Angiotensin-(1-7) Treatment Early in Life Prevents Cardiac Hypertrophy in Adult Hypertensive Rats.

ABSTRACT: Angiotensin (Ang)-(1-7) is a cardioprotective peptide of the renin-angiotensin system. Prepuberty has been considered as a later susceptible window of development, and stressful factors in this life phase can induce chronic diseases in adulthood. We aimed to investigate whether the treatment with Ang-(1-7) during the prepuberty could attenuate the development of hypertension and cardiac injury in adult spontaneously hypertensive rats (SHRs). SHRs were treated with Ang-(1-7) (24 µg/kg/h) from age 4 to 7 weeks. Systolic blood pressure was measured by tail-cuff plethysmography up to 17th week. Thereafter, echocardiography was performed, and the rats were euthanized for the collection of tissues and blood. Ang-(1-7) did not change the systolic blood pressure but reduced the septal and posterior wall thickness, and cardiomyocyte hypertrophy and fibrosis in SHR. In addition, Ang-(1-7) reduced the gene expression of atrial natriuretic peptide and brain natriuretic peptide, increased the metalloproteinase 9 expression, and reduced the extracellular signal-regulated kinases 1/2 phosphorylation. Ang-(1-7) also prevented the reduction of Mas receptor but did not change the protein expression of angiotensin-converting enzyme, angiotensin-converting enzyme 2, AT1, and AT2. The treatment with Ang-(1-7) decreased the malondialdehyde (MDA) levels and increased superoxide dismutase-1 and catalase activities and protein expression of catalase. Our findings demonstrate that the treatment of SHR with Ang-(1-7) for 3 weeks early in life promotes beneficial effects in the heart later in life, even without altering blood pressure, through mechanisms involving the reduction of oxidative stress and ERK1/2 phosphorylation. In addition, this study supports the prepuberty as an important programming window.

Expression, purification and preliminary characterisation of the choline transporter LicB from opportunistic bacterial pathogens.

Many opportunistic bacteria that infect the upper respiratory tract decorate their cell surface with phosphorylcholine to support colonisation and outgrowth. These surface modifications require the active import of choline from the host environment, a process thought to be mediated by a family of dedicated integral membrane proteins that act as choline permeases. Here, we present the expression and purification of the archetype of these choline transporters, LicB from Haemophilus influenzae. We show that LicB can be recombinantly produced in Escherichia coli and purified to homogeneity in a stable, folded state using the detergent n-dodecyl-ß-d-maltopyranoside. Equilibrium binding studies with the fluorescent ligand dansylcholine suggest that LicB is selective towards choline, with reduced affinity for acetylcholine and no apparent activity towards other small molecules including glycine, carnitine and betaine. We also identify a conserved sequence motif within the LicB family and show that mutations within this motif compromise protein structure and function. Our results are consistent with previous observations that LicB is a specific high-affinity choline transporter, and provide an experimental platform for further studies of this permease family.

Investigating method effects associated with the wording direction of items of the Social Physique Anxiety Scale.

PURPOSE: The use of psychometric instruments to measure latent concepts is common. The development of these instruments usually involves mechanisms to reduce response bias, such as the inclusion of reversed items. The aim of this study was to investigate method effects related to the wording direction of the Social Physique Anxiety Scale (SPAS) items, a one-dimensional instrument that assesses individual's level of anxiety when others observe their body. METHODS: In total, 152 Brazilian adults (65.8% female) answered 2 formats of the SPAS: the original with 12 items (7 regular and 5 reversed); and a new format with all items written in the same direction (i.e., regular). Both formats were filled out at different times and alternately. Differential item functioning analysis (DIF) and confirmatory factor analysis were conducted. RESULTS: The original SPAS did not fit the data, but after allowing covariances between all reversed items, the fit improved. The wording effect was supported by the DIF, indicating a better fit to the data for the new format with all items worded in the same direction. CONCLUSION: The wording of the SPAS items had effect on the psychometric properties of instrument. When the wording of the reversed items was modified, the factor model fitted the data. Future studies should take these findings into account and evaluate the SPAS with all items worded in the same direction in different contexts. LEVEL OF EVIDENCE: Descriptive (cross-sectional) study, Level V.

A psychometric investigation of Brazilian Portuguese versions of the Caregiver Eating Messages Scale and Intuitive Eating Scale-2.

The Caregiver Eating Messages Scale (CEMS) was developed to assess perceived restrictive or critical caregiver messages in relation to food intake and pressure to eat, whereas the Intuitive Eating Scale-2 (IES-2) measures one's tendency to follow internal cues of hunger and satiety when making eating-related decisions. Both scales are useful in the arsenal of eating behaviour scholars. Here, we developed Brazilian Portuguese translations of both scales and assessed their psychometric properties in Brazilian adults. A total of 288 participants (men = 52.8%) completed the CEMS, IES-2, Body Appreciation Scale (BAS), and a demographic questionnaire. The results of confirmatory factor analysis indicated that the factor structure of both scales had adequate fit following the elimination of items and addition of covariances. Evidence of adequate factorial, convergent and discriminant validity, as well as reliability was identified. Furthermore, correlations of CEMS and IES-2 with BAS scores and body mass index were obtained. Both instruments' models were found to be invariant across sex, with men having significantly higher scores on three subscales of the IES-2 only. These results provide evidence for the psychometric properties of the CEMS and IES-2 in Brazilian Portuguese-speaking adults.Level of Evidence: V, cross-sectional descriptive study.

Mas receptor blockade impairs exercise-induced cardiac hypertrophy.

Exercise training leads to physiological cardiac hypertrophy and the protective axis of the renin-angiotensin system composed of angiotensin-converting enzyme 2, angiotensin-(1-7), and Mas receptor seems involved in this process. However, the role of the basal activity of the Mas receptor in exercise-induced physiological cardiac hypertrophy is still unclear. We evaluated the effects of the Mas receptor blockade on the left ventricular structure and function of rats submitted to running training. Rats were assigned to 4 groups: sedentary (S), sedentary + A-779 (Mas receptor antagonist, 120 µg/kg/day, i.p.; SA), trained (60-minute treadmill running sessions, five days a week, 8 weeks; T), and trained + A-779 (TA). Systolic blood pressure was higher in sedentary and trained rats treated with A-779 at the end of the experimental period. The A-779 treatment prevented the left ventricular hypertrophy evoked by physical exercise and increased collagen deposition in sedentary and trained rats. Cardiomyocytes from the SA group presented increased length and thickness of the sarcomeres, elongated mitochondria, glycogen deposits, and enlarged cisterns of the sarcoplasmic reticulum. TA group presented a reduced sarcomere thickness and cytoplasm with a degenerative aspect. These findings show that the basal activity of the Mas receptor is essential for the proper turnover of the extracellular matrix in the myocardium and the maintenance of the sarcomeric structure of cardiomyocytes.

Development of a maturity model for additive manufacturing: A conceptual model proposal.

Additive manufacturing (AM) is an emerging area with the potential to modify present business models in the near future. In contrast with conventional manufacturing (CM), AM allows the development of a product from a smaller amount of raw material, while allowing an improvement in properties in terms of weight and functionality. Its production flexibility and creativity in terms of materials have enabled not only the industry to use this technology, but also has been used in healthcare (e.g., in the production of human tissue) and by the final consumer. Despite the invaluable opportunities that this technology could provide, the uncertainties concerning its future developments and impacts on business models remain. New business models in AM will convey the need to: specialize the workforce in the design of new parts produced locally or remotely; regulation in the use and sharing of intellectual property rights by partner companies or between users; regulate the possibility of reverse engineering of highly customized products; etc. The present research proposes a conceptual maturity model to support the phases of evolution of AM in the industry, in supply chains, and in terms of open business models.

Measuring adherence to inhaled control medication in patients with asthma: Comparison among an asthma app, patient self-report and physician assessment.

BACKGROUND: Previous studies have demonstrated the feasibility of using an asthma app to support medication management and adherence but failed to compare with other measures currently used in clinical practice. However, in a clinical setting, any additional adherence measurement must be evaluated in the context of both the patient and physician perspectives so that it can also help improve the process of shared decision making. Thus, we aimed to compare different measures of adherence to asthma control inhalers in clinical practice, namely through an app, patient self-report and physician assessment. METHODS: This study is a secondary analysis of three prospective multicentre observational studies with patients (≥13 years old) with persistent asthma recruited from 61 primary and secondary care centres in Portugal. Patients were invited to use the InspirerMundi app and register their inhaled medication. Adherence was measured by the app as the number of doses taken divided by the number of doses scheduled each day and two time points were considered for analysis: 1-week and 1-month. At baseline, patients and physicians independently assessed adherence to asthma control inhalers during the previous week using a Visual Analogue Scale (VAS 0-100). RESULTS: A total of 193 patients (72% female; median [P25-P75] age 28 [19-41] years old) were included in the analysis. Adherence measured by the app was lower (1 week: 31 [0-71]%; 1 month: 18 [0-48]%) than patient self-report (80 [60-95]) and physician assessment (82 [51-94]) (p < 0.001). A negligible non-significant correlation was found between the app and subjective measurements (ρ 0.118-0.156, p > 0.05). There was a moderate correlation between patient self-report and physician assessment (ρ = 0.596, p < 0.001). CONCLUSIONS: Adherence measured by the app was lower than that reported by the patient or the physician. This was expected as objective measurements are commonly lower than subjective evaluations, which tend to overestimate adherence. Nevertheless, the low adherence measured by the app may also be influenced by the use of the app itself and this needs to be considered in future studies.

Robust, maintainable, emergency invasive mechanical ventilator. / Ventilador mecânico invasivo de emergência resistente e de fácil manutenção.

OBJECTIVE: To develop a simple, robust, safe and efficient invasive mechanical ventilator that can be used in remote areas of the world or war zones where the practical utility of more sophisticated equipment is limited by considerations of maintainability, availability of parts, transportation and/or cost. METHODS: The device implements the pressure-controlled continuous mandatory ventilation mode, complemented by a simple assist-control mode. Continuous positive airway pressure is also possible. The consumption of compressed gases is minimized by avoiding a continuous flow of oxygen or air. Respiratory rates and inspiration/expiration time ratios are electronically determined, and an apnea/power loss alarm is provided. RESULTS: The pressure profiles were measured for a range of conditions and found to be adjustable within a ± 2.5cmH2O error margin and stable well within this range over a 41-hour period. Respiratory cycle timing parameters were precise within a few percentage points over the same period. The device was tested for durability for an equivalent period of four months. Chemical and biological tests failed to identify any contamination of the gas by volatile organic compounds or microorganisms. A ventilation test on a large animal, in comparison with a well established ventilator, showed that the animal could be adequately ventilated over a period of 60 minutes, without any noticeable negative aftereffects during the subsequent 24-hour period. CONCLUSION: This ventilator design may be viable, after further animal tests and formal approval by the competent authorities, for clinical application in the abovementioned atypical circumstances.

OBJETIVO: Desenvolver um ventilador mecânico invasivo simples, resistente, seguro e eficiente que possa ser utilizado em áreas remotas do mundo ou zonas de guerra, em que a utilidade prática de equipamentos mais sofisticados é limitada por questões de manutenção, disponibilidade de peças, transporte e/ou custo. MÉTODOS: O dispositivo implementa o modo de ventilação mandatória contínua com pressão controlada, complementado por um simples modo assisto-controlado. Pode-se também utilizar a pressão positiva contínua nas vias aéreas. Ao se evitar o fluxo contínuo de oxigênio ou ar, minimiza-se o consumo de gases comprimidos. As taxas respiratórias e as relações de tempo de inspiração e expiração são determinadas eletronicamente. Além disso, conta com um alarme de apneia/falta de energia. RESULTADOS: Os perfis de pressão foram medidos para uma série de condições, sendo considerados ajustáveis dentro de uma margem de erro de ± 2,5cmH2O, e foram considerados bem estáveis dentro dessa variação durante um período de 41 horas. Os parâmetros de tempo do ciclo respiratório foram precisos dentro de alguns pontos percentuais durante o mesmo período. O dispositivo foi testado quanto à durabilidade por um período equivalente a 4 meses. Os testes químicos e biológicos não conseguiram identificar qualquer contaminação do gás por compostos orgânicos voláteis ou micro-organismos. Em comparação com um ventilador bem estabelecido, o teste de ventilação em um animal de grande porte mostrou que este poderia ser ventilado adequadamente durante um período de 60 minutos, sem quaisquer efeitos negativos perceptíveis durante o período subsequente de 24 horas. CONCLUSÃO: Este projeto de ventilador pode ser viável após novos testes em animais e aprovação formal pelas autoridades competentes, para aplicação clínica nas circunstâncias atípicas anteriormente mencionadas.

A Portuguese Adaptation of the Teruel Orthorexia Scale and a Test of Its Utility with Brazilian Young Adults.

The aims for this study were to perform a Portuguese language cross-cultural adaptation of the Teruel Orthorexia Scale (TOS) and to evaluate the scale's psychometric properties, including verifying the frequency of behaviors characteristic of orthorexia nervosa and healthy orthorexia, among a group of Brazilian gym users. First, we adapted the Spanish version of the TOS to the Brazilian Portuguese language following international protocols to guarantee idiomatic, semantic, conceptual, and cultural equivalence. Then participants completed both the new Portuguese version of the TOS and a socioeconomic questionnaire. Among our sample of 226 young Brazilian adults (63.7% men; M age = 28.8, SD = 5.1 years), we assessed the bi-factorial model of the TOS through factorial, convergent, and discriminant validity, reliability, and factorial invariance. We calculated the mean scores of the TOS factors and the frequency of behaviors of both orthorexia nervosa and healthy orthorexia. The new Portuguese version was well understood by participants, and the TOS bi-factorial model presented adequate psychometric properties and showed invariance in independent subsamples and in men and women. The mean scores were different between sexes only for orthorexia nervosa, with women obtaining higher values. The frequency of orthorexia nervosa behaviors was 5.3% and of healthy orthorexia was 41.2%. Based on these findings, the Brazilian Portuguese version of the TOS can be a useful tool for investigating orthorexia-like behaviors in future research.

Advances in the automated synthesis of 6-[18F]Fluoro-L-DOPA.

The neurotracer 6-[18F] FDOPA has been, for many years, a powerful tool in PET imaging of neuropsychiatric diseases, movement disorders and brain malignancies. More recently, it also demonstrated good results in the diagnosis of other malignancies such as neuroendocrine tumours, pheochromocytoma or pancreatic adenocarcinoma.The multiple clinical applications of this tracer fostered a very strong interest in the development of new and improved methods for its radiosynthesis. The no-carrier-added nucleophilic 18F-fluorination process has gained increasing attention, in recent years, due to the high molar activities obtained, when compared with the other methods although the radiochemical yield remains low (17-30%). This led to the development of several nucleophilic synthetic processes in order to obtain the product with molar activity, radiochemical yield and enantiomeric purity suitable for human PET studies.Automation of the synthetic processes is crucial for routine clinical use and compliance with GMP requirements. Nevertheless, the complexity of the synthesis makes the production challenging, increasing the chance of failure in routine production. Thus, for large-scale clinical application and wider use of this radiopharmaceutical, progress in the automation of this complex radiosynthesis is of critical importance.This review summarizes the most recent developments of 6-[18F]FDOPA radiosynthesis and discusses the key issues regarding its automation for routine clinical use.