Antinociceptive and anti-inflammatory activities of Ayapana triplinervis essential oil rich in thymohydroquinone dimethyl ether from Brazil.

Ayapana triplinervis (M.Vahl) R.M.King & H.Rob. (Asteraceae), popularly known as japana, is a tropical, aromatic subshrub widely used as tea to combat some diseases. The essential oil was obtained from the leaves by hydrodistillation (3 h), and the chemical composition was analyzed by gas chromatography coupled to mass spectrometry. For in vivo assays, Mus musculus/Swiss mice were used to evaluate oral acute toxicological (at dose of 2000 mg/kg); peripheral and central analgesic for abdominal contortion (doses of 6.25, 12.5, 25, 50 and 100 mg/kg), hot plate test (12.5, 25, 50, and 100 mg/kg) and formalin (25, 50 and 100 mg/kg); open field test (100 mg/kg); and anti-inflammatory by ear swelling induced by xylene (6.25,12.5, 25, 50, and 100 mg/kg). The yield of A. triplinervis essential oil (AtEO) was 4.6%, and the oxygenated monoterpene 2,5-dimethoxy-p-cymene was the major compound in this study (63.6%). AtEO at a dose of 2,000 mg/kg orally did not change the behavior patterns or mortality of the animals; liver and kidney biochemical levels were similar to the control group, indicating no liver and kidney toxicity. Moreover, AtEO, at doses of 6.25, 12.5, 25, 50, and 100 mg/kg, reduced abdominal contortions by 21%, 54%, 91%, 58%, and 55%, respectively. In the hot plate test, AtEO showed a significant increase in latency time in the 60-min interval at doses of 25 mg/kg (11.3 ± 3.3 s) and 100 mg/kg (11.9 ± 0.9 s). In the first phase of the formalin test, AtEO decreased paw licking time at doses of 25, 50, and 100 mg/kg, with inhibition of 22%, 38%, and 83%; in the second phase, the same doses, decreased licking time with inhibition of 24%, 34%, and 76%. AtEO did not present a significant change in the spontaneous locomotor activity of the animals. Doses of 6.25, 12.5, 25, 50, and 100 mg/kg significantly reduced ear edema induced by topical application of xylene with percentages of 40%, 39%, 54%, 45%, and 45%, respectively. So, AtEO demonstrated low acute oral toxicity and exhibited significant antinociceptive and anti-inflammatory actions, consistent with the use of A. triplinervis in traditional medicine.

Cultivating global antimicrobial stewardship: linguistic and cultural validation of the Australian National Antimicrobial Prescribing Survey appropriateness assessment definitions for Portugal.

BACKGROUND: Antimicrobial resistance is driven by inappropriate antimicrobial prescribing. The National Antimicrobial Prescribing Survey (NAPS) is an Australian-developed auditing platform to assist in the assessments of antimicrobial quality by antimicrobial stewardship programmes using consensus-based definitions. The NAPS has demonstrated to be transferable to other countries. Its adaptation to Portugal could improve knowledge about the quality of antimicrobial prescribing in the country. OBJECTIVES: To translate, culturally adapt, and validate the Australian Hospital NAPS appropriateness assessment definitions of antimicrobial prescribing for Portugal. METHODS: International recommendations on translation and adaptation of instruments were followed. Two panels of experts participated in the process, using Zoom® for discussions and interviews, and Google Forms® for assessing vignettes. A native English-speaking person proficient in Portuguese conducted the back-translation. SPSS v.28 and Excel® were used for validity calculation. RESULTS: The Portuguese version was well accepted, its implementation being perceived as desirable and feasible by the experts. Validation process showed a Fleiss' κ score of 0.483 (95% CI, 0.415-0.551, P < 0.005) for appropriateness, and an average agreement with the Australian NAPS team of 0.8 and 0.9, respectively, for appropriateness and reasons for inappropriateness. CONCLUSIONS: The Portuguese version of the Australian Hospital NAPS appropriateness assessment definitions of antimicrobial prescribing, the first to be translated from English, was deemed non-inferior to the original, was well accepted, considered to be desirable and feasible, and could inspire other countries, particularly other Portuguese-speaking countries, to adapt and validate them in their own contexts, reinforcing the possibility of transferring NAPS use beyond Australia.

Case report: Equine metacarpophalangeal joint partial and full thickness defects treated with allogenic equine synovial membrane mesenchymal stem/stromal cell combined with umbilical cord mesenchymal stem/stromal cell conditioned medium.

Here, we describe a case of a 5-year-old show-jumping stallion presented with severe lameness, swelling, and pain on palpation of the left metacarpophalangeal joint (MCj). Diagnostic imaging revealed full and partial-thickness articular defects over the lateral condyle of the third metacarpus (MC3) and the dorsolateral aspect of the first phalanx (P1). After the lesion's arthroscopic curettage, the patient was subjected to an innovative regenerative treatment consisting of two intra-articular injections of equine synovial membrane mesenchymal stem/stromal cells (eSM-MSCs) combined with umbilical cord mesenchymal stem/stromal cells conditioned medium (UC-MSC CM), 15 days apart. A 12-week rehabilitation program was accomplished, and lameness, pain, and joint effusion were remarkably reduced; however, magnetic resonance imaging (MRI) and computed tomography (CT) scan presented incomplete healing of the MC3's lesion, prompting a second round of treatment. Subsequently, the horse achieved clinical soundness and returned to a higher level of athletic performance, and imaging exams revealed the absence of lesions at P1, fulfillment of the osteochondral lesion, and cartilage-like tissue formation at MC3's lesion site. The positive outcomes suggest the effectiveness of this combination for treating full and partial cartilage defects in horses. Multipotent mesenchymal stem/stromal cells (MSCs) and their bioactive factors compose a novel therapeutic approach for tissue regeneration and organ function restoration with anti-inflammatory and pro-regenerative impact through paracrine mechanisms.

Impact of Transplantation Timing on Renal Graft Survival Outcomes and Perioperative Complications.

Nighttime organ transplantation aims to decrease cold ischemia duration, yet conflicting data exists on its impact on graft function and perioperative complications. This multicenter TRANSPLANT'AFUF study including 2,854 patients, transplanted between 1 January 2011, and 31 December 2022, investigated nighttime kidney transplantation's impact (8:00 p.m.-8:00 a.m.) versus daytime (8:00 a.m.-8:00 p.m.) on surgical complications and graft survival. Overall, 2043 patients (71.6%) underwent daytime graft, while 811 (28.4%) underwent nighttime graft. No impact was observed of timing of graft surgery on graft survival with a median survival of 98 months and 132 months for daytime and nightime grafting, respectively (p = 0.1749). Moreover, no impact was observed on early surgical complications (Clavien I-II = 20.95% for DG and 20.10% for NG; Clavien III-IV-V = 15.42% for DG and 12.94% for NG; p = 0.0889) and late complications (>30 days) (Clavien I-II = 6.80% for DG and 5.67% for NG; Clavien III-IV-V = 12.78% for DG and 12.82% for NG; p = 0.2444). Noteworthy, we found a significant increase in Maastricht 3 donors' rates in nighttime transplantation (5.53% DG vs. 21.45% NG; p < 0.0001). In conclusion, nighttime kidney transplantation did not impact early/late surgical complications nor graft survival.

Radiofrequency therapy as an effective treatment for granulomatous cheilitis: A CARE case report.

INTRODUCTION: Granulomatous cheilitis is a rare disorder characterized by recurrent, idiopathic, and painless lip swelling. The diagnosis is proven by histopathological examination. The unknown aetiology and poorly understood underlying mechanism contribute to the difficulty in establishing an effective treatment. This case study proposes the effectiveness of radiofrequency therapy in the management of refractory granulomatous cheilitis. CASE SUMMARY: A 68-year-old patient presented with hypertrophy and swelling of the lower lip, and a biopsy revealed actinic cheilitis. The patient underwent lip shaving and an advancement mucosal flap, and definitive histologic examination confirmed the diagnosis of granulomatous cheilitis. No other signs of orofacial granulomatosis were observed, and the complementary aetiological study was negative for systemic disease. The lip swelling reappeared and persisted, which interfered with the quality of life. Hence, radiofrequency therapy was performed in the submucosal and subdermal layers of the lip, resulting in significant aesthetic and functional improvement and no further relapses after five years. DISCUSSION: The management of granulomatous cheilitis is challenging. The current mainstay treatment is corticotherapy or reduction cheiloplasty in severe cases. Radiofrequency has potential as a treatment option in debilitating macrocheilia, presenting worthy long-lasting functional and aesthetical results, with minimal morbidity.

Seasonal Variation in Essential Oil Composition and Antioxidant Capacity of Aniba canelilla (Lauraceae): A Reliable Source of 1-Nitro-2-phenylethane.

Aniba canelilla (Kunth) Mez essential oil has many biological activities due to its main compound 1-nitro-2-phenylethane (1N2F), followed by methyleugenol, a carcinogenic agent. This study analyzed the influence of seasonality on yields, antioxidant capacity, and 1N2F content of A. canelilla leaf and twig essential oils. Essential oils (EOs) were extracted with hydrodistillation and analyzed with gas chromatography coupled to mass spectrometry and a flame ionization detector. Antioxidant capacity was measured using the free radical scavenging method (DPPH). Chemometric analyses were carried out to verify the influence of climatic factors on the production and composition of EOs. 1-Nitro-2-phenylethane was the major constituent in A. canelilla EOs throughout the seasonal period (68.0-89.9%); methyleugenol was not detected. Essential oil yields and the 1N2F average did not show a statistically significant difference between the dry and rainy seasons in leaves and twigs. Moderate and significant correlations between major compounds and climate factor were observed. The twig oils (36.0 ± 5.9%) a showed greater antioxidant capacity than the leaf oils (20.4 ± 5.0%). The PCA and HCA analyses showed no statistical differences between the oil samples from the dry and rainy seasons. The absence of methyleugenolin in all months of study, described for the first time, makes this specimen a reliable source of 1N2F.

Inappropriate Hospital Admission According to Patient Intrinsic Risk Factors: an Epidemiological Approach.

BACKGROUND: Inappropriate hospital admissions compromise the efficiency of the health care system. This work analyzes, for the first time, the prevalence of inappropriate admission and its association with clinical and epidemiological patient characteristics. OBJECTIVES: To estimate the prevalence, associated risk factors, and economic impact of inappropriate hospital admissions. DESIGN AND PARTICIPANTS: This was a cross-sectional observational study of all hospitalized patients in a high complexity hospital of over 901 beds capacity in Spain. The prevalence of inappropriate admission and its causes, the association of inappropriateness with patients' intrinsic risk factors (IRFs), and associated financial costs were analyzed with the Appropriateness Evaluation Protocol in a multivariate model. MAIN MEASURES AND KEY RESULTS: A total of 593 patients were analyzed, and a prevalence of inappropriate admissions of 11.9% (95% CI: 9.5 to 14.9) was found. The highest number of IRFs for developing health care-related complications was associated with inappropriateness, which was more common among patients with 1 IRF (OR [95% CI]: 9.68 [3.6 to 26.2.] versus absence of IRFs) and among those with surgical admissions (OR [95% CI]: 1.89 [1.1 to 3.3] versus medical admissions). The prognosis of terminal disease reduced the risk (OR [95% CI]: 0.28 [0.1 to 0.9] versus a prognosis of full recovery based on baseline condition). Inappropriate admissions were responsible for 559 days of avoidable hospitalization, equivalent to €17,604.6 daily and €139,076.4 in total, mostly attributable to inappropriate emergency admissions (€96,805.3). CONCLUSIONS: The prevalence of inappropriate admissions is similar to the incidence found in previous studies and is a useful indicator in monitoring this kind of overuse. Patients with a moderate number of comorbidities were subject to a higher level of inappropriateness. Inappropriate admission had a substantial and avoidable financial impact.

The influence of soil dry-out on the record-breaking hot 2013/2014 summer in Southeast Brazil.

The 2013/2014 summer in Southeast Brazil was marked by historical unprecedented compound dry and hot (CDH) conditions with profound socio-economic impacts. The synoptic drivers for this event have already been analyzed, and its occurrence within the context of the increasing trend of CDH conditions in the area evaluated. However, so far, the causes for these record temperatures remain poorly understood. Here, a detailed characterization of the 2013/2014 austral summer season over Southeast Brazil is proposed, emphasizing the role played by land-atmosphere interactions in temperature escalation. We demonstrate that a strong soil moisture-temperature coupling regime promoted record-breaking temperatures levels exceeding almost 5 °C over the previous highest record, and played a key role in triggering an outstanding 'mega-heatwave' that lasted for a period of around 20 days. This pronounced soil desiccation occurred within a current climate change trend defined by drier and hotter conditions in the region. The soil dry-out, coupled with strong radiative processes and low entrainment of cooler air masses through mesoscale sea-breeze circulation processes, led to a water-limited regime and to an enhancement of sensible heat fluxes that, ultimately, resulted in a sharp increase of surface temperatures.

Análise dos golos no mundial de futebol da Rússia 2018 / Análisis de goles en la copa del mundo de Rusia 2018 / Goals analysis in the Russian world cup 2018

O golo é um indicador crucial da análise de desempenho no futebol. O objetivo do nosso estudo foi analisar o golo e fases anteriores desde a recuperação da bola. Foram analisados um total de 169 golos da fase de grupos e eliminação do Mundial de 2018. As observações foram feitas através do programa LINCE e os dados foram analisados utilizando o programa HOISAN e SPSS Statistics 24. Os dados foram analisados através de estatística descritiva, gráfica, teste exato de Fisher, U-Mann Whitney e coordenadas polares. Foi verificado que a recuperação da bola acontece preferencialmente por falta do adversário, nas zonas de meio-campo ofensivo. O último passe é registado com muita frequência nas zonas ofensivas, em resultado do ataque posicional, com o pé-direito e dentro da grande área. Foi ainda verificado a importância dos esquemas táticos na obtenção do golo. As coordenadas polares mostram relações de ativação entre a finalização e os outros comportamentos técnico-táticos, reforçando e complementando a análise notacional. Concluímos que a análise notacional, complementada com tratamento estatístico e análise de coordenadas polares revelam informações relevantes para analisar o desempenho em competição e planear o processo de treino. (AU)

El gol es un indicador crucial del análisis del rendimiento del fútbol. El objetivo de nuestro estudio fue analizar el gol y etapas anteriores desde la recuperación del balón. Se analizaron un total de 169 goles en la fase de grupos y eliminación del Mundial 2018. Las observaciones se realizaron con el programa LINCE y los datos se analizaron con el programa HOISAN y SPSS Statistics 24. Los datos se analizaron mediante estadísticas descriptivas y gráfica, prueba exacta de Fisher, U-Mann Whitney y coordenadas polares. Se verificó que la recuperación del balón ocurre preferentemente por falta del oponente, en las zonas del mediocampo ofensivo. El último pase se registra muy a menudo en las zonas ofensivas, como consecuencia del ataque posicional, con el pie derecho y dentro del área de penalti. También se comprobó la importancia de los esquemas tácticos para obtener el gol. Las coordenadas polares muestran las relaciones de activación entre la finalización y los otros comportamientos técnico-tácticos, reforzando y complementando el análisis notacional. Concluimos que el análisis notacional, complementado con el tratamiento estadístico y análisis de coordenadas polares, revela información relevante para analizar el desempeño en competición y planificar el proceso de entrenamiento. (AU)

The goal is a crucial indicator of performance analysis in football. The aim of our study was to analyze the goal and previous phases since the recovery of the ball. 169 goals from group stage and elimination of the 2018 World Cup were analyzed. The observations were made through the LINCE program and the data were analyzed using the HOISAN and SPSS Statistics 24 program. The data were analyzed using descriptive, graphic statistics, Fisher's exact test, U-Mann Whitney and polar coordinates. It was verified that the recovery of the ball happens preferably due to fault of the opponent, in the areas of offensive midfield. The last pass is recorded very often in the offensive zones, as a result of the positional attack, with the right foot and inside the large area. It was also verified the importance of tactical schemes in obtaining the goal. The polar coordinates show activation relationships between the finalization and the other technical-tactical behaviors, reinforcing and complementing the notational analysis. We conclude that the notational analysis, complemented with statistical analysis and polar coordinate analysis, reveal relevant information to analyze performance in competition and plan the training process. (AU)

Standardization of a rapid quadruplex PCR method for the simultaneous detection of bovine, buffalo, Salmonella spp, and Listeria monocytogenes DNA in milk / [Padronização de um método rápido de PCR quadriplex para a detecção simultânea de DNA de bovino, bubalino, Salmonella spp. e Listeria monocytogenes em leite]

The objective of the present study was to Standardize a Polymerase Chain Reaction (PCR) protocol for the authentication of bovine and buffalo milk, and to detect the presence of Salmonella spp. and Listeria monocytogenes. For this, the target DNA was extracted, mixed, and subjected to a PCR assay. Milk samples were defrauded and experimentally contaminated with microorganisms to assess the detection of target DNA at different times of cultivation, bacterial titers, and concentration of genetic material. In addition, the protocol was tested with DNA extracted directly from food, without a pre-enrichment step. The proposed quadruplex PCR showed good accuracy in identifying target DNA sequences. It was possible to simultaneously identify all DNA sequences at the time of inoculation (0h), when the samples were contaminated with 2 CFU/250mL and with 6h of culture when the initial inoculum was 1 CFU/250mL. It was also possible to directly detect DNA sequences from the food when it was inoculated with 3 CFU/mL bacteria. Thus, the proposed methodology showed satisfactory performance, optimization of the analysis time, and a potential for the detection of microorganisms at low titers, which can be used for the detection of fraud and contamination.

O objetivo do presente estudo foi padronizar um protocolo de reação em cadeia da polimerase (PCR) para a autenticação de leite bovino e bubalino e a detecção da presença de Salmonella spp. e Listeria monocytogenes. Para isso, o DNA-alvo foi extraído, misturado e submetido ao ensaio de PCR. Amostras de leite foram fraudadas e contaminadas experimentalmente com os micro-organismos, para se avaliar a detecção do DNA-alvo em diferentes tempos de cultivo, os títulos bacterianos e a concentração de material genético. Além disso, o protocolo foi testado com DNA extraído diretamente do alimento, sem a etapa de pré-enriquecimento. A PCR quadriplex proposta mostrou boa precisão na identificação de sequências de DNA-alvo. Foi possível identificar simultaneamente todas as sequências de DNA no momento da inoculação (0h), quando as amostras estavam contaminadas com 2 UFC/250mL, e com seis horas de cultura, quando o inóculo inicial foi de 1 UFC/250mL. Também foi possível detectar diretamente as sequências de DNA do alimento quando este foi inoculado com 3 UFC/mL de bactérias. Dessa forma, a metodologia proposta apresentou desempenho satisfatório, otimização do tempo de análise e potencial para detecção de micro-organismos em baixos títulos, podendo ser utilizada para detecção de fraude e contaminação.

Designing a mobile app to promote healthy behaviors and prevent obesity: analysis of adolescents' preferences.

To ensure that adolescents adhere to programmes promoting healthy behaviors, these programmes must be appealing and interesting. This study aims to characterize and assess the devices, operating system and type of mobile apps frequently used by adolescents; understand the features that mHealth apps should have to be appealing; comprehend the facilitators and barriers for adolescents to use mHealth apps. The sample comprised 165 adolescents (12-18 years) from the main population, recruited in 2018. Most participants used smartphones and the Android system. Food and physical activity suggestions were considered the most important features for an mHealth app. 62.6% had never tried an mHealth app. For those who had tried one, 26.0% stated it was to improve health status/lifestyle. Their favorite feature was physical exercise tips/plans (41.8%). Adolescents pointed out that the reasons that made them keep using the app were utility and interest (35.7%). Regarding possible barriers, 48.4% reported a lack of a senseof need/practical utility, and 18.8% considered notifications as their least favorite feature. Lack of interest was pointed out for 38.2% as the main reason for stopping use. Results provide practical information for the planning, design, and implementation of future mHealth apps for the promotion of healthy behaviors - an important implication for future research in this area.

Impacto tardio da hipertensão pulmonar e da insuficiência tricúspide após troca transcateter de valva aórtica / Late impact of pulmonary hypertension and tricuspid regurgitation after transcatheter aortic valve replacement

INTRODUÇÃO: Troca transcateter de valva aórtica (TAVR) é cada vez mais utilizada no tratamento da estenose aórtica (EA) senil. EA é comumente associada a hipertensão pulmonar (HP) e insuficiência tricúspide (IT). Nosso OBJETIVO foi avaliar o impacto tardio no curso da HP e IT. MÉTODOS: Pacientes submetidos a TAVR foram acompanhados quanto aos dados ecocardiográficos da HP e da IT por 24 meses. Todos os ecocardiogramas foram realizados em centro único. Foram divididos em grupos de acordo com IT e HP após 24 meses (pressão sistólica da artéria pulmonar = or < 45 mmHg) com follow-up de até 96 meses. Resultados clínicos e mortalidade foram comparados. RESULTADOS: 156 e 151 pacientes foram selecionados para acompanhamento da HP e da IT respectivamente. Média de follow-up foi de 42,23±17,53 meses e 42,60±17,67 meses para grupos de HP e IT. HP se reduziu após o TAVR (32,7% pre-TAVR vs. 20,5% pos-TAVR, p<0,001), mas não foi encontrada mudança significativa na IT (11,9% pre-TAVR vs. 10,6% pos-TAVR). Aumento de átrio esquerdo (AE) foi associado a manutenção de HP (p=0,002). Além disso, o aumento do diâmetro do AE (p=0,015) e EuroSCORE II elevado (p=0,041) foram correlacionados ao surgimento de nova HP. Na análise multivariada, surgimento de nova HP (HR 6,17, 95% CI 1,71­22,29,p=0,005), disfunção diastólica tipo II ou III (HR 1,06, 95% CI 1,06-1,11, p=0,036) e diâmetro de AE (HR 1,11, 95% CI 1,02­1,21, p=0,02) foram preditores independentes de mortalidade. CONCLUSÃO: TAVR foi capaz de reduzir a gravidade da HP, mas não da IT. Além disso, a sobrevida a longo prazo foi afetada pela HP, disfunção diastólica e tamanho do AE.

Saharan dust intrusions in the Iberian Peninsula: Predominant synoptic conditions.

The Iberian Peninsula (IP) is recurrently affected by dust transport from the Sahara Desert and from the semi-arid Sahel regions. African dust is one of the most important sources of particulate matter in the southern Mediterranean. Therefore, it is vital to understand the underlying processes that lead to episodes of air pollution associated to the occurrence of dust intrusions. This work proposes to make an extended characterization of the preferential circulation weather patterns associated to the onset of dust events affecting the IP between 2006 and 2016. Saharan dust intrusions were analysed and an automatic objective classification procedure was used to classify circulation weather patterns associated to dust events. The spatial distribution of intrusion episodes is not homogeneous throughout the IP, occurring less frequently at northern and northwestern locations than at central and southern sites. Moreover, days with Saharan dust intrusions were more frequent in summer months, and more probable to occur under regimes with a southerly component. Finally, two extreme events with high concentration of particulate matter were analysed relatively to their life-cycle and particle trajectories. The distinct extreme episodes can be associated to different synoptic situations. However, and despite different large-scale configurations, a south or south-easterly component over the region is responsible for the establishment of a dust transport from the Saharan region towards Iberia, and thus leading to the intrusion onset. These results were supported by the calculation of back-trajectories which allowed to source apportioning the particles' origin, through a clear trajectory of air parcels originating from northern Africa in both events. The proposed framework can be useful to the prediction of dust and air pollution events based on the forecast of circulation weather patterns, as the results show that these events across the IP are mainly induced by specific patterns.

Long-term analysis of pulmonary hypertension and tricuspid regurgitation after transcatheter aortic valve replacement

INTRODUCTION: transcatheter aortic valve replacement (TAVR) is increasingly utilized in treatment of aortic stenosis (AS). AS is commonly associated to pulmonary hypertension (PH) and tricuspid regurgitation (TR). We aimed to evaluate the long-term post-TAVR course of PH and TR. METHODS: Patients undergoing TAVR were screened for 24-month echocardiographic data on PH and TR. All echocardiograms were performed by a sing le team. Patients were divided in groups according to TR and PH (pulmonary systolic pressure ≥ or < 45 mmHg) grading at 24 months with follow-up of up to 96 months. Standardized clinical outcomes and survival were compared. RESULTS: 156 and 151 patients were se le cted for PH and TR follow-up, respectively. Mean follow-up was 42.23±17.53 months and 42.60±17.67 months for PH and TR groups. Maximum follow-up was 96 months. PH was reduced post-TAVR (32.7% pre-TAVR vs. 20.5% post-TAVR, p<0.001), but no significant difference in TR was found (11.9% pre-TAVR vs. 10.6% post-TAVR). Increased le ft atrial (LA) diameter (p = 0.002) was associated to maintenance PH. Moreover, increased LA diameter (p=0.015) and increased EuroSCORE II (p=0.041) were correlated to new onset PH. On a multivariab le Cox regression model, new onset PH (HR 6.17, 95% CI 1.71­22.29, p=0.005), diastolic dysfunction type II or III (HR 1.06, 95% CI 1.06-1.11, p=0.036) and LA diameter (HR 1.11, 95% CI 1.02­1.21, p=0.02) were independent predictors of long-term mortality. CONCLUSIONS: TAVR was ab le to reduce the severity of PH, but not TR, in this cohort. Additionally, long-term survival was affected by PH, diastolic dysfunction and LA sizing.

Experimental designs for optimizing the purification of immunoglobulin G by mixed-mode chromatography.

The main aim of this study was to define the optimal adsorption and elution conditions for the purification of human immunoglobulin G (IgG) by mixed-mode chromatography using the multimodal resin Capto MMC. To this end, Central Composite Experimental Design (ED) was performed for both the adsorption and desorption stages. In the first case, the conditions were systematically studied in batch mode while in the latter case, these were performed in column. For both studies, the experimental design was conducted using high-purity human IgG samples. Buffer pH and concentration as well as the salt concentration were the parameters under study in the ED. Adsorption kinetics and equilibrium experiments were performed under the best conditions defined in the ED (phosphate buffer 60 mmol/L, pH 6.75, no salt). The equilibrium experimental data were fit to the Langmuir equation, with maximum uptake qmax equal to 549.2 mg/g. The qmax value found for IgG in Capto MMC was quite high as compared to other chromatographic techniques that employ single modes of interaction. Regarding elution, the best conditions were obtained with acetate buffer (56.40 mmol/L), pH 5.2 and 0.2 mol/L NaCl. An ultimate recovery of 46.96% for high-purity IgG was achieved. Thus, the effectiveness of Capto MMC for IgG adsorption and recovery could be confirmed. Moreover, electrophoretic runs in the human serum indicated that although co-elution of HSA and IgG proteins occurs, substantial HSA removal and a high IgG recovery were achieved in the elution step.

Trends of case-fatality rate by acute coronary syndrome in Portugal: Impact of a fast track to the coronary unit.

INTRODUCTION: Efforts were made to improve management of coronary disease as the fast-track system to the Coronary Unit. We aim to analyse case-fatality rates by acute coronary syndrome in Portugal from 2000 to 2016, mainly the impact of the fast-track system and the proportion of patients that activate the fast-track system. METHODS: We analysed monthly acute coronary syndrome case-fatality before and after the implementation of the fast-track system in 2007. Impact of the system was assessed through regression models for interrupted time-series. We calculated annual proportion of fast-track system admissions. RESULTS: After 2007 case-fatality by acute coronary syndrome decreased (ß=-1.27, p-value < 0.01). The estimates obtained for ST Elevation Myocardial Infarction suggest a reduction of nearly 86 monthly deaths prevented after 2007. The highest percentage of patients admitted through the fast-track system was 35%. CONCLUSIONS: Our results suggest fast-track system may have contributed to a decline in acute coronary syndrome case-fatality. However, more than half of patients were not admitted through the system. This should encourage health authorities to make efforts to ensure compliance.

Epigenetic variation at the SLC6A4 gene promoter in mother-child pairs with major depressive disorder.

BACKGROUND: Genetic and epigenetic variations of the serotonin transporter gene (SLC6A4) have been related to the etiology of depression. The 5-HTTLPR polymorphism at the SLC6A4 promoter region has two variants, a short allele (S) and a long allele (L), in which the S allele results in lower gene transcription and has been associated with depression. The short S-allele of 5-HTTLPR polymorphism of this gene has been associated with depression. In addition to molecular mechanisms, exposure to early life risk factors such as maternal depression seems to affect the development of depression in postnatal life. The present study investigated the association of 5-HTTLPR polymorphism and CpG DNA methylation (5mC) levels of an AluJb repeat element at the SLC6A4 promoter region in mother-child pairs exposed to maternal depression. METHODS: We analyzed DNA samples from 60 subjects (30 mother-child pairs) split into three groups, with and without major depression disorder (DSM-IV) among children and mothers. The genotyping of 5-HTTLPR polymorphism and quantification of 5mC levels was performed by qualitative PCR and methylation-sensitive restriction enzyme digestion, and real-time quantitative PCR (MSRED-qPCR), respectively. RESULTS: The sample analyzed presented a higher frequency of S allele of 5-HTTLPR (67.5%). Despite the high frequency of this allele, we did not find statistically significant differences between individuals carrying at least one S allele between the depression and healthy control subjects, or among the mother-child pair groups with different patterns of occurrence of depression. In the group where the mother and child were both diagnosed with depression, we found a statistically significant decrease of the 5mC level at the SLC6A4 promoter region. LIMITATIONS: The limitations are the relatively small sample size and lack of gene expression data available for comparison with methylation data. CONCLUSION: In this study, we demonstrated a repeat element specific 5mC level reduction in mother-child pairs, concordant for the diagnosis of depression.

Identification and management of a subacute right ventricular perforation by an active-fixation permanent pacemaker lead in a dog.

A 5-year-old short-haired dachshund was referred with a history of repeated syncope associated with a third-degree atrioventricular block. A permanent transvenous pacemaker with an active-fixation lead was implanted. In the following 3 weeks, the syncopal episodes reappeared owing to a loss of ventricular capture. The pacemaker was reprogrammed to higher output, and effective pacing was re-established. Thoracic radiographs and echocardiography failed to identify any evidence of lead displacement. One month later, the patient presented a new episode of loss of capture. After fluoroscopy, cardiac perforation was suspected and subsequently confirmed by thoracotomy. An epicardial pacemaker lead was implanted without removing the perforating lead as there were no bleeding complications or damage to adjacent organs, and the length of time elapsed since implantation was assumed to have allowed for significant fibrotic adhesions to develop. Nineteen months after epicardial pacemaker implantation, endocardial lead dislodgement occurred. Simultaneously, the dog presented with gastrointestinal and respiratory abnormalities and severe thrombocytopenia. Once the dog was stabilized, the endocardial lead was percutaneously removed. One month later, loss of ventricular capture recurred. The owners declined any further treatment, and euthanasia was elected. Cardiac perforation after pacemaker implantation is an infrequent complication. In this case, the dog lived 22 months after subacute right ventricular perforation. Despite the poor prognosis associated with cardiac perforation by pacemaker leads, different approaches are possible to successfully manage this major complication. Extraction of the displaced lead remains controversial as, if the lead is not removed, late lead migration can occur.

Cardiovascular disease and high blood pressure trend analyses from 2002 to 2016: after the implementation of a salt reduction strategy.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death around the world; however, many CVD events could be prevented if we focused on modification of the main risk factors. Increased salt consumption is estimated to have caused millions of deaths, mostly related to CVD, particularly stroke, which is the leading cause of death in Portugal. In our study, we aim to assess trends in the proportion of high blood pressure (HBP) in Acute Coronary Syndrome (ACS) patients as well as the trends in stroke and ACS in Portugal, especially after a set of public health initiatives were implemented to reduce salt intake. METHODS: The monthly proportion of ACS patients presenting with previously diagnosed HBP and the monthly rate of CVD admissions into public hospitals in Portugal were calculated. CVD rates were stratified into ACS rate and stroke rates. Data were stratified by demographics variables. An interrupted time-series model was used to assess changes over time. RESULTS: Breakpoint analysis revealed an estimated breakpoint around the year 2013 for the proportion of HBP patients, the following year there was a decreasing trend, however it was not significant. Analyses showed the trend before 2013 was increasing and started to decrease after this year. This decreased in proportion of HBP patients can be translated into a reduction of 555 people per year presenting with HBP in the ACS population. We analysed trends for ACS and stroke and tested the significance for a breakpoint in the year 2013. Although none of the remaining trends were significant for ACS crude rates and stroke crude rate, a decreasing trend was observed. CONCLUSIONS: This research provides an indication about the impact a population-wide approach to CVD risk factors has on CVD trends themselves. Our results suggest that population-wide approaches can have an impact on the prevention and improvement of CVD control, reducing the number of CVD events, and eventually reducing premature death by CVD. As more restrictions on salt intake are being planned in Portugal in the next years, it is highly relevant to assess what is the current panorama and what further reductions we can expect.