Enhanced dispersion of atrial refractoriness as an electrophysiological substrate for vulnerability to atrial fibrillation in patients with paroxysmal atrial fibrillation.

Atrial electrical remodeling plays a part in recurrence of atrial fibrillation (AF). It has been related to an increase in heterogeneity of atrial refractoriness that facilitates the occurrence of multiple reentry wavelets and vulnerability to AF. AIM: To examine the relationship between dispersion of atrial refractoriness (Disp_A) and vulnerability to AF induction (A_Vuln) in patients with clinical paroxysmal AF (PAF). METHODS: Thirty-six patients (22 male; age 55+/-13 years) with > or =1 year of history of PAF (no underlying structural heart disease--n=20, systemic hypertension--n=14, mitral valve prolapse--n=1, surgically corrected pulmonary stenosis--n=1), underwent electrophysiological study (EPS) while off medication. The atrial effective refractory period (AERP) was assessed at five different sites--high (HRA) and low (LRA) lateral right atrium, high interatrial septum (IAS), proximal (pCS) and distal (dCS) coronary sinus--during a cycle length of 600 ms. AERP was taken as the longest S1-S2 interval that failed to initiate a propagation response. Disp_A was calculated as the difference between the longest and shortest AERP. A_Vuln was defined as the ability to induce AF with 1-2 extrastimuli or with incremental atrial pacing (600-300 ms) from the HRA or dCS. The EPS included analysis of focal electrical activity based on the presence of supraventricular ectopic beats (spontaneous or with provocative maneuvers). The patients were divided into group A--AF inducible (n=25) and group B--AF not inducible (n=11). Disp_A was analyzed to determine any association with A_Vuln. Disp_A and A_Vuln were also examined in those patients with documented repetitive focal activity. Logistic regression was used to determine any association of the following variables with A_Vuln: age, systemic hypertension, left ventricular hypertrophy, left atrial size, left ventricular function, duration of PAF, documented atrial flutter/tachycardia and Disp_A. RESULTS: There were no significant differences between the groups with regard to clinical characteristics and echocardiographic data. AF was inducible in 71% of the patients and noninducible in 29%. Group A had greater Disp_A compared to group B (105+/-78 ms vs. 49+/-20 ms; p=0.01). Disp_A was >40 ms in 50% of the patients without A_Vuln and in 91% of those with A_Vuln (p=0.05). Focal activity was demonstrated in 14 cases (39%), 57% of them with A_Vuln. Disp_A was 56+/-23 ms in this group and 92+/-78 ms in the others (p=0.07). Using logistic regression, the only predictor of A_Vuln was Disp_A (p=0.05). CONCLUSION: In patients with paroxysmal AF, Disp_A is a major determinant of A_Vuln. Nevertheless, the degree of nonuniformity of AERP appears to be less important as an electrophysiological substrate for AF due to focal activation.     

Impact of a specialized outpatient heart failure follow-up program on hospitalization frequency and functional status of patients with advanced heart failure.

BACKGROUND: High rates of morbidity and mortality are observed in patients with advanced heart failure (AHF). AHF is now considered the most costly syndrome in cardiology owing to the substantial economic burden associated with hospitalizations for acute decompensation. A management program that involves specialized follow-up by a multidisciplinary team has been suggested as a desirable strategy for improving outcomes for these patients. ObjectivE: To evaluate the impact of a specialized outpatient heart failure (HF) follow-up program for patients with AHF on frequency and duration of hospitalization for HF and functional status. METHODS: We retrospectively studied 167 consecutive patients with AHF who were referred to the outpatient HF follow-up program in our institution between January and November 2002, of whom 147 followed for > or =30 days were included in the analysis. In addition to demographic and baseline clinical characteristics, HF medication and NYHA functional class, the number and duration of hospitalizations for HF during the previous 12 months were recorded and compared at the time of referral and after a follow-up period of 6.5+/-3 months. RESULTS: Of the 147 patients analyzed (aged 60.8+/-13 years; 79% male; left ventricular ejection fraction 27+/-11%), 67% were in NYHA functional class III, 20% in class II and 13% in class IV at the time of referral. There was a significant improvement in functional class during the mean follow-up period: 55% of the patients were in class III, 37% in class II, 5% in class I and 3% in class IV (p<0.0001). The proportion of patients on beta-blockers or spironolactone increased from 33% and 51% at the time of referral to 69% and 71% respectively after referral (p<0.0001). In the 12 months before referral, 39% of the patients had been hospitalized for acute decompensation of HF (87 hospitalizations - mean 7.2/month) versus 13% of the patients during the mean follow-up period (25 hospitalizations - 3.8/month, p<0.0001). No significant differences were found in the proportion of patients on angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, digoxin or diuretics, or in the mean duration of hospitalization before and after referral. ConclusioN: The specialized follow-up of patients with AHF by a team with expertise in HF resulted in significant therapeutic optimization. Increased use of beta-blockers and spironolactone was associated with significant improvement in functional capacity and significant reduction in hospitalizations.     

P-cadherin expression is associated with high-grade ductal carcinoma in situ of the breast

Cadherins are calcium-dependent cell-cell adhesion glycoproteins, separated into several subclasses with distinct adhesive specificities and tissue distribution, which play an important role in many cellular events. We analyse the expression of E-, N- and P-cadherin in a series of ductal carcinoma in situ (DCIS) of the breast, since this disease represents a heterogeneous group, with different risks of progression to invasive breast carcinoma. We also studied the correlation between cadherin expression and DCIS classification systems, namely the Van Nuys and the Holland et al. classification, this latter based on cytonuclear differentiation and cell polarity. Our results showed that, regardless the classification applied, P-cadherin expression is strongly associated with high histological grade of DCIS (P=0.0047) and lack of estrogen receptors (P=0.0008). The use of Holland et al. classification showed a significant correlation between P-cadherin expression and decreased cell polarity (P=0.01). In conclusion, P-cadherin expression seems to be more relevant in DCIS pathogenesis than the altered expression of any other cadherin, including the decrease of E-cadherin expression.     

Family-based and case-control studies reveal no association of lipocalin-type prostaglandin D2 synthase with schizophrenia.

Several observations point to the involvement of disturbed lipid biology in schizophrenia. Reduced response to niacin flushing test, which involves vasodilatation induced by prostaglandin D2 (PGD2), is among the evidences, together with decreased CSF levels of lipocalin-type prostaglandin D2 synthase (PTGDS), the enzyme responsible for the synthesis of PGD2 in the brain. Since PTGDS is also a carrier for lipophilic molecules such as retinoids and thyroid hormones, altered PTGDS levels might influence both PGD2-mediated signaling, and vitamin A and thyroid hormone availability. To test whether genetic variants of PTGDS are involved in the etiology of schizophrenia, we searched for variants in the coding and regulatory regions of the gene. We identified four previously described polymorphisms. Using two case-control samples from Portugal and Brazil, none of the polymorphisms tested was associated with the disease. In addition, no transmission distortion was observed in an independent parents-offspring sample from the Azorean Islands. Our data do not support the involvement of the PTGDS gene in the etiology of schizophrenia.     

Functional Health Literacy: Psychometric Properties of the Newest Vital Sign for Portuguese Adolescents (NVS-PTeen)

Self-management of health requires skills to obtain, process, understand, and use health-related information. Assessment of adolescents’ functional health literacy requires valid, reliable, and low-burden tools. The main objective of this study was to adapt and study the psychometric properties of the Newest Vital Sign for the Portuguese adolescents’ population (NVS-PTeen). Classic psychometric indicators of reliability and validity were combined with item response theory (IRT) analyses in a cross-sectional survey, complemented with a 3-month test-retest assessment. The NVS-PTeen was self-administered to students enrolled in grades 8 to 12 (12 to 17 years old) in a school setting. Overall, 386 students (191 girls) from 16 classes of the same school participated in the study (mean age = 14.5; SD = 1.5). Internal reliability of the NVS-PTeen was α = 0.60. The NVS-PTeen total score was positively and significantly correlated with Portuguese (r = 0.28) and mathematics scores (r = 0.31), school years (r = 0.31), and age (r = 0.19). Similar to the original scale (for the U.S.), the NVS-PTeen is composed of two dimensions, reading-related literacy and numeracy. Temporal reliability is adequate, though with a learning effect. IRT analyses revealed differences in difficulty and discriminative capacity among items, all with adequate outfit and infit values. Results showed that the NVS-PTeen is valid and reliable, sensible to inter-individual educational differences, and adequate for regular screening of functional health literacy in adolescents.     

Analytical Assessment and Nutritional Adequacy of School Lunches in Sintra’s Public Primary Schools

School meals present several cost benefits overtime at the short, medium, and long term for individuals and society. This cross-sectional study aims to analyse the nutritional composition and evaluate the adequacy of school lunches. One hundred and fifty-eight samples were collected and analysed from 10 primary schools in Sintra’s municipality, served during one week. On average, energy (27.7% daily energetic requirements) and carbohydrate (48.1%) contents did not reach the reference values, and the content of protein (19.5%) exceeded the reference value (p < 0.05). The mean total fat (28.8%) and saturated fatty acids (5.4%) content complied with the recommendations. The mean salt (1.7 g) and dietary fibre (8.3 g) content exceeded the reference value but did not differ significantly from the recommendations. Addressing school canteens is crucial, not only in a nutritional approach, but also as an opportunity to achieve healthier, sustainable, and accessible food systems, aligned with the Sustainable Development Goals 2030. We highlighted the importance of evaluating evidence-based practices and disseminated practice-based evidence regarding the adequacy of school lunches.     

Machine learning and national health data to improve evidence: Finding segmentation in individuals without private insurance

ObjectiveIndividuals without private health insurance have less access to healthcare, therefore are more prone to experience poor health when compared to those who have. Segmentation is an approach to find homogenous groups of people with the purpose of tailoring services and products. In public policy, segmentation might be used to identify characteristics and needs of specific groups and deliver targeted programs and spare costs. We aim to identify and describe segments within the uninsured population to aid targeted policy actions and improve health.MethodsWe used secondary data collected from a representative, nationwide health survey (n=18,204). For the purpose of our analysis, we included data from individuals who answered “no” to the question: “Do you have private health insurance?” (n=12,134). Variables pertaining information on socio-demographic, health status, access and care were used. A multiple correspondence analysis was performed to find principal components followed by a hierarchical cluster.ResultsWe found three clusters. The first (54.12% of our sample) composed by a group of young, middle aged and professionally active individuals without health problems. The second (36.70%), a cluster of aging individuals composed especially by elderly women, either retired or fulfilling domestic tasks, with a long-term health problem. The last (9.17%) composed by elder people, with long-term health problem and scoring low in mental health related questions.ConclusionOur study found three clusters (profiles of individuals) among the uninsured. Ultimately, our findings aim to support policy makers to deliver customized actions to improve health and provide cost-effective policies.     

Thyroid hormones,Sertoli cell proliferation and differentiation in progenies from carbamazepine-treated rat dams during pregnancy and lactation

Carbamazepine (CBZ) is used in the control of seizure and affective disorders, causing hypothyroidism. Thyroid hormones regulate the Sertoli cell proliferation and differentiation. Clinical aspects must be considered since epileptic fertile women need to continuously use CBZ during pregnancy and lactation. This study aimed to evaluate the effects of CBZ on testis development of rat offspring from dams treated during pregnancy/lactation. Rat dams received CBZ (20 mg kg⁻¹ day⁻¹) or vehicle by intra-peritoneal route during gestation and lactation. Progenies were euthanised at 4, 14, 41, 63 and 93-days post-partum (dpp) for the evaluation of T3, T4 and TSH plasma total levels. Testicular cross sections were submitted to anti-Ki67, anti-PCNA, anti-p27^kip1 and anti-transferrin immunolabelling for the evaluation of Sertoli cells. There was a significant reduction in p27^kip1-positive Sertoli cell numerical densities and an increase in TSH level at 14 dpp. CBZ exposure affected the volume density of transferrin-positive immunolabelling at 63 dpp. These results suggest that CBZ may cause a dysregulation of the controller system of thyroid hormones homeostasis leading to an increase in the proliferation rate at the neonatal phase and a differentiation delay of the Sertoli cell, culminating in an altered function at late puberty. The occurrence of hypothyroidism cannot be completely discarded.