Goldman Rhonda N. , Greenberg Leslie
Published: February 2013

This paper will outline new developments in Emotion‐Focused Therapy for Couples (EFT‐C) (Greenberg & Goldman, Emotion‐focused couples therapy: The dynamics of emotion, love, and power, Washington, DC, American Psychological Association, 2008). People are seen as primarily motivated by their affective goals and the regulation of emotional states. The three motivational systems of attachment, identity, and attraction/liking, viewed as reflective of the core concerns people bring to therapy, are briefly outlined and elaborated. The five‐stage model of EFT‐C is briefly described. The paper will then provide two illustrations, one that demonstrates how EFT‐C therapists work with core issues related to identity, and the other that shows how therapy can promote self‐soothing. In the first example, annotated transcripts taken from therapy sessions illustrate how an EFT therapist addresses issues of identity in a highly distressed couple. The second example demonstrates how to facilitate work with individuals within the couples' context to engender and develop capacities for self‐soothing, seen as fundamental for the promotion of healthy emotion regulation and couples' overall health.
Human dermal exposure to galaxolide from personal care products
Authors: Correia P. , Cruz A. , Santos L. , Alves A.
Published: February 2013

Synopsis

Musks are synthetic fragrances applied on personal care and household products as fixatives, by retarding the release of other fragrances with higher volatility. Galaxolide is the most used polycyclic musk since the 90th decade, and it has been detected in several environmental and biological matrices, particularly in human tissues and fluids. For exposure assessment purposes, large‐monitoring data need to be obtained and rapid but reliable analytical techniques are requested. The main objective of this study is to develop and validate a new and fast analytical methodology to quantify galaxolide in personal care products and to apply this method to real matrices like skin care products (creams and lotions), shower products (soap bar), hair care products (shampoo and hair conditioner) and oral care products (toothpaste), to evaluate the human dermal exposure risk. A dispersive solid‐phase extraction is proposed, using QuEChERS methodology, followed by HPLC with fluorescence detection. Some extraction parameters were studied, like the ratio of sample/solvent amounts, the homogenization time, the salt addition effect and the used sorbents. The validation parameters of the developed method were the following: a linearity range of 0.005–1.002 mg kg−1 sample, a limit of detection of 0.001 mg kg−1 sample, repeatability between 0.7% and 11.3% (variation coefficient of six standard injections), an intermediate precision of 2.5% (variation coefficient of six independent analysis of the same sample), mean recoveries ranging from 65% (soap bar) to 95% (body cream) and 3% of global uncertainty in most of the working range. The time of analysis, including the extraction steps, is 60 min, allowing a throughput of 4 samples h−1. Galaxolide was detected in all of the seven analysed products in concentrations ranging from 0.04 ± 0.01 mg kg−1 sample (toothpaste) to 280.78 ± 8.19 mg kg−1 sample (perfumed body cream), which may correspond to a significant estimated daily human dermal exposure of 904 μg day−1.
Long‐Run Stock and Operating Performance of Underwriter Warrants: Evidence from Seasoned Equity Offerings
Authors: Bae Sung C. , Chang Kiyoung , Jo Hoje
Published: February 2013

We examine the long‐run stock and operating performance of firms issuing underwriter warrants. Using matched samples, we found significant long‐run underperformance of seasoned equity offerings (SEOs) with warrant compensation, relative to SEOs with cash compensation, following offering announcements. Profitability measures of firms issuing underwriter warrants are also significantly lower over the post‐offering period. In sharp contrast to these results, growth measures of warrant‐issuing firms are greater for both pre‐ and post‐offering periods. Combined together, our results suggest that underwriter warrants are offered in a way to take advantage of the higher growth potential of issuing firms in the short term, whose growth trend is, however, transitory and not materialized into higher stock or operating performance over the long‐run, post‐offering period. We interpret our results as suggesting that the certification effect of SEOs with warrant compensation through growth signaling does not last in the long run. We further offer a behavioral approach as explanations of the short‐run outperformance of SEO firms with warrant compensation with empirical evidence supporting the Miller's divergence of opinion hypothesis.
A ‘Property‐Owning Democracy’ or ‘Generation Rent’?
Authors: Lund Brian
Published: February 2013

‘A property owning democracy’ has been at the centre of Conservative Party social policy since Noel Skelton coined the phrase in 1924. The idea has been underpinned by contrasting the independent, hygienic, suburban homeowner with the urban, managed, flat‐dwelling, high‐density council tenant. No Conservative‐led government has left office with a homeownership rate lower than when it came to power and the right to buy has enabled this growth to be maintained. However, in 2005, homeownership started to decline and this drop has continued into the Coalition government's term of office with more households now exiting owner‐occupation into the private landlord sector than entering owner‐occupation from private renting. The ‘reinvigorating’ the right to buy is an attempt put a ‘property owning democracy’ back on track but, should it fail, the Conservative Party may turn to more radical policies such as sale on vacant possession of ‘high value’ local authority and housing association houses.
Public Opinion and Military Intervention: Afghanistan, Iraq and Libya
Authors: Clements Ben
Published: February 2013

Britain has participated in several military interventions of varying duration, extent and political controversy in recent years. This article analyses public opinion towards the most recent intervention in Libya in 2011, looking at three different aspects of the topic. First, it examines differences in cross‐national attitudes towards military action in Libya amongst NATO countries. Secondly, it then looks in detail at which social groups were more or less likely to approve of British involvement, comparing this with group attitudes towards Britain's role in Afghanistan and Iraq. Thirdly, it assesses how public opinion shifted during the course of the action in Libya, looking at three key indicators of the popular mood: whether Britain was right or wrong to take military action; how well the war is going; and assessments of David Cameron's handling of the conflict. Broader reflections are then made about public opinion towards British involvement in future military action.
Arrogant Posh Boys? The Social Composition of the Parliamentary Conservative Party and the Effect of Cameron's ‘A’ List
Authors: Hill Michael
Published: February 2013

In the light of the recent controversy over Andrew Mitchell's alleged ‘pleb’ comments to police officers and Nadine Dorries’ characterisation of David Cameron and George Osborne as ‘arrogant posh boys, this article examines the social composition of the parliamentary Conservative Party. It looks at previous attempts to widen the social base of the PCP and analyses the effect of Cameron's priority or ‘A’ list of candidates on the composition of the 2010 PCP. The article asks whether the perception that the Conservatives are the party of the rich has damaged the party's electoral appeal and if so what can be done to rectify the situation.
Visual Perspectives on Majority‐World Adolescent Thriving
Authors: Cameron Catherine Ann , Theron Linda , Tapanya Sombat , Li Chun , Lau Cindy , Liebenberg Linda , Ungar Michael
Published: February 2013

This paper offers socio‐ecological, situated perspectives on adolescent resilience derived from an application of interpretive visual methodologies to deepen understanding of adaptive youth development in diverse majority‐world cultural contexts (SouthAfrica,Thailand,China,Mexican migration toCanada). The research is not “cross‐cultural”; by contrast, it situates youth engagement contextually, using local perspectives, especially perspectives of adolescents themselves, on “growing up well” under adverse circumstances, to interrogate conceptions of resilience in cultural context. Participants are viewed as members of cultural communities: observations with a small number of individuals are not generalized to national groups. Rather, knowledge gained by these methods is employed to enrich knowledge of the processes of majority‐world youth thriving despite such adversities as poverty and social displacement.
Future Discounting by Slum‐Dwelling Youth Versus University Students in Rio de Janeiro
Authors: Ramos Dandara , Victor Tânia , Seidl‐de‐Moura Maria Lucia , Daly Martin
Published: February 2013

We compared Future Discounting (FD, preference for smaller, sooner rewards over larger, later ones) by 160 Brazilian youth (16–30 years old; 71 women and 89 men). University students and slum‐dwelling (favela) youth were compared. Participants completed a monetary FD task, a scale of youngsters′ view of their neighborhood, and self‐reported exposure to violence (EV). Favela youth discounted the future more than students; favela men more than women. However, university women discounted more than men, an unexpected result. Predicted differences in the participants′ view of their neighborhood between the two groups were observed. The interaction context × EV scores was a significant predictor of FD. These youth have apparently adjusted trade‐offs between the short and long term in a context‐sensitive, adaptive manner.
Building Developmental Assets to Empower Adolescent Girls in Rural Bangladesh: Evaluation of Project Kishoree Kontha
Authors: Scales Peter C. , Benson Peter L. , Dershem Larry , Fraher Kathleen , Makonnen Raphael , Nazneen Shahana , Syvertsen Amy K. , Titus Sarah
Published: February 2013

Kishoree Kontha (“Adolescent Girls' Voices”) was implemented in Bangladeshi villages to build the developmental assets (e.g., support from others, social competencies) of rural girls through peer education in social skills, literacy, and school learning. The Developmental Assets Profile (DAP) measured the project's impact on ecological and individual assets. Analysis of two cohorts involving more than 600 intervention and 400 control adolescents (Mage = 13.5) showed a significant increase in project girls' developmental assets, with an average effect size, net of contamination and control group scores, of .80. The results suggest the Project's effectiveness in improving human and social capital for vulnerable adolescent girls living in rural Bangladesh villages, and the utility of the DAP as a cross‐culturally relevant measurement tool.
Stress With Parents and Peers: How Adolescents From Six Nations Cope With Relationship Stress
Authors: Seiffge‐Krenke Inge , Persike Malte , Karaman Neslihan Güney , Cok Figen , Herrera Dora , Rohail Iffat , Macek Petr , Hyeyoun Han
Published: February 2013

This study investigated how 2000 adolescents from middle‐class families in six countries perceived and coped with parent‐related and peer‐related stress. Adolescents from Costa Rica, Korea, and Turkey perceived parent‐related stress to be greater than peer‐related stress, whereas stress levels in both relationship types were similar in the Czech Republic, Germany, and Pakistan. Female adolescents predominantly reported higher levels of peer‐related stress than male adolescents. Adolescents in all countries used negotiating and support‐seeking to cope with relationship stress more often than emotional outlet or withdrawal. Withdrawal occurred more often to deal with parent‐related than with peer‐related stress. Results suggest that adolescents across countries competently coped with relationship stress. However, patterns of what adolescents perceived as stressful and how they coped varied between countries.
Angiographic and Clinical Outcomes after Implantation of Drug Eluting Stents in Bifurcation Lesions with Crush or Kissing Stent Technique
Authors: CHEEMA ASIM N. , JOLLY SANJIT S. , BURSTEIN JASON M. , SHARIEFF WASEEM , MOHAMMAD ATIF , YEOH EUNICE , MANCINI G.B. JOHN , CANTOR WARREN J. , KUTRYK MICHAEL J.B. , STRAUSS BRADLEY H. , CHISHOLM ROBERT J.
Published: February 2013

Background

Long‐term outcome after bifurcation stenting with drug‐eluting stents (DES) for obstructive coronary artery disease is poorly understood. In this study, we report 6–9‐month angiographic follow‐up and long‐term clinical outcomes after implantation of drug‐eluting stents by crush and kissing stent technique for coronary bifurcation lesions.

Methods

Consecutive patients undergoing bifurcation stenting with DES by crush or kissing stent technique were enrolled in a prospective registry. Angiographic follow‐up was obtained at 6–9 months and clinical follow‐up completed for a median of 38 months.

Results

A total of 86 patients participated in the study. Bifurcation stenting by crush technique was performed in 73 (85%) and by kissing stent in 13 (15%) patients. Stenting of left main bifurcation was applied in 24 (28%) patients. Angiographic follow‐up was completed in 75 (87%) patients and showed restenosis in the main for 8 (11%) and side branch for 20 (27%) patients. Clinical follow‐up was available for a median duration of 38 months. During follow‐up, 2 (2%) patients died, 4 (5%) experienced myocardial infarction (MI), and 11 (13%) underwent target vessel revascularization (TVR) with an overall major adverse cardiac event (MACE) rate of 16%. In left main cohort, angiographic restenosis occurred in 9 (37%) patients, and 3 (12%) patients required TVR. There were no deaths or stent thrombosis. A comparison of crush and kissing stent technique showed significantly higher angiographic restenosis with crush (26% vs 13% in kissing stent patients, P = 0.046) and 95% of restenosis in crush group involved ostium of the side branch. There was no difference in clinical outcomes between the crush and kissing stent groups. Final kissing balloon dilatation (FKB) was successful in 65 (89%) patients in the crush group and associated with a significant reduction in MACE (8% in FKB successful vs 37% in FKB unsuccessful, P = 0.04) during follow‐up.

Conclusion

Bifurcation stenting with crush or kissing stent technique is safe and associated with a low rate of TLR and MACE on long‐term follow‐up. Crush stenting is associated with a significantly higher rate of side branch restenosis compared to kissing stent technique. FKB is associated with significant reduction in MACE during follow‐up. (J Interven Cardiol 2013;26:145–152)
Perceptions of Effective Support Services to Families with Disabled Children whose Behaviour is Severely Challenging: A Multi‐Informant Study
Authors: McConkey Roy , Gent Clare , Scowcroft Emma
Published: February 2013

Background

Specialist short break services aim to provide enhanced support to family carers as a means of preventing children whose behaviours severely challenge from being placed in full‐time residential care. To date, there is limited evidence as to the functioning and effectiveness of such services.

Methods

In all, 17 children were selected at random from the 123 who were currently receiving services or had done so in the past 2 years from three specialist short break and community support services. For each child, interviews were conducted with a parent, the child's key worker within the service and the professional (mostly social workers) who had referred families to the services.

Results

Five core themes captured the informants’ common experiences: the complexities underlying the provision of services; the negotiations required to implement, maintain and adjust service packages; the relationships forged by the services; and the benefits they brought to children and families plus concerns about the future also featured.

Conclusions

Specialist short break services can make a vital contribution to retaining children within their families, but under some important conditions which this study has identified: notably, the management of complexity, the formation of trusted relationships and creation of tangible benefits for the family and for the child.
Family history of diabetes, lifestyle factors, and the 7‐year incident risk of type 2 diabetes mellitus in middle‐aged Japanese men and women
Authors: Sakurai Masaru , Nakamura Koshi , Miura Katsuyuki , Takamura Toshinari , Yoshita Katsushi , Sasaki Satoshi , Nagasawa Shin‐ya , Morikawa Yuko , Ishizaki Masao , Kido Teruhiko , Naruse Yuchi , Suwazono Yasushi , Nakagawa Hideaki
Published: February 2013

Aims/Introduction

This cohort study of middle‐aged Japanese participants investigated the relationship between family history of diabetes, the incident risk of type 2 diabetes and the interaction of these variables with other factors.

Materials and Methods

Study participants were 3,517 employees (2,037 men and 1,480 women) of a metal products factory in Japan. Baseline health examinations included questions about medical history, physical examination, anthropometric measurements, questions about lifestyle factors, such as smoking, alcohol consumption and habitual exercise, and a self‐administered diet history questionnaire. Family history of diabetes was defined as having at least one‐first‐degree relative with diabetes. The incidence of diabetes was determined in annual medical examinations over a 7‐year period. Hazard ratios (HRs) for type 2 diabetes were estimated by Cox proportional hazards analysis.

Results

Of the 3,517 participants, 630 (18%) had a family history of diabetes mellitus. During the study, 228 participants developed diabetes. The age and sex‐adjusted HR for type 2 diabetes in participants with a family history of diabetes was 1.82 (95% confidence interval 1.36–2.43) as compared with those without a family history of diabetes. HRs did not change after adjustment for body mass index and lifestyle factors. We found no interactions with body mass index, insulin resistance, pancreatic β‐cell function or lifestyle factors.

Conclusions

Family history of diabetes was associated with the incident risk of diabetes, and these associations were independent of other risk factors, such as obesity, insulin resistance, and lifestyle factors in Japanese men and women.
Morningness–eveningness questionnaire score correlates with glycated hemoglobin in middle‐aged male workers with type 2 diabetes mellitus
Authors: Iwasaki Masato , Hirose Takahisa , Mita Tomoya , Sato Fumihiko , Ito Chiharu , Yamamoto Risako , Someya Yuki , Yoshihara Tomoaki , Tamura Yoshifumi , Kanazawa Akio , Kawamori Ryuzo , Fujitani Yoshio , Watada Hirotaka
Published: February 2013

Aims/Introduction

‘Morningness’ and ‘eveningness’ represent the sleep–wake patterns of the circadian rhythm might also affect glycemic control in patients with type 2 diabetes. The aim of this study was to examine the relationship between the morningness–eveningness trait and metabolic parameters.

Materials and Methods

The study participants comprised 101 Japanese male workers with type 2 diabetes treated in an outpatient clinic. Blood samples were obtained, and a morningness–eveningness questionnaire (MEQ), where a high score represents morningness; and the Pittsburg Sleep Quality Index (PSQI), where the higher the score the worse the sleep quality, were carried out.

Results

MEQ correlated positively with age, and high‐density lipoprotein cholesterol (HDL‐C), and negatively with glycated hemoglobin (HbA1c) and PSQI. Multivariate regression analysis showed that MEQ was significantly associated with HbA1c and HDL‐C. In addition, we classified the study patients into three groups: ‘morning type’, ‘neither type’ and ‘evening type’ according to the sum of the MEQ score, and analyzed the difference between morning type (n = 32) and evening type (n = 11). We found that HbA1c, low‐density lipoprotein cholesterol and PSQI of the morning type group were significantly lower than those of the evening type group.

Conclusions

The present study suggests that ‘eveningness’ type male Japanese workers with type 2 diabetes suffer inadequate glycemic control.
Targeting nascent soluble Aβ42 for potential Alzheimer drug development
Authors: Zhang Mingming , Hausmann Laura , Song Weihong
Published: February 2013

Read the full article ‘Amelioration of cognitive deficits in plaque‐bearing Alzheimer's disease model mice through selective reduction of nascent soluble Ab42 without affecting other Ab pools’ on doi: 10.1111/jnc.12125.
Loss of Bace2 in zebrafish affects melanocyte migration and is distinct from Bace1 knock out phenotypes
Authors: van Bebber Frauke , Hruscha Alexander , Willem Michael , Schmid Bettina , Haass Christian
Published: February 2013

Alzheimer's disease is the most frequent dementia. Pathologically, Alzheimer's disease is characterized by the accumulation of senile plaques composed of amyloid β‐peptide (Aβ). Two proteases, β‐ and γ‐secretase proteolytically generate Aβ from its precursor, the ß‐amyloid precursor protein (APP). Inhibition of β‐secretase, also referred to as beta‐site APP cleaving enzyme (BACE1) or γ‐secretase is therefore of prime interest for the development of amyloid‐lowering drugs. To assess the in vivo function of zebrafish Bace1 (zBace1), we generated zBace1 knock out fish by zinc finger nuclease‐mediated genome editing. bace1 mutants (bace1−/−) are hypomyelinated in the PNS while the CNS is not affected. Moreover, the number of mechanosensory neuromasts is elevated in bace1−/−. Mutations in zebrafish Bace2 (zBace2) revealed a distinct melanocyte migration phenotype, which is not observed in bace1−/−. Double homozygous bace1−/−; bace2−/− fish do not enhance the single mutant phenotypes indicating non‐redundant distinct physiological functions. Single homozygous bace1 mutants as well as double homozygous bace1 and bace2 mutants are viable and fertile suggesting that Bace1 is a promising drug target without major side effects. The identification of a specific bace2 −/− associated phenotype further allows improving selective Bace1 inhibitors and to distinguish between Bace 1 and Bace 2 inhibition in vivo.

image

Inhibition of BACE1 protease activity has therapeutic importance for Alzheimer's disease. Analysis of BACE1 and BACE2 knock‐out zebrafish revealed that they exhibit distinct phenotypes. bace1 mutants display hypomyelination in the PNS and supernumerary neuromasts while in bace2 mutants the shape and migration of melanocytes is affected. These phenotypes are not further enhanced in the viable double mutants. Our data suggest that blocking BACE1 activity is a safe therapeutic approach.
Inhibition of neuronal nitric oxide synthase activity promotes migration of human‐induced pluripotent stem cell‐derived neural stem cells toward cancer cells
Authors: Chen Can , Wang Yi , Goh Sally S. L. , Yang Jing , Lam Dang Hoang , Choudhury Yukti , Tay Felix Chang , Du Shouhui , Tan Wee Kiat , Purwanti Yovita Ida , Fan Weimin , Wang Shu
Published: February 2013

The breakthrough in derivation of human‐induced pluripotent stem cells (hiPSCs) provides an approach that may help overcome ethical and allergenic challenges posed in numerous medical applications involving human cells, including neural stem/progenitor cells (NSCs). Considering the great potential of NSCs in targeted cancer gene therapy, we investigated in this study the tumor tropism of hiPSC‐derived NSCs and attempted to enhance the tropism by manipulation of biological activities of proteins that are involved in regulating the migration of NSCs toward cancer cells. We first demonstrated that hiPSC‐NSCs displayed tropism for both glioblastoma cells and breast cancer cells in vitro and in vivo. We then compared gene expression profiles between migratory and non‐migratory hiPSC‐NSCs toward these cancer cells and observed that the gene encoding neuronal nitric oxide synthase (nNOS) was down‐regulated in migratory hiPSC‐NSCs. Using nNOS inhibitors and nNOS siRNAs, we demonstrated that this protein is a relevant regulator in controlling migration of hiPSC‐NSCs toward cancer cells, and that inhibition of its activity or down‐regulation of its expression can sensitize poorly migratory NSCs and be used to improve their tumor tropism. These findings suggest a novel application of nNOS inhibitors in neural stem cell‐mediated cancer therapy.
Alzheimer's Aβ42 and Aβ40 peptides form interlaced amyloid fibrils
Authors: Gu Lei , Guo Zhefeng
Published: February 2013

Deposition of amyloid β (Aβ) in the brain is a pathological hallmark of Alzheimer's disease. There are two major isoforms of Aβ: the 42‐residue Aβ42 and the 40‐residue Aβ40. The only difference between Aβ42 and Aβ40 is that Aβ42 has two extra residues at the C‐terminus. The amyloid plaques in Alzheimer's brains consist of mostly Aβ42 and some plaques contain only Aβ42, even though Aβ40 concentration is several‐fold more than Aβ42. Using electron paramagnetic resonance, we studied the formation of amyloid fibrils using a mixture of Aβ42 and Aβ40 in vitro. We show that Aβ42 and Aβ40 form mixed fibrils in an interlaced manner, although Aβ40 is not as efficient as Aβ42 in terms of being incorporated into Aβ42 fibrils. Our results suggest that both Aβ42 and Aβ40 would be present in amyloid plaques if in vivo aggregation of Aβ were similar to the in vitro process. Therefore, there must be some mechanisms that lead to the preferential deposition of Aβ42 at the extracellular space. Identifying such mechanisms may open new avenues for therapeutic interventions to treat Alzheimer's disease.
Inflammatory factors gene polymorphism in recurrent oral ulceration
Authors: Sun Mao , Fu Shan‐Min , Dong Guang‐Ying , Wu Dan , Wang Guo‐Xia , Wu Yuanming
Published: February 2013

Background

Some inflammatory factors play an important role in recurrent oral ulceration (ROU). The genetics mechanism of expression level of inflammatory factors is not clear in ROU, but from genetics the expression level of inflammatory factors at least partly depend on the gene polymorphisms. Therfore, we decided to investigate inflammatory factors gene polymorphism and its association with the susceptibility of recurrent oral ulceration in Chinese.

Methods

Genomic DNA was obtained from 42 subjects with recurrent oral ulceration, 86 subjects of healthy control individuals.Genotypes and alleles of 10 genes and 17 polymorphisms sites were analyzed by Mass‐ARRAY Analyzer method. Then, the differences in distribution of each genotype and allele were compared.

Results

The statistical differences in distribution of TNF‐α (rs1800629 and rs1800630) genotype and allele were observed among the groups with recurrent oral ulceration and healthy control individuals (P < 0.01), while VEGFA (rs1570360, rs833061, and rs2010963), EGF (rs4444903), TNF (rs361525), IL10 (rs1800896, rs1800872), IL2 (rs2069762), IL4 (rs2243250), Fas (rs1800682, rs2234767), IL12A (rs2243115, rs568408), IL12B (rs3212227), and IFNG (rs2430561) showed no statistical differences of genotype and allele in controls as compared to those in patients.

Conclusions

This study suggests that the TNF‐α (rs1800629 and rs1800630) genotype is an indicator for the susceptibility of recurrent oral ulceration.
Decline in pulmonary function during chronic hepatitis C virus therapy with modified interferon alfa and ribavirin
Authors: Foster G. R. , Zeuzem S. , Pianko S. , Sarin S. K. , Piratvisuth T. , Shah S. , Andreone P. , Sood A. , Chuang W.‐L. , Lee C.‐M. , George J. , Gould M. , Flisiak R. , Jacobson I. M. , Komolmit P. , Thongsawat S. , Tanwandee T. , Rasenack J. , Sola R. , Messina I. , Yin Y. , Cammarata S. , Feutren G. , Brown K. K.
Published: February 2013

Rare interstitial lung disease cases have been reported with albinterferon alfa‐2b (albIFN) and pegylated interferon alfa‐2a (Peg‐IFNα‐2a) in chronic hepatitis C virus (HCV) patients. Systematic pulmonary function evaluation was conducted in a study of albIFN q4wk vs Peg‐IFNα‐2a qwk in patients with chronic HCV genotypes 2/3. Three hundred and ninety‐one patients were randomly assigned 4:4:4:3 to one of four, open‐label, 24‐week treatment groups including oral ribavirin 800 mg/d: albIFN 900/1200/1500 μg q4wk or Peg‐IFNα‐2a 180 μg qwk. Standardized spirometry and diffusing capacity of the lung for carbon monoxide (DLCO) were recorded at baseline, weeks 12 and 24, and 6 months posttreatment, and chest X‐rays (CXRs) at baseline and week 24. Baseline spirometry and DLCO were abnormal in 35 (13%) and 98 (26%) patients, respectively. Baseline interstitial CXR findings were rare (4 [1%]). During the study, clinically relevant DLCO declines (≥15%) were observed in 173 patients (48%), and were more frequent with Peg‐IFNα‐2a and albIFN 1500 μg; 24 weeks posttreatment, 57 patients (18%) still had significantly decreased DLCO, with a pattern for greater rates with albIFN vs Peg‐IFNα‐2a. One patient developed new interstitial CXR abnormalities, but there were no clinically relevant interstitial lung disease cases. The risk of persistent posttreatment DLCO decrease was not related to smoking, alcohol, HCV genotype, sustained virologic response, or baseline viral load or spirometry. Clinically relevant DLCO declines occurred frequently in chronic HCV patients receiving IFNα/ribavirin therapy and commonly persisted for ≥6 months posttherapy. The underlying mechanism and clinical implications for long‐term pulmonary function impairment warrant further research.
A perturbation of multimodal GABA functions underlying the formation of focal cortical malformations: Assessments by using animal models
Authors: Fukuda Atsuo , Wang Tianying
Published: February 2013

In order to study how the formation of focal cortical malformations is attributed to perturbation of developmentally multimodal γ‐aminobutyric acid (GABA) functions, we made a focal cortical freeze‐lesion on a rodent cerebral cortex at P0 (postnatal day 0). The microgyrus was formed at P7. GABA neurons were accumulated in the region surrounding necrosis at P4. Cortical plate cells born at E17.5 gathered, surrounding the GABA neurons, forming the cell dense portions in layer 2 of the microgyrus. Ambient GABA level was increased in the area corresponding to populated GABA neurons at P4. A KCC2 expression was downregulated, whereas an NKCC1 expression was upregulated in both the gathering GABA and cortical plate neurons, suggesting these cells had high intracellular Cl− concentration rendering GABA action depolarizing. GABAA receptor activation was involved in Ca2+ oscillation in these gathering cells. In vivo blockade of GABAA receptor prevented the above characteristic pattern of cell accumulation and hence microgyrus formation. Thus, neonatal freeze‐lesion causes characteristic accumulation of differential populations of neurons preceded by characteristic release of GABA at an early stage, which induces GABAA receptor‐mediated depolarization and Ca2+ oscillation. This paracrine/autocrine GABA may underlie the formation of neocortical malformations such as polymicrogyria.
Development of a nursing model for life adjustment in patients with lung cancer inJapan
Authors: Horii Naoko , Maekawa Atsuko
Published: February 2013

The aim of this study was to obtain basic data about the support for life adjustment in lung cancer patients inJapan. We identified factors that affect life adjustment in people with lung cancer, developed a model for life adjustment support of lung cancer patients, and investigated its validity. A survey was conducted using self‐completed questionnaires, and responses were received by 203 individuals. Analysis of the responses revealed that life adjustment was regulated by six factors associated with positive self‐evaluation: stress dissipation, fighting spirit, helplessness/hopelessness, full discussion with doctor about treatment, clarity of thought, and support network size. A model search with covariance structure analysis was conducted. The resulting model was revealed to have a goodness‐of‐fit index of 0.963, an adjusted goodness‐of‐fit index of 0.930, a comparative fit index of 0.974, and a root mean square error of approximation of 0.040. The findings suggest that improvements in quality of life can be expected by combining a positive self‐evaluation in lung cancer patients and interventions to raise self‐adjustment ability with the use of this Model, although it requires further testing.
Taxes and Benefits: Two Options to Cheat on the State
Authors: Halla Martin , Schneider Friedrich G.
Published: February 2013

In this article we study the social norms to abstain from cheating on the state via benefit fraud and tax evasion. We interpret these norms (called benefit morale and tax morale) as moral goods, and derive testable hypotheses on whether their demand is determined by prices. Employing a large survey data set from OECD‐member countries we provide robust evidence that the demand responds to price proxy variables as predicted by theory. The main general conclusion of this article is that social norms (which are widely accepted as determinants of individual economic behaviour) are themselves influenced by economic factors.
Clinical evaluation of fitting toric soft contact lenses to current non‐users
Authors: Sulley Anna , Young Graeme , Lorenz Kathrine Osborn , Hunt Chris
Published: February 2013

Purpose

To evaluate the ease with which astigmats from three groups of current non‐wearers of toric contact lenses can be fitted with current toric soft lenses, and to determine toric lens‐wearing success.

Methods

This was a 1‐month, randomized, bilateral, open‐label, daily wear study involving 200 subjects and 16 investigational sites in the UK. Three groups of astigmatic subjects aged from 16 to 60 and with a mean age of 36 years (67 spherical soft contact lens users, SW; 72 contact lens drop‐outs, DO; and 61 neophytes, Neo) were fitted with one of two toric soft lens types: a daily disposable toric soft lens (1 Day Acuvue Moist for Astigmatism, Johnson & Johnson Vision Care) or a 2‐weekly replacement, re‐usable toric soft lens (Acuvue Oasys for Astigmatism, Johnson & Johnson Vision Care). Subjects were evaluated after 1 month of wear and success rates calculated according to pre‐set criteria for acceptable fit, orientation stability, visual acuity, quality of vision, and overall comfort.

Results

Eighty‐eight percent of lenses were fitted at the first attempt. Of 198 subjects dispensed with lenses, 182 (92%) completed the study. When analysed by subject group, the success rates according to the pre‐set criteria were 80% (53/66), 74% (52/70), and 70% (39/56) for the SW, DO and Neo groups respectively. Comfort was the most common reason for failure with all three groups; however, visual problems were more common in the DO and Neo groups (13% vs 6%). VA with the study lenses was significantly better in the SW group compared to their habitual lenses. For the DO and Neo groups combined (i.e. spectacle wearers), visual acuity was comparable to their habitual spectacles.

Conclusions

A high proportion of astigmats who are not using toric soft contact lenses can be fitted with current lenses. Previous contact lens drop‐outs and neophyte wearers achieve visual acuity comparable to spectacles when fitted with toric soft lenses. Spherical contact lens wearing astigmats achieve superior visual acuity when refitted with toric soft lenses. These findings suggest that many astigmats who are not currently using toric soft contact lenses could do so successfully.
Genetic variation for secondary seed dormancy and seed longevity in a set of black‐seeded European winter oilseed rape cultivars
Authors: Schatzki Jörg , Allam Mai , Klöppel Coretta , Nagel Manuela , Börner Andreas , Möllers Christian
Published: February 2013

Secondary seed dormancy in oilseed rape is a phenomenon that allows seeds to survive in the soil for many years without germination. Following soil cultivation, dormant seeds may germinate in subsequent years, and they are the main reason for the occurrence of volunteer oilseed rape plants in successive crops. Inheritance of secondary dormancy may be related to seed longevity (SL) in the soil. Genetic reduction in secondary dormancy and SL could provide a mean to reduce the frequency of volunteer plants and especially the dispersal of transgenic oilseed rape. The aim of the present study was to analyse secondary dormancy, germination rate and SL of 28 black‐seeded winter oilseed rape cultivars using in vitro laboratory tests. The material was tested in field experiments at six different locations in Germany in 2008/2009. Significant effects of the genotype and the location on all traits were found. Heritability was high for secondary dormancy (0.97) and moderate for germination rate (0.70) and SL (0.71). Results indicate that a selection for low secondary dormancy would be effective.
Is There a Role for the Detection of Autoantibodies in the Clinical Practice of Treating Infants with Bullous Pemphigoid? A Case Report
Authors: Brazzelli Valeria , Grasso Vincenzo , Bossi Grazia , Borroni Giovanni
Published: February 2013

We present a case of infantile bullous pemphigoid (BP) triggered by primary infection with varicella zoster virus and we analyze the correlation between autoantibody levels and disease activity. With this report we suggest that serum autoantibody titers may not necessarily mirror the clinical course of the disease or represent a helpful tool in guiding therapeutic decisions in infantile BP.
Congenital Circumscribed Acral Hypokeratosis
Authors: Santamarina‐Albertos Alba , Noguera‐Morel Lucero , Feito‐Rodríguez Marta , Beato‐Merino María‐José , de Lucas‐Laguna Raúl
Published: February 2013

Circumscribed acral hypokeratosis (CAH) is a rare dermatosis that typically appears as well‐dermarcated erythema with a scaly border on the palms or soles of middle‐age patients. A pediatric case of CAH has been recently reported in a 10‐year‐old boy affecting the medial foot since birth. In this report we describe the second congenital case of CAH on the sole.
Propranolol and Infantile Hemangiomas Four Years Later: A Systematic Review
Authors: Marqueling Ann L. , Oza Vikash , Frieden Ilona J. , Puttgen Katherine B.
Published: February 2013

To systematically review the literature evaluating efficacy and adverse events of propranolol treatment for infantile hemangiomas, we searched the MEDLINE and Cochrane databases for all studies examining the response of infantile hemangiomas (IHs) to propranolol published between June 12, 2008, and June 15, 2012. Forty‐one studies with 1,264 patients were included; 74% of patients were female and approximately 30% had received other treatments before propranolol. Propranolol was initiated at a mean age of 6.6 months at a mean dose of 2.1 mg/kg/day and for a mean treatment duration of 6.4 months. The response rate for patients with IHs treated with propranolol was 98% (range 82%–100%), with response rate defined as any improvement with propranolol. Treatment response rates were comparable for studies evaluating IHs at specific sites, such as periorbital IHs. Studies that followed patients after treatment completion reported IH rebound growth in 17% of patients. There were 371 adverse events reported in 1,189 patients. The most common adverse events were changes in sleep (n = 136) and acrocyanosis (n = 61). Serious adverse events were rare, with reports of symptomatic hypotension in five patients, hypoglycemia in four, and symptomatic bradycardia in one. This systematic review of 1,264 patients treated with propranolol for IHs showed a high rate of efficacy and a low rate of serious adverse events.
Severe Encephalopathy Following Cerebral Arteriogram in a Patient with End‐Stage Renal Disease
Authors: Yan Jingyin , Ramanathan Venkat
Published: February 2013

Disruption of blood brain barrier (BBB) with subsequent subarachnoid contrast extravasation and cerebral edema is a rare complication of intra‐arterial contrast administration. We report a patient with end‐stage renal disease (ESRD) who developed such a complication. A 63‐year‐old man with a history of left orbital apex syndrome on hemodialysis (HD) was admitted with massive epistaxis. A pseudo‐aneurysm of the left internal carotid artery (ICA) required a cerebral arteriogram with coil embolization; a total of 910 ml of isosmolar intra‐arterial contrast was used. Shortly thereafter, the patient developed severe alteration in his mental status. A CT study without contrast of the head showed bilateral subarachnoid hyper‐attenuation with diffuse cerebral edema consistent with contrast‐induced encephalopathy syndrome. The patient was urgently and repetitively dialyzed to remove the contrast leading to a remarkable improvement in his mental status and resolution of both subarachnoid hyper‐attenuation and brain edema. The large volume of intra‐arterial contrast that may be required in neurologic interventional procedures is occasionally associated with breakdown of BBB leading to subarachnoid accumulation and cerebral edema resulting in a severe encephalopathy syndrome. Hemodialysis seems particularly well suited for the patient who has renal failure in whom this syndrome develops.
Auxin controls Arabidopsis anther dehiscence by regulating endothecium lignification and jasmonic acid biosynthesis
Authors: Cecchetti Valentina , Altamura Maria Maddalena , Brunetti Patrizia , Petrocelli Valentina , Falasca Giuseppina , Ljung Karin , Costantino Paolo , Cardarelli Maura
Published: February 2013

It has been suggested that, in Arabidopsis, auxin controls the timing of anther dehiscence, possibly by preventing premature endothecium lignification. We show here that auxin content in anthers peaks before the beginning of dehiscence and decreases when endothecium lignification occurs. We show that, in the auxin‐perception mutants afb1‐3 and tir1 afb2 afb3, endothecium lignification and anther dehiscence occur earlier than wild‐type, and the gene encoding the transcription factor MYB26, which is required for endothecium lignification, is over‐expressed specifically at early stages; in agreement, MYB26 expression is reduced in naphthalene acetic acid‐treated anthers, and afb1 myb26 double mutants show no endothecial lignification, suggesting that auxin acts through MYB26. As jasmonic acid (JA) controls anther dehiscence, we analysed how auxin and JA interact. In the JA‐defective opr3 mutant, indehiscent anthers show normal timing of endothecium lignification, suggesting that JA does not control this event. We show that expression of the OPR3 and DAD1 JA biosynthetic genes is enhanced in afb1‐3 and tir1 afb2 afb3 flower buds, but is reduced in naphthalene acetic acid‐treated flower buds, suggesting that auxin negatively regulates JA biosynthesis. The double mutant afb1 opr3 shows premature endothecium lignification, as in afb1‐3, and indehiscent anthers due to lack of JA, which is required for stomium opening. By treating afb1 opr3 and opr3 inflorescences with JA, we show that a high JA content and precocious endothecium lignification both contribute to induction of early anther dehiscence. We propose that auxin controls anther dehiscence timing by negatively regulating two key events: endothecium lignification via MYB26, and stomium opening via the control of JA biosynthesis.