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Four years after the EAT-Lancet landmark report, worldwide movements call for action to reorient food systems to healthy diets that respect planetary boundaries. Since dietary habits are inherently local and personal, any shift toward healthy and sustainable diets going against this identity will have an uphill road. Therefore, research should address the tension between the local and global nature of the biophysical (health, environment) and social dimensions (culture, economy). Advancing the food system transformation to healthy, sustainable diets transcends the personal control of engaging consumers. The challenge for science is to scale-up, to become more interdisciplinary, and to engage with policymakers and food system actors. This will provide the evidential basis to shift from the current narrative of price, convenience, and taste to one of health, sustainability, and equity. The breaches of planetary boundaries and the environmental and health costs of the food system can no longer be considered externalities. However, conflicting interests and traditions frustrate effective changes in the human-made food system. Public and private stakeholders must embrace social inclusiveness and include the role and accountability of all food system actors from the microlevel to the macrolevel. To achieve this food transformation, a new "social contract," led by governments, is needed to redefine the economic and regulatory power balance between consumers and (inter)national food system actors.
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Dieta , Nível de Saúde , Humanos , Alimentos , Biofísica , GovernoRESUMO
Supercontinuum sources based on intrapulse difference frequency generation (IDFG) from mode-locked lasers open new opportunities in mid-infrared gas spectroscopy. These sources provide high power and ultra-broadband spectral coverage in the molecular fingerprint region with very low relative intensity noise. Here, we demonstrate the performance of such a light source in combination with a multipass cell and a custom-built Fourier transform spectrometer (FTS) for multispecies trace gas detection. The light source provides a low-noise, ultra-broad spectrum from 2-11.5 µm with â¼3 W output power, outperforming existing mid-infrared supercontinuum sources in terms of noise, spectral coverage, and output power. This translates to an excellent match for spectroscopic applications, establishing (sub-)ppb sensitivity for molecular hydrocarbons (e.g., CH4, C2H4), oxides (e.g., SO2, NOx), and small organic molecules (e.g., acetone, ethyl acetate) over the spectral range of the supercontinuum source with a measurement time varying from seconds to minutes. We demonstrate a practical application by measuring the off-gas composition of a bioreactor containing an acidic ammonia-oxidizing culture with the simultaneous detection of multiple nitrogen oxides (NO, NO2, N2O, etc.). As the different species absorb various parts of the spectrum, these results highlight the functionality of this spectroscopic system for biological and environmental applications.
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Gold nanoparticles (Au-NPs) are used as catalysts for a diverse range of industrial applications. Currently, Au-NPs are synthesized chemically, but studies have shown that plants fed Au deposit, this element naturally as NPs within their tissues. The resulting plant material can be used to make biomass-derived catalysts. In vitro studies have shown that the addition of specific, short (â¼10 amino acid) peptide/s to solutions can be used to control the NP size and shape, factors that can be used to optimize catalysts for different processes. Introducing these peptides into the model plant species, Arabidopsis thaliana (Arabidopsis), allows us to regulate the diameter of nanoparticles within the plant itself, consequently influencing the catalytic performance in the resulting pyrolyzed biomass. Furthermore, we show that overexpressing the copper and gold COPPER TRANSPORTER 2 (COPT2) in Arabidopsis increases the uptake of these metals. Adding value to the Au-rich biomass offers the potential to make plant-based remediation and stabilization of mine wastes financially feasible. Thus, this study represents a significant step toward engineering plants for the sustainable recovery of finite and valuable elements from our environment.
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Arabidopsis , Ouro , Nanopartículas Metálicas , Ouro/química , Nanopartículas Metálicas/química , Arabidopsis/metabolismo , Catálise , Biomassa , Tamanho da Partícula , Cobre/químicaRESUMO
The cyclic nucleotide cyclic guanosine monophosphate (cGMP) is a powerful cell signaling molecule involved in biotic and abiotic stress perception and signal transduction. In the model plant Arabidopsis thaliana, salt and osmotic stress rapidly induce increase in cGMP which plays role by modulating the activity of monovalent cation transporters, possibly by direct binding to these proteins and by altering the expression of many abiotic stress responsive genes. In a recent study, a membrane permeable analogue of cGMP (8-bromo-cGMP) was found to have a promotive effect on soluble sugar, flavonoids and lignin content, and membrane integrity in Solanum lycopersicum seedlings under salt stress. However, it remains to be elucidated how salt stress affects the endogenous cGMP level in S. lycopersicum and if Br-cGMP-induced improvement in salt tolerance in S. lycopersicum involves altered cation fluxes. The current study was conducted to answer these questions. A rapid increase (within 30 s) in endogenous cGMP level was determined in S. lycopersicum roots after treatment with 100 mM NaCl. Addition of membrane permeable Br-cGMP in growth medium remarkably ameliorated the inhibitory effects of NaCl on seedlings' growth parameters, chlorophyll content and net photosynthesis rate. In salt stressed plants, Br-cGMP significantly decreased Na+ content by reducing its influx and increasing efflux while it improved plants K+ content by reducing its efflux and enhancing influx. Furthermore, supplementation with Br-cGMP improved plant's proline content and total antioxidant capacity, resulting in markedly decreased electrolyte leakage under salt stress. Br-cGMP increased the expression of Na+/H+ antiporter genes in roots and shoots of S. lycopersicum growing under salt stress, potentially enhancing plant's ability to sequester Na+ into the vacuole. The findings of this study provide insights into the mechanism of cGMP-induced salt stress tolerance in S. lycopersicum.
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Solanum lycopersicum , Solanum lycopersicum/genética , Guanosina Monofosfato/metabolismo , Guanosina Monofosfato/farmacologia , Tolerância ao Sal/genética , Cloreto de Sódio/farmacologia , PlântulaRESUMO
Infants' use of pointing gestures to direct and share attention develops during the first 2 years of life. Shyness, defined as an approach-avoidance motivational conflict during social interactions, may influence infants' use of pointing. Recent research distinguished between positive (gaze and/or head aversions while smiling) and non-positive (gaze and/or head aversions without smiling) shyness, which are related to different social and cognitive skills. We investigated whether positive and non-positive shyness in 12-month-old (n = 38; 15 girls) and 15-month-old (n = 45; 15 girls) infants were associated with their production of pointing gestures. Infants' expressions of shyness were observed during a social-exposure task in which the infant entered the laboratory room in their parent's arms and was welcomed by an unfamiliar person who provided attention and compliments. Infants' pointing was measured with a pointing task involving three stimuli: pleasant, unpleasant, and neutral. Positive shyness was positively associated with overall pointing at 15 months, especially in combination with high levels of non-positive shyness. In addition, infants who displayed more non-positive shyness pointed more frequently to direct the attention of the social partner to an unpleasant (vs. neutral) stimulus at both ages. Results indicate that shyness influences the early use of pointing to emotionally charged stimuli.
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Gestos , Timidez , Humanos , Feminino , Masculino , Lactente , Comportamento do Lactente , Desenvolvimento Infantil , Interação Social , AtençãoRESUMO
Inflammation plays a prominent role in the development of atherosclerosis and other cardiovascular diseases, and anti-inflammatory agents may improve cardiovascular outcomes. For years, colchicine has been used as a safe and well-tolerated agent in diseases such as gout and familial Mediterranean fever. The widely available therapeutic has several anti-inflammatory effects, however, that have proven effective in a broad spectrum of cardiovascular diseases as well. It is considered standard-of-care therapy for pericarditis, and several clinical trials have evaluated its role in postoperative and postablation atrial fibrillation, postpericardiotomy syndrome, coronary artery disease, percutaneous coronary interventions, and cerebrovascular disease. We aim to summarize colchicine's pharmacodynamics and the mechanism behind its anti-inflammatory effect, outline thus far accumulated evidence on treatment with colchicine in cardiovascular disease, and present ongoing randomized clinical trials. We also emphasize real-world clinical implications that should be considered on the basis of the merits and limitations of completed trials. Altogether, colchicine's simplicity, low cost, and effectiveness may provide an important addition to other standard cardiovascular therapies. Ongoing studies will address complementary questions pertaining to the use of low-dose colchicine for the treatment of cardiovascular disease.
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Doenças Cardiovasculares/tratamento farmacológico , Colchicina/uso terapêutico , Supressores da Gota/uso terapêutico , Colchicina/farmacologia , Supressores da Gota/farmacologia , HumanosRESUMO
In response to herbivory, many grasses, including crops such as wheat, accumulate significant levels of silicon (Si) as an antiherbivore defence. Damage-induced increases in Si can be localized in damaged leaves or be more systemic, but the mechanisms leading to these differences in Si distribution remain untested. Ten genetically diverse wheat landraces (Triticum aestivum) were used to assess genotypic variation in Si induction in response to mechanical damage and how this was affected by exogenous Si supply. Total and soluble Si levels were measured in damaged and undamaged leaves as well as in the phloem to test how Si was allocated to different parts of the plant after damage. Localized, but not systemic, induction of Si defences occurred, and was more pronounced when plants had supplemental Si. Damaged plants had significant increases in Si concentration in their damaged leaves, while the Si concentration in undamaged leaves decreased, such that there was no difference in the average Si concentration of damaged and undamaged plants. The increased Si in damaged leaves was due to the redirection of soluble Si, present in the phloem, from undamaged to damaged plant parts, potentially a more cost-effective defence mechanism for plants than increased Si uptake.
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Silício , Triticum , Triticum/metabolismo , Silício/metabolismo , Poaceae/metabolismo , Plantas/metabolismo , Herbivoria , Folhas de Planta/metabolismoRESUMO
BACKGROUND: Ibuprofen is a nonsteroidal anti-inflammatory drug that is commonly used to stimulate closure of a patent ductus arteriosus (PDA) in very premature infants and may lead to aberrant neonatal lung development and bronchopulmonary dysplasia (BPD). METHODS: We investigated the effect of ibuprofen on angiogenesis in human umbilical cord vein endothelial cells (HUVECs) and the therapeutic potential of daily treatment with 50 mg/kg of ibuprofen injected subcutaneously in neonatal Wistar rat pups with severe hyperoxia-induced experimental BPD. Parameters investigated included growth, survival, lung histopathology and mRNA expression. RESULTS: Ibuprofen inhibited angiogenesis in HUVECs, as shown by reduced tube formation, migration and cell proliferation via inhibition of the cell cycle S-phase and promotion of apoptosis. Treatment of newborn rat pups with ibuprofen reduced pulmonary vessel density in the developing lung, but also attenuated experimental BPD by reducing lung inflammation, alveolar enlargement, alveolar septum thickness and small arteriolar wall thickening. CONCLUSIONS: In conclusion, ibuprofen has dual effects on lung development: adverse effects on angiogenesis and beneficial effects on alveolarization and inflammation. Therefore, extrapolation of the beneficial effects of ibuprofen to premature infants with BPD should be done with extreme caution.
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Displasia Broncopulmonar , Hiperóxia , Recém-Nascido , Animais , Ratos , Humanos , Ibuprofeno/farmacologia , Ibuprofeno/uso terapêutico , Células Endoteliais/metabolismo , Animais Recém-Nascidos , Ratos Wistar , Pulmão , Displasia Broncopulmonar/tratamento farmacológico , Displasia Broncopulmonar/prevenção & controle , Displasia Broncopulmonar/patologia , Hiperóxia/metabolismoRESUMO
BACKGROUND: The Patient-Reported Outcomes Measurement Information System (PROMIS®) has been recommended for computerized adaptive testing (CAT) of health-related quality of life. This study compared the content, validity, and reliability of seven PROMIS CATs to the 12-item Short-Form Health Survey (SF-12) in patients with advanced chronic kidney disease. METHODS: Adult patients with chronic kidney disease and an estimated glomerular filtration rate under 30 mL/min/1.73 m2 who were not receiving dialysis treatment completed seven PROMIS CATs (assessing physical function, pain interference, fatigue, sleep disturbance, anxiety, depression, and the ability to participate in social roles and activities), the SF-12, and the PROMIS Pain Intensity single item and Dialysis Symptom Index at inclusion and 2 weeks. A content comparison was performed between PROMIS CATs and the SF-12. Construct validity of PROMIS CATs was assessed using Pearson's correlations. We assessed the test-retest reliability of all patient-reported outcome measures by calculating the intraclass correlation coefficient and minimal detectable change. RESULTS: In total, 207 patients participated in the study. A median of 45 items (10 minutes) were completed for PROMIS CATs. All PROMIS CATs showed evidence of sufficient construct validity. PROMIS CATs, most SF-12 domains and summary scores, and Dialysis Symptom Index showed sufficient test-retest reliability (intraclass correlation coefficient ≥ 0.70). PROMIS CATs had a lower minimal detectable change compared with the SF-12 (range, 5.7-7.4 compared with 11.3-21.7 across domains, respectively). CONCLUSION: PROMIS CATs showed sufficient construct validity and test-retest reliability in patients with advanced chronic kidney disease. PROMIS CATs required more items but showed better reliability than the SF-12. Future research is needed to investigate the feasibility of PROMIS CATs for routine nephrology care.
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Qualidade de Vida , Insuficiência Renal Crônica , Humanos , Reprodutibilidade dos Testes , Teste Adaptativo Computadorizado , Inquéritos e Questionários , Diálise Renal , Medidas de Resultados Relatados pelo Paciente , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/terapia , Sistemas de InformaçãoRESUMO
BACKGROUND: In chronic haemodialysis (HD) patients, the relationship between long-term peridialytic blood pressure (BP) changes and mortality has not been investigated. METHODS: To evaluate whether long-term changes in peridialytic BP are related to mortality and whether treatment with HD or haemodiafiltration (HDF) differs in this respect, the combined individual participant data of three randomized controlled trials comparing HD with HDF were used. Time-varying Cox regression and joint models were applied. RESULTS: During a median follow-up of 2.94 years, 609 of 2011 patients died. As for pre-dialytic systolic BP (pre-SBP), a severe decline (≥21 mmHg) in the preceding 6 months was independently related to increased mortality [hazard ratio (HR) 1.61, P = .01] when compared with a moderate increase. Likewise, a severe decline in post-dialytic diastolic BP (DBP) was associated with increased mortality (adjusted HR 1.96, P < .0005). In contrast, joint models showed that every 5-mmHg increase in pre-SBP and post-DBP during total follow-up was related to reduced mortality (adjusted HR 0.97, P = .01 and 0.94, P = .03, respectively). No interaction was observed between BP changes and treatment modality. CONCLUSION: Severe declines in pre-SBP and post-DBP in the preceding 6 months were independently related to mortality. Therefore peridialytic BP values should be interpreted in the context of their changes and not solely as an absolute value.
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Hemodiafiltração , Hipertensão , Humanos , Pressão Sanguínea , Diálise Renal/efeitos adversos , Diálise Renal/métodos , Hemodiafiltração/métodos , Modelos de Riscos ProporcionaisRESUMO
INTRODUCTION: Hyperoxia-induced lung injury is characterized by acute alveolar injury, disrupted epithelial-mesenchymal signaling, oxidative stress, and surfactant dysfunction, yet currently, there is no effective treatment. Although a combination of aerosolized pioglitazone (PGZ) and a synthetic lung surfactant (B-YL peptide, a surfactant protein B mimic) prevents hyperoxia-induced neonatal rat lung injury, whether it is also effective in preventing hyperoxia-induced adult lung injury is unknown. METHOD: Using adult mice lung explants, we characterize the effects of 24 and 72-h (h) exposure to hyperoxia on 1) perturbations in Wingless/Int (Wnt) and Transforming Growth Factor (TGF)-ß signaling pathways, which are critical mediators of lung injury, 2) aberrations of lung homeostasis and injury repair pathways, and 3) whether these hyperoxia-induced aberrations can be blocked by concomitant treatment with PGZ and B-YL combination. RESULTS: Our study reveals that hyperoxia exposure to adult mouse lung explants causes activation of Wnt (upregulation of key Wnt signaling intermediates ß-catenin and LEF-1) and TGF-ß (upregulation of key TGF-ß signaling intermediates TGF-ß type I receptor (ALK5) and SMAD 3) signaling pathways accompanied by an upregulation of myogenic proteins (calponin and fibronectin) and inflammatory cytokines (IL-6, IL-1ß, and TNFα), and alterations in key endothelial (VEGF-A and its receptor FLT-1, and PECAM-1) markers. All of these changes were largely mitigated by the PGZ + B-YL combination. CONCLUSION: The effectiveness of the PGZ + B-YL combination in blocking hyperoxia-induced adult mice lung injury ex-vivo is promising to be an effective therapeutic approach for adult lung injury in vivo.
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Hiperóxia , Lesão Pulmonar , Animais , Camundongos , Hiperóxia/complicações , Hiperóxia/metabolismo , Pulmão , Lesão Pulmonar/etiologia , Lesão Pulmonar/prevenção & controle , Lesão Pulmonar/metabolismo , Pioglitazona/farmacologia , Pioglitazona/metabolismo , PPAR gama/agonistas , PPAR gama/metabolismo , Agonistas PPAR-gama , Tensoativos/metabolismo , Tensoativos/farmacologia , Fator de Crescimento Transformador beta/farmacologiaRESUMO
Public-private partnerships are subject to intense scrutiny. This is specifically the case for sensitive health-related topics such as alcohol consumption. The brewing sector and representatives of the scientific community therefore stressed the need for specific principles for the proper and transparent governance of research and other collaborations between the brewing sector and research entities. At a 1-day seminar, a group of scientists and representatives from the brewing and food sector reached a consensus for such principles. They adhere to the following four fundamental conditions: Freedom of research, Accessibility, Contextualisation and Transparency. The points of focus in the FACT principles are open science, meaning that the methods and results are made accessible and reusable, and relationships are clearly disclosed. Actions to be taken for dissemination and implementation of the FACT Principles are, for instance, publishing them on public websites, including them in formal research agreements, and citing them in scientific publications. Scientific journals and (research) societies are encouraged to support the FACT Principles. In conclusion, the FACT Principles provide a framework for increased transparency and control of funding-related bias in research and other collaborations between the brewing sector and research entities. Monitoring their use and evaluating their impact will help to further refine and enforce the FACT Principles in the future.
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Parcerias Público-PrivadasRESUMO
PURPOSE: Our aim is to advance response shift research by explicating the implications of published syntheses by the Response Shift - in Sync Working Group in an integrative way and suggesting ways for improving the quality of future response shift studies. METHODS: Members of the Working Group further discussed the syntheses of the literature on definitions, theoretical underpinnings, operationalizations, and response shift methods. They outlined areas in need of further explication and refinement, and delineated additional implications for future research. RESULTS: First, the proposed response shift definition was further specified and its implications for the interpretation of results explicated in relation to former, published definitions. Second, the proposed theoretical model was further explained in relation to previous theoretical models and its implications for formulating research objectives highlighted. Third, ways to explore alternative explanations per response shift method and their implications for response shift detection and explanation were delineated. The implications of the diversity of the response shift methods for response shift research were presented. Fourth, the implications of the need to enhance the quality and reporting of the response shift studies for future research were sketched. CONCLUSION: With our work, we intend to contribute to a common language regarding response shift definitions, theory, and methods. By elucidating some of the major implications of earlier work, we hope to advance response shift research.
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Modelos Teóricos , Qualidade de Vida , Humanos , Qualidade de Vida/psicologia , Projetos de PesquisaRESUMO
BACKGROUND: Cognitive behavioral therapy (CBT) is an evidence-based intervention for severe fatigue. Changes in patients' fatigue scores following CBT might reflect not only the intended relief in fatigue but also response shift, a change in the meaning of patients' self-evaluation. Objectives were to (1) identify the occurrence of response shift in patients undergoing CBT, (2) determine the impact of response shift on the intervention effect, and (3) investigate whether changes in fatigue-related cognitions and perceptions, targeted during CBT, are associated with response shift. METHODS: Data of three randomized controlled trials testing the efficacy of CBT in individuals with chronic fatigue syndrome (CFS, n = 222), cancer (n = 123), and diabetes (n = 107) were re-analyzed. Fatigue severity was measured with 8 items from the Checklist Individual Strength, a valid and widely used self-report questionnaire. Structural equation modelling was applied to assess lack of longitudinal measurement invariance, as indication of response shift. RESULTS: As expected, in all three trials, response shift was indicated in the CBT groups, not the control groups. Response shift through reprioritization was indicated for the items "Physically, I feel exhausted" (CFS) and "I tire easily" (cancer, diabetes), which became less vs. more important to the measurement of fatigue, respectively. However, this did not affect the intervention effects. Some changes in cognitions and perceptions were associated with the response shifts. CONCLUSIONS: CBT seems to induce response shift through reprioritization across patient groups, but its occurrence does not affect the intervention effect. Future research should corroborate these findings and investigate whether patients indeed change their understanding of fatigue.
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Terapia Cognitivo-Comportamental , Síndrome de Fadiga Crônica , Humanos , Síndrome de Fadiga Crônica/terapia , Síndrome de Fadiga Crônica/psicologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Inquéritos e Questionários , Autorrelato , Resultado do TratamentoRESUMO
Lung surfactant is a complex mixture of phospholipids and surfactant proteins that is produced in alveolar type 2 cells. It prevents lung collapse by reducing surface tension and is involved in innate immunity. Exogenous animal-derived and, more recently, synthetic lung surfactant has shown clinical efficacy in surfactant-deficient premature infants and in critically ill patients with acute respiratory distress syndrome (ARDS), such as those with severe COVID-19 disease. COVID-19 pneumonia is initiated by the binding of the viral receptor-binding domain (RBD) of SARS-CoV-2 to the cellular receptor angiotensin-converting enzyme 2 (ACE2). Inflammation and tissue damage then lead to loss and dysfunction of surface activity that can be relieved by treatment with an exogenous lung surfactant. Surfactant protein B (SP-B) is pivotal for surfactant activity and has anti-inflammatory effects. Here, we study the binding of two synthetic SP-B peptide mimics, Super Mini-B (SMB) and B-YL, to a recombinant human ACE2 receptor protein construct using molecular docking and surface plasmon resonance (SPR) to evaluate their potential as antiviral drugs. The SPR measurements confirmed that both the SMB and B-YL peptides bind to the rhACE2 receptor with affinities like that of the viral RBD-ACE2 complex. These findings suggest that synthetic lung surfactant peptide mimics can act as competitive inhibitors of the binding of viral RBD to the ACE2 receptor.
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COVID-19 , Surfactantes Pulmonares , Animais , Humanos , SARS-CoV-2 , Enzima de Conversão de Angiotensina 2/química , Simulação de Acoplamento Molecular , Peptídeos , Proteínas Associadas a Surfactantes Pulmonares , Ligação Proteica , Receptores Virais , Surfactantes Pulmonares/farmacologia , TensoativosRESUMO
School absenteeism and its underlying causes can have negative effects on the cognitive, psychosocial and health development of a child. Research in primary education shows high rates of sickness absence. Many stakeholders are involved in addressing school absenteeism, including primary school professionals, child and youth healthcare physicians, school attendance officers and parents. This study explores these stakeholders' perspectives, their approaches and what they envisage to be necessary in order to improve. It also aims to unveil opportunities and challenges in addressing sickness absence among primary school pupils. Qualitative research was performed with six semi-structured focus group interviews and involving 27 participants from the West-Brabant and Amsterdam regions of the Netherlands. Thematic analysis was used. The overarching theme was aiming for the child's wellbeing. Each focus group interview started with low awareness of sickness absence as a threat to this wellbeing, but awareness grew during the interviews. The participating stakeholders regarded problematic sickness absence as complex due to a wide variety of causes, and felt that each other's expertise was necessary to reduce sickness absence. Schools registered absence, but only occasionally used planned steps; they based the identification of problematic sickness on gut feeling rather than any agreed-upon criteria. To be able to systematically address sickness absence and thus improve the wellbeing of children, stakeholders felt the need for a clearly structured approach, including monitoring of sickness absence of all pupils, identifying problematic absence and promoting collaboration with other stakeholders. An approach should allow for tailoring solutions to the individual child.
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Disorders of the long arm of chromosome 11 (11q) are rare and involve various chromosomal regions. Patients with 11q disorders, including Jacobsen syndrome, often present with a susceptibility for bacterial and prolonged viral and fungal infections partially explained by hypogammaglobulinemia. Additional T lymphocyte or granular neutrophil dysfunction may also be present. In order to evaluate infectious burden and immunological function in patients with 11q disorders, we studied a cohort of 14 patients with 11q deletions and duplications. Clinically, 12 patients exhibited prolonged and repetitive respiratory tract infections, frequently requiring (prophylactic) antibiotic treatment (n = 7), ear-tube placement (n = 9), or use of inhalers (n = 5). Complicated varicella infections (n = 5), chronic eczema (n = 6), warts (n = 2), and chronic fungal infections (n = 4) were reported. Six patients were on immunoglobulin replacement therapy. We observed a high prevalence of low B lymphocyte counts (n = 8), decreased T lymphocyte counts (n = 5) and abnormal T lymphocyte function (n = 12). Granulocyte function was abnormal in 29% without a clinical phenotype. Immunodeficiency was found in patients with terminal and interstitial 11q deletions and in one patient with terminal 11q duplication. Genetically, FLI1 and ETS1 are seen as causative for the immunodeficiency, but these genes were deleted nor duplicated in 4 of our 14 patients. Alternative candidate genes on 11q may have a role in immune dysregulation. In conclusion, we present evidence that inborn errors of immunity are present in patients with 11q disorders leading to clinically relevant infections. Therefore, broad immunological screening and necessary treatment is of importance in this patient group.
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Síndromes de Imunodeficiência , Síndrome da Deleção Distal 11q de Jacobsen , Humanos , Síndrome da Deleção Distal 11q de Jacobsen/diagnóstico , Síndrome da Deleção Distal 11q de Jacobsen/genética , Deleção Cromossômica , Aberrações Cromossômicas , Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/genética , Contagem de Linfócitos , Linfócitos T , CromossomosRESUMO
BACKGROUND: Little is known about the impact of timing as opposed to frequency and intensity of daily physical activity on metabolic health. Therefore, we assessed the association between accelerometery-based daily timing of physical activity and measures of metabolic health in sedentary older people. METHODS: Hourly mean physical activity derived from wrist-worn accelerometers over a 6-day period was collected at baseline and after 3 months in sedentary participants from the Active and Healthy Ageing study. A principal component analysis (PCA) was performed to reduce the number of dimensions (e.g. define periods instead of separate hours) of hourly physical activity at baseline and change during follow-up. Cross-sectionally, a multivariable-adjusted linear regression analysis was used to associate the principal components, particularly correlated with increased physical activity in data-driven periods during the day, with body mass index (BMI), fasting glucose and insulin, HbA1c and the homeostatic model assessment for insulin resistance (HOMA-IR). For the longitudinal analyses, we calculated the hourly changes in physical activity and change in metabolic health after follow-up. RESULTS: We included 207 individuals (61.4% male, mean age: 64.8 [SD 2.9], mean BMI: 28.9 [4.7]). Higher physical activity in the early morning was associated with lower fasting glucose (-2.22%, 95% CI: -4.19, -0.40), fasting insulin (-13.54%, 95%CI: -23.49, -4.39), and HOMA-IR (-16.07%, 95%CI: -27.63, -5.65). Higher physical activity in the late afternoon to evening was associated with lower BMI (-2.84%, 95% CI: -4.92, -0.70). Higher physical activity at night was associated with higher BMI (2.86%, 95% CI: 0.90, 4.78), fasting glucose (2.57%, 95% CI: 0.70, 4.30), and HbA1c (2.37%, 95% CI: 1.00, 3.82). Similar results were present in the prospective analysis. CONCLUSION: Specific physical activity timing patterns were associated with more beneficial metabolic health, suggesting particular time-dependent physical activity interventions might maximise health benefits.
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Glicemia , Resistência à Insulina , Idoso , Glicemia/metabolismo , Índice de Massa Corporal , Peso Corporal , Estudos Transversais , Exercício Físico , Feminino , Hemoglobinas Glicadas/análise , Humanos , Insulina/metabolismo , Masculino , Pessoa de Meia-IdadeRESUMO
Human activity and natural processes have led to the widespread dissemination of metals and metalloids, many of which are toxic and have a negative impact on plant growth and development. Roots, as the first point of contact, are essential in endowing plants with tolerance to excess metal(loid) in the soil. The most important root processes that contribute to tolerance are: adaptation of transport processes that affect uptake efflux and long-distance transport of metal(loid)s; metal(loid) detoxification within root cells via conjugation to thiol rich compounds and subsequent sequestration in the vacuole; plasticity in root architecture; the presence of bacteria and fungi in the rhizosphere that impact on metal(loid) bioavailability; the role of root exudates. In this review, we provide details on these processes and assess their relevance on the detoxification of arsenic, cadmium, mercury and zinc in crops. Furthermore, we assess which of these strategies have been tested in field conditions and whether they are effective in terms of improving crop metal(loid) tolerance.
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Arsênio , Metaloides , Metais Pesados , Poluentes do Solo , Arsênio/toxicidade , Produtos Agrícolas , Metais , Rizosfera , Poluentes do Solo/toxicidadeRESUMO
BACKGROUND: Although the number of patients with end-stage kidney disease is growing, the number of patients who perform dialysis at home has decreased during the past two decades. The aim of this study was to explore time trends in the use of home dialysis in the Netherlands. METHODS: Dialysis episodes of patients who started dialysis treatment were studied using Dutch registry data (RENINE). The uptake of home dialysis between 1997 through 2016 was evaluated in time periods of 5 years. Home dialysis was defined as start with peritoneal dialysis or home haemodialysis, or transfer to either within 2 years of dialysis initiation. All analyses were stratified for age categories. Mixed model logistic regression analysis was used to adjust for clustering at patient level. RESULTS: A total of 33 340 dialysis episodes in 31 569 patients were evaluated. Mean age at dialysis initiation increased from 62.5 ± 14.0 to 65.5 ± 14.5 years in in-centre haemodialysis patients, whereas it increased from 51.9 ± 15.1 to 62.5 ± 14.6 years in home dialysis patients. In patients <65 years, the uptake of home dialysis was significantly lower during each 5-year period compared with the previous period, whereas kidney transplantation occurred more often. In patients ≥65 years, the incidence of home dialysis remained constant, whereas mortality decreased. CONCLUSIONS: In patients <65 years, the overall use of home dialysis declined consistently over the past 20 years. The age of home dialysis patients increased more rapidly than that of in-centre dialysis patients. These developments have a significant impact on the organization of home dialysis.