Antivirulence and antipathogenic activity of Mayan herbal remedies against Pseudomonas aeruginosa.

ETHNOPHARMACOLOGICAL RELEVANCE: The Yucatan Peninsula has a privileged wealth of vascular plants with which various Mayan herbal formulations have been developed. However, studies on their antipathogenic and antivirulence properties are scarce. AIM OF THE STUDY: Identify antivirulence properties in Mayan herbal remedies and determine their antipathogenic capacity in burn wounds infected with Pseudomonas aeruginosa. MATERIALS AND METHODS: An ethnobotanical study was conducted in Mayan communities in central and southern Quintana Roo, Mexico. Furthermore, the antipathogenic capacity of three Mayan herbal remedies was analyzed using an animal model of thermal damage and P. aeruginosa infection. Antivirulence properties were determined by inhibiting phenotypes regulated by quorum sensing (pyocyanin, biofilm, and swarming) and by the secretion of the ExoU toxin. The chemical composition of the most active herbal remedy was analyzed using molecular network analysis. RESULTS: It was found that topical administration of the remedy called "herbal soap" (HS) for eleven days maintained 100% survival of the animals, reduced establishment of the bacteria in the burn and prevented its systemic dispersion. Although no curative effect was recorded on tissue damaged by HS treatment, its herbal composition strongly reduced swarming and ExoU secretion. Through analysis of Molecular Networks, it was possible to carry out a global study of its chemical components, and identify the family of oxindole monoterpenoid alkaloids and carboline and tetrahydropyrididole alkaloids. In addition, flavonols, flavan-3-ols, and quinic acid derivatives were detected. CONCLUSIONS: The antipathogenic and antivirulence capacity of ancient Mayan remedies makes them a potential resource for developing new antibacterial therapies to treat burns infected by P. aeruginosa.

From No Disease to Stage IV Colon Cancer in Four Months: A Case Report.

Colorectal cancer remains one of the most common cancers in the population. Meanwhile, steroids or other immunosuppressive drugs are usually given in rheumatological diseases as a treatment for flare-ups. Herein, we present the case of a 61-year-old female diagnosed with metastatic colorectal cancer merely four months following the commencement of glucocorticoid therapy for a recently diagnosed rheumatologic condition, despite a clear colorectal cancer screening colonoscopy conducted four months prior. The case report discusses the possible impact of corticosteroids on the fast disease progression of colorectal cancer and raises awareness regarding this potential risk.

Synergistic Interaction Effect of Artemisia cina n-hexane Extract and Tagetes lucida Ethyl Acetate Extract on Haemonchus Contortus.

PURPOSE: We analysed the possible synergistic activity among active extracts from Artemisia cina and Tagetes lucida combinations on Haemonchus contortus, a nematode parasitising sheep. METHODS: The work was carried out in vitro on eggs and infective larvae (L3) of H. contortus. The results were analysed with SAS 9.1, applying the ANOVA and Tukey test, and the lethal concentration (LC) values LC50 and LC90 were determined with regression analysis, employing Proc Probit of SAS 9.1. Additionally, the lethal concentration (LC) was calculated with LC50 and LC90 to determine the synergistic effect. RESULTS: The results demonstrated a high efficacy of the two plants studied on both nematode eggs and L3 larvae as well as of their combinations. The highest egg hatching inhibition was obtained with a 50/50 combination, and the best larvae mortality was obtained with 25% A. cina and 75% T. lucida at 10 mg/mL. Additionally, this combination showed a synergistic effect. CONCLUSION: The two plant species studied here can be applied as natural anthelmintic alternatives due to their high bioactive effect and synergistic response.

How Dedicated Ribosomes Translate a Leaderless mRNA.

In bacteriophage λ lysogens, the λcI repressor is encoded by the leaderless transcript (lmRNA) initiated at the λpRM promoter. Translation is enhanced in rpsB mutants deficient in ribosomal protein uS2. Although translation initiation of lmRNA is conserved in bacteria, archaea, and eukaryotes, structural insight of a lmRNA translation initiation complex is missing. Here, we use cryo-EM to solve the structures of the uS2-deficient 70S ribosome of host E. coli mutant rpsB11 and the wild-type 70S complex with λcI lmRNA and fMet-tRNAfMet. Importantly, the uS2-deficient 70S ribosome also lacks protein bS21. The anti-Shine-Dalgarno (aSD) region is structurally supported by bS21, so that the absence of the latter causes the aSD to divert from the normal mRNA exit pathway, easing the exit of lmRNA. A π-stacking interaction between the monitor base A1493 and A(+4) of lmRNA potentially acts as a recognition signal. Coulomb charge flow, along with peristalsis-like dynamics within the mRNA entrance channel due to the increased 30S head rotation caused by the absence of uS2, are likely to facilitate the propagation of lmRNA through the ribosome. These findings lay the groundwork for future research on the mechanism of translation and the co-evolution of lmRNA and mRNA that includes the emergence of a defined ribosome-binding site of the transcript.

Antecedentes de Andragogía en el proceso de gestión de personas mayores por profesionales de enfermería

Introducción: La gestión del cuidado de enfermería en personas mayores es todo un desafío en la actualidad para la profesión y más aún desde un enfoque andragógico. Objetivo: Exponer la fundamentación de los antecedentes de la andragogía en el proceso de gestión del cuidado de personas mayores por profesionales de enfermería. Métodos: Se realizó una revisión con el método de análisis bibliográfico a través de una búsqueda realizada entre los años 2010 al 2022, donde se consultaron bases de datos especializadas y se seleccionaron 33 publicaciones científicas sobre el tema. Resultados: El cuidado de personas mayores requiere una mirada transdisciplinaria y profesionales comprometidos con su cuidado. El profesional de enfermería responsable de la gestión debe considerar valores, actitudes y conocimientos de la disciplina que brindan una visión distinta y específica de la gestión de los cuidados. El avance científico ha permitido el incremento de la expectativa de vida de las personas, produciéndose un aumento significativo de personas mayores en el mundo manteniendo un adecuado cuidado como eslabón importante. La andragogía se encarga de la educación entre, para y por adultos y la asume como su objeto de estudio y realización, vista o concebida esta, como autoeducación, por lo cual, cobra importancia en los cuidados, pues interpreta el hecho educativo como un hecho andragógico, donde la educación y los cuidados se realizan como autoeducación. Conclusiones: Resulta importante la ejecución de investigaciones que beneficien el desarrollo del profesional de enfermería, para ayudar a disminuir las brechas que constan en la formación investigativa de estos profesionales y en las estructuras organizativas en las que estos se incorporan, dado en el proceso de gestión del cuidado de personas mayores desde un enfoque andragógico como mecanismo esencial.

Introduction: The management of nursing care in older people is a challenge for the profession today and even more so from an andragogical approach. Objective: To present the foundation of the background of andragogy in the process of managing the care of elderly people by nursing professionals. Methods: A review was carried out using the bibliographic analysis method through a search carried out between the years 2010 to 2022, where specialized databases were consulted and 33 scientific publications on the topic were selected. Results: Caring for the elderly requires a transdisciplinary approach and professionals committed to their care. The nursing professional responsible for the management must consider values, attitudes and knowledge of the discipline that provide a different and specific vision of care management. Scientific advances have allowed an increase in people's life expectancy, producing a significant increase in the number of older people in the world, maintaining adequate care as an important link. Andragogy is responsible for education among, for and by adults and assumes it as its object of study and realization, seen or conceived, as self-education, which is why andragogy gains importance in care, since it interprets the educational fact as an andragogical fact, where education and care are carried out as self-education. Conclusions: It is important to carry out research that benefits the development of nursing professionals, to help reduce the gaps that exist in the research training of these professionals and in the organizational structures in which they are incorporated, given in the care management process of older people from an andragogical approach as an essential mechanism.

A Novel Passive Back-Support Exoskeleton With a Spring-Cable-Differential for Lifting Assistance.

Lower back injuries are the most common work-related musculoskeletal disorders. As a wearable device, a back-support exoskeleton (BSE) can reduce the risk of lower back injuries and passive BSEs can achieve a low device weight. However, with current passive BSEs, there is a problem that the user must push against the device when lifting the leg to walk, which is perceived as particularly uncomfortable due to the resistance. To solve this problem, we propose a novel passive BSE that can automatically distinguish between lifting and walking. A unique spring-cable-differential acts as a torque generator to drive both hip joints, providing adequate assistive torque during lifting and low resistance during walking. The optimization of parameters can accommodate the asymmetry of human gait. In addition, the assistive torque on both sides of the user is always the same to ensure the balance of forces. By using a cable to transmit the spring force, we placed the torque generator on the person's back to reduce the weight on the legs. To test the effectiveness of the device, we performed a series of simulated lifting tasks and walking trials. When lifting a load of 10 kg in a squatting and stooping position, the device was able to reduce the activation of the erector spinae muscles by up to 41%. No significant change in the activation of the leg and back muscles was detected during walking.

Structural insight into translation initiation of the λcl leaderless mRNA.

In bacteriophage λ lysogens, the λcI repressor is encoded by the leaderless transcript (lmRNA) initiated at the λpRM promoter. Translation is enhanced in rpsB mutants deficient in ribosomal protein uS2. Although translation initiation of lmRNA is conserved in bacteria, archaea, and eukaryotes, structural insight of a lmRNA translation initiation complex is missing. Here, we use cryo-EM to solve the structures of the uS2-deficient 70S ribosome of host E. coli mutant rpsB11 and the wild-type 70S complex with λcI lmRNA and fmet-tRNAfMet. Importantly, the uS2-deficient 70S ribosome also lacks protein bS21. The anti-Shine-Dalgarno (aSD) region is structurally supported by bS21, so that the absence of the latter causes the aSD to divert from the normal mRNA exit pathway, easing the exit of lmRNA. A π-stacking interaction between the monitor base A1493 and A(+4) of lmRNA potentially acts as a recognition signal. Coulomb charge flow, along with peristalsis-like dynamics within the mRNA entry channel due to the increased 30S head rotation caused by the absence of uS2, are likely to facilitate the propagation of lmRNA through the ribosome. These findings lay the groundwork for future research on the mechanism of translation and the co-evolution of lmRNA and mRNA that includes the emergence of a defined ribosome-binding site of the transcript.

Hans Hugo Bruno Selye y el estrés, hito en la historia de la Medicina moderna / Hans Hugo Bruno Selye and the stress, a milestone in the modern medical history

Fundamento: Hans Hugo Bruno Selye, fisiólogo y médico austrohúngaro nació el 26 de enero de 1907, posteriormente se naturalizó canadiense, este hombre que vivió 75 años y llegó a ser director del Instituto de Medicina y Cirugía Experimental de la Universidad de Montreal, Canadá, hasta su retiro en 1970. Falleció en 1982, en esa misma ciudad. Objetivo: Describir la vida y obra del ilustre académico Hans Hugo Bruno Selye y la historia del estrés como hito en la historia de la Medicina moderna. Metodología: Se realizó un estudio retrospectivo de corte histórico donde se utilizaron métodos teóricos como el análisis documental y el histórico-lógico. Desarrollo: El doctor empezó a desarrollar su famosa teoría acerca de la influencia del estrés en la capacidad de las personas para enfrenarse o amoldarse a las consecuencias de lesiones o enfermedades en el segundo año de sus estudios de Medicina (1926). Esta investigación le permitió descubrir que los pacientes con variedad de dolencias manifestaban síntomas similares, los cuales podían ser atribuidos a los esfuerzos del organismo para responder a esta condición de estar enfermo. Él llamó a este conjunto de síntomas síndrome del estrés o síndrome de adaptación general (GAS). Conclusiones: Este médico es una de las personalidades más importantes de la historia de la Medicina; su teoría del estrés proporcionó un marco conceptual transcendental para cuestiones posteriores de los mecanismos y manifestaciones de las reacciones del mismo.

Background: Hans Hugo Bruno Selye, Austro-Hungarian physiologist and physician, born January 26, 1907, later naturalized Canadian citizen, this man who lived 75 years and became the Director of Experimental Medicine and Surgery Institute of Montreal University in Canada, until his retirement in 1970. He passed away in 1982, in the same city. Objective: Describe the life and achievements of the distinguished academic Hans Hugo Bruno Selye and the history of stress as a milestone in modern medical history. Methodology: A historical retrospective study was conducted using theoretical methods such as documental and historical-logical analysis. Methodology: The doctor began to build his famous theory about the influence of stress on the ability of persons to cope or adjust to the injury or illness consequences in the second year of his medical studies (1926). He discovered with this investigation that patients with a variety of ailments exhibited similar symptoms, which could be attributed to the organism efforts to respond to the condition of being sick. He named this set of symptoms stress syndrome or general adaptation syndrome (GAS). Conclusions: This physician is one of the greatest personalities in medical history; his stress theory provided a transcendental conceptual framework for later issues of the mechanisms and manifestations for stress reactions.

Are There Long-Term Effects of Behavior Therapy for Adolescent ADHD? A Qualitative Study.

We utilized qualitative methodology to characterize potential long-term effects (therapeutic and iatrogenic) of behavior therapy for adolescents with ADHD. Forty-two in-depth interviews were conducted with adolescents with ADHD and parents, 4 years post-treatment. Grounded theory methods identified and reported prevalence of themes. All reported long-term effects were classified as benefits; no iatrogenic effects were noted. Long-term impact themes reported for a majority of participants included: development of organization skills (81.0%), enhanced motivation (57.1%), improved self-awareness (57.1%), improved parental knowledge of ADHD (76.2%), increased parent autonomy granting (61.9%), enhanced parental engagement with the youth (52.4%), and improved parent-teen relationships (52.4%). Fourteen themes were present for smaller subsamples, including reduced need for medication (3 of 9 medicated participants). Experimental studies of behavior therapy for adolescent ADHD should measure themes detected herein and directly test the possibility of long-term treatment effects.

Diabetes mellitus, COVID-19, modelos educativos en salud. Importancia del autocuidado

Introducción : El primer trimestre de 2020 se ha visto influenciado por la propagación de una pandemia ocasionada por el virus SARS-CoV-2, el cual origina una afección (COVID-19), la diabetes mellitus es una de las enfermedades que cuando este se padece causa complicaciones y mortalidad. Objetivo : Identificar la relación existente entre la importancia de la educación para la diabetes mellitus y la COVID-19. Métodos : Se realizó una revisión con el método de análisis bibliográfico a través de una búsqueda realizada entre los años 2006 al 2021, donde se consultaron bases de datos especializadas y se seleccionaron 27 publicaciones científicas sobre el tema. Resultados : La educación, el autocuidado y los modelos educativos son importantes. En la diabetes, los cambios en los estilos de vida son esenciales: realizar actividad física, buenos hábitos alimentarios y evitar comportamientos poco saludables, pues son algunos de los factores que propician la enfermedad. Las recomendaciones estándar dictadas por la OMS para prevenir la propagación de la infección COVID-19 incluyen: lavarse las manos de manera regular, especialmente después del contacto con personas enfermas o su entorno, cubrirse la boca y la nariz al toser y estornudar, cocinar bien la carne y los huevos, evitar el contacto cercano con cualquier persona que presente síntomas de enfermedades respiratorias, evitar viajar a las ciudades y áreas afectadas. En el caso de los viajeros con síntomas de infección respiratoria aguda, deben practicar la etiqueta de la tos, ambas enfermedades se pueden prevenir. Conclusiones : Tanto en la diabetes como en la COVID-19 la educación es esencial para prevenirla, de ahí la importancia de velar por la salud y fomentar una cultura educativa basada en el autocuidado.

Introduction: The first quarter of 2020 has been influenced by the spread of a pandemic caused by the SARS-CoV-2 virus, which causes a condition (COVID-19), diabetes mellitus is one of the diseases that causes complications and mortality when a patient suffers COVID-19. Objective: To identify the relationship between the importance of education for diabetes mellitus and COVID-19. Methods: A bibliographic review was carried out with the bibliographic analysis method through a search carried out between the years 2006 and 2021, where specialized databases were consulted and 27 scientific publications on the subject were selected. Results: Education, self-care and educational models are important. In diabetes, changes in lifestyles are essential: physical activity, good eating habits and avoiding unhealthy behaviors, as they are some of the factors that promote diabetes. The standard recommendations issued by the WHO to prevent the spread of the COVID-19 infection include: regular hand washing, especially after contact with sick people or their surroundings, covering the mouth and nose when coughing and sneezing, cooking well meat and eggs, avoid close contact with anyone showing symptoms of respiratory illness, avoid traveling to affected cities and areas. In the case of travelers with symptoms of acute respiratory infection, they should practice cough etiquette, both diseases can be prevented. Conclusions: In both diabetes and COVID-19, education is essential to prevent it, hence the importance of ensuring health and promoting an educational culture based on self-care.

A novel passive shoulder exoskeleton for assisting overhead work.

Shoulder exoskeletons (SEs) can assist the shoulder joint of workers during overhead work and are usually passive for good portability. However, current passive SEs face the challenge that their torque generators are often attached to the human arm, which adds a significant amount of weight to the user's arms, resulting in additional energy consumption of the user. In this paper, we present a novel passive SE whose torque generator is attached to the user's back and assists the shoulder joint through Bowden cables. Our approach greatly reduces the weight on the user's arms and can accommodate complex shoulder joint movements with simple and lightweight mechanical structure based on Bowden cables. In addition, to match the nonlinear torque requirements of the shoulder joint, a unique spring-cam mechanism is proposed as the torque generator. To verify the effectiveness of the device, we conducted a usability test based on muscle activations of 10 healthy subjects. When assisting overhead work, the SE significantly reduced the mean and maximum electromyography signals of the shoulder-related muscles by up to 25%. The proposed SE contributes to further research on passive SE design to improve usability, especially in terms of reducing weight on human arms.

Análisis bibliométrico de la investigación española de impacto en Enfermería Educativa / Bibliometric analysis of the Spanish research with impact in Nursing Educatio

El objetivo de este estudio es elaborar una revisión bibliométrica de la producción española en Enfermería Educativa. Se indaga el tópico de la Enfermería Educativa española a través de documentos indexados en las bases de la Web of Science (WoS) desde 1991 a 2021 usando un diseño descriptivo y cuantitativo (bibliométrico) en una muestra de 927 documentos (artículos, ensayos clínicos y revisiones). La producción diacrónica muestra una tendencia creciente. Las universidades más productivas suelen ser las del arco mediterráneo español. Nurse Education Today es la revista más editora y también la más citada. El promedio de citas por documento es 11 y un índice h de Hirsch de 46. Se exponen los documentos más citados. Se confirma la Enfermería Educativa española como un tópico de investigación científica relevante (hot topic) homologable a cualquier tópico cualificado de las disciplinas de las Ciencias de la Salud.(AU)

The objective of this study is to elaborate a bibliometric review of the Spanish production in Educational Nursing. The topic of Spanish Nursing Education is explored through research documents indexed in the bases of the Web of Science from 1991 to 2021 using a descriptive and quantitative (bibliometric) design with a sample of 927 documents (articles, clinical trials and reviews). Longitudinal production shows an increasing trend. The most productive universities are from the Spanish Mediterranean arc. The journal Nurse Education Today is the most important publisher and the most cited journal. The average number of citations per document is 11 citations with a Hirsch h-index of 46. Spanish Nursing Education is confirmed as a relevant scientific research topic (hot topic) with bibliometric patterns comparable to those of any qualified topic of the Health Sciences.(AU)

Curso en WhatsApp: "Determinantes sociales de la salud, educación y objetivos desarrollo sostenible" / Course through WhatsApp: "Social determinants of health, education and sustainable development objectives"

Fundamento: dotar a los profesionales de la Red Iberoamericana de Pedagogía (Redipe) de conocimientos para su actuación frente a la pandemia de la COVID-19 es una necesidad; realizarlo en un ambiente virtual, un desafío. Objetivo: describir el uso de la aplicación WhatsApp en un curso precongreso sobre determinantes sociales de la salud, educación y objetivos del desarrollo sostenible en tiempos de la COVID-19. Métodos: se realizó una investigación descriptiva en los meses de julio a agosto de 2022 con profesionales que forman parte de Redipe, Cuba. Se utilizaron métodos teóricos: análisis-síntesis y enfoque sistémico; empíricos: revisión bibliográfica para la selección y fundamentación de contenidos del curso precongreso, técnica de lo positivo, negativo e interesante y el criterio de especialistas para la valoración del producto diseñado. Resultados: el curso precongreso estuvo estructurado en tres temas, con sus objetivos, contenidos, orientaciones metodológicas, tareas docentes y bibliografía básica. Concluido su diseño, fue valorado por especialistas e implementado en un ambiente virtual durante dos días. Se destacaron sus aspectos: positivo, la pertinencia de los contenidos aportados; negativo, la restricción de la tecnología por insuficiencias de teléfonos móviles; e interesante, la modernización indisoluble de los temas en conformidad con los artículos publicados en línea, entre otros criterios. Conclusiones: la aplicación WhatsApp se presenta como una herramienta para promover la colaboración e interacción durante el curso precongreso y como un recurso didáctico que fomentó el aprendizaje desde la educación a distancia.

Background: providing the professionals of the Ibero-American Network of Pedagogy (Redipe) with knowledge for their action when facing the COVID-19 pandemic is a necessity; doing it in a virtual environment, a challenge. Objective: to describe the use of the WhatsApp application in a pre-congress course on social determinants of health, education and sustainable development goals in times of COVID-19. Methods: a descriptive investigation was carried out from July to August 2022 with professionals who are part of Redipe, Cuba. Theoretical methods were used: analysis-synthesis and systemic approach; Empirical ones: bibliographic review for the selection and foundation of the contents of the pre-congress course, technique of the positive, negative and interesting and the criteria of specialists for the evaluation of the designed product. Results: the pre-congress course was structured in three topics, with its objectives, contents, methodological orientations, teaching tasks and basic bibliography. Once its design was completed, it was evaluated by specialists and implemented in a virtual environment for two days. Its aspects were highlighted: positive, the relevance of the content provided; negative, the restriction of technology due to insufficiencies of mobile phones; and interesting, the indissoluble modernization of the topics in accordance with the articles published online, among other criteria. Conclusions: the WhatsApp application is presented as a tool to promote collaboration and interaction during the pre-congress course and as a didactic resource that fostered learning from distance education.

Diffusion and Velocity Correlations of the Phase Transitions in a System of Macroscopic Rolling Spheres.

We study an air-fluidized granular monolayer composed of plastic spheres which roll on a metallic grid. The air current is adjusted so that the spheres never lose contact with the grid and so that the dynamics may be regarded as pseudo two dimensional (or two dimensional, if the effects of the sphere rolling are not taken into account). We find two surprising continuous transitions, both of them displaying two coexisting phases. Moreover, in all the cases, we found the coexisting phases display a strong energy non-equipartition. In the first transition, at a weak fluidization, a glass phase coexists with a disordered fluid-like phase. In the second transition, a hexagonal crystal coexists with the fluid phase. We analyze, for these two-phase systems, the specific diffusive properties of each phase, as well as the velocity correlations. Surprisingly, we find a glass phase at a very low packing fraction and for a wide range of granular temperatures. Both phases are also characterized by strong anticorrelated velocities upon a collision. Thus, the dynamics observed for this quasi two-dimensional system unveil phase transitions with peculiar properties, very different from the predicted behavior in well-know theories for their equilibrium counterparts.

Recovery of Conformational Continuum From Single-Particle Cryo-EM Images: Optimization of ManifoldEM Informed by Ground Truth.

This work is based on the manifold-embedding approach to study biological molecules exhibiting continuous conformational changes. Previous work established a method-now termed ManifoldEM-capable of reconstructing 3D movies and accompanying free-energy landscapes from single-particle cryo-EM images of macromolecules exercising multiple conformational degrees of freedom. While ManifoldEM has proven its viability in several experimental studies, critical limitations and uncertainties have been found throughout its extended development and use. Guided by insights from studies with cryo-EM ground-truth data, simulated from atomic structures undergoing conformational changes, we have built a novel framework, ESPER, able to retrieve the free-energy landscape and respective 3D Coulomb potential maps for all states simulated. As shown by a direct comparison of ground truth vs. recovered maps, and analysis of experimental data from the 80S ribosome and ryanodine receptor, ESPER offers substantial improvements relative to the previous work.

How decadal predictions entered the climate services arena: an example from the agriculture sector.

Predicting the variations in climate for the coming 1-10 years is of great interest for decision makers, as this time horizon coincides with the strategic planning of stakeholders from climate-vulnerable sectors such as agriculture. This study attempts to illustrate the potential value of decadal predictions in the development of climate services by establishing interactions and collaboration with stakeholders concerned with food production and security. Building on our experience from interacting with users and the increased understanding of their needs gathered over the years through our participation in various European activities and initiatives, we developed a decadal forecast product that provides tailored and user-friendly information about multi-year dry conditions for the coming five years over global wheat harvesting regions. This study revealed that the coproduction approach, where the interaction between the user and climate service provider is established at an early stage of forecast product development, is a fundamental step to successfully provide useful and ultimately actionable information to the interested stakeholders. The study also provides insights that shed light on the reasons for the delayed entry of decadal predictions in the climate services discourse and practice, obtained from surveying climate scientists and discussing with decadal prediction experts. Finally, it shows the key challenges that this new source of climate information still faces.

Uncovering translation roadblocks during the development of a synthetic tRNA.

Ribosomes are remarkable in their malleability to accept diverse aminoacyl-tRNA substrates from both the same organism and other organisms or domains of life. This is a critical feature of the ribosome that allows the use of orthogonal translation systems for genetic code expansion. Optimization of these orthogonal translation systems generally involves focusing on the compatibility of the tRNA, aminoacyl-tRNA synthetase, and a non-canonical amino acid with each other. As we expand the diversity of tRNAs used to include non-canonical structures, the question arises as to the tRNA suitability on the ribosome. Specifically, we investigated the ribosomal translation of allo-tRNAUTu1, a uniquely shaped (9/3) tRNA exploited for site-specific selenocysteine insertion, using single-molecule fluorescence. With this technique we identified ribosomal disassembly occurring from translocation of allo-tRNAUTu1 from the A to the P site. Using cryo-EM to capture the tRNA on the ribosome, we pinpointed a distinct tertiary interaction preventing fluid translocation. Through a single nucleotide mutation, we disrupted this tertiary interaction and relieved the translation roadblock. With the continued diversification of genetic code expansion, our work highlights a targeted approach to optimize translation by distinct tRNAs as they move through the ribosome.

Continued expansion of the genetic code has required the use of synthetic tRNAs for decoding. Some of these synthetic tRNAs have unique structural features that are not observed in canonical tRNAs. Here, the authors applied single-molecule, biochemical and structural methods to determine whether these distinct features were deleterious for efficient protein translation on the ribosome. With a focus on selenocysteine insertion, the authors explored an allo-tRNA with a 9/3 acceptor domain. They observed a translational roadblock that occurred in A to P site tRNA translocation. This block was mediated by a tertiary interaction across the tRNA core, directing the variable arm position into an unfavorable conformation. A single-nucleotide mutation disrupted this interaction, providing flexibility in the variable arm and promoting efficient protein production.

Investigating routine care non-pharmacological treatment for adolescents with ADHD.

Objective: To characterize routine non-pharmacological care for youth with ADHD. Methods: 76 audio-recorded work-samples were collected from community mental health therapists in a large metropolitan area in the United States and were analyzed for operationally defined practice elements commonly included in evidence-based non-pharmacological treatment for ADHD. Analyses characterized community provider practices and examined predictors of using evidence-based (vs.low-value) practices. Results: Individually delivered social skills training was the most commonly detected practice element (31.6% of practice samples). Parent involvement in routine care was uncommon (53.9% of sessions had no parental presence). Core elements of evidence-based practices were rarely delivered (e.g., organization skills training: 18.4% of tapes; operant reinforcement: 13.2%); when evidence-based content was introduced, it was typically implemented at a very low intensity. Patient and provider characteristics did not predict use of evidence-based practices. Conclusions: Routine non-pharmacological care for adolescent ADHD primarily consisted of low value practices such as youth-directed treatment and social skills training with low parent involvement and only occasional therapy homework. To improve quality of care, efforts to de-implement low value practices should be coupled with efforts to implement evidence-based practices (i.e., parent involvement, measurement-based care, organization skills training, use of operant reinforcement).