Evaluating the impact of marketing interventions on sugar-free and sugar-sweetened soft drink sales and sugar purchases in a fast-food restaurant setting.

BACKGROUND: Beverages high in added sugar, such as sugar-sweetened soft drinks, continue to be associated with various health issues. This study examines the effects of a manufacturer-initiated multicomponent intervention on the sales of sugar-free (SFD) and sugar-sweetened (SSD) soft drinks and the amount of sugar people purchase from soft drinks in a fast-food restaurant setting. METHODS: A database of monthly sales data of soft drinks from January 2016 to December 2018 was obtained from three treatment and three control fast-food restaurants. A multicomponent intervention consisting of free coupons, point-of-purchase displays, a menu board, and two sugar-free replacements for sugar-sweetened soft drinks was introduced in August 2018 for five months in Western Sydney, Australia. A retrospective interrupted time series analysis was used to model the data and examine the effects of the interventions on SFD and SSD sales and their consequential impact on sugar purchases from soft drinks. The analyses were carried out for volume sales in litres and sugar in grams per millilitre of soft drinks sales. A comparison of these measures within the treatment site (pre- and post-intervention) and between sites (treatment and control) was conducted. RESULTS: The interventions had a statistically significant impact on SFDs but not SSDs. On average, SFD sales in the treatment site were 56.75% higher than in the control site. Although SSD sales were lower in the treatment site, the difference with the control site was not statistically significant. The net reduction of 6.34% in the amount of sugar purchased from soft drinks between sites during the experimental period was attributed to the interventions. CONCLUSIONS: The interventions significantly increased SFD sales and reduced sugar purchases in the short run. Aside from free coupons, the findings support the recommendation for fast food restaurants to nudge customers towards choosing SFDs through point-of-purchase displays and the replacement of popular SSDs with their SFD counterparts.

Molecular alterations in retinoblastoma beyond RB1.

Retinoblastoma is the most common malignant ocular tumor in children. Although RB1 alterations are most frequently involved in the etiology of retinoblastoma, candidate driver events and somatic alterations leading to cell transformation, tumor onset and progression remain poorly understood. In this study, we identified novel genomic alterations in tumors with a panel of 160 genes. Sanger sequencing and Multiplex Ligation-dependent Probe Amplification (MLPA) were initially performed for identifying patients without apparent RB1 alterations in blood DNA. Subsequently, NGS analyses of 24 paired (blood/tumor) samples of these patients were carried out for identifying somatic mutations and copy number variation in RB1 and other 159 genes. One novel pathogenic RB1 mutation and seven novel VUS were identified as well as 90 novel pathogenic mutations in 61 other genes. Twenty-three genes appeared exclusively mutated in tumors without altered RB1 alleles and three frequently affected biological pathways while five other tumors did not show pathogenic RB1 alterations or SNV/indels in 159 other genes. Curiously, deletion of GATA2, AKT1, ARID1A, DNMT3A, MAP2K2, MEN1, MTOR, PTCH1 and SUFU (in homo- or heterozygosity) were exclusively found in these tumors when compared to those with any pathogenic alterations, probably indicating genes that might be essential for the development of retinoblastoma regardless of a functional RB1. Identification of genes associated with retinoblastoma will contribute to understanding presently unknown aspects of this malignancy, which might be essential for its initiation and progression, as well as providing valuable molecular markers.

Gestão do cuidado à tuberculose: da formação à prática do enfermeiro / Care management for tuberculosis: from education to the nurse practice / Gestión del cuidado a la tuberculosis: de la formación a la práctica del enfermero

O estudo objetivou analisar a relação entre a formação do enfermeiro e as ações direcionadas à gestão do cuidado à tuberculose. De natureza qualitativa, foi realizada em um dos municípios da região metropolitana de João Pessoa-PB. Participaram do estudo dez enfermeiros da Estratégia Saúde da Família. A coleta de dados foi realizada em fevereiro de 2010 através de um roteiro de entrevista semiestruturado. Para análise do material empírico, utilizou-se a técnica de análise de conteúdo. Nos depoimentos dos enfermeiros há predominância da temática TB no espaço hospitalar, abordando tanto a superficialidade quanto o distanciamento do cuidado à TB no que concerne à relação entre a teoria e a prática, e a ausência de cuidados direto ao doente de TB durante a formação; a organização dos serviços aponta para uma prática mecanicista e tarefeira. Há necessidade das instituições formadoras se aproximarem dos serviços de saúde, numa relação dialógica, para melhor organizar os espaços de aprendizagem.

The study aimed to analyze the relation between the training of the nurse and the actions directed to the management of the care to the tuberculosis. With qualitative nature, it was performed in one of the cities of the metropolitan region of João Pessoa-PB. The subjects were ten nurses of the Health Family Strategy. The data collection was performed in February 2010 using a semi structured interview script. To examine the empiric material it was used the technique of content analyzes. In the testimonies of the nurses there was predominance of the thematic TB in the hospital space; they approach either the superficiality and the distance of the care to TB related to the relation between the theory and the practice, and the absence of direct care to the patient of TB during training; according to them, the organization of the services points to a mechanicist and task based practice. One concluded that there is necessity of training institutions to come close to the health services, in a dialogic relation, to organize better the learning spaces.

El estudio objetivó analizar la relación entre la formación del enfermero y las acciones direccionadas a la gestión del cuidado a la tuberculosis. De naturaleza cualitativa, fue realizado en uno de los municipios de la región metropolitana de João Pessoa-PB. Los sujetos fueron diez enfermeros de la Estrategia Salud de la Familia. La recopilación de datos fue realizada en febrero de 2010 a través de un guión de entrevista semi estructurada. Para análisis del material empírico se utilizó la técnica de análisis de contenido. En las declaraciones de los enfermeros hay predominancia de la temática TB en el espacio hospitalario, en que ellos abordaron tanto la superficialidad como el distanciamiento del cuidado a la TB en lo que se refiere a la relación entre teoría y práctica, y la ausencia de cuidados directos al enfermo de TB durante la formación; la organización de los servicios apunta para una práctica mecanicista y rutinaria. Hay necesidad de que las instituciones formadoras se aproximen de los servicios de salud, en una relación dialógica, para organizar mejor los espacios del aprendizaje.

[Care management for tuberculosis: from education to the nurse practice]. / Gestão do cuidado à tuberculose: da formação à prática do enfermeiro.

The study aimed to analyze the relation between the training of the nurse and the actions directed to the management of the care to the tuberculosis. With qualitative nature, it was performed in one of the cities of the metropolitan region of João Pessoa-PB. The subjects were ten nurses of the Health Family Strategy. The data collection was performed in February 2010 using a semi structured interview script. To examine the empiric material it was used the technique of content analyzes. In the testimonies of the nurses there was predominance of the thematic TB in the hospital space; they approach either the superficiality and the distance of the care to TB related to the relation between the theory and the practice, and the absence of direct care to the patient of TB during training; according to them, the organization of the services points to a mechanicist and task based practice. One concluded that there is necessity of training institutions to come close to the health services, in a dialogic relation, to organize better the learning spaces.

Influence of rs5065 atrial natriuretic peptide gene variant on coronary artery disease.

OBJECTIVES: The aim of this study was to investigate the impact of rs5065 atrial natriuretic peptide (ANP) gene variant on coronary artery disease (CAD) and its outcomes and to gain potential mechanistic insights on the association with CAD. BACKGROUND: Either modified ANP plasma levels or peptide structural alterations have been involved in development of cardiovascular events. METHODS: Three hundred ninety-three control subjects and 1,004 patients undergoing coronary angiography for suspected CAD (432 stable angina [SA], 572 acute coronary syndrome [ACS]) were genotyped for rs5065 ANP gene variant. Data in SA and ACS groups were replicated in an independent population of 482 stable angina patients (rSA) and of 675 ACS patients, respectively. Clinical follow-up was available for both SA and rSA patients. Plasma N-terminal-proANP, myeloperoxidase, lipoprotein-associated phospholipase A2, and oxidized low-density lipoprotein were assessed in a subgroup of rSA patients. RESULTS: rs5065 minor allele (MA) was an independent predictor of ACS (odds ratio: 1.90; 95% confidence interval: 1.40 to 2.58, p < 0.001). At follow-up, rs5065 MA was independently associated with a significantly higher rate of major adverse cardiovascular events in the SA group, p < 0.001. Data were replicated in the rSA group at follow-up (p = 0.008). Cox proportional hazard analysis tested by 4 models confirmed higher major adverse cardiovascular events risk in rs5065 MA carriers in both SA and rSA cohorts. Significantly higher myeloperoxidase levels were detected in rs5065 MA carriers (n = 597 [345 to 832 µg/l] vs. n = 488 [353 to 612 µg/l], p = 0.038). No association of rs5065 was observed with N-terminal-proANP levels. CONCLUSIONS: The MA of rs5065 ANP gene variant associates with increased susceptibility to ACS and has unfavorable prognostic value in CAD.

Identification of a novel MYBPC3 gene variant in a patient with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a genetic disorder characterized by cardiac hypertrophy caused by mutations in sarcomere protein genes. MYBPC3 mutations are reported as a frequent cause of HCM. We aimed to identify the gene mutation underlying HCM in an Italian patient and his family composed of 13 relatives. Mutation screening of 658 known mutations was performed using a rapid and efficient mutation detection system based on semiautomated MALDI-TOF mass spectrometry using the Sequenom MassArray System and iPLEX Gold genotyping chemistry. Subsequently, direct sequencing of the coding exons and flanking intronic regions was performed for the most suitable HCM genes (MYBPC3, MYH7, TNNT2, TNNI3, and TPM1) in the index patient. We found a novel MYBPC3 gene mutation: G13999T (Gln689His). No other sarcomere gene mutation was found in this family. This genetic variant, which changes the last amino acid of MYBPC3 exon 21, affects a highly conserved residue. Furthermore, the Gln689His does not appear in public databases and has never been described as a polymorphism. The potential pathogenic role of this novel mutation was underlined by its absence in a sample of healthy subjects (n = 122) from the general Italian population. In summary, a novel MYBPC3 gene mutation has been identified in a patient affected by HCM, whereas it was absent in 244 reference alleles.

Determinants of N-terminal proatrial natriuretic peptide plasma levels in a survey of adult male population from Southern Italy.

OBJECTIVES: Natriuretic peptides control cardiovascular functions through diuretic, natriuretic, and vasodilatory properties. Several anthropometric, cardiac and renal variables were found to be independently correlated to their levels. Few studies, however, systematically investigated the independent determinants of natriuretic peptide levels in large populations. DESIGN: The present analysis was carried out in a large unselected sample of adult male population in Southern Italy (The Olivetti Heart Study, n = 806 men, mean age = 59.5, range 35-82 years). We examined the relationship of plasma natriuretic peptide-proatrial natriuretic peptide (NT-proANP) levels with relevant anthropometric, clinical and biochemical variables; the impact of age; and the association of NT-proANP levels with cardiovascular risk. RESULTS: NT-proANP was directly associated to age, pulse pressure (PP), renal sodium fractional excretion (FENa) (P < 0.005), and inversely to diastolic blood pressure (DBP), heart rate (HR), creatinine clearance, body mass index (BMI), arm and leg circumferences (P < 0.005). After adjustment for age, DBP, creatinine clearance, FENa and HR remained independent determinants of NT-proANP levels (all P < 0.01, cumulative R = 0.186). Upon stratification of our population by tertile of age, NT-proANP was significantly associated (P

Reactive oxygen species-mediated effects on vascular remodeling induced by human atrial natriuretic peptide T2238C molecular variant in endothelial cells in vitro.

OBJECTIVES: T2238C ANP (atrial natriuretic peptide) gene variant has been associated with increased cardiovascular risk in humans and with a significant pharmacogenomic effect on cardiovascular disease outcome in hypertensive patients. We investigated the impact of T2238C ANP gene variant on oxidative stress production, cell proliferation and migration, angiogenesis and vascular remodeling in human umbilical vein endothelial cells in vitro. METHODS: Differentially expressed genes in human umbilical vein endothelial cells exposed to either wild-type (TT2238) or mutant (CC2238) alpha-ANP were characterized by real time-PCR-macroarray analysis using human oxidative stress, angiogenesis and matrix arrays. Reactive oxygen species (ROS) production was determined by dihydroethidium and by evaluation of dichlorofluorescein content. NADPH oxidase gp91phox subunit was investigated by western blotting. Endothelial cell proliferation, migration and tube formation were characterized both in the presence and in the absence of NADPH oxidase inhibition. RESULTS: Compared with TT2238, CC2238 alpha-ANP altered the redox state balance of the cells in a more significant manner, favoring ROS production and reducing antioxidative stress response. Gene expression of molecules involved in atherogenesis and vascular remodeling was enhanced. In contrast to TT2238 peptide, CC2238 was unable to stimulate cell proliferation and it markedly inhibited endothelial cell tube formation. NADPH oxidase inhibition restored the cell proliferative properties under CC2238 peptide exposure. CONCLUSION: CC2238 alpha-ANP led to ROS accumulation and increased expression of genes related to atherosclerosis and vascular remodeling in human umbilical vein endothelial cells. As a consequence of NADPH-derived ROS, blunted endothelial cell proliferation and impaired endothelial cell tube formation were observed. These in-vitro effects may link the T2238C alpha-ANP variant to enhanced susceptibility to vascular damage in vivo.

Phosphodiesterase 4D and 5-lipoxygenase activating protein genes and risk of ischemic stroke in Sardinians.

Genetic factors contribute to the risk of ischemic stroke (IS). The phosphodiesterase-4D (PDE4D) and the 5-lipoxygenase activating protein (ALOX5AP) genes were identified as contributors to stroke in an Icelandic population. In an attempt to better define the contributory role of PDE4D and ALOX5AP genes to the risk of IS in humans, we carried out the present association study in a well-characterized, earlier published, genetically homogenous population from the island of Sardinia, Italy. In this cohort, including 294 cases and 235 controls, age, hypertension, hypercholesterolemia, and atrial fibrillation represent risk factors for IS. The PDE4D gene was evaluated by four single nucleotide polymorphisms (SNP32, SNP45, SNP83, SNP87) and by the microsatellite AC008818-1; the ALOX5AP gene was characterized by three SNPs (SG13S32, SG13S89, ALO2A). The results of our study provide no evidence of association between any single PDE4D and ALOX5AP gene variant with the risk of IS in the Sardinian cohort. Haplotype analysis, including that constructed with allele 0 of microsatellite AC008818-1 and SNP45 of the PDE4D gene, was also negative. In conclusion, we found no evidence of association between PDE4D and ALOX5AP genes and the risk of IS in a genetically homogenous population from Sardinia.

Beta2-adrenergic receptor gene polymorphisms and risk of ischemic stroke.

BACKGROUND: Beta2-adrenergic receptors (beta2-AR) mediate vasorelaxation in response to adrenergic agents. Genetic polymorphisms of beta2-AR were implicated in various cardiovascular and noncardiovascular traits. METHODS: We tested the role of the beta2AR-16 and beta2AR-27 gene variants in the susceptibility to the development of ischemic stroke in a genetically homogenous and clinically well-characterized case-control sample that included 294 cases and 286 controls from Sardinia, Italy. This population was shown to be an optimal study sample for carrying out genetic analyses. RESULTS: Age, hypertension, dyslipidemia, and atrial fibrillation were independent risk factors for stroke in this cohort. We found that the presence of the Glu27 allelic variant was associated with a significantly increased risk of stroke when assuming a recessive mode of inheritance (odds ratio [OR], 1.68; 95% confidence interval [CI], 1.17-2.41; P = .005). The same results were obtained for the subgroup of ischemic strokes of arterial origin (n = 215): OR, 1.71; 95% CI, 1.14-2.57; P = .009. Furthermore, haplotype analysis confirmed that the presence of the Glu27 allele increased the risk of cerebrovascular accidents. CONCLUSIONS: Our data suggest that the Glu27 allelic variant of the beta2-AR gene may be a determinant of ischemic stroke.

Association of atrial natriuretic peptide and type a natriuretic peptide receptor gene polymorphisms with left ventricular mass in human essential hypertension.

OBJECTIVES: The goal of our study was to investigate the relationships between atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and type A natriuretic peptide receptor (NPRA) gene polymorphisms and left ventricular structure in human essential hypertension. BACKGROUND: Experimental evidence supports a key role for natriuretic peptides in the modulation of cardiac mass. This relationship has not yet been described in human disease. METHODS: A total of 203 hypertensive patients were studied by mono-bidimensional echocardiography. Three markers of the ANP gene (-C664G, G1837A, and T2238C polymorphisms) and a microsatellite marker of both NPRA and BNP genes were characterized. RESULTS: Patients carrying the ANP gene promoter allelic variant had increased left ventricular mass index (117.4 +/- 1.7 g vs. 95.7 +/- 1.7 g, p = 0.005), left ventricular posterior wall thickness (1.14 +/- 0.07 cm vs. 0.96 +/- 0.01 cm, p < 0.0001), left ventricular septal thickness (1.12 +/- 0.10 cm vs. 1.04 +/- 0.01 cm, p = 0.01), and relative wall thickening (47.5 +/- 4.1% vs. 39.4 +/- 5.3%, p = 0.001) as compared with the wild-type genotype. These associations were independent from anthropometric factors and major clinical features and were confirmed in a large subgroup of never-treated hypertensive patients (n = 148). Carrier status of the ANP gene promoter allelic variant was associated with significantly lower plasma proANP levels: 1,395 +/- 104 fmol/ml versus 3,110 +/- 141 fmol/ml in hypertensive patients carrying the wild-type genotype (p < 0.05). A significant association for NPRA gene variants with left ventricular mass index and left ventricular septal thickness was found. The analysis of BNP did not reveal any effect on cardiac phenotypes. CONCLUSIONS: Our findings show that the ANP/NPRA system significantly contributes to ventricular remodeling in human essential hypertension.

Reciprocal congenic lines for a major stroke QTL on rat chromosome 1.

We previously identified a quantitative trait locus (QTL) for stroke proneness between the kallikrein (Klk) and Mt1pa markers on rat chromosome 1. To gain functional insights, we constructed congenic strains by introgressing either the whole or selected chromosomal segments from the stroke-prone (SHRsp) onto the stroke-resistant (SHRsr) spontaneously hypertensive rat genome and vice versa. The phenotype was the latency to develop stroke under a Japanese high-salt, low-potassium diet for 3 mo [known as Japanese diet (JD)]. Blood pressure (BP) was measured by tail cuff throughout the experiment. Urinary protein excretion was monitored in all lines under JD. The SHRsp-derived lines carrying the SHRsr allele, and particularly the D1Rat134-Mt1pa chromosomal segment, had a significant delay of stroke occurrence and improved survival compared with SHRsp (P < 0.001). On the other hand, a significant occurrence of stroke events (20%) was detected in the reciprocal lines by the end of the 3-mo treatment with JD (P = 0.003). The stroke phenotype was also associated with increased proteinuria. Our results underscore the functional importance of the Chr 1 stroke QTL. Furthermore, they underscore the utility of stroke/congenic lines in dissecting the genetics of stroke.

Polymorphisms in prothrombotic genes and their impact on ischemic stroke in a Sardinian population.

Genetic factors are involved in the individual predisposition to develop ischemic stroke (IS). In the present study we tested the role of the Factor VII G10976A and -C122T polymorphisms on the susceptibility to develop IS in a genetically homogenous and clinically well ascertained case-control study including 294 cases (median age 75 years; 176 males/118 females) and 286 controls (median age 73 years; 163 males/123 females) in Sardinia, Italy. In addition, we carried out an exploratory analysis with respect to other frequently studied polymorphisms of haemostatic factor genes:Factor II G20210A, Factor V G1691A,,Fibrinogen alpha-chain Thr312Ala, Fibrinogen beta-chain -C148T, Factor XIII G185T, GPIIb/IIIa T1565C. Among all the genes tested, FVII -C122T showed a significant, independent contribution to IS predisposition both in crude and adjusted analyses (crude OR 1.52, 95% CI 1.09-2.10, P=0.013; adjusted OR 1.48, 95% CI 1.04-2.09, P=0.028, respectively). Haplotype analyses revealed a conserved population structure with high linkage disequilibrium between both FVII mutations tested. Blood levels of FVII had an inverse relationship with the polymorphism involved. Apart from genetic influence, there was a significant role for hypertension (OR=1.7, 95% CI 1.19-2.43, P=0.003), hypercholesterolemia (OR=2.21, 95% CI 1.38-3.54, P=0.001) and atrial fibrillation (OR=1.66, 95% CI 1.06-2.58, P=0.026) on IS occurrence. In summary, we describe evidence for a possible direct association of FVII gene molecular variants with the occurrence of IS in a genetically homogenous human sample.

Gene polymorphisms of the renin-angiotensin-aldosterone system and the risk of ischemic stroke: a role of the A1166C/AT1 gene variant.

OBJECTIVE: The role of the renin-angiotensin-aldosterone system (RAAS) genes on predisposition to develop stroke, a multifactorial and polygenic cardiovascular trait, is still under investigation. In the present study we characterized the contributory role of RAAS genes in the susceptibility to develop ischemic stroke in humans. METHODS: Allele and genotype frequencies of RAAS genes were characterized in a population of 215 cases (including only atherothrombotic and lacunar forms) and 236 controls selected in Sardinia, a large Mediterranean island with a well-known segregated population. Statistical analysis was performed in the whole population and, based on a significant interaction between angiotensin II receptor (AT1) genotype and hypertension, was also repeated in the hypertensive subgroup. RESULTS: A significant association of the C1166/AT1 gene allelic variant with stroke was found when assuming a dominant model of transmission [unadjusted odds ratio (OR)=1.5, 95% confidence interval (CI) 1.1-2.2, P=0.024]. The strength of the association became more evident in the subgroup of hypertensive individuals (135 cases and 110 controls). In fact, in this cohort the independent OR for the AT1 gene was 2.1, 95% CI 1.2-3.7, P=0.006 in the dominant model and 2.0, 95% CI 1.3-3.2, P=0.002 in the additive model. No other RAAS gene was identified as a contributor to stroke. CONCLUSIONS: Our findings support a predisposing role of an AT1 gene variant in the development of ischemic stroke. In particular, the AT1 gene variant exerted a major impact on ischemic stroke occurrence in the presence of hypertension.

Atrial natriuretic peptide gene polymorphisms and risk of ischemic stroke in humans.

BACKGROUND AND PURPOSE: A precise definition of genetic factors responsible for common forms of stroke is still lacking. The purpose of the present study was to investigate the contributory role of the genes encoding atrial natriuretic peptide (ANP) and type A natriuretic peptide receptor (NPRA) in humans' susceptibility to develop ischemic stroke. METHODS: Allele and genotype frequencies of ANP and NPRA were characterized in an Italian case-control study with patients affected by vascular disease or risk factors. Subjects were recruited from the island of Sardinia (206 cases, 236 controls). RESULTS: A significant association between the ANP/TC2238 polymorphic site and stroke occurrence was found when a recessive model of inheritance was assumed. The risk conferred by this mutant genotype, when estimated by multivariate logistic regression analysis, was 3.8 (95% confidence interval, 1.4 to 10.9). A significantly increased risk of stroke recurrence was observed among cases carrying the ANP/CC2238 genotype compared with cases carrying the ANP/TT2238 genotype (P=0.04). No direct association of NPRA with stroke occurrence was detected. However, a significant epistatic interaction between the ANP/CC2238 genotype and an allelic variant of NPRA led to a 5.5-fold increased risk of stroke (95% confidence interval, 1.5 to 19.4). CONCLUSIONS: Our findings support a direct contributory role of ANP to stroke in humans. A significant interaction between ANP and NPRA on stroke occurrence was found.