CRAFTing Delivery of Membrane Proteins into Protocells using Nanodiscs

For the successfulgenerativeengineeringof functionalartificialcells,a convenientandcontrollablemeansof deliveringmembraneproteinsinto membranelipidbilayersis necessary.Herewereporta deliverysystemthatachievesthis by employingmembraneprotein-carryingnanodiscsandthecalcium-dependentfusionofphosphatidylserinelipidmembranes.We showthat lipidnanodiscscanfuse a transportedlipidbilayerwith the lipidbilayersof smallunilamellarvesicles(SUVs)or giantunilamellarvesicles(GUVs)whileavoidingrecipientvesiclesaggregation.Thisis triggeredby a simple,transientincreasein calciumconcentration,whichresultsin efficientand rapidfusionin a one-potreaction.Furthermore,nanodiscscan be loadedwithmembraneproteinsthatcan be deliveredintotargetSUVor GUVmembranesin a detergent-independentfashionwhileretainingtheirfunctionality.Nanodiscshavea provenabilityto carrya widerangeof membraneproteins,controltheiroligomericstate,and arehighlyadaptable.Giventhis, our approachmay be the basisfor the developmentof usefultoolsthat will allowbespokedeliveryofmembraneproteinsto protocells,equippingthemwith the cell-likeabilityto exchangematerialacrossouter/subcellularmembranes

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Os registros conventuais como fonte para a história econômica: Aproximações metodológicas a partir do caso de Santa Fé (Argentina), 1700-1850

Objetivo/contexto: El artículo pone el foco en una problemática común a la historia económica de América Latina preestadística: la carestía de fuentes y las dificultades metodológicas para estudiar la evolución de los niveles de vida en el largo plazo. Metodología: Se parte para ello de un estudio de caso, la ciudad de Santa Fe, un enclave comercial del Río de la Plata tardocolonial, donde se asentaron cuatro órdenes religiosas desde el siglo XVII. Se exponen series seculares (1700-1850) de precios de dos alimentos básicos (yerba mate y azúcar), elaboradas a partir de libros contables de conventos, con la intención de demostrar las ventajas y las dificultades que presenta esta fuente para el estudio de los hábitos de consumo, la evolución de los precios de los alimentos y de las condiciones de vida en determinados ámbitos urbanos de la época colonial. La presentación incluye comparaciones de los precios en distintos conventos a lo largo del período, y se discuten específicamente las dificultades para la construcción de índices ponderados. Originalidad: Si bien se trata de una fuente ampliamente utilizada por la literatura académica que analizó el período, nunca se habían realizado comparaciones específicas entre las contabilidades de las distintas órdenes religiosas, en particular para una ciudad periférica del Virreinato del Río de la Plata. Conclusiones: Los resultados obtenidos no sólo muestran la utilidad de la fuente, sino también evidencian las dificultades que existen para la construcción de series que permitan analizar niveles de vida en el largo plazo. Alertan en este sentido sobre la necesidad de estudiar detalladamente las particularidades de cada caso antes de realizar grandes comparaciones internacionales.Objective/context: This article focuses on a problem common to the pre-statistical economic history of Latin America: the scarcity of sources and the methodological difficulties in studying the evolution of standards of living over time. Methodology: We begin with a case study done on the city of Santa Fe, a commercial enclave of the late-colonial Río de la Plata, where four religious orders had settled since the 17th century. Long-term records (1700-1850) from accounting books of convents, which included prices of two basic foodstuffs (yerba mate and sugar), are shown in order to demonstrate the advantages and difficulties of using this source in studying habits of consumption, the evolution of food prices and living conditions in certain urban areas of the colonial era. The exposition includes comparisons of the prices in different convents throughout the period, and specifically discusses the challenges in constructing the weighted indexes. Originality: Although these records are widely used by the academic literature analyzing this period, no specific comparisons had been made between the accounts of the different religious orders, particularly for a peripheral city of the Viceroyalty of the Río de la Plata. Conclusions: The final results show not only the usefulness of the source, but also the difficulties in constructing long run series to analyze living standards. Specific and detailed case studies are useful tools in order to improve broad international comparisons.Objetivo/contexto: O artigo coloca o foco numa problemática comum à história econômica da América Latina do período pré-estatístico: a falta de fontes e as dificuldades metodológicas para estudar a evolução dos níveis de vida a longo prazo. Metodologia: Para isso, parte-se de um estudo de caso: a cidade de Santa Fé, uma estratégica praça comercial do Rio da Prata no período colonial tardio, onde desde o século XVII se instalaram quatro ordens religiosas desde o século XVII. Apresentam-se séries seculares (1700-1850) de preços de dois alimentos básicos (erva-mate e açúcar), elaboradas a partir de livros contábeis de conventos, com a intenção de demonstrar as vantagens e as dificuldades que essa fonte apresenta para o estudo dos hábitos de consumo, da evolução dos preços dos alimentos e das condições de vida em determinados âmbitos urbanos da época colonial. O estudo inclui comparações dos preços em diferentes conventos ao longo do período e analisa vários quesitos que devem ser atendidos na construção de índices ponderados. Originalidade: Apesar de ser uma fonte amplamente utilizada pela literatura acadêmica que analisou o período, nunca foram realizadas comparações específicas entre as contabilidades das diferentes ordens religiosas, em particular para uma cidade periférica do Vice-reinado do Rio da Prata. Conclusões: Os resultados obtidos não somente mostram a utilidade da fonte, mas também evidenciam as dificuldades que existem para a construção de séries que permitam analisar níveis de vida a longo prazo. Alertam, nesse sentido, sobre a necessidade de estudar detalhadamente as peculiaridades de cada caso antes de realizar grandes comparações internacionais.Fil: Djenderedjian, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Instituto de Historia Argentina y Americana "Dr. Emilio Ravignani". Universidad de Buenos Aires. Facultad de Filosofía y Letras. Instituto de Historia Argentina y Americana "Dr. Emilio Ravignani"; ArgentinaFil: Frid, Carina Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario; ArgentinaFil: Martiren, Juan Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Instituto de Historia Argentina y Americana "Dr. Emilio Ravignani". Universidad de Buenos Aires. Facultad de Filosofía y Letras. Instituto de Historia Argentina y Americana "Dr. Emilio Ravignani"; Argentin

Concepts for the Development of Person-Centered, Digitally Enabled, Artificial Intelligence–Assisted ARIA Care Pathways (ARIA 2024)

Abstract The traditional healthcare model is focused on diseases (medicine and natural science) and does not acknowledge patients' resources and abilities to be experts in their own lives based on their lived experiences. Improving healthcare safety, quality, and coordination, as well as quality of life, is an important aim in the care of patients with chronic conditions. Person-centered care needs to ensure that people's values and preferences guide clinical decisions. This paper reviews current knowledge to develop (1) digital care pathways for rhinitis and asthma multimorbidity and (2) digitally enabled, person-centered care.1 It combines all relevant research evidence, including the so-called real-world evidence, with the ultimate goal to develop digitally enabled, patient-centered care. The paper includes (1) Allergic Rhinitis and its Impact on Asthma (ARIA), a 2-decade journey, (2) Grading of Recommendations, Assessment, Development and Evaluation (GRADE), the evidence-based model of guidelines in airway diseases, (3) mHealth impact on airway diseases, (4) From guidelines to digital care pathways, (5) Embedding Planetary Health, (6) Novel classification of rhinitis and asthma, (7) Embedding real-life data with population-based studies, (8) The ARIA-EAACI (European Academy of Allergy and Clinical Immunology) strategy for the management of airway diseases using digital biomarkers, (9) Artificial intelligence, (10) The development of digitally enabled, ARIA person-centered care, and (11) The political agenda. The ultimate goal is to propose ARIA 2024 guidelines centered around the patient to make them more applicable and sustainable.info:eu-repo/semantics/publishedVersio

Concepts for the Development of Person-Centered, Digitally Enabled, Artificial Intelligence–Assisted ARIA Care Pathways (ARIA 2024)

Funding Information: This work has received funding from ARIA (Allergic Rhinitis and its Impact of Asthma); CATALYSE (Climate Action To Advance HeaLthY Societies in Europe), the European Union\u2019s Horizon Europe research and innovation program under grant agreement no. 101057131; FRAUNHOFER Institute for Translational Medicine and Pharmacology (ITMP), Immunology and Allergology, Berlin, Germany; University of Porto, Portugal; and MASK-air, which has been supported by EU grants (Impact of air Pollution on Asthma and Rhinitis [POLLAR] project of the European Institute of Innovation and Technology Health; Structural and Development Funds, R\u00E9gion Languedoc Roussillon and Provence-Alpes-C\u00F4te d\u2019Azur; Twinning, European Innovation Partnership on Active and Healthy Ageing, DG Sant\u00E9 and DG Connect); educational grants from Mylan-Viatris, Allergologisk Laboratorium K\u00F8benhavn, GlaxoSmithKline, Novartis, Stallerg\u00E8nes-Greer, and Noucor; and funding from Breathing Together Onlus Association (Associazione Respiriamo Insieme Onlus), Italy; Esp\u00EDritu Santo University, Samborond\u00F3n, Ecuador; Finnish Anti-Tuberculosis Association Foundation and Tampere Tuberculosis Foundation; GA 2 LEN; German Allergy Society AeDA (\u00C4rzteverband Deutscher Allergologen); IPOKRaTES (International Postgraduate Organization for Knowledge transfer, Research and Teaching Excellent Students) Lithuania Fund; Polish Society of Allergology (POLSKIE TOWARZYSTWO ALLERGOLOGICZNE); and University of Li\u00E8ge, Belgium. Funding Information: Conflicts of interest: J. Bousquet reports personal fees from Cipla, Menarini, Mylan, Novartis, Purina, Sanofi-Aventis, Teva, Noucor, other from KYomed-Innov, and other from Mask-air-SAS, outside the submitted work. M. Blaiss reports personal fees from Sanofi, personal fees from Regeneron, personal fees from ALK, personal fees from Merck, personal fees from AstraZeneca, personal fees from GSK, personal fees from Prollergy, personal fees from Lanier Biotherapeutics, and nonfinancial support from Bryn Phama, outside the submitted work. J. Lity\u0144ska reports personal fees from Evidence Prime Sp. z o.o., outside the submitted work. T. Iinuma reports grants from Sanofi, outside the submitted work. P. Tantilipikorn reports grants from Abbott, other from GSK, and other from Sanofi Aventis, outside the submitted work. T. Haahtela reports personal fees from Orion Pharma, outside the submitted work. Publisher Copyright: © 2024 The AuthorsThe traditional healthcare model is focused on diseases (medicine and natural science) and does not acknowledge patients’ resources and abilities to be experts in their own lives based on their lived experiences. Improving healthcare safety, quality, and coordination, as well as quality of life, is an important aim in the care of patients with chronic conditions. Person-centered care needs to ensure that people's values and preferences guide clinical decisions. This paper reviews current knowledge to develop (1) digital care pathways for rhinitis and asthma multimorbidity and (2) digitally enabled, person-centered care.1 It combines all relevant research evidence, including the so-called real-world evidence, with the ultimate goal to develop digitally enabled, patient-centered care. The paper includes (1) Allergic Rhinitis and its Impact on Asthma (ARIA), a 2-decade journey, (2) Grading of Recommendations, Assessment, Development and Evaluation (GRADE), the evidence-based model of guidelines in airway diseases, (3) mHealth impact on airway diseases, (4) From guidelines to digital care pathways, (5) Embedding Planetary Health, (6) Novel classification of rhinitis and asthma, (7) Embedding real-life data with population-based studies, (8) The ARIA-EAACI (European Academy of Allergy and Clinical Immunology) strategy for the management of airway diseases using digital biomarkers, (9) Artificial intelligence, (10) The development of digitally enabled, ARIA person-centered care, and (11) The political agenda. The ultimate goal is to propose ARIA 2024 guidelines centered around the patient to make them more applicable and sustainable.proofinpres

Concepts for the development of person-centred, digitally-enabled, Artificial Intelligence-assisted ARIA care pathways (ARIA 2024)

The traditional healthcare model is focused on diseases (medicine and natural science) and does not acknowledge patients' resources and abilities to be experts in their own life based on their lived experiences. Improving healthcare safety, quality and coordination, as well as quality of life, are important aims in the care of patients with chronic conditions. Person-centred care needs to ensure that people's values and preferences guide clinical decisions. This paper reviews current knowledge to develop (i) digital care pathways for rhinitis and asthma multimorbidity and (ii) digitally-enabled person-centred care (1). It combines all relevant research evidence, including the so-called real-world evidence, with the ultimate goal to develop digitally-enabled, patient-centred care. The paper includes (i) Allergic Rhinitis and its Impact on Asthma (ARIA), a two-decade journey, (ii) Grading of Recommendations, Assessment, Development and Evaluation (GRADE), the evidence-based model of guidelines in airway diseases, (iii) mHealth impact on airway diseases, (iv) from guidelines to digital care pathways, (v) embedding Planetary Health, (vi) novel classification of rhinitis and asthma, (vi) embedding real-life data with population-based studies, (vii) the ARIA-EAACI strategy for the management of airway diseases using digital biomarkers, (viii) Artificial Intelligence, (ix) the development of digitally-enabled ARIA Person-Centred Care and (x) the political agenda. The ultimate goal is to propose ARIA 2024 guidelines centred around the patient in order to make them more applicable and sustainable

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe