Collaborative research in myositis-related disorders: MIHRA, a global shared community model.

Myositis International Health and Research Collaborative Alliance (MIHRA) is a newly formed purpose-built non-profit charitable research organization dedicated to accelerating international clinical trial readiness, global professional and lay education, career development and rare disease advocacy in IIM-related disorders. In its long form, the name expresses the community's scope of engagement and intent. In its abbreviation, MIHRA, conveys linguistic roots across many languages, that reflects the IIM community's spirit with meanings such as kindness, community, goodness, and peace. MIHRA unites the global multi-disciplinary community of adult and pediatric healthcare professionals, researchers, patient advisors and networks focused on conducting research in and providing care for pediatric and adult IIM-related disorders to ultimately find a cure. MIHRA serves as a resourced platform for collaborative efforts in investigator-initiated projects, consensus guidelines for IIM assessment and treatment, and IIM-specific career development through connecting research networks.MIHRA's infrastructure, mission, programming and operations are designed to address challenges unique to rare disease communities and aspires to contribute toward transformative models of rare disease research such as global expansion and inclusivity, utilization of community resources, streamlining ethics and data-sharing policies to facilitate collaborative research. Herein, summarises MIHRA operational cores, missions, vision, programming and provision of community resources to sustain, accelerate and grow global collaborative research in myositis-related disorders.

Myositis-specific antibodies and clinical characteristics in patients with autoimmune inflammatory myopathies: reported by the Argentine Registry of Inflammatory Myopathies of the Argentine Society of Rheumatology.

INTRODUCTION/OBJECTIVES: To describe clinical features in patients with inflammatory myopathies (IMs) from the Argentine Registry of Inflammatory Myopathies, and their relationship with myositis-specific antibodies (MSAs). METHODS: This cross-sectional study included 360 adult patients with dermatomyositis (DM), polymyositis (PM), and inclusion body myositis. Demographics, clinical, and serological characteristics were retrospectively recorded (2016-2019). MSAs were determined by immunoblotting. Patients who were positive for anti-Jo-1, Mi-2, and MDA5 were compared against a group of patients, taken as reference group, who were negative for all MSAs. RESULTS: Women 72%, median age at diagnosis was 47.3 years (18-82). The most frequent subtypes were DM (43.9%) followed by PM (30%).The most frequent MSAs were anti-Jo-1 (51/317), 16.1%; MDA5 (12/111), 10.8%, and Mi-2 (23/226), 10.2%. Anti-Jo-1 was associated (p < 0.05) with a higher frequency of chronic disease course, interstitial lung disease (ILD), arthritis, and mechanic's hands. Anti-Mi-2 was found in patients who had higher frequency of skin manifestations and higher CK values (p < 0.001). Patients with anti-MDA5 had normal or low CK levels. Anti-MDA5 was associated (p < 0.05) with skin manifestations, arthritis, and ILD. The rest of MSAs had frequencies lower than 8%. Anti-TIF1ϒ was found in eight DM patients and one had cancer. Anti-SRP was found in seven patients who had PM and elevated CK. CONCLUSION: Anti-Jo-1 was the most frequent MSA, and was associated with ILD; MDA5 was associated with CADM and ILD, and Mi-2, with classical DM. Despite the different prevalence with respect to other cohorts, the clinical characteristics for each MSA group were similar to the data reported in other studies. Key Points • This study describes the prevalence of MSAs in the Argentine Registry of IMs. • Anti-Jo-1 and anti-MDA5 were associated with ILD. • Anti-Mi-2 was the third most frequent MSA, associated with classical DM.

Métodos de diagnóstico en el estudio de las Miopatías Inflamatorias Autoinmunes: Datos del Registro Argentino de Miopatías Inflamatorias de la Sociedad Argentina de Reumatología / Diagnostic methods in the study of Inflammatory Myopathies. Data from the Argentine Register: Argentine Rheumatology Society

Las Miopatías Inflamatorias Autoinmunes (MI) comprenden un grupo de enfermedades heterogéneas con presentación y características clínicas variables. Se distinguen subtipos clínicos como Polimiositis (PM), Dermatomiositis (DM), Miositis por cuerpos de Inclusión (MCI), Miopatía Necrotizante Inmunomediada (MNIM), Miositis de los Síndromes de Superposición, formas juveniles de MI (DMJ), Síndrome Antisintetasa (SAS) y Miopatía Asociada a Cáncer (MAC). La presencia de anticuerpos séricos y el infiltrado inflamatorio en la biopsia de músculo sugiere que se trata de una condición autoinmune. Realizar el diagnóstico de las MI suele ser un desafío y las herramientas diagnósticas no siempre están disponibles en la práctica diaria. Se obtuvo información sobre la disponibilidad de estos métodos del Registro Argentino de Miopatías Inflamatorias. El estudio de enzimas musculares, Anticuerpos Antinucleares (ANA), anticuerpo anti-Jo-1 y la tomografía computada de tórax, estuvieron disponibles para la mayoría de los pacientes mientras que la Resonancia Magnética de musculo (RM), el estudio de difusión de monóxido de carbono (DLco) y la biopsia muscular se realizaron en menos del 50% de los casos. La determinación de otros anticuerpos específicos de miositis, de importancia en el diagnóstico y pronóstico de la enfermedad se realizó, en mayor parte, a través de un subsidio de la SAR.

The Idiopathic Inflammatory Myopathies (IIM) comprise a heterogeneous group of acquired muscle diseases classified as polymyositis (PM), dermatomyositis (DM), Inclusion Body Myositis (IBM), Immuno Mediated Necrotizing Myopathies (IMNM), Overlap Myositis (OM), juvenile myositis, Antisynthethase Syndrome (ASS) and cancer related myositis (CAM). The presence of myositis specific antibodies in the serum and autoantibodies against target antigens and inflammatory infiltrates in muscle tissue suggests the autoimmune condition of the disease. The diagnosis of inflammatory myopathies is often a challenge and the disposal of diagnostic tools are not always available in daily practice. Information on the accessibility of these methods was obtained from the Argentine Register of Myopathies. The study of muscle enzymes, ANA, anti-Jo-1 antibodies and chest tomography were easy to get to most patients while muscle MRI, lung diffusion capacity for carbon monoxide (DLco) and muscle biopsy were performed in less than 50% of cases. Other myositis specific antibodies, necessary for disease diagnosis and prognosis, were mostly done through a subsidy from the Argentine Rheumatology Society.

Métodos de diagnóstico en el estudio de las Miopatías Inflamatorias Autoinmunes: Datos del Registro Argentino de Miopatías Inflamatorias de la Sociedad Argentina de Reumatología / Diagnostic methods in the study of myopathies Inflammatory Autoimmune: Data from the Argentine Registry of Inflammatory Myopathies of the Argentine Society of Rheumatology

Las Miopatías Inflamatorias Autoinmunes (MI) comprenden un grupo de enfermedades heterogéneas con presentación y características clínicas variables. Se distinguen subtipos clínicos como Polimiositis (PM), Dermatomiositis (DM), Miositis por cuerpos de Inclusión (MCI), Miopatía Necrotizante Inmunomediada (MNIM), Miositis de los Síndromes de Superposición, formas juveniles de MI (DMJ), Síndrome Antisintetasa (SAS) y Miopatía Asociada a Cáncer (MAC).La presencia de anticuerpos séricos y el infiltrado inflamatorio en la biopsia de músculo sugiere que se trata de una condición autoinmune. Realizar el diagnóstico de las MI suele ser un desafío y las herramientas diagnósticas no siempre están disponibles en la práctica diaria. Se obtuvo información sobre la disponibilidad de estos métodos del Registro Argentino de Miopatías Inflamatorias. El estudio de enzimas musculares, Anticuerpos Antinucleares (ANA), anticuerpo anti-Jo-1 y la tomografía computada de tórax, estuvieron disponibles para la mayoría de los pacientes mientras que la Resonancia Magnética de musculo (RM), el estudio de difusión de monóxido de carbono (DLco) y la biopsia muscular se realizaron en menos del 50% de los casos. La determinación de otros anticuerpos específicos de miositis, de importancia en el diagnóstico y pronóstico de la enfermedad se realizó, en mayor parte, a través de un subsidio de la SAR.

The Idiopathic Inflammatory Myopathies (IIM) comprise a heterogeneous group of acquired muscle diseases classified as polymyositis (PM), dermatomyositis (DM), Inclusion Body Myositis(IBM), ImmunoMediated Necrotizing Myopathies, (IMNM), Overlap Myositis(OM), juvenile myositis, Antisynthethase Syndrome (ASS) and cancer related myositis(CAM).The presence of myositis specific antibodies in the serum and autoantibodies against target antigens and inflammatory infiltrates in muscle tissue suggests the autoimmune condition of the disease. The diagnosis of inflammatory myopathies is often a challenge and the disposal of diagnostic tools are not always available in daily practice. Information on the accessibility of these methods was obtained from the Argentine Register of Myopathies. The study of muscle enzymes, ANA, anti-Jo-1 antibodies and chest tomography were easy to get to most patients while muscle MRI, lung diffusion capacity for carbon monoxide (DLco%) and muscle biopsy were performed in less than 50% of cases. Other myositis specific antibodies, necessary for disease diagnosis and prognosis, were mostly done through a subsidy from the Argentine Rheumatology Society.

Changing rate of serious infections in biologic-exposed rheumatoid arthritis patients. Data from South American registries BIOBADABRASIL and BIOBADASAR.

OBJECTIVE: Most reports on serious infections (SI) in rheumatoid arthritis (RA) patients treated with biological disease-modifying antirheumatic drugs (bDMARDs) are from the USA and Western Europe. Data from other regions are largely missing. We report data from South American countries with different backgrounds and health-care systems but similar registries. METHODS: We merged 2010-2016 data from two registries, BIOBADABRASIL (Brazil) and BIOBADASAR (Argentina), which share the same protocol, online platform and data monitoring process. Patients with active RA were included when they began the first bDMARD or a conventional synthetic DMARD (csDMARD, control group). The SI incidence rate (IR) per 1000 patient/years and adjusted IR ratio (aIRR) were estimated for bDMARDs and csDMARDs. RESULTS: Data were analysed for 3717 RA patients with an exposure of 13,380 patient/years. The 2591 patients treated with bDMARDs (64% tumour necrosis factor-α inhibitors (TNFi)) had a follow-up of 9300 years, and the 1126 treated with csDMARDs had an exposure of 4081 patient/years. The SI IR was 30.54 (CI 27.18-34.30) for all bDMARDs and 5.15 (CI 3.36-7.89) for csDMARDs. The aIRR between the two groups was 2.03 ([1.05, 3.9] p = 0.034) for the first 6 months of treatment but subsequently increased to 8.26 ([4.32, 15.76] p < 0.001). The SI IR for bDMARDs decreased over time in both registries, dropping from 36.59 (28.41-47.12) in 2012 to 7.27 (4.79-11.05) in 2016. CONCLUSION: While SI remains a major concern in South American patients with RA treated with bDMARDs, a favourable trend toward a reduction was observed in the last years.Key Points• New comprehensive data on biologic drugs safety from international collaboration in South America.• First proposal for national registries data merging in South America.• Serious infections remain a major concern in RA patients treated with biologics.• A significant reduction of serious infections in RA patients exposed to biologics was observed over a 7 years period.

Adherencia al tratamiento en pacientes con artritis reumatoidea / Adherence to treatment in patients with rheumatoid arthritis

Objetivo: Este estudio se propone evaluar el cumplimiento del tratamiento farmacológico en pacientes con AR e identificar los factores que pueden afectar al mismo. Materiales y métodos: Estudio observacional, analítico, transversal. Se realizaron encuestas a 176 pacientes de la base de datos, seleccionados al azar de un centro privado especializado en Reumatología ubicado en el conurbano sur de la provincia de Buenos Aires (Instituto Médico CER - Quilmes). Entre septiembre de 2015 y julio de 2016 fueron realizadas de manera telefónica por voluntarios no médicos de la Fundación Articular entrenados a tal fin. Se utilizaron los cuestionarios BAM, CQR19 y se indagó la percepción del paciente sobre su grado de adhesión al tratamiento dividiéndolo en dos grupos: cumplimiento total o cumplimiento parcial/nulo. Se recabaron datos sociodemográficos, estado de enfermedad, tratamiento, comorbilidades y hábitos. Se utilizaron las siguientes pruebas estadísticas: ANOVA de un factor para evaluar diferencias en niveles medios de CQR19 y variables cualitativas; prueba de Brown-Forsythe para determinar asociación entre CRQ y diversas variables, correlación no paramétrica Rho de Spearman entre CQR19 y variables cuantitativas y regresión logística para explicar adherencia al tratamiento (CQR19 agrupada). Los datos fueron analizados usando el programa SPSS (versión 19.0). Resultados: El 85,8% eran mujeres y la edad promedio fue de 55,1 años. El 51,1% de los pacientes considera que su salud es buena con relación a la AR y el 40,9% considera que es regular. El tratamiento más frecuente fue MTX oral (79%). La monoterapia fue la modalidad terapéutica más referida (79,5%) y el tiempo medio de tratamiento es de 4,4 años. La actitud de los pacientes hacia los medicamentos mostró acuerdo en los 5 ítems que corresponden a la dimensión necesidad del BAM. El nivel de acuerdo-desacuerdo resultó más heterogéneo en los ítems de la dimensión preocupación. CQR19 mostró alto nivel de acuerdo en la mayor parte de los ítems positivos y alto nivel de desacuerdo en la mayor parte de los ítems negativos. Las únicas variables que se asociaron a mayor CQR fueron la presencia de comorbilidades (Brown-Forsythe=7,960; p=0,005) y medicación concomitante (Brown-Forsythe=7,529; p=0,007). También se encontró asociación significativa entre CRQ19 y tabaquismo (F=0,019; p=0,981). Se observó correlación significativa entre CQR y BAM Específico-Necesidad (Rho=0,379; p <0,001) y entre CQR y BAM Específico-Preocupación (Rho=-0,188; p=0,012). Se observó mayor adherencia cuando el paciente siente la necesidad de cumplir con la medicación (O.R.=1,342; p=0,012) y cuando menos preocupado está por la misma (O.R.=0,870; p=0,047). Detectamos menor cumplimiento del tratamiento en pacientes casados o que viven en pareja (Chi²=7,448; p=0,024) y con mayor nivel educativo (Chi²=6,313; p=0,043). Cuando se evalúa el cumplimiento de la medicación prescrita por indagación directa a los pacientes, el nivel de cumplimiento es más elevado. Conclusión: Se trata de una población con nivel moderado de adherencia. Mayor conciencia de necesidad de medicación y menor nivel de preocupación acerca de la misma generan mayor adherencia. Los pacientes sobreestiman el cumplimiento de la medicación cuando se los interroga de manera directa por lo cual es mandatorio utilizar otro método de evaluación. El mayor conocimiento de la adherencia de los pacientes con AR nos permitirá desarrollar herramientas que mejoren este aspecto a largo plazo.

Objective: This study aims to evaluate the compliance of pharmacological treatment in patients with RA and identify the factors that may affect it. Materials and methods: Observational, analytical and cross-sectional study. Surveys were conducted on 176 randomly selected patients from a private center specialized in Rheumatology located in the southern suburbs of the province of Buenos Aires (CER Medical Institute - Quilmes), between September 2015 and July 2016, by telephone by trained non-medical volunteers of the Articular Foundation. The BAM, CQR19 questionnaires were used and the patient's perception of their degree of adherence to the treatment was investigated, dividing it into two groups: total compliance or partial/no compliance. Sociodemographic data, disease status, treatment, comorbidities and habits were collected. The following statistical tests were used: one-way ANOVA to evaluate differences in mean levels of CQR19 and qualitative variables; Brown-Forsythe test to determine the association between CRQ and various variables, non-parametric Spearman's Rho correlation between CQR19 and quantitative variables and logistic regression to explain adherence to treatment (CQR19 grouped). The data was analyzed using the SPSS program (version 19.0). Results: 85.8% were women and the average age was 55.1 years. 51.1% of patients consider that their health is good in relation to RA and 40.9% consider it to be fair. The most frequent treatment was oral MTX (79%). Monotherapy was the most referred therapeutic modality (79.5%) and the mean treatment time is 4.4 years. The attitude of the patients towards the medicines showed agreement in the 5 items that correspond to the dimension of necessity of the BAM. The level of agreement-disagreement was more heterogeneous in the items of the concern dimension. CQR19 showed a high level of agreement in most of the positive items and a high level of disagreement in most of the negative items. The only variables that were associated with higher CQR were the presence of comorbidities (Brown-Forsythe=7.960, p=0.005) and concomitant medication (Brown-Forsythe=7.529, p=0.007). There was also a significant association between CRQ19 and smoking (F=0.019, p=0.981). Significant correlation was observed between CQR and BAM Specific-Necessity (Rho=0.379, p <0.001) and between CQR and BAM Specific-Concern (Rho=-0.188; p=0.012). Greater adherence was observed when the patient felt the need to comply with the medication (O.R.=1.342, p=0.012) and when least concerned about it (O.R.=0.870, p=0.047). We detected less compliance with treatment in married patients or those living with a partner (Chi²=7.448, p=0.024) and with a higher educational level (Chi²=6.313, p=0.043). When the compliance of the prescribed medication is evaluated by direct inquiry to the patients, the level of compliance is higher. Conclusion: It is a population with a moderate level of adherence. Greater awareness of the need for medication and a lower level of concern about it generate greater adherence. Patients overestimate medication compliance when they are interrogated directly, which is why it is mandatory to use another evaluation method. The greater knowledge of the adherence of patients with RA will allow us to develop tools that improve this aspect in the long term.

Evaluación infectológica inicial y seguimiento prospectivo de una cohorte de pacientes sometidos a inmunosupresión inducida / Initial assessment and prospective follow-up of a cohort of patients with immunosuppressive therapy by an infectious diseases physician

El uso de inmunosupresores generó una población creciente de pacientes con defectos en el sistema inmune. Creamos un consultorio especializado en la atención infectológica de dichos pacientes. Objetivos: Describir los antecedentes clínicos y la prevalencia de infecciones latentes, evaluar el estado de vacunación, determinar la necesidad de profilaxis antimicrobiana. Describir la frecuencia de aparición infecciones oportunistas (IO). Materiales y métodos: estudio descriptivo, prospectivo de pacientes atendidos en un consultorio que estuvieran bajo tratamiento inmunosupresor (noviembre 2015-enero 2017). Se recolectaron datos demográficos, clínicos y factores de riesgo para IO. Se realizó pesquisa de tuberculosis (TB), serologías para HIV, hepatitis A, B y C, sífilis, toxoplasmosis, Chagas, búsqueda de Strongyloides spp. Se indicaron vacunas de acuerdo con las recomendaciones actuales. Se realizó seguimiento para detección de IO. Resultados: n=197, media de edad 50,7 años (DE 14), mujeres 79,7%. Enfermedades de base: artritis reumatoidea 52%, lupus 12%. Drogas inmunosupresoras: metotrexato 45%, corticoides 16%, biológicos anti-TNF 15%, micofenolato 10%, ciclofosfamida 4%. Se diagnosticaron 49 (25%) infecciones: 15 Chagas, 15 anti-HBc positivo aislado, 7 sífilis, 4 HIV, 4 TB latentes, 2 HBV, 1 HCV, 1 estrongiloidiosis. Se indicó profilaxis antimicrobiana en 27 (14%) pacientes. En todos se intervino indicando o completando los esquemas de vacunación. Se detectaron 7 IO. Conclusiones: En el 39% de los pacientes, la evaluación sistematizada arrojó hallazgos que motivaron intervenciones, ya sea terapéuticas o de monitoreo. En el 100% fue necesaria la prescripción de vacunas. Esto pone en evidencia la importancia de evaluar sistemáticamente en consultorios especializados a estos pacientes

Introduction: The extensive use of immunosuppressive drugs resulted in a growing population of patients with defects in the immune system. We opened an infectious diseases practice focused on the attention of these patients. Our objectives were to describe the clinical history and prevalence of latent infections, evaluate the vaccination status, determine the need for antimicrobial prophylaxis and describe the frequency of opportunistic infections (OI). Methods: We performed a descriptive and prospective study of patients seen at a medical practice who were under immunosuppressive therapy (November 2015-January 2017). Demographic and clinical history, as well as risk factors for OI were collected. Tuberculosis (TB) screening, serologies for HIV, hepatitis A, B and C, syphilis, toxoplasmosis, Chagas and Strongyloides spp. screening were performed. Vaccines were indicated according to current recommendations. Follow-up was performed for IO detection. Results: n=197. Mean age: 50.7 years (SD 14). Female 79.7%. Underlying diseases: rheumatoid arthritis 52%, 12% lupus. Immunosuppressive drugs: methotrexate 45%, corticoids 16%, biological anti-TNF agents 15%, mycophenolate 10%, cyclophosphamide 4%. Forty-nine (25%) infections were diagnosed: 15 Chagas, 15 anti-HBc positive isolated, 7 syphilis, 4 HIV, 4 latent TB, 2 HBV, 1 HCV, 1 strongyloidiosis. Antimicrobial prophylaxis was indicated in 27 (14%) patients. In all cases, vaccination schemes were indicated or completed. Seven IO were detected. Conclusions: In 39% of the patients, the systematized evaluation revealed findings that motivated interventions, either therapeutic or monitoring. In 100% the prescription of vaccines was necessary. These findings highlight the importance of a systematically evaluation of these patients in specialized care centers.

Counterion Size and Nature Control Structural and Mechanical Response in Cellulose Nanofibril Nanopapers.

Nanopapers formed from aqueous dispersions of cellulose nanofibrils (CNFs) combine stiffness, strength, and toughness. Yet, delicate interactions operate between the CNFs during nanopaper formation and mechanical deformation. We unravel in detail how counterions, being either of the organic alkyl ammonium kind (NR4+) or of the earth metal series (Li+, Na+, Cs+), need to be chosen to achieve outstanding combinations of stiffness, strength, and toughness, extending to previously unreached territories. We relate structure formation processes in terms of colloidal stabilization to nanostructural details such as porosity and ability for swelling, as well as to interfibrillar interactions in bulk and macroscale mechanical properties. We demonstrate that our understanding also leads to new levels of ductility in bioinspired CNF/polymer nanocomposites at high levels of reinforcements. These results contribute to future rational design of CNF-based high-performance materials.

Understanding Toughness in Bioinspired Cellulose Nanofibril/Polymer Nanocomposites.

Cellulose nanofibrils (CNFs) are considered next generation, renewable reinforcements for sustainable, high-performance bioinspired nanocomposites uniting high stiffness, strength and toughness. However, the challenges associated with making well-defined CNF/polymer nanopaper hybrid structures with well-controlled polymer properties have so far hampered to deduce a quantitative picture of the mechanical properties space and deformation mechanisms, and limits the ability to tune and control the mechanical properties by rational design criteria. Here, we discuss detailed insights on how the thermo-mechanical properties of tailor-made copolymers govern the tensile properties in bioinspired CNF/polymer settings, hence at high fractions of reinforcements and under nanoconfinement conditions for the polymers. To this end, we synthesize a series of fully water-soluble and nonionic copolymers, whose glass transition temperatures (Tg) are varied from -60 to 130 °C. We demonstrate that well-defined polymer-coated core/shell nanofibrils form at intermediate stages and that well-defined nanopaper structures with tunable nanostructure arise. The systematic correlation between the thermal transitions in the (co)polymers, as well as its fraction, on the mechanical properties and deformation mechanisms of the nanocomposites is underscored by tensile tests, SEM imaging of fracture surfaces and dynamic mechanical analysis. An optimum toughness is obtained for copolymers with a Tg close to the testing temperature, where the soft phase possesses the best combination of high molecular mobility and cohesive strength. New deformation modes are activated for the toughest compositions. Our study establishes quantitative structure/property relationships in CNF/(co)polymer nanopapers and opens the design space for future, rational molecular engineering using reversible supramolecular bonds or covalent cross-linking.

Bioinspired Mechanical Gradients in Cellulose Nanofibril/Polymer Nanopapers.

Mechanical gradients are important as tough joints, for strain field engineering in printable electronics, for actuators, and for biological studies, yet they are difficult to prepare and quantitatively characterize. We demonstrate the additive fabrication of gradient bioinspired nanocomposites based on stiff, renewable cellulose nanofibrils that are bottom-up toughened via a tailor-made copolymer. Direct filament writing of different nanocomposite hydrogels in patterns, and subsequent healing of the filaments into continuous films while drying leads to a variety of linear, parabolic and striped bulk gradients. In situ digital image correlation under tensile deformation reveals important differences in the strain fields regarding asymmetry and step heights of the patterns. We envisage that merging top-down and bottom-up structuring of nanocellulose hybrids opens avenues for aperiodic and multiscale, bioinspired nanocomposites with optimized combinations of stiffness and toughness.

Supramolecular Engineering of Hierarchically Self-Assembled, Bioinspired, Cholesteric Nanocomposites Formed by Cellulose Nanocrystals and Polymers.

Natural composites are hierarchically structured by combination of ordered colloidal and molecular length scales. They inspire future, biomimetic, and lightweight nanocomposites, in which extraordinary mechanical properties are in reach by understanding and mastering hierarchical structure formation as tools to engineer multiscale deformation mechanisms. Here we describe a hierarchically self-assembled, cholesteric nanocomposite with well-defined colloid-based helical structure and supramolecular hydrogen bonds engineered on the molecular level in the polymer matrix. We use reversible addition-fragmentation transfer polymerization to synthesize well-defined hydrophilic, nonionic polymers with a varying functionalization density of 4-fold hydrogen-bonding ureidopyrimidinone (UPy) motifs. We show that these copolymers can be coassembled with cellulose nanocrystals (CNC), a sustainable, stiff, rod-like reinforcement, to give ordered cholesteric phases with characteristic photonic stop bands. The dimensions of the helical pitch are controlled by the ratio of polymer/CNC, confirming a smooth integration into the colloidal structure. With respect to the effect of the supramolecular motifs, we demonstrate that those regulate the swelling when exposing the biomimetic hybrids to water, and they allow engineering the photonic response. Moreover, the amount of hydrogen bonds and the polymer fraction are decisive in defining the mechanical properties. An Ashby plot comparing previous ordered CNC-based nanocomposites with our new hierarchical ones reveals that molecular engineering allows us to span an unprecedented mechanical property range from highest inelastic deformation (strain up to ∼13%) to highest stiffness (E ∼ 15 GPa) and combinations of both. We envisage that further rational design of the molecular interactions will provide efficient tools for enhancing the multifunctional property profiles of such bioinspired nanocomposites.

Percepción de la AR en una población fuera del ámbito sanitario / Perception of RA in a population outside health services

Objetivos: El acceso temprano a la población de pacientes con artritis reumatoidea (AR) a la asistencia especializada es un predictor de buen pronóstico. Sin embargo, la demora en la consulta es una constante; fueron identificados factores tales como los vinculados al paciente, el médico generalista o al sistema de salud. El objeto del estudio fue el de explorar la percepción de la población fuera del ámbito asistencial en un escenario potencial de sintomatología compatible con AR. Material y métodos: Se realizó un muestreo aleatorio de 1073 individuos mayores de 18 años, se realizó en la vía pública de los partidos de Quilmes y Berazategui. La encuesta fue efectuada por voluntarias entrenadas a tal fin las que indagaron acerca de a qué profesional consultaría si tuviera dolor e inflamación de los nudillos y muñecas de ambas manos, si cree padecer estos síntomas y si conoce la diferencia entre artritis y artrosis. Resultados: Frente a la posibilidad de padecer síntomas que remedan AR, la población encuestada eligió a los siguientes especialistas: traumatólogo (61%), clínico (17%), reumatólogo (15%), otros (7%). Un tercio de los encuestados refirió padecer esos síntomas y la mayoría (61%) referían no conocer la diferencia entre artritis y artrosis. Quienes más eligieron al reumatólogo como opción (56%) fueron del sexo femenino de entre 51 y 80 años y que conocían la diferencia entre AR y OA. Conclusiones: La ausencia relativa del reumatólogo en la preferencia de la población encuestada, así como la confusión respecto de la presencia de sintomatología compatible con la enfermedad o de la diferencia entre artritis y artrosis señalan la necesidad de ejecutar campañas de concientización pública dirigidas a la reafirmación de la especialidad frente a la patología articular inflamatoria.

Objectives: Early access to specialized care is a predictor of goodprognosis in patients recently diagnosed rheumatoid arthritis (RA).However, the delay in the consultation is a constant; they wereidentified factors such as those related to the patient, the generalpractitioner or the health system. The purpose of the study wasto explore the perception of the population outside the healthcaresetting in a potential scenario of symptoms compatible with RA.Material and methods: A random sample of 1073 individualsaged 18 and over was conducted. It was held in public matches ofQuilmes and Berazategui. The survey was conducted by volunteerstrained for this purpose which were asked which professional (interms of specialty) would consult if they had pain and swellingof the knuckles and wrists of both hands, and "if you know thedifference between arthritis and osteoarthritis".Results: Facing the possibility of having symptoms that mimic RA,the population surveyed chose the following specialists: orthopedicsurgeons (61%), clinicians (17%), rheumatologists (15%), others(7%). A third of respondents have referred these symptoms and most(61%) reported not knowing the difference between arthritis andosteoarthritis. People who chose rheumatologist an option (56%)were female between 51 and 80 years and knew the differencebetween RA and OA.Conclusions: The relative absence of rheumatologist in thepreference of the surveyed population, as well as confusion aboutthe presence of symptoms compatible with the disease or thedifference between arthritis and osteoarthritis indicate the needto implement public awareness campaigns aimed at reaffirmingspecialty against inflammatory joint disease.

Hierarchical Nacre Mimetics with Synergistic Mechanical Properties by Control of Molecular Interactions in Self-Healing Polymers.

Designing the reversible interactions of biopolymers remains a grand challenge for an integral mimicry of mechanically superior biological composites. Yet, they are the key to synergistic combinations of stiffness and toughness by providing sacrificial bonds with hidden length scales. To address this challenge, dynamic polymers were designed with low glass-transition temperature T(g) and bonded by quadruple hydrogen-bonding motifs, and subsequently assembled with high-aspect-ratio synthetic nanoclays to generate nacre-mimetic films. The high dynamics and self-healing of the polymers render transparent films with a near-perfectly aligned structure. Varying the polymer composition allows molecular control over the mechanical properties up to very stiff and very strong films (E≈45 GPa, σ(UTS)≈270 MPa). Stable crack propagation and multiple toughening mechanisms occur in situations of balanced dynamics, enabling synergistic combinations of stiffness and toughness. Excellent gas barrier properties complement the multifunctional property profile.

Humidity and multiscale structure govern mechanical properties and deformation modes in films of native cellulose nanofibrils.

Nanopapers formed by stiff and strong native cellulose nanofibrils are emerging as mechanically robust and sustainable materials to replace high-performance plastics or as flexible, transparent and "green" substrates for organic electronics. The mechanical properties endowed by nanofibrils crucially depend on mastering structure formation processes and on understanding interfibrillar interactions as well as deformation mechanisms in bulk. Herein, we show how different dispersion states of cellulose nanofibrils, that is, unlike tendencies to interfibrillar aggregation, and different relative humidities influence the mechanical properties of nanopapers. The materials undergo a humidity-induced transition from a predominantly linear elastic behavior in dry state to films displaying plastic deformation due to disengagement of the hydrogen-bonded network and lower nanofibrillar friction at high humidity. A concurrent loss of stiffness and tensile strength of 1 order of magnitude is observed, while maximum elongation stays near constant. Scanning electron microscopy imaging in plastic failure demonstrates pull-out of individual nanofibrils and bundles of nanofibrils, as well as larger mesoscopic layers, stemming from structures organized on different length scales. Moreover, multiple yielding phenomena and substantially increased elongation in strongly disengaged networks, swollen in water, show that strain at break in such nanofibril-based materials is coupled to relaxation of structural entities, such as cooperative entanglements and aggregates, which depend on the pathway of material preparation. The results demonstrate the importance of controlling the state of dispersion and aggregation of nanofibrils by mediating their interactions, and highlight the complexity associated with understanding hierarchically structured nanofibrillar networks under deformation.