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INTRODUCTION: Femoral vein transposition is one of the final resorts for vascular access in patients with exhaustion of upper limb venous patrimony and central venous occlusive disease. Its major pitfalls include hemodialysis access-induced distal ischemia and infection. Surgical procedures may be warranted to preserve vascular access if ischemia develops. Several techniques are reported in the literature for femoral vein transposition. CASE REPORT: We expose an endoscopic femoral vein harvesting as an alternative to the single thigh incision in order to avoid its associated complications. In the setting of ischemia, proximalization of arterial inflow was used to manage femoral vein transposition associated limb ischemia. CONCLUSION: This case report aims to expose the aforementioned unreported surgical techniques for lower limb arteriovenous fistula, its advantages, and pitfalls, as well as considerations on its future use.
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Metabolic bone disorders and associated fragility fractures are major causes of disability and mortality worldwide and place an important financial burden on the global health systems. These disorders result from an unbalance between bone anabolic and resorptive processes and are characterized by different pathophysiological mechanisms. Drugs are available to treat bone metabolic pathologies, but they are either poorly effective or associated with undesired side effects that limit their use. The molecular mechanism underlying the most common metabolic bone disorders, and the availability, efficacy, and limitations of therapeutic options currently available are discussed here. A source for the unmet need of novel drugs to treat metabolic bone disorders is marine organisms, which produce natural osteoactive compounds of high pharmaceutical potential. In this review, we have inventoried the marine osteoactive compounds (MOCs) currently identified and spotted the groups of marine organisms with potential for MOC production. Finally, we briefly examine the availability of in vivo screening and validation tools for the study of MOCs.
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Produtos Biológicos , Doenças Ósseas Metabólicas , Humanos , Produtos Biológicos/farmacologiaRESUMO
BACKGROUND: Estimating the risks and impacts of COVID-19 for different health groups at the population level is essential for orienting public health measures. Adopting a population-based approach, we conducted a systematic review to explore: (1) the etiological role of multimorbidity and frailty in developing SARS-CoV-2 infection and COVID-19-related short-term outcomes; and (2) the prognostic role of multimorbidity and frailty in developing short- and long-term outcomes. This review presents the state of the evidence in the early years of the pandemic. It was conducted within the European Union Horizon 2020 program (No: 101018317); Prospero registration: CRD42021249444. METHODS: PubMed, Embase, World Health Organisation COVID-19 Global literature on coronavirus disease, and PsycINFO were searched between January 2020 and 7 April 2021 for multimorbidity and 1 February 2022 for frailty. Quantitative peer-reviewed studies published in English with population-representative samples and validated multimorbidity and frailty tools were considered. RESULTS: Overall, 9,701 records were screened by title/abstract and 267 with full text. Finally, 14 studies were retained for multimorbidity (etiological role, n = 2; prognostic, n = 13) and 5 for frailty (etiological role, n = 2; prognostic, n = 4). Only short-term outcomes, mainly mortality, were identified. An elevated likelihood of poorer outcomes was associated with an increasing number of diseases, a higher Charlson Comorbidity Index, different disease combinations, and an increasing frailty level. DISCUSSION: Future studies, which include the effects of recent virus variants, repeated exposure and vaccination, will be useful for comparing the possible evolution of the associations observed in the earlier waves.
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COVID-19 , Fragilidade , Multimorbidade , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , Fragilidade/epidemiologia , Prognóstico , IdosoRESUMO
This work evaluates the use of a programmable logic controller (PLC) from Phoenix Contact's PLCnext ecosystem as an image processing platform. PLCnext controllers provide the functions of "classical" industrial controllers, but they are based on the Linux operating system, also allowing for the use of software tools usually associated with computers. Visual processing applications in the Python programming language using the OpenCV library are implemented in the PLC using this feature. This research is focused on evaluating the use of this PLC as an image processing platform, particularly for industrial machine vision applications. The methodology is based on comparing the PLC's performance against a computer using standard image processing algorithms. In addition, a demonstration application based on a real-world scenario for quality control by visual inspection is presented. It is concluded that despite significant limitations in processing power, the simultaneous use of the PLC as an industrial controller and image processing platform is feasible for applications of low complexity and undemanding cycle times, providing valuable insights and benchmarks for the scientific community interested in the convergence of industrial automation and computer vision technologies.
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The functional reach test (FRT) is a clinical tool used to evaluate dynamic balance and fall risk in older adults and those with certain neurological diseases. It provides crucial information for developing rehabilitation programs to improve balance and reduce fall risk. This paper aims to describe a new tool to gather and analyze the data from inertial sensors to allow automation and increased reliability in the future by removing practitioner bias and facilitating the FRT procedure. A new tool for gathering and analyzing data from inertial sensors has been developed to remove practitioner bias and streamline the FRT procedure. The study involved 54 senior citizens using smartphones with sensors to execute FRT. The methods included using a mobile app to gather data, using sensor-fusion algorithms like the Madgwick algorithm to estimate orientation, and attempting to estimate location by twice integrating accelerometer data. However, accurate position estimation was difficult, highlighting the need for more research and development. The study highlights the benefits and drawbacks of automated balance assessment testing with mobile device sensors, highlighting the potential of technology to enhance conventional health evaluations.
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Aplicativos Móveis , Doenças do Sistema Nervoso , Humanos , Idoso , Reprodutibilidade dos Testes , Algoritmos , SmartphoneRESUMO
Complex, chronic or hard-to-heal wounds are a prevalent health problem worldwide, with significant physical, psychological and social consequences. This study aims to identify factors associated with the healing process of these wounds and develop a mobile application for wound care that incorporates these factors. A prospective multicentre cohort study was conducted in nine health units in Portugal, involving data collection through a mobile application by nurses from April to October 2022. The study followed 46 patients with 57 wounds for up to 5 weeks, conducting six evaluations. Healing time was the main outcome measure, analysed using the Mann-Whitney test and three Cox regression models to calculate risk ratios. The study sample comprised various wound types, with pressure ulcers being the most common (61.4%), followed by venous leg ulcers (17.5%) and diabetic foot ulcers (8.8%). Factors that were found to impair the wound healing process included chronic kidney disease (U = 13.50; p = 0.046), obesity (U = 18.0; p = 0.021), non-adherence to treatment (U = 1.0; p = 0.029) and interference of the wound with daily routines (U = 11.0; p = 0.028). Risk factors for delayed healing over time were identified as bone involvement (RR 3.91; p < 0.001), presence of odour (RR 3.36; p = 0.007), presence of neuropathy (RR 2.49; p = 0.002), use of anti-inflammatory drugs (RR 2.45; p = 0.011), stalled wound (RR 2.26; p = 0.022), greater width (RR 2.03; p = 0.002), greater depth (RR 1.72; p = 0.036) and a high score on the healing scale (RR 1.21; p = 0.001). Integrating the identified risk factors for delayed healing into the assessment of patients and incorporating them into a mobile application can enhance decision-making in wound care.
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Pé Diabético , Úlcera Varicosa , Humanos , Estudos de Coortes , Estudos Prospectivos , Cicatrização , Úlcera Varicosa/terapia , Pé Diabético/tratamento farmacológicoRESUMO
Type I diabetes is a prominent human pathology with increasing incidence in the population; however, its cause is still unknown. This disease promotes detrimental effects on reproduction, such as lower sperm motility and DNA integrity. Hence, the investigation of the underlying mechanisms of this metabolic disturbance in reproduction and its transgenerational consequences is of the utmost importance. The zebrafish is a useful model for this research considering its high homology with human genes as well as its fast generation and regeneration abilities. Therefore, we aimed to investigate sperm quality and genes relevant to diabetes in the spermatozoa of Tg(ins:nfsb-mCherry) zebrafish, a model for type I diabetes. Diabetic Tg(ins:nfsb-mCherry) males showed significantly higher expression of transcripts for insulin a (insa) and glucose transporter (slc2a2) compared to controls. Sperm obtained from the same treatment group showed significantly lower sperm motility, plasma membrane viability, and DNA integrity compared to that from the control group. Upon sperm cryopreservation, sperm freezability was reduced, which could be a consequence of poor initial sperm quality. Altogether, the data showed similar detrimental effects related to type I diabetes in zebrafish spermatozoa at the cellular and molecular levels. Therefore, our study validates the zebrafish model for type I diabetes research in germ cells.
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Diabetes Mellitus Tipo 1 , Peixe-Zebra , Animais , Masculino , Humanos , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Insulina/metabolismo , Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Motilidade dos Espermatozoides , Espermatozoides/metabolismo , Criopreservação , Insulina Regular Humana , Diabetes Mellitus Tipo 1/metabolismo , DNA/metabolismoRESUMO
Disruptions in the MBD5 gene have been linked with an array of clinical features such as global developmental delay, intellectual disability, autistic-like symptoms, and seizures, through unclear mechanisms. MBD5 haploinsufficiency has been associated with the disruption of primary cilium-related processes during early cortical development, and this has been reported in many neurodevelopmental disorders. In this study, we describe the clinical history of a 12-year-old child harboring a novel MBD5 rare variant and presenting psychomotor delay and seizures. To investigate the impact of MBD5 haploinsufficiency on neural primary cilia, we established a novel patient-derived cell line and used CRISPR-Cas9 technology to create an isogenic control. The patient-derived neural progenitor cells revealed a decrease in the length of primary cilia and in the total number of ciliated cells. This study paves the way to understanding the impact of MBD5 haploinsufficiency in brain development through its potential impact on neural primary cilia.
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Epilepsia , Deficiência Intelectual , Transtornos do Neurodesenvolvimento , Criança , Humanos , Deficiência Intelectual/genética , Cílios/genética , Epilepsia/genética , Convulsões , Proteínas de Ligação a DNA/genéticaRESUMO
Bimetallic oxides and MOFs have been used as catalysts for the ORR via two-electron and Fenton-based processes. This work reports the development of a new green one-step route for obtaining Co2V2O7. The Co2V2O7 oxide was immobilized on Printex-L6 carbon and used as a catalyst for the oxygen reduction reaction (ORR) and in heterogeneous Fenton-based processes. The PL6C/2.5% Co2V2O7 sample exhibited the best performance in the ORR via a two-electron pathway, increasing the selectivity for H2O2 generation. Electrochemical impedance spectroscopy analysis showed a decrease in charge transfer resistance in the Co2V2O7/PL6C matrix. The application of a gas diffusion electrode (GDE) modified with 2.5% Co2V2O7 resulted in a 30% increase in H2O2 production compared to the unmodified GDE. The unmodified GDE promoted methyl-paraben (MeP) removal of â¼80% after 90 min treatment, whereas the modified GDE promoted â¼90% of MeP removal in 30 min. The results obtained point to the potential of Co2V2O7 in improving the efficiency of GDE when applied for the treatment of organic pollutants.
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Peróxido de Hidrogênio , Poluentes Químicos da Água , Catálise , Eletrodos , Peróxido de Hidrogênio/química , Oxirredução , Óxidos , Poluentes Químicos da Água/químicaRESUMO
BACKGROUND: Cachaça is the distilled beverage typical of Brazil and can be subjected to the aging process in wooden barrels. In addition to oak barrels, cachaça is also aged in barrels of different Brazilian native woods, resulting in a wide variety of its sensory characteristics. In this work, 172 cachaças aged in bálsamo, jequitibá, oak, and umburana barrels were analyzed by synchronous fluorescence spectroscopy and by the classification methods of principal component analysis and partial least squares discriminant analysis. Spectra were preprocessed by the first derivative by Savitzky-Golay smoothing, using a filter width and polynomial order determined through face-centered central composite designs. Multivariate analysis was realized using the spectra recorded at different wavelength differences, and models were compared by the classification errors in the test sets. RESULTS: The principal component analysis applied to the synchronous fluorescence spectra presented a tendency of separation by the wood used in the aging process, and the partial least squares discriminant analysis model constructed using the fluorescence spectra recorded at a wavelength difference of 30 nm provided better performance parameters (efficiency 91-97%, sensitivity 81-100%, and specificity 91-100%). CONCLUSION: Synchronous fluorescence spectroscopy offers a promising approach for the classification of cachaças aged in bálsamo, oak, jequitibá, and umburana barrels, and the discriminant model can be used for routine analysis as a screening method. © 2022 Society of Chemical Industry.
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Bebidas Alcoólicas , Saccharum , Espectrometria de Fluorescência , Madeira , Bebidas Alcoólicas/análise , Análise Discriminante , Análise dos Mínimos Quadrados , Análise Multivariada , Análise de Componente Principal , Saccharum/química , Espectrometria de Fluorescência/métodos , Madeira/análise , Madeira/químicaRESUMO
INTRODUCTION: In order to assess and to follow up the evolution of chronic wounds, it is advisable to apply measurement scales. This procedure allows clinicians to verify the appropriateness of their activities and whether the healing process is evolving as expected. AIM: To conduct a cross-cultural adaptation and psychometric analysis of Portuguese version of RESVECH 2.0. METHODS: A quantitative and correlational study was designed and, to perform the cross-cultural adaptation of RESVECH 2.0, we followed the classic sequential approach for linguistic equivalence to European Portuguese. The study occurred at a Portuguese oncology hospital and the sample encompassed 281 patients with multiple chronic wounds. RESULTS: RESVECH 2.0 is a practical measurement instrument, easy to use, and well accepted by nurses to know all kinds of wounds' etiologies. The reliability test revealed an acceptable internal consistency and high proportion of agreement between two raters assessing the same patient. Construct validity was considered average/good and the principal component factor analysis with varimax rotation obtained six factors corresponding to 59.5% of explained variance. When comparing the domains from RESVECH 2.0 with those from BWAT we found statistically significant correlations. CONCLUSION: The adapted version of RESVECH 2.0 scale presents a good internal consistency and is valid for the Portuguese language and culture, being useful and effective in clinical practice.
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Idioma , Linguística , Humanos , Reprodutibilidade dos Testes , Inquéritos e Questionários , Portugal , Psicometria , População Europeia , Comparação TransculturalRESUMO
The objective was to evaluate the efficacy of multi-layered silicone foam (intervention) compared with transparent polyurethane film (control) in preventing heel pressure injuries caused by surgical positioning of individuals undergoing elective surgery. It was designed an intra-patient, open, parallel, randomised controlled trial was conducted in a university hospital in southern Brazil, from March 2019 to February 2020, with patients undergoing elective surgeries of cardiac and gastrointestinal specialties. The patients who met the selection criteria constituted, simultaneously, a single group receiving the intervention and active control, through paired analysis of the cutaneous sites (right heel and left heel). The outcome was the occurrence of PI, within the follow-up period was 72 hours. Brazilian Registry of Clinical Trials: RBR-5GKNG5. There was analysis of 135 patients/270 heels, with an overall incidence of 36.7%. The pressure injury incidence was significantly lower in the intervention group (26.7%), compared with the control group (P = .001); relative risk of 0.57. In the intervention group, the estimated pressure injury-free time (survival) was 57.5 hours and in the control group, 43.9 hours. It was concluded that Multi-layered silicone foam (intervention) is more efficacious than transparent polyurethane film (control) in the prevention of pressure injuries caused by surgical positioning of individuals undergoing elective surgery.
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Calcanhar , Úlcera por Pressão , Bandagens , Brasil , Feminino , Humanos , Masculino , Salas Cirúrgicas , Úlcera por Pressão/prevenção & controleRESUMO
BACKGROUND: Critically ill patients show a high, albeit variable, prevalence of augmented renal clearance (ARC). This condition has relevant consequences on the elimination of hydrophilic drugs. Knowledge of risk factors for ARC helps in the early identification of ARC. The aims of this study were evaluation of (1) risk factors for ARC and (2) the prevalence of ARC in critically ill patients over a period of 1 year. METHODS: A retrospective cohort study was performed for all consecutive patients admitted to our intensive care unit (ICU). Augmented renal clearance was defined by a creatinine clearance ≥130 mL/min/1.73 m2. "Patient with ARC" was defined as a patient with a median of creatinine clearance ≥130 mL/min/1.73 m2 over the period of admission. Four variables were tested, Simplified Acute Physiology Score II (SAPS II), male gender, age, and trauma as cause for ICU admission. An analysis (patient based and clearance based) was performed with logistic regression. RESULTS: Of 475 patients, 446 were included in this study, contributing to 454 ICU admissions and 5586 8-hour creatinine clearance (8h-CLCR). Overall, the prevalence of patients with ARC was 24.9% (n = 113). In a subset of patients with normal serum creatinine levels, the prevalence was 43.0% (n = 104). Of the set of all 8h-CLCR measurements, 25.4% (1418) showed ARC. In the patient-based analysis, the adjusted odds ratio was: 2.0 (confidence interval [CI]:1.1-3.7; P < .05), 0.93 (CI: 0.91-0.94; P < .01), 2.7 (CI: 1.4-5.3; P < .01), and 0.98 (CI: 0.96 -1.01; P = .15), respectively, for trauma, age, male sex, and SAPS II. In the clearance-based analysis, the adjusted odds ratio were 1.7 (CI: 1.4-1.9; P < .01), 0.94 (CI: 0.932-0.942; P < .01), and 2.9 (CI: 2.4-3.4; P < .01), respectively, for trauma, age, and male sex. CONCLUSIONS: Trauma, young age, and male sex were independent risk factors for ARC. This condition occurs in a considerable proportion of critical care patients, which was particularly prevalent in patients without evidence of renal dysfunction.
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Creatinina/sangue , Eliminação Renal/fisiologia , Insuficiência Renal/epidemiologia , Fatores Etários , Idoso , Estado Terminal , Feminino , Humanos , Unidades de Terapia Intensiva , Rim/fisiopatologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prevalência , Insuficiência Renal/sangue , Insuficiência Renal/etiologia , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Escore Fisiológico Agudo SimplificadoRESUMO
BACKGROUND: Preventing childhood obesity is a public health challenge of the twenty-first century and it must be a priority. Governments play a major role in creating and supporting a healthy school environment and should prioritise actions to improve children's health. Sintra Grows Healthy aims to promote healthy lifestyles to prevent childhood obesity and improve children's health-related quality of life and social and emotional skills, through the development of a school evidence-based and sustainable model. METHODS: This protocol describes a quasi-experimental design and community-based participatory research. The participants included in the study are the school community of Portuguese public primary schools from the municipality of Sintra. Data will be collected on demographic and socio-economic characterization, nutritional status, eating habits and behaviours, physical activity, sedentary behaviours and sleep, health-related quality of life, and social and emotional skills. DISCUSSION: There is evidence to support interventions in school settings as strategies for obesity prevention. Up-to-date homogeneous and community-based interventions for preventing childhood obesity are lacking, therefore Sintra Grows Healthy intends to fill this gap. Furthermore, Sintra Grows Healthy aims to contribute with relevant scientific findings that will allow the development of better strategies for policymakers and society to manage this major public health problem.
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Obesidade Infantil , Qualidade de Vida , Criança , Exercício Físico , Promoção da Saúde , Humanos , Estado Nutricional , Obesidade Infantil/prevenção & controle , Serviços de Saúde Escolar , Instituições AcadêmicasRESUMO
This study aimed to prepare and characterize organogels containing microparticles of ascorbic acid (AA) obtained from propolis by-product. The formulations F1 (5% of microparticles) and F2 (10% of microparticles) were evaluated regarding rheological and textural properties, antioxidant and radical scavenging activity, in vitro release and cellular studies. The organogels showed plastic flow behavior and rheopexy. The textural parameters were within acceptable values for semisolid formulations. The antioxidant capacity of organogels F1 and F2 by the DPPH assay demonstrated IC50 ranging from 1523.59 to 1166.97 µg/mL, respectively. For the FRAP assay, the values found were 842.88 and 956.14 µmol of FSE/g formulation, respectively. Good scavenging activity against nitrogen species was observed. The concentration of 63 µg/mL did not present toxicity on HaCaT and HFF-1 cells. In vitro release profile of AA from organogels showed a slow pattern of drug release, mainly for F2. Therefore, the proposed organogel containing AA microparticles with propolis by-product matrix represents a promising platform for topical drug delivery with antioxidant effect.
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Ácido Ascórbico/química , Géis/química , Própole/química , Antioxidantes/química , Química Farmacêutica/métodos , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos/efeitos dos fármacos , Viscosidade/efeitos dos fármacosRESUMO
The aim of this study was to evaluate the antimicrobial activity of ethanoic extract of P. amarus (PAEE) and its compound Phyllanthin, as well as, investigate if these natural products could modulate the fluoroquinolone-resistance in S. aureus SA1199-B by way of overexpression of the NorA efflux pump. Microdilution tests were carried out to determine the minimal inhibitory concentration (MIC) of the PAEE or Phyllanthin against several bacterial and yeast strains. To evaluate if PAEE or Phyllanthin were able to act as modulators of the fluoroquinolone-resistance, MICs for Norfloxacin and ethidium bromide were determined in the presence or absence of PAEE or Phyllanthin against S. aureus SA1199-B. PAEE showed antimicrobial activity against Gram-negative strains, meanwhile Phyllanthin was inactive against all strains tested. Addition of PAEE or Phyllanthin, to the growth media at sub-inhibitory concentrations enhanced the activity of the Norfloxacin as well as, Ethidium Bromide, against S. aureus SA1199-B. These results indicate that Phyllanthin is able to modulate the fluoroquinolone-resistance possibly by inhibition of NorA. This hypothesis was supported by in silico docking analysis which confirmed that Phyllantin is a NorA ligand. Thus, this compound could be used as a potentiating agent of the Norfloxacin activity in the treatment of infections caused by fluoroquinolone-resistant S. aureus.
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Antibacterianos/farmacologia , Proteínas de Bactérias/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Lignanas/farmacologia , Proteínas Associadas à Resistência a Múltiplos Medicamentos/antagonistas & inibidores , Phyllanthus/química , Extratos Vegetais/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/isolamento & purificação , Farmacorresistência Bacteriana/efeitos dos fármacos , Sinergismo Farmacológico , Inibidores Enzimáticos/isolamento & purificação , Etídio/farmacologia , Lignanas/isolamento & purificação , Testes de Sensibilidade Microbiana , Norfloxacino/farmacologia , Extratos Vegetais/isolamento & purificação , Staphylococcus aureus/enzimologiaRESUMO
OBJECTIVE: To model the reduction in premature deaths attributed to noncommunicable diseases if targets for reformulation of processed food agreed between the Portuguese health ministry and the food industry were met. METHODS: The 2015 co-regulation agreement sets voluntary targets for reducing sugar, salt and trans-fatty acids in a range of products by 2021. We obtained government data on dietary intake in 2015-2016 and on population structure and deaths from four major noncommunicable diseases over 1990-2016. We used the Preventable Risk Integrated ModEl tool to estimate the deaths averted if reformulation targets were met in full. We projected future trends in noncommunicable disease deaths using regression modelling and assessed whether Portugal was on track to reduce baseline premature deaths from noncommunicable diseases in the year 2010 by 25% by 2025, and by 30% before 2030. FINDINGS: If reformulation targets were met, we projected reductions in intake in 2015-2016 for salt from 7.6 g/day to 7.1 g/day; in total energy from 1911 kcal/day to 1897 kcal/day due to reduced sugar intake; and in total fat (% total energy) from 30.4% to 30.3% due to reduced trans-fat intake. This consumption profile would result in 248 fewer premature noncommunicable disease deaths (95% CI: 178 to 318) in 2016. We projected that full implementation of the industry agreement would reduce the risk of premature death from 11.0% in 2016 to 10.7% by 2021. CONCLUSION: The co-regulation agreement could save lives and reduce the risk of premature death in Portugal. Nevertheless, the projected impact on mortality was insufficient to meet international targets.
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Dieta , Indústria Alimentícia/legislação & jurisprudência , Mortalidade Prematura/tendências , Doenças não Transmissíveis/mortalidade , Humanos , Portugal/epidemiologia , Fatores de RiscoRESUMO
AIMS: To evaluate the relative bioavailability of oral amoxicillin (AMX) tablets in comparison to AMX suspension in Roux-en-Y gastric bypass bariatric subjects. METHODS: A randomized, double-blind, cross-over study was performed on the bioavailability of oral AMX tablets and suspension in Roux-en-Y gastric bypass subjects operated at least 3 months previously . Doses of 875 mg of the AMX tablet or 800 mg of the AMX suspension were given to all the subjects, allowing a washout of 7 days between the periods. Blood samples were collected at 0, 0.25, 0.5, 1, 1.5, 2, 4, 6 and 8 hours after drug administration and the AMX levels were quantified by liquid chromatography coupled with triple quadrupole tandem mass spectrometry. The pharmacokinetic parameters were calculated by noncompartmental analysis, normalized to an 875 mg dose and the bioavailability of the AMX from the tablets was compared to that from the suspension formulation. RESULTS: Twenty subjects aged 42.65 ± 7.21 years and with a body mass index of 29.88 ± 4.36 kg/m2 were enrolled in the study. The maximum AMX plasma concentration of the tablets and the suspension (normalized to 875 mg) were 7.42 ± 2.99 mg/L and 8.73 ± 3.26 mg/L (90% confidence interval of 70.71-99.11), and the total area under the curve from time zero to infinity were 23.10 ± 7.41 mg.h/L and 27.59 ± 8.32 mg.h/L (90% confidence interval of 71.25-97.32), respectively. CONCLUSION: The tablets presented a lower bioavailability than the suspension formulation and the total absorbed amount of AMX in these subjects was lower in comparison to the standard AMX absorption rates in nonbariatric subjects, regardless of the formulation.
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Amoxicilina/farmacocinética , Antibacterianos/farmacocinética , Derivação Gástrica/efeitos adversos , Administração Oral , Adulto , Amoxicilina/administração & dosagem , Amoxicilina/sangue , Antibacterianos/administração & dosagem , Antibacterianos/sangue , Área Sob a Curva , Disponibilidade Biológica , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Suspensões , ComprimidosRESUMO
Paracoccidioidomycosis (PCM) is the most prevalent systemic mycosis in Latin American countries. Amphotericin B, sulfonamides, and azoles may be used in the treatment of PCM. However, the high toxicity, prolonged course of treatment, and significant frequency of disease relapse compromise their use. Therefore, there is a need to seek new therapeutic options. We conducted tests with thiosemicarbazone of lapachol (TSC-lap) to determine the antifungal activity and phenotypic effects against several isolates of Paracoccidioides spp. In addition, we evaluated the toxicity against murine macrophages and the ability to enhance phagocytosis. Further, we verified that TSC-lap was active against yeasts but did not show any interaction with the drugs tested. The TSC-lap showed no toxicity at the concentration of 40 µg/ml in macrophages, and at 15.6 µg/ml it could increase the phagocytic index. We observed that this compound induced in vitro ultrastructural changes manifested as withered and broken cells beyond a disorganized cytoplasm with accumulation of granules. We did not observe indications of activity in the cell wall, although membrane damages were noted. We observed alterations in the membrane permeability, culminating in a significant increase in K+ efflux and a gradual loss of the cellular content with increase in the concentration of TSC-lap. In addition, we showed a significant reduction of ergosterol amount in the Pb18 membrane. These data reinforce the possible mechanism of action of this compound to be closely associated with ergosterol biosynthesis and reaffirms the antifungal potential of TSC-lap against Paracoccidioides spp.
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Antifúngicos/farmacologia , Membrana Celular/efeitos dos fármacos , Naftoquinonas/farmacologia , Paracoccidioides/efeitos dos fármacos , Tiossemicarbazonas/farmacologia , Animais , Ergosterol/biossíntese , Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Paracoccidioidomicose/tratamento farmacológico , Paracoccidioidomicose/microbiologia , Fagocitose/efeitos dos fármacosRESUMO
In Portugal, measles vaccination coverage and population immunity are high, and no endemic measles cases had been reported since 2004. The World Health Organization classified measles as eliminated in the country in 2015 and 2016, based on data from the previous 3 years. However, in a context of increasing incidence in several European countries in 2016 and 2017, Portugal experienced two simultaneous measles outbreaks with a total of 27 laboratory-confirmed cases (0.3 cases/100,000 population) in two health regions between February and May 2017. Nineteen cases (70.1%) were adults, of whom 12 were healthcare workers. Overall, 17 cases (63.0%) were not vaccinated, of whom five were infants younger than 12 months of age. One unvaccinated teenager died. Genotype B3 was identified in 14 cases from both regions. Measles virus sequencing identified different possible origins of the virus in each region affected. Although measles transmission was stopped in less than 2 months from the first case being notified, these outbreaks represent an opportunity to reinforce awareness of measles diagnosis. We highlight the intensity of the control measures taken and their impact on the rapid control of the outbreaks and also the fact that high vaccination coverage was crucial to stop transmission.