Responses of higher plants to boron deficiency

Dissertation presented to obtain the degree of Doctorate in Biochemistry by Instituto de Tecnologia Química e Biológica of Universidade Nova de LisboaDespite being known for more than 80 years that B is essential for plant growth, the role of this element in plant metabolism remains elusive. Until now, B involvement in the plant cell wall structure is the only well-documented participation of B. However, this participation can not explain all the symptoms observed in Bdeficient plants nor the requirement of B for early animal developmental processes. The aim of this study was to acquire additional data on the role(s) of B in the growth and development of higher plants. For that purpose, Lupinus albus, an important crop plant, was used to study long-term B deficiency responses, characterizing the proteomes of the leaf apoplast (Chapter 2) and of the root system (Chapter 3). A metabolite analysis was also performed in the different organs (leaf-blades, petioles, apexes, hypocotyls and roots) of L. albus plants (Chapter 4). Some consistent responses were observed with these different approaches.(...)The investigation was co-financed by Fundação da Ciência e Tecnologia (FCT) POCI 2010 and Fundo Social Europeu (FSE) through the PhD fellowship SFRH/BD/18273/2004

Use of CPAP to reduce arterial stiffness in moderate-to-severe obstructive sleep apnoea, without excessive daytime sleepiness (STIFFSLEEP): an observational cohort study protocol

Introduction: Sleepiness is a cardinal symptom in obstructive sleep apnoea (OSA) but most patients have unspecific symptoms. Arterial stiffness, evaluated by pulse wave velocity (PWV), is related to atherosclerosis and cardiovascular (CV) risk. Arterial stiffness was reported to be higher in patients with OSA, improving after treatment with continuous positive airway pressure (CPAP). This study aims to assess whether the same effect occurs in patients with OSA and without sleepiness. Methods and analysis: This observational study assesses the CV effect of CPAP therapy on a cohort of patients with moderate-to-severe OSA; the effect on the subcohorts of sleepy and non-sleepy patients will be compared. A systematic and consecutive sample of patients advised CPAP therapy will be recruited from a single outpatient sleep clinic (Centro Hospitalar de Lisboa Central-CHLC, Portugal). Eligible patients are male, younger than 65 years, with confirmed moderate-to-severe OSA and apnoea-hypopnea index (AHI) above 15/hour. Other sleep disorders, diabetes or any CV disease other than hypertension are exclusion criteria. Clinical evaluation at baseline includes Epworth Sleepiness Scale (ESS), and sleepiness is defined as ESS above 10. OSA will be confirmed by polygraphic study (cardiorespiratory, level 3). Participants are advised to undertake an assessment of carotid-femoral PWV (cf-PWV) and 24 hours evaluation of ambulatory blood pressure monitoring (ABPM), at baseline and after 4 months of CPAP therapy. Compliance and effectiveness of CPAP will be assessed. The main outcome is the variation of cf-PWV over time. Ethics and dissemination: This protocol was approved by the Ethics Committees of CHLC (reference number 84/2012) and NOVA Medical School (number36/2014/CEFCM), Lisbon. Informed, written consent will be obtained. Its results will be presented at conferences and published in peer-reviewed journals.publishersversionpublishe

“Quando ninguém se entende”: conflitos bioéticos num caso real de fim de vida

Introduction: The technical-scientific evolution of the last decades is reflected in the extension of life expectancy, in the reduction of the mortality rate due to infectious diseases and in the increase in mortality due to chronic-degenerative diseases. Added to this is the formation of medical education, increasingly equipped with a model oriented towards the use of highly sophisticated technologies, seeming to neglect the traditional field of the doctor-patient relationship. When the ultimate goal is the cure, death is considered a failure, an unacceptable result. Despite all the effort and technology used, death remains an inevitable outcome. The sick person, when in the background, ceases to be the protagonist of his story. Bioethics is a branch of knowledge that aims to indicate the limits and purposes of man's intervention in life, based on recognition for the dignity of the Human Person. “What should i do against what can I do?” End-of-life care commonly involves ethical issues that lead health professionals, patients and family members to face dilemmas, conflicts. Aim: This paper’s purpose is to show how challenging the decision-making process can be for those involved, namely health professionals, family members and users. Materials and methods: Facing a real case, ethical principles are presented and developed respecting the perspective of bioethics. Results: Starting with the conceptions of dignity, as well as possible weaknesses, covering more technical aspects such as the adequacy of therapeutic effort and proportionality of interventions, contemplating the concepts of obstinacy and therapeutic futility, exploring the dimension of autonomy (including some of its legal aspects) and ending in the field of justice and equity. Having these in hands, it becomes clear the complexity that the decision-making process gains when the humane and multidimensional aspect of the person who suffers, the patient (and family and their loved ones), is called into question. Conclusion: The considerations listed by the bioethical principles help us to base our professional actions, in order to, assist and consider, the environment and principles of the patient, the patient’s family and closed ones along with ours, as an assistance team. Resulting in the neglection of simple and absolute certainties, the lessening of doubts regarding this process and the election of the best possible answer for that specific patient, team and the context that surrounds them. Similarly, on this particular end of life situation, the concept of palliative care is highlighted as a tool of similar impact.Introdução: A evolução técnico-científica das últimas décadas traduz-se no alargamento da expectativa de vida, na diminuição da taxa de mortalidade por doenças infectocontagiosas e no aumento da mortalidade devido às doenças crônico-degenerativas. Soma-se a isso a formação da educação médica, dotada cada vez mais de um modelo orientado para o uso de tecnologias altamente sofisticadas, parecendo negligenciar o tradicional campo da relação médico-utente. Quando o objetivo final é a cura, a morte passa a ser considerada um fracasso, um resultado inaceitável. Apesar de todo o esforço e tecnologia usada, a morte continua sendo um desfecho inevitável. A pessoa doente, quando em segundo plano, deixa de ser o protagonista da sua história. A bioética é um ramo do conhecimento que visa indicar os limites e as finalidades da intervenção do homem sobre a vida, tendo como fundamento o reconhecimento pela dignidade da Pessoa Humana. “o que devo fazer frente ao que posso fazer?” Os cuidados de fim de vida comumente envolvem questões éticas que levam os profissionais de saúde, pacientes e familiares a enfrentarem dilemas, conflitos. Objetivo: O presente trabalho propõe mostrar o quanto pode ser desafiador o processo de tomada de decisão para os envolvidos, nomeadamente os profissionais de saúde, familiares e utentes. Materiais e métodos: Diante de um caso real, os princípios éticos são apresentados e desenvolvidos respeitando a ótica da bioética. Resultados: A começar pelas concepções de dignidade, assim como suas possíveis fragilidades, perpassando aspectos mais técnicos como a adequação de esforço terapêutico e proporcionalidade de intervenções, contemplando os conceitos de obstinação e futilidade terapêutica, explorando a dimensão da autonomia (inclusive alguns de seus aspectos legais) e encerrando no campo da justiça e equidade, faz-se clara a complexidade que o processo de tomada de decisões ganha quando o aspecto humano e multifacetado da pessoa que sofre, o utente (e família), é posto em causa. Conclusão: As ponderações elencadas pelos princípios bioéticos auxiliam-nos a fundamentar o nosso agir profissional, de forma a considerar o mundo do utente, de seus familiares e/ou pessoas próximas e o nosso enquanto equipa assistencial. Como resultado, é suposto o abandono de certezas dogmáticas e simplistas, o abrandamento das incertezas inerentes ao processo e a eleição de uma melhor resposta possível: individualizada para aquele utente, por aquela equipa, naquele contexto. Aproximando-se do caso em questão, nas situações de fim de vida, a filosofia dos cuidados paliativos destaca-se como ferramenta de semelhante impacto

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

The role of sleepiness on arterial stiffness improvement after CPAP therapy in males with obstructive sleep apnea: a prospective cohort study

Abstract Background Obstructive sleep apnea (OSA) is associated with increased cardiovascular risk. This study aim to assess differences in changes in arterial stiffness of two groups of patients, defined as having daytime sleepiness or not, after continuous positive airway pressure (CPAP) treatment. Methods A selected cohort of consecutive male patients, under 65 years old, with moderate to severe OSA and without great number of comorbidities was studied. The diagnosis was confirmed by home respiratory poligraphy. Sleepiness was considered with an Epworth Sleepiness Scale (ESS) > 10. An ambulatory blood pressure (BP) monitoring and carotid-femoral pulse wave velocity (cf-PWV) measurements were performed, before and after four months under CPAP. Compliant patients, sleepy and non-sleepy, were compared using linear mixed effects regression models. A further stratified analysis was performed with non-sleepy patients. Results Thirty-four patients were recruited, with mean age 55.2 (7.9) years, 38.2% were sleepy, 79.4% with hypertension, 61.8% with metabolic syndrome and 82.4% with dyslipidaemia. In univariable analysis, cf-PWV was strongly related to systolic BP parameters and age, but also to antihypertensive drugs (p = 0.030), metabolic syndrome (p = 0.025) and daytime sleepiness (p = 0.004). Sleepy patients had a more severe OSA, with AHI 44.8 (19.0) vs 29.7 (15.7) events/h (p = 0.018), but sleep study parameters were not associated with cf-PWV values. On multivariable regression, a significant interaction between time (CPAP) and sleepiness (p = 0.033) was found. There was a weak evidence of a cf-PWV reduction after CPAP treatment (p = 0.086), but the effects of treatment differed significantly between groups, with no changes in non-sleepy patients, while in sleepy patients a significant decrease was observed (p = 0.012). Evaluating non-sleepy patients group under CPAP therapy, results showed that both higher pulse pressure (p = 0.001) and lower LDL-cholesterol levels (p = 0.015) at baseline were associated to higher cf-PWV changes. Conclusions Patients with daytime sleepiness had a more severe OSA and presented a greater arterial stiffness improvement after CPAP therapy, independently from age and BP. Besides sleepiness, cf-PWV reduction after CPAP therapy was mainly associated to CV risk factors, and less to sleep study parameters. Trial registration Clinicaltrials.gov NCT02273089 23.10.2014 retrospectively registered

Characterisation of microbial attack on archaeological bone

As part of an EU funded project to investigate the factors influencing bone preservation in the archaeological record, more than 250 bones from 41 archaeological sites in five countries spanning four climatic regions were studied for diagenetic alteration. Sites were selected to cover a range of environmental conditions and archaeological contexts. Microscopic and physical (mercury intrusion porosimetry) analyses of these bones revealed that the majority (68%) had suffered microbial attack. Furthermore, significant differences were found between animal and human bone in both the state of preservation and the type of microbial attack present. These differences in preservation might result from differences in early taphonomy of the bones. © 2003 Elsevier Science Ltd. All rights reserved

Intraoperative transfusion practices in Europe

© 2016 The Author. Published by Oxford University Press on behalf of the British Journal of Anaesthesia.Background: Transfusion of allogeneic blood influences outcome after surgery. Despite widespread availability of transfusion guidelines, transfusion practices might vary among physicians, departments, hospitals and countries. Our aim was to determine the amount of packed red blood cells (pRBC) and blood products transfused intraoperatively, and to describe factors determining transfusion throughout Europe. Methods: We did a prospective observational cohort study enrolling 5803 patients in 126 European centres that received at least one pRBC unit intraoperatively, during a continuous three month period in 2013. Results: The overall intraoperative transfusion rate was 1.8%; 59% of transfusions were at least partially initiated as a result of a physiological transfusion trigger- mostly because of hypotension (55.4%) and/or tachycardia (30.7%). Haemoglobin (Hb)- based transfusion trigger alone initiated only 8.5% of transfusions. The Hb concentration [mean (sd)] just before transfusion was 8.1 (1.7) g dl-1 and increased to 9.8 (1.8) g dl-1 after transfusion. The mean number of intraoperatively transfused pRBC units was 2.5 (2.7) units (median 2). Conclusions: Although European Society of Anaesthesiology transfusion guidelines are moderately implemented in Europe with respect to Hb threshold for transfusion (7-9 g dl-1), there is still an urgent need for further educational efforts that focus on the number of pRBC units to be transfused at this threshold