Dynamics of CD44+ bovine nucleus pulposus cells with inflammation.

Intervertebral Disc (IVD) degeneration has been associated with a chronic inflammatory response, but knowledge on the contribution of distinct IVD cells, namely CD44, to the progression of IVD degeneration remains elusive. Here, bovine nucleus pulposus (NP) CD44 cells were sorted and compared by gene expression and proteomics with the negative counterpart. NP cells were then stimulated with IL-1b (10 ng/ml) and dynamics of CD44 gene and protein expression was analyzed upon pro-inflammatory treatment. The results emphasize that CD44 has a multidimensional functional role in IVD metabolism, ECM synthesis and production of neuropermissive factors. CD44 widespread expression in NP was partially associated with CD14 and CD45, resulting in the identification of distinct cell subsets. In conclusion, this study points out CD44 and CD44-based cell subsets as relevant targets in the modulation of the IVD pro-inflammatory/degenerative cascade.

Effectiveness of photo-ozone therapy against equine Pythium insidiosum.

Cutaneous pythiosis is a life-threatening infectious disease. Low-level laser therapy (LLLT) and ozone (O3) have been used individually in the treatment of infected wounds. The goals of the study were a) to characterize the antimicrobial action of the photo-ozone therapy (LLLT-O3) against equine Pythium insidiosum, and b) to assess the cytotoxic potential of the LLLT-O3 in keratinocytes. Specimens of pathogen were isolated from 10 horses. After culturing, 120 hyphae plugs were distributed among four groups (n=30 hyphae plugs/group): LLLT (laser irradiation for 160 sec;), O3 (exposition to O3 for 15 min;), LLLT-O3 (LLLT and O3 treatments in sequence) and control (untreated plugs). The hyphae growth was measured during the first 14 days post-treatment. Where there was an absence of hyphae growth, the plug was recultured for an additional 7 days. The cytotoxic potential of the treatments against HaCaT keratinocytes was assessed by colorimetric assays. The LLLT-O3 and O3 treatments inactivated, respectively, 92.3% (28/30) and 30% (9/30) of the samples. No growth was detected after 7 days reculture of inactivated hyphae plugs on new media. Hyphae growth was visualized in 100% of the control and LLLT hyphae plugs. The viability of HaCaT cells was not affected by the isolated treatments (LLLT and O3), while the LLLT-O3 showed slight cytotoxic effect (20%) when compared to the control group (P<0.05). Photo-ozone therapy inactivated equine P. insidiosum hyphae with minimal cytotoxicity in skin cells in vitro.

Assessing the reaction to and efficacy of the Screener drug discovery and development board game as a pedagogical tool in postgraduate courses.

Screener, a board game supplemented with online resources, was introduced and distributed by the Brazilian Society of Pharmacology and Experimental Therapeutics to postgraduate programs as an instructional tool for the process of drug discovery and development (DDD). In this study, we provided a comprehensive analysis of five critical aspects for evaluating the quality of educational games, namely: 1) description of the intervention; 2) underlying pedagogical theory; 3) identification of local educational gaps; 4) impact on diverse stakeholders; and 5) elucidation of iterative quality enhancement processes. We also present qualitative and quantitative assessments of the effectiveness of this game in 11 postgraduate courses. We employed the MEEGA+ online survey, comprising thirty-three close-ended unipolar items with 5-point Likert-type response scales, to assess student perceptions of the quality and utility of Screener. Based on 115 responses, the results indicated a highly positive outlook among students. In addition, we performed a preliminary evaluation of learning outcomes in two courses involving 28 students. Pre- and post-quizzes were applied, each consisting of 20 True/False questions directly aligned with the game's content. The analysis revealed significant improvement in students' performance following engagement with the game, with scores rising from 8.4 to 13.3 (P<0.0001, paired t-test) and 9.7 to 12.7 (P<0.0001, paired t-test). These findings underscore the utility of Screener as an enjoyable and effective tool for facilitating a positive learning experience in the DDD process. Notably, the game can also reduce the educational disparities across different regions of our continental country.

Detection of microemboli in patients with acute ischaemic stroke and atrial fibrillation suggests poor functional outcome.

INTRODUCTION: We investigated the burden of microembolic signals (MES) in patients with acute ischaemic stroke (AIS) and atrial fibrillation (AF), assessing their impact on functional outcomes. PATIENTS AND METHODS: This multicentre international prospective cohort study involved patients with AIS and either a known or newly diagnosed anticoagulant-naïve AF. All centres utilised the same transcranial Doppler machine for 1-h monitoring with bilateral 2 MHz probes within 24 h of symptom onset. Recordings underwent MES analysis by a blinded central reader. The primary objectives were to ascertain the MES proportion and its association with functional outcomes assessed by the modified Rankin scale (mRS) score at 90 days. RESULTS: Between September 2019 and May 2021, we enrolled 61 patients, with a median age of 78 years (interquartile range 73-83) and a median stroke severity score of 11 (interquartile range 4-18). MES were observed in 14 patients (23%), predominantly unilateral (12/14, 86%), with a median rate of 6 counts/hour (interquartile range 4-18). MES occurrence was higher post-thrombectomy and among those with elevated brain natriuretic peptide levels (p < 0.05). A worse mRS score of 3-6 was more frequent in patients with MES, occurring in 11/14 (79%), compared to those without MES, 20/47 (43%), with an adjusted odds ratio of 5.04 (95% CI, 1.15-39.4), p = 0.04. CONCLUSIONS: Nearly a quarter of patients with AIS and AF exhibited silent microembolization after the index event. Detecting MES within 24 h post-stroke (using transcranial Doppler) could signify a marker of poor functional outcomes. Subsequent trials will assess if very early antithrombotic treatment might enhance outcomes in this highly selective group of cardioembolic stroke patients. (Clinicaltrials.gov ID: NCT06018090).

Spatio-temporal analysis of the visceral leishmaniasis in the state of Alagoas, Brazil

Abstract Visceral leishmaniosis is a neglected tropical disease. We evaluated the spatial distribution of cases of visceral leishmaniosis in the state of Alagoas, Brazil. All cases of VL, registered by the health department, were analyzed and georeferenced. Results: Between 2008 and 2017, 97.1% of the municipalities presented sporadic classification of transmission. With temporal evolution, the incidence of cases of visceral leishmaniosis was concentrated in most municipalities in the microregion of Santana do Ipanema-AL. Space-time analysis, if considered, may promote the improvement of surveillance and control actions of visceral leishmaniosis.

Resumo A leishmaniose visceral é uma doença tropical negligenciada. Foram avaliadas a distribuição espacial dos casos de leishmaniose visceral no estado de Alagoas. Todos os casos de LV, registrados pela secretaria de saúde, foram analisados e georreferenciados. Entre 2008 e 2017, 97,1% dos municípios apresentaram classificação esporádica de transmissão. Com a evolução temporal, a incidência de casos de leishmaniose visceral se concentrou na maioria dos municípios da microrregião de Santana do Ipanema-AL. A análise espaço-tempo, se considerada, pode promover o aprimoramento das ações de vigilância e controle da leishmaniose visceral.

Assessing the reaction to and efficacy of the Screener drug discovery and development board game as a pedagogical tool in postgraduate courses

Screener, a board game supplemented with online resources, was introduced and distributed by the Brazilian Society of Pharmacology and Experimental Therapeutics to postgraduate programs as an instructional tool for the process of drug discovery and development (DDD). In this study, we provided a comprehensive analysis of five critical aspects for evaluating the quality of educational games, namely: 1) description of the intervention; 2) underlying pedagogical theory; 3) identification of local educational gaps; 4) impact on diverse stakeholders; and 5) elucidation of iterative quality enhancement processes. We also present qualitative and quantitative assessments of the effectiveness of this game in 11 postgraduate courses. We employed the MEEGA+ online survey, comprising thirty-three close-ended unipolar items with 5-point Likert-type response scales, to assess student perceptions of the quality and utility of Screener. Based on 115 responses, the results indicated a highly positive outlook among students. In addition, we performed a preliminary evaluation of learning outcomes in two courses involving 28 students. Pre- and post-quizzes were applied, each consisting of 20 True/False questions directly aligned with the game's content. The analysis revealed significant improvement in students' performance following engagement with the game, with scores rising from 8.4 to 13.3 (P<0.0001, paired t-test) and 9.7 to 12.7 (P<0.0001, paired t-test). These findings underscore the utility of Screener as an enjoyable and effective tool for facilitating a positive learning experience in the DDD process. Notably, the game can also reduce the educational disparities across different regions of our continental country.

Nutritional value of meat lipid fraction obtained from mallard duck (Anas platyrhynchos) reared in semiextensive conditions for hunting purposes.

The mallard duck or wild duck (Anas platyrhynchos) is the world's most widespread and numerous dabbling duck, being traditionally hunted across many countries in Europe and North America. This study aims to provide a detailed characterization of mallard duck's meat lipid fraction obtained from farmed specimens, reared for hunting purposes, under semiextensive conditions. The mallard's duck meat total lipid content averaged 2.0 and 4.26 g/100 g of fresh meat in breast and leg meat portions, and its meat comprised 23 individual fatty acids (FA) and 3 dimethylacetals (DMA), independently of the sex or meat portion. The oleic (C18:1 cis-9), palmitic (C16:0), stearic (C18:0), linoleic (C18:2n-6), arachidonic (C20:4n-6), palmitoleic (C16:1 cis-9), and cis-vaccenic (C18:1 cis-11) acids were the predominant FA (representing >1% of total fatty acids in both breast and leg meat portions and independently of the sex), and together, these 7 fatty acids were accountable for 92.4 to 96.5% of total FA plus DMA in mallard duck meat. The monounsaturated, saturated and polyunsaturated fatty acids were accountable for 40.4, 35.0, and 21.0% of total FA plus DMA in breast and 54.6, 38.7, and 5.7% of total fatty acids in leg, while total DMA were liable for 3.6 and 0.9% of total FA plus DMA in breast and leg, respectively. The mallard duck meat total cholesterol content averaged 49.8 and 57.1 mg/100 g of fresh meat for breast and leg meat portions. Five tocochromanols were quantified in mallard duck meat, affording it with a total vitamin E content of 5.48 and 3.63 µg/g of fresh meat in breast and leg portions. The sex had no influence (P > 0.05) on mallard's duck meat lipid composition, but meat portion had a strong influence on mallard's duck meat lipid composition, influencing total lipid, total cholesterol, total vitamin E contents, FA partial sums, FA ratios (exception made for the n-6/n-3 ratio), and all nutritional lipid indices. The breast meat presented lower total lipid and total cholesterol contents, better FA ratios and nutritional quality indices and higher vitamin E content, being regarded as a healthier meat than leg. The study presented herein shows that mallard duck production in semiextensive conditions, similar to those used herein, could be used for the production of mallard duck beyond hunting. A production of duck's meat under natural or organic production practices, oriented to a market niche within the gourmet/organic markets.

Spatio-temporal analysis of the visceral leishmaniasis in the state of Alagoas, Brazil / Análise espacial-temporal da leishmaniose visceral no estado de Alagoas

Visceral leishmaniosis is a neglected tropical disease. We evaluated the spatial distribution of cases of visceral leishmaniosis in the state of Alagoas, Brazil. All cases of VL, registered by the health department, were analyzed and georeferenced. Results: Between 2008 and 2017, 97.1% of the municipalities presented sporadic classification of transmission. With temporal evolution, the incidence of cases of visceral leishmaniosis was concentrated in most municipalities in the microregion of Santana do Ipanema-AL. Space-time analysis, if considered, may promote the improvement of surveillance and control actions of visceral leishmaniosis.

A leishmaniose visceral é uma doença tropical negligenciada. Foram avaliadas a distribuição espacial dos casos de leishmaniose visceral no estado de Alagoas. Todos os casos de LV, registrados pela secretaria de saúde, foram analisados e georreferenciados. Entre 2008 e 2017, 97,1% dos municípios apresentaram classificação esporádica de transmissão. Com a evolução temporal, a incidência de casos de leishmaniose visceral se concentrou na maioria dos municípios da microrregião de Santana do Ipanema-AL. A análise espaço-tempo, se considerada, pode promover o aprimoramento das ações de vigilância e controle da leishmaniose visceral.

Combined effects of Limonene and Ivermectin on P-glycoprotein-9 gene expression of lambs Infected with Haemonchus contortus.

Although ivermectin (IVM) has a wide spectrum and long half-life, its frequent use as an anthelmintic for the last 42 years led to its worldwide tolerance by Haemonchus contortus. We evaluated the combination of limonene (LIM), a P-glycoprotein (Pgp) modulator, with IVM in lambs infected with a multidrug-resistant H. contortus. Twenty-four male Dorper lambs were artificially infected with two doses (seven days apart) of 8000 infective larvae of a multidrug-resistant isolate of H. contortus. The infection was patent 25 days later. Fifteen days before treatment with IVM (DAY -15), animals were divided into 4 groups: Infected-untreated control (CTL), IVM, LIM, and LIM+IVM. From DAY -15 to DAY + 14, groups LIM and LIM+IVM received 200 mg/kg of body weight/day of LIM via oral. On DAY 0, a single dose of IVM at 200 µg/kg of body weight was administered orally to groups IVM and LIM+IVM. On DAY + 7 and DAY + 14, fecal egg counts (FEC) were performed and on DAY + 14 animals were euthanized for total worm count (TWC), worm length, fecundity of females, and Pgp-9 gene expression. On DAY + 7, group LIM+IVM had 96.29% efficacy based on Fecal Egg Count Reduction TEST (FECRT) and a highly significant reduction in FEC (P = 0.0005) when compared to CTL. On DAY + 14, the efficacy of LIM+IVM was 82.87% on FECRT, although no differences were found among groups for FEC, TWC, worm length, or Pgp-9 gene expression. Female worms from the CTL group had higher egg counts in their uterus when compared to LIM. No differences were found for hematological or biochemical parameters, body weight, or weight gain among groups. Thus, LIM given daily at 200 mg/kg was safe for animals and, when combined with IVM, decreased egg shedding and could reduce pasture contamination, although it was unable to kill multidrug-resistant H. contortus.

Radiographic evaluation of the bicipital groove morphology does not predict intraarticular changes in the long head of biceps tendon.

INTRODUCTION AND OBJECTIVES: This study aimed to examine the clinical utility of the radiographic evaluation of the bicipital groove in predicting long head of biceps tendon (LHBT) pathology. MATERIAL AND METHODS: A prospective study was conducted, and sixty consecutive patients proposed to shoulder arthroscopic surgery were selected. Before surgery, a radiographic evaluation was performed with a supine and a Fisk radiograph. Most supine radiographs (>75%) were non-interpretable and were excluded from the study. As some Fisk radiographs (26.7%) were also non-interpretable, that left 44 interpretable radiographs in the study. These were measured for medial opening angle, total opening angle, width and depth of the bicipital groove. The radiographic measurements and the presence of LHBT pathology, as assessed at arthroscopy, were correlated. RESULTS: Radiographic evaluation of the bicipital groove showed a mean medial opening angle of 53 ±â€¯15° (23-90), a mean total opening angle of 80 ±â€¯26° (30-135), a mean width of 10.3 ±â€¯2.5 mm (6-19) and a mean depth of 4.1 ±â€¯1.5 mm (1-8). Men had higher medial opening angle (60 vs 50°, p = 0.044) and wider grooves (11.9 vs 9.7 mm, p = 0.019). Twenty-five patients (56.8%) were found to have an abnormal LHBT. No correlation was found between the radiographic measurements and LHBT pathology. Only age was correlated with a LHBT lesion (61.8 vs 46.3 years, p < 0.001). CONCLUSIONS: Our results show that there is no correlation between radiographic morphologic evaluation of the bicipital groove and LHBT pathology.

Prevalence of negative behaviour in the dental setting and association with sociodemographic, oral health-related and psychosocial factors amongst Brazilian preschool children.

PURPOSE: To investigate the prevalence of negative behaviour in preschool children attending dental clinics and its association with sociodemographic, oral health-related and parental psychosocial factors. METHODS: A cross-sectional study was carried out with 145 parents/guardians and their children aged 4-6 years attending paediatric dentistry training programmes in a capital city of Midwest Brazil. Data were obtained from children's dental records, interviews, and questionnaires for parents/guardians. The outcome was negative child behaviour, based on the dentists' use or indication of behavioural control measures during the dental appointments, as registered in the children's dental records. Covariates were sociodemographic, clinical and parent/guardian psychosocial factors religiosity (DUREL index) and Sense of Coherence (SOC-13 scale). Bivariate analyses and Poisson regression with robust variance were performed. RESULTS: The prevalence of negative behaviour was 24.1% (95% CI = 17.9-31.7). In the bivariate analyses, the variables initially selected for the regression models (p < 0.25) were the parent/guardians' number of children and religiosity, and the children's dental pain and caries status in deciduous teeth. After adjustment, the prevalence of negative behaviour was 2.12 higher in children with teeth extracted due to caries. CONCLUSION: The prevalence of negative behaviour was high and associated with the presence of missing teeth due to caries, regardless of sociodemographic, psychosocial, and other oral health factors.

Adhesión real al dimetilfumarato en pacientes con esclerosis múltiple remitente-recurrente / Actual adherence to dimethyl fumarate in patients with relapsing-remitting multiple sclerosis

Introducción: La esclerosis múltiple es una enfermedad neurológica crónica con numerosos tratamientos modificadores de la enfermedad disponibles, incluido el dimetilfumarato (DMF), una terapia de primera línea para la esclerosis múltiple remitente-recurrente. Aunque las tasas de discontinuación del DMF suelen ser bajas en los ensayos clínicos, la falta de adhesión al tratamiento se asocia con peores resultados clínicos. Evaluar la adhesión en el mundo real y los factores predictivos es fundamental para mejorar los resultados clínicos de los pacientes. Este estudio evaluó la adhesión al DMF durante 24 meses en una cohorte de pacientes tratados en un centro portugués. Pacientes y métodos: Estudio prospectivo no intervencionista, de un solo centro, con un seguimiento de 24 meses. El estudio incluyó a pacientes adultos con esclerosis múltiple remitente-recurrente tratados con DMF en la práctica clínica habitual. Se calculó la adhesión al DMF y se consideró que los pacientes eran adherentes si el valor estaba por encima del 80%. Se compararon variables clínicas y sociodemográficas entre grupos. Resultados: De los 80 pacientes incluidos, el 74% eran mujeres, con una edad media de 39 años y una edad media en el momento del diagnóstico de 32 años. Veintiséis pacientes no habían recibido tratamiento previo. La adhesión varió entre el 93, el 82 y el 87,5% a los 6, 12 y 24 meses, respectivamente. No se encontraron diferencias entre los pacientes que no habían recibido tratamiento previo y los que sí lo habían recibido. Conclusión: Este análisis en el mundo real mostró una adhesión significativa al tratamiento con DMF durante dos años por parte de los pacientes portugueses. No obstante, estos resultados deben interpretarse considerando los cambios sustanciales en las consultas externas y las diversas restricciones periódicas debidas a la pandemia de COVID-19, que afectaron en gran medida al seguimiento de los pacientes y a la recopilación de datos.(AU)

Introduction: Multiple sclerosis is a chronic neurological disease with numerous disease-modifying treatments available, including dimethyl fumarate (DMF), a first-line therapy for relapsing-remitting multiple sclerosis. Although rates of discontinuation of DMF are generally low in clinical trials, non-adherence to treatment is associated with poorer clinical outcomes. Assessing real-world adherence and predictive factors is critical to be able to improve clinical outcomes for patients. This study evaluated adherence to DMF over 24 months in a cohort of patients treated in a Portuguese healthcare centre. Patients and methods: A prospective, non-interventional, single-centre study with 24 months’ follow-up was conducted. The study included adult patients with relapsing-remitting multiple sclerosis treated with DMF in routine clinical practice. Adherence to DMF was calculated and patients were considered to have adhered if the value was above 80%. Clinical and socio-demographic variables were compared between groups. Results: Of the 80 patients included, 74% were women, with a mean age of 39 years and a mean age of 32 years at diagnosis. Twenty-six patients had not received any previous treatment. Adherence varied between 93, 82 and 87.5% at 6, 12 and 24 months, respectively. No differences were found between patients who had not received any prior treatment and those who had been treated. Conclusion: This real-world analysis showed significant adherence to DMF treatment by Portuguese patients over a period of two years. However, these results must be interpreted in the light of the substantial changes in outpatient consultations and the various periodic restrictions due to the COVID-19 pandemic, which had an important effect on patient follow-up and data collection.(AU)

Influence of essential oils on the quality of Vigna unguiculata L. (Walp.) seeds compared by traditional method, image and multivariate analysis.

The extracts of medicinal plants are used for the treatment of seeds in order to reduce the action of phytopathogens and increase the vigor of the seeds. Currently, computerized image analysis has been used to assess the physiological quality of seed lots. The objective was to evaluate the efficiency of the Vigor-S® software in the evaluation of the physiological quality of cowpea seeds treated with essential oils, comparing with a traditional test and the principal component analysis. Two cowpea cultivars were analyzed, BRS Tumucumaque and BRS Guariba, treated with doses of natural extracts of Alfavaca, garlic, horsetail, citronella and pyroligneous acid. The traditional method consisted of evaluations for germination, first germination count, seedling emergence, emergence speed index, accelerated aging, fresh matter and dry matter of seedling and the image analysis for: seedling length, growth index, uniformity index, vigor index, and germination. A Principal component analysis was applied to reduce the number of variables. Horsetail, Alfavaca and citronella extracts were efficient in increasing the physiological quality of the seeds of at least one cultivar. The Vigor-S® software proved to be efficient compared to traditional tests to assess the physiological quality of seeds. Principal Component Analysis is an ally to identify the best extracts and doses to be used. The image analysis method proved to be effective when compared to the traditional method and can therefore be used.

Adolescent and parental decision-making for the MenACWY vaccination: influential predictors and parental-adolescent differences among households in the Netherlands.

BACKGROUND: Between 2015 and 2018 The Netherlands experienced increases of invasive meningococcal disease (IMD) serogroup W (MenW). Therefore in 2018 the MenACWY vaccination was introduced in the National Immunisation Programme (NIP) and a catch-up campaign was initiated targeting adolescents. This study aimed to gain insight into what factors played a role in the decision-making process regarding the MenACWY vaccination. The focus was on the differences in the decision-making of parents and adolescents in order to assess what factors influence the decisions made. METHODS: An online questionnaire was offered to adolescents and one of their parents. We used random forest analyses to determine which factors best predict the outcome of the MenACWY vaccination decision. We carried out ROC (receiver-operator characteristics) analyses to confirm the predictive value of the variables. RESULTS: Among parents several factors stand out, centring on the process of the decision, their attitude about the MenACWY vaccination, trust in the vaccination, and ideas of important people around them. Among adolescents the three stand-out predictors are the ideas of important people around them, the process of the decision and trust in the vaccination. Parents have prominent influence in the decision-making, while the adolescent's influence in the household decision-making is more limited. Adolescents tend to be less engaged and spend less time thinking about the decision compared to parents. Opinions of parents and adolescents from the same households concerning the factors that are influential do not differ a lot in the final decision-making. CONCLUSIONS: Information about MenACWY vaccination might be mainly addressed to the parents of the adolescents and whereby the dialogue about MenACWY vaccination between parents and adolescents will be stimulated. With regard to the predictor trust in vaccination, raising the frequency of use of certain sources, especially those deemed very reliable among households such as conversations with a GP or the provider of the vaccination (GGD/JGZ), might prove a useful strategy to solidify vaccination uptake numbers.

Salicylic acid concentrations and forms of application mitigate water stress in sour passion fruit seedlings.

The present study aimed to evaluate concentrations and forms of application of salicylic acid used for water stress mitigation on the gas exchange and growth of yellow passion fruit. The experimental design was arranged in randomized blocks in a 4 × 4 × 2 factorial scheme, with four concentrations of salicylic acid (SA) via foliar application (0.0, 0.7, 1.4, and 2.1 mM), four SA concentrations via fertigation (0.0, 0.7, 1.4, and 2.1 mM), and two irrigation depths estimated based on the actual evapotranspiration - ETr (50 and 100% of ETr), with three replications. Water stress negatively affected the physiology and growth of yellow passion fruit seedlings at 75 days after sowing (DAS). The application of salicylic acid, regardless of the form of application, attenuates the effects of water stress on gas exchange and growth of yellow passion fruit, with the best results obtained when applying a concentration of 1.30 mM via leaf or 0.90 mM via fertirrigation. The combination of foliar application of AS and fertigation contributed to improve photosynthetic and growth parameters under water conditions of 50 and 100% of ETr. The foliar application of AS presents superior responses to the application via fertigation. These results reinforce the hypothesis that the attenuation of water stress by salicylic acid is related to the maintenance of gas exchange, which depends on the concentration and form of application, and studies testing combinations throughout the crop cycle become promising for advances in knowledge from the action of this phytohormone on abiotic stress.

Unsupervised clustering to differentiate rheumatoid arthritis patients based on proteomic signatures.

OBJECTIVE: Patients with rheumatoid arthritis (RA) have different presentations and prognoses. Cluster analysis based on proteomic signatures creates independent phenogroups of patients with different pathophysiological backgrounds. We aimed to identify distinct pathophysiological clusters of RA patients based on circulating proteomic biomarkers. METHOD: This was a cohort study including 399 RA patients. Clustering was performed on 94 circulating proteins (92 CVDII Olink®, high-sensitivity troponin T, and C-reactive protein). Unsupervised clustering was performed using a partitioning cluster algorithm. RESULTS: The clustering algorithm identified two distinct clusters: cluster 1 (n = 223) and cluster 2 (n = 176). Compared with cluster 1, cluster 2 included older patients with a higher burden of comorbidities (cardiovascular and RA related), more erosive and longer RA duration, more dyspnoea and fatigue, walking a shorter distance in the Six-Minute Walk Test, with more severe diastolic dysfunction, and a 4.5-fold higher risk of death or hospitalization for cardiovascular reasons. Tumour necrosis factor (TNF) receptor superfamily-related pathways were mainly responsible for the model's discriminative ability. CONCLUSION: Using unsupervised cluster analysis based on proteomic phenotypes, we identified two clusters of RA patients with distinct biomarkers profiles, clinical characteristics, and different outcomes that could reflect different pathophysiological backgrounds. TNF receptor superfamily-related proteins may be used to distinguish subgroups.

Facing the challenges of air quality and health in a future climate: The Aveiro Region case study.

Air pollution and climate change are the most important environmental issues for European citizens. Despite the air quality improvements achieved in recent years, with most pollutants' concentrations below the European Union legislated values, it is necessary to understand whether this will continue in the future due to expected climate changes impacts. In this context, this work tries to answer two main questions: (i) What is the relative contribution of emission source regions/activities to air quality, now and in the future, considering a climate change scenario?; and (ii) What additional policies are needed to support win-win strategies for air quality and climate mitigation and/or adaptation, at urban scale? For that, a climate and air quality modelling system, with source apportionment tools, was applied to the Aveiro Region, in Portugal. Main results show that in the future, due to the implementation of carbon neutrality measures, air quality in the Aveiro Region may improve, with reduction up to 4 µg.m-3 for particulate matter (PM) concentrations and 22 µg.m-3 for nitrogen dioxide (NO2), and consequently, the premature deaths due to air pollution exposure will also decrease. The expected air quality improvement will ensure that, in the future, the limit values of the European Union (EU) Air Quality Directive will not be exceeded, but the same will not happen if the proposed revision of the EU Air Quality Directive is approved. Results also shown that, in the future, industrial sector will be the one with higher relative contribution for PM concentrations and the second one for NO2. For that sector, additional emission abatement measures were tested, showing that, in the future, it is possible to comply with all the new limit values proposed by the EU.

Emerging microalgae-based biofuels: Technology, life-cycle and scale-up.

Microalgae biomass is a versatile feedstock with a variable composition that can be submitted to several conversion routes. Considering the increasing energy demand and the context of third-generation biofuels, algae can fulfill the increasing global demand for energy with the additional benefit of environmental impact mitigation. While biodiesel and biogas are widely consolidated and reviewed, emerging algal-based biofuels such as biohydrogen, biokerosene, and biomethane are cutting-edge technologies in earlier stages of development. In this context, the present study covers their theoretical and practical conversion technologies, environmental hotspots, and cost-effectiveness. Scaling-up considerations are also addressed, mainly through Life Cycle Assessment results and interpretation. Discussions on the current literature for each biofuel directs researchers towards challenges such as optimized pretreatment methods for biohydrogen and optimized catalyst for biokerosene, besides encouraging pilot and industrial scale studies for all biofuels. While presenting studies for larger scales, biomethane still needs continuous operation results to consolidate the technology further. Additionally, environmental improvements on all three routes are discussed in light of life-cycle models, highlighting the ample research opportunities on wastewater-grown microalgae biomass.

Aspirin in diabetic patients at primary prevention: insights of the VITAL cohort.

PURPOSE: Aspirin use among patients with diabetes in primary prevention is still a matter of debate. We aimed to evaluate the potential cardiovascular risk benefit of aspirin in primary prevention, using data from a contemporary cohort. METHODS: Retrospective analysis of the VITAL cohort with > 20,000 individuals at primary prevention who were followed for a median of 5.3 years. The population was evaluated according to the baseline diabetes status, and then aspirin use was evaluated among diabetic patients. Cox regression models were used to estimate the risks of mortality and cardiovascular outcomes. The estimates were reported using adjusted hazard ratio (HR) and 95% confidence intervals (95%CI). RESULTS: Diabetic patients (n = 3549; 13.7%) showed to increase the risk of all-cause mortality (HR 1.61, 95%CI 1.33-1.94), and major adverse cardiovascular events (MACE) (HR 1.36 95%CI 1.11-1.68) than non-diabetic population. Diabetic patients taking aspirin were older, more frequently man, hypertensive, current users of statins, and current smokers compared with diabetic patients who did not use aspirin at baseline. There was no difference between diabetic aspirin users and non-users regarding all-cause mortality (HR 0.80, 95%CI 0.59, 1.10), MACE (HR 0.92, 95%CI 0.64, 1.33), coronary heart disease (HR 0.98, 95%CI 0.67, 1.43), or stroke (HR 0.87, 95%CI 0.48, 1.58). CONCLUSIONS: The VITAL data confirmed diabetes as an important risk factor for cardiovascular events in a contemporary cohort but did not show cardiovascular benefits of aspirin in primary prevention among people with diabetes who were shown to be at higher risk of cardiovascular events.