bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of the Hypocretin (Orexin) Receptor 2 (Hcrt-r2) in the Regulation of Hypocretin Level and Cataplexy
Authors: Wu Ming-Fung , Nienhuis Robert , Maidment Nigel , Lam Hoa A. , Siegel Jerome M.
Published: April 2011

Hypocretin receptor-2 (Hcrt-r2)-mutated dogs exhibit all the major symptoms of human narcolepsy and respond to drugs that increase or decrease cataplexy as do narcoleptic humans; yet, unlike narcoleptic humans, the narcoleptic dogs have normal hypocretin levels. We find that drugs that reduce or increase cataplexy in the narcoleptic dogs, greatly increase and decrease, respectively, hypocretin levels in normal dogs. The effects of these drugs on heart rate and blood pressure, which were considerable, were not correlated with their effects on cataplexy. Administration of these drugs to Hcrt-r2-mutated dogs produced indistinguishable changes in heart rate and blood pressure, indicating that neither central nor peripheral Hcrt-r2 is required for these cardiovascular effects. However, in contrast to the marked Hcrt level changes in the normal dogs, these drugs did not alter hypocretin levels in the Hcrt-r2 mutants. We conclude that Hcrt-r2 is a vital element in a feedback loop integrating Hcrt, acetylcholine, and norepinephrine function. In the absence of functional Hcrt-r2, Hcrt levels are not affected by monoaminergic and cholinergic drugs, despite the strong modulation of cataplexy by these drugs. Conversely, strong transient reductions of Hcrt level by these drugs do not produce episodes of cataplexy in normal dogs. The Hcrt-r2 mutation causes drug-induced cataplexy by virtue of its long-term effect on the functioning of other brain systems, rather than by increasing the magnitude of phasic changes in Hcrt level. A similar mechanism may be operative in spontaneous cataplexy in narcoleptic dogs as well as in narcoleptic humans.
Gli3Is Required for Maintenance and Fate Specification of Cortical Progenitors
Authors: Wang Hui , Ge Guannan , Uchida Yutaka , Luu Brian , Ahn Sohyun
Published: April 2011

Gli3, one of three vertebrate Gli transcription factors in Hedgehog (Hh) pathway, is processed into a repressor form (Gli3R) in the absence of Hh signal and acts as the major negative transducer of the pathway. Although the role ofGli3in embryonic patterning has been extensively studied, its role in cortical neurogenesis, especially in the regulation of neural progenitors in proliferation and cell fate specification, is largely unknown. To bypass the patterning defects caused by loss ofGli3, we conditionally deletedGli3after patterning was complete in mouse. Our results from birthdating andin uteroelectroporation experiments demonstrate that theGli3, specifically Gli3R, is critical for specifying the fate of cortical neurons that are generated following a stereotypical temporal order. Moreover,Gli3is required for maintaining the cortical progenitors in active cell cycle, suggesting that cells may acquire differentiated status as they turn offGli3expression during neurogenesis.
Development, Maturation, and Necessity of Transcription Factors in the Mouse Suprachiasmatic Nucleus
Authors: VanDunk Cassandra , Hunter Lindsay A. , Gray Paul A.
Published: April 2011

The suprachiasmatic nucleus (SCN) of the hypothalamus is the master mammalian circadian clock. The SCN is highly specialized because it is responsible for generating a near 24 h rhythm, integrating external cues, and translating the rhythm throughout the body. Currently, our understanding of the developmental origin and genetic program involved in the proper specification and maturation of the SCN is limited. Herein, we provide a detailed analysis of transcription factor (TF) and developmental-gene expression in the SCN from neurogenesis to adulthood in mice (Mus musculus). TF expression within the postmitotic SCN was not static but rather showed specific temporal and spatial changes during prenatal and postnatal development. In addition, we found both global and regional patterns of TF expression extending into the adult. We found that the SCN is derived from a distinct region of the neuroepithelium expressing a combination of developmental genes: Six3, Six6, Fzd5, and transient Rx, allowing us to pinpoint the origin of this region within the broader developing telencephalon/diencephalon. We tested the necessity of two TFs in SCN development, RORα and Six3, which were expressed during SCN development, persisted into adulthood, and showed diurnal rhythmicity. Loss of RORα function had no effect on SCN peptide expression or localization. In marked contrast, the conditional deletion of Six3 from early neural progenitors completely eliminated the formation of the SCN. Our results provide the first description of the involvement of TFs in the specification and maturation of a neural population necessary for circadian behavior.
PSD-95 Is Required to Sustain the Molecular Organization of the Postsynaptic Density
Authors: Chen Xiaobing , Nelson Christopher D. , Li Xiang , Winters Christine A. , Azzam Rita , Sousa Alioscka A. , Leapman Richard D. , Gainer Harold , Sheng Morgan , Reese Thomas S.
Published: April 2011

PSD-95, a membrane-associated guanylate kinase, is the major scaffolding protein in the excitatory postsynaptic density (PSD) and a potent regulator of synaptic strength. Here we show that PSD-95 is in an extended configuration and positioned into regular arrays of vertical filaments that contact both glutamate receptors and orthogonal horizontal elements layered deep inside the PSD in rat hippocampal spine synapses. RNA interference knockdown of PSD-95 leads to loss of entire patches of PSD material, and electron microscopy tomography shows that the patchy loss correlates with loss of PSD-95-containing vertical filaments, horizontal elements associated with the vertical filaments, and putative AMPA receptor-type, but not NMDA receptor-type, structures. These observations show that the orthogonal molecular scaffold constructed from PSD-95-containing vertical filaments and their associated horizontal elements is essential for sustaining the three-dimensional molecular organization of the PSD. Our findings provide a structural basis for understanding the functional role of PSD-95 at the PSD.
Impaired Limbic Gamma Oscillatory Synchrony during Anxiety-Related Behavior in a Genetic Mouse Model of Bipolar Mania
Authors: Dzirasa Kafui , McGarity DeAnna L. , Bhattacharya Anirban , Kumar Sunil , Takahashi Joseph S. , Dunson David , McClung Colleen A. , Nicolelis Miguel A. L.
Published: April 2011

Alterations in anxiety-related processing are observed across many neuropsychiatric disorders, including bipolar disorder. Though polymorphisms in a number of circadian genes confer risk for this disorder, little is known about how changes in circadian gene function disrupt brain circuits critical for anxiety-related processing. Here we characterize neurophysiological activity simultaneously across five limbic brain areas (nucleus accumbens, amygdala, prelimbic cortex, ventral hippocampus, and ventral tegmental area) as wild-type (WT) mice and mice with a mutation in the circadian gene, CLOCK (Clock-Δ19 mice) perform an elevated zero maze task. In WT mice, basal limbic gamma oscillatory synchrony observed before task performance predicted future anxiety-related behaviors. Additionally, dynamic changes in limbic gamma oscillatory synchrony were observed based on the position of WT mice in the zero maze.Clock-Δ19 mice, which displayed an increased propensity to enter the open section of the elevated maze, showed profound deficits in these anxiety-related circuit processes. Thus, our findings link the anxiety-related behavioral deficits observed inClock-Δ19 mice with dysfunctional gamma oscillatory tuning across limbic circuits and suggest that alterations in limbic oscillatory circuit function induced by circadian gene polymorphisms may contribute to the behavioral manifestations seen in bipolar mania.
Anisotropic Distribution of Thalamocortical Boutons in Barrels
Authors: Furuta Takahiro , Deschênes Martin , Kaneko Takeshi
Published: April 2011

A characteristic feature of the somatosensory cortex in rodents is the presence of discrete cellular aggregates in layer 4 (barrels) that process input from the mystacial vibrissae. Just like thalamic cells that relay vibrissal information to the barrels, barrel cells display directional preference to whisker motion. The present study examined whether the projection of single thalamic cells into a barrel is consistent with the existence of an orderly map of direction preference. The direction preference of single thalamic cells was assessed, and axonal projections were visualized after juxtacellular labeling with biotinylated dextran. Results show that the terminal field of individual thalamic neurons in a barrel is markedly anisotropic and that the location of boutons with respect to the somatotopic map is either positively or negatively correlated with the angular tuning of the thalamic neuron. These results indicate that angular tuning is not represented across a systematic map with fixed anteroposterior/mediolateral coordinates in a barrel. The actual significance of the direction-dependent segregation of thalamocortical terminals in barrels may only come to light in the context of active sensing.
Differential Roles of Orexin Receptor-1 and -2 in the Regulation of Non-REM and REM Sleep
Authors: Mieda Michihiro , Hasegawa Emi , Kisanuki Yaz Y. , Sinton Christopher M. , Yanagisawa Masashi , Sakurai Takeshi
Published: April 2011

Orexin-A and orexin-B are hypothalamic neuropeptides that play critical roles in the maintenance of wakefulness. Intracerebroventricular (ICV) administration of orexin-A has been shown to promote wakefulness and suppress both rapid eye movement (REM) sleep and non-REM (NREM) sleep through the orexin receptor-1 (OX1R) and orexin receptor-2 (OX2R). Here, we elucidated the differential roles of orexin receptors in the regulation of sleep and wakefulness by comparing the effects of ICV orexin-A administration in wild-type,OX1R−/−, andOX2R−/−mice. The effects of orexin-A on wakefulness and NREM sleep were significantly attenuated in both knock-out mice as compared with wild-type mice, with substantially larger attenuation inOX2R−/−mice than inOX1R−/−mice. These results suggest that although the OX2R-mediated pathway has a pivotal role in the promotion of wakefulness, OX1R also plays additional roles in promoting arousal. In contrast, suppression of REM sleep by orexin-A administration was slightly and similarly attenuated in bothOX1R−/−andOX2R−/−mice, suggesting a comparable contribution of the two receptors to REM sleep suppression. Histological studies demonstrated differential distributions of each receptor subtype in distinct neuronal populations with specific neurotransmitter identities in brainstem cholinergic/monoaminergic neurons. In the laterodorsal tegmental and pedunculopontine tegmental nuclei especially, cholinergic neurons exclusively expressedOX1RmRNA, butOX2RmRNA was expressed mainly in GABAergic putative interneurons. Thus, each orexin receptor subtype plays differential roles in gating NREM and REM sleep through distinct neuronal pathways.
Biophysical Mechanisms of Multistability in Resting-State Cortical Rhythms
Authors: Freyer Frank , Roberts James A. , Becker Robert , Robinson Peter A. , Ritter Petra , Breakspear Michael
Published: April 2011

The human alpha (8–12 Hz) rhythm is one of the most prominent, robust, and widely studied attributes of ongoing cortical activity. Contrary to the prevalent notion that it simply “waxes and wanes,” spontaneous alpha activity bursts erratically between two distinct modes of activity. We now establish a mechanism for this multistable phenomenon in resting-state cortical recordings by characterizing the complex dynamics of a biophysical model of macroscopic corticothalamic activity. This is achieved by studying the predicted activity of cortical and thalamic neuronal populations in this model as a function of its dynamic stability and the role of nonspecific synaptic noise. We hence find that fluctuating noisy inputs into thalamic neurons elicit spontaneous bursts between low- and high-amplitude alpha oscillations when the system is near a particular type of dynamical instability, namely a subcritical Hopf bifurcation. When the postsynaptic potentials associated with these noisy inputs are modulated by cortical feedback, the SD of power within each of these modes scale in proportion to their mean, showing remarkable concordance with empirical data. Our state-dependent corticothalamic model hence exhibits multistability and scale-invariant fluctuations—key features of resting-state cortical activity and indeed, of human perception, cognition, and behavior—thus providing a unified account of these apparently divergent phenomena.
Leiomyosarcoma Protruding into the Left Ventricle during Diastole: Report of a Case
Authors: Deniz Hayati , Koruk Senem , Kirbas Ahmet , Atik Cem , Ozcaliskan Ozerdem , Ustunsoy Hasim
Published: April 2011

Cardiac leiomyosarcoma is a rare tumor with poor survival prospects. Surgery prolongs survival, but the tumor often recurs early after surgery. The diagnosis is often made by transthoracic echocardiography. Magnetic resonance imaging and computed tomography are required to characterize the location and extent of cardiac masses. In this report, we present a patient with a leiomyosarcoma that was resected completely. The tumor was located in the left atrium, mimicked a myxoma, and protruded into the left ventricle during diastole.
Pericardial Tamponade due to Perforation of a Posterolateral Branch of the Circumflex Artery Caused by a Perforating Edge of a Resected Rib following Orthopedic Surgery in a 14-Year-Old Patient
Authors: Schachner Thomas , Laufer Guenther , Wiedemann Dominik , Chevtchik Orest
Published: April 2011

A 14-year-old female patient with Marfan syndrome was resuscitated because of pericardial tamponade following orthopedic surgery to correct scoliosis. The emergency sternotomy revealed injury to a posterolateral branch of the circumflex artery caused by pericardial perforation by the stump of a previously resected rib. Cardiopulmonary bypass immediately restored the circulation, and the primarily dilated, noncontractile heart regained its contractile function. The small posterolateral branch was sewn over, and the sharp edge of the rib stump was smoothed by abrasion and covered with a Gore-Tex membrane. The patient recovered completely during the remainder of her postoperative stay.
Process Review of a Departmental Change from Conventional Coronary Artery Bypass Grafting to Totally Arterial Coronary Artery Bypass and Its Effects on the Incidence and Severity of Postoperative Stroke
Authors: Albert Alexander , Sergeant Paul , Florath Ines , Ismael Mohammed , Rosendahl Ulrich , Ennker J�rgen
Published: April 2011

Background: We evaluated the process of changing from conventional coronary artery bypass grafting (CABG) to totally arterial off-pump coronary artery bypass (TOPCAB) at a single heart center in Germany.Methods: We (1) used multivariate statistical methods to assess real-time monitoring of OPCAB effects, (2) conducted a case review to assess preventable deaths and identify areas of improvement, (3) conducted a team survey, and (4) evaluated benchmarking results.Results: All surgeons and assistants (n = 18) at this center were involved and were guided by the department head and one of the consultants, who was trained in this procedure in 2004 at the Leuven OPCAB school. The frequency of OPCAB operations increased abruptly in 2005 from 5% to 43% and then increased gradually to 67% (n = 546) by 2008 (total, 1781 OPCAB cases and 1563 on-pump cases). The in-hospital and 30-day mortality rates for OPCAB surgeries (n = 10 [0.6%] and 21 [1.2%], respectively) were lower than for on-pump surgeries (n = 27 [1.7%] and 26 [1.7%], respectively). Stroke rates were also lower for OPCAB surgeries (7 cases [0.4%] versus 15 cases [1%]). The lower risk of stroke in the OPCAB group was significant (P < .05) after risk adjustment. Monitoring curves and case reviews demonstrated a preventable death percentage of at least 30%. The attitude of the team was mostly positive because of the promising results (eg, fewer strokes, increasing TOPCAB popularity, and a top national rank).Conclusions: The change from conventional CABG to TOPCAB was effective in decreasing the incidence and severity of stroke, in developing a team routine and a positive team attitude, and in producing excellent benchmarking results. The presence of a training and communication deficiency at the beginning of the study suggested an area for further improvement. After 6 years TOPCAB had largely replaced conventional CABG.
Vacinação contra influenza em idosos: prevalência, fatores associados e motivos da não-adesão em Campinas, São Paulo, Brasil
Authors: Francisco Priscila Maria Stolses Bergamo , Barros Marilisa Berti de Azevedo , Cordeiro Maria Rita Donalisio
Published: April 2011

O objetivo do estudo foi avaliar a prevalência de vacinação contra influenza em idosos e identificar os fatores associados e motivos da não-adesão à imunização. Estudo transversal de base populacional, com amostra estratificada por conglomerados e em dois estágios, realizado em Campinas, São Paulo, Brasil, em 2008 e 2009. Dos 1.517 idosos, 62,6% referiram vacinação no ano prévio. Atividade ocupacional, atividade física no lazer, diabetes, internação hospitalar e orientação de profissional de saúde estiveram associadas à vacina. Exceto para diabéticos, a vacinação em portadores de condições crônicas não atingiu níveis adequados. Os principais motivos para a não-adesão foram não considerar necessária e crença de que provoca reação. Condições socioeconômicas, estilo de vida e mobilidade física não restringiram o acesso, mas a cobertura esteve abaixo da meta estabelecida pelo Ministério da Saúde. Campanhas focadas nos idosos com 60 a 69 anos e nos portadores de doenças crônicas, bem como orientação do profissional de saúde, podem ampliar as coberturas em grupos que vêm apresentando baixa adesão às campanhas.
Perfil epidemiológico do beribéri notificado de 2006 a 2008 no Estado do Maranhão, Brasil
Authors: Padilha Estela Maura , Fujimori Elizabeth , Borges Ana Luiza Vilela , Sato Ana Paula Sayuri , Gomes Murilo Novaes , Branco Maria dos Remédios Freitas Carvalho , Santos Henrique Jorge dos , Lermen Junior Nulvio
Published: April 2011

O objetivo do estudo foi descrever o perfil epidemiológico dos casos e óbitos de beribéri notificados de 2006-2008 no Estado do Maranhão, Brasil. Informações foram obtidas de fichas de notificação da Secretaria de Estado da Saúde do Maranhão e utilizou-se o Índice Global de Moran para avaliar autocorrelação espacial. Foram notificados 1.207 casos e 40 óbitos. Regiões oeste e central mostraram forte presença de autocorrelação espacial da incidência. Ocorrência de casos e óbitos concentrou-se de maio a agosto, em homens jovens (20-40 anos). Hábito de consumir álcool e fumar esteve presente entre os óbitos; baixa renda e ocupação com atividade pesada, entre os casos. Os sintomas mais comuns foram diminuição da força, dormência e edema das pernas, dificuldade para caminhar e dor na panturrilha. O perfil dos acometidos e os sintomas, exceto edema de membros inferiores, são característicos de beribéri seco. É pertinente que estudos sobre seu ressurgimento no país sejam aprofundados.
Adaptação transcultural de um instrumento de avaliação do handicap auditivo para portadores de perda auditiva induzida pelo ruído ocupacional
Authors: Holanda Wanessa Tenório Gonçalves , Lima Maria Luiza Carvalho de , Figueiroa José Natal
Published: April 2011

A Perda Auditiva Induzida pelo Ruído Ocupacional (PAIRO) é uma doença crônica e irreversível resultante da exposição a elevados níveis de ruído no trabalho que, mesmo no estágio inicial, pode comprometer em vários graus a qualidade de vida do trabalhador. Não existia disponível para a língua portuguesa um instrumento específico de avaliação das implicações psicossociais para portadores de PAIRO. O objetivo desse trabalho foi realizar a adaptação transcultural de um instrumento de avaliação do handicap auditivo da língua original para o português e avaliar sua confiabilidade e validade. O instrumento selecionado passou por um processo de equivalência semântica, que envolveu as etapas de tradução, retradução, apreciação formal da equivalência, pré-teste e crítica final por uma equipe multiprofissional para a elaboração da versão final para uso corrente no Brasil. A Escala de Inabilidades e Handicap Auditivo obteve medidas psicométricas consideradas, em geral, aceitáveis, considerando o tamanho reduzido da amostra e o fato de os participantes não possuírem perdas auditivas muito acentuadas. Portanto, tal escala precisa ser testada em amostras maiores e representativas de trabalhadores brasileiros portadores de PAIRO, a fim de ser ratificada a sua utilidade para a avaliação do handicap auditivo nessa população.
Surdez, redes sociais e proteção social
Authors: Bittencourt Zélia Zilda Lourenço de Camargo , Françozo Maria de Fátima de Campos , Monteiro Claudia Rodrigues , Francisco Débora Durante
Published: April 2011

A surdez traz repercussões na vida do indivíduo que por ela é afetado, assim como na vida da família, que usualmente deve modificar sua dinâmica para adequar-se às necessidades e demandas que a perda auditiva impõe. Muitas vezes, para isso, a família mobiliza recursos internos, mas também busca apoio e ajuda fora de seu núcleo, em uma rede de recursos externos. Descrever as redes sociais acessadas pelas famílias de surdos na busca de sua reprodução cotidiana é um dos objetivos a que este texto se propõe. Ainda, busca discutir o significado dessas redes no contexto da proteção social. Para isso, pesquisa qualitativa foi desenvolvida, através de entrevistas semiestruturadas com dezoito pais de crianças ou adolescentes surdos, usuários de programas de atendimento em um centro de reabilitação. O mapeamento das redes de relacionamentos e de recursos sociais acessados por famílias de pessoas surdas mostrou o entrelaçamento de relações entre os familiares, demais parentes, amigos, vizinhos, profissionais, organizações privadas e serviços públicos. As redes cumprem papel de apoio e proteção social para a família da pessoa surda na reprodução cotidiana da vida.
Surveillance of birth defects: Brazil and the US
Authors: Luquetti Daniela Varela , Koifman Rosalina Jorge
Published: April 2011

The impacts of birth defects in the society have substantially increased over the last decades in countries where the reduction of infant mortality by other causes has occurred. Birth defects surveillance represents an important source of information for planning X health policies and resource allocation. In this article, we discuss the potential utilizations, methodology options, limitations, and policy issues related to birth defects surveillance. Also, the birth defects surveillance programs from US and Brazil are described and compared as an illustration of the development of surveillance systems in two countries with clearly dissimilar health systems and resource allocation for birth defects programs. Finally, we propose measures for the improvement of the existing systems in both countries focusing at the utilization of preexisting resources.
Termo de consentimento livre e esclarecido aos usuários de clínicas odontológicas brasileiras: aspectos éticos e legais
Authors: Sales-Peres Sílvia Helena de Carvalho , Sales-Peres Arsênio , Eleutério Adriana Silveira de Lima , Oliveira José Luiz Góes de , Gigliotti Mariana Pracucio
Published: April 2011

O consentimento do paciente antes do início de qualquer procedimento é uma condição a ser respeitada pelos profissionais da odontologia, sem nenhuma exceção. É necessário que o paciente esteja ciente de seu status de saúde, de suas necessidades específicas, do propósito de cada tratamento, conheça os planejamentos alternativos (incluindo o não tratamento), saiba do seu prognóstico, riscos, consequências, limitações e se conscientize das suas responsabilidades e as do seu cirurgião-dentista, proporcionando o sucesso do tratamento. O termo de consentimento livre e esclarecido (TCLE) visa fortalecer e esclarecer a posição do paciente, estabelecendo os direitos e deveres de ambas as partes paciente e profissional. O conhecimento integral do tratamento diminuirá a ansiedade do paciente e as complicações de tratamento, promoverá maior qualidade dos serviços odontológicos e maior satisfação do dentista e do paciente. Entretanto, no Brasil, poucos artigos são encontrados e existem alguns problemas éticos envolvendo as clínicas odontológicas, no que diz respeito a este documento de esclarecimento para o paciente. Diante disso, este trabalho tem por objetivo realizar uma revisão crítica sobre o tema abordado, demonstrando a importância do TCLE na clínica odontológica brasileira e na vida profissional dos cirurgiões-dentistas.
Personality, Drug Preference, Drug Use, and Drug Availability
Authors: Feldman Marc , Boyer Bret , Kumar V. K. , Prout Maurice
Published: April 2011

This study examined the relationship between drug preference, drug use, drug availability, and personality among individuals ( n = 100) in treatment for substance abuse in an effort to replicate the results of an earlier study (Feldman, Kumar, Angelini, Pekala, & Porter, 2007) designed to test prediction derived from Eysenck's (1957, 1967) theories. Drug preference was measured by the method of paired-comparison and personality was measured with the Zuckerman-Kuhlman Personality Questionnaire-50 CC. Contrary to expectations, high compared with low scorers on Sociability and Impulsive-Sensation Seeking preferred depressants. Surprisingly, low compared with high scorers on neuroticism did not differ in preference for alcohol. As in the previous study, drug preference, use, and availability were highly correlated, although ease of availability was slightly more predictive of drug use than drug preference. Clinical and theoretical implications are discussed.
In Vivo Conditional Pax4 Overexpression in Mature Islet β-Cells Prevents Stress-Induced Hyperglycemia in Mice
Authors: He Kai Hui Hu , Lorenzo Petra I. , Brun Thierry , Jimenez Moreno Carmen M. , Aeberhard Deborah , Ortega Jorge Vallejo , Cornu Marion , Thorel Fabrizio , Gjinovci Asllan , Thorens Bernard , Herrera Pedro L. , Meda Paolo , Wollheim Claes B. , Gauthier Benoit R.
Published: April 2011

OBJECTIVE

To establish the role of the transcription factor Pax4 in pancreatic islet expansion and survival in response to physiological stress and its impact on glucose metabolism, we generated transgenic mice conditionally and selectively overexpressing Pax4 or a diabetes-linked mutant variant (Pax4R129W) in β-cells.

RESEARCH DESIGN AND METHODS

Glucose homeostasis and β-cell death and proliferation were assessed in Pax4- or Pax4R129W-overexpressing transgenic animals challenged with or without streptozotocin. Isolated transgenic islets were also exposed to cytokines, and apoptosis was evaluated by DNA fragmentation or cytochrome C release. The expression profiles of proliferation and apoptotic genes and β-cell markers were studied by immunohistochemistry and quantitative RT-PCR.

RESULTS

Pax4 but not Pax4R129W protected animals against streptozotocin-induced hyperglycemia and isolated islets from cytokine-mediated β-cell apoptosis. Cytochrome C release was abrogated in Pax4 islets treated with cytokines. Interleukin-1β transcript levels were suppressed in Pax4 islets, whereas they were increased along with NOS2 in Pax4R129W islets. Bcl-2, Cdk4, and c-myc expression levels were increased in Pax4 islets while MafA, insulin, and GLUT2 transcript levels were suppressed in both animal models. Long-term Pax4 expression promoted proliferation of a Pdx1-positive cell subpopulation while impeding insulin secretion. Suppression of Pax4 rescued this defect with a concomitant increase in pancreatic insulin content.

CONCLUSIONS

Pax4 protects adult islets from stress-induced apoptosis by suppressing selective nuclear factor-κB target genes while increasing Bcl-2 levels. Furthermore, it promotes dedifferentiation and proliferation of β-cells through MafA repression, with a concomitant increase in Cdk4 and c-myc expression.
Liver Enzymes Are Associated With Hepatic Insulin Resistance, Insulin Secretion, and Glucagon Concentration in Healthy Men and Women
Authors: Bonnet Fabrice , Ducluzeau Pierre-Henri , Gastaldelli Amalia , Laville Martine , Anderwald Christian H. , Konrad Thomas , Mari Andrea , Balkau Beverley ,   for the RISC Study Group
Published: April 2011

OBJECTIVE

The pathophysiological mechanisms to explain the association between risk of type 2 diabetes and elevated concentrations of γ-glutamyltransferase (GGT) and alanineaminotransferase (ALT) remain poorly characterized. We explored the association of liver enzymes with peripheral and hepatic insulin resistance, insulin secretion, insulin clearance, and glucagon concentration.

RESEARCH DESIGN AND METHODS

We studied 1,309 nondiabetic individuals from the Relationship between Insulin Sensitivity and Cardiovascular disease (RISC) study; all had a euglycemic-hyperinsulinemic clamp and an oral glucose tolerance test (OGTT) with assessment of insulin secretion and hepatic insulin extraction. The hepatic insulin resistance index was calculated in 393 individuals.

RESULTS

In both men and women, plasma concentrations of GGT and ALT were inversely related with insulin sensitivity (M/I) (all P < 0.01). Likewise, the hepatic insulin resistance index was positively correlated with both GGT (r = 0.37, P < 0.0001, men; r = 0.36, P < 0.0001, women) and ALT (r = 0.25, P = 0.0005, men; r = 0.18, P = 0.01, women). These associations persisted in multivariable models. Increased GGT and ALT were significantly associated with higher insulin secretion rates and with both reduced endogenous clearance of insulin and hepatic insulin extraction during the OGTT (P = 0.0005 in men; P = 0.003 in women). Plasma fasting glucagon levels increased over ALT quartiles (men, quartile 4 vs. quartile 1 11.2 ± 5.1 vs. 9.3 ± 3.8 pmol/L, respectively, P = 0.0002; women, 9.0 ± 4.3 vs. 7.6 ± 3.1, P = 0.001).

CONCLUSIONS

In healthy individuals, increased GGT and ALT were biomarkers of both systemic and hepatic insulin resistance with concomitant increased insulin secretion and decreased hepatic insulin clearance. The novel finding of a positive correlation between ALT and fasting glucagon level concentrations warrants confirmation in type 2 diabetes.
Vitamin D Levels, Microvascular Complications, and Mortality in Type 1 Diabetes
Authors: Joergensen Christel , Hovind Peter , Schmedes Anne , Parving Hans-Henrik , Rossing Peter
Published: April 2011

OBJECTIVE

To evaluate vitamin D as a predictor of all-cause mortality, progression from normoalbuminuria to micro- or macroalbuminuria, and the development of background or proliferative retinopathy in patients with type 1 diabetes.

RESEARCH DESIGN AND METHODS

A prospective observational follow-up study in which an inception cohort of type 1 diabetic patients was followed from onset of diabetes diagnosed between 1979 and 1984. Plasma vitamin D [25(OH)D3] levels were determined by high performance liquid chromatography/tandem mass spectrometry in 227 patients before the patients developed microalbuminuria. Values equal to or below the 10% percentile (15.5 nmol/L) were considered severe vitamin D deficiency.

RESULTS

Median (range) vitamin D was 44.6 (1.7–161.7) nmol/L. Vitamin D level was not associated with age, sex, urinary albumin excretion rate (UAER), or blood pressure. During follow-up, 44 (18%) patients died. In a Cox proportional hazards model, the hazard ratio for mortality in subjects with severe vitamin D deficiency was 2.7 (1.1–6.7), P = 0.03, after adjustment for UAER, HbA1c, and conventional cardiovascular risk factors (age, sex, blood pressure, cholesterol, smoking). Of the 220 patients, 81 (37%) developed microalbuminuria and 27 (12%) of these progressed to macroalbuminuria. Furthermore, 192 (87%) patients developed background retinopathy, whereas 34 (15%) progressed to proliferative retinopathy. Severe vitamin D deficiency at baseline did not predict the development of these microvascular complications.

CONCLUSIONS

In patients with type 1 diabetes, severe vitamin D deficiency independently predicts all-cause mortality but not development of microvascular complications in the eye and kidney. Whether vitamin D substitution in type 1 diabetic patients can improve the prognosis remains to be investigated.
Diabetic Retinopathy Predicts All-Cause Mortality and Cardiovascular Events in Both Type 1 and 2 Diabetes
Authors: Kramer Caroline K. , Rodrigues Ticiana C. , Canani Luis H. , Gross Jorge L. , Azevedo Mirela J.
Published: April 2011

OBJECTIVE

The prognostic significance of diabetic retinopathy (DR) for death and cardiovascular (CV) outcomes is debated. We investigated the association of DR with all-cause mortality and CV events in patients with diabetes by a systematic review and meta-analysis.

RESEARCH DESIGN AND METHODS

The electronic databases Medline and Embase were searched for cohort studies that evaluated DR in type 2 or type 1 diabetic patients and reported total mortality and/or fatal and nonfatal CV events, including myocardial infarction, angina pectoris, coronary artery bypass graft, ischemic changes on a conventional 12-lead electrocardiogram, transient ischemic attack, nonfatal stroke, or lower leg amputation. Data extraction was performed by two reviewers independently. Pooled effect estimates were obtained by using random-effects meta-analysis.

RESULTS

The analysis included 20 studies that fulfilled the inclusion criteria, providing data from 19,234 patients. In patients with type 2 diabetes (n = 14,896), the presence of any degree of DR increased the chance for all-cause mortality and/or CV events by 2.34 (95% CI 1.96–2.80) compared with patients without DR. In patients with type 1 diabetes (n = 4,438), the corresponding odds ratio was 4.10 (1.50–11.18). These associations remained after adjusting for traditional CV risk factors. DR was also predictive of all-cause mortality in type 2 diabetes (odds ratio 2.41 [1.87–3.10]) and type 1 diabetes (3.65 [1.05–12.66]).

CONCLUSIONS

The presence of DR was associated with an increased risk of all-cause mortality and CV events in both type 2 and type 1 diabetic patients.
Myocardial, Perivascular, and Epicardial Fat
Authors: Iozzo Patricia
Published: April 2011

Myocardial fat content refers to the storage of triglyceride droplets within cardiomyocytes. In addition, the heart and arteries are surrounded by layers of adipose tissue, exerting vasocrine and paracrine control of the subtending tissues. The rapid development of the field of noninvasive imaging has made it possible to quantify ectopic fat masses and contents with an increasing degree of accuracy. Myocardial triglyceride stores are increased in obesity, impaired glucose tolerance, and type 2 diabetes. The role of intramyocardial triglyceride accumulation in the pathogenesis of left ventricular (LV) dysfunction remains unclear. Increased triglyceride content is associated with states of fatty acid overload to the heart, saturating the oxidative capacity. It may initially serve as a fatty acid sink to circumscribe the formation of toxic lipid species and subsequently foster cardiac damage. Epicardial and perivascular fat depots may exert a protective modulation of vascular function and energy partition in a healthy situation, but their expansion turns them into an adverse lipotoxic, prothrombotic, and proinflammatory organ. They are augmented in patients with metabolic disorders and coronary artery disease (CAD). However, the progressive association between the quantity of fat and disease severity in terms of extent of plaque calcification or noncalcified areas, markers of plaque vulnerability, and number of vessels involved is less confirmed. Functional or hybrid imaging may contribute to a better definition of disease severity and unveil the direct myocardial and vascular targets of adipose tissue action.
Subnormal, permutable, and embedded subgroups in finite groups
Authors: Beidleman James , Ragland Mathew
Published: April 2011

The purpose of this paper is to study the subgroup embedding properties of S-semipermutability, semipermutability, and seminormality. Here we say H is S-semipermutable (resp. semipermutable) in a group Gif H permutes which each Sylow subgroup (resp. subgroup) of G whose order is relatively prime to that of H. We say H is seminormal in a group G if H is normalized by subgroups of G whose order is relatively prime to that of H. In particular, we establish that a seminormal p-subgroup is subnormal. We also establish that the solvable groups in which S-permutability is a transitive relation are precisely the groups in which the subnormal subgroups are all S-semipermutable. Local characterizations of this result are also established.
Ethephon and Aventrol as tools to enhance spring rape productivity
Authors: Darginavičienė Jūratė , Novickienė Leonida , Gavelienė Virgilija , Jurkonienė Sigita , Kazlauskienė Danguolė
Published: April 2011

Ethephon and Aventrol were used as tools to provoke the processes taking part in the formation of rape seed yield and quality. Investigations on spring rape (Brassica napus L.) cultivars ‘Terra’ and ‘Landmark’ were carried out from 2008–2010. Ethephon (10 mM) and Aventrol (1 l/ha — pinolene 960 g/l) were used on different plant growth stages: BBCH-62–64 and BBCH-72–74, BBCH-80–82, respectively. Impact of ethephon manifested itself as activation of ethylene evocation by siliqua and a slight activation of growth of siliqua dehiscence zone. Siliqua cell plasmalemma and tonoplast H+-ATPases activation under the influence of ethephon occurred but did not lead to the destruction of transmembrane electrochemical potential. Extra seed yield and crude fat yield increased; tendency towards a lowering of the saturated/unsaturated fatty acid ratio was observed. Under the influence of Aventrol the dehiscence zone of siliqua was more closed when compared to the control and the ethephon treated variants, seed loss was significantly lowered and transmembrane cation transport was not damaged. The seed yield increased, and this was due to the accumulation of extra crude fat. Aventrol did not change the fatty acid content in rape seed oil. The positive impacts of ethephon and Aventrol for spring rape seed yield formation and possible mechanisms are discussed.
Genetic differences within natural and planted stands of Quercus petraea
Authors: Dostálek Jiří , Frantík Tomáš , Lukášová Miroslava
Published: April 2011

Five sessile oak [Quercus petraea (Matt.) Liebl.] stands from the Czech Republic were studied to learn about the impact of different types of forest management regimes on the genetic differences among tree populations and on population structures. One population had not been markedly affected by human activity, two populations represented unplanted stands that were extensively managed for a long period of time using the coppice system, and two populations were planted stands. Approximately 100 trees from each stand were mapped and subsequently genotyped using 10 nuclear microsatellite loci. We determined the spatial genetic structure of each population and the genetic differentiation among the populations. We found that: (i) the populations were genetically differentiated, but the differences between the unplanted and planted stands were not markedly significant; (ii) the genetic differentiation among the populations depended on the geographical distribution of the populations; (iii) within unplanted stands, a strong spatial genetic structure was seen; and (iv) within planted stands, no spatial genetic structure was observed. Our findings implies that the analysis of spatial genetic structure of the sessile oak forest stand can help reveal and determine its origin.
Polymorphisms of interleukin-4, -10 and 12B genes and diabetic retinopathy
Authors: Cilenšek Ines , Hercegovac Amela , Starčević Jovana , Vukojević Katarina , Babić Mirna , Živin Aleksandra
Published: April 2011

In diabetic retinopathy (DR) and other angiogenesis-associated diseases, increased levels of cytokines, inflammatory cells, and angiogenic factors are present. We investigated the hypothesis that rs2243250 polymorphism of the interleukin 4 (IL-4) gene or rs1800896 polymorphism of the interleukin 10 (IL-10) gene, and rs3212227 polymorphism of the 3’ untranslated region (3’ UTR) of the interleukin-12 p40 gene (IL12B) may be associated with the development of proliferative diabetic retinopathy (PDR) in Caucasians with type 2 diabetes (DM2). This cross sectional case — control study included 189 patients with PDR and 187 patients with type 2 diabetes without PDR. Polymorphisms rs1800896 of the IL-10 gene, rs2243250 of the IL-4 gene, and rs3212227 of IL12B gene were analyzed by ARMS -PCR and RFLP -PCR methods. Multivariate analysis demonstrated the GG genotype of the rs1800896 polymorphism of the IL-10 gene to be associated with increased risk for PDR (OR=1.99; 95% CI=1.11–3.57; P=0.02), whereas the TT genotype of the rs2243250 polymorphism of the IL-4 gene and the AA genotype of the rs3212227 polymorphism of the IL-12 gene were not independent risk factors for PDR. Our findings suggest that the genetic variations at the IL-10 promoter gene might be a genetic risk factor for PDR in Caucasians with type 2 diabetes.
A New Monitoring Protocol for Clozapine-Induced Myocarditis Based on an Analysis of 75 Cases and 94 Controls
Authors: Ronaldson Kathlyn J. , Fitzgerald Paul B. , Taylor Andrew J. , Topliss Duncan J. , McNeil John J.
Published: April 2011

Objective: To develop an evidence-based monitoring protocol for clozapine-induced myocarditis.

Methods: Potential cases of clozapine-related myocarditis occurring between January 1994 and January 2009 and a comparative group of patients taking clozapine for at least 45 days without cardiac disease were documented from the patients’ medical records.

Results: A total of 75 cases and 94 controls were included. Nine cases died. The time to onset was 10–33 days with 83% of cases developing between days 14 and 21 inclusive.

At least twice the upper limit of normal troponin was found in 90% of cases, but 5 cases had C-reactive protein more than 100 mg/L and left ventricular impairment by echocardiography without a clinically significant rise in troponin.

The proposed monitoring protocol recommends obtaining baseline troponin I/T, C-reactive protein and echocardiography, and monitoring troponin and C-reactive protein on days 7, 14, 21 and 28. Mild elevation in troponin or C-reactive protein, persistent abnormally high heart rate or signs or symptoms consistent with infective illness should be followed by daily troponin and C-reactive protein investigation until features resolve. Cessation of clozapine is advised if troponin is more than twice the upper limit of normal or C-reactive protein is over 100 mg/L. Combining these two parameters has an estimated sensitivity for symptomatic clozapine-induced myocarditis of 100%. The sensitivity for asymptomatic disease is unknown.

Conclusion: This protocol recommends active monitoring for 4 weeks, relying predominantly on troponin and C-reactive protein results. It encourages continuation of clozapine in the presence of mild illness, but defines a threshold for cessation.
Options for REDD+ Voluntary Certification to Ensure Net GHG Benefits, Poverty Alleviation, Sustainable Management of Forests and Biodiversity Conservation
Authors: Merger Eduard , Dutschke Michael , Verchot Louis
Published: April 2011

Our objective was to compare and evaluate the practical applicability to REDD+ of ten forest management, social, environmental and carbon standards that are currently active worldwide: Climate, Community and Biodiversity (CCB), CCB REDD+ Social and Environmental Standards (CCBA REDD+ S&E), CarbonFix Standard (CFS), Forest Stewardship Council (FSC), Global Conservation Standard (GCS), ISO 14064:2006, Plan Vivo Standard, Programme for Endorsement of Forest Certification (PEFC), SOCIALCARBON Standard and the Voluntary Carbon Standard (VCS). We developed a framework for evaluation of these standards relative to each other using four substantive criteria: (1) poverty alleviation, (2) sustainable management of forests (SMF), (3) biodiversity protection, (4) quantification and assessment of net greenhouse gas (GHG) benefits; and two procedural criteria: (5) monitoring and reporting, and (6) certification procedures. REDD programs require assessment of GHG benefits, monitoring, reporting and certification. Our analysis shows that only the Voluntary Carbon Standard (VCS) treats these three criteria comprehensively. No standard provides comprehensive coverage of the social and other environmental criteria. FSC, PEFC and CarbonFix provide comprehensive assessments of the sustainable forest management criterion. CCBA REDD+ S&E, CCB, and GCS provide comprehensive coverage of the biodiversity and poverty alleviation criteria. Experience in using these standards in pilot projects shows that projects are currently combining several standards as part of their strategy to improve their ability to attract investment, but costs of implementing several certification schemes is a concern. We conclude that voluntary certification provides useful practical experience that should feed into the design of the international REDD+ regime.
Surface Modification of Poly(L-lactic acid) Nanofiber with Oligo(D-lactic acid) Bioactive-Peptide Conjugates for Peripheral Nerve Regeneration
Authors: Kakinoki Sachiro , Uchida Sho , Ehashi Tomo , Murakami Akira , Yamaoka Tetsuji
Published: April 2011

In some traumatic nerve injuries, autologous nerve grafting is the first choice for bridging the gap between the severed nerve ends. However, this therapeutic strategy has some disadvantages, including permanent loss of donor function and requirement of multiple surgeries. An attractive alternative to this therapeutic technique is the use of artificial nerve conduit. Poly (L-lactic acid) (PLLA) is widely used as a substrate for artificial nerve conduit because it is readily biodegradable, but it is not inherently biologically active. In this study, we developed a PLLA nanofibrous nerve conduit, modified with a conjugate of oligo (D-lactic acid) (ODLA) and the neurite outgrowth, thereby promoting peptide AG73 (RKRLQVQLSIRT) to improve nerve regeneration. PLA/ODLA-AG73 nanofibrous conduit was fabricated by electrospinning and then transplanted at the 10 mm gap of rat sciatic nerve. After six months, electrophysiological evaluation revealed that it achieved better functional reinnervation than silicone tube (used as a reference) or unmodified PLLA nanofibrous conduit.
Automated Generation of Digital Terrain Model using Point Clouds of Digital Surface Model in Forest Area
Authors: Bandara Kande R.M.U. , Samarakoon Lal , Shrestha Rajendra P. , Kamiya Yoshikazu
Published: April 2011

At present, most of the digital data acquisition methods generate Digital Surface Model (DSM) and not a Digital Elevation Model (DEM). Conversion from DSM to DEM still has some drawbacks, especially the removing of off terrain point clouds and subsequently the generation of DEM within these spaces even though the methods are automated. In this paper it was intended to overcome this issue by attempting to project off terrain point clouds to the terrain in forest areas using Artificial Neural Networks (ANN) instead of removing them and then filling gaps by interpolation. Five sites were tested and accuracies assessed. They all give almost the same results. In conclusion, the ANN has ability to obtain the DEM by projecting the DSM point clouds and greater accuracies of DEMs were obtained. If the size of the hollow areas resulting from the removal of DSM point clouds are larger the accuracies are reduced.