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As the sole obligate symbiotic birds in Africa, oxpeckers offer a unique model for studying symbiotic relationships. Due to the multitrophic level they occupy and the context dependent foraging behavior they exhibit, the type of symbiotic relationship can be variable. In addition to providing a cleaning service to the host by removing ticks, oxpeckers frequently feed on blood, mucus, and saliva, inflicting potential damage on the host. Here, we used DNA metabarcoding on faecal samples to analyze the taxonomic composition of the trophic interactions of the Yellow-billed Oxpecker (Buphagus africanus) and Red-billed Oxpecker (B. erythrorhynchus) in northeastern Namibia. In contrast to conventional methods, DNA metabarcoding allows for a detailed identification of dietary resources encompassing both mammal hosts and consumed arthropods within the same samples. With this information, we examined differences in the diet composition between oxpecker species and localities, as well as the co-occurrence between host and arthropod species. Our findings revealed that oxpeckers predominantly source their diet from mammals, ticks, and flies; however, ticks and flies rarely co-occur in the diet of an individual. We observed variability among individuals in their feeding ecology, which is strongly correlated with locality and, to a lesser extent, with the mammal host. We noted a high degree of mobility between hosts within relatively short periods, with 32% of the samples showing traces of at least two mammal hosts. This study illustrates the dynamic foraging behavior of these specialized symbiotic birds, shedding light on their potential role in pest control services and disease transmission.

Abstract Autoantibodies are produced within germinal centers (GC), in a process regulated by interactions between B, T follicular helper (Tfh), and T follicular regulatory (Tfr) cells. The GC dysregulation in human autoimmunity has been inferred from circulating cells, albeit with conflicting results due to diverse experimental approaches. We applied a consistent approach to compare circulating Tfr and Tfh subsets in patients with different autoimmune diseases. We recruited 97 participants, including 72 patients with Hashimoto’s thyroiditis (HT, n = 18), rheumatoid arthritis (RA, n = 16), or systemic lupus erythematosus (SLE, n = 32), and 31 matched healthy donors (HD). We found that the frequency of circulating T follicular subsets differed across diseases. Patients with HT had an increased frequency of blood Tfh cells (p = 0.0215) and a reduced Tfr/Tfh ratio (p = 0.0338) when compared with HD. This was not observed in patients with systemic autoimmune rheumatic diseases (RA, SLE), who had a reduction in both Tfh (p = 0.0494 and p = 0.0392, respectively) and Tfr (p = 0.0003 and p = 0.0001, respectively) cells, resulting in an unchanged Tfr/Tfh ratio. Activated PD-1+ICOS+Tfh and CD4+PD-1+CXCR5–Tph cells were raised only in patients with SLE (p = 0.0022 and p = 0.0054), without association with disease activity. Our data suggest that GC dysregulation, assessed by T follicular subsets, is not uniform in human autoimmunity. Specific patterns of dysregulation may become potential biomarkers for disease and patient stratification.

BackgroundIn manufacturing industries, tasks requiring poor posture, high repetition, and long duration commonly induce fatigue and lead to an increased risk of work-related musculoskeletal disorders. Smart devices assessing biomechanics and providing feedback to the worker for correction may be a successful way to increase postural awareness, reducing fatigue, and work-related musculoskeletal disorders. However, evidence in industrial settings is lacking. ObjectiveThis study protocol aims to explore the efficacy of a set of smart devices to detect malposture and increase postural awareness, reducing fatigue, and musculoskeletal disorders. MethodsA longitudinal single-subject experimental design following the ABAB sequence will be developed in a manufacturing industry real context with 5 workers. A repetitive task of screw tightening of 5 screws in a standing position into a piece placed horizontally was selected. Workers will be assessed in 4 moments per shift (10 minutes after the beginning of the shift, 10 minutes before and after the break, and 10 minutes before the end of the shift) in 5 nonconsecutive days. The primary outcomes are fatigue, assessed by electromyography, and musculoskeletal symptoms assessed by the Nordic Musculoskeletal Questionnaire. Secondary outcomes include perceived effort (Borg perceived exertion scale); range of motion of the main joints in the upper body, speed, acceleration, and deceleration assessed by motion analysis; risk stratification of range of motion; and cycle duration in minutes. Structured visual analysis techniques will be conducted to observe the effects of the intervention. Results for each variable of interest will be compared among the different time points of the work shift and longitudinally considering each assessment day as a time point. ResultsEnrollment for the study will start in April 2023. Results are expected to be available still in the first semester of 2023. It is expected that the use of the smart system will reduce malposture, fatigue, and consequently, work-related musculoskeletal pain and disorders. ConclusionsThis proposed study will explore a strategy to increase postural awareness in industrial manufacturing workers who do repetitive tasks, using smart wearables that provide real-time feedback about biomechanics. Results would showcase a novel approach for improving self-awareness of risk for work-related musculoskeletal disorders for these workers providing an evidence base support for the use of such devices. International Registered Report Identifier (IRRID)PRR1-10.2196/43637

Abstract Introduction Wilson disease is an autosomal recessive disease of liver copper metabolism with predominant hepatic and neurological manifestations. Long-term data on the clinical follow-up and treatment efficacy are limited due to the low frequency of the disease. We evaluated a large cohort of Wilson disease patients from Northern Portugal during a 20-year follow-up period. Methods Twenty-four patients, diagnosed from 1975 to 2020 in a tertiary care center in Portugal, were retrospectively evaluated according to their clinical presentation, therapies and outcomes. Results Most of the patients were males (54%), with a median age at diagnosis of 19 years old (interquartile range 15–25). The main manifestations of Wilson disease were hepatic (71%) and neurological (25%). Family history was positive in 5 (21%) patients. Four patients (17%) presented with acute liver failure and fifteen (63%) individuals had cirrhosis at diagnosis. Penicillamine therapy was used by 11 (46%) patients, while trientine and zinc were given to 8 (33%) and 1 (4%) patient, respectively. Ten (42%) individuals underwent liver transplantation. The majority of patients (83%) had stable disease or improved outcomes during follow-up. Conclusion This is the largest cohort of adult patients with Wilson disease reported in Northern Portugal. We show that Wilson disease has favorable outcomes with long overall survival, assuming adherence to therapy and lack of other insults to their liver.

Treatment options for hypertension have been evolving over time. However, prevalence rates keep increasing and perpetuate hypertension as a major cardiovascular risk factor. Exercise training is effective in reducing blood pressure, cardiovascular disease risk factors and mortality, besides improving quality of life. However, participation rates for hypertensive patients remain shockingly low and adherence to exercise training tends to decline following exercise programs. These trends emphasize the need to deepen our knowledge of modifiable intrapersonal, interpersonal, and socioeconomic and environmental factors that help explain exercise adherence among people with hypertension. The present review focuses on the determinants of adherence and long-term maintenance of a physically active lifestyle in hypertensive individuals.

Given the increased risk of cardiovascular events associated with resistant hypertension, predictive cardiovascular prognosis is extremely important. Ambulatory blood pressure monitoring (ABPM) is mandatory for resistant hypertension diagnosis, but its use for prognosis is scarce. This observational longitudinal study included 258 patients (mean age of 60.4 ± 11.2 years; 61.2% male), who underwent 24 h ABPM in a hypertension unit from 1999 to 2019. The outcomes were global cardiovascular events (cerebrovascular, coronary, and other cardiovascular events). The mean follow-up period was 6.0 ± 5.0 years. Sixty-eight cardiovascular events (61 nonfatal) were recorded. Patients who experienced cardiovascular events were generally older, with higher rates of chronic kidney disease and prior cardiovascular events. The 24 h systolic blood pressure (hazard ratio 1.44; 95% CI 1.10–1.88), night systolic blood pressure (1.35; 95% CI 1.01–1.80), and 24 h pulse pressure (2.07; 95% CI 1.17–3.67) were independent predictors of global cardiovascular events. Multivariate Cox analysis revealed a higher risk of future cardiovascular events, particularly in patients with a 24 h daytime and nighttime pulse pressure > 60 mm Hg with respective hazard ratios of 1.95; 95% CI 1.01–3.45; 2.15; 95% CI 1.21–3.83 and 2.07; 95% CI 1.17–3.67. In conclusion, APBM is a fundamental tool not only for the diagnosis of resistant hypertension, but also for predicting future cardiovascular events.

MicroRNAs (miRNAs) are key regulators of several plant developmental processes including embryogenesis. Most miRNA families are conserved across major groups of plant species, but their regulatory roles have been studied mainly in model species like Arabidopsis and other angiosperms. In gymnosperms, miRNA-dependent regulation has been less studied since functional approaches in these species are often difficult to establish. Given the fundamental roles of auxin signaling in somatic embryogenesis (SE) induction and embryo development, we investigated a previously predicted interaction between miR160 and a putative target encoding AUXIN RESPONSE FACTOR 18 in Pinus pinaster (PpARF18) embryonic tissues. Phylogenetic analysis of AUXIN RESPONSE FACTOR 18 (ARF18) from Pinus pinaster and Picea abies, used here as a model system of conifer embryogenesis, showed their close relatedness to AUXIN RESPONSE FACTOR (ARF) genes known to be targeted by miR160 in other species, including Arabidopsis ARF10 and ARF16. By using a luciferase (LUC) reporter system for miRNA activity in Arabidopsis protoplasts, we have confirmed that P. pinaster miR160 (ppi-miR160) interacts in vivo with PpARF18 target site. When the primary miR160 from P. pinaster was overexpressed in protoplasts under non-limiting levels of ARGONAUTE1, a significant increase of miR160 target cleavage activity was observed. In contrast, co-expression of the primary miRNA and the target mimic MIM160 led to a decrease of miR160 activity. Our results further support that this interaction is functional during consecutive stages of SE in the conifer model P. abies. Expression analyses conducted in five stages of development, from proembryogenic masses (PEMs) to the mature embryo, show that conifer ARF18 is negatively regulated by miR160 toward the fully developed mature embryo when miR160 reached its highest expression level. This study reports the first in vivo validation of a predicted target site of a conifer miRNA supporting the conservation of miR160 interaction with ARF targets in gymnosperms. The approach used here should be useful for future characterization of miRNA functions in conifer embryogenesis.

The therapeutic potential of exercise training in the mobilization of endothelial progenitor cells (EPCs) into the peripheral blood in patients with cardiovascular disease is not yet clear. A systematic review and meta-analysis was performed in order to assess the effectiveness of exercise training in increasing the number of circulating EPCs in patients with cardiovascular disease. A literature search was conducted across the PubMed, Scopus, Web of Science and EBSCO databases, including the reference lists of relevant papers. The quality of randomized clinical trials was evaluated using the PEDro scale. The primary outcome data were circulating EPC levels. Six studies (236 participants) – three on heart failure (n=111), one on peripheral arterial disease (n=40) and two on coronary artery disease (n=85) – were included. There was an increase in EPC levels in the exercise training groups (effect size [ES]=0.57; 95% CI: 0.01-1.12), with considerable heterogeneity (I2=75.6%; p

Aquaculture farms and estuarine environments close to human activities play a critical role in the interaction between aquatic and terrestrial surroundings and animal and human health. The AquaRAM project aimed to study estuarine aquaculture farms in Portugal as a reservoir of antibiotic resistance genes and the potential of its spread due to mobile genetic elements. We have assembled a collection of metagenomic data from 30 sediment samples from oysters, mussels, and gilt-head sea bream aquaculture farms. This collection includes samples of the estuarine environment of three rivers and one lagoon located from the north to the south of Portugal, namely, the Lima River in Viana do Castelo, Aveiro Lagoon in Aveiro, Tagus River in Alcochete, and Sado River in Setúbal. Statistical data from the raw metagenome files, as well as the file sizes of the assembled nucleotide and protein sequences, are also presented. The link to the statistics and the download page for all the metagenomes is also listed below.

INTRODUÇÃO: O objetivo foi caracterizar os episódios referenciados pelos cuidados de saúde primários (CSP) ao serviço de urgência (SU) do Centro Hospitalar do Médio Ave, assim como classificar a adequabilidade da referenciação. MATERIAL E MÉTODOS: Foi realizado um estudo observacional retrospetivo, incluindo todos os utentes com idade inferior a 18 anos referenciados por parte dos CSP ao SU, durante o ano de 2017. A referenciação foi considerada adequada sempre que foram realizados exames complementares de diagnóstico ou terapêuticas não disponíveis nos CSP. Assim como, a observação por outra especialidade que não a pediatria, a necessidade de internamento e a transferência para outro hospital. RESULTADOS: Foram obtidos 406 episódios de urgência, dos quais 25,9% obtiveram como diagnóstico de saída a patologia gastrointestinal e 29,4% a patologia respiratória. Foram consideradas adequadas 65,3% das referenciações, sendo as mais frequentes a patologia gastrointestinal, respiratória e trauma. As patologias genitourinária e infecciológica foram as mais constantes quanto à referenciação inadequada (OR = 11,5 e OR = 3,49, respetivamente, ajustado à idade). Verificou-se concordância entre o motivo de referenciação e o diagnóstico de saída nas patologias gastrointestinal, otorrinolaringológica, trauma e oftalmológica (kappa > 0,7). A grande maioria (92,2%) das crianças teve alta clínica. CONCLUSÃO: A taxa de referenciação adequada aos serviços hospitalares no presente estudo foi semelhante à descrita na literatura. No entanto, a otimização da comunicação entre os CSP e o SU, a implementação de protocolos, bem como, a formação dos profissionais dos CSP permitirão melhorar a referenciação.

Endoscopic ultrasound (EUS) morphology can aid in the discrimination between mucinous and non-mucinous pancreatic cystic lesions (PCLs) but has several limitations that can be overcome by artificial intelligence. We developed a convolutional neural network (CNN) algorithm for the automatic diagnosis of mucinous PCLs. Images retrieved from videos of EUS examinations for PCL characterization were used for the development, training, and validation of a CNN for mucinous cyst diagnosis. The performance of the CNN was measured calculating the area under the receiving operator characteristic curve (AUC), sensitivity, specificity, and positive and negative predictive values. A total of 5505 images from 28 pancreatic cysts were used (3725 from mucinous lesions and 1780 from non-mucinous cysts). The model had an overall accuracy of 98.5%, sensitivity of 98.3%, specificity of 98.9% and AUC of 1. The image processing speed of the CNN was 7.2 ms per frame. We developed a deep learning algorithm that differentiated mucinous and non-mucinous cysts with high accuracy. The present CNN may constitute an important tool to help risk stratify PCLs.

Introduction and aim: Primary biliary cholangitis is a rare disease with scarce epidemiological data in Southern Europe. The authors aimed to evaluate treatment response in a cohort of patients. Materials and methods: This retrospective observational single-centre study included patients with diagnostic criteria of primary biliary cholangitis. Data on disease presentation, laboratory results, treatment and clinical endpoints were collected and analyzed. Results: Fifty-three patients were included, 89% women, with mean age of 62 ± 15 years at diagnosis. The majority was asymptomatic (49%), tested positive for antimitochondrial antibodies (96%) and had increased alkaline phosphatase (median = 214 U/L). 75% of the patients had liver histology and the majority were in Ludwig's stage I (42%). Autoimmune hepatitis (AIH) features were found in seven patients (13%). All were treated with ursodeoxycholic acid (UDCA) and 56% achieved biochemical response at one year; patients with AIH features exhibited steeper decreases in alkaline phosphatase (p = 0.007) and reached the endpoint of 40% decrease in alkaline phosphatase more frequently (p = 0.017). Conclusion: In conclusion a significant proportion of patients failed to achieve an adequate response to UDCA treatment. The response rate of patients with AIH features was better, which could be related to a different phenotype or to the potential impact of immunosuppressive agents.

Background and Purpose: Patency capsule (PC) examination is usually performed – previously to capsule endoscopy – to evaluate small-bowel patency in patients with established Crohn’s disease (CD). The reported PC retention rate is significantly higher than expected. Our aims were to assess small-bowel patency, to determine the precise location of the retained PC in patients with CD, and to determine the false positive rate of evaluation with a radiofrequency identification tag (RFIT) scanner. Methods: This is a prospective single-center study including CD patients with clinical indication for small-bowel capsule endoscopy. PillCam® PC examination was performed on all patients to assess small-bowel patency. On all patients with a positive identification of the PC using an RFIT scanner, 30 h after ingestion, an abdominal CT was performed in order to identify its precise location. Results: Fifty-four patients were included. The PC retention rate, according to evaluation with the RFIT scanner, was 20% (in 11 patients) 30 h after ingestion. These patients were then submitted to abdominal CT, which revealed that there was small-bowel retention in 5 cases (9%). Higher CRP levels, penetrating disease, and a history of abdominal surgery were associated with an increased risk of PC retention (p = 0.007, p = 0.011, and p = 0.033, respectively). On multivariate analysis, there was an independent association between small-bowel PC retention and CRP levels >5 mg/dL (OR = 15.5; p = 0.03). Discussion: The small-bowel PC retention rate (9%) was considerably lower than those found in previous reports. Our results show that, with this protocol, the false-positive cases of RFIT scans or plain abdominal X-rays may be avoided. This may contribute to more extensive application of capsule endoscopy without the risk of small-bowel retention.

Abstract Primary ciliary dyskinesia (PCD) is a chronic suppurative airways disease that is usually recessively inherited and has marked clinical phenotypic heterogeneity. Classic symptoms include neonatal respiratory distress, chronic rhinitis since early childhood, chronic otitis media, recurrent airway infections leading to bronchiectasis, chronic sinusitis, laterality defects with and without congenital heart disease including abnormal situs in approximately 50% of the cases, and male infertility. Lung function deteriorates progressively from childhood throughout life. ‘Better Experimental Approaches to Treat Primary Ciliary Dyskinesia’ (BEAT-PCD) is a network of scientists and clinicians coordinating research from basic science through to clinical care with the intention of developing treatments and diagnostics that lead to improved long-term outcomes for patients. BEAT-PCD activities are supported by EU funded COST Action (BM1407). The third BEAT-PCD conference and fourth PCD training school were held jointly in February 2018 in Lisbon, Portugal. Presentations and workshops focussed on advancing the knowledge and skills relating to PCD in: basic science, epidemiology, diagnostic testing, clinical management and clinical trials. The multidisciplinary conference provided an interactive platform for exchanging ideas through a program of lectures, poster presentations, breakout sessions and workshops. Three working groups met to plan consensus statements. Progress with BEAT-PCD projects was shared and new collaborations were fostered. In this report, we summarize the meeting, highlighting developments made during the meeting.

Background and study aims The utility of suction during endoscopic ultrasound (EUS) fine-needle biopsy (FNB) using Franseen-tip needle remains unclear and has not been evaluated in randomized trials. We designed a randomized crossover trial to compare the diagnostic yield during EUS-FNB using a 22G Franseen-tip needle, with and without standard suction. Patients and methods Consecutive patients undergoing EUS-guided sampling of solid pancreatic lesions were recruited. A minimum of two passes were performed for each case: one with 20-mL syringe suction (S+) and another without (S–). The order of passes was randomized and the pathologist blinded. The endpoints were the diagnostic yield and the impact of blood contamination in the diagnosis. Results Fifty consecutive patients were enrolled. The overall diagnostic accuracy was 84 %. A diagnosis of malignancy was obtained in 70 samples: 36 in the S+group and 34 in the S–group. A statistically significant difference was seen in the diagnostic accuracy (S+: 78 % vs. S–: 72 %, P

Although infliximab (IFX) is an efficient therapy for ulcerative colitis (UC) patients, a considerably high rate of therapeutic failures still occurs. This study aimed at a better understanding of IFX pharmacokinetics and pharmacodynamics among clinically-asymptomatic UC patients. This was a multicentric and prospective study involving 65 UC patients in the maintenance phase of IFX therapy. There were no significant differences between patients with positive and negative clinical, endoscopic and histological outcomes concerning their IFX trough levels (TLs), area under the IFX concentration vs. time curve (AUC), clearance and antibodies to infliximab (ATI) levels. However, the need to undergo therapeutic escalation later in disease development was significantly associated with higher ATI levels (2.62 μg/mL vs. 1.15 μg/mL, p = 0.028). Moreover, and after adjusting for disease severity, the HR (hazard ratio) for therapeutic escalation was significantly decreased for patients with an ATI concentration below 3 μg/mL (HR = 0.119, p = 0.010), and increased for patients with fecal calprotectin (FC) level above 250 μg/g (HR = 9.309, p = 0.018). In clinically-stable UC patients, IFX pharmacokinetic features cannot predict therapeutic response on a short-term basis. However, high levels of ATIs or FC may be indicative of a future therapeutic escalation.

Patients with inflammatory bowel disease present a higher risk of colorectal cancer, especially patients with a high degree of disease activity. Although rare, carcinoid tumors can also be associated with inflammatory bowel disease. Mixed adenoneuroendocrine tumor is defined as a neoplasm with dual differentiation (neuroendocrine and adenoma) with each component accounting for at least 30% of the tumor. We present a case of a mixed adenoneuroendocrine tumor in a patient with inflammatory bowel disease.

Background: Suppressor of Tumorigenicity 2 (ST2) is an IL33 receptor detected in the mucosa and serum of ulcerative colitis (UC) patients. We evaluated soluble ST2 (sST2) as a surrogate biomarker of disease outcome and therapeutic response, in moderate-to-severe UC patients treated with golimumab. Methods: We conducted an open-label single-arm multicentre prospective study. At screening/baseline, week 6 (W6) and week 16 (W16), clinical and endoscopic activity (total Mayo score), histologic activity (Geboes index) and biomarkers were evaluated. Results: From 38 patients, 34 (89.5%) completed W6 and 29 (76.3%) completed W16. Mean age (±SD) was 34.6 ± 12.6 years; 55.9% were female. At W16, 62.1% achieved clinical response. Patients with endoscopic activity at W6 ( n = 20) had higher baseline sST2 (median, 24.5 versus 18.7 ng/ml, p = 0.026) and no decrease from baseline (median change, 0.8 versus −2.7, p = 0.029). At W6, sST2 levels correlated with endoscopic activity ( rs = 0.45, p = 0.007) but not with histological activity ( rs = 0.25, p = 0.151). The best cut-offs for endoscopic activity were sST2 = 16.9 ng/ml (sensitivity = 85%; specificity = 71%) and faecal calprotectin (FC) = 353 μg/g (sensitivity = 90%, specificity = 67%). Patients with histological activity at W6 ( n = 27) had higher baseline ST2 levels (median, 23.0 versus 13.7 ng/ml, p = 0.035). sST2 did not correlate with FC or serum C-reactive protein. FC levels correlated with histological activity and baseline FC were higher when Geboes ⩾3.1 at W6. Conclusions: sST2 may be a surrogate biomarker of UC activity and therapeutic response as it correlates with endoscopic and clinical activity at W6 of golimumab treatment, and subjects with endoscopic and histological activity at W6 had higher baseline ST2 levels.

Background: Resistant Hypertension (RH) is associated with an increased risk of cardiovascular events and poor prognosis. Exercise training studies in RH patients have shown promising outcomes, nonetheless, none determine the impact of exercise on endothelial damage and repair. Circulating endothelial cells (CECs) are a reliable indicator of vascular damage and dysfunction. Recent studies in hypertension suggest that increased levels of endothelial progenitor cells (EPCs), a marker of endothelial repair, are related to increased CECs in order to compensate endothelial damage. Purpose: This study aimed to determine the effect of 12-week aerobic exercise program on the percentage of EPCs and CECs in RH patients. Methods: Patients with RH were randomized to a 12-week aerobic exercise program (3 xs/week) (n = 13) and a usual care control group (n = 8). Outcome measures included clinical data, ambulatory blood pressure data and circulating levels of EPCs, hematopoietic stem cells (HSC) and CECs, quantified by flow cytometry. (ClinicalTrials.gov: NCT03090529). Results: Baseline characteristics were similar between groups, including the number of antihypertensive drugs (5.0 ± 0.9 vs. 4.8 ± 0.7, p = 0.517). After 12 weeks, no significant changes were found in the levels of HSCs in both groups. The levels of CECs decreased in the exercise group [0.0073 (0.0016)% to 0.0058 (0.0029), p = 0.019]; no changes were observed in the control group. EPC’s decreased only in the exercise group [0.0071 (0.0027)% to 0.0052 (0.0037)%, p = 0.046]. Conclusions: Exercise training reduces endothelial injury/damage (reduced CECs levels) in RH patients, a specific group who is a challenge for clinicians as the available treatment options have reduced success.

Background: The relationship between arterial stiffness, blood pressure (BP) and cardiorespiratory fitness (CRF) has been studied in healthy populations and cardiovascular patients, since all of which proved to be independent predictors of all-cause mortality. We aimed to investigate the association of CRF with arterial stiffness and peripheral and central hemodynamics, in patients with resistant hypertension (RT). Methods: In this cross-sectional study, 30 patients (13 men, 17 women; age, 57.7 ± 8.1 years; weight, 79.2 ± 11.6 kg; body mass index, 29.7 ± 4.0 kg/m2) with resistant hypertension were recruited in the Hospital Infante D. Pedro (Aveiro) and Hospital Pedro Hispano (Matosinhos). Outcome measures included CRF (VO2peak), peripheral and central BP, and carotid-femoral pulse wave velocity (cf-PWV). Correlation analysis was conducted to assess the association between variables. Results: A significant negative correlation was found between VO2peak (33.7 ± 6.2 mLO2/kg/min) and central (141.0±21.3 mmHg; r = −0.395, p = 0.031) and peripheral systolic BP (148.4 ± 21.3 mmHg; r = −0.363, p = 0.049). VO2peak was also correlated with pulse pressure (PP) amplification ratio (1.2 ± 0.1 mmHg; r = 0.361, p = 0.050). The association with central systolic BP (r = −0.403, p = 0.035) and PP amplification ratio (r = 0.408, p = 0.033) remained significant after adjusted for age. VO2peak showed no correlation with PWV (9.4 ± 2.9 m/s; r = −0.075, p = 0.694) and peripheral (88.1 ± 12.2 mmHg; r = −0.138 p = 0.467) and central diastolic BP (88.5 ± 12.7 mmHg; r = −0.133, p = 0.483). Conclusion: This study confirms the inverse relationship between CRF and central systolic BP and PP amplification ratio in RH patients, regardless of age.

Objective: Carotid-femoral Pulse Wave velocity (cfPWV), the gold standard for measuring stiffness, is a marker of organ damage (OLD). Even though cfPWV correlates with casual (BPc), central (CBP) and ambulatory (ABPM) blood pressure (BP), evidence is limited for resistant hypertension (RH). Method: Thirty-three patients (age, 56.1 ± 8.2 years; weight, 78.0 ± 12.4 kg; height, 1.62 ± 0.08 m) with RH participated in a cross-sectional study. Outcomes included clinical data, BPc, ABPM, and carotid-femoral, cfPWV. Correlation analysis was conducted to assess the association between variables; independent t-tests were conducted to compare variables between those participants with cfPWV < and ≥ 10 m/s. Results: Patients (20 women and 13 men) presented a peripheral systolic and diastolic BPc of 144.0 ± 3.8 mmHg and 82.0 ± 1.9 mmHg, respectively. The cfPWV correlated with age (r = 0.356, p = 0.045), 24 h systolic BP (24 h SBP) nightime pulse pressure (night PP), 24 h pulse pressure (24hPP), casual systolic (SBPc) and diastolic BP (DBPc), central systolic (CSBP), diastolic (CDBP) and central pulse pressure (CPP); controlled for age the correlation remained significant for 24h SBP (r=0.446, p=0.009) 24hPP (r=0.464, p=0.007), nightPP (r=0.365, p=0.036), SBPc (r=0.620, p

Partindo do entendimento da cidade como um lugar polissémico, parcela de espaço e tempo proporcionador de aprendizagem quer através das suas infra- estruturas quer através das suas comunidades, analisa-se a capacidade da cidade como escola através dos programas de serviço educativo da Escola Superior de Educação (ESE/IPP) para poder em projetos de intervenção artística urbana da cidade do Porto, promovidos pela empresa municipal Porto Lazer. Reflete-se acerca de um sistema educativo integrado numa rede de parcerias fomentadoras da cultura, do conhecimento e da criação que constroem uma identidade socialmente participada e participativa.Palavra Chave: cidade, escola, mediação, arte, comunidade Can the city be a school? – Educational Service ESE/Porto LazerStarting from the understanding of the city as a polysemous place a space and time proportion that provides learning through its infrastructures and through its communities, the capacity of the city as a school is analyzed through the educational service programs of the Escola Superior de Educação in projects of Porto´s urban artistic intervention, promoted by the municipal company Porto Lazer. It reflects on an educational system integrated in a network of partnerships fostering culture, knowledge and creation that build a socially participatory identity.Key words: City; school; mediation; art; community

Background: Patency capsule was developed to avoid small bowel video capsule endoscopy retention, namely in patients with Crohn's disease. Aims: To evaluate the predictive factors of small bowel patency in Crohn's disease patients. Patients and methods: Retrospective analysis including 151 Crohn's disease patients submitted to patency capsule (Agile® Patency Capsule) from 2011 to 2012. Patients that excreted the intact patency capsule were classified as having a patent small bowel (without patency capsule retention), other patients were considered to have negative patency of the small bowel (patency capsule retention). Results: Patients had a mean age of 41±14 years, 54% were female and 25% had been previously submitted to surgery. Stricturing disease was seen in 20% of cases and penetrating disease in 16% of cases. Left-sided colonic lesions and ileal strictures were observed at colonoscopy in 13% and 9% of patients, respectively. In our sample, 28% of patients had negative patency of the small bowel (patency capsule retention). In multivariate analysis, independent factors that were associated with negative patency of the small bowel in Crohn's disease patients were stricturing (OR 10.16, p < 0.001) and penetrating phenotypes (OR 11.73, p = 0.001), left-sided colonic lesions (OR 3.77, p = 0.038), ileal stricture (OR 9.76, p = 0.003); previous intestinal surgery was found to be protective (OR 0.16, p = 0.006). Conclusions: Stricturing or penetrating disease, ileal strictures, no previous surgery and left-sided colonic lesions were the factors associated with negative small bowel patency in Crohn's disease patients.

Background: The treatment goal of Crohn’s disease (CD) has moved towards achieving mucosal healing, resolution of transmural inflammation, and normalization of biomarkers. The purpose of this study was to evaluate how well computed tomography enterography (CTE) and fecal calprotectin (FC) correlated with endoscopic activity in newly diagnosed patients with CD and after 1 year of therapy. Methods: Consecutive patients with newly diagnosed CD were evaluated by endoscopy, CTE, and FC at diagnosis and 12 months after beginning immunosuppression. Endoscopic severity was assessed using the Simplified Endoscopic Score for Crohn’s Disease (SES-CD). Biomarkers, clinical indexes, and FC were recorded on the day of ileocolonoscopy at diagnosis and 1 year after diagnosis. We adapted a CTE score for disease activity based on radiological signs of inflammation (i.e. mural thickness, mural hyperenhancement, mesenteric fat proliferation, mesenteric fat densification, comb sign, presence of strictures, fistulas, abscesses, ascites, and lymphadenopathy). Correlations between endoscopy, CTE, and FC were assessed using Spearman’s rank correlation. Results: A total of 29 patients (48% women; median age 30 (24.5–35.5) years) were included in this prospective cohort. CTE findings significantly correlated with endoscopic findings. Endoscopic remission (ER) at 1-year follow up significantly correlated with improvement in mural hyperenhancement ( p = 0.004), mesenteric fat densification ( p = 0.001), comb sign ( p = 0.004), and strictures ( p = 0.008) in CTE. None of the CTE findings improved in patients without ER. FC correlated with SES-CD ( rs = 0.696, p < 0.001) and with CTE features of inflammation ( rs = 0.596, p < 0.001). A cut-off of 100 µg/g predicted ER with 92% sensitivity, 65% specificity, and 83% accuracy (area under curve 0.878, p < 0.001). Conclusions: CTE findings and FC levels correlated with endoscopic activity in CD both at diagnosis and at 1-year follow up. These two noninvasive markers of disease activity may be used as an alternative to endoscopy to monitor disease response to therapy.

Background and Aims: Despite the increasing use of noninvasive methods for the assessment of liver fibrosis and steatosis, the effect of fasting and food intake on these parameters is not yet clear. Our aims were to evaluate the effect of food intake on liver stiffness (LS) (measured by transient elastography) and controlled attenuation parameter (CAP) in patients with different degrees of liver disease and healthy volunteers, and secondarily, to assess possible factors associated with variations of LS and CAP. Methods: We performed a prospective single-center study including patients with liver disease and healthy volunteers. LS and CAP were evaluated using FibroScan® (Echosens, Paris, France), before (fasting ≥8 h) and 30 min after intake of a standardized breakfast. We used common cutoffs for LS: > 7 kPa for significant fibrosis (F2 to F4) and > 11 to 14 kPa (mean 12.5 kPa) for cirrhosis. Results: Fifty-nine (72%) patients with liver disease and 22 (28%) healthy volunteers were included. LS significantly increased 30 min after food intake (pre-meal 6.1 kPa [IQR: 4.7–9.8] vs. after-meal 6.8 kPa [IQR: 5.5–10.6]; p < 0.001). This difference was only significant in patients with chronic liver disease (p = 0.02) and not in healthy volunteers (p = 0.106). CAP values did not increase significantly after food intake. Gender, body mass index, mass of body fat, lean body mass, and percent of body fat were not related with significant variations of LS and CAP values after meal intake. Conclusions: Significant variations of LS were observed after ingestion of a standard meal, which may have consequences for patient management. CAP values were not significantly affected by food intake. Therefore, we consider that before the isolated evaluation of CAP, it is not necessary to perform any fasting period.

Background: Therapeutic drug monitoring (TDM)-based algorithms can be used to guide infliximab (IFX) adjustments in inflammatory bowel disease (IBD) patients. This study aimed to explore a rapid IFX-quantification test from a clinical perspective. Methods: This manuscript describes a prospective cohort study involving 110 ulcerative colitis (UC) patients on the maintenance phase of IFX. IFX trough levels were quantified using a rapid quantification assay and a commonly-used reference kit. Results: Irrespective of the assay used to measure IFX, its through levels were statistically different between patients with and without endoscopic remission (Mayo endoscopic score = 0), as well as between patients stratified by their faecal calprotectin (FC) levels. Despite the fact that the two methods correlated well with each other [Spearman’s rank correlation coefficient = 0.843, p < 0.001; intraclass correlation coefficients = 0.857, 95% confidence interval (CI): 0.791–0.903], there was a discernible systematic variation; values obtained with the reference kit were on average 2.62 units higher than those obtained with the rapid assay. Notwithstanding, 3 µg/ml was shown to be an acceptable cut-off to assess endoscopic status and inflammatory burden levels using both assays. The percentage of patients that had a positive outcome when the IFX concentration measured by the rapid assay ranked above 3 µg/ml was 88% both for a Mayo endoscopic score ⩽ 1 and for an FC concentration

Background: Cholangiocarcinoma is the second most frequent primitive liver malignancy and is responsible for 3% of the malignant gastrointestinal neoplasms. The aims of this study were to determine the association of serum levels of CA 19-9 at diagnosis with other clinical data and serum liver function tests and to identify possible factors that influence the survival rates during follow-up. Methods: Retrospective observational study of 89 patients with a diagnosis of cholangiocarcinoma followed at the Department of Gastroenterology during 5 years. Statistical analyses were performed using SPSS version 20.0. Results: Patients were followed up for a median time of 127 days (IQR: 48-564), and the median age at diagnosis was 71.0 years (IQR: 62.0-77.5). The median survival rate was 14.0 months (IQR: 4.3-23.7), and the mortality rate was 79%. Patients with CA 19-9 levels ≥103 U/L had lower albumin levels and higher levels of alanine aminotransferase and γ-glutamyltransferase. CA 19-9 levels ≥103 U/L were associated with a higher probability of metastization (p = 0.001) and lower rates of treatment with curative intent (p = 0.024). In a multivariate analysis, CA 19-9 levels Conclusion: Predictive factors for overall survival were identified, namely presence of metastasis, surgery, and chemotherapy. CA 19-9 levels ≥103 U/L were predictive factors for survival and metastization.

Background: There is scant information on the accuracy of different assays used to measure anti-infliximab antibodies (ADAs), especially in the presence of detectable infliximab (IFX). We thus aimed to evaluate and compare three different assays for the detection of IFX and ADAs and to clarify the impact of the presence of circulating IFX on the accuracy of the ADA assays. Methods: Blood samples from 79 ulcerative colitis (UC) patients treated with infliximab were assessed for IFX levels and ADAs using three different assays: an in-house assay and two commercial kits, Immundiagnostik and Theradiag. Sera samples with ADAs and undetectable levels of IFX were spiked with exogenous IFX and analyzed for ADAs. Results: The three assays showed 81–96% agreement for the measured IFX level. However, the in-house assay and Immundiagnostik assays detected ADAs in 34 out of 79 samples, whereas Theradiag only detected ADAs in 24 samples. Samples negative for ADAs with Theradiag, but ADA-positive in both the in-house and Immundiagnostik assays, were positive for IFX or IgG4 ADAs. In spiking experiments, a low concentration of exogenous IFX (5 µg/ml) hampered ADA detection with Theradiag in sera samples with ADA levels of between 3 and 10 µg/ml. In the Immundiagnostik assay detection interference was only observed at concentrations of exogenous IFX higher than 30 µg/ml. However, in samples with high levels of ADAs (>25 µg/ml) interference was only observed at IFX concentrations higher than 100 µg/ml in all three assays. Binary (IFX/ADA) stratification of the results showed that IFX+/ADA- and IFX-/ADAs+ were less influenced by the assay results than the double-positive (IFX+/ADAs+) and double-negative (IFX-/ADAs-) combination. Conclusions: All three methodologies are equally suitable for measuring IFX levels. However, erroneous therapeutic decisions may occur when patients show double-negative (IFX-/ADAs-) or double-positive (IFX+/ADAs+) status, since agreement between assays is significantly lower in these circumstances.

Apresenta-se o caso de um jovem de 25 anos, raça caucasiana, com diagnóstico de dermatite atópica desde os 7 anos de idade com agravamento a partir dos 18 anos. Foi medicado com anti-histamínicos orais, corticóides tópicos, ciclos de corticoterapia sistémica em altas doses e fototerapia com raios ultra violeta A combinada com psoraleno (PUVA), sem melhoria evidente e com agravamento clínico com a redução da dose de corticóides sistémicos. Foi referenciado à consulta de Imunoalergologia aos 25 anos, onde se fizeram vários reajustes terapêuticos sem sucesso antes de iniciar terapêutica com imunoglobulina G polivalente por via endovenosa. Descreve-se a evolução clínica do doente sob terapêutica com imunoglobulina G endovenosa e discute-se o papel desta no tratamento da dermatite atópica.

Our study illustrates how complex population processes over the Late Pleistocene have shaped the patterns of genetic divergence in Palearctic buzzards, due to the effects of population expansions and contractions, with hybridization at contact zones leading to admixture, introgression and incomplete lineage sorting. Here we report in advance the study that is being currently ultimated for publication.

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Background and study aims: One of the indications for capsule endoscopy (CE) is the detection of proximal small bowel (SB) involvement in Crohn's disease (CD) patients. Our aim was to assess clinical, laboratory and endoscopic predictors associated with proximal SB involvement in CD patients submitted to CE. Patients and methods: Retrospective multicenter study in which Lewis score (LS) was systematically determined in 190 CE of patients diagnosed with CD between 2003 and 2014. Results: Significant inflammatory activity (LS > 135) was present in 23 % of the patients in the first tertile and in 31 % of the patients in the second tertile. Albumin, haemoglobin, and total proteins were significantly lower in patients with a LS > 790 compared to patients with a LS 0.249 predicts proximal SB involvement with 90 % sensitivity and 40 % specificity (AUROC 0.732). Conclusions: One-third of patients had proximal SB involvement. Predictive factors were significant weight loss, stricturing behaviour, and ileal involvement at ileocolonoscopy. These data help to select CD patients that benefit the most from performing a CE.

Faba bean (Vicia faba L.) is a facultative cross-pollinating legume crop with a great importance for food and feed due to its high protein content as well as the important role in soil fertility and nitrogen fixation. In this work we evaluated genetic diversity and population structure of faba bean accessions from the Western Mediterranean basin and wild related species. For that purpose we screened 53 V. faba, 2 V. johannis and 7 V. narbonensis accessions from Portugal, Spain and Morocco with 28 faba bean Single Sequence Repeats (SSR). SSR genotyping showed that the number of alleles detected per locus for the polymorphic markers ranged between 2 and 10, with Polymorphic Information Content (PIC) values between 0.662 and 0.071, and heterozygosity (HO) between 0-0.467. Heterozygosity and inbreeding coefficient levels indicate a higher level of inbreeding in wild related species than in cultivated Vicia. The analysis of molecular variance (AMOVA) showed a superior genetic diversity within accessions than between accessions even from distant regions. These results are in accordance to population structure analysis showing that individuals from the same accession can be genetically more similar to individuals from far away accessions, than from individuals from the same accession. In all three levels of analysis (whole panel of cultivated and wild accessions, cultivated faba bean accessions and Portuguese accessions) no population structure was observed based on geography or climatic factors. Differences between V. narbonensis and V. johannis are undetectable although these wild taxa are clearly distinct from V. faba accessions. Thus, a limited gene flow occurred between cultivated accessions and wild relatives. Contrastingly, the lack of population structure seems to indicate a high degree of gene flow between V. faba accessions, possibly explained by the partially allogamous habit in association with frequent seed exchange/introduction.

Over thousands of years humans changed the genetic and phenotypic composition of several organisms and in the process transformed wild species into domesticated forms. From this close association, domestic animals emerged as important models in biomedical and fundamental research, in addition to their intrinsic economical and cultural value. The domestic rabbit is no exception but few studies have investigated the impact of domestication on its genetic variability. In order to study patterns of genetic structure in domestic rabbits and to quantify the genetic diversity lost with the domestication process, we genotyped 45 microsatellites for 471 individuals belonging to 16 breeds and 13 wild localities. We found that both the initial domestication and the subsequent process of breed formation, when averaged across breeds, culminated in losses of ~20% of genetic diversity present in the ancestral wild population and domestic rabbits as a whole, respectively. Despite the short time elapsed since breed diversification we uncovered a well-defined structure in domestic rabbits where the FST between breeds was 22%. However, we failed to detect deeper levels of structure, probably consequence of a recent and single geographic origin of domestication together with a non-bifurcating process of breed formation, which were often derived from crosses between two or more breeds. Finally, we found evidence for intrabreed stratification that is associated with demographic and selective causes such as formation of strains, colour morphs within the same breed, or country/breeder of origin. These additional layers of population structure within breeds should be taken into account in future mapping studies.

Local anesthetics (LA) are frequently used in medical and surgical and dental procedures. Adverse reactions to LA are rare, and hypersensitivity reactions are very rare. Nevertheless, they are the third more frequent cause of referral to Allergy Clinics due to drug allergy, after betalactamic antibiotics and non-steroidal anti-inflammatory agents. In this paper we review hypersensitivity reactions to LA and propose a diagnostic approach to them.