Dose efetiva de sedação em ecocardiograma transesofágico: relação com idade, área de superfície e função do ventrículo esquerdo

FUNDAMENTO: A sedação com midazolam e meperidina é amplamente utilizada em ecocardiografia transesofágica, entretanto, não existe dose média estabelecida para cada caso. OBJETIVO: Correlacionar as doses médias de midazolam e meperidina para sedação adequada em ecocardiografia transesofágica com faixa etária, área de superfície corpórea e fração de ejeção do ventrículo esquerdo. MÉTODOS: Estudo retrospectivo envolvendo 1.841 pacientes submetidos à sedação baseada na escala de Ramsay, com solução contendo midazolam 1,5 mg (1,5 ml), meperidina 1 mg (1 ml) e água destilada (7,5 ml). Analisamos quatro grupos etários: G1: < 24 anos; G2: 25 a 44 anos; G3: 45 a 64 anos; e G4: > 65 anos. Obtivemos a área de superfície corpórea pela fórmula: {[(altura x 100)0,725] x (peso0,425) x 0,0071}. Com relação à fração de ejeção do ventrículo esquerdo, estudamos dois grupos: GA: < 55%; e GB: > 55%. Na análise estatística utilizamos o teste de Kruskal-Wallis para correlação com idade e fração de ejeção do ventrículo esquerdo, e correlação linear simples para área de superfície corpórea. RESULTADOS: No estudo da idade, as doses médias de sedação necessárias foram significativamente menores no G3 e G4 (p < 0,01). Na análise da fração de ejeção do ventrículo esquerdo, esta foi significativamente menor no GA (p < 0,01). O coeficiente de correlação linear entre dose de sedação e área de superfície corpórea foi 0,09 (nulo). CONCLUSÃO: Houve menor dose média necessária de sedativos nos indivíduos com maior idade e em portadores de disfunção sistólica do ventrículo esquerdo, e não houve correlação com área de superfície corpórea.

Perfil eletrocardiográfico e conteúdo glicogênico muscular de ratos tratados com nandrolona

FUNDAMENTO: Considerou-se o uso indiscriminado de esteroides tanto por atletas de elite quanto por praticantes de atividades físicas. OBJETIVO: Avaliar os efeitos do decanoato de nandrolona sobre o perfil eletrocardiográfico, conteúdo glicogênico e de proteínas totais dos músculos cardíacos e esqueléticos, bem como as concentrações plasmática de albumina. MÉTODOS: Os animais do grupo tratado receberam a droga na concentração 5 mg/kg pela via subcutânea, duas vezes por semana, durante três semanas. Uma vez por semana, os ratos foram anestesiados com Pentobarbital sódico (50 mg/kg, ip) e submetidos à avaliação por meio do eletrocardiograma (ECG). Após o período experimental, amostras dos músculos cardíaco (ventrículo esquerdo - VE), sóleo (S), gastrocnêmio branco (GB), gastrocnêmio vermelho (GV), peitoral (P), intercostal (IC) e diafragma (D) foram prontamente coletadas e analisadas. Os dados (média ± epm) foram avaliados de acordo com ANOVA, segundo teste de Tukey (p>0,05). RESULTADOS: Os ratos do grupo tratado apresentaram alterações nos seguintes parâmetros cardíacos: intervalo QRS, intervalo QTc e frequência cardíaca, caracterizados por um aumento desses, tendo o ápice no intervalo da semana de pré-tratamento para a primeira semana. As reservas de glicogênio no VE apresentaram aumento de 127%. Em relação à quantidade de proteínas totais, a diferença significativa foi constatada no S, GV e D. Quanto ao perfil bioquímico e ao hematócrito, foi observado um aumento na porcentagem de eritrócitos. CONCLUSÃO: O estudo mostra que importantes alterações cardíacas são deflagradas precocemente, sugerindo uma hierarquia na sequência de modificações que comprometem a homeostasia do organismo.

Cirurgia valvar mitral e da comunicação interatrial: abordagem minimamente invasiva ou por esternotomia

FUNDAMENTO: Para diminuir o trauma cirúrgico em procedimentos cardiovasculares, técnicas Minimamente Invasivas (MI) foram alternativamente introduzidas. OBJETIVO: Comparar o acesso cirúrgico MI com a Esternotomia Mediana (EM) para tratar a cardiopatia valvar mitral (VM) e a Comunicação Interatrial (CIA). MÉTODOS: Estudo prospectivo onde quarenta pacientes foram submetidos a cirurgia para correção de cardiopatia VM ou CIA. Foram divididos em: grupo A (GA) (n = 20), de acesso por minitoracotomia direita com videoassistência, e grupo B (GB) (n = 20), de acesso por EM. Comparamos: tempo de pinçamento aórtico e circulação extracorpórea, tempo de permanência na Unidade de Terapia Intensiva (UTI), tempo de hospitalização e morbidade. RESULTADOS: Quinze pacientes foram submetidos a procedimento VM e 5 a correção de CIA, em cada grupo. Houve nove trocas mitrais (sete bioprotéticas e duas mecânicas) e seis reconstruções no GA, e 10 trocas (todas bioprotéticas) e cinco reconstruções no GB. As médias de tempo de pinçamento aórtico e circulação extracorpórea, em minutos, foram 65,1 ± 29,3 no GA, e 50,2 ± 21,4 no GB (p = 0,074); e 91,8 ± 35 no GA, e 63,7 ± 27,3 no GB (p = 0,008). As médias de tempo de UTI, em horas, foram 51,7 ± 16,3 no GA, e 55,8 ± 17,5 no GB (p = 0,45). Os tempos de hospitalização, em dias, foram 5,2 ± 1 no GA, e 6,4 ± 1,5 no GB (p = 0,009). CONCLUSÃO: O acesso MI para correção da cardiopatia VM e da CIA implicaram em maior tempo de circulação extracorpórea para a finalização do procedimento principal sem, no entanto, afetar a recuperação do paciente. Os pacientes tratados de forma MI tiveram alta hospitalar mais cedo que os pacientes tratados com esternotomia.

Psychoedukation bei Menschen mit geistiger Behinderung und Angststörungen

Das Risiko eine psychische Störung zu entwickeln ist für Menschen mit geistiger Behinderung im Gegensatzzu Menschen ohne geistiger Behinderung (GB) insgesamt 3-4 fach erhöht. Jenes rührt mitunterdaher, dass der Entwicklung gesundheitsförderlicher und stressbewältigender Ressourcen vergleichsweiseeine größere Anzahl an Einschränkungen unterliegt. Darunter zählen eine geringereFähigkeit in Kommunikation, Selbstreflexion, dem Wahrnehmen, anders als andere zu sein und einemdamit einhergehenden verminderten Selbstbewusstsein, etc.Betrachtet man nun die Störungsgruppe der Angststörungen, deuten die Prävalenzen darauf, dassErkrankungen aus diesem Formenkreis in der Allgemeinbevölkerung am häufigsten auftreten. Dapsychische Erkrankungen bei Menschen mit GB derselben Ätiologie unterliegen, wie bei Menschenohne GB, verwundert das ebenfalls hohe Auftreten der Angststörungen bei Menschen mit GB nicht.Aufgrund diagnostischer Schwierigkeiten und verminderter Forschungen gelten diese sogar noch alsunterdiagnostiziert.Nicht nur die Forschungsansätze und Assessmentverfahren sind bei Menschen mit GB in vermindertemAngebot auffindbar, sondern auch Behandlungsansätze. Behandlungen wären bei Menschen mitGB nicht ohne weiteres anwendbar, sondern bedürften einer auf deren spezielle Bedürfnisse angepassteModifizierung. Diese soll die Therapien für Menschen mit Einschränkungen in Kognition,Kommunikation, Aufmerksamkeitskapazität etc. zugänglich und nachhaltig wirksam gestalten. Hierfürbieten sich einige Techniken an, wie die Anwendung des umfassenden Regelwerks der Leichten Sprache,einer verkürzten Sitzungsdauer bei gleichzeitiger erhöhter Sitzungsfrequenz, sowie das Abstrahierender Inhalte auf möglichst konkrete Darstellungen.Menschen mit Behinderungen steht ein gleichgestellter, multidim

Ocorrência de Salmonella em gânglios linfáticos de suínos aparentemente normais, abatidos no matadouro de Santa Cruz, cidade do Rio de Janeiro, Guanabara

Foi realizada uma investigação sobre a presença de Salmonella em gânglios linfáticos pré-escapulares, pré-crurais e mesentéricos, de 59 suínos aparentemente normais, abatidos no Matadouro de Sanata Cruz, Rio de Janeiro, GB. De um total de 177 gãnglios examinados isolaram-se 27 amostras de salmonelas, das quais 14 (51,84%) eram de gânglios mesentéricos: 5 (18.51%) de gânglios pré-escapulares e 8 (29,62%), de gânglios pré-crurais. A identificação sorológica das 27 Salmonella isoladas, revelou a existência de 4 sorotipos diferentes de Salmonella enteritidis distribuídos em dois grupos, com dominância do grupo somático B (soro tipo Typhimurium), para os gânglios mesentéricos, e 3 sorotipos distribuídos em 3 grupos, com dominância do grupo somático El (Sorotipo Anatum), para os gânglios pré-escapulares e pré-crurais. Considerando a presença de salmonellas em gãnglios pré-escapulares e pré-crurais, em 8,4% dos suínos examinados, os autores sugerem que estes gãnglios, sejam durante a fase de evisceração, retirados das carcaças dos animais, antes das mesmas serem enviadas para o consumo oúblico a fim de diminuir a contaminação pós-morte das carnes.

Ant genomics sheds light on the molecular regulation of social organization.

Ants are powerful model systems for the study of cooperation and sociality. In this review, we discuss how recent advances in ant genomics have contributed to our understanding of the evolution and organization of insect societies at the molecular level.

Conserved microRNA editing in mammalian evolution, development and disease.

BACKGROUND: Mammalian microRNAs (miRNAs) are sometimes subject to adenosine-to-inosine RNA editing, which can lead to dramatic changes in miRNA target specificity or expression levels. However, although a few miRNAs are known to be edited at identical positions in human and mouse, the evolution of miRNA editing has not been investigated in detail. In this study, we identify conserved miRNA editing events in a range of mammalian and non-mammalian species. RESULTS: We demonstrate deep conservation of several site-specific miRNA editing events, including two that date back to the common ancestor of mammals and bony fishes some 450 million years ago. We also find evidence of a recent expansion of an edited miRNA family in placental mammals and show that editing of these miRNAs is associated with changes in target mRNA expression during primate development and aging. While global patterns of miRNA editing tend to be conserved across species, we observe substantial variation in editing frequencies depending on tissue, age and disease state: editing is more frequent in neural tissues compared to heart, kidney and testis; in older compared to younger individuals; and in samples from healthy tissues compared to tumors, which together suggests that miRNA editing might be associated with a reduced rate of cell proliferation. CONCLUSIONS: Our results show that site-specific miRNA editing is an evolutionarily conserved mechanism, which increases the functional diversity of mammalian miRNA transcriptomes. Furthermore, we find that although miRNA editing is rare compared to editing of long RNAs, miRNAs are greatly overrepresented among conserved editing targets.

Impact of genetic polymorphisms in cytomegalovirus glycoprotein B on outcomes in solid-organ transplant recipients with cytomegalovirus disease.

BACKGROUND:It is unknown whether specific viral polymorphisms affect in vivo therapeutic response in patients with cytomegalovirus (CMV) disease. Polymorphisms in the CMV glycoprotein B (gB) gene allow discrimination of 4 distinct genotypes (gB1-gB4). We assessed the influence of gB genotypes on the clinical and virologic outcome of CMV disease. METHODS:Solid-organ transplant recipients enrolled in a multicenter trial of CMV disease treatment (VICTOR study) were included in this study. CMV gB genotyping was performed using quantitative real-time polymerase chain reaction at day 0 (start of antiviral therapy). RESULTS:Among 239 patients with CMV disease, the prevalence of gB strain types was 26% for gB1, 10% for gB2, 10% for gB3, and 5% for gB4, whereas mixed infections were present in 49%. Donor-seropositive/recipient-seropositive patients were more likely to have mixed gB infection than donor-seropositive/recipient-seronegative patients (40% vs. 12%; P = .001). Median baseline viral loads were higher and time to viral eradication was longer ( P = .006 and P = .026 , respectively) for mixed infection versus infection with a single genotype. In a multivariate model, mixed gB infection was a significant predictor of failure to eradicate virus by day 21 (mixed vs single genotype; odds ratio, 2.66; 95% confidence interval, 1.31-5.38; P = .007 ) after controlling for baseline viral load, CMV serostatus at baseline, ganciclovir resistance, and antiviral treatment. No effect of gB genotype was seen on virologic or clinical CMV recurrence. CONCLUSIONS:No specific gB genotype appears to confer a specific CMV virulence advantage. However, mixed gB genotype infections are associated with higher viral loads and delayed viral clearance.

Selección de péptidos sintéticos del Virus de la Hepatitis G (GBV-C/HGV) inhibidores del Péptido de Fusión HIV-I

El GB virus C (GBV-C) o virus de l'hepatitis G (HGV) es un virus format per una única cadena de RNA que pertany a la familia Flaviviridae. En els últims anys, s'han publicat nombrosos treballs en els quals s'associa la coinfecció del GBV-C i del virus de la immunodeficiència humana (VIH) amb una menor progressió de l'esmentada malaltia així com amb una major supervivència dels pacients una vegada que la SIDA s'ha desenvolupat. El mecanisme pel qual el virus GBV-C/HGV exerceix un “efecte protector” en els pacients amb VIH encara no està descrit. L’estudi de la interacció entre els virus GBVC/HGV i VIH podria donar lloc al desenvolupament de nous agents terapèutics per al tractament de la SIDA.Treballs recents mostren com la capacitat inhibitòria del virus del GBV-C/HGV és deguda a la seva glicoproteina estructural E2. S’ha vist que aquesta proteina seria capaç d’inhibir la primera fase de replicació de VIH, així com la unió i la fusió amb les membranes cel•lulars. Sobre la base d’aquests estudis, l’objectiu d’aquest treball ha estat seleccionar inhibidors del pèptid de fusió del VIH utilitzant pèptids sintètics de la proteina E2 del GBV-C/HGV. El treball realitzat ha consistit en estudiar, utilitzant assajos biofísics de leakage i de lipid mixing, la capacitat dels pèptids de la proteina estructural del virus del GBV-C/HGV per inhibir la interacció i el procés de desestabilització de membranes induïdes pel pèptid de fusió de la glicoproteina de l’embolcall, GP41, del VIH. Aquests assajos, com es descriu en treballs anteriors, han resultat útils per a la selecció i la identificació de compostos amb activitat específica anti-GP41. Es pot afirmar que efectivament els pèptids seleccionats de la proteina E2 del virus del GBV-C/HGV inhibeixen l’activitat del pèptid de fusió del VIH probablement com a consequència d’un canvi conformacional en aquest darrer.

Characteristic bimodal profiles of RNA polymerase II at thousands of active mammalian promoters.

BACKGROUND: In mammals, ChIP-seq studies of RNA polymerase II (PolII) occupancy have been performed to reveal how recruitment, initiation and pausing of PolII may control transcription rates, but the focus is rarely on obtaining finely resolved profiles that can portray the progression of PolII through sequential promoter states. RESULTS: Here, we analyze PolII binding profiles from high-coverage ChIP-seq on promoters of actively transcribed genes in mouse and humans. We show that the enrichment of PolII near transcription start sites exhibits a stereotypical bimodal structure, with one peak near active transcription start sites and a second peak 110 base pairs downstream from the first. Using an empirical model that reliably quantifies the spatial PolII signal, gene by gene, we show that the first PolII peak allows for refined positioning of transcription start sites, which is corroborated by mRNA sequencing. This bimodal signature is found both in mouse and humans. Analysis of the pausing-related factors NELF and DSIF suggests that the downstream peak reflects widespread pausing at the +1 nucleosome barrier. Several features of the bimodal pattern are correlated with sequence features such as CpG content and TATA boxes, as well as the histone mark H3K4me3. CONCLUSIONS: We thus show how high coverage DNA sequencing experiments can reveal as-yet unnoticed bimodal spatial features of PolII accumulation that are frequent at individual mammalian genes and reminiscent of transcription initiation and pausing. The initiation-pausing hypothesis is corroborated by evidence from run-on sequencing and immunoprecipitation in other cell types and species.

Structural prediction of peptides bound to MHC class I.

An ab initio structure prediction approach adapted to the peptide-major histocompatibility complex (MHC) class I system is presented. Based on structure comparisons of a large set of peptide-MHC class I complexes, a molecular dynamics protocol is proposed using simulated annealing (SA) cycles to sample the conformational space of the peptide in its fixed MHC environment. A set of 14 peptide-human leukocyte antigen (HLA) A0201 and 27 peptide-non-HLA A0201 complexes for which X-ray structures are available is used to test the accuracy of the prediction method. For each complex, 1000 peptide conformers are obtained from the SA sampling. A graph theory clustering algorithm based on heavy atom root-mean-square deviation (RMSD) values is applied to the sampled conformers. The clusters are ranked using cluster size, mean effective or conformational free energies, with solvation free energies computed using Generalized Born MV 2 (GB-MV2) and Poisson-Boltzmann (PB) continuum models. The final conformation is chosen as the center of the best-ranked cluster. With conformational free energies, the overall prediction success is 83% using a 1.00 Angstroms crystal RMSD criterion for main-chain atoms, and 76% using a 1.50 Angstroms RMSD criterion for heavy atoms. The prediction success is even higher for the set of 14 peptide-HLA A0201 complexes: 100% of the peptides have main-chain RMSD values &lt; or =1.00 Angstroms and 93% of the peptides have heavy atom RMSD values &lt; or =1.50 Angstroms. This structure prediction method can be applied to complexes of natural or modified antigenic peptides in their MHC environment with the aim to perform rational structure-based optimizations of tumor vaccines.

Effects of gastric bypass and gastric banding on glucose kinetics and gut hormone release.

BACKGROUND: Bariatric surgery markedly improves glucose homeostasis in patients with type 2 diabetes even before any significant weight loss is achieved. Procedures that involve bypassing the proximal small bowel, such as Roux-en-Y gastric bypass (RYGBP), are more efficient than gastric restriction procedures such as gastric banding (GB). OBJECTIVE: To evaluate the effects of RYGBP and GB on postprandial glucose kinetics and gastro-intestinal hormone secretion after an oral glucose load. METHODS AND PROCEDURES: This study was a cross-sectional comparison among non-diabetic, weight-stable women who had undergone RYGBP (n = 8) between 9 and 48 months earlier or GB (n = 6) from 25 to 85 months earlier, and weight- and age-matched control subjects (n = 8). The women were studied over 4 h following ingestion of an oral glucose load. Total glucose and meal glucose kinetics were assessed using glucose tracers and plasma insulin, and gut hormone concentrations were simultaneously monitored. RESULTS: Patients who had undergone RYGBP showed a a more rapid appearance of exogenous glucose in the systemic circulation and a shorter duration of postprandial hyperglycemia than patients who had undergone GB and C. The response in RYGBP patients was characterized by early and accentuated insulin response, enhanced postprandial levels of glucagon-like peptide-1 (GLP-1) and polypeptide YY (PYY), and greater postprandial suppression of ghrelin. DISCUSSION: These findings indicate that RYGBP is associated with alterations in glucose kinetics and glucoregulatory hormone secretion. These alterations are probably secondary to the anatomic rearrangement of the foregut, given the fact that they are not observed after GB. Increased PYY and GLP-1 concentrations and enhanced ghrelin suppression are compatible with reduced food intake after RYGBP.

The fine-scale architecture of structural variants in 17 mouse genomes.

BACKGROUND: Accurate catalogs of structural variants (SVs) in mammalian genomes are necessary to elucidate the potential mechanisms that drive SV formation and to assess their functional impact. Next generation sequencing methods for SV detection are an advance on array-based methods, but are almost exclusively limited to four basic types: deletions, insertions, inversions and copy number gains. RESULTS: By visual inspection of 100 Mbp of genome to which next generation sequence data from 17 inbred mouse strains had been aligned, we identify and interpret 21 paired-end mapping patterns, which we validate by PCR. These paired-end mapping patterns reveal a greater diversity and complexity in SVs than previously recognized. In addition, Sanger-based sequence analysis of 4,176 breakpoints at 261 SV sites reveal additional complexity at approximately a quarter of structural variants analyzed. We find micro-deletions and micro-insertions at SV breakpoints, ranging from 1 to 107 bp, and SNPs that extend breakpoint micro-homology and may catalyze SV formation. CONCLUSIONS: An integrative approach using experimental analyses to train computational SV calling is essential for the accurate resolution of the architecture of SVs. We find considerable complexity in SV formation; about a quarter of SVs in the mouse are composed of a complex mixture of deletion, insertion, inversion and copy number gain. Computational methods can be adapted to identify most paired-end mapping patterns.

Poverty and social exclusion in Northern Ireland

Northern Ireland’s labour market and poverty rates have deteriorated in the last five years, in addition to longstanding issues of mental health and community divisions – and welfare reforms are likely to exacerbate these problems.��New research��by the New Policy Institute for JRF brings together the latest data to show the extent and nature of poverty in Northern Ireland (NI), focusing on the links between poverty, work, disability and age. It finds that:��•��between 2006/07 and 2011/12 the average (median) income in NI fell by almost 10 per cent compared with 7 per cent for the UK as a whole;��•��the proportion of unemployed working-age people in NI almost doubled between 2007/08 and 2012/13 to reach 5.8 per cent. Growth in the proportion working part-time and wanting full-time work has been greater – up from 1.7 per cent, the same as in Great Britain (GB), to 4.4 per cent (compared with 3.5 per cent in GB);��•��the proportion of pensioners in poverty in NI fell from 19 per cent to 16 per cent in the five years to 2011/12. The poverty rate rose over this period for working-age adults and children;��•��in the five years to 2011/12, the poverty rate among adults aged 16 to 29 rose by 8 percentage points to reach 26 per cent. Poverty has also increased among those aged 30 to 59, solely among those in working families.��For more information about this research and forthcoming work, please contact Aleks Collingwood, programme manager:��Aleks.Collingwood@jrf.org.uk