Blood-brain barrier biomarkers.

The blood-brain barrier (BBB) is a dynamic interface that regulates the exchange of molecules and cells between the brain parenchyma and the peripheral blood. The BBB is mainly composed of endothelial cells, astrocytes and pericytes. The integrity of this structure is essential for maintaining brain and spinal cord homeostasis and protection from injury or disease. However, in various neurological disorders, such as traumatic brain injury, Alzheimer's disease, and multiple sclerosis, the BBB can become compromised thus allowing passage of molecules and cells in and out of the central nervous system parenchyma. These agents, however, can serve as biomarkers of BBB permeability and neuronal damage, and provide valuable information for diagnosis, prognosis and treatment. Herein, we provide an overview of the BBB and changes due to aging, and summarize current knowledge on biomarkers of BBB disruption and neurodegeneration, including permeability, cellular, molecular and imaging biomarkers. We also discuss the challenges and opportunities for developing a biomarker toolkit that can reliably assess the BBB in physiologic and pathophysiologic states.

Specific nanoprobe design for MRI: Targeting laminin in the blood-brain barrier to follow alteration due to neuroinflammation.

Chronic neuroinflammation is characterized by increased blood-brain barrier (BBB) permeability, leading to molecular changes in the central nervous system that can be explored with biomarkers of active neuroinflammatory processes. Magnetic resonance imaging (MRI) has contributed to detecting lesions and permeability of the BBB. Ultra-small superparamagnetic particles of iron oxide (USPIO) are used as contrast agents to improve MRI observations. Therefore, we validate the interaction of peptide-88 with laminin, vectorized on USPIO, to explore BBB molecular alterations occurring during neuroinflammation as a potential tool for use in MRI. The specific labeling of NPS-P88 was verified in endothelial cells (hCMEC/D3) and astrocytes (T98G) under inflammation induced by interleukin 1ß (IL-1ß) for 3 and 24 hours. IL-1ß for 3 hours in hCMEC/D3 cells increased their co-localization with NPS-P88, compared with controls. At 24 hours, no significant differences were observed between groups. In T98G cells, NPS-P88 showed similar nonspecific labeling among treatments. These results indicate that NPS-P88 has a higher affinity towards brain endothelial cells than astrocytes under inflammation. This affinity decreases over time with reduced laminin expression. In vivo results suggest that following a 30-minute post-injection, there is an increased presence of NPS-P88 in the blood and brain, diminishing over time. Lastly, EAE animals displayed a significant accumulation of NPS-P88 in MRI, primarily in the cortex, attributed to inflammation and disruption of the BBB. Altogether, these results revealed NPS-P88 as a biomarker to evaluate changes in the BBB due to neuroinflammation by MRI in biological models targeting laminin.

Inequalities in noise will affect urban wildlife.

Understanding how systemic biases influence local ecological communities is essential for developing just and equitable environmental practices that prioritize both human and wildlife well-being. With over 270 million residents inhabiting urban areas in the United States, the socioecological consequences of racially targeted zoning, such as redlining, need to be considered in urban planning. There is a growing body of literature documenting the relationships between redlining and the inequitable distribution of environmental harms and goods, green space cover and pollutant exposure. However, it remains unknown whether historical redlining affects the distribution of urban noise or whether inequitable noise drives an ecological change in urban environments. Here we conducted a spatial analysis of how urban noise corresponds to the distribution of redlining categories and a systematic literature review to summarize the effects of noise on wildlife in urban landscapes. We found strong evidence to indicate that noise is inequitably distributed in redlined urban communities across the United States, and that inequitable noise may drive complex biological responses across diverse urban wildlife, reinforcing the interrelatedness of socioecological outcomes. These findings lay a foundation for future research that advances relationships between acoustic and urban ecology through centring equity and challenging systems of oppression in wildlife studies.

Clinical evaluation of peripheral tissue perfusion as a predictor of mortality in sepsis and septic shock in the intensive care unit: Systematic review and meta-analysis / Evaluación clínica de la perfusión tisular periférica como predictor de mortalidad en sepsis y choque séptico en la unidad de terapia intensiva: Revisión sistemática y metaanálisis

Objective: To determine the diagnostic performance of the clinical evaluation of peripheral tissue perfusion in the prediction of mortality. Design: Systematic review and meta-analysis. Setting: Intensive care unit. Patients and participants: Patients with sepsis and septic shock. Intervention: Studies of patients with sepsis and/or septic shock that associated clinical monitoring of tissue perfusion with mortality were included. A systematic review was performed by searching the PubMed/MEDLINE, Cochrane Library, SCOPUS, and OVID databases. Main variables of interest: The risk of bias was assessed with the QUADAS-2 tool. Sensitivity and specificity were calculated to evaluate the predictive accuracy for mortality. Review Manager software version 5.4 was used to draw the forest plot graphs, and Stata version 15.1 was used to build the hierarchical summary receiver operating characteristic model. Results: Thirteen studies were included, with a total of 1667 patients and 17 analyses. Two articles evaluated the temperature gradient, four evaluated the capillary refill time, and seven evaluated the mottling in the skin. In most studies, the outcome was mortality at 14 or 28 days. The pooled sensitivity of the included studies was 70%, specificity 75.9% (95% CI, 61.6%–86.2%), diagnostic odds ratio 7.41 (95% CI, 3.91–14.04), and positive and negative likelihood ratios 2.91 (95% CI, 1.80–4.72) and 0.39 (95% CI, 0.30–0.51), respectively. Conclusions: Clinical evaluation of tissue perfusion at the bedside is a useful tool, with moderate sensitivity and specificity, to identify patients with a higher risk of death among those with sepsis and septic shock. (AU)

Objetivo: Determinar el rendimiento diagnóstico de la evaluación clínica de la perfusión tisular periférica en la predicción de mortalidad. Diseño: Revisión sistemática y metaanálisis. Ámbito: Unidad de cuidados intensivos. Pacientes y participantes: Pacientes con sepsis y shock séptico. Intervenciones: Se incluyeron estudios de pacientes con sepsis y/o shock séptico que asociaron la monitorización clínica de la perfusión tisular con la mortalidad. Se realizó una revisión sistemática buscando en las bases de datos PubMed/MEDLINE, Cochrane Library, SCOPUS y OVID. Variables de interés principales: El riesgo de sesgo se evaluó con la herramienta QUADAS-2. Se calcularon la sensibilidad y la especificidad para evaluar la precisión predictiva de la mortalidad. Resultados: Se incluyeron trece estudios, con un total de 1667 pacientes y 17 análisis. Dos artículos evaluaron gradiente de temperatura, cuatro evaluaron tiempo de llenado capilar y siete evaluaron moteado en la piel. La mayoría de los estudios midieron mortalidad a 14 o 28 días. La sensibilidad agrupada de los estudios incluidos fue 70% y especificidad 75,9% (IC del 95%, 61,6%–86,2%), la razón de probabilidad diagnóstica 7,41 (IC del 95%, 3,91–14,04) y la razón de probabilidad positiva y negativa 2,91 (IC del 95%, IC, 1,80–4,72) y 0,39 (IC 95%, 0,30–0,51), respectivamente. Conclusiones: La evaluación clínica de la perfusión tisular es una herramienta útil, con sensibilidad y especificidad moderadas, para identificar pacientes con sepsis y shock séptico con mayor riesgo de muerte. (AU)

ß-Phase Enhancement of Force Spun Composite Nanofibers for Sensing Applications.

In this study, a piezoelectric harvesting device was developed using polyvinylidene fluoride (PVDF) nanofibers reinforced with either BaTiO3 nanoparticles or graphene powder. BaTiO3 nanoparticles were synthesized through the sol-gel method with an average size of approximately 32 nm. The PVDF nanofibers, along with the nanoparticle composites in an acetone-N,N-dimethylformamide mixture, were produced using a centrifugal Forcespinning™ machine, resulting in a heterogeneous arrangement of fiber meshes, with an average diameter of 1.6 µm. Experimental tests revealed that the electrical performance of the fabricated harvester reached a maximum value of 35.8 Voc, demonstrating the potential of BaTiO3/ PVDF-based piezoelectric devices for designing wearable applications such as body-sensing and energy-harvesting devices.

Magnetic and Viscoelastic Response of Magnetorheological Elastomers Based on a Combination of Iron Nano- and Microparticles.

In this paper, we discuss the creation of a hybrid magnetorheological elastomer that combines nano- and microparticles. The mixture contained 45 wt.% fillers, with combinations of either 0% nanoparticles and 100% microparticles or 25% nanoparticles and 75% microparticles. TGA and FTIR testing confirmed the materials' thermal and chemical stability, while an SEM analysis determined the particles' size and morphology. XRD results were used to determine the crystal size of both nano- and microparticles. The addition of reinforcing particles, particularly nanoparticles, enhanced the stiffness of the composite materials studied, but their overall strength was only minimally affected. The computed interaction parameter relative to the volume fraction was consistent with the previous literature. Furthermore, the study observed a magnetic response increment in composite materials reinforced with nanoparticles above 30 Hz. The isotropic material containing only microparticles had a lower storage modulus than the isotropic sample with nanoparticles without a magnetic field. However, when a magnetic field was applied, the material with only microparticles exhibited a higher storage modulus than the samples with nanoparticles.

Clinical evaluation of peripheral tissue perfusion as a predictor of mortality in sepsis and septic shock in the intensive care unit: Systematic review and meta-analysis.

OBJECTIVE: To determine the diagnostic performance of the clinical evaluation of peripheral tissue perfusion in the prediction of mortality. DESIGN: Systematic review and meta-analysis. SETTING: Intensive care unit. PATIENTS AND PARTICIPANTS: Patients with sepsis and septic shock. INTERVENTIONS: Studies of patients with sepsis and/or septic shock that associated clinical monitoring of tissue perfusion with mortality were included. A systematic review was performed by searching the PubMed/MEDLINE, Cochrane Library, SCOPUS, and OVID databases. MAIN VARIABLES OF INTEREST: The risk of bias was assessed with the QUADAS-2 tool. Sensitivity and specificity were calculated to evaluate the predictive accuracy for mortality. Review Manager software version 5.4 was used to draw the forest plot graphs, and Stata version 15.1 was used to build the hierarchical summary receiver operating characteristic model. RESULTS: Thirteen studies were included, with a total of 1667 patients and 17 analyses. Two articles evaluated the temperature gradient, four evaluated the capillary refill time, and seven evaluated the mottling in the skin. In most studies, the outcome was mortality at 14 or 28 days. The pooled sensitivity of the included studies was 70%, specificity 75.9% (95% CI, 61.6%-86.2%), diagnostic odds ratio 7.41 (95% CI, 3.91-14.04), and positive and negative likelihood ratios 2.91 (95% CI, 1.80-4.72) and 0.39 (95% CI, 0.30-0.51), respectively. CONCLUSIONS: Clinical evaluation of tissue perfusion at the bedside is a useful tool, with moderate sensitivity and specificity, to identify patients with a higher risk of death among those with sepsis and septic shock. REGISTRATION: PROSPERO CRD42019134351.

Medium-chain fatty acids modify macrophage expression of metabolic and inflammatory genes in a PPAR ß/δ-dependent manner.

There is great interest on medium chain fatty acids (MCFA) for cardiovascular health. We explored the effects of MCFA on the expression of lipid metabolism and inflammatory genes in macrophages, and the extent to which they were mediated by the nuclear receptor peroxisome proliferator-activated receptor beta/delta (PPAR ß/δ). J774A.1 murine macrophages were exposed to octanoate or decanoate as MCFA, a long-chain fatty acid control (palmitate), or the PPAR ß/δ agonist GW501516, with or without lipopolysaccharide (LPS) stimulation, and with or without an siRNA-induced knockdown of PPAR ß/δ. MCFA increased the expression of Plin2, encoding a lipid-droplet associated protein with anti-inflammatory effects in macrophages, in a partially PPAR ß/δ-dependent manner. Both MCFA stimulated expression of the cholesterol efflux pump ABCA1, more pronouncedly under LPS stimulation and in the absence of PPAR ß/δ. Octanoate stimulated the expression of Pltp, encoding a phospholipid transfer protein that aids ABCA1 in cellular lipid efflux. Only palmitate increased expression of the proinflammatory genes Il6, Tnf, Nos2 and Mmp9. Non-stimulated macrophages exposed to MCFA showed less internalization of fluorescently labeled lipoproteins. MCFA influenced the transcriptional responses of macrophages favoring cholesterol efflux and a less inflammatory response compared to palmitate. These effects were partially mediated by PPAR ß/δ.

CD4+ T cells regulate sickness-induced anorexia and fat wasting during a chronic parasitic infection.

Infections cause catabolism of fat and muscle stores. Traditionally, studies have focused on understanding how the innate immune system contributes to energy stores wasting, while the role of the adaptive immune system remains elusive. In the present study, we examine the role of the adaptive immune response in adipose tissue wasting and cachexia using a murine model of the chronic parasitic infection Trypanosoma brucei, the causative agent of sleeping sickness. We find that the wasting response occurs in two phases, with the first stage involving fat wasting caused by CD4+ T cell-induced anorexia and a second anorexia-independent cachectic stage that is dependent on CD8+ T cells. Fat wasting has no impact on host antibody-mediated resistance defenses or survival, while later-stage muscle wasting contributes to disease-tolerance defenses. Our work reveals a decoupling of adaptive immune-mediated resistance from the catabolic response during infection.

Age-dependent roles of cardiac remodeling in sepsis defense and pathogenesis.

Disease tolerance is a defense strategy essential for survival of infections, limiting physiological damage without killing the pathogen. The disease course and pathology a pathogen may cause can change over the lifespan of a host due to the structural and functional physiological changes that accumulate with age. Since successful disease tolerance responses require the host to engage mechanisms that are compatible with the disease course and pathology caused by an infection, we predicted that this defense strategy would change with age. Animals infected with a lethal dose 50 (LD50) of a pathogen often display distinct health and sickness trajectories due to differences in disease tolerance, and thus can be used to delineate tolerance mechanisms. Using a polymicrobial sepsis model, we found that despite having the same LD50, old and young susceptible mice exhibited distinct disease courses. Young survivors employed a cardioprotective mechanism via FoxO1-mediated regulation of the ubiquitin-proteosome system that was necessary for survival and protection from cardiomegaly. This same mechanism was a driver of sepsis pathogenesis in aged hosts, causing catabolic remodeling of the heart and death. Our findings have implications for the tailoring of therapy to the age of an infected individual and suggest that disease tolerance alleles may exhibit antagonistic pleiotropy.

DDC_Calc, software para diagnosticar la displasia del desarrollo de cadera en lactantes (versión 1)

Fundamento la displasia del desarrollo de la cadera constituye la afección más frecuente del desarrollo del sistema musculoesquelético. En el contexto del diagnóstico radiográfico de esta enfermedad en el lactante, las radiografías digitales ofrecen ventajas que pudieran ser aprovechadas para un diagnóstico más preciso. Objetivo describir el funcionamiento del software DDC_Calc para realizar mediciones radiográficas en formato digital. Métodos se realizó un estudio de innovación tecnológica durante el año 2019, en el Hospital Pediátrico Universitario Paquito González Cueto, de Cienfuegos, concretamente en el Servicio de Ortopedia y con la contribución de personal de la Facultad de Matemática, Física y Computación, de la Universidad Central "Marta Abreu", de Las Villas. Se utilizó el algoritmo de visión artificial Viola-Jones para la detección de las estructuras, así como un sistema basado en reglas con vistas a una sugerencia del diagnóstico. Resultados el software integró las herramientas necesarias para la realización de las mediciones utilizadas (ángulos, distancias, posiciones) en el diagnóstico radiográfico de la displasia del desarrollo de cadera. Fueron descritas sus funcionalidades, requisitos y funcionamiento de la aplicación, partiendo de un caso clínico real, todo esto ilustrado con imágenes. Conclusiones el empleo del software facilita la realización de mediciones más exactas por parte del médico, de modo que garantiza mayor calidad en el diagnóstico y la preservación de los hallazgos radiográficos iniciales, los cuales resultan de gran utilidad en el seguimiento radiográfico de la afección en el tiempo.

Background developmental dysplasia of the hip constitutes the most frequent affection for the development of the musculoskeletal system. In the context of radiographic diagnosis of this disease in infants, digital radiographs offer advantages that could be used for a more accurate diagnosis. Objective to describe the DDC_Calc software operation to perform radiographic measurements in digital format. Methods a technological innovation study was carried out during 2019, at the Paquito González Cueto University Pediatric Hospital, in Cienfuegos, specifically in the Orthopedics Service and with the specialists' contribution from the "Marta Abreu" Central University' Mathematics, Physics and Computing Faculty, Las Villas. The Viola-Jones artificial vision algorithm was used for the detection of the structures, as well as a rule-based system with a view to a diagnostic suggestion. Results the software integrated the necessary tools to carry out the measurements used (angles, distances, positions) in the radiographic diagnosis of developmental dysplasia of the hip. Its functionalities, requirements and operation of the application were described, based on a real clinical case, all illustrated with images. Conclusions the use of the software facilitates the performance of more accurate measurements by the doctor, thus guaranteeing higher quality in the diagnosis and the preservation of the initial radiographic findings, which are very useful in the radiographic follow-up of the condition in time.

Mediciones radiográficas y diagnóstico de la displasia de cadera del lactante mediante visión computacional y sistema basado en reglas / Radiographic Measurements and Diagnosis of Hip Dysplasia in Infants Using Computer Vision and a Rule-Based System

RESUMEN Fundamento el uso de radiografías digitales para el diagnóstico de la displasia del desarrollo de la cadera permite, además del diagnóstico precoz y mayor eficiencia del trabajo, realizar mediciones más precisas, el seguimiento del paciente y la planificación quirúrgica. Objetivo describir una herramienta capaz de detectar estructuras y puntos de interés de forma semiautomática para realizar las mediciones y cálculos necesarios con vistas al diagnóstico de la displasia de cadera en lactantes. Métodos estudio de innovación tecnológica, donde se utilizó el algoritmo de visión artificial Viola-Jones para la detección de las estructuras, así como un sistema basado en reglas con vistas a una sugerencia del diagnóstico. La herramienta propuesta (Software para las mediciones radiográficas con vistas al diagnóstico de la displasia del desarrollo de cadera en lactantes) se encuentra en fase de prueba y explotación en el Hospital Pediátrico Universitario Paquito González Cueto, de Cienfuegos. Para validar los resultados se tomaron estudios radiográficos de 12 casos, a los cuales se aplicaron las mediciones con el método tradicional y luego mediante el software. Resultados se obtuvo un sistema con vistas a determinar estructuras en las imágenes de radiografía de cadera, las cuales permiten obtener puntos y líneas para calcular los indicadores de displasia. La tasa de acierto al detectar las estructuras fue del 100 %. Conclusión existió una alta coincidencia entre las medidas calculadas por el algoritmo y las calculadas manualmente. La correspondencia entre el diagnóstico predicho por el sistema y el emitido por los médicos especialistas también fue elevada.

ABSTRACT Background the use of digital radiographs for the diagnosis of developmental dysplasia of the hip allows, in addition to early diagnosis and greater work efficiency, more precise measurements, patient monitoring and surgical planning. Objective to describe a tool capable of detecting structures and points of interest in a semi-automatic way to carry out the necessary measurements and calculations with a view to diagnosing hip dysplasia in infants. Methods study of technological innovation, where the Viola-Jones artificial vision algorithm was used for the detection of structures, as well as a rule-based system with a view to a diagnosis suggestion. The proposed tool (Software for radiographic measurements for diagnosing developmental dysplasia of the hip in infants) is in the testing and exploitation phase at the Paquito González Cueto University Pediatric Hospital, in Cienfuegos. To validate the results, radiographic studies of 12 cases were chosen, to which measurements were applied using the traditional method and then using the software. Results a system was obtained with a view to determining structures in hip radiography images, which allow points and lines to be obtained to calculate dysplasia indicators. The success rate in detecting the structures was 100%. Conclusion there was a high coincidence between the measures calculated by the algorithm and those calculated manually. The correspondence between the diagnosis predicted by the system and that issued by specialist doctors was also high.

Chronic Leptin Deficiency Improves Tolerance of Physiological Damage and Host-Pathogen Cooperation during Yersinia pseudotuberculosis Infection.

To combat infections, hosts employ a combination of antagonistic and cooperative defense strategies. The former refers to pathogen killing mediated by resistance mechanisms, while the latter refers to physiological defense mechanisms that promote host health during infection independent of pathogen killing, leading to an apparent cooperation between the host and the pathogen. Previous work has shown that Leptin, a pleiotropic hormone that plays a central role in regulating appetite and energy metabolism, is indispensable for resistance mechanisms, while a role for Leptin signaling in cooperative host-pathogen interactions remains unknown. Using a mouse model of Yersinia pseudotuberculosis (Yptb) infection, an emerging pathogen that causes fever, diarrhea, and mesenteric lymphadenitis in humans, we found that the physiological effects of chronic Leptin-signaling deficiency conferred protection from Yptb infection due to increased host-pathogen cooperation rather than greater resistance defenses. The protection against Yptb infection was independent of differences in food consumption, lipolysis, or fat mass. Instead, we found that the chronic absence of Leptin signaling protects from a shift to lipid utilization during infection that contributes to Yptb lethality. Furthermore, we found that the survival advantage conferred by Leptin deficiency was associated with increased liver and kidney damage. Our work reveals an additional level of complexity for the role of Leptin in infection defense and demonstrates that in some contexts, in addition to tolerating the pathogen, tolerating organ damage is more beneficial for survival than preventing the damage.

Analysis of the Chemical Composition and Morphological Characterization of Tissue Osseointegrated to a Dental Implant after 5 Years of Function.

Osseointegration implies the coexistence of a biocompatible implant subjected to masticatory loads and living bone tissue adhered to its surface; this interaction is a critical process for the success of implants. The objective of this work is to analyze the osseoformation and osseointegration of a dental implant in operation for 5 years microscopically through morphological analysis of the surface and chemical composition through a variable pressure scanning electron microscope (VP-SEM) and energy dispersive X-ray spectrometry (EDX). The chemical composition and general characteristics of the structural morphology of random areas of the surfaces of an osseointegrated dental implant from an ex vivo sample were analyzed. On the surface of the implant free of bone tissue, titanium (TI) was mainly identified in the area of the implant threads and carbon (C) in the depth of the implant threads. Phosphorus (P), calcium (Ca), oxygen (O), carbon (C), with dense and homogeneous distribution, and, to a lesser extent, sodium (Na) were detected on the bone surface around the contour of the implant. Regarding the morphological characteristics of the implant surface, a rough structure with some irregularities and detachments of the implant lodged in the bone tissue was observed. Microscopic analysis showed calcified bone tissue distributed in an orderly manner on the coronal and medial surface and sinuous and irregular in the apical area, with the presence of red blood cells. The composition of the implant allows a dynamic process of bone remodeling and regeneration subject to the biological and mechanical needs of the operation. Dental implants are shown to have exceptional and long-lasting biocompatibility that enables the formation of mature peri-implant bone tissue.

Engineering and Evaluation of Forcespun Gelatin Nanofibers as an Isorhamnetin Glycosides Delivery System.

Opuntia ficus-indica (L.) Mill (OFI) is considered a natural source of bioactive phytochemicals, mainly isorhamnetin glycosides (IRGs). These compounds have demonstrated antioxidant, anti-inflammatory, and anticancer activities, among others. The development of a suitable delivery system for these compounds is needed to improve their chemical and biological stability. This study aimed to evaluate the feasibility of fabrication and characterization of IRG-loaded gelatin (GL) forcespun fibers and crosslinking with glutaraldehyde (GTA). Two different percentages (25% and 30% w/v) of GL were evaluated with 12% (w/v) OFI flour to obtain nanofibers GL/OFI1 and GL/OFI2, respectively. The morphology and physicochemical properties of the fibers were investigated. The results indicated that the diameters of the fibers were on the nanoscale. The amount of IRGs was determined using high-performance liquid chromatography (HPLC). The IRGs release and the cytocompatibility of the nanofibers were also evaluated. GL concentration significantly affected the IRG release. Among both nanofibers, the GL/OFI2 nanofiber achieved a cumulative IRGs release of 63% after 72 h. Both fibers were shown to be biocompatible with human skin/fibroblast cells. Specifically, GL/OFI1 nanofibers exhibited favorable features for their application as an extract-coupled release system. The IRGs-embedded GL nanofiber mats may become a good alternative for the delivery of phytochemicals for the health sector and biomedical applications.

Laminin as a Biomarker of Blood-Brain Barrier Disruption under Neuroinflammation: A Systematic Review.

Laminin, a non-collagenous glycoprotein present in the brain extracellular matrix, helps to maintain blood-brain barrier (BBB) integrity and regulation. Neuroinflammation can compromise laminin structure and function, increasing BBB permeability. The aim of this paper is to determine if neuroinflammation-induced laminin functional changes may serve as a potential biomarker of alterations in the BBB. The 38 publications included evaluated neuroinflammation, BBB disruption, and laminin, and were assessed for quality and risk of bias (protocol registered in PROSPERO; CRD42020212547). We found that laminin may be a good indicator of BBB overall structural integrity, although changes in expression are dependent on the pathologic or experimental model used. In ischemic stroke, permanent vascular damage correlates with increased laminin expression (ß and γ subunits), while transient damage correlates with reduced laminin expression (α subunits). Laminin was reduced in traumatic brain injury and cerebral hemorrhage studies but increased in multiple sclerosis and status epilepticus studies. Despite these observations, there is limited knowledge about the role played by different subunits or isoforms (such as 411 or 511) of laminin in maintaining structural architecture of the BBB under neuroinflammation. Further studies may clarify this aspect and the possibility of using laminin as a biomarker in different pathologies, which have alterations in BBB function in common.

Optimal Morphometric Characteristics of a Tubular Polymeric Scaffold to Promote Peripheral Nerve Regeneration: A Scoping Review.

Cellular behavior in nerve regeneration is affected by the architecture of the polymeric nerve guide conduits (NGCs); therefore, design features of polymeric NGCs are critical for neural tissue engineering. Hence, the purpose of this scoping review is to summarize the adequate quantitative/morphometric parameters of the characteristics of NGC that provide a supportive environment for nerve regeneration, enhancing the understanding of a previous study. 394 studies were found, of which 29 studies were selected. The selected studies revealed four morphometric characteristics for promoting nerve regeneration: wall thickness, fiber size, pore size, and porosity. An NGC with a wall thickness between 250-400 µm and porosity of 60-80%, with a small pore on the inner surface and a large pore on the outer surface, significantly favored nerve regeneration; resulting in an increase in nutrient permeability, retention of neurotrophic factors, and optimal mechanical properties. On the other hand, the superiority of electrospun fibers is described; however, the size of the fiber is controversial in the literature, obtaining optimal results in the range of 300 nm to 30 µm. The incorporation of these optimal morphometric characteristics will encourage nerve regeneration and help reduce the number of experimental studies as it will provide the initial morphometric parameters for the preparation of an NGC.

Ventilación mecánica invasiva en pacientes con COVID-19 en un hospital privado de México. Una serie de casos: descripción y evolución de un protocolo de intubación temprana / Invasive mechanical ventilation in patients with COVID-19 in a private hospital in Mexico. A case series: description and evolution of an early intubation protocol / Ventilação mecânica invasiva em pacientes com COVID-19 em um hospital privado no México. Uma série de casos: descrição e evolução de um protocolo de intubação precoce

Resumen: La mortalidad de los pacientes de COVID-19 en ventilación mecánica y las estrategias empleadas varían en la literatura. El objetivo de esta serie de casos es describir el curso clínico de pacientes en ventilación mecánica invasiva con COVID-19 y su desenlace a 28 días. Se incluyeron 21 pacientes con un promedio de edad de 49 ± 13 años, 81% de sexo masculino y 38% con al menos una comorbilidad. Las variables ventilatorias iniciales fueron PaO2/FiO2 de 135 ± 53, PEEP 12 cmH2O, presión meseta 26 ± 4.8 cmH2O, distensibilidad estática 32 ± 8.5 mL/cmH2O, driving pressure 15 ± 3.9 cmH2O y poder mecánico 19.2 ± 4 J/min. El 67% de los pacientes estuvieron en posición prono y en 76% se empleó bloqueante neuromuscular. Los desenlaces a 28 días fueron 21 días libres de ventilación mecánica y 14% de mortalidad.

Abstract: The mortality and ventilation strategies of COVID-19 ARDS vary in the literature. The objective of this case series is to describe the clinical course of patients on invasive mechanical ventilation with COVID-19 and its outcome at 28 days. Twenty-one patients were included with an average age of 49 ± 13 years, 81% male and 38% with at least one comorbidity. The initial ventilatory variables were PaO2/FiO2 of 135 ± 53, PEEP 12 cmH2O, plateau pressure 26 ± 4.8 cmH2O, static compliance 32 ± 8.5 mL/cmH2O, driving pressure 15 ± 3.9 cmH2O, and mechanical power 19.2 ± 4 J/min. 67% of the patients received prone position and in 76% a neuromuscular blocker was used. The 28-day outcomes were 21 days of mechanical ventilation-free days and 14% mortality.

Resumo: A mortalidade de pacientes com COVID-19 em ventilação mecânica e as estratégias utilizadas variam na literatura. O objetivo desta série de casos é descrever a evolução clínica de pacientes em ventilação mecânica invasiva com COVID-19 e sua evolução em 28 dias. Incluíram-se 21 pacientes com média de idade de 49 ± 13 anos, 81% do sexo masculino e 38% com pelo menos uma comorbidade. As variáveis ventilatórias iniciais foram PaO2/FiO2 135 ± 53, PEEP 12 cmH2O, pressão de platô 26 ± 4.8 cmH2O, complacência estática 32 ± 8.5 mL/cmH2O, pressão motriz 15 ± 3.9 cmH2O e potência mecânica 19.2 ± 4 J/min. 67% dos pacientes estavam em decúbito ventral e em 76% foi utilizado bloqueador neuromuscular. Os resultados aos 28 dias foram 21 dias sem ventilação mecânica e 14% de mortalidade.

Multi-Criteria Analysis for the Prioritization of Areas for the In Situ Conservation of Crataegus L., an Underutilized Fruit Tree in Mexico.

Complementary ex situ and in situ conservation, including the on-farm alternative, is a highly desired and dynamic strategy that allows the natural evolution of the conserved germplasm. Due to the high costs involved, in addition to the limitations of both economic and human resources, in situ conservation must focus on areas where the greatest benefits are obtained, and the efforts made result in better impacts. Therefore, using spatial multi-criteria analysis and expert knowledge, 22 and 23 criteria were obtained as important for the conservation of wild and cultivated hawthorn, respectively. Criteria weights were calculated by the analytic hierarchy process and expert knowledge. The results showed species richness, phenotypic and ecogeographic diversity, and areas not covered by the official protected areas network were the most important criteria for in situ conservation of wild hawthorn. Prioritized areas were particularly focused in Chiapas, State of Mexico and Morelos. The prioritized areas for the in situ conservation of cultivated hawthorn were mostly defined by criteria such as number of cultivated varieties, number of uses, phenotypic diversity, ecogeographical diversity, and areas with rainfed agriculture. These areas were located mainly in Puebla. From this study, we propose a list of priority areas for the in situ conservation of both cultivated and wild hawthorn.

Main Morphological Characteristics of Tubular Polymeric Scaffolds to Promote Peripheral Nerve Regeneration-A Scoping Review.

The "nerve guide conduits" (NGC) used in nerve regeneration must mimic the natural environment for proper cell behavior. OBJECTIVE: To describe the main morphological characteristics of polymeric NGC to promote nerve regeneration. METHODS: A scoping review was performed following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) criteria in the PubMed, Web of Science, Science Direct, and Scientific Electronic Library Online (SciELO) databases. Primary studies that considered/evaluated morphological characteristics of NGC to promote nerve regeneration were included. RESULT: A total of 704 studies were found, of which 52 were selected. The NGC main morphological characteristics found in the literature were: (I) NGC diameter affects the mechanical properties of the scaffold. (II) Wall thickness of NGC determines the exchange of nutrients, molecules, and neurotrophins between the internal and external environment; and influences the mechanical properties and biodegradation, similarly to NGC (III) porosity, (IV) pore size, and (V) pore distribution. The (VI) alignment of the NGC fibers influences the phenotype of cells involved in nerve regeneration. In addition, the (VII) thickness of the polymeric fiber influences neurite extension and orientation. CONCLUSIONS: An NGC should have its diameter adjusted to the nerve with wall thickness, porosity, pore size, and distribution of pores, to favor vascularization, permeability, and exchange of nutrients, and retention of neurotrophic factors, also favoring its mechanical properties and biodegradability.