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Background General practice is facing an unprecedented challenge in managing the consequences of the pandemic. In the midst of a policy drive to balance remote and in-person service provision, substantial workload pressures remain, together with increasing prevalence of long-term conditions, and declining staff numbers and morale. To address these challenges, some practices in the UK have been delivering video and hybrid group consultations (VHGCs) providing clinical care to multiple patients at the same time. Despite positive initial findings and enthusiasm, there are still gaps in our understanding of the influence VHGCs have on patient experience, healthcare utilisation, quality, safety, equity and affordability. Objectives To generate an in-depth understanding of VHGCs for chronic conditions in general practice, surface assumptions and sociotechnical dynamics, inform practice and extend theorisation. Methods Mixed-methods, multi-site research study using co-design and participatory methods, from qualitative, quantitative and cost-related perspectives. WP1 includes a national, cross-sectional survey on VHGC provision across the UK. In WP2 we will engage patients and general practice staff in co-design workshops to develop VHGC models with emphasis on digital inclusion and equity. In WP3 we will carry out a mixed-methods process evaluation in up to 10 GP practices across England (5 sites already running VHGCs and 5 comparison sites). Qualitative methods will include interviews, focus groups and ethnographic observation to examine the experiences of patients, carers, clinical and non-clinical NHS staff, commissioners and policy-makers. Quantitative methods will examine the impact of VHGCs on healthcare utilisation in primary and secondary care, patient satisfaction, engagement and activation. We will also assess value for money of group and individual care models from a health economics perspective. Conclusions We aim to develop transferable learning on sociotechnical change in healthcare delivery, using VHGCs as an exemplar of technology-supported innovation. Findings will also inform the design of a future study.

The pre-Bötzinger complex, situated in the ventrolateral medulla, serves as the central generator for the inspiratory phase of the respiratory rhythm. Evidence strongly supports its pivotal role in generating, and, in conjunction with the post-inspiratory complex and the lateral parafacial nucleus, in shaping the respiratory rhythm. While there remains an ongoing debate concerning the mechanisms underlying these nuclei’s ability to generate and modulate breathing, transgenic rodent models have significantly contributed to our understanding of these processes. However, there is a significant knowledge gap regarding the spectrum of transgenic rodent lines developed for studying respiratory rhythm, and the methodologies employed in these models. In this study, we conducted a scoping review to identify commonly used transgenic rodent lines and techniques for studying respiratory rhythm generation and modulation. Following PRISMA guidelines, we identified relevant papers in PubMed and EBSCO on 29 March 2023, and transgenic lines in Mouse Genome Informatics and the International Mouse Phenotyping Consortium. With strict inclusion and exclusion criteria, we identified 80 publications spanning 1997–2022 using 107 rodent lines. Our findings revealed 30 lines focusing on rhythm generation, 61 on modulation, and 16 on both. The primary in vivo method was whole-body plethysmography. The main in vitro method was hypoglossal/phrenic nerve recordings using the en bloc preparation. Additionally, we identified 119 transgenic lines with the potential for investigating the intricate mechanisms underlying respiratory rhythm. Through this review, we provide insights needed to design more effective experiments with transgenic animals to unravel the mechanisms governing respiratory rhythm. The identified transgenic rodent lines and methodological approaches compile current knowledge and guide future research towards filling knowledge gaps in respiratory rhythm generation and modulation.

This review synthesises past research into how machine and deep learning can improve the cyto- and histopathology processing pipelines for thyroid cancer diagnosis. The current gold-standard preoperative technique of fine-needle aspiration cytology has high interobserver variability, often returns indeterminate samples and cannot reliably identify some pathologies; histopathology analysis addresses these issues to an extent, but it requires surgical resection of the suspicious lesions so cannot influence preoperative decisions. Motivated by these issues, as well as by the chronic shortage of trained pathologists, much research has been conducted into how artificial intelligence could improve current pipelines and reduce the pressure on clinicians. Many past studies have indicated the significant potential of automated image analysis in classifying thyroid lesions, particularly for those of papillary thyroid carcinoma, but these have generally been retrospective, so questions remain about both the practical efficacy of these automated tools and the realities of integrating them into clinical workflows. Furthermore, the nature of thyroid lesion classification is significantly more nuanced in practice than many current studies have addressed, and this, along with the heterogeneous nature of processing pipelines in different laboratories, means that no solution has proven itself robust enough for clinical adoption. There are, therefore, multiple avenues for future research: examine the practical implementation of these algorithms as pathologist decision-support systems; improve interpretability, which is necessary for developing trust with clinicians and regulators; and investigate multiclassification on diverse multicentre datasets, aiming for methods that demonstrate high performance in a process- and equipment-agnostic manner.

Resumen: Objetivo: Caracterizar el perfil del cuidador primario informal (CPI) de pacientes adultos con diabetes tipo 2 (DT2) y los posibles factores asociados al colapso del cuidador (CC). Diseño: Estudio observacional, descriptivo, transversal y analítico, Emplazamiento: Unidad Médica de Atención Ambulatoria. Participantes: CPI mexicanos de pacientes adultos con DT2. Mediciones principales: Se recopilaron datos mediante un diseño prolectivo utilizando la escala de Zarit y una encuesta estructurada sobre factores sociodemográficos. Se realizó un análisis estadístico descriptivo y modelos de regresión logística univariantes y multivariantes. Resultados: El perfil del CPI es asumido por: mujeres, personas de 36-58 años, hijas, personas con un nivel educativo de secundaria y preparatoria, casados, católicos, con ingresos 5 años al cuidado de su paciente, sin capacitación y con enfermedades crónicas. Los factores de riesgo que incrementan el riesgo del CC son: ser mujer (OR = 11,03; IC 95%: 1,49-81,95), tener el antecedente de más de 5 años de haber asumido el papel de cuidador (OR = 2,65; IC 95%: 1,07-6,55), vivir en una casa propia (OR = 3,03; IC 95%: 1,04-8,82), con 6 o más habitantes (OR = 2,41; IC 95%: 1,08-5,38). El apoyo de redes se asoció como factor protector (OR = 0,15; IC 95: 0,07-0,33). Conclusiones: Se requieren programas de prevención para evitar el CC y sus complicaciones, así como, intervenciones para mejorar la calidad de vida de los CPI y la de los pacientes cuidados, incorporando estrategias para generar y/o incrementar sus redes de apoyo familiar y social. Abstract: Objective: To characterize the profile of the informal primary caregiver (IPC) of adult patients with type 2 diabetes (T2D) and the possible factors associated with caregiver collapse (CC). Design: Observational, descriptive, cross-sectional and analytical study. Site: Ambulatory Care Medical Unit. Participants: Mexican CPIs of adult patients with T2D. Main measurements: Data were collected through a prolective design using the Zarit scale and a structured survey on sociodemographic factors. A descriptive statistical analysis and univariate and multivariate logistic regression models were performed. Results: The CPI profile is assumed by: women, people aged 36-58, daughters, people with a secondary and high school educational level, married, Catholic, with income 5 years to the care of their patient, without training and with chronic diseases. The risk factors that increase the risk of CC are: being a woman (OR = 11.03; 95% CI: 1.49-81.95), having a history of more than 5 years of having assumed the role of caregiver (OR = 2, 65; 95% CI: 1.07-6.55), living in one's own house (OR = 3.03; 95% CI: 1.04-8.82), with 6 or more inhabitants (OR = 2.41; 95% CI: 1.08-5.38). The support of other family members and/or friends was associated as a protective factor (OR = 0.15; 95% CI: 0.07-0.33). Conclusions: Prevention programs are required to avoid CC and complications, as well as interventions to improve the quality of life of the CPI and patients in care, incorporating strategies to generate and/or increase their family and social support networks.

Abstract Objective The goal of this research was to evaluate the effect of DM type 2 (DM2) on SE severity, neurodegeneration, and brain oxidative stress (OS) secondary to seizures. Methods DM2 was induced in postnatal day (P) 3 male rat pups by injecting streptozocin (STZ) 100 mg/kg; control rats were injected with citrate buffer as vehicle. At P90, SE was induced by the lithium–pilocarpine administration and seizure latency, frequency, and severity were evaluated. Neurodegeneration was assessed 24 h after SE by Fluoro‐Jade B (F‐JB) staining, whereas OS was estimated by measuring lipid peroxidation and reactive oxygen species (ROS). Results DM2 rats showed an increase in latency to the first generalized seizure and SE onset, had a higher number and a longer duration of seizures, and displayed a larger neurodegeneration in the hippocampus (CA3, CA1, dentate gyrus, and hilus), the piriform cortex, the dorsomedial nucleus of the thalamus and the cortical amygdala. Our results also show that only SE, neither DM2 nor the combination of DM2 with SE, caused the increase in ROS and brain lipid peroxidation. Significance DM2 causes higher seizure severity and neurodegeneration but did not exacerbate SE‐induced OS under these conditions. Plain Language Summary Our research performed in animal models suggests that type 2 diabetes mellitus (DM2) may be a risk factor for causing higher seizure severity and seizure‐induced neuron cell death. However, even when long‐term seizures promote an imbalance between brain pro‐oxidants and antioxidants, DM2 does not exacerbate that disproportion.

Abstract The pancreas fat content has been poorly investigated in essential hypertension. The authors aim to relate pancreas and liver fat content with parameters measuring insulin resistance, beta‐cell function and also with markers of endothelial dysfunction and platelet or endothelial cell destruction. The authors studied a group of 40 male hypertensive patients with well‐controlled blood pressure, maintaining a stable weight, and having not changed their medication during the last year. Pancreas fat content was correlated with HOMA‐IR (r = .616, p

Neuroglobin (Ngb) is a protein expressed in the central and peripherical nervous systems of the vertebrate. The Ngb has different functions in neurons, including regulating O2 homeostasis, oxidative stress, and as a neuroprotector after ischemia/hypoxia events. The Ngb is a hemoprotein of the globin family, structurally like myoglobin and hemoglobin. Ngb has higher expression in the cortex, hypothalamus, thalamus, brainstem, and cerebellum in mammals. Interestingly, Ngb immunoreactivity oscillates according to the sleep-wake cycle and decreases after 24 hours of sleep deprivation, suggesting that sleep homeostasis regulates Ngb expression. In addition, Ngb expresses in brain areas related to REM sleep regulation. Therefore, in the present review, we discuss the potential role of the Ngb in the sleep-wake regulation of mammals.

Este estudio de tiene por objetivo utilizar clasificadores de machine learning para predecir el reino al que pertenece un organismo por la frecuencia de uso de codones de ADN. Para ello se ha tomado 13 028 datos de organismos del GenBank distribuidos en once reinos y se los redujo a seis reinos (arqueas, bacterias, invertebrados, plantas, virus y vertebrados) con 9027 datos reagrupados. El proceso requirió la, depuración de atributos irrelevantes, el empleo de métricas de medición de clasificadores de exactitud, precisión, sensibilidad y puntuación, así como el ajuste de hiperparámetros de los modelos. Los algoritmos de clasificación fueron voting, bagging, boosting y stacking, usando KNN, AD, MLP, SVC y RF. La selección de atributos se hizo con random forest. El ensamble stacking, con sus modelos, predice mejor la clasificación de organismos en el presente estudio.

Abstract From aerial parts of Austroeupatorium inulifolium was isolated the ent-nor-furano triol labdane austroeupatol 1. The compound 1 was treated with IBX showing an unexpected selectivity at the potentially oxidizable sites of the substrate yielding the 2-oxoaustroeupatol (2) and 2,19-dioxoaustroeupatol (3). The treatment of 2 with sodium periodate yields a heterocyclic derivative (ε-caprolactone derivate 4) formed by oxidative cleavage and unexpected intramolecular attack of the hydroxymethylene (C-19) oxygen to the ketonic carbon (C-2). A plausible mechanistic pathway for the obtention of compound 4 is proposed. Graphical Abstract

Introducción: La población creciente en la Tierra requiere la expansión e intensificación de la producción acuícola. El interés en los sistemas basados en biofloc ha aumentado porque pueden proporcionar bioseguridad, son financieramente sostenibles y pueden aplicarse en diversos sistemas. Objetivo: Realizar una revisión de la literatura científica sobre la importancia del biofloc en la acuicultura. Materiales y métodos: Se realizó una búsqueda de información en la literatura científica especializada; sintetizándose lo más importante, por lo que se logró definir el concepto de Biofloc, sus características más relevantes, condiciones de desarrollo; así como otros aspectos de vital importancia para su aplicación. Resultados y discusión: Los bioflocs son una comunidad formada por microorganismos asociados entre sí en un sustrato suspendido que responde a una dinámica de malla trófica. El desarrollo del biofloc se ve afectado por una serie de factores y su calidad nutricional es similar a la del alimento obtenido por las especies cultivadas en su hábitat natural. Las fuentes de carbono más utilizadas en los sistemas biofloc son: azúcar, melaza y almidón; sin embargo, los residuos agroindustriales son ricos en compuestos bioactivos, por lo que pueden ser utilizados como materia prima para el crecimiento microbiano. Conclusiones: Aunque queda mucho por saber, el hecho de que la tecnología de bioflocs trate conceptualmente los desechos como una oportunidad para la producción en el sitio, lo convierte en una alternativa posible y amigable con el ecosistema.

Introducción: La biomasa lignocelulósica y en especial los subproductos agroindustriales han dejado de ser productos desecho-problema, para convertirse en materia prima potencial para diversos procesos, siendo la producción de bioetanol uno de los más importantes. Objetivo: Analizar alternativas tecnológicas de producción de bioetanol a partir de bagazo de caña de azúcar para que el proceso sea eficiente técnica, económica y ambientalmente, mediante la simulación del proceso. Materiales y Métodos: Se partió del diseño tecnológico de un caso base de una planta para la producción de bioetanol y se simularon tres alternativas tecnológicas: (1) la influencia de la humedad del bagazo, (2) la influencia de la velocidad de dilución y (3) la sacarificación y fermentación simultáneas. Resultados y Discusión: Con la comparación de los análisis técnicos, económicos y ambientales, se determinó que los mejores resultados se obtuvieron con la alternativa 3, que incluye el proceso de sacarificación y fermentación simultánea. Conclusiones: Con la alternativa 3 se obtiene una producción de 1 275 279,0 L/año de bioetanol a 95,85% de pureza, una productividad de 2,51 g/Lh, el costo unitario de 8,79 $/L y con resultados ambientales satisfactorios.

Abstract SARS‐CoV‐2 is causing devastation both in human lives and economic resources. When the world seems to start overcoming the pandemics scourge, the threat of long‐term complications of COVID‐19 is rising. Reports show that some of these long‐term effects may contribute to the main cause of morbimortality worldwide: the vascular diseases. Given the evidence of damage in the endothelial cells due to SARS‐CoV‐2 and that endothelial dysfunction precedes the development of arteriosclerosis, the authors propose to measure endothelial function around 6–12 months after acute disease in hypertensive patients, especially if they have other cardiovascular risk factors or overt vascular disease. The methods the authors propose are cost‐effective and can be made available to any hypertension unit. These methods could be the “in vivo” assessment of endothelial function by flow mediated vasodilatation after ischemia by Laser‐Doppler flowmetry and the measurement of plasma free circulating DNA and microparticles of endothelial origin.

Objetivo: Aplicar la modelación físico-matemática a la dinámica de la COVID-19 para la toma de decisiones asociadas a la mitigación y erradicación de la pandemia en Cuba. Métodos: La modelación se aplicó para caracterizar el pronóstico del pico y el comportamiento reproductivo de la pandemia, mediante herramientas y funciones de MATLAB. El pico se determinó aplicando el modelo SIR, luego de adecuaciones. Este se ajustó con la estrategia de optimización GlobalSearch. Para su solución se empleó la función ode23tb que usa un algoritmo combinado de Runge-Kutta con otro de regla trapezoidal. Para el comportamiento reproductivo se realizó el ajuste de un modelo exponencial empleando la herramienta Curve Fitting. Principales resultados: Se identificaron los parámetros del modelo SIR y se logró el pronóstico del pico con dos semanas de anticipación y una precisión satisfactoria. Se pronosticaron los susceptibles, infectados acumulados y recuperados. El número de reproducción básico (R0) calculado permitió determinar que, para erradicar la pandemia por vacunación, la población inmunizada debe ser superior al 72 %. El número de reproducción efectivo (Ref) permitió evaluar la eficacia de las medidas de mitigación. Se reflexionó sobre la conducta a seguir para su erradicación. Conclusiones: El modelo SIR demostró capacidad para predecir el pico de la pandemia. El R0 del SARS-CoV-2 permitió corroborar su elevada transmisibilidad. Las medidas de mitigación han sido efectivas y deben mantenerse hasta erradicar la pandemia, incluso para Ref < 1, mientras no se inmunice el 72 % de la población, para lograr la erradicación irreversible.

La purificación de enzimas celulasas constituye un paso crítico para su producción debido a que a menudo resulta ser muy costoso. El objetivo de este estudio fue evaluar la precipitación salina de celulasas producidas por Aspergillus niger UC33 en fermentación en estado sólido, para incrementar el rendimiento y pureza de la enzima con el menor costo posible. Se empleó el programa Design-Expert 11.1.2 para el diseño experimental y la optimización de las condiciones experimentales. El sulfato de amonio se utilizó para la precipitación entre 60 y 90 % de saturación, se emplearon entre 1 y 3 h de precipitación y las temperaturas utilizadas fueron 4 y 25 °C. Las condiciones óptimas encontradas para maximizar el rendimiento y la pureza fueron 68,97 % de saturación con sulfato de amonio, tiempo de precipitación de 1,28 h y temperatura de 25 °C. En estas condiciones los valores de rendimiento, pureza y costo, fueron: 74,81 %, 1,26 y USD $ 0,2609, respectivamente. El peso molecular de la enzima fue 38,47 kDa y la actividad celulolítica fue de 31,854 UI.

Three-dimensional insights into the microstructure of composite materials are vital for enhancing their performance under operational conditions. Phase-sensitive methods can offer supplementary data, especially for materials with low absorption, compared to standard absorption-based techniques. This work presents the correlative X-ray imaging and computed tomography results of polymer composites reinforced with glass fibers using an inverted Hartmann mask. This method identified areas with enhanced refraction and scattering due to glass fibers and discriminated signals based on their orientation, offering an advantage in evaluating anisotropic materials. The simplicity of the setup, adding the inverted Hartmann mask, makes integration feasible in commercial CT scanners and existing radiography laboratories, enabling simultaneous phase, scattering, and absorption information extraction. Our approach, which combines refraction and scattering with absorption signals, exposes intricate structures beyond the usual spatial resolution threshold. Despite the distinct absorption coefficients of air, polymer-based, and glass fibers, the inverted Hartmann mask is crucial for examining similar absorption composites and low-absorbing materials. This research offers profound insights into the microstructures of fiber-reinforced polymer composites, laying the groundwork for studies of nanostructured functional composite materials.