Molecular Donor-Acceptor Dyads for Single-Material Organic Solar Cells.

A series of ambipolar covalently linked oligothiophene-fullerene dyads have been synthesized by systematical structural variations. In this respect, the length of linker between donor and acceptor unit was altered and in a second series the terminal acceptor units in the donor unit of the dyads were varied. Characterization of the optical and redox properties gave valuable structure-property relationships and were correlated to the photovoltaic performance in single-material organic solar cells, in which power conversion efficiencies of up to 4.3 % were reached.

Advanced Acceptor-Substituted S,N-Heteropentacenes for Application in Organic Solar Cells.

Ambifunctional heterpentacenes with the heteroatom sequence SSNSS in the ladder-type backbone were used either as donor or as nonfullerenic acceptor in solution-processed bulk-heterojunction solar cells. Different acceptor moieties and side chains were inserted. Synthesis and characterization of the systematically varied structural motifs provided insight in structure-property relationships. Moreover, a dimeric heteroacene was synthesized, and the optoelectronic properties were compared to those of its monomeric counterpart.

Broadly Applicable Synthesis of Arylated Dithieno[3,2-b:2',3'-d]pyrroles as Building Blocks for Organic Electronic Materials.

A novel and versatile method for the N-arylation of dithieno[3,2-b:2',3'-d]pyrrole (DTP) is presented. By Pd- or Cu-catalyzed coupling a variety of arenes and acenes were directly attached at the DTP-nitrogen yielding a variety of functionalized DTPs. Investigations on optical and redox properties led to valuable structure-property relationships, which were corroborated by quantum chemical calculations. Further functionalization and elongation of the conjugation of an acceptor-substituted DTP was elaborated to result in complex cruciform-type donor-acceptor oligomers, which were investigated and implemented in single material organic solar cells.

Angioimmunoblastic T cell lymphoma: an unusual presentation of posttransplant lymphoproliferative disorder in a pediatric patient.

Posttransplant lymphoproliferative disorders (PTLD) are a potentially life-threatening complication of immunosuppression in transplant recipients. The majority of cases are Epstein-Barr virus-associated lesions of B cell origin. T cell PTLD is rare, particularly in pediatric patients. We present an unusual case of monomorphic T cell PTLD with features of angioimmunoblastic T cell lymphoma in an 8-year-old heart transplant patient, presenting with cranial nerve palsy.

Value of follow-up diagnostic radioiodine scans in differentiated thyroid cancer.

Background: The most important part of the follow-up of differentiated thyroid carcinoma (DTC) is the measurement of serum thyroglobulin (Tg). An increase of Tg levels indicates likely tumor recurrence. According to the guidelines of the European Society of Medical Oncology (ESMO), the follow-up should consist of serum Tg assays and a neck ultrasound, while the American Thyroid Association (ATA) recommends serum Tg assays, neck ultrasounds, and a diagnostic radioiodine whole-body scan (WBS) if non-stimulated Tg is greater than 10 ng/mL or if Tg is rising. This study questions the necessity of a diagnostic WBS in patients with low stimulated Tg levels during the initial follow-up. Design: This study is a retrospective data analysis. Methods: The data of 185 patients, who were in regular treatment and aftercare between 2015 and 2018 at the Department of Nuclear Medicine in Vienna, as well as the data of 185 patients who were treated in Tbilisi between 2015 and 2019, were analyzed. Results: There was a highly significant relationship between low stimulated Tg levels (<0.5 ng/mL) and the outcome of the diagnostic WBS at the first follow-up (χ 2 = 14.7, P < 0.001). In total, 31 out of 370 patients (8.4%) had positive findings in the diagnostic WBS. Seventy-five of 370 patients (19.74%) had stimulated Tg levels >0.5 ng/mL. Conclusion: Our data suggest that the first follow-up, 4-12 months after the initial therapy of DTC, including the measurement of basal and stimulated Tg levels and Tg antibody levels, does not mandate a diagnostic WBS on all patients. Significance statement: In this study, we examined the still commonly used routine diagnostic radioiodine whole-body scan in the first follow-up of patients with differentiated thyroid carcinoma. We questioned the necessity of the scan in patients with low stimulated thyroglobulin levels. Therefore, we combined retrospective data from the University Hospital in Vienna and in Tbilisi to analyze 370 patients. We were able to demostrate a highly significant relationship between low stimulated thyroglobulin levels (<0.5 ng/mL) and the outcome of the diagnostic scan at the first follow-up (χ = 14.7, P < 0.001).

Implications of the COVID-19 Pandemic on the Family Structural Dimensions: A Correlational Study.

The COVID-19 pandemic caused changes in the families' social support network, employment status, and family income, which are the focus of attention of family health nurses. This study aims to describe the pandemic's repercussions in the areas of attention of the structural dimension of families according to the Dynamic Model of Family Assessment and Intervention, as perceived by Portuguese families, and to relate the changes in their employment status according to the variables of the structural dimension. A quantitative, descriptive, and correlational study was conducted using snowball sampling. A questionnaire of sociodemographic characterization and assessment of the family structural dimension according to the model's operational matrix was applied to 235 family members. Changes were found in their employment status; family income; intensity and frequency of contact with family, friends, and coworkers; frequency of contact with educational/health/religious institutions and community groups; cultural activities; and housing comfort conditions such as the use of heating/air conditioning, gas, and water consumption. Changes in employment status were related to family income, interaction with friends, frequency of cultural activities, and use of air conditioning and heating. Knowing the implications of the pandemic on the family's structural dimension results in a nursing intervention more focused on family needs.

Validation of the Demand Control Support Questionnaire for European Portuguese.

Background: The Demand Control Support model is useful for studying work-related stress. The combination of high demand and a low level of control generates "job strain" ("job iso-strain" if poor support is added), with implications for the worker's health and well-being. The aims of this study were to adapt, examine the factor structure of, and determine the reliability of, the Demand Control Support Questionnaire (DCSQ) short version for European Portuguese (DCSQ-PT). Methods: The scale was translated into Portuguese following a rigorous process and then applied to 501 workers from various professional sectors. An online survey was used to collect sociodemographic, professional, and Demand Control Support data. Validation was based on reliability and validity tests. Results: The mean age of the sample was 41.8 ± 10.3 years, and 50.1% of the participants were female. The results reveal good reliability (Cronbach's alpha = 0.807) and validity. Confirmatory factor analyses demonstrated that a four-factor solution of the DCSQ-PT scale had a good fit to the data, as was the case for the original scale. The DCSQ-PT© with 16 items is composed of the following factors: social support at work; psychological demands; skill discretion; and decision authority. Conclusions: This validation allows an instrument to be obtained with 16 items for studying work-related stress in Portuguese workers.

Introdução: O Demand Controle Support Model é indicado para estudar o stress relacionado com o trabalho. A combinação de um alto nível de exigência laboral com um baixo nível de controle e suporte, geram "tensão laboral", com implicações para a saúde e bem-estar dos trabalhadores. Os objetivos deste estudo foram adaptar, avaliar a estrutura fatorial e determinar a fidelidade da versão breve da escala Demand Control Support Questionnaire (DCSQ-PT) para português europeu. Método: A escala foi inicialmente traduzida para o português europeu seguindo as guidelines internacionais, sendo posteriormente aplicada a 510 trabalhadores de vários setores de atividade profissional. Os dados foram colhidos através da aplicação online de um questionário, constituído por dados sociodemográficos, profissionais e da escala Demand Control Support Questionnaire (DCSQ-PT). Para a determinação das características psicométricas foram utilizados testes de consistência interna e de analise fatorial. Resultados: A idade média da amostra foi de 41.8 ± 10.3 anos sendo 50.1% do sexo feminino. Os resultados revelaram boa fiabilidade (Alfa de Cronbach = 0.807) e validade. A análise fatorial confirmatória da escala DCSQ-PT demonstrou uma solução de quatro fatores, semelhante à escala original sendo que os 16 itens da DCSQ-PT© agregam-se nos seguintes fatores: Apoio Social no trabalho; Exigências Psicológicas; Desenvolvimento de Habilidades; Autoridade para a tomada de Decisão. Conclusões: Os resultados permitem afirmar que a escala DCSQ-PT é um instrumento adequado para o estudo do stress de trabalhadores portugueses.

Diagnostic Value of 2-[18F]FDG PET/CT in a Patient with Atypical Subacute Thyroiditis: A Case Report.

BACKGROUND: Positron emission tomography/computed tomography (PET/CT) imaging with 2-deoxy-2-[18F]fluoro-d-glucose (2-[18F]FDG) is a sensitive diagnostic imaging modality in oncology and could be a useful diagnostic tool in patients with fever of unknown origin (FUO) or with inflammation of unknown origin (IUO). CASE PRESENTATION: We report a case of a patient originally presenting with a clinical history of FUO and later with persistent high-sensitivity C-reactive protein (hsCRP) levels, even after antibiotic therapy. The patient underwent 2-[18F]FDG PET/CT to investigate and to localize a possible focus of infection or inflammation. 2-[18F]FDG hotspots were detected in both thyroid lobes. Thyroid diagnostic examinations and follow up were performed. Subacute thyroiditis (SAT) was then diagnosed by thyroid examinations, and other possible causes of FUO or IUO were not found. CONCLUSION: This case illustrates the potential diagnostic value of 2-[18F]FDG PET/CT in patients with atypical SAT, who originally present with only a clinical history of FUO.

Molecular Oligothiophene-Fullerene Dyad Reaching Over 5% Efficiency in Single-Material Organic Solar Cells.

A novel donor-acceptor dyad, 4, in which the conjugated oligothiophene donor is covalently connected to fullerene PC71 BM by a flexible alkyl ester linker, is synthesized and applied as photoactive layer in solution-processed single-material organic solar cells (SMOSCs). Excellent photovoltaic performance, including a high short-circuit current density (JSC ) of 13.56 mA cm-2 , is achieved, leading to a power conversion efficiency of 5.34% in an inverted cell architecture, which is substantially increased compared to other molecular single materials. Furthermore, dyad 4-based SMOSCs display excellent stability maintaining 96% of the initial performance after 750 h (one month) of continuous illumination and operation under simulated AM 1.5G irradiation. These results will strengthen the rational molecular design to further develop SMOSCs for potential industrial application.

Effects of an education program on knowledge and self-perception of school personnel in preparing to care for type 1 diabetes students.

OBJECTIVE: To assess the academic and professional background of school personnel; to assess the impact of the Diabetes + Support given by School Personnel to Children with Type 1 Diabetes Program on the school personnel's knowledge and confidence to support students with type 1 diabetes; to compare their level of knowledge with the academic and professional variables of the school personnel. METHODS: A quasi-experimental pre-test/post-test study design without a Control Group. Study with a sample of 129 (before intervention - T0) and 113 (after intervention - T1) pre-school to secondary school personnel from participating schools, with at least one student with type 1 diabetes. The project was approved by the Ethics Committee of the Portuguese Ministry of Education. RESULTS: Most school personnel included in the study were teachers (51.2%). After training, they were more confident than before to support children with type 1 diabetes (p<0.05). Regarding knowledge levels, the differences between T0 (10.8±2.8; P 50 =11) and T1 (13.7±2.1; P 50 =11) were statistically significant (p<0.001). Of the 113 school personnel who participated in the final assessment, 89 (78.85%) increased their level of knowledge. CONCLUSION: The program was effective to enhance knowledge and boost confidence to support students with diabetes.

Does a febrile reaction to platelets predispose recipients to red blood cell alloimmunization?

BACKGROUND: A variable effect of inflammation on alloimmunization to transfused red blood cells (RBCs) in mice has been recently reported. We investigated whether RBC alloimmunization in humans was affected by transfusion of blood products in temporal proximity to experiencing a febrile transfusion reaction (FTR) to platelets (PLTs), an event predominantly mediated by inflammatory cytokines. STUDY DESIGN AND METHODS: Blood bank databases were used to identify patients who experienced an FTR or possible FTR to PLTs from August 2000 to March 2008 (FTR group). The control group of patients received a PLT transfusion on randomly selected dates without experiencing an FTR. The "event" was defined as the PLT transfusion that caused the FTR in the FTR group or the index PLT transfusion in the control group. The number of transfused blood products and their proximity to the event were recorded along with other recipient data. The primary endpoint was the rate of RBC alloimmunization between the two groups. RESULTS: There were 190 recipients in the FTR group and 245 in the control group. Overall, the recipients in the control group were younger and received more blood products on the day of their event and over the subsequent 10 days. The alloimmunization rate among recipients in the FTR group was higher than in the control group (8% vs. 3%, respectively; p = 0.026). CONCLUSIONS: These preliminary data support our hypothesis that recipient inflammation may affect RBC alloimmunization in humans; however, a more detailed understanding of the pathophysiologic association between inflammation and alloimmunization is required before definitive conclusions can be reached.

A novel mouse model of red blood cell storage and posttransfusion in vivo survival.

BACKGROUND: Storage of red blood cells (RBCs) is necessary for an adequate blood supply. However, reports have identified potential negative sequelae of transfusing stored RBCs. An animal model would be useful to investigate the pathophysiology of transfusing stored RBCs. However, it has been reported that storage of rat RBCs in CPDA-1 resulted in an unexpected sudden decline in posttransfusion survival. A mouse model of RBC storage and transfusion was developed to assess survival kinetics of mouse RBCs. STUDY DESIGN AND METHODS: RBCs expressing green fluorescent protein were collected in CPDA-1, filter leukoreduced, adjusted to a 75% hematocrit, and stored at 4°C. At weekly intervals, stored RBCs were transfused into C57BL/6 recipients. RBC survival was measured by flow cytometry and chromium-51 labeling. Phosphatidylserine externalization and CD47 expression was also evaluated. RESULTS: Mean 24-hour survivals of transfused RBCs were 99, 91, 64, 54, 30, and 18% after 0, 7, 14, 21, 28, and 35 days of storage, respectively. Stored RBCs showed an initial rapid clearance with subsequent extended survival. Increased surface phosphatidylserine and decreased CD47 expression were also observed. CONCLUSIONS: Mouse RBCs showed a progressive decline in survival, as a function of storage time, unlike the precipitous loss of viability reported for rat RBCs. Moreover, changes in the measured surface markers were analogous to trends reported for human RBCs. Together, these findings provide an initial characterization of a novel mouse model of RBC storage with the potential to serve as an experimental platform for studying the pathophysiologic consequences of transfusing stored RBCs.

Test models for the evaluation of immunogenicity of protein aggregates.

Protein aggregates have been discussed for a long time as a potential risk factor for immunogenicity in patients. Meanwhile, many research groups have investigated the immunogenicity of differently produced aggregates using in vitro or in vivo models. Despite all knowledge gained in these studies still little is known about the mechanisms of immunogenicity and the kind of protein aggregates bearing the greatest risk for immunogenicity. The choice of a suitable test model regarding the predictability of immunogenicity of protein aggregates in humans plays a major role and influences results and conclusions substantially. In this review we will provide an overview of the test models recently used for the evaluation of immunogenicity of protein aggregates; we will discuss advantages and drawbacks regarding their usability and predictive power for immunogenicity in humans.

Evaluation of a 3D Human Artificial Lymph Node as Test Model for the Assessment of Immunogenicity of Protein Aggregates.

The immunogenicity of protein aggregates has been investigated in numerous studies. Nevertheless, it is still unknown which kind of protein aggregates enhance immunogenicity the most. The ability of the currently used in vitro and in vivo systems regarding their predictability of immunogenicity in humans is often questionable, and results are partially contradictive. In this study, we used a 2D in vitro assay and a complex 3D human artificial lymph node model to predict the immunogenicity of protein aggregates of bevacizumab and adalimumab. The monoclonal antibodies were exposed to different stress conditions such as light, heat, and mechanical stress to trigger the formation of protein aggregates and particles, and samples were analyzed thoroughly. Cells and culture supernatants were harvested and analyzed for dendritic cell marker and cytokines. Our study in the artificial lymph node model revealed that bevacizumab after exposure to heat triggered a TH1- and proinflammatory immune response, whereas no trend of immune responses was seen for adalimumab after exposure to different stress conditions. The human artificial lymph node model represents a new test model for testing the immunogenicity of protein aggregates combining the relevance of a 3D human system with the rather easy handling of an in vitro setup.

Fatores associados às atitudes dos enfermeiros quanto à importância da família nos cuidados de enfermagem / Factors associated with nurses' attitudes toward the family involvement in nursing care / Factores asociados a las actitudes de los enfermeros respecto a la importancia de la familia en los cuidados de enfermería

Resumo Enquadramento: A participação da família nos cuidados potencia ganhos em saúde, sendo a atitude dos enfermeiros, influenciada por múltiplos fatores. Objetivo: Conhecer as atitudes dos enfermeiros quanto à importância atribuida à integração das famílias nos cuidados e determinar a relação entre essas atitudes e a idade, habilitações académicas, tempo na carreira, categoria profissional, sentido de vida e sintomatologia depressiva/ansiosa dos enfermeiros. Metodologia: Estudo transversal, descritivo-correlacional, realizado com 317 enfermeiros de um Centro Hospitalar da Região Centro de Portugal. Aplicou-se um questionário sociodemográfico, a escala Importância das Famílias nos Cuidados de Enfermagem-Atitudes dos Enfermeiros, o Inventário da Saúde Mental e a Escala dos Objetivos de Vida. Resultados: A maioria dos participantes documenta atitudes integrativas, sendo as correlações da variável em estudo com os fatores associados, coerentes com o esperado. Conclusão: Apesar da maioria dos enfermeiros documentar atitudes inclusivas da família, são os mais velhos, com mais habilitações e tempo na carreira, detentores de categoria profissional mais elevada, com maior extensão de sentido de vida e menor sintomatologia depressiva/ansiosa que mais priorizam o envolvimento da família nos cuidados.

Abstract Background: Family involvement in care increases health gains, and multiple factors influence nurses' attitudes toward family involvement. Objective: To identify nurses' attitudes toward family involvement in care and determine the association between nurses' attitudes and their age, education level, years in the profession, professional category, purpose in life, and symptoms of depression/anxiety. Methodology: Cross-sectional, descriptive-correlational study, carried out 317 nurses from a hospital center in the central region of Portugal. Nurses answered a sociodemographic questionnaire and completed the Families' Importance in Nursing Care-Nurses' Attitudes scale, the Mental Health Inventory, and the Purpose in Life Test. Results: Most participants reported supportive attitudes toward family involvement in care. The correlations between the variable under study and the associated factors were consistent with the expected. Conclusion: Most participants have supportive attitudes toward family involvement in care. Older nurses, with higher education levels, more years in the profession, higher professional category, a higher sense of purpose in life, and fewer symptoms of depression/anxiety attach more importance to family involvement in nursing care.

Resumen Marco contextual: La participación de la familia en los cuidados optimiza los beneficios para la salud y la actitud de los enfermeros hacia esta participación se ve influida por múltiples factores Objetivo: Identificar las actitudes de los enfermeros con respecto a la importancia que conceden a la integración de las familias en los cuidados y determinar la relación entre las actitudes de los enfermeros y su edad, titulación académica, tiempo en la profesión, categoría profesional, sentido de la vida y sintomatología depresiva/ansiedad. Metodología: Estudio transversal, descriptivo-correlacional, que se realizó con 317 enfermeros de un centro hospitalario de la Región Centro de Portugal. Los participantes respondieron a un cuestionario sociodemográfico, a la escala "La Importancia de la Familia en los Cuidados de Enfermería-Actitudes de los Enfermeros", al "Inventario de Salud Mental" y a la "Escala de los Objetivos de Vida". Resultados: La mayoría de los participantes documentan actitudes integradoras de la familia hacia el cuidado y el resultado de las correlaciones de la variable objeto de estudio con los factores asociados es coherente con lo esperado. Conclusión: La mayoría de los participantes mostraron actitudes integradoras hacia la familia en los cuidados de enfermería, y fueron los enfermeros de mayor edad, con más titulación y tiempo en la profesión, mayor categoría profesional, mayores extensiones del sentido de vida y menores índices de sintomatología depresiva/ansiedad los que atribuyeron más importancia a la familia en los cuidados de enfermería.

Tradução, adaptação cultural e validação do Meaning in Suffering Test para português europeu / Translation, cross-cultural adaptation, and validation of the Meaning in Suffering Test for European Portuguese / Traducción, adaptación cultural y validación del Meaning in Suffering Test al portugués europeo

Resumo Enquadramento: As diferenças paradoxais identificadas entre a forma como as pessoas experienciam a dor, independente da sua intensidade, e o sofrimento a ela associado, relacionam-se com os sistemas de crenças e valores. Objetivos: Validar o Meaning in Suffering Test (MIST) para a população portuguesa e determinar as suas características psicométricas. Metodologia: Este estudo apresenta o processo de adaptação transcultural, realizado numa amostra de 187 pessoas com doença reumática músculo-esquelética (DRM), com recurso a questionário sociodemográfico, clínico e o MIST-P. Resultados: A amostra, maioritariamente do sexo feminino, tinha 49,9±12,1 anos. O MIST-P apresenta bons valores de fidelidade (alfa de Cronbach de 0,833). A análise fatorial determinou a organização dos 12 itens em 2 fatores: Sentido e respostas face ao sofrimento e Características subjetivas face ao sofrimento. A escala é estável no tempo (r = 0,844). Conclusão: O MIST-P é válido e fiável para a população portuguesa com DRM, tendo potencial para ser aplicado na investigação e na prática clínica de prevenção, controlo e integração do sofrimento inevitável.

Abstract Background: The paradoxical differences identified between the way people experience pain, regardless of its intensity, and the suffering associated with it relate to value and belief systems. Objective: To validate the Meaning in Suffering Test (MIST) for the Portuguese population and determine its psychometric characteristics. Methodology: This study presents the process of cross-cultural adaptation, carried out on a sample of 187 people with rheumatic and musculoskeletal diseases (RMDs), using a sociodemographic and clinical data questionnaire and the Teste de Sentido no Sofrimento (Portuguese version of the MIST - MIST-P). Results: The sample was mostly composed of women, with a mean age of 49.9±12.1 years. The MIST-P obtained a Cronbach's Alpha of 0.833, meaning a good reliability. The factorial analysis organized the 12 items into two factors: Meaning and responses to suffering and Subjective characteristics in the face of suffering. The scale shows stability over time (r = 0.844). Conclusion: The MIST-P is a valid and reliable tool for the Portuguese population with RMDs and can be applied in research and clinical practices aimed at the prevention, control, and integration of inevitable suffering.

Resumen Marco contextual: Las paradójicas diferencias identificadas entre la forma en que las personas experimentan el dolor, independientemente de su intensidad, y el sufrimiento asociado a este se relacionan con los sistemas de creencias y valores. Objetivos: Validar el Meaning in Suffering Test (MIST) para la población portuguesa y determinar sus características psicométricas. Metodología: Este estudio presenta el proceso de adaptación intercultural, llevado a cabo en una muestra de 187 personas con enfermedad reumática musculoesquelética (ERM), para lo cual se utilizó un cuestionario sociodemográfico, clínico y el MIST-P. Resultados: La muestra, mayoritariamente del sexo femenino, tenía 49,9±12,1 años. El MIST-P presenta buenos valores de fiabilidad (alfa de Cronbach de 0,833). El análisis factorial determinó la organización de los 12 ítems en 2 factores: Sentido y respuestas al sufrimiento y Características subjetivas ante el sufrimiento. La escala es estable a lo largo del tiempo (r = 0,844). Conclusión: El MIST-P es válido y fiable para la población portuguesa con ERM, y tiene el potencial de ser aplicado en la investigación y la práctica clínica para la prevención, el control y la integración del sufrimiento inevitable.

Biodegradable Three-Layered Micelles and Injectable Hydrogels.

Polymeric micelles have found a growing interest as gene vectors due to the serious safety concerns associated with viral vectors. In particular, the cationic polymer polyethylene imine (PEI) has shown relatively high condensation and transfection efficiencies. Additionally, polyethylene glycol (PEG) modification of polymeric gene vectors has dramatically improved their biological properties, including enhanced biocompatibility, prolonged circulation time, and increased bio-distribution. However, PEG grafting of PEI for subsequent condensation of nucleic acids (NAs) does not necessarily result in the formation of a PEI/NAs core with a PEG corona. But often times, the presence of PEG interferes with PEI's electrostatic interaction with NAs. We describe here a facile method to prepare multilayered biodegradable micelles which address some of the critical drawbacks associated with current PEI-based systems. The polyplex micelles have superb stability and stealth properties. Moreover, we describe a method to prepare fully biodegradable and biocompatible injectable hydrogels for use in localized gene therapy.

Folate receptor targeted three-layered micelles and hydrogels for gene delivery to activated macrophages.

New folic acid (FA) coupled three layered micelles (3LM) were designed to encapsulate DNA, and their application as delivery system that specifically targets activated macrophages was investigated for new treatment options in rheumatoid arthritis (RA). FA coupled poly(l-lactide)-b-poly(ethylene glycol) (FA-PEG-PLLA) was synthesized via the NHS-ester activated/amine coupling method. Fluorescein labeled folic acid was used for flow cytometric detection of the expression of functional folic receptor ß in LPS-activated and resting macrophages. FA coupled 3LM were formulated in a two-step procedure and characterized regarding hydrodynamic diameters and zeta potentials. The presence of the targeting ligand was shown not to increase the size of the 3LM compared to their non-targeted counterparts. Targeted and non-targeted 3LM were used in vitro to optimize uptake conditions in the RAW 264.7 macrophage cell line. The amount of FA coupled polymer in the final formulation was found to be optimal at 75% FA-PEG-PLLA and 25% PLLA-PEG-PLLA. Subsequently, transgene expression in vitro in RAW 264.7 cells and ex vivo in primary activated and resting mouse macrophages was determined as a function of FR-mediated internalization of 3LM encapsulating GFP expressing plasmid. FR-overexpressing activated cells, as successfully identified by internalization of FA-fluorescein, showed significantly higher GFP expression in vitro and ex vivo than resting macrophages with only a basal level of FR expression. Lastly, injectable hydrogels as depot formulation were formed by stereocomplexation, and their degradation, DNA release profiles, and dissociation into intact 3LM were found to be beneficial for potential in vivo application. Our findings confirm that FA-3LM are taken up by activated macrophages via folate receptor mediated endocytosis and that their hydrogels release intact 3LM for efficient transfection of primary macrophages. Therefore, FA-3LM could become a promising delivery system for receptor-mediated drug or gene delivery and novel therapy for rheumatoid arthritis in an in situ forming gel formulation.

Three-Layered Biodegradable Micelles Prepared by Two-Step Self-Assembly of PLA-PEI-PLA and PLA-PEG-PLA Triblock Copolymers as Efficient Gene Delivery System.

"Three-layered micelles" (3LM) composed of two triblock copolymers, poly(L-lactide)-b-polyethyleneimine-b-poly(L-lactide) (PLLA-PEI-PLLA) and poly(L-lactide)-b-poly(ethylene glycol)-b-poly(L-lactide) (PLLA-PEG-PLLA) are designed to combine electrostatic interaction and solvent-induced condensation of DNA. The low molecular weight PLLA-PEI-PLLA is synthesized by a facile amine-protection/deprotection approach and employed as a gene vector, compacting DNA as a polyplex core in the organo-micelles. The individual organo-micelle is further encapsulated within a PLLA-PEG-PLLA amphiphilic micelle leading to an aqueous stable colloidal dispersion. The resulting spherical 3LM possess a hydrodynamic diameter of ca. 200 nm and zeta potential close to neutral and display excellent stability to competing polyanions such as dextran sulfate in neutral pH (7.4). Such high stability is attributed to the complete shielding of the PEI/DNA polyplex core with an impermeable hydrophobic intermediate layer. However, greater than 90% of the encapsulated DNA are released within 30 min when exposed to slightly acidic pH (4.5). Based on our findings, a new class of non-viral delivery system for nucleic acids with superb stability and stealth properties is identified.

Effects of an education program on knowledge and self-perception of school personnel in preparing to care for type 1 diabetes students / Efeitos de um programa de educação nos conhecimentos e na autopercepção dos educadores escolares na preparação para cuidar de crianças diabéticas tipo 1

ABSTRACT Objective To assess the academic and professional background of school personnel; to assess the impact of the Diabetes + Support given by School Personnel to Children with Type 1 Diabetes Program on the school personnel's knowledge and confidence to support students with type 1 diabetes; to compare their level of knowledge with the academic and professional variables of the school personnel. Methods A quasi-experimental pre-test/post-test study design without a Control Group. Study with a sample of 129 (before intervention - T0) and 113 (after intervention - T1) pre-school to secondary school personnel from participating schools, with at least one student with type 1 diabetes. The project was approved by the Ethics Committee of the Portuguese Ministry of Education. Results Most school personnel included in the study were teachers (51.2%). After training, they were more confident than before to support children with type 1 diabetes (p<0.05). Regarding knowledge levels, the differences between T0 (10.8±2.8; P 50 =11) and T1 (13.7±2.1; P 50 =11) were statistically significant (p<0.001). Of the 113 school personnel who participated in the final assessment, 89 (78.85%) increased their level of knowledge. Conclusion The program was effective to enhance knowledge and boost confidence to support students with diabetes.

RESUMO Objetivo Avaliar a formação acadêmica e profissional dos educadores escolares; avaliar o impacto do Diabetes + Apoio dado pelo Programa Responsáveis Escolares pelas Crianças com Diabetes Tipo 1 no nível de conhecimento e de confiança dos educadores escolares, para apoiar os alunos com diabetes tipo 1; comparar o nível de conhecimento dos educadores escolares com suas variáveis acadêmicas e profissionais. Métodos Estudo quasi-experimental, do tipo pré-teste/pós-teste sem Grupo Controle, realizado em amostra de 129 (antes da intervenção - T0) e 113 (pós-intervenção - T1) educadores escolares, da pré-escola ao ensino secundário, que trabalhavam em escolas com pelo menos uma criança/jovem com diabetes tipo 1. O projeto foi aprovado pelo Comitê de Ética do Ministério da Educação de Portugal. Resultados A maioria dos educadores escolares incluídos no estudo era professor (51,2%). Após a intervenção, os educadores escolares sentiram-se mais confiantes do que antes, para apoiar crianças com diabetes tipo 1 (p<0,05). Em relação aos níveis de conhecimento, as diferenças entre T0 (10,8±2,8; P50=11) e T1 (13,7±2,1; P50=11) foram estatisticamente significantes (p<0,001). Dos 113 educadores escolares que participaram da avaliação final, 89 (78,85%) aumentaram seu nível de conhecimento. Conclusão O programa foi eficaz para aumentar o conhecimento e a confiança dos educadores escolares para apoiar as crianças/jovens com diabetes tipo 1.