Informação e prevenção não farmacológica da COVID-19 no território de uma unidade de saúde da família em Pernambuco / Information and non-pharmacological prevention of COVID-19 in the territory of a family health unit in Pernambuco / Información y prevención no farmacológica del COVID-19 en el territorio de una unidad de salud de la familia en Pernambuco

Introdução: O conhecimento da magnitude em que a população implementa medidas de proteção emitidas pelas autoridades de saúde pública é essencial na prevenção da doença do novo coronavírus (COVID-19). A eficácia de medidas não farmacológicas de prevenção e das políticas públicas destinadas a reduzir o contágio pela COVID-19 depende de quão bem os indivíduos são informados sobre as consequências da infecção e as medidas que devem adotar para reduzir sua propagação. O entendimento, as atitudes e as práticas das pessoas em relação à COVID-19 e sua prevenção são basilares para a compreensão da dinâmica epidemiológica, demandando a realização de pesquisas sobre o cumprimento de medidas não farmacológicas de prevenção do contágio em diversos territórios. Para isso, em 2020, medidas não farmacológicas contra a COVID-19 foram divulgadas por fontes diversas, estatais e privadas, para a maior parte da população brasileira, com a finalidade de orientar comportamentos para conter a crise sanitária. As equipes da Estratégia Saúde da Família têm um papel fundamental neste processo de educação em saúde, pois compreendem elementos socioculturais das suas comunidades, alcançando-as tanto em capilaridade quanto em adequação local da informação técnico-científica. Este artigo abrange uma pesquisa de campo, parte de um projeto multicêntrico nacional. Objetivo: Avaliar se a população do território de uma unidade da Estratégia Saúde da Família da cidade de Condado-PE entende e aplica as informações que recebeu sobre medidas não farmacológicas de prevenção em suas práticas de proteção contra a COVID-19. Mais especificamente, a pesquisa visou determinar que informações foram recebidas pelos respondentes, quais as suas fontes, o grau de confiabilidade atribuído a estas, além da adesão deles às medidas não farmacológicas e sua relação com variáveis sociodemográficas. Métodos: O modelo do estudo foi observacional e descritivo, com abordagem quantitativa, a partir da coleta de dados primários com 70 usuários por entrevista presencial com questionário estruturado. Resultados: Os resultados mostraram que a população recebeu vasta informação sobre prevenção da doença. Conclusão: Com níveis variados de confiabilidade das fontes, atribuindo importância relevante às medidas de prevenção e adotou a maioria delas, com exceção do isolamento social total.

Introduction: Knowledge of the magnitude to which the population implements protective measures issued by public health authorities is essential in preventing coronavirus disease 2019 (COVID-19). The effectiveness of non-pharmacological prevention measures (NPM) and public policies aimed at reducing the spread of COVID-19 depends on how well individuals are informed about the consequences of the infection and the measures they must adopt to reduce its spread. The understanding, attitudes, and practices of people in relation to COVID-19 and its prevention are fundamental for understanding the epidemiological dynamics, demanding research on compliance with NPM to prevent contagion in different territories. To this end, in 2020, NPM against COVID-19 were released by various sources, state and private, for most of the Brazilian population, with the aim of guiding behaviors to contain the health crisis. The Family Health Strategy (FHS) teams play a key role in this health education process, as they comprise sociocultural elements of their communities, reaching them both in capillarity and in local adequacy of technical-scientific information. This article covers field research, part of a national multicenter project. Objective: To evaluate whether the population of the territory of an FHS unit in the city of Condado, Pernambuco, understands and applies the information it received about NPM prevention in their practices to protect against COVID-19. More specifically, the research aimed to determine what information was received by the respondents, what are their sources, the degree of reliability attributed to these, in addition to their adherence to the NPM and their relationship with sociodemographic variables. Methods: The study model was observational and descriptive, with a quantitative approach, based on the collection of primary data with 70 users through face-to-face interviews with a structured questionnaire. Results: The results showed that the population received extensive information on disease prevention. Conclusion: With varying levels of reliability of the sources, attributing relevant importance to prevention measures and adopted most of them, with the exception of total social isolation.

El conocimiento de la magnitud con la que la población implementa las medidas de protección emitidas por las autoridades de salud pública es fundamental en la prevención de la enfermedad por coronavirus 2019 (COVID-19). La efectividad de las medidas de prevención no farmacológicas (MFN) y de las políticas públicas dirigidas a reducir la propagación de la COVID-19 depende de qué tan bien se informe a las personas sobre las consecuencias de la infección y las medidas que deben adoptar para reducir su propagación. La comprensión, actitudes y prácticas de las personas con relación al COVID-19 y su prevención son fundamentales para comprender la dinámica epidemiológica, exigiendo investigaciones sobre el cumplimiento de las MNF para prevenir el contagio en diferentes territorios. Con ese fin, en 2020, MNF contra el COVID-19 fueron divulgados por diversas fuentes, estatales y privadas, para la mayoría de la población brasileña, con el objetivo de orientar comportamientos para contener la crisis sanitaria. Los equipos de la Estrategia de Salud de la Familia (ESF) juegan un papel fundamental en este proceso de educación en salud, ya que integran elementos socioculturales de sus comunidades, alcanzándolas tanto en la capilaridad como en la adecuación local de la información técnico-científica. Este artículo aborda una investigación de campo, parte de un proyecto multicéntrico nacional, con el objetivo de evaluar si la población del territorio de una unidad de la ESF en la ciudad de Condado-PE comprende y aplica la información recibida sobre la prevención de MNF en sus prácticas de protección contra el COVID -19. Más específicamente, la investigación tuvo como objetivo determinar qué información recibieron los encuestados, cuáles son sus fuentes, el grado de confiabilidad atribuido a estas, además de su adherencia al MNF y su relación con variables sociodemográficas. El modelo de estudio fue observacional y descriptivo, con enfoque cuantitativo, basado en la recolección de datos primarios con 70 usuarios a través de entrevistas cara a cara con un cuestionario estructurado. Los resultados mostraron que la población recibió amplia información sobre prevención de la enfermedad, con diversos niveles de confiabilidad de las fuentes, atribuyendo importancia relevante a las medidas de prevención y adoptando la mayoría de ellas, con excepción del aislamiento social total.

Experiência no uso das ferramentas de abordagem familiar por uma equipe da Estratégia Saúde da Família / Experiencia en el uso de herramientas de abordaje familiar por un equipo de Estrategia de Salud de la Familia / Family Health Strategy team's experience in the use of family approach tools

Problema: Experiência da intervenção de uma equipe multiprofissional da Estratégia Saúde da Família (ESF) em uma família por meio das ferramentas de abordagem familiar. Entre os problemas identificados no caso estão a sobrecarga de trabalho da paciente índice, diagnóstico de Transtorno do Espectro Autista (TEA) nos filhos dela, etilismo crônico do esposo e relacionamento hostil no ciclo familiar. Método: Estudo descritivo, qualitativo, de relato de experiência, desenvolvido em uma família da área de abrangência da equipe da ESF no segundo semestre de 2019, escolhida em razão da hiperutilização do serviço pela paciente índice. As ferramentas aplicadas foram o genograma, ecomapa, Fundamental Interpersonal Relations Outcome (FIRO), problem, roles, affect, communication, time in life, illness, coping with stress, environment/ecology (PRACTICE) e ciclo de vida familiar. Resultados: Com a aplicação das ferramentas foram identificadas as estruturas e modos de compartilhamento das relações familiares, os problemas de saúde presentes, os possíveis vínculos identificados e o estágio no ciclo de vida. Como modos de intervenção, a equipe propôs consultas de cuidado em saúde, assistência psicológica e escutas qualificadas. Além disso, por meio de reuniões intersetoriais, foi solucionado o problema escolar que afetava a condição de saúde da paciente. Conclusão: A aplicação das ferramentas foi um excelente método para realizar o estudo, pois permitiu uma visão global da família, além de identificar fragilidades a serem corrigidas ou minimizadas com recurso a intervenções pela equipe de saúde.

Problem: Intervention experience of a multidisciplinary team of the Family Health Strategy (ESF) through family approach tools. Among the problems identified in the case are the work overload of the index patient, diagnosis of autism spectrum disorder (ASD) in her children, husband's chronic alcoholism and hostile relationship within the family circle. Method: Descriptive and qualitative experience report. Developed by an ESF team in a family in the coverage area. Experience conducted in the second half of 2019. The tools applied were the genogram, ecomap, FIRO, PRACTICE and the family life cycle. The tools were chosen because of the index patient's frequent use of the ESF's services. Results: Through the application of the tools, the structures and ways of sharing family relationships, the health problems, the possible bonds identified and the stage in the life cycle were identified. As modes of intervention, the team proposed health care consultations, psychological assistance and qualified listening. In addition, through intersectional meetings, a school problem that affected the patient's health condition was solved. Conclusion: The application of the tools was an excellent method to carry out the study. It allowed a global view of the family, in addition to identifying weaknesses to be corrected or minimized, through interventions by the health team.

Problema: Experiencia de la intervención de un equipo multidisciplinario de la Estrategia Salud de la Familia (ESF) en una familia a través de herramientas de abordaje familiar. Entre los problemas identificados en el caso están la sobrecarga de trabajo de la paciente índice, diagnóstico de Trastorno del Espectro Autista (TEA) en sus hijos, alcoholismo crónico del marido y relación hostil dentro del ciclo familiar. Método: Estudio descriptivo, cualitativo de relato de experiencia desarrollado en una familia de la zona de cobertura del equipo de la ESF en el segundo semestre de 2019. Las herramientas aplicadas fueron el genograma, ecomapa, F.I.R.O., P.R.A.C.T.I.C.E. y el ciclo de vida familiar, elegido por la sobreutilización del paciente índice de los servicios de la ESF. Resultados: Mediante la aplicación de las herramientas se identificaron las estructuras y formas de compartir las relaciones familiares, los problemas de salud presentes, los posibles vínculos identificados y la etapa del ciclo de vida. Como modos de intervención, el equipo propuso la consulta de salud, la asistencia psicológica y la escucha cualificada. Además, a través de reuniones intersectoriales se solucionó un problema escolar que afectaba el estado de salud del paciente. Conclusión: La aplicación de las herramientas fue un método excelente para la realización del estudio, ya que permitió una visión global de la familia, además de identificar debilidades a ser corregidas o minimizadas, a través de intervenciones del equipo de salud.

Representações sociais sobre o planejamento reprodutivo entre mulheres em gravidez não planejada / Social representations of reproductive planning among women with unplanned pregnancies / Representaciones sociales sobre la planificación reproductiva de las mujeres con embarazo no planificado

Objetivo: conhecer as representações sociais sobre o planejamento reprodutivo entre mulheres em gravidez não planejada na Estratégia Saúde da Família. Método: estudo qualitativo, orientado pela Teoria das Representações Sociais, realizado com 15 gestantes, entre abril e maio de 2019. Utilizou-se a entrevista semiestruturada. Os dados foram organizados por meio do Discurso do Sujeito Coletivo, com auxílio do software DSCsoft©. Protocolo de pesquisa aprovado pelo Comitê de Ética em Pesquisa. Resultados: as representações sociais das mulheres em gravidez não planejada evidenciadas pelo Discurso do Sujeito Coletivo foram representadas por oito ideias centrais, a saber: "eu não me preveni, nem ele", "nós nos prevenimos", "eu comprava", "pegava no posto", "construir uma família", "ter esse acesso", "estou por fora" e "eu sei que é disponível". Conclusão: as representações sociais nos discursos das mulheres em gravidez não planejada estavam pautadas no desconhecimento acerca do planejamento reprodutivo, dos anticoncepcionais disponíveis e seu uso correto.

Objective: to understand the social representations of reproductive planning among women with unplanned pregnancies in the Family Health Strategy. Method: qualitative study, guided by the Theory of Social Representations, carried out with 15 pregnant women between April and May 2019. Semi-structured interviews were used. The data was organized using the Discourse of the Collective Subject, with the aid of DSCsoft© software. Research protocol approved by the Research Ethics Committee. Results: the social representations of women with unplanned pregnancies as evidenced by the Collective Subject Discourse were represented by eight central ideas, namely: "I didn't prevent myself, nor did he", "we prevented ourselves", "I would buy it", "I would get it at the health center", "build a family", "have this access", "I am not aware" and "I know it is available". Conclusion: the social representations in the women's speeches about unplanned pregnancies were based on a lack of knowledge about reproductive planning, the contraceptives available and their correct use.

Objetivo: conocer las representaciones sociales sobre la planificación reproductiva de las mujeres con embarazo no planificado en la Estrategia Salud de la Familia. Método: estudio cualitativo, basado en la Teoría de las Representaciones Sociales, realizado con 15 mujeres embarazadas, entre abril y mayo de 2019. Se utilizaron entrevistas semiestructuradas. Los datos fueron organizados mediante el Discurso del Sujeto Colectivo, con ayuda del software DSCsoft©. El protocolo de investigación fue aprobado por el Comité de Ética en Investigación. Resultados: las representaciones sociales de las mujeres con embarazo no planificado reveladas por el Discurso del Sujeto Colectivo fueron representadas por ocho ideas centrales, a saber: "yo no me cuidé y él tampoco", "nos cuidamos", "yo los compraba", "los buscaba en el centro de salud", "construir una familia", "tener acceso", "no participo" y "sé que está disponible". Conclusión: las representaciones sociales en los discursos de las mujeres con embarazo no planificado se basaron en la falta de conocimiento sobre la planificación reproductiva, en los anticonceptivos disponibles y su uso correcto.

Do the benefits of learning to write a compare-contrast text transfer to other types of writing task? Analysing the effects of strategy-focused instruction / ¿Es posible transferir el aprendizaje de un texto de comparación-contraste a otro tipo de tareas? Análisis de los efectos de la instrucción estratégica

El programa de Instrucción de la Autorregulación Cognitiva (CSRI) se basa en la instrucción centrada en la estrategia e incluye tres componentes para la mejora del producto textual (enseñanza directa, modelado y práctica entre iguales). Se plantearon como objetivosanalizar si la instrucción con el programa CSRI en un género textual (texto de comparación) conducía a la transferencia espontánea en el producto textual (mejor coherencia, estructura y calidad) en un género no instruido (texto de opinión); y examinar si el orden de los componentes instruccionales presentaba algún efecto. Participaron 126 estudiantes de cuarto de educación primaria que fueron asignados a una de las dos condiciones experimentales en las que se aplicaba el programa CSRI (con diferente secuencia de los componentes instructivos), o a una condición de control en la que se seguía la enseñanza tradicional. Los resultados reflejaron que las dos secuencias de instrucción del programa CSRI mostraban beneficios en la estructura y coherencia del producto textual de los estudiantes en el posttest pero no 8 meses después. Para que los alumnos sean capaces de transferir adecuadamente lo aprendido a géneros textuales no instruidos, necesitan que los profesores les enseñen cómo hacerlo eficazmente.(AU)

Cognitive Self-Regulation Instruction (CSRI) program is a strategy-focused instruction with three instructional components for im-proving students’ writing product (direct teaching, modelling, and peer-practice). The present study aimed to explore whether the CSRI program leads to spontaneous transfer, improving the writing product (in terms of quality, structure, and text coherence) of an uninstructed genre (opinion text); and to examine whether the order in which the instructional compo-nents were implemented had an effect. A total of 126 students in their 4thyear of primary school participated in the study. They were randomly as-signed to one of two experimental conditions which received the CSRI but differed in the order the instructional components were delivered, or to a control condition which followed the traditional teaching approach. Our findings show that both CSRI sequences produced benefits in terms of greater structure and coherence of the writing product in the opinion text at post-test but not 8months after the intervention. In consequence, for students to be able to adequately transfer strategies to uninstructed text genres, they need teachers to teach them how to do it effectively.(AU)

"Mid-P strategy" versus "internal target volume strategy in locally advanced non small cell lung cancer: Clinical results from the randomized non-comparative phase II study Mid-P.

BACKGROUND: Locally advanced non-small cell lung cancer (LA-NSCLC) reported poor 5-year survival rates with frequent local or regional recurrences. Personalized RT may contribute to improve control and clinical outcome. We investigated efficacy and tolerance of "Mid-position" (Mid-P) strategy versus the conventional Internal Target Volume (ITV) strategy in LA-NSCLC patients treated by definitive conformal radiotherapy. METHODS: This prospective non-comparative randomized monocentric phase II trial included adult patients with non-resected, non-metastatic, non-previously irradiated proven LA-NSCLC treated with definitive normo-fractionated conformal radiotherapy (+/- chemotherapy). Allocated patients (randomisation 2:1) were treated using Mid-P or ITV strategy. A Fleming single-stage design (1-sided α = 0.1, 80 % power, P0 = 30 %, P1 = 50 %) planned enrolment of 36 patients in the Mid-P group. The ITV group ensured the absence of selection bias. The primary outcome was 1-year progression-free- survival (1y-PFS) rate. RESULTS: Among 54 eligible patients included from September 2012 to May 2018, 51 patients were analyzed (Mid-P: N = 34; ITV: 17). The 1y-PFS was 38 % (1-sided 95 %CI 25 %-not reached) with Mid-P strategy, and 47 % (95 %CI [27 %-not reached[) with ITV. Loco-regional failure as first event mainly occurred within radiation-field regardless the strategy. Acute and middle-term radiation toxicities were observed with both strategies. CONCLUSION: Local control and survival remain poor using the Mid-P strategy in this prospective randomized non-comparative monocentric study investigating Mid-P strategy versus ITV strategy in LA-NSCLC. Since the Mid-P strategy is not integrated into routine software, and perceived as a time-consuming method, Mid-P strategy cannot be recommended in LA-NSCLCC treated by definitive normo-fractionated conformal radiotherapy outside clinical trials.

National-scale antimicrobial resistance surveillance in wastewater: A comparative analysis of HT qPCR and metagenomic approaches.

Wastewater serves as an important reservoir of antimicrobial resistance (AMR), and its surveillance can provide insights into population-level trends in AMR to inform public health policy. This study compared two common high-throughput screening approaches, namely (i) high-throughput quantitative PCR (HT qPCR), targeting 73 antimicrobial resistance genes, and (ii) metagenomic sequencing. Weekly composite samples of wastewater influent were taken from 47 wastewater treatment plants (WWTPs) across Wales, as part of a national AMR surveillance programme, alongside 4 weeks of daily wastewater effluent samples from a large municipal hospital. Metagenomic analysis provided more comprehensive resistome coverage, detecting 545 genes compared to the targeted 73 genes by HT qPCR. It further provided contextual information critical to risk assessment (i.e. potential bacterial hosts). In contrast, HT qPCR exhibited higher sensitivity, quantifying all targeted genes including those of clinical relevance present at low abundance. When limited to the HT qPCR target genes, both methods were able to reflect the spatiotemporal dynamics of the complete metagenomic resistome, distinguishing that of the hospital and the WWTPs. Both approaches revealed correlations between resistome compositional shifts and environmental variables like ammonium wastewater concentration, though differed in their interpretation of some potential influencing factors. Overall, metagenomics provides more comprehensive resistome profiling, while qPCR permits sensitive quantification of genes significant to clinical resistance. We highlight the importance of selecting appropriate methodologies aligned to surveillance aims to guide the development of effective wastewater-based AMR monitoring programmes.

Precision cancer medicine platform trials: Concepts and design of AcSé-ESMART.

Precision cancer medicine brought the promise of improving outcomes for patients with cancer. High-throughput molecular profiling of tumors at treatment failure aims to direct a patient to a treatment matched to the tumor profile. In this way, improved outcome has been achieved in a small number of patients whose tumors exhibit unique targetable oncogenic drivers. Most cancers, however, contain multiple genetic alterations belonging to and of various hallmarks of cancer; for most of these alterations, there is limited knowledge on the level of evidence, their hierarchical roles in oncogenicity, and utility as biomarkers for response to targeted treatment(s). We developed a proof-of-concept trial that explores new treatment strategies in a molecularly-enriched tumor-agnostic, pediatric population. The evaluation of novel agents, including first-in-child molecules, alone or in combination, is guided by the available understanding of or hypotheses for the mechanisms of action of the diverse cancer events. Main objectives are: to determine 1) recommended phase 2 doses, 2) activity signals to provide the basis for disease specific development, and 3) to define new predictive biomarkers. Here we outline concepts, rationales and designs applied in the European AcSé-ESMART trial and highlight the feasibility but also complexity and challenges of such innovative platform trials.

Covalent versus noncovalent attachments of [FeFe]­hydrogenase models onto carbon nanotubes for aqueous hydrogen evolution reaction.

In an effort to develop the biomimetic chemistry of [FeFe]­hydrogenases for catalytic hydrogen evolution reaction (HER) in aqueous environment, we herein report the integrations of diiron dithiolate complexes into carbon nanotubes (CNTs) through three different strategies and compare the electrochemical HER performances of the as-resulted 2Fe2S/CNT hybrids in neutral aqueous medium. That is, three new diiron dithiolate complexes [{(µ-SCH2)2N(C6H4CH2C(O)R)}Fe2(CO)6] (R = N-oxylphthalimide (1), NHCH2pyrene (2), and NHCH2Ph (3)) were prepared and could be further grafted covalently to CNTs via an amide bond (this 2Fe2S/CNT hybrid is labeled as H1) as well as immobilized noncovalently to CNTs via π-π stacking interaction (H2) or via simple physisorption (H3). Meanwhile, the molecular structures of 1-3 are determined by elemental analysis and spectroscopic as well as crystallographic techniques, whereas the structures and morphologies of H1-H3 are characterized by various spectroscopies and scanning electronic microscopy. Further, the electrocatalytic HER activity trend of H1 > H2 ≈ H3 is observed in 0.1 M phosphate buffer solution (pH = 7) through different electrochemical measurements, whereas the degradation processes of H1-H3 lead to their electrocatalytic deactivation in the long-term electrolysis as proposed by post operando analysis. Thus, this work is significant to extend the potential application of carbon electrode materials engineered with diiron molecular complexes as heterogeneous HER electrocatalysts for water splitting to hydrogen.

Digital infrastructure expansion and carbon intensity of small enterprises: Evidence from China.

While the growth of digital infrastructure theoretically offers increased opportunities for enterprises, the policy implications may vary depending on the firm size. We utilize the pilot policy of the Broadband China Strategy as an exogenous shock for firms and adopt a unique dataset from the National Tax Survey to investigate the impact of digital infrastructure expansion on the carbon intensity of small enterprises. The results indicate that digital infrastructure expansion leads to a notable increase of 9.04% in small firm's carbon intensity. These results exhibit resilience, withstanding rigorous testing through various robustness checks. This increase is primarily attributed to two channels: the competition effect, which results in a decline in small firm's output, and the change in energy structure, which leads to an increase in small firm's carbon emissions. Heterogeneity analysis reveals a more pronounced increase for small enterprises located in regions with less stringent environmental regulations and in industries with higher degree of market concentration. Our conclusion suggests that the government should pay attention to the survival and development of small enterprises. This entails ensuring fair market competition on digital platforms and preventing the dominant enterprises from abusing their information advantages to jeopardize the interests of small enterprises.

Spontaneous aggregation-enhanced electrochemiluminescence via galvanic strategy.

Researchers unremittingly strive to develop innovative luminophores to enhance intrinsic electrochemiluminescence (ECL) performance. However, the potential to harness facile strategies, such as manipulating the physical properties of luminophores while retaining functional chemical properties to fabricate cost-effective ECL complexes, remains underexplored. Herein, we reported a novel and efficient one-step galvanic technique to actualize aggregation-enhanced ECL (AEECL) of ruthenium complexes. It marked the first instance of the galvanic process being employed to synthesize aggregate luminophores through electrostatic attraction. The ECL intensity and efficiency of the prepared ruthenium complexes with AEECL properties surpassed traditional ruthenium complexes by 8.9 and 13.6 times, respectively, outperforming most reported luminophores. Remarkably, the target luminophore exhibited high stability across varied scan rates and temperatures. Furthermore, a binder-free and carbon paper-based AEECL analytical device for lidocaine detection was fabricated, achieving a satisfactory detection limit (0.34 nM) and selectivity. The convenient modulation strategy of aggregate structure, along with the transformative leap from insufficient ECL to AEECL, bring forth a new revenue in aggregate science. This research also promises a universally applicable and versatile protocol for future biological analysis and bioimaging applications.

Single-round QuikChange PCR for engineering multiple site-directed mutations in plasmid DNA.

Mutational study is a cornerstone methodology in biochemistry and genetics, and many mutagenesis strategies have been invented to promote the efficiency of gene engineering. In this study, we developed a simple and timesaving approach to integrate simultaneous mutagenesis at discrete sites. By using plasmid as a template and compatible oligonucleotide primers per the QuikChange strategy, our method was able to introduce multiple nucleotide insertions, deletions and replacements in one round of polymerase chain reaction. The longest insertion and deletion were achieved with 28 bp and 16 bp mismatch respectively. For minor nucleotide replacements (mismatch no more than 4 bp), mutations were achieved at up to 4 discrete locations. Usually, a successful clone with all desired mutations was found by screening 5 colonies. Clones with a subset of mutations may be stocked into the library of mutants or used as templates in the next rounds of mutagenic PCR to accomplish the entire construction project. This method can be applied to build up a combinatory library of mutants through saturation mutagenesis at multiple sites. It is promising to facilitate the research of protein biochemistry, forward genetics and synthetic biology.

Regulating Spin Polarization via Axial Nitrogen Traction at Fe-N5 Sites Enhanced Electrocatalytic CO2 Reduction for Zn-CO2 Batteries.

Single Fe sites have been explored as promising catalysts for the CO2 reduction reaction to value-added CO. Herein, we introduce a novel molten salt synthesis strategy for developing axial nitrogen-coordinated Fe-N5 sites on ultrathin defect-rich carbon nanosheets, aiming to modulate the reaction pathway precisely. This distinctive architecture weakens the spin polarization at the Fe sites, promoting a dynamic equilibrium of activated intermediates and facilitating the balance between *COOH formation and *CO desorption at the active Fe site. Notably, the synthesized FeN5, supported on defect-rich in nitrogen-doped carbon (FeN5@DNC), exhibits superior performance in CO2RR, achieving a Faraday efficiency of 99% for CO production (-0.4 V vs. RHE) in an H-cell, and maintaining a Faraday efficiency of 98% at a current density of 270 mA cm-2 (-1.0 V vs. RHE) in the flow cell. Furthermore, the FeN5@DNC catalyst is assembled as a reversible Zn-CO2 battery with a cycle durability of 24 hours. In-situ IR spectroscopy and density functional theory (DFT) calculations reveal that the axial N coordination traction induces a transformation in the crystal field and local symmetry, therefore weakening the spin polarization of the central Fe atom and lowering the energy barrier for *CO desorption.

Comparing different postoperative sedation strategies for patients in the intensive care unit after cardiac surgery: A systematic review of randomized controlled trials and network meta-analysis.

BACKGROUND: Various postoperative sedation protocols with different anaesthetics lead to profound effects on the outcomes for post-cardiac surgery patients. However, a comprehensive analysis of optimal postoperative sedation strategies for patients in the intensive care unit (ICU) after cardiac surgery is lacking. METHODS: We systematically searched for randomized controlled trials (RCTs) in databases including PubMed and Embase. The primary outcome measured the duration of mechanical ventilation (MV) in the ICU, and the secondary outcome encompassed the length of stay (LOS) in the ICU and hospital and the monitoring adverse events. RESULTS: The literature included 18 RCTs (1652 patients) with 13 sedation regimens. Dexmedetomidine plus ketamine and sevoflurane were associated with a significantly reduced duration of MV when compared with propofol. Our results also suggested that dexmedetomidine plus ketamine may associated with a shorter LOS in ICU, and sevoflurane associated with a shorter LOS in the hospital, respectively. CONCLUSIONS: The combination of dexmedetomidine and ketamine seems to be a better option for adult patients needing sedation after cardiac surgery, and the incidence of side effects is lower with dexmedetomidine. These findings have potential implications for medication management in the perioperative pharmacotherapy of cardiac surgery patients.

Phylogenetic variations in a novel family of hyperstable apple snail egg proteins: insights into structural stability and functional trends.

The relationship between protein stability and functional evolution is little explored in proteins purified from natural sources. Here we investigate a novel family of egg proteins (Perivitellin-1, PV1) from Pomacea snails. Their remarkable stability and clade-related functions in most derived clades (Canaliculata and Bridgesii) make them excellent candidates for exploring this issue. To that aim, we studied PV1 (PpaPV1) from the most basal lineage, Flagellata. PpaPV1 displays unparalleled structural and kinetic stability, surpassing PV1s from derived clades, ranking among the most hyperstable proteins documented in nature. Its spectral features contribute to a pale egg coloration, exhibiting a milder glycan binding lectin activity with a narrower specificity than PV1s from the closely related Bridgesii clade. These findings provide evidence for substantial structural and functional changes throughout the genus' PV1 evolution. We observed that structural and kinetic stability decreases in a clade-related fashion and was associated with large variations in defensive traits. For instance, pale PpaPV1 lectin turns potent in the Bridgesii clade adversely affecting gut morphology, while giving rise to brightly colored PV1s providing eggs with a conspicuous, likely warning signal in the Canaliculata clade. This work provides a comprehensive comparative analysis of PV1s from various apple snail species within a phylogenetic framework, offering insights into the interplay among their structural features, stability profiles, and functional roles. More broadly, our work provides one of the first examples from natural evolution showing the crucial link among protein structure, stability, and evolution of new functions.

TURALIO® Risk Evaluation and Mitigation Strategy Program (tREMS): 3-year retrospective hepatic safety assessment.

Aim: Hepatic safety data assessment from the TURALIO® (pexidartinib) Risk Evaluation and Mitigation Strategy (tREMS) Program. Methods: Retrospective 3-year assessment (August 2019 to June 2022) of hepatic events from the TURALIO® (pexidartinib) Risk Evaluation and Mitigation Strategy Program. Results: A total of 451 patients, 369 prescribers, 2 wholesalers/distributors and 2 pharmacies were enrolled and certified. Twenty-one (4.7%) patients met the criteria for a hepatic adverse event or laboratory abnormality suggestive of serious and potentially fatal liver injury, all with onset within 2 months of therapy. No new hepatic safety signals were identified. Conclusion: Results are consistent with the phase 3 ENLIVEN trial data. Liver enzyme monitoring, combined with early intervention, including dose modification and discontinuation, conducted in patients treated with pexidartinib mitigate the risk of potential hepatotoxicity.

Safety findings from the 3-year data collected in the TURALIO^® Risk Evaluation and Mitigation Strategy ProgramPexidartinib (TURALIO^®) is an oral drug that is used to treat adults with tenosynovial giant cell tumor (TGCT) that cannot be fixed with surgery. TGCTs are rare, noncancerous tumors that cause pain, stiffness and difficulty moving. Pexidartinib works by blocking a protein that helps these tumors grow. Before pexidartinib, there were no good treatments for TGCT and surgery often could not remove all the tumors, so they would frequently grow back.Pexidartinib was approved in 2019 after a clinical trial showed it worked well in adults with TGCT. However, pexidartinib can sometimes cause serious liver harm for some patients. To handle this risk, a program called the tREMS (TURALIO^® Risk Evaluation and Mitigation Strategy) was established to ensure that pexidartinib is used safely.The tREMS Program teaches doctors, pharmacists and patients about the safe use of pexidartinib and potential liver risks and enrolls patients in a registry to watch their health. Doctors and pharmacies must be certified, and patients need regular liver tests. In the first 3 years, 451 patients and 369 doctors joined the program. Unintended liver issues were found in around 5% of patients, a rate that is about the same as that seen in pexidartinib clinical trials, and no new safety concerns were found. About half of patients with liver issues could reverse them by stopping pexidartinib. No patient had permanent liver damage, needed a transplant or died from liver problems. These results show that the tREMS Program is working well to keep patients with TGCT safe while taking pexidartinib.

Using the Preparation Phase of the Multiphase Optimization Strategy to Design an Antiextremism Program in Bahrain: Formative and Pilot Research.

BACKGROUND: Extremism continues to raise concerns about conflict and violent attacks that can lead to deaths, injuries, trauma, and stress. Adolescents are especially vulnerable to radicalization by extremists. Given its location in a region that often experiences extremism, Bahrain developed 4 peaceful coexistence lessons and 4 antiextremism lessons to be implemented as part of their Drug Abuse Resistance Education (D.A.R.E.) program. OBJECTIVE: The aim of this study is to report the results of the preparation phase of the multiphase optimization strategy (MOST) to develop a peaceful coexistence program and an antiextremism program implemented by D.A.R.E. officers in Bahrain. METHODS: We developed conceptual models for the peaceful coexistence and antiextremism programs, indicating which mediators each lesson should target, the proximal outcomes that should be shaped by these mediators, and the distal and ultimate outcomes that the intervention should change. We recruited 20 middle schools to pilot test our research protocol, survey measures, and the existing intervention lessons. A total of 854 seventh and ninth grade students completed a pretest survey, 4 peaceful coexistence intervention lessons, and an immediate posttest survey; and a total of 495 ninth grade students completed the pretest survey, 4 antiextremism lessons, and an immediate posttest survey. A series of 3-level models, nesting students within classrooms within schools, tested mean differences from pretest to posttest. RESULTS: Pilot test results indicated that most measures had adequate reliability and provided promising evidence that the existing lessons could change some of the targeted mediators and proximal outcomes. Specifically, students who completed the peaceful coexistence lessons reported significant changes in 5 targeted mediating variables (eg, injunctive norms about intolerance, P<.001) and 3 proximal outcomes [eg, social skills empathy (P=.008); tolerance beliefs (P=.041)]. Students who completed the antiextremism lessons reported significant changes in 3 targeted mediators [eg, self-efficacy to use resistance skills themselves (P<.001)], and 1 proximal outcome (ie, social skills empathy, P<.001). CONCLUSIONS: An effective antiextremism program has the potential to protect youth from radicalization and increase peaceful coexistence. We used the preparation phase of MOST to (1) develop a conceptual model, (2) identify the 4 lessons in each program as the components we will evaluate in the optimization phase of MOST, (3) pilot test the existing lessons, our newly developed measures, and research protocol, and (4) determine that our optimization objective will be all effective components. We will use these results to revise the existing lessons and conduct optimization trials to evaluate the efficacy of the individual lessons.

Multimaterial Metamaterials: Customize Targeted Thermal Deformation Modes Responding to Time- and Space-Variant Temperature Stimuli.

Customizing the engineering targeted thermal deformations is of vital significance for dimensional stability or shape morphing in materials and structures. However, current metamaterials are designed solely in the homogeneous form to respond only to the time-variant temperature (TVT) stimuli, far behind the practical engineering scenario and demands. Here, a new strategy is originally proposed and experimentally verified to design a series of both homogeneous and inhomogeneous multimaterial metamaterials, which uniquely output various thermal deformation modes, responding to time-variant and space-variant temperature (SVT) stimuli. Specifically, in addition to the regular isotropic thermal deformations, the metamaterials could exclusively output the entirely different positive and negative thermal deformations along the two orthotropic directions. Besides, stimulated by both TVT and SVT, the metamaterials provide more flexibility to customize the targeted thermal deformations. That is, the uniform thermal deformations could be well customized by the metamaterials stimulated by either TVT or SVT. More importantly, the customizability is remarkably broadened, as the nonuniform, specifically, mathematicized linear and nonlinear thermal deformations, are elaborately customized. Overall, these originally devised metamaterials open a new avenue for the purpose of customizing the engineering targeted thermal deformations in various modes under both TVT and SVT stimuli.

Performance and eye movement patterns of industrial design students reading sustainable design articles.

Sustainable design education plays a crucial role in cultivating sustainability awareness and competencies among students studying industrial design. This research investigates their sustainability levels, reading performance when engaging with articles, and fixation patterns during reading. 60 industrial design students participated in the study. We evaluated their sustainability levels using the Sustainable Consumption Measurement Scale. After reading both theoretical and case article, they completed tests assessing their recall and perspective scores. We collected eye-tracking data to analyze fixation duration and conducted lag sequential analysis on fixation transitions. Students were categorized into higher and lower sustainability groups based on their sustainability scores. Female students demonstrated higher sustainability levels, and students with design experience performed better in the higher sustainability group. While recall scores did not differ significantly, the higher sustainability group exhibited elevated perspective scores in theory article. Perspective scores were generally higher for case article compared to theory article. The higher sustainability group exhibited longer fixation durations in theory article, while the case article had longer fixation durations on images. Fixation transition patterns varied between theoretical and case article, with the former featuring transitions from images to texts, and the latter demonstrating transitions between images. This study provides valuable insights into sustainable design education for students studying industrial design.

Urinary concerns among older adults: a qualitative analysis in the context of healthy aging.

BACKGROUND: Urinary concerns increase with age impacting health and quality of life. The aims of this study were to describe: (1) urinary concerns as an age-related change (ARC); (2) the challenges of urinary concerns; (3) adaptation strategies used to manage urinary concerns; and (4) the value of engaging with aging (EWA) as a framework to promote self-management of urinary concerns. METHODS: Data was used from semi-structured interviews with 29 older adults (mean age 77 years). An iterative coding process was used. A codebook was developed based on a-priori themes derived from the EWA framework, our previous publication, and a line-by-line coding of one of the transcripts. As the analysis progressed, additional codes emerged, enriching the codebook. RESULTS: Six themes emerged: (1) the participants' experiences; (2) responses to urinary concerns, (3) adaptation and management strategies; (4) knowledge and understanding of urinary concerns; (5) available capacities and resources; and (6) the impact of the COVID-19 pandemic on urinary concerns. Participants tended to address their urinary concerns by adjusting routines, medication schedules, or diet patterns. They tried to secure restroom locations or use tools or reminders to resolve their urinary concerns. COVID-19 led to increased inconvenience for older adults to engage in outdoor activities due to the closure of public restrooms. CONCLUSIONS: Our in-depth qualitative analysis found that participants developed personalized adjustments to address their needs and abilities to their urinary concerns. These findings offer insights into the individual aging experience, which will further enhance our understanding and advancement of person-centered care.

Bio-inspired compensatory strategies for damage to flapping robotic propulsors.

Natural swimmers and flyers can fully recover from catastrophic propulsor damage by altering stroke mechanics: some fish can lose even 76% of their propulsive surface without loss of thrust. We consider applying these principles to enable robotic flapping propulsors to autonomously repair functionality. However, direct transference of these alterations from an organism to a robotic flapping propulsor may be suboptimal owing to irrelevant evolutionary pressures. Instead, we use machine learning techniques to compare these alterations with those optimal for a robotic system. We implement an online artificial evolution with hardware-in-the-loop, performing experimental evaluations with a flexible plate. To recoup thrust, the learned strategy increased amplitude, frequency and angle of attack (AOA) amplitude, and phase-shifted AOA by approximately 110°. Only amplitude increase is reported by most fish literature. When recovering side force, we find that force direction is correlated with AOA. No clear amplitude or frequency trend is found, whereas frequency increases in most insect literature. These results suggest that how mechanical flapping propulsors most efficiently adjust to damage may not align with natural swimmers and flyers.