Prediction of sarcomere mutations in subclinical hypertrophic cardiomyopathy.

BACKGROUND: Sarcomere protein mutations in hypertrophic cardiomyopathy induce subtle cardiac structural changes before the development of left ventricular hypertrophy (LVH). We have proposed that myocardial crypts are part of this phenotype and independently associated with the presence of sarcomere gene mutations. We tested this hypothesis in genetic hypertrophic cardiomyopathy pre-LVH (genotype positive, LVH negative [G+LVH-]). METHODS AND RESULTS: A multicenter case-control study investigated crypts and 22 other cardiovascular magnetic resonance parameters in subclinical hypertrophic cardiomyopathy to determine their strength of association with sarcomere gene mutation carriage. The G+LVH- sample (n=73) was 29 ± 13 years old and 51% were men. Crypts were related to the presence of sarcomere mutations (for ≥1 crypt, β=2.5; 95% confidence interval [CI], 0.5-4.4; P=0.014 and for ≥2 crypts, β=3.0; 95% CI, 0.8-7.9; P=0.004). In combination with 3 other parameters: anterior mitral valve leaflet elongation (β=2.1; 95% CI, 1.7-3.1; P<0.001), abnormal LV apical trabeculae (β=1.6; 95% CI, 0.8-2.5; P<0.001), and smaller LV end-systolic volumes (β=1.4; 95% CI, 0.5-2.3; P=0.001), multiple crypts indicated the presence of sarcomere gene mutations with 80% accuracy and an area under the curve of 0.85 (95% CI, 0.8-0.9). In this G+LVH- population, cardiac myosin-binding protein C mutation carriers had twice the prevalence of crypts when compared with the other combined mutations (47 versus 23%; odds ratio, 2.9; 95% CI, 1.1-7.9; P=0.045). CONCLUSIONS: The subclinical hypertrophic cardiomyopathy phenotype measured by cardiovascular magnetic resonance in a multicenter environment and consisting of crypts (particularly multiple), anterior mitral valve leaflet elongation, abnormal trabeculae, and smaller LV systolic cavity is indicative of the presence of sarcomere gene mutations and highlights the need for further study

Characteristics and outcomes of heart failure hospitalization before implementation of a heart failure clinic: The PRECIC study

Objective: This study aims to characterize patients hospitalized for acute heart failure (HF) in an internal medicine department and their one-year mortality and rate of rehospitalization for decompensated HF. Methods: This retrospective observational study enrolled all patients discharged in 2012 after hospitalization for acute HF. Discharge summaries, clinical records and telephone interviews were analysed. The data reports to the year before implementation of a heart failure clinic. Results: Four hundred and twenty-nine patients were enrolled, with a mean age of 79 years, 62.5% female. The most prevalent comorbidity and etiology was hypertension (86.7%) and the most frequent decompensation trigger was infection. HF with preserved ejection fraction (HFpEF) was present in 70.5%. In-hospital mortality was 7.9%. At discharge more than half of the patients were prescribed beta-blockers (52.8%) and angiotensin-converting enzyme inhibitors (52%). Women presented a significantly higher proportion of HFpEF than men (75.3% vs. 62.7%, p=0.01). Patients with diabetes and those with ischemic etiology had significantly higher pro-portions of HF with reduced ejection fraction (HFrEF) (34.8% vs. 24.3% in non-diabetic patients,p=0.027, and 56.2% vs. 15.6% for other etiologies, p<0.001). The HFrEF group were more fre-quently discharged under beta-blockers and spironolactone (75.2% vs. 46.4% in the HFpEF group,p<0.001 and 31.2% vs. 12.6% in the HFpEF group, p<0.001, respectively). Mortality was 34.3%and rehospitalization for HF was 30.5% in one-year follow-up.Conclusions: The population characterized is an elderly one, mainly female and with HFpEF.Nearly a third of patients died and/or were rehospitalized in the year following discharge

TEORIAS DE ENFERMAGEM: IMPORTÂNCIA DA CORRETA APLICAÇÃO DOS CONCEITOS

Theoretical-reflexive research, whose aim is to analyze the clarity of concept stimulus in the Roy Model, for best comprehension in nursing practice. It was developed in three phases: 1- Search of studies that utilized the Roy Model; 2- Conducted reading for comprehension of the concept stimulus and 3- Analysis of clarity of the concept. The three studies were conducted at master level. The analysis of the studies shows deficiency in the clarity of the concept stimulus, being predominant the ambiguity in the classification and differentiation of the focal and contextual stimuli, without the existence of consistency and uniformity. The need arises to deepen the theories of nursing for adequate application in the areas of research: nursing education and practice, optimizing and improving its use, as well as, enabling the comprehension of determined concepts that are not sufficiently clear. The worries that arise among the nurses will provide a more profound approach to the study, enabling the advance of theories, as well as new findings, leading to necessary changes.  Investigación teórico-reflexiva cuyo objetivo fue analizar la claridad del concepto estímulo según el  modelo de Roy, para mayor comprensión en la práctica de enfermería. Desarrollada en tres etapas: 1ª- Levantamiento de estudios que utilizaron el Modelo de Roy; 2ª - Lectura dirigida hacia la comprensión del concepto estímulo y 3ª - Análisis de la claridad del concepto. Fueron utilizados tres estudios, a  nivel de maestrado. El análisis de los estudios demuestra deficiencia en la claridad del concepto estímulo, predominando ambigüedad en la clasificación y diferenciación de los estímulos focales y contextuales, sin consistencia y uniformidad. Se evidencia la necesidad de profundizar en las teorías de enfermería, para su aplicación adecuada en las áreas de investigación, enseñanza y práctica, optimizando y mejorando su uso, además de posibilitar la comprensión de determinados conceptos no suficientemente claros. Las inquietudes surgidas entre los enfermeros podrán motivar un abordaje más profundo de los estudios, posibilitando el avance de las teorías, así  como nuevos descubrimientos, dirigiendo los cambios necesariosPesquisa teórico-reflexiva, objetivando analisar a clareza do conceito estímulo no modelo de Roy, para maior compreensão na prática de enfermagem. Desenvolvido em três etapas: 1ª- Levantamento de estudos que utilizaram o Modelo de Roy; 2ª - Leitura dirigida para a compreensão do conceito estímulo e 3ª - Análise da clareza do conceito. Foram utilizados três estudos, em nível de mestrado. A análise dos estudos demonstra deficiência na clareza do conceito estímulo, predominando ambigüidade na classificação e diferenciação dos estímulos focais e contextuais, não existindo consistência e uniformidade. Evidencia-se a necessidade do aprofundamento nas teorias de enfermagem, para a aplicação adequada nas áreas de pesquisa, ensino e prática, otimizando e aprimorando seu uso, além de possibilitar a compreensão de determinados conceitos, não suficientemente claros. As inquietações surgidas entre os enfermeiros poderão proporcionar o aprofundamento nos estudos, possibilitando o avanço das teorias, assim como novos achados, direcionando as mudanças necessárias

Rpgrip1 is required for rod outer segment development and ciliary protein trafficking in zebrafish

The authors would like to thank the Royal Society of London, the National Eye Research Centre, the Visual Research Trust, Fight for Sight, the W.H. Ross Foundation, the Rosetrees Trust, and the Glasgow Children’s Hospital Charity for supporting this work. This work was also supported by the Deanship of Scientific Research at King Saud University for funding this research (Research Project) grant number ‘RGP – VPP – 219’.Mutations in the RPGR-interacting protein 1 (RPGRIP1) gene cause recessive Leber congenital amaurosis (LCA), juvenile retinitis pigmentosa (RP) and cone-rod dystrophy. RPGRIP1 interacts with other retinal disease-causing proteins and has been proposed to have a role in ciliary protein transport; however, its function remains elusive. Here, we describe a new zebrafish model carrying a nonsense mutation in the rpgrip1 gene. Rpgrip1homozygous mutants do not form rod outer segments and display mislocalization of rhodopsin, suggesting a role for RPGRIP1 in rhodopsin-bearing vesicle trafficking. Furthermore, Rab8, the key regulator of rhodopsin ciliary trafficking, was mislocalized in photoreceptor cells of rpgrip1 mutants. The degeneration of rod cells is early onset, followed by the death of cone cells. These phenotypes are similar to that observed in LCA and juvenile RP patients. Our data indicate RPGRIP1 is necessary for rod outer segment development through regulating ciliary protein trafficking. The rpgrip1 mutant zebrafish may provide a platform for developing therapeutic treatments for RP patients.Publisher PDFPeer reviewe

Doppler and birth weight Z score: predictors for adverse neonatal outcome in severe fetal compromise

BACKGROUND: An adequate placental perfusion is crucial for the normal growth and well being of the fetus and newborn. The blood flow through the placenta can be compromised in a variety of clinical situations, always causing important damage to the gestation. Our objective is to identify significant predictors for adverse neonatal outcome in severe fetal compromise. METHODS: Consecutive premature fetuses at between 25 and 32 weeks with severe placental insufficiency were examined prospectively. Inclusion criteria were: (i) singletons (ii) normal anatomy; (iii) abnormal umbilical artery Doppler pulsatility index (PI); (iv) abnormal cerebroplacental ratio; (v) middle cerebral artery (MCA) PI < - 2SD ("brain sparing"); (vi) last Doppler examination performed within 24 hours prior to delivery. All 46 patients that met criteria and started the study were followed to the end. We considered as independent potential predicting variables: absent or reversed end diastolic flow in umbilical artery, abnormal ductus venosus S/A ratio, absent or reversed flow during atrial contraction in the ductus venosus and birth weight Z score. Outcome parameters were: neonatal mortality and severe neonatal morbidity. RESULTS: Backward stepwise logistic regression analysis was used to determine the optimal model for the prediction of neonatal mortality and severe neonatal morbidity. In this analysis birth weight Z score index showed the strongest association OR = 1,87 [1,17-2,99] with all neonatal outcome, all other independent variables were excluded for the optimal model. There was no mortality for the group with normal birth weight Z score. CONCLUSION: Our study suggests that birth weight Z score is the strongest predictor of adverse neonatal outcome in severe placental insufficiencies. Such use of Z scores, allowing to get rid of gestational age or sex covariates could be extended to estimated fetal weight and might help in making important decisions in the management of compromised pregnancies

Risk Factors and Characterization of Plasmodium Vivax-Associated Admissions to Pediatric Intensive Care Units in the Brazilian Amazon

BACKGROUND: Plasmodium vivax is responsible for a significant proportion of malaria cases worldwide and is increasingly reported as a cause of severe disease. The objective of this study was to characterize severe vivax disease among children hospitalized in intensive care units (ICUs) in the Western Brazilian Amazon, and to identify risk factors associated with disease severity. METHODS AND FINDINGS: In this retrospective study, clinical records of 34 children, 0-14 years of age hospitalized in the 11 public pediatric and neonatal ICUs of the Manaus area, were reviewed. P. falciparum monoinfection or P. falciparum/P. vivax mixed infection was diagnosed by microscopy in 10 cases, while P. vivax monoinfection was confirmed in the remaining 24 cases. Two of the 24 patients with P. vivax monoinfection died. Respiratory distress, shock and severe anemia were the most frequent complications associated with P. vivax infection. Ninety-one children hospitalized with P. vivax monoinfections but not requiring ICU were consecutively recruited in a tertiary care hospital for infectious diseases to serve as a reference population (comparators). Male sex (p = 0.039), age less than five years (p = 0.028), parasitemia greater than 500/mm(3) (p = 0.018), and the presence of any acute (p = 0.023) or chronic (p = 0.017) co-morbidity were independently associated with ICU admission. At least one of the WHO severity criteria for malaria (formerly validated for P. falciparum) was present in 23/24 (95.8%) of the patients admitted to the ICU and in 17/91 (18.7%) of controls, making these criteria a good predictor of ICU admission (p = 0.001). The only investigated criterion not associated with ICU admission was hyperbilirubinemia (p = 0.513)]. CONCLUSIONS: Our study points to the importance of P. vivax-associated severe disease in children, causing 72.5% of the malaria admissions to pediatric ICUs. WHO severity criteria demonstrated good sensitivity in predicting severe P. vivax infection in this small case series

Genetic Variants of Diabetes Risk and Incident Cardiovascular Events in Chronic Coronary Artery Disease

Objective: To determine whether information from genetic risk variants for diabetes is associated with cardiovascular events incidence. Methods: From the about 30 known genes associated with diabetes, we genotyped single-nucleotide polymorphisms at the 10 loci most associated with type-2 diabetes in 425 subjects from the MASS-II Study, a randomized study in patients with multi-vessel coronary artery disease. The combined genetic information was evaluated by number of risk alleles for diabetes. Performance of genetic models relative to major cardiovascular events incidence was analyzed through Kaplan-Meier curve comparison and Cox Hazard Models and the discriminatory ability of models was assessed for cardiovascular events by calculating the area under the ROC curve. Results: Genetic information was able to predict 5-year incidence of major cardiovascular events and overall-mortality in non-diabetic individuals, even after adjustment for potential confounders including fasting glycemia. Non-diabetic individuals with high genetic risk had a similar incidence of events then diabetic individuals (cumulative hazard of 33.0 versus 35.1% of diabetic subjects). The addition of combined genetic information to clinical predictors significantly improved the AUC for cardiovascular events incidence (AUC = 0.641 versus 0.610). Conclusions: Combined information of genetic variants for diabetes risk is associated to major cardiovascular events incidence, including overall mortality, in non-diabetic individuals with coronary artery disease.FAPESP[2007/54138-2