Increased vascularization during early healing after biologic augmentation in repair of chronic rotator cuff tears using autologous leukocyte- and platelet-rich fibrin (L-PRF): a prospective randomized controlled pilot trial

HYPOTHESIS We hypothesized that arthroscopic rotator cuff repairs using leukocyte- and platelet-rich fibrin (L-PRF) in a standardized, modified protocol is technically feasible and results in a higher vascularization response and watertight healing rate during early healing. METHODS Twenty patients with chronic rotator cuff tears were randomly assigned to 2 treatment groups. In the test group (N = 10), L-PRF was added in between the tendon and the bone during arthroscopic rotator cuff repair. The second group served as control (N = 10). They received the same arthroscopic treatment without the use of L-PRF. We used a double-row tension band technique. Clinical examinations including subjective shoulder value, visual analog scale, Constant, and Simple Shoulder Test scores and measurement of the vascularization with power Doppler ultrasonography were made at 6 and 12 weeks. RESULTS There have been no postoperative complications. At 6 and 12 weeks, there was no significant difference in the clinical scores between the test and the control groups. The mean vascularization index of the surgical tendon-to-bone insertions was always significantly higher in the L-PRF group than in the contralateral healthy shoulders at 6 and 12 weeks (P = .0001). Whereas the L-PRF group showed a higher vascularization compared with the control group at 6 weeks (P = .001), there was no difference after 12 weeks of follow-up (P = .889). Watertight healing was obtained in 89% of the repaired cuffs. DISCUSSION/CONCLUSIONS Arthroscopic rotator cuff repair with the application of L-PRF is technically feasible and yields higher early vascularization. Increased vascularization may potentially predispose to an increased and earlier cellular response and an increased healing rate.

RADIANCE: A Randomized Controlled Study of Ranibizumab in Patients with Choroidal Neovascularization Secondary to Pathologic Myopia.

OBJECTIVE To compare the efficacy and safety of ranibizumab 0.5 mg, guided by visual acuity (VA) stabilization or disease activity criteria, versus verteporfin photodynamic therapy (vPDT) in patients with visual impairment due to myopic choroidal neovascularization (CNV). DESIGN Phase III, 12-month, randomized, double-masked, multicenter, active-controlled study. PARTICIPANTS Patients (N = 277) with visual impairment due to myopic CNV. METHODS Patients were randomized to receive ranibizumab on day 1, month 1, and thereafter as needed guided by VA stabilization criteria (group I, n = 106); ranibizumab on day 1 and thereafter as needed guided by disease activity criteria (group II, n = 116); or vPDT on day 1 and disease activity treated with ranibizumab or vPDT at investigators' discretion from month 3 (group III, n = 55). MAIN OUTCOME MEASURES Mean average best-corrected visual acuity (BCVA) change from baseline to month 1 through months 3 (primary) and 6, mean BCVA change and safety over 12 months. RESULTS Ranibizumab treatment in groups I and II was superior to vPDT based on mean average BCVA change from baseline to month 1 through month 3 (group I: +10.5, group II: +10.6 vs. group III: +2.2 Early Treatment Diabetic Retinopathy Study [ETDRS] letters; both P< 0.0001). Ranibizumab treatment guided by disease activity was noninferior to VA stabilization-guided retreatment based on mean average BCVA change from baseline to month 1 through month 6 (group II: +11.7 vs. group I: +11.9 ETDRS letters; P< 0.00001). Mean BCVA change from baseline to month 12 was +13.8 (group I), +14.4 (group II), and +9.3 ETDRS letters (group III). At month 12, 63.8% to 65.7% of patients showed resolution of myopic CNV leakage. Patients received a median of 4.0 (group I) and 2.0 (groups II and III) ranibizumab injections over 12 months. No deaths or cases of endophthalmitis and myocardial infarction occurred. CONCLUSIONS Ranibizumab treatment, irrespective of retreatment criteria, provided superior BCVA gains versus vPDT up to month 3. Ranibizumab treatment guided by disease activity criteria was noninferior to VA stabilization criteria up to month 6. Over 12 months, individualized ranibizumab treatment was effective in improving and sustaining BCVA and was generally well tolerated in patients with myopic CNV.

Long-term elevation of β-hydroxybutyrate in dairy cows through infusion: effects on feed intake, milk production, and metabolism.

Elevation of ketone bodies in dairy cows frequently occurs in early lactation, usually concomitantly with a lack of energy and glucose. The objective of this study was to induce an elevated plasma β-hydroxybutyrate (BHBA) concentration over 48 h in mid-lactating dairy cows (i.e., during a period of positive energy balance and normal glucose plasma concentrations). Effects of BHBA infusion on feed intake, metabolism, and performance were investigated. Thirteen cows were randomly assigned to 1 of 2 infusion groups, including an intravenous infusion with Na-dl-β-OH-butyrate (1.7 mol/L) to achieve a plasma concentration of 1.5 to 2.0 mmol/L of BHBA (HyperB; n=5), or an infusion of 0.9% saline solution (control; n=8). Blood was sampled before and hourly during the 48 h of infusion. In the liver, mRNA transcripts related to gluconeogenesis (pyruvate carboxylase, glucose 6-phosphatase, mitochondrial phosphoenolpyruvate carboxykinase), phosphofructokinase, pyruvate dehydrogenase complex, and fatty acid synthesis (acetyl-coenzyme A carboxylase, fatty acid synthase) were measured by real-time PCR. Glyceraldehyde-3-phosphate dehydrogenase and ubiquitin were used as housekeeping genes. Changes (difference between before and after 48-h infusion) during the infusion period were evaluated by ANOVA with treatment as fixed effect, and area under the curve of variables was calculated on the second day of experiment. The plasma BHBA concentration in HyperB cows was 1.74 ± 0.02 mmol/L (mean ± SE) compared with 0.59 ± 0.02 mmol/L for control cows. The change in feed intake, milk yield, and energy corrected milk did not differ between the 2 experimental groups. Infusion of BHBA reduced the plasma glucose concentration (3.47 ± 0.11 mmol/L) in HyperB compared with control cows (4.11 ± 0.08 mmol/L). Plasma glucagon concentration in HyperB was lower than the control group. All other variables measured in plasma were not affected by treatment. In the liver, changes in mRNA abundance for the selected genes were similar between 2 groups. Results demonstrate that intravenous infusion of BHBA decreased plasma glucose concentration in dairy cows, but this decrease could not be explained by alterations in insulin concentrations or key enzymes related to gluconeogenesis. Declined glucose concentration is likely functionally related to decreased plasma glucagon concentration.

Post-immigration education of adult immigrants in Switzerland

In 2000, 20 per cent of the Swiss resident population was constituted by foreigners (Fibbi and Wanner 2009). As in other European countries, the migrant population in Switzerland can broadly be differentiated into three groups: 1) Migrant groups from less-developed regions with substantially lower educational attainments and an increased risk for unemployment than in the reference population, 2) Migrant groups that are rather more successful, although still somewhat behind the majority population, 3) Migrant groups who even outperform the majority population in terms of educational and employment success (Heath et al. 2008). Given these inequalities – in particular in the first migrant group – participation in further education in the country of destination might contribute to better integrate migrants in the Swiss society in general and the labour market in particular. On the basis of the pooled SAKE data set (1991-2000), patterns of participation in further education of adult migrants are analysed. As the results show, many migrant groups differ from the Swiss reference population regarding participation in further education. While inequalities are often explained by educational attainments and occupational status, in some cases they hold even if controlled for the determinants explaining participation in further education in general. Regarding migrant-specific determinants, type of residence permit proved to be an important indicator explaining the disadvantages in access to further education encountered by migrants originating from Former Yugoslavia.

Usefulness of electrocardiographic parameters for risk prediction in arrhythmogenic right ventricular dysplasia

The value of electrocardiographic findings predicting adverse outcome in patients with arrhythmogenic right ventricular dysplasia (ARVD) is not well known. We hypothesized that ventricular depolarization and repolarization abnormalities on the 12-lead surface electrocardiogram (ECG) predict adverse outcome in patients with ARVD. ECGs of 111 patients screened for the 2010 ARVD Task Force Criteria from 3 Swiss tertiary care centers were digitized and analyzed with a digital caliper by 2 independent observers blinded to the outcome. ECGs were compared in 2 patient groups: (1) patients with major adverse cardiovascular events (MACE: a composite of cardiac death, heart transplantation, survived sudden cardiac death, ventricular fibrillation, sustained ventricular tachycardia, or arrhythmic syncope) and (2) all remaining patients. A total of 51 patients (46%) experienced MACE during a follow-up period with median of 4.6 years (interquartile range 1.8 to 10.0). Kaplan-Meier analysis revealed reduced times to MACE for patients with repolarization abnormalities according to Task Force Criteria (p = 0.009), a precordial QRS amplitude ratio (∑QRS mV V1 to V3/∑QRS mV V1 to V6) of ≤ 0.48 (p = 0.019), and QRS fragmentation (p = 0.045). In multivariable Cox regression, a precordial QRS amplitude ratio of ≤ 0.48 (hazard ratio [HR] 2.92, 95% confidence interval [CI] 1.39 to 6.15, p = 0.005), inferior leads T-wave inversions (HR 2.44, 95% CI 1.15 to 5.18, p = 0.020), and QRS fragmentation (HR 2.65, 95% CI 1.1 to 6.34, p = 0.029) remained as independent predictors of MACE. In conclusion, in this multicenter, observational, long-term study, electrocardiographic findings were useful for risk stratification in patients with ARVD, with repolarization criteria, inferior leads TWI, a precordial QRS amplitude ratio of ≤ 0.48, and QRS fragmentation constituting valuable variables to predict adverse outcome.

Comparison of hepatic adaptation in extreme metabolic phenotypes observed in early lactation dairy cows on-farm

The aim was to study the variation in metabolic responses in early-lactating dairy cows (n = 232) on-farm that were pre-selected for a high milk fat content (>45 g/l) and a high fat/protein ratio in milk (>1.5) in their previous lactation. Blood was assayed for concentrations of metabolites and hormones. Liver was measured for mRNA abundance of 25 candidate genes encoding enzymes and receptors involved in gluconeogenesis (6), fatty acid β-oxidation (6), fatty acid and triglyceride synthesis (5), cholesterol synthesis (4), ketogenesis (2) and the urea cycle (2). Two groups of cows were formed based on the plasma concentrations of glucose, non-esterified fatty acids (NEFA) and β-hydroxybutyric acid (BHBA) (GRP+, high metabolic load; glucose <3.0 mm, NEFA >300 μm and BHBA >1.0 mm, n = 30; GRP-, low metabolic load; glucose >3.0 mm, NEFA <300 μm and BHBA <1.0 mm, n = 30). No differences were found between GRP+ and GRP- for the milk yield at 3 weeks post-partum, but milk fat content was higher (p < 0.01) for GRP+ than for GRP-. In week 8 post-partum, milk yield was higher in GRP+ in relation to GRP- (37.5 vs. 32.5 kg/d; p < 0.01). GRP+ in relation to GRP- had higher (p < 0.001) NEFA and BHBA and lower glucose, insulin, IGF-I, T3 , T4 concentrations (p < 0.01). The mRNA abundance of genes related to gluconeogenesis, fatty acid β-oxidation, fatty acid and triglyceride synthesis, cholesterol synthesis and the urea cycle was different in GRP+ compared to GRP- (p < 0.05), although gene transcripts related to ketogenesis were similar between GRP+ and GRP-. In conclusion, high metabolic load post-partum in dairy cows on-farm corresponds to differences in the liver in relation to dairy cows with low metabolic load, even though all cows were pre-selected for a high milk fat content and fat/protein ratio in milk in their previous lactation.

Hyperketonemia during lipopolysaccharide-induced mastitis affects systemic and local intramammary metabolism in dairy cows

Hyperketonemia interferes with the metabolic regulation in dairy cows. It is assumed that metabolic and endocrine changes during hyperketonemia also affect metabolic adaptations during inflammatory processes. We therefore studied systemic and local intramammary effects of elevated plasma β-hydroxybutyrate (BHBA) before and during the response to an intramammary lipopolysaccharide (LPS) challenge. Thirteen dairy cows received intravenously either a Na-DL-β-OH-butyrate infusion (n = 5) to achieve a constant plasma BHBA concentration (1.7 ± 0.1 mmol/L), with adjustments of the infusion rates made based on immediate measurements of plasma BHBA every 15 min, or an infusion with a 0.9% NaCl solution (control; n = 8) for 56 h. Infusions started at 0900 h on d 1 and continued until 1700 h 2 d later. Two udder quarters were challenged with 200 μg of Escherichia coli LPS and 2 udder quarters were treated with 0.9% saline solution as control quarters at 48 h after the start of infusion. Blood samples were taken at 1 wk and 2h before the start of infusions as reference samples and hourly during the infusion. Mammary gland biopsies were taken 1 wk before, and 48 and 56 h (8h after LPS challenge) after the start of infusions. The mRNA abundance of key factors related to BHBA and fatty acid metabolism, and glucose transporters was determined in mammary tissue biopsies. Blood samples were analyzed for plasma glucose, BHBA, nonesterified fatty acid, urea, insulin, glucagon, and cortisol concentrations. Differences were not different for effects of BHBA infusion on the mRNA abundance of any of the measured target genes in the mammary gland before LPS challenge. Intramammary LPS challenge increased plasma glucose, cortisol, glucagon, and insulin concentrations in both groups but increases in plasma glucose and glucagon concentration were less pronounced in the Na-DL-β-OH-butyrate infusion group than in controls. In response to LPS challenge, plasma BHBA concentration decreased in controls and decreased also slightly in the BHBA-infused animals because the BHBA concentration could not be fully maintained despite a rapid increase in BHBA infusion rate. The change in mRNA abundance of citrate synthase in LPS quarters was significant between the 2 treatment groups. The results indicate that elevated circulating BHBA concentration inhibits gluconeogenesis before and during immune response to LPS challenge, likely because BHBA can replace glucose as an energy source.

Effect of an intervertebral disk spacer on stiffness after monocortical screw/polymethylmethacrylate fixation in simulated and cadaveric canine cervical vertebral columns.

OBJECTIVE To determine the biomechanical effect of an intervertebral spacer on construct stiffness in a PVC model and cadaveric canine cervical vertebral columns stabilized with monocortical screws/polymethylmethacrylate (PMMA). STUDY DESIGN Biomechanical study. SAMPLE POPULATION PVC pipe; cadaveric canine vertebral columns. METHODS PVC model-PVC pipe was used to create a gap model mimicking vertebral endplate orientation and disk space width of large-breed canine cervical vertebrae; 6 models had a 4-mm gap with no spacer (PVC group 1); 6 had a PVC pipe ring spacer filling the gap (PCV group 2). Animals-large breed cadaveric canine cervical vertebral columns (C2-C7) from skeletally mature dogs without (cadaveric group 1, n = 6, historical data) and with an intervertebral disk spacer (cadaveric group 2, n = 6) were used. All PVC models and cadaver specimens were instrumented with monocortical titanium screws/PMMA. Stiffness of the 2 PVC groups was compared in extension, flexion, and lateral bending using non-destructive 4-point bend testing. Stiffness testing in all 3 directions was performed of the unaltered C4-C5 vertebral motion unit in cadaveric spines and repeated after placement of an intervertebral cortical allograft ring and instrumentation. Data were compared using a linear mixed model approach that also incorporated data from previously tested spines with the same screw/PMMA construct but without disk spacer (cadaveric group 1). RESULTS Addition of a spacer increased construct stiffness in both the PVC model (P < .001) and cadaveric vertebral columns (P < .001) compared to fixation without a spacer. CONCLUSIONS Addition of an intervertebral spacer significantly increased construct stiffness of monocortical screw/PMMA fixation.

Riesgo del consumo de cannabis para la práctica físico-deportiva

El consumo de cannabis es uno de los principales problemas de salud pública, especialmente entre los jóvenes, dadas sus prevalencias de consumo. Esta droga puede provocar alteraciones psicomotrices en el individuo, por ello, el presente trabajo de investigación tiene como objetivo principal comprobar si el consumo de cannabis supone un riesgo añadido a la práctica físico-deportiva. Para alcanzar dicho objetivo, se dividió el trabajo en dos estudios interrelacionados entre sí. En el primer estudio o Estudio 1, “Repercusión del consumo de cannabis en las clases de Educación Física”, se realizó un cuestionario autoadministrado, dirigido al profesorado de Educación Física de la Comunidad de Madrid, con el fin de recoger su opinión sobre la posible presencia de consumidores de cannabis en sus aulas. El segundo estudio o Estudio 2, “Influencia del cannabis en el equilibrio, la coordinación, el tiempo de respuesta y la percepción temporal”, consistió en la realización de una serie de pruebas por parte de un grupo control y un grupo de consumidores de cannabis, para así cuantificar y cualificar los efectos de la inhalación de esta droga en la condición motriz. La encuesta que se utilizó para el Estudio 1, “El cannabis, los adolescentes y la práctica físico-deportiva”, pasó primero por una fase de elaboración, corrección y validación, y después, utilizándose la técnica de muestreo aleatorio por conglomerados, fue distribuido por los centros públicos de enseñanzas secundarias de la Comunidad de Madrid seleccionados. Se obtuvo respuesta de 93 profesores de Educación Física pertenecientes a 76 centros, es decir el 22,35% de los centros de la comunidad. Por último, se procedió al análisis, discusión y difusión de los resultados. En el Estudio 2, primero se procedió al diseño de la batería de pruebas a realizar, compuesta por 7 tests con 16 variables que valoraron el equilibrio, la coordinación, el tiempo de respuesta y la percepción temporal de los sujetos. Después se procedió a la selección de la muestra, formada por dos grupos de voluntarios de entre 18 y 30 años: un grupo control de 52 participantes, y un grupo de consumidores de cannabis, de 28 participantes con un hábito de consumo diferente. Los sujetos del grupo de consumidores realizaron las pruebas 20 minutos después de la inhalación de cannabis. Tras la realización de las pruebas por parte de todos los sujetos se procedió al análisis de los resultados obtenidos, segmentándolos por sexo y apareando las variables para evitar posibles efectos confundidores. Los resultados del primer estudio indicaron que el 75,27% del profesorado ha pensado alguna vez que sus alumnos consumían cannabis antes del inicio de su clase, hecho asociado a alteraciones psicológicas (90,63%) y cognitivo-conductuales (68,75%); no siendo factores influyentes el sexo o la experiencia docente de los encuestados (p>0,05). El segundo estudio aportó como principal resultado el empeoramiento de la percepción temporal y la conducta motriz de los sujetos que consumieron cannabis, en especial de su equilibrio y su coordinación (p<0,05). También indicó que hubo ligeras diferencias en función del hábito de consumo de esta droga, si bien los resultados se vieron influenciados por el tamaño de la muestra. Las conclusiones extraídas mostraron que el profesorado de Educación Física percibe la presencia de consumidores de cannabis en sus aulas, utiliza el diálogo con el alumnado como herramienta de actuación, y conoce la influencia negativa que tiene el consumo de esta droga en el rendimiento motor. También demuestran que el cannabis supone un riesgo añadido a la práctica físico-deportiva, debido al empeoramiento de la conducta motriz, en especial de la coordinación y el equilibrio. Además, las diferencias surgidas en base al hábito de consumo no son concluyentes pero si apuntan a que el consumo esporádico puede conllevar un peor rendimiento motor que el consumo habitual. ABSTRACT Cannabis use is one of the most important concerns of public health, particularly among young people, given their use prevalence. This drug can produce psychomotor alterations in the subject; therefore, this research work has as main aim to check if cannabis use is an added risk for physical and sporting practices. In order to achieve the objectives pursued, work was divided in two interrelated studies. First study or Study 1, “Cannabis use impact in Physical Education lessons”, a self-managed questionnaire addressed to Physical Education teachers in Community of Madrid was carried out, in order to gather the opinion about the possible existence of Cannabis users in their classes. Second Study or Study 2, “Cannabis influence in balance, coordination, reaction time and temporal perception”, consisted in a series of tests performed by a control group and a cannabis users group, in order to quantify and qualify the effects of inhalation of this drug in the motor skills. The questionnaire used for Study 1, “Cannabis, teenagers, and physical and sporting practices”, firstly went through an elaboration y correction phase, and then, using cluster sampling technique, was distributed within selected Secondary Education Centres from Community of Madrid. Response from 93 Physical Education teachers from 76 High Schools were obtained, this is 22,35% of total High Schools in Madrid. Finally, analysis, discussion and dissemination of results were held. In Study 2, first of all design of tests to be made was done, consisting on 7 different test with 16 variables that measured balance, coordination, response time and temporal perception in subjects. After that, sample selection was performed, comprised of 2 volunteers groups of ages between 18-30 years: a control group of 52 participants, and a Cannabis Users Group of 28 participants with different consumption habits. Users group subjects carried out tests 20 minutes after cannabis inhalation. After tests were performed by all subjects, results were analyzed and segmented by sex and matching variables in order to avoid confusion effects. First study results brought out that 75,27% of teachers have ever thought that their pupils used cannabis before getting into class, this fact is linked to psychological alterations (90,63%) and cognitive-behavioral (68,75%); not being influencing factors sex or teaching experience of the surveyed (p>0,05). Second study provided as most significant result the worsening of temporal perception and motor tasks behavior in subjects that had used cannabis, especially in regards of their balance and coordination (p<0,05). Also resulted that there were slight differences in consumption habits, although results were influenced by the sample size. Conclusions drawn showed that Physical Education teachers notice the presence of cannabis users in lessons, use dialogue with pupils as an action tool and acknowledge the negative influence this drug has in motor tasks performance. Also, it is shown that cannabis is an additional risk for physical and sporting practices due to deteriorating in motor skills, particularly in coordination and balance. In addition, the differences that may arise depending on the consumption habits are not conclusive, but they suggest that the sporadic drug use may be related to a worse motor performance than usual consumption.

The Kinetics of Zeaxanthin Formation Is Retarded by Dicyclohexylcarbodiimide1

The de-epoxidation of violaxanthin to antheraxanthin (Anth) and zeaxanthin (Zeax) in the xanthophyll cycle of higher plants and the generation of nonphotochemical fluorescence quenching in the antenna of photosystem II (PSII) are induced by acidification of the thylakoid lumen. Dicyclohexylcarbodiimide (DCCD) has been shown (a) to bind to lumen-exposed carboxy groups of antenna proteins and (b) to inhibit the pH-dependent fluorescence quenching. The possible influence of DCCD on the de-epoxidation reactions has been investigated in isolated pea (Pisum sativum L.) thylakoids. The Zeax formation was found to be slowed down in the presence of DCCD. The second step (Anth → Zeax) of the reaction sequence seemed to be more affected than the violaxanthin → Anth conversion. Comparative studies with antenna-depleted thylakoids from plants grown under intermittent light and with unstacked thylakoids were in agreement with the assumption that binding of DCCD to antenna proteins is probably responsible for the retarded kinetics. Analyses of the DCCD-induced alterations in different antenna subcomplexes showed that Zeax formation in the PSII antenna proteins was predominantly influenced by DCCD, whereas Zeax formation in photosystem I was nearly unaffected. Our data support the suggestion that DCCD binding to PSII antenna proteins is responsible for the observed alterations in xanthophyll conversion.

Self-assembly of a heteroduplex helicate from two different ligand strands and Cu(II) cations.

Cu(II) ions have been reacted with a 1/1 mixture of two linear ligands, one containing three 2,2'- bipyridine groups and the other three 2,2':6',2"-terpyridine groups. Absorption spectroscopy and fast atom bombardment mass spectrometry indicate the formation of a trinuclear complex containing one ligand of each kind. Determination of the crystal structure of this compound has confirmed that it is indeed a linear trinuclear complex in which two different ligands are wrapped in a helical fashion around the pentacoordinated metal ions. The central coordination geometry is trigonal bipyramidal; the two lateral Cu(II) ions are in a square pyramidal environment. Thus, a heteroduplex helicate is formed by the self-assembly of two different ligand strands and three specific metal ions induced by the coordination number and geometry of the latter. The self-assembly process may be considered to result from the reading of the steric and binding information present in the two ligands by Cu(II) ions through a pentacoordination algorithm. The same ligands have been shown earlier to yield homoduplex helicates from ions of tetrahedral and octahedral coordination geometry and strands of bidentate bipyridines and tridentate terpyridines, respectively. These two types of artificial double helical species may be related on one hand to the natural homoduplex nucleic acids and on the other hand to the DNA:RNA heteroduplex.

Total chemical synthesis of a ribozyme derived from a group I intron.

We describe the complete chemical synthesis of a ribozyme that catalyzes template-directed oligonucleotide ligation. The specific activity of the synthetic ribozyme is nearly identical to that of the same enzyme generated by in vitro transcription with T7 RNA polymerase. The ribozyme is derived from a group I intron and consists of three RNA fragments of 36, 43, and 59 nt that self-assemble to form a catalytically active complex. We have site-specifically substituted ribonucleotide analogs into this enzyme and have identified two 2'-hydroxyl groups that are required for full catalytic activity. In contrast, neither the 2'-hydroxyl nor the exocyclic amino group of the conserved guanosine in the guanosine binding site is necessary for catalysis. By allowing the ribozyme to be modified as easily as its substrates, this synthetic ribozyme system should be useful for testing specific hypotheses concerning ribozyme-substrate interactions and tertiary interactions within the ribozyme.

Educação Alimentar e Nutricional na Atenção Primária à Saúde na perspectiva do profissional não nutricionista

Introdução: O Direito Humano a Alimentação Adequada (DHAA), na perspectiva da Segurança Alimentar e Nutricional (SAN), destacou-se devido à compreensão dos determinantes para a Promoção da Saúde (PS). A Educação Alimentar e Nutricional (EAN) é uma ferramenta capaz de promover a reflexão dos cidadãos sobre como realizar esse direito. No Brasil, o quadro de insegurança alimentar entre crianças e adolescentes torna os profissionais de saúde da Atenção Primária à Saúde (APS) atores promissores para a reversão desse quadro, já que esses trabalham com os principais influenciadores desse público: a família. Objetivo: Analisar a atuação de profissionais de saúde não nutricionistas coordenadores de grupos educativos com conteúdo de alimentação e nutrição, desenvolvidos na APS do município de São Paulo. Métodos: Estudo qualitativo, com aplicação de entrevistas semiestruturadas e análise por meio do Discurso do Sujeito Coletivo. Foram levantados os dados a respeito da formação desses profissionais e identificadas suas percepções sobre seus papéis nos grupos que coordenam e a importância atribuída a eles. Resultados: A profissão dos 21 entrevistados reflete a atual configuração da Estratégia Saúde da Família. Há predominância de profissionais do sexo feminino com pós-graduação em temas de saúde coletiva. Foram identificadas 13 Ideias Centrais dividas em 2 Eixos Temáticos. Levantaram-se percepções contrárias e outras a favor aos referenciais teóricos trabalhados. Como favoráveis, identificou-se a valorização dos grupos como espaços de participação, troca de experiências e criação de vínculo entre seus membros, sendo o coordenador do grupo responsável pela condução desses. A importância na atuação interprofissional para o atendimento integral à saúde e atualização entre os profissionais também foi destacada. Já as desfavoráveis trouxeram a desvalorização das atividades em grupo, ou a atribuição de sua importância como forma de acesso a serviços, medicamentos ou informação, a identificação dos coordenadores como responsáveis por mudanças de comportamentos nos participantes, modelos a serem seguidos, e sendo considerados detentores do conhecimento, o que parece sobrecarregá-los, desmotivá-los e frustrá-los. Assim, alguns buscam seu reconhecimento trazendo atividades que agradam os usuários, independentemente da constatação das necessidades do território. Conclusões: A percepção dos profissionais parece refletir a forma em que atuam, evidenciando um momento heterogêneo sobre as formas de se abordar os aspectos relacionados à alimentação, além do despreparo para a coordenação de grupos. Dessa forma, recomenda-se a aproximação entre os campos da saúde e da educação, visando práticas mais significativas e libertadoras, bem como a reflexão sobre a formação desses profissionais, já que suas atuações parecem refletir a educação na qual foram moldados. Os princípios da PS, do DHAA, da SAN, da EAN e das características essenciais a um coordenador de grupos, devem ser trabalhados com esses atores, e, para tanto, como produto dessa pesquisa, sugeriu-se um curso de atualização.

Avaliação da musculatura inspiratória e expiratória na doença pulmonar obstrutiva crônica leve e grave comparada aos indivíduos saudáveis

Introdução: A DPOC é uma doença respiratória prevenível e tratável, caracterizada por limitação persistente ao fluxo aéreo, hiperinsuflação e aprisionamento aéreo. A dispneia e a intolerância aos esforços, decorrentes destas alterações fisiopatológicas sofre influência de vários fatores. Dentre estes, o recrutamento e a sobrecarga imposta aos músculos inspiratórios e expiratórios são de fundamental importância, porém a participação destes ainda não foi completamente elucidada em diferentes gravidades da doença. Objetivos: O objetivo principal deste estudo foi avaliar a mecânica ventilatória, e o grau de recrutamento da musculatura inspiratória e expiratória na DPOC leve e grave, na condição de repouso e durante um teste máximo de exercício, comparado a um grupo de indivíduos saudáveis. Metodologia: Trata-se de um estudo transversal envolvendo 36 indivíduos, sendo 24 pacientes portadores de DPOC e 12 voluntários sadios. As avaliações foram divididas em 2 visitas. No D1, foram realizadas uma avaliação clínica, avaliação de dispneia (mMRC) e de qualidade de vida (SGRQ), além da prova de função pulmonar completa. Na 2ª visita, realizada com intervalo de 1 semana, foram avaliadas: as pressões respiratórias máximas estáticas por meio de métodos volitivos (PImax, PEmax, SNIP, Pes sniff, Pga sniff e Pdi sniff) e não volitivos (Twitch cervical bilateral e T10); avaliação da sincronia toracoabdominal por pletismografia de indutância; avaliação do recrutamento dos músculos inspiratórios e expiratórios ao repouso pela eletromiografia de superfície; e, posteriormente, um teste de exercício cardiopulmonar incremental para estudo de todas essas variáveis no esforço. Resultados: Foram avaliados 24 pacientes (12 leves e 12 graves) e 12 indivíduos saudáveis da mesma faixa etária. A maioria dos pacientes apresentava comprometimento significativo da qualidade de vida e os pacientes do grupo grave eram mais sintomáticos. A função pulmonar encontrava-se alterada na maioria dos pacientes. Destes, 79,2% apresentavam aprisionamento aéreo e 70,8% tinham redução da DLCO. Tais alterações foram semelhantes nos 2 grupos de pacientes. A força muscular estática medida por métodos volitivos e não volitivos estava reduzida nos 2 grupos e mostrou relação com o VEF1. No exercício, a dispneia foi o principal motivo para interrupção do teste em 70% dos pacientes. A HD esteve presente em 87,5% dos pacientes. O comportamento das pressões respiratórias foi significativamente diferente entre os 3 grupos. Os pacientes com DPOC apresentaram maior atividade diafragmática (Pdi) comparado aos controles e a participação da musculatura expiratória também foi maior neste grupo, principalmente nos graves. Apesar disso, os pacientes com DPOC apresentaram uma eficiência mecânica reduzida, ou seja, esse incremento da força muscular foi insuficiente para manter uma ventilação adequada para uma determinada carga. Com o aumento da demanda ventilatória, houve recrutamento precoce e progressivo dos músculos inspiratórios e expiratórios durante o exercício. O trabalho resistivo e o expiratório foram significativamente diferentes entre os controles e os pacientes com DPOC desde o início do exercício. Como consequência destas alterações, a intensidade da dispneia durante o TECP foi maior nos pacientes com DPOC (leve e grave) para a mesma carga e mesma ventilação-minuto (VE), quando comparada aos indivíduos do grupo-controle. Conclusões: O conjunto destes achados demonstra que o comprometimento dos músculos inspiratórios e expiratórios contribuiu significativamente para a dispneia e a intolerância ao exercício tanto no DPOC leve quanto no DPOC grave. E que este comprometimento pode não ser detectado com os testes máximos de força ao repouso

Regeneração hepática em animais jovens com estenose da veia porta ou ligadura da artéria hepática: estudos histológicos, moleculares e avaliação dos efeitos da insulina e do tacrolimus como agentes regenerativos

INTRODUÇÃO: O transplante hepático é o único tratamento efetivo para uma variedade de doenças hepáticas irreversíveis. No entanto, o número limitado de doadores pediátricos leva ao uso de enxertos hepáticos de doadores adultos, com necessidade de anastomoses vasculares mais complexas. Essas anastomoses tornam-se complicadas pela diferença no calibre dos vasos entre o doador e o receptor, resultando em alterações do fluxo sanguíneo, estenose da anastomose venosa ou arterial e trombose. Os efeitos para regeneração hepática decorrentes da privação do fluxo sanguíneo pela veia porta ou pela artéria hepática não estão completamente elucidados. Experimentalmente, quando um lobo do fígado não recebe o fluxo venoso portal, é observada atrofia deste segmento e hipertrofia do restante do órgão perfundido. Embora existam vários modelos experimentais para estudo da regeneração hepática, poucos são focados em animais em crescimento. Além disso, os efeitos regenerativos de drogas como o tacrolimus e a insulina precisam ser pesquisados, com o objetivo de encontrar um tratamento ideal para a insuficiência hepática ou um método de estimular a regeneração do fígado após ressecções ou transplantes parciais. O objetivo do presente estudo é descrever modelos de regeneração hepática em ratos em crescimento com: 1) ausência de fluxo hepático arterial e 2) redução do fluxo portal. Adicionalmente, o estudo avalia o efeito pró-regenerativo do tacrolimus e da insulina nesses modelos descritos. MÉTODOS: cento e vinte ratos (entre 50 e 100g de peso) foram divididos em 6 grupos, de acordo com o tipo de intervenção cirúrgica: Grupo 1, incisão abdominal sem intervenção hepática; Grupo 2, hepatectomia a 70%; Grupo 3, hepatectomia a 70% + estenose de veia porta; Grupo 4, hepatectomia a 70% + ligadura da artéria hepática; Grupo 5, hepatectomia a 70% + estenose de veia porta + insulina; Grupo 6, hepatectomia a 70% + estenose de veia porta + tacrolimus. Os animais dos grupos 1 ao 4 foram subdivididos em 5 subgrupos de acordo com o momento da morte: 1, 2, 3, 5 e 10 dias após a intervenção cirúrgica. Os animais dos grupos 5 e 6 foram subdividos em 2 subgrupos de acordo com o momento da morte: 2 e 10 dias após a intervenção cirúrgica. Os lobos hepáticos remanescentes foram submetidos à análise histomorfométrica, imuno-histoquímica e molecular. RESULTADOS: Verificou-se que no grupo com hepatectomia a 70% houve recuperação do peso do fígado no terceiro dia com aumento da atividade mitótica, enquanto que no grupo com estenose portal não se observou esse fenômeno (p < 0,001). A insulina e o tacrolimus promoveram aumento do peso do fígado e do índice mitótico. A atividade mitótica foi considerada aumentada nos animais dos grupos hepatectomia, hepatectomia + ligadura da artéria, insulina e tacrolimus; e esse parâmetro estava reduzido no grupo submetido à hepatectomia + estenose portal (p < 0,001). A expressão de interleucina 6 estava presente em todos os animais, sendo significativamente maior nos grupos hepatectomia, hepatectomia + ligadura da artéria e significativamente menor no grupo hepatectomia + estenose portal. Entretanto, a administração de tacrolimus ou insulina recuperou os níveis teciduais de interleucina 6 no grupo com estenose portal. CONCLUSÕES: No presente estudo foi padronizado um modelo simples e facilmente reprodutível para estudar a regeneração hepática em ratos em crescimento com redução do fluxo arterial ou venoso para o fígado. Foi demonstrado que a administração de insulina ou tacrolimus é capaz de reverter os efeitos deletérios da estenose portal na regeneração hepática. A obstrução do fluxo arterial não afetou a capacidade regenerativa hepática