bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of emotional, physical and sexual abuse among pregnant women in six European countries
Authors: Lukasse Mirjam , Schroll Anne‐Mette , Ryding Elsa Lena , Campbell Jacquelyn , Karro Helle , Kristjansdottir Hildur , Laanpere Made , Steingrimsdottir Thora , Tabor Ann , Temmerman Marleen , Van Parys An‐Sofie , Wangel Anne‐Marie , Schei Berit
Published: April 2014

Objectives

The primary objective was to investigate the prevalence of a history of abuse among women attending routine antenatal care in six northern European countries. Second, we explored current suffering from reported abuse.

Design

A prospective cohort study.

Setting

Routine antenatal care in Belgium, Iceland, Denmark, Estonia, Norway, and Sweden between March 2008 and August 2010.

Population

A total of 7174 pregnant women.

Methods

A questionnaire including a validated instrument measuring emotional, physical and sexual abuse.

Main outcome measure

Proportion of women reporting emotional, physical and sexual abuse. Severe current suffering defined as a Visual Analogue Scale score of ≥6.

Results

An overall lifetime prevalence of any abuse was reported by 34.8% of the pregnant women. The ranges across the six countries of lifetime prevalence were 9.7–30.8% for physical abuse, 16.2–27.7% for emotional abuse, and 8.3–21.1% for sexual abuse. Few women reported current sexual abuse, 0.4% compared with 2.2% current physical abuse and 2.7% current emotional abuse. Current severe suffering was reported by 6.8% of the women who reported physical abuse, 9.8% of those who reported sexual abuse and 13.5% for emotional abuse.

Conclusion

A high proportion of pregnant women attending routine antenatal care report a history of abuse. About one in ten of them experiences severe current suffering from the reported abuse. In particular, these women might benefit from being identified in the antenatal care setting and being offered specialized care.
Numerical Estimation of Hemolysis From the Point of View of Signal and System
Authors: Li Huan , Ruan Xiaodong , Qian Wenwei , Fu Xin
Published: April 2014

The power‐law based models for predicting shear‐induced hemolysis are widely used in the optimization design of blood‐contacting devices. However, this category of models has fallen short of accuracy when compared with the results of the in vitro experiments. The aim of this study is to develop an alternative model from the point of view of signal and system. Under the action of constant shear stress, the released hemoglobin was regarded as the output of system, and the system function that characterized the resistance to hemolysis was derived from the power‐law equation. Two state variables were introduced to adequately capture the history of the system. The proposed model takes into account another known empirical formula, the threshold equation, by setting a nonzero initial condition of the blood. By comparing the estimated results with the published experimental data, it showed that the accuracy of the proposed model was notably improved. Furthermore, the analysis in frequency domain indicated that the damage contribution of the time‐varying shear stress decreased with the increase of frequency. As the frequency domain analysis is important in many fields, it may play a role in the estimation of hemolysis in the future.
Direct Expansion of Chondrocytes in a Dynamic Three‐Dimensional Culture System: Overcoming Dedifferentiation Effects in Monolayer Culture
Authors: Gharravi Anneh Mohammad , Orazizadeh Mahmoud , Hashemitabar Mahmoud
Published: April 2014

Maintenance of the chondrocyte phenotype during cell culture to successful transplantation of cartilage is highly challenging. However, the question of the optimal method of isolation and expansion of chondrocytes for tissue engineering has not previously been investigated in detail. The present study investigates the possibility of improved in vitro maturation of chondrocytes through a method of cell duplication that does not subject chondrocytes to dedifferentiation. The culture chamber of the bioreactor was designed with an internal geometry that mimicked that of a ball‐and‐socket joint. The shear stresses exerted on the surface of the bioreactor chamber wall by a peristaltic pump operating at flow rates of 2 mL/min were simulated by computational fluid dynamics (CFD) modeling. Small pieces (5 mm) of calf nasal septum cartilage were prepared and exposed to trypsin and 0.2% collagenase type II in Dulbecco's modified Eagle's medium (DMEM), which was then replaced with unsupplemented DMEM. The cells were harvested and then immediately seeded into alginate scaffolds. All cell‐seeded scaffolds were cultured for 3–5 days in flasks, then transferred to the bioreactor and dynamically cultured for 3–5 days under direct perfusion with 2 mL/min DMEM. After culture in the bioreactor, all cell‐seeded scaffolds were fixed in Bouin fixative, dehydrated, cleared, and then embedded in paraffin wax. Sections of 5–7 μm were cut and stained with several histochemical staining methods. The results of CFD modeling indicated peak velocity and maximum wall shear stress were 3.406 × 10−3 m/s and 0.0482 dyn/cm2 (1 Pa = 10 dyn/cm2), respectively. Histological examination of chondrocytes cultured in the bioreactor revealed evidence of cartilage‐like tissue with lacuna and chondron formation. The cartilage‐like matrix had accumulated within the lumen of clusters of round mature chondrocytes, with the cells surrounding the metachromatic territorial matrix‐staining strongly with toluidine blue. Sections stained with the hematoxylin/safranin O/fast green and Alcian blue/nuclear fast red methods show sulfated glycosaminoglycans in the matrix (produced by the chondrocytes) as intense red and blue, respectively. The findings of the present study indicate that incubation in DMEM supplemented with enzymes followed by explant isolation and culture in a bioreactor is the optimal method for the direct expansion of chondrocytes for cartilage tissue engineering.
Activation of Basophils Is a New and Sensitive Marker of Biocompatibility in Hemodialysis
Authors: Aljadi Zenib , Mansouri Ladan , Nopp Anna , Paulsson Josefin M. , Winqvist Ola , Russom Aman , Ståhl Mårten , Hylander Britta , Jacobson Stefan H. , Lundahl Joachim
Published: April 2014

The hemodialysis procedure involves contact between peripheral blood and the surface of dialyzer membranes, which may lead to alterations in the pathways of innate and adaptive immunity. We aimed to study the effect of blood–membrane interaction on human peripheral basophils and neutrophils in hemodialysis with high‐ and low‐permeability polysulfone dialyzers. The surface expression of CD203c (basophil selection marker) and CD63 (activation marker) after activation by the bacterial peptide formyl‐methionyl‐leucyl‐phenylalanine (fMLP) or anti‐Fcε receptor I (FcεRI) antibody and the absolute number of basophils was investigated before and after hemodialysis with each of the dialyzers. Moreover, the expression on neutrophils of CD11b, the CD11b active epitope, and CD88 was analyzed in the same groups of individuals. The expression of CD63 in basophils following activation by fMLP was significantly higher in the patient group compared with that in healthy controls, but no differences were observed after activation by anti‐FcεRI. During the hemodialysis procedure, the low‐flux membrane induced up‐regulation of CD63 expression on basophils, while passage through the high‐flux membrane did not significantly alter the responsiveness. In addition, the absolute number of basophils was unchanged after hemodialysis with either of the dialyzers and compared with healthy controls. We found no significant differences in the expression of the neutrophil activation markers (CD11b, the active epitope of CD11b, and CD88) comparing the two different dialyzers before and after dialysis and healthy controls. Together, these findings suggest that alterations in basophil activity may be a useful marker of membrane bioincompatibility in hemodialysis.
The Hemodynamic Effect of Phase Differences Between the BJUT‐II Ventricular Assist Device and Native Heart on the Cardiovascular System
Authors: Gu Kaiyun , Gao Bin , Chang Yu , Zeng Yi
Published: April 2014

The BJUT‐II VAD (which was previously called the intra‐aorta pump) is a novel left ventricular assist device (LVAD) with a special structure and connection with the native heart. The hemodynamic effect of the phase difference of this pump on the cardiovascular system is still unclear. In this work, seven speed waveforms, whose phase differences vary from 0° to 180°, are used to evaluate the hemodynamic effect of change in phase difference on the cardiovascular system. The external work (EW), equivalent afterload (EAL), pulsatile ratio (PR), and mean aortic pressure during diastolic period (MAPD) are chosen to evaluate the hemodynamic state of the circulatory system. Mathematical study results show that the support levels generated by the BJUT‐II VAD under various phase differences are comparable. In contrast, EW, EAL, PR, and MAPD are significantly affected by change in phase difference. It is found that EW reaches its maximum value when the phase difference equals 30°. Similarly, EAL declines with increasing phase difference. PR reaches its maximum value when the phase difference is at 60°. In addition, MAPD decreases with increasing phase difference and then achieves its maximum value at 30°. To obtain comprehensive evaluation of the hemodynamic effects of phase difference on the cardiovascular system, a weight detection algorithm (WDA) whose output indicates the hemodynamic state of the circulatory system is also designed, with EW, PR, and MAPD chosen as the inputs. The minimum value of the output of the WDA indicates the optimal hemodynamic state and optimal phase difference for the BJUT‐II VAD. According to the output of the WDA, 30° is considered to be the optimal phase difference for the BJUT‐II VAD.
Platelet Function During Cardiopulmonary Bypass Using Multiple Electrode Aggregometry: Comparison of Centrifugal and Roller Pumps
Authors: Kehara Hiromu , Takano Tamaki , Ohashi Noburo , Terasaki Takamitsu , Amano Jun
Published: April 2014

Blood trauma may be lower with centrifugal pumps (CPs) than with roller pumps (RPs) during cardiopulmonary bypass (CPB), because, unlike RPs, CPs do not compress the tubing, and shear stress is considered lower in CPs than in RPs. However, relative platelet function remains unclear. Using multiple electrode aggregometry (MEA), we compared platelet function with CP and RP. Ten swine underwent CPB for 3 h, with five weaned off using CP and five using RP. Platelet function was measured using MEA, as were hemoglobin concentration and platelet count, before sternotomy, after heparin infusion, 30 min and 3 h after starting CPB, after protamine infusion, and 60 min after stopping CPB. Platelet activation was initiated with adenosine diphosphate (ADP), arachidonic acid (AA), and thrombin receptor‐activating protein 6 (TRAP). Fibrinogen, platelet factor 4 (PF4), and β‐thromboglobin (β‐TG) concentrations were measured before sternotomy and 60 min after stopping CPB. In the CP group and using ADP, aggregation was significantly reduced 30 min (P = 0.019) and 3 h (P = 0.027) after starting CPB, recovering to baseline 60 min after CPB was stopped. In the RP group, aggregation was significantly decreased 30 min (P = 0.007) and 3 h (P = 0.003) after starting CPB and after protamine administration (P = 0.028). With AA, aggregation significantly decreased 30 min after starting CPB in both the CP (P = 0.012) and RP (P = 0.016) groups, slightly increasing 3 h after starting CPB and after protamine infusion, and recovering to baseline 60 min after CPB cessation. With TRAP, aggregation in the CP and RP groups decreased 30 min after starting the pump, although changes were not significant; aggregation gradually recovered after 3 h and returned to baseline 60 min after the pumps were stopped. There were no significant differences at all sampling points of MEA. In both groups, fibrinogen, PF4, and β‐TG concentrations were similar 60 min after pump cessation and before sternotomy. Platelet function, evaluated with MEA, was lowest 30 min after CPB was started but did not decrease over time in either group. As assessed by MEA, platelet function using CP and RP did not differ significantly. Platelet dysfunction was caused mainly by initial contact with foreign materials and may not be dependent on type of pump.
Deconstructing Social Class in Economically, Racially, and Ethnically Diverse Schools
Authors: Cunningham Michael , Rious Jennifer B.
Published: April 2014

The commentary offers a critique of the strategy to have critical discussions about social class in schools without simultaneously considering racial and ethnic backgrounds of students and the teachers. By highlighting the unique opportunity afforded to South Bay Elementary to discuss these complex issues, we highlight an example of school that attempted similar discussions. We also offer developmental specific examples of how schools can attempt these difficult discussions.
Evaluation of Tunisian milk quality in dairy herds: Inter‐relationship between chemical, physical and hygienic criteria
Authors: Gargouri Ahmed , Hamed Houda , Ben Ali Besma , Elfeki Abdelfettah , Gdoura Radhouane
Published: April 2014

The objective of this paper was to evaluate the global milk quality in Tunisian dairy herds. Samples of milk were analyzed for chemical, physical and hygienic parameters. Milk total solids, fat content and density were consistently correlated and one of them can be used as a chemical indicator of milk quality. The somatic cell count value of 689 × 103/mL was higher than the recommended threshold. All milk samples were positive for the major pathogen Staphylococcus aureus. These hygienic parameters were related more closely with chloride content, minerals and electrical conductivity, which allows them to be used as indicators of mammary gland infection. It was concluded that milk producers have at hand rapid and easy tools for assessing the overall quality of milk.
Associations of novel genetic variations in the folate‐related and ARID5B genes with the pharmacokinetics and toxicity of high‐dose methotrexate in paediatric acute lymphoblastic leukaemia
Authors: Csordas Katalin , Lautner‐Csorba Orsolya , Semsei Agnes F. , Harnos Andrea , Hegyi Marta , Erdelyi Daniel J. , Eipel Oliver T. , Szalai Csaba , Kovacs Gabor T.
Published: April 2014

High‐dose methotrexate (HD‐MTX) plays an important role in the consolidation therapy of acute lymphoblastic leukaemia (ALL) in many treatment regimens worldwide. However, there is a large interpatient variability in the pharmacokinetics and toxicity of the drug. We investigated the influence of single nucleotide polymorphisms (SNPs) in genes of the folate metabolic pathway, transporter molecules and transcription proteins on the pharmacokinetics and toxicity of MTX and 7‐hydroxy‐methotrexate (7‐OH‐MTX). 63 SNPs of 14 genes were genotyped and a total of 463 HD‐MTX courses (administered according to the ALL‐BFM 95 and ALL IC‐BFM 2002 protocols) were analysed. Haematological, hepatic and renal toxicities, estimated by routine laboratory parameters were evaluated. Random forest and regression trees were used for variable selection and model building. Linear mixed models were established to prove the significance of the selected variables. SNPs (rs4948502, rs4948496, rs4948487) of the ARID5B gene were associated with the serum levels of MTX (P < 0·02), serum levels and area under the curve of 7‐OH‐MTX (P < 0·02) and with hypoproteinaemia (P = 0·004). SLCO1B1 rs4149056 also showed a significant association with serum MTX levels (P < 0·001). Our findings confirm the association of novel genetic variations in folate‐related and ARID5B genes with the serum MTX levels and acute toxicity.
The Cuban Experience in East Germany: Academic Migration from 1960 to 2000
Authors: HOLTZ MENJA
Published: April 2014

The partnership between revolutionary Cuba and the German Democratic Republic (GDR) offered a route for migration that had not been possible before. While academic exchange aimed to construct a socialist society in Cuba and strengthen the Socialist Bloc, as well as serving the economic and political interests of both states, the creation of a transnational academic elite and of intellectual collectives across borders also occurred as a by‐product of the exchange. This article shows how these ‘by‐products’ came into existence, and how academic exchange can be influenced by political, financial and organisational limitations.
Novel Fluorescently Labeled Peptide Compounds for Detection of Oxidized Low‐Density Lipoprotein at High Specificity
Authors: Sato Akira , Yamanaka Hikaru , Oe Keitaro , Yamazaki Yoji , Ebina Keiichi
Published: April 2014

The probes for specific detection of oxidized low‐density lipoprotein (ox‐LDL) in plasma and in atherosclerotic plaques are expected to be useful for the identification, diagnosis, prevention, and treatment for atherosclerosis. In this study, to develop a fluorescent peptide probe for specific detection of ox‐LDL, we investigated the interaction of fluorescein isothiocyanate (FITC)‐labeled peptides with ox‐LDL using polyacrylamide gel electrophoresis. Two heptapeptides (KWYKDGD and KP6) coupled through the ε‐amino group of K at the N‐terminus to FITC in the presence/absence of 6‐amino‐n‐caproic acid (AC) linker to FITC—(FITC‐AC)KP6 and (FITC)KP6—both bound with high specificity to ox‐LDL in a dose‐dependent manner. In contrast, a tetrapeptide (YKDG) labeled with FITC at the N‐terminus and a pentapeptide (YKDGK) coupled through the ε‐amino group of K at the C‐terminus to FITC did not bind selectively to ox‐LDL. Furthermore, (FITC)KP6 and (FITC‐AC)KP6 bound with high specificity to the protein in mouse plasma (probably ox‐LDL fraction). These findings strongly suggest that (FITC)KP6 and (FITC‐AC)KP6 may be effective novel fluorescent probes for specific detection of ox‐LDL.
Long‐term routine dental attendance: influence on tooth loss and oral health‐related quality of life in Swedish older adults
Authors: Åstrøm Anne N. , Ekback Gunnar , Ordell Sven , Nasir Elwalid
Published: April 2014

Objectives

Few studies have investigated the effect of long‐term routine dental attendance on oral health between middle‐aged and older adults, using a prospective cohort design. This study aimed to assess routine dental attendance (attending dentist in the previous 12 months for dental checkups) from age 50 to 65 years. Moreover, this study examined whether long‐term routine dental attendance contributes to oral health‐related quality of life, OHRQoL, and major tooth loss independent of social factors and the type of treatment sector utilized. Whether oral health impacts of long‐term routine attendance varied with type of treatment sector utilized was also investigated.

Method

In 1992, a census of the 1942 cohort in two counties of Sweden participated in a longitudinal questionnaire survey conducted at age 50 and again after 5, 10, and 15 years. Information was collected on a wide range of health‐ and oral health‐related aspects. Of the 6346 subjects who completed the 1992 survey, 4143 (65%) completed postal follow‐ups in 1997, 2002, and 2007.

Results

Routine dental attendance decreased from 69.1% at age 50–64.2% at age 65. Adjusted logistic regression analyses revealed that individuals reporting long‐term routine attendance (routine attendance in both 1992 and 2007) were 0.3 (95% CI 0.2–0.5) times less likely than their counterparts who were nonroutine attenders to report oral impacts. According to generalized estimating equations (GEE), individuals who reported long‐term routine attendance were 0.6 (95% CI 0.4–0.7) times less likely than nonroutine attenders to have major tooth loss across the survey years. The effect of long‐term routine attendance on OHRQoL was stronger in public than in private dental healthcare attenders.

Conclusion

Routine attendance decreased from age 50–65 years. Long‐term routine attendance had positive impact on major tooth loss and OHRQoL supporting the principle of encouraging annual dental attendance for preventive checkups among older people.
Clinical, imaging, and molecular findings in a sample of Mexican families with pantothenate kinase‐associated neurodegeneration
Authors: Morales‐Briceño H. , Chacón‐Camacho O.F. , Pérez‐González E.A. , Arteaga‐Vázquez J. , Rodríguez‐Violante M. , Cervantes‐Arriaga A. , Pérez‐Rodríguez L. , Zenteno J.C. , Mutchinick O.M.
Published: April 2014

Pantothenate kinase‐associated neurodegeneration (PKAN) is an autosomal recessive disorder characterized by iron accumulation in the brain, because of mutations in the PANK2 gene. Phenotypic and genotypic characteristics of 11 patients from five Mexican families with PKAN disease are reported. Sequencing of PANK2 confirmed the diagnosis. The 11 patients had dysarthria associated with dystonia and Parkinsonism in six. Brain magnetic resonance imaging (MRI) showed the ‘eye‐of‐the‐tiger’ sign in all patients. Three different mutations were identified, a novel one (p.A469P) and two (p.G219V and p.N404I) very rare. Homozygous sibs for the p.G219V mutation had a severe disease progression with early death. Dystonia predominated in the p.A469P/p.N404I compound heterozygous patients. Homozygous for p.N404I showed Parkinsonism, tics and personality and speech disorders. Early and late disease onset and variable expression was present in carriers of the different identified mutations. The ‘eye‐of‐the‐tiger’ is an excellent neuroimaging hallmark to predict PANK2 mutations. We detected a ‘cluster’ of patients harboring the p.N404I mutation, strongly suggesting a founder effect for this mutation. This is the first familial clinical‐genetic PKAN disease study accomplished in Mexico.
Transnasal oesophagoscopy: diagnostic and management outcomes in a prospective cohort of 257 consecutive cases and practice implications
Authors: Abou‐Nader L. , Wilson J.A. , Paleri V.
Published: April 2014

Objectives

To determine the success rate, patient tolerability and impact of introducing transnasal oesophagoscopy on clinical practices.

Design

Prospective cohort with review of electronic patient records for outcomes.

Setting

UK tertiary centre Otolaryngology Department.

Participants

The cohort comprised of two hundred and fifty‐seven patients, 128 females (50%) and 129 males (50%) with an age range of 20–91 years; mean age 59 years (sd 13.6).

Main outcome measures

Success rates, indications, findings and outcomes of patients undergoing transnasal oesophagoscopy and impact on rigid examinations of the pharynx and oesophagus were also considered.

Results

Transnasal oesophagoscopy has a high success rate of 97%; it is well tolerated by patients, and poor views are uncommon. Pathology was detected in 44% of patients. The most common indications for transnasal oesophagoscopy were unexplained throat symptoms (50%) and dysphagia (25%). Common positive findings were hiatus hernia (7%), Barrett's oesophagus (5%), dysmotility (5%) and oesophageal candidiasis (5%). Following transnasal oesophagoscopy, 59% of patients were discharged to their referring clinician, 17% continued to undergo otolaryngology follow‐up, and 13% were referred to our gastrointestinal colleagues. Following the introduction of transnasal oesophagoscopy, there was a reduction in the number of rigid examinations of the pharynx and oesophagus in the subsequent years, despite an increase in total referrals.

Conclusions

Transnasal oesophagoscopy is a well‐tolerated procedure that allows otolaryngologists to make management decisions on common referrals swiftly in the clinic setting avoiding unnecessary investigations, follow‐up and referral.
Recommendation to increase the test concentration of methylchloroisothiazolinone/methylisothiazolinone in the European baseline patch test series – on behalf of the European Society of Contact Dermatitis and the European Environmental and Contact Dermatitis Research Group
Authors: Bruze Magnus , Goossens An , Isaksson Marléne
Published: April 2014

Background

Methylchloroisothiazolinone (MCI)/methylisothiazolinone (MI) in aqua is present in the European baseline patch test series at 100 ppm, whereas 200 ppm has been used in Sweden since 1986, in Spain in the late 1980s, and, in recent years, also in the United Kingdom and Ireland.

Objectives

With regard to MCI/MI, to investigate the data on contact allergy rates in dermatitis patients, the frequencies of allergic contact dermatitis in the same group, and adverse reactions, particularly patch test sensitization in tested dermatitis patients, and to find the optimal patch test concentration as dose in mg/cm2.

Materials and methods

We performed a survey of the literature found via the National Library of Medicine (PubMed, http://www.ncbi.nlm.nih.gov/pubmed, last accessed 20 February 2014).

Results

MCI/MI at 200 ppm aq. diagnosis substantially more contact allergy and allergic contact dermatitis, without any registered increase in patch test sensitization, than the presently used concentration of 100 ppm.

Conclusion

MCI/MI at 200 ppm aq. is recommended to be included in the European baseline patch test series. To avoid patch test sensitization, a dose of 0.006 mg/cm2 must not be exceeded, which means a volume of 15 µl for Finn Chambers® (Ø 8 mm).
Neurogenin2‐d4Venus and Gadd45g‐d4Venus transgenic mice: Visualizing mitotic and migratory behaviors of cells committed to the neuronal lineage in the developing mammalian brain
Authors: Kawaue Takumi , Sagou Ken , Kiyonari Hiroshi , Ota Kumiko , Okamoto Mayumi , Shinoda Tomoyasu , Kawaguchi Ayano , Miyata Takaki
Published: April 2014

To achieve highly sensitive and comprehensive assessment of the morphology and dynamics of cells committed to the neuronal lineage in mammalian brain primordia, we generated two transgenic mouse lines expressing a destabilized (d4) Venus controlled by regulatory elements of the Neurogenin2 (Neurog2) or Gadd45g gene. In mid‐embryonic neocortical walls, expression of Neurog2‐d4Venus mostly overlapped with that of Neurog2 protein, with a slightly (1 h) delayed onset. Although Neurog2‐d4Venus and Gadd45g‐d4Venus mice exhibited very similar labeling patterns in the ventricular zone (VZ), in Gadd45g‐d4Venus mice cells could be visualized in more basal areas containing fully differentiated neurons, where Neurog2‐d4Venus fluorescence was absent. Time‐lapse monitoring revealed that most d4Venus+ cells in the VZ had processes extending to the apical surface; many of these cells eventually retracted their apical process and migrated basally to the subventricular zone, where neurons, as well as the intermediate neurogenic progenitors that undergo terminal neuron‐producing division, could be live‐monitored by d4Venus fluorescence. Some d4Venus+ VZ cells instead underwent nuclear migration to the apical surface, where they divided to generate two d4Venus+ daughter cells, suggesting that the symmetric terminal division that gives rise to neuron pairs at the apical surface can be reliably live‐monitored. Similar lineage‐committed cells were observed in other developing neural regions including retina, spinal cord, and cerebellum, as well as in regions of the peripheral nervous system such as dorsal root ganglia. These mouse lines will be useful for elucidating the cellular and molecular mechanisms underlying development of the mammalian nervous system.
Social‐communicative abilities as treatment goals for preschool children with autism spectrum disorder: the importance of imitation, joint attention, and play
Authors: Warreyn Petra , van der Paelt Sara , Roeyers Herbert
Published: April 2014

Autism spectrum disorder (ASD) is a pervasive developmental disorder with a lifelong impact on multiple domains of functioning. Often, a diagnosis is possible by 3 years of age. Given the benefits of early intervention, it is advisable to start treatment as soon as possible after the diagnosis has been made. Among other factors, early intervention should focus on social‐communicative abilities such as imitation, joint attention, and play. In this review, the typical developmental course and functions of these social‐communicative abilities are described, and the problems young children with ASD experience in this domain. In addition, different approaches to promoting these abilities are explained. The authors recommend the inclusion of imitation, joint attention, and play as treatment goals in community settings for children with ASD.
Signature of subclinical femoral artery atherosclerosis in peripheral blood mononuclear cells
Authors: Llorente‐Cortés Vicenta , de Gonzalo‐Calvo David , Orbe Josune , Páramo Jose Antonio , Badimon Lina
Published: April 2014

Background

Peripheral arterial disease is a relevant public health problem associated with increased risk of morbimortality. Most of the patients with this condition are asymptomatic. Therefore, the development of accessible biochemical markers seems to be necessary to anticipate diagnosis. Our hypothesis is that asymptomatic subjects with objectively confirmed femoral artery atherosclerosis could be distinguished from control subjects by gene expression analysis in peripheral blood mononuclear cells (PBMC).

Materials and methods

A total of 37 asymptomatic males over 50 years old were recruited at the University Clinic of Navarra (Spain). Nineteen participants were free from atherosclerotic vascular disease and 18 participants presented subclinical femoral artery atherosclerosis defined by means of Doppler ultrasound. PBMC were isolated from blood and the RNA extracted. A panel of atherosclerotic‐related genes were evaluated by Taqman low‐density array.

Results

In univariate logistic regression models, we found a direct relationship between IL4, ITGAM and TLR2 expression levels in PBMC and femoral atherosclerosis, even when the models were adjusted for age and hypertension prevalence. Multivariate logistic regression models showed that elevated IL4 expression levels were intimately associated with subclinical femoral atherosclerosis after adjusting for the same potential confounders.

Conclusions

Current data suggest that gene expression in PBMC, in particular IL4 expression, could be a useful tool in the diagnosis of femoral artery atherosclerosis in asymptomatic patients. Furthermore, in patients with no differences in cardiovascular risk factors except for hypertension, the results point to the immune and inflammatory deregulation as a feature of subclinical peripheral atherosclerosis.
Confucius on Educational Failure: Three Types of Misguided Students
Authors: Black David W.
Published: April 2014

In this essay David Black claims that, if one pieces together the many sketches of educational decorum found in the Confucian Analects, one will discover three types of misguided student; that is, one will come to recognize that Confucius admonishes three types of insensitive learners who, due to the lure of personal advantage and social rhetoric, begin to mismanage the exchanges of respect particular to the educational process. These students misappropriate key rituals of decorum and dialogue, and consequently create a degree of disorder that, for Confucius, actually threatens the existence of civil society.
The Fundamental Ontology of Study
Authors: Lewis Tyson E.
Published: April 2014

In an effort to disrupt the hegemonic dominance of learning theory, in this article Tyson Lewis explores the unique educational logic of studying. Drawing on the work of Giorgio Agamben, we can understand the operation of study as one of suspension through three modes: preferring not; no longer, not yet; and as not. But the relationship between the operation of suspension and the everyday mode of learning remains an open question requiring further analysis. In order to accomplish this task, it is important to remember that for Agamben, study is a kind of profanation or improper life. Through examining Heidegger's analytic of Dasein's everyday being, Lewis demonstrates that the nature of study is always already saturated with the everyday, and is itself a contaminated process that is neither simply everyday living nor “authentic” existence. To be absolutely precise, the studier engages in idle talk, is curious, and is caught up in ambiguity in order to explore the seemingly uninhabitable zone that rests between everyday falling and authentically standing. Lewis concludes by offering Agamben's own work as a paradigm of study, illustrating how the smallest of freedoms opens to the studier: the freedom to dwell in potentiality.
On Consumerism, Collective Action, and Whether Art Teaches Anything
Authors: Ruitenberg Claudia W.
Published: April 2014

In this review essay, Claudia Ruitenberg discusses Trevor Norris's Consuming Schools, René Arcilla's Mediumism, and Martha Nussbaum's Not for Profit. While the primary focus of each book is different — with Norris concentrating on the pressures of consumerism and commercialism on K–12 schooling, Arcilla analyzing modernist art and existentialist education, and Nussbaum emphasizing the role of the humanities in educating for democratic citizenship — each of the books in some way addresses the question of how people can be educated to resist consumerism and how education itself can resist being absorbed by consumerism. Here, Ruitenberg considers this common theme as well as the more specific question of what special role — if any — the arts might play in anticonsumerist education.
Temperature–growth patterns of individually tagged anadromousArctic charrSalvelinus alpinusinUngava andLabrador,Canada
Authors: Murdoch Alyssa , Dempson J. Brian , Martin Francois , Power Michael
Published: April 2014

Individual measurements of annual, or within‐season growth were determined from tag‐recapturedArctic charr and examined in relation to summer sea surface temperatures and within‐season capture timing in theUngava andLabrador regions of EasternCanada. Differences between two years of growth (2010–2011) were significant forUngavaBayArctic charr, with growth being higher in the warmer year. Growth ofLabradorArctic charr did not vary significantly among years (1982–1985). Regional comparisons demonstrated thatUngavaArctic charr had significantly higher annual growth rates and experienced warmer temperatures thanLabradorArctic charr. The higher annual growth ofUngavaBayArctic charr was attributed to the high sea surface temperatures experienced in 2010–2011 and the localised differences in nearshore productivity as compared toLabrador. Within‐season growth rates ofLabradorArctic charr peaked inJune, declined towardsAugust and were negatively correlated with the length of time spent at sea and mean experienced sea surface temperatures. A quadratic model relating growth rate to temperature best explained the pattern of within‐season growth. Collectively, results suggest that increases in water temperature may have profound consequences for Arctic charr growth in theCanadian sub‐Arctic, depending on the responses of local marine productivity to those same temperature increases.
The lateral habenula in addiction and depression: an anatomical, synaptic and behavioral overview
Authors: Lecca Salvatore , Meye Frank J. , Mameli Manuel
Published: April 2014

The lateral habenula (LHb) is an epithalamic region with a crucial role in the regulation of midbrain monoaminergic systems. Over the past few years a renewed interest in the LHb has emerged due to studies highlighting its central role in encoding rewarding and aversive aspects of stimuli. Moreover, an increasing number of functional as well as behavioral indications provide substantial evidence supporting a role of LHb in neuropsychiatric diseases, including mood disorders and drug addiction. Cellular and synaptic adaptations in the LHb may therefore represent a critical phenomenon in the etiology of these diseases. In the current review we describe the anatomical and functional connections allowing the LHb to control the dopamine and serotonin systems, as well as possible roles of these connections in motivated behaviors and neuropsychiatric disorders. Finally, we discuss how drug exposure and stressful conditions alter the cellular physiology of the LHb, highlighting a role for the LHb in the context of drug addiction and depression.
Reversal of activity‐mediated spine dynamics and learning impairment in a mouse model of Fragile X syndrome
Authors: Boda Bernadett , Mendez Pablo , Boury‐Jamot Benjamin , Magara Fulvio , Muller Dominique
Published: April 2014

Fragile X syndrome (FXS) is characterized by intellectual disability and autistic traits, and results from the silencing of the FMR1 gene coding for a protein implicated in the regulation of protein synthesis at synapses. The lack of functional Fragile X mental retardation protein has been proposed to result in an excessive signaling of synaptic metabotropic glutamate receptors, leading to alterations of synapse maturation and plasticity. It remains, however, unclear how mechanisms of activity‐dependent spine dynamics are affected in Fmr knockout (Fmr1‐KO) mice and whether they can be reversed. Here we used a repetitive imaging approach in hippocampal slice cultures to investigate properties of structural plasticity and their modulation by signaling pathways. We found that basal spine turnover was significantly reduced in Fmr1‐KO mice, but markedly enhanced by activity. Additionally, activity‐mediated spine stabilization was lost in Fmr1‐KO mice. Application of the metabotropic glutamate receptor antagonist α‐Methyl‐4‐carboxyphenylglycine (MCPG) enhanced basal turnover, improved spine stability, but failed to reinstate activity‐mediated spine stabilization. In contrast, enhancing phosphoinositide‐3 kinase (PI3K) signaling, a pathway implicated in various aspects of synaptic plasticity, reversed both basal turnover and activity‐mediated spine stabilization. It also restored defective long‐term potentiation mechanisms in slices and improved reversal learning in Fmr1‐KO mice. These results suggest that modulation of PI3K signaling could contribute to improve the cognitive deficits associated with FXS.
The synapse in schizophrenia
Authors: Pocklington Andrew J. , O'Donovan Michael , Owen Michael J.
Published: April 2014

It has been several decades since synaptic dysfunction was first suggested to play a role in schizophrenia, but only in the last few years has convincing evidence been obtained as progress has been made in elucidating the genetic underpinnings of the disorder. In the intervening years much has been learned concerning the complex macromolecular structure of the synapse itself, and genetic studies are now beginning to draw upon these advances. Here we outline our current understanding of the genetic architecture of schizophrenia and examine the evidence for synaptic involvement. A strong case can now be made that disruption of glutamatergic signalling pathways regulating synaptic plasticity contributes to the aetiology of schizophrenia.
Stress andVTAsynapses: implications for addiction and depression
Authors: Polter Abigail M. , Kauer Julie A.
Published: April 2014

While stressful experiences are a part of everyone's life, they can also exact a major toll on health. Stressful life experiences are associated with increased substance abuse, and there exists significant co‐morbidity between mental illness and substance use disorders [N.D. Volkow & T.K. Li (2004)Nat. Rev. Neurosci.,5, 963–970; G. Koob & M.J. Kreek (2007)Am. J. Psych.,164, 1149–1159; R. Sinha (2008)Annals N.Y. Acad. Sci.,1141, 105–130]. The risk for development of mood or anxiety disorders after stress is positively associated with the risk for substance use disorders [R. Sinha (2008)Annals N.Y. Acad. Sci.,1141, 105–130], suggesting that there are common substrates for vulnerability to addictive and affective disorders. Understanding the molecular and physiological substrates of stress may lead to improved therapeutic interventions for the treatment of substance use disorders and mental illnesses.
Disrupted in schizophrenia 1 and synaptic function in the mammalian central nervous system
Authors: Randall Andrew D. , Kurihara Mai , Brandon Nicholas J. , Brown Jon T.
Published: April 2014

The disrupted in schizophrenia 1 (DISC1) gene is found at the breakpoint of an inherited chromosomal translocation, and segregates with major mental illnesses. Its potential role in central nervous system (CNS) malfunction has triggered intensive investigation of the biological roles played by DISC1, with the hope that this may shed new light on the pathobiology of psychiatric disease. Such work has ranged from investigations of animal behavior to detailed molecular‐level analysis of the assemblies that DISC1 forms with other proteins. Here, we discuss the evidence for a role of DISC1 in synaptic function in the mammalian CNS.
Interplay between synaptic endocannabinoid signaling and metaplasticity in neuronal circuit function and dysfunction
Authors: Melis Miriam , Greco Barbara , Tonini Raffaella
Published: April 2014

Synaptic neuromodulation acts across different functional domains to regulate cognitive processing and behavior. Recent challenges are related to elucidating the molecular and cellular mechanisms through which neuromodulatory pathways act on multiple time scales to signal state‐dependent contingencies at the synaptic level or to stabilise synaptic connections during behavior. Here, we present a framework with the synaptic neuromodulators endocannabinoids (eCBs) as key players in dynamic synaptic changes. Modulation of various molecular components of the eCB pathway yields interconnected functional activation states of eCB signaling (prior, tonic, and persistent), which may contribute to metaplastic control of synaptic and behavioral functions in health and disease. The emerging picture supports aberrant metaplasticity as a contributor to cognitive dysfunction associated with several pathological states in which eCB signaling, or other neuromodulatory pathways, are deregulated.
Tau acts as a mediator for Alzheimer's disease‐related synaptic deficits
Authors: Liao Dezhi , Miller Eric C. , Teravskis Peter J.
Published: April 2014

The two histopathological hallmarks of Alzheimer's disease (AD) are amyloid plaques containing multiple forms of amyloid beta (Aβ) and neurofibrillary tangles containing phosphorylated tau proteins. As mild cognitive impairment frequently occurs long before the clinical diagnosis of AD, the scientific community has been increasingly interested in the roles of Aβ and tau in earlier cellular changes that lead to functional deficits. Therefore, great progress has recently been made in understanding how Aβ or tau causes synaptic dysfunction. However, the interaction between the Aβ and tau‐initiated intracellular cascades that lead to synaptic dysfunction remains elusive. The cornerstone of the two‐decade‐old hypothetical amyloid cascade model is that amyloid pathologies precede tau pathologies. Although the premise of Aβ‐tau pathway remains valid, the model keeps evolving as new signaling events are discovered that lead to functional deficits and neurodegeneration. Recent progress has been made in understanding Aβ‐PrPC‐Fyn‐mediated neurotoxicity and synaptic deficits. Although still elusive, many novel upstream and downstream signaling molecules have been found to modulate tau mislocalization and tau hyperphosphorylation. Here we will discuss the mechanistic interactions between Aβ‐PrPC‐mediated neurotoxicity and tau‐mediated synaptic deficits in an updated amyloid cascade model with calcium and tau as the central mediators.
Fluorescence‐activated sorting of fixed nuclei: a general method for studying nuclei from specific cell populations that preserves post‐translational modifications
Authors: Marion‐Poll Lucile , Montalban Enrica , Munier Annie , Hervé Denis , Girault Jean‐Antoine
Published: April 2014

Long‐lasting brain alterations that underlie learning and memory are triggered by synaptic activity. How activity can exert long‐lasting effects on neurons is a major question in neuroscience. Signalling pathways from cytoplasm to nucleus and the resulting changes in transcription and epigenetic modifications are particularly relevant in this context. However, a major difficulty in their study comes from the cellular heterogeneity of brain tissue. A promising approach is to directly purify identified nuclei. Using mouse striatum we have developed a rapid and efficient method for isolating cell type‐specific nuclei from fixed adult brain (fluorescence‐activated sorting of fixed nuclei; FAST‐FIN). Animals are quickly perfused with a formaldehyde fixative that stops enzymatic reactions and maintains the tissue in the state it was at the time of death, including nuclear localisation of soluble proteins such as GFP and differences in nuclear size between cell types. Tissue is subsequently dissociated with a Dounce homogeniser and nuclei prepared by centrifugation in an iodixanol density gradient. The purified fixed nuclei can then be immunostained with specific antibodies and analysed or sorted by flow cytometry. Simple criteria allow distinction of neurons and non‐neuronal cells. Immunolabelling and transgenic mice that express fluorescent proteins can be used to identify specific cell populations, and the nuclei from these populations can be efficiently isolated, even rare cell types such as parvalbumin‐expressing interneurons. FAST‐FIN allows the preservation and study of dynamic and labile post‐translational protein modifications. It should be applicable to other tissues and species, and allow study of DNA and its modifications.
Auxiliary proteins promote modal gating of AMPA‐ and kainate‐type glutamate receptors
Authors: Zhang Wei , Devi Suma Priya Sudarsana , Tomita Susumu , Howe James R.
Published: April 2014

The gating behavior of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) and kainate receptors is modulated by association with the auxiliary proteins: transmembrane AMPA receptor regulatory proteins (TARPs) and neuropilin tolloid‐like (Netos), respectively. Although the mechanisms underlying receptor modulation differ for both AMPA and kainate receptors, association with these auxiliary subunits results in the appearance of a slow component in the decay of ensemble responses to rapid applications of saturating concentrations of glutamate. We show here that these components arise from distinct gating behaviors, characterized by substantially higher open probability (Popen), which we only observe when core subunits are associated with their respective auxiliary partners. We refer to these behaviors as gating modes, because individual receptors switch between the low‐ and high‐Popen gating on a time‐scale of seconds. At any given time, association of AMPA and kainate receptors with their auxiliary subunits results in a heterogeneous receptor population, some of which are in the high‐Popen mode and others that display gating behavior similar to that seen for receptors formed from core subunits alone. While the switching between modes is infrequent, the presence of receptors displaying both types of gating has a large impact on both the kinetics and amplitude of ensemble currents similar to those seen at synapses.