Immune-mediated hepatitis: Basic concepts and treatment.

Immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized advanced cancer management. Nevertheless, the generalized use of these medications has led to an increase in the incidence of adverse immune-mediated events and the liver is one of the most frequently affected organs. Liver involvement associated with the administration of immunotherapy is known as immune-mediated hepatitis (IMH), whose incidence and clinical characteristics have been described by different authors. It often presents as mild elevations of amino transferase levels, seen in routine blood tests, that spontaneously return to normal, but it can also manifest as severe transaminitis, possibly leading to the permanent discontinuation of treatment. The aim of the following review was to describe the most up-to-date concepts regarding the epidemiology, diagnosis, risk factors, and progression of IMH, as well as its incidence in different types of common cancers, including hepatocellular carcinoma. Treatment recommendations according to the most current guidelines are also provided.

Pre- versus Post-synaptic Forms of LTP in Two Branches of the Same Hippocampal Afferent.

There has been considerable controversy about pre- versus postsynaptic expression of memory-related long-term potentiation (LTP), with corresponding disputes about underlying mechanisms. We report here an instance in male mice, in which both types of potentiation are expressed but in separate branches of the same hippocampal afferent. Induction of LTP in the dentate gyrus (DG) branch of the lateral perforant path (LPP) reduces paired-pulse facilitation, is blocked by antagonism of cannabinoid receptor type 1, and is not affected by suppression of postsynaptic actin polymerization. These observations are consistent with presynaptic expression. The opposite pattern of results was obtained in the LPP branch that innervates the distal dendrites of CA3: LTP did not reduce paired-pulse facilitation, was unaffected by the cannabinoid receptor blocker, and required postsynaptic actin filament assembly. Differences in the two LPP termination sites were also noted for frequency facilitation of synaptic responses, an effect that was reproduced in a two-step simulation by small adjustments to vesicle release dynamics. These results indicate that different types of glutamatergic neurons impose different forms of filtering and synaptic plasticity on their afferents. They also suggest that inputs are routed to, and encoded by, different sites within the hippocampus depending upon the pattern of activity arriving over the parent axon.

Scorpion sting envenomation outbreak in Mexico. Strategies for prevention and control.

In Mexico occurs 25% of all worldwide cases of scorpion sting envenomation (SSE). An outbreak of SSE was identified in Villa Unión, Sinaloa, Mexico. The objective of this study is to describe the outbreak, and prevention and control strategies implemented. The design was a cross-sectional study. Eligibility criteria included confirmed cases (n = 425) identified from the date the outbreak was recognized (from November 08, 2023 to July 10, 2023). The cases from Villa Unión (n = 231) were included for the analysis of epidemiological and clinical findings. The research followed the recommendations of the Initiative Reporting of studies Conducted Using Observational Routinely collected Data (RECORD). Of the total cases (n = 425), 398 (93.6%) were from the municipality of Mazatlán, and 231 (58%) were from Villa Unión. The incidence rate was 13.64 per 1000 persons. The average cases per week was 51.5(SD ± 12). The male-to-female ratio was 3:4, the average age was 30.7(SD ± 19) years. Most of cases occurred in the 25-44 age group. The sting occurred mostly inside houses (n = 200, 86.5%). The predominant symptoms were local pain (95.2%), and local paresthesia (75.8%). The Case fatality rate was 0%. Implementation of prevention and control strategies based on field epidemiological research and scientific evidence are necessary to reduce the incidence and prevent fatal complications.

Marginalization and tooth loss in older Mexican adults.

OBJECTIVE: To examine the association between the level of marginalization and tooth loss in adults aged ≥50 years in Mexico. METHODS: A retrospective cross­sectional study was conducted on 2098 adults selected from communities presenting both high and medium levels of marginalization, with data obtained from the annual reports of the Epidemiological Surveillance System of Oral Pathologies 2019-2022. Analysis considered sociodemographic characteristics such as sex, age, and years of education. The prevalence of tooth loss was determined using the Decayed, Missing and Filled teeth (DMFT) index. Negative binomial regression was used to estimate rate ratio (RR) and 95% confidence intervals (CIs), using the presence of lost teeth as an outcome. RESULTS: Most (62.4%) participants had lost at least one tooth, of whom 60.3% had a medium level of marginalization, 28.8% a high level, and 10.9% a very high level. More adults who lived in high or very high marginalization communities had lost teeth [RR=1.19 (95% CI 1.08 - 1.30)] than those living in communities with a medium level of marginalization. More males [RR=1.19 (95% CI 1.09 - 1.31)], adults ≥70 years [RR=1.77 (95% CI 1.57 - 1.99)], people who were illiterate [RR=1.60 (95% CI 1.35 - 1.88)] or who had poor oral hygiene [RR=1.26 (95% CI 1.15 - 1.38)] had also lost teeth. CONCLUSION: High and very high marginalization was associated with tooth loss in adults ≥50 years in Mexico. Effective oral health strategies are required to prevent tooth loss, as are interventions to improve access to and quality of dental services for marginalized communities.

Validation of a sub-epidermal moisture scanner for early detection of pressure ulcers in an ex vivo porcine model of localized oedema.

Pressure ulcers (PUs) remain a chronic health problem with severe impacts on healthcare systems. Early detection is crucial to providing effective interventions. However, detecting PUs currently relies on subjective tissue evaluations, such as visual skin assessment, precluding interventions prior to the development of visible tissue damage. There is an unmet need for solutions that can detect early tissue damage before visual and tactile signs occur. Assessments based on sub-epidermal moisture (SEM) measurements represent an opportunity for robust and objective early detection of PUs, preventing broken skin PUs in more high-risk patients at high-risk anatomical locations. While SEM assessment technology has been validated in computational, bench and tissue phantom models, validation in soft tissue was absent. In this study, we successfully validated the ability of a commercially available SEM assessment device to measure and detect sub-epidermal moisture changes in a novel ex vivo porcine soft tissue model of localised oedema. When controlled and incremental fluid volumes (Phosphate Buffer Solution) were injected into porcine soft tissues, statistically significant differences were found in SEM values between fluid-injected sites, representing an inflammatory oedematous condition, and healthy tissue control sites, as measured by the SEM device. The device provided reproducible readings by detecting localised oedema changes in soft tissues, reflecting the build-up of fluid as small as 1 ml into the underlying tissue. Spatial characterization experiments described the ability of the device technology to differentiate between healthy and oedematous tissue. Our findings validate the use of SEM assessment technology to measure and quantify localized oedema.

The percentage of CD39+ monocytes is higher in pregnant COVID-19+ patients than in nonpregnant COVID-19+ patients.

Current medical guidelines consider pregnant women with COVID-19 to be a high-risk group. Since physiological gestation downregulates the immunological response to maintain "maternal-fetal tolerance", SARS-CoV-2 infection may constitute a potentially threatening condition to both the mother and the fetus. To establish the immune profile in pregnant COVID-19+ patients, a cross-sectional study was conducted. Pregnant women with COVID-19 (P-COVID-19+; n = 15) were analyzed and compared with nonpregnant women with COVID-19 (NP-COVID-19+; n = 15) or those with physiological pregnancy (P-COVID-19-; n = 13). Serological cytokine and chemokine concentrations, leucocyte immunophenotypes, and mononuclear leucocyte responses to polyclonal stimuli were analyzed in all groups. Higher concentrations of serological TNF-α, IL-6, MIP1b and IL-4 were observed within the P-COVID-19+ group, while cytokines and chemokines secreted by peripheral leucocytes in response to LPS, IL-6 or PMA-ionomicin were similar among the groups. Immunophenotype analysis showed a lower percentage of HLA-DR+ monocytes in P-COVID-19+ than in P-COVID-19- and a higher percentage of CD39+ monocytes in P-COVID-19+ than in NP-COVID-19+. After whole blood polyclonal stimulation, similar percentages of T cells and TNF+ monocytes between groups were observed. Our results suggest that P-COVID-19+ elicits a strong inflammatory response similar to NP-COVID19+ but also displays an anti-inflammatory response that controls the ATP/adenosine balance and prevents hyperinflammatory damage in COVID-19.

Transcriptomic responses and apoptosis in larval red drum (Sciaenops ocellatus) co-exposed to crude oil and ultraviolet (UV) radiation.

Ultraviolet (UV) radiation can significantly increase the toxicity of polycyclic aromatic hydrocarbons (PAHs) in crude oil to early life stage (ELS) fishes through photo-induced /photo-enhanced toxicity. However, little is known about the sub-lethal effects and mechanisms of photo-induced PAH toxicity in ELS fishes. The present study investigated apoptosis and global transcriptomic effects in larval red drum (Sciaenops ocellatus) (24-72 h post-fertilization) following co-exposure to oil (0.29-0.30 µg/L ∑PAH50) and UV. Apoptosis was quantified using the TUNEL assay, and transcriptomic effects were assessed using RNA sequencing analysis. Apoptotic fluorescence was greatest in the eyes and skin following 24 and 48 h co-exposure to oil and UV, indicating photo-induced toxicity. Consistent with these phenotypic responses, pathways associated with phototransduction, eye development, and dermatological disease were among the top predicted pathways impacted. The present study is the first to provide global transcriptomic analysis of UV and oil co-exposure in an ELS fish.

Food, energy, and nutrient supply in Mexican households from 1984 to 2018 / Disponibilidad de alimentos, energía y nutrientes en hogares mexicanos de 1984 a 2018

Introduction: information about changes in food and energy supply, macronutrient and micronutrient availability by processing level is required to understand the nutritional transition in Mexican society. Objective: to describe the food, energy, and nutrient supply in Mexican households from 1984 to 2018. Methods: five waves of a Mexican cross-sectional survey were analyzed to identify changes in food, energy, and nutrient supplies in households. Food groups were created using the NOVA classification. The content of energy and nutrients was estimated using Mexican and U.S. databases. The education and income interaction with energy and nutritional supply was analyzed. Results: in this period, the supply of fresh and processed fruits and vegetables, processed meat and dairy, fish and seafood, prepared food, and ultra-processed food and drinks increased, whereas unprocessed or minimally processed (UMP) cereals and tubers, legumes, meat, dairy, eggs, and all processed culinary ingredients decreased. These changes have implied a higher supply of protein, total fat, cholesterol, vitamins A and C, calcium and sodium. Total energy, energy density, carbohydrates, and magnesium and potassium density decreased. Across waves, UMP and processed cereals were the main supply for energy, carbohydrates, fiber, iron and potassium. Dairy was the main supply of saturated fat. UMP and processed cereals were the main source of sodium in 1984, whereas ultra-processed cereals were the main source of sodium in 2018. Conclusions: although UMP foods remain the main group in most Mexican households, their supply has decreased over the years, whereas the supply of ultra-processed foods has increased (AU)

Introducción: se requiere información sobre los cambios de la disponibilidad de alimentos, energía y nutrientes, por nivel de procesamiento, para entender la transición nutricional en México. Objetivo: describir la disponibilidad de alimentos, energía y nutrientes en los hogares mexicanos de 1984 a 2018. Métodos: se crearon grupos usando la clasificación NOVA. El contenido de energía y nutrientes se estimó usando bases de datos mexicanas y estadounidenses. Se analizó la interacción de la educación y el ingreso con la disponibilidad de energía y nutrientes. Resultados: en este periodo aumentó la disponibilidad de verduras naturales y procesadas, carnes y lácteos procesados, pescados y mariscos, comida preparada y comida y bebida ultraprocesada, mientras que los cereales sin procesar o mínimamente procesados (SPMP), las leguminosas, las carnes, los lácteos, los huevos y los ingredientes culinarios procesados disminuyeron. Estos cambios implican una mayor disponibilidad de proteína, grasa total, colesterol, vitamina A y C, calcio y sodio. La energía total, la densidad energética, los carbohidratos y la densidad de magnesio y potasio disminuyeron. A lo largo el tiempo, los cereales SPMP y procesados fueron la principal fuente de energía, carbohidratos, fibra, hierro y potasio. Los lácteos fueron la principal fuente de grasas saturadas. Los cereales SPMP y procesados fueron la principal fuente de sodio en 1984, mientras que los cereales ultraprocesados lo fueron en el 2018. Conclusiones: aunque los alimentos SPMP siguen siendo el grupo más disponible en los hogares, su disponibilidad ha disminuido a lo largo de los años, mientras que la de los ultraprocesados ha aumentado (AU)

Single molecule DNA origami nanoarrays with controlled protein orientation.

The nanoscale organization of functional (bio)molecules on solid substrates with nanoscale spatial resolution and single-molecule control-in both position and orientation-is of great interest for the development of next-generation (bio)molecular devices and assays. Herein, we report the fabrication of nanoarrays of individual proteins (and dyes) via the selective organization of DNA origami on nanopatterned surfaces and with controlled protein orientation. Nanoapertures in metal-coated glass substrates were patterned using focused ion beam lithography; 88% of the nanoapertures allowed immobilization of functionalized DNA origami structures. Photobleaching experiments of dye-functionalized DNA nanostructures indicated that 85% of the nanoapertures contain a single origami unit, with only 3% exhibiting double occupancy. Using a reprogrammed genetic code to engineer into a protein new chemistry to allow residue-specific linkage to an addressable ssDNA unit, we assembled orientation-controlled proteins functionalized to DNA origami structures; these were then organized in the arrays and exhibited single molecule traces. This strategy is of general applicability for the investigation of biomolecular events with single-molecule resolution in defined nanoarrays configurations and with orientational control of the (bio)molecule of interest.

Dynamical response of a rocking rigid block.

This paper investigates the complex dynamical behavior of a rigid block structure under harmonic ground excitation, thereby mimicking, for instance, the oscillation of the system under seismic excitation or containers placed on a ship under periodic acting of sea waves. The equations of motion are derived, assuming a large frictional coefficient at the interface between the block and the ground, in such a way that sliding cannot occur. In addition, the mathematical model assumes a loss of kinetic energy when an impact with the ground takes place. The resulting mathematical model is then formulated and studied in the framework of impulsive dynamical systems. Its complex dynamical response is studied in detail using two different approaches, based on direct numerical integration and path-following techniques, where the latter is implemented via the continuation platform COCO (Dankowicz and Schilder). Our study reveals the presence of various dynamical phenomena, such as branching points, fold and period-doubling bifurcation of limit cycles, symmetric and asymmetric periodic responses, and chaotic motions. By using the basin stability method, we also investigate the properties of solutions and their ranges of existence in phase and parameter spaces. Moreover, the study considers ground excitation conditions leading to the overturning of the block structure and shows parameter regions wherein such behavior can be avoided.

Integration of chronological omics data reveals mitochondrial regulatory mechanisms during the development of hepatocellular carcinoma.

Mitochondria participate in multiple functions in eukaryotic cells. Although disruption of mitochondrial function has been associated with energetic deregulation in cancer, the chronological changes in mitochondria during cancer development remain unclear. With the aim to assess the role of mitochondria throughout cancer development, we analyzed samples chronologically obtained from induced hepatocellular carcinoma (HCC) in rats. In our analyses, we integrated mitochondrial proteomic data, mitochondrial metabolomic data and nuclear genome transcriptomic data. We used pathway over-representation and weighted gene co-expression network analysis (WGCNA) to integrate expression profiles of genes, miRNAs, proteins and metabolite levels throughout HCC development. Our results show that mitochondria are dynamic organelles presenting specific modifications in different stages of HCC development. We also found that mitochondrial proteomic profiles from tissues adjacent to nodules or tumor are determined more by the stage of HCC development than by tissue type, and we evaluated two models to predict HCC stage of the samples using proteomic profiles. Finally, we propose an omics integration pipeline to massively identify molecular features that could be further evaluated as key regulators, biomarkers or therapeutic targets. As an example, we show a group of miRNAs and transcription factors as candidates, responsible for mitochondrial metabolic modification in HCC.

Bactericidal and fungicidal capacity of Ag2O/Ag nanoparticles synthesized with Aloe vera extract.

This research aims to provide an alternative eco-friendly way to obtain silver species and assess their bactericidal activity. This study reports the synthesis of Ag2O nanoparticles and Ag nanoparticles reduced with a green synthesis method, using a low-cost and commercial Aloe vera extract. The crystalline phases of Ag and Ag2O nanoparticles were analyzed by X-ray diffraction. The oxidation states for both species were determined by X-ray photoelectron spectroscopy. The optical properties of the material were studied through optical absorption, which resulted in well-defined band centered at 545 nm. This result is attributed to the morphology and size of the silver nanoparticles. In addition, antibacterial tests were performed on AgNPs biosynthesized with A. vera with the Kirby-Bauer protocol on Gram-negative and Gram-positive bacteria Escherichia coli and Staphylococcus aureaus, respectively. Moreover, antifungal tests were performed with various species from Candida.

The Increased Expression of Regulator of G-Protein Signaling 2 (RGS2) Inhibits Insulin-Induced Akt Phosphorylation and Is Associated with Uncontrolled Glycemia in Patients with Type 2 Diabetes.

Experimental evidence in mice models has demonstrated that a high regulator of G-protein signaling 2 (RSG2) protein levels precede an insulin resistance state. In the same context, a diet rich in saturated fatty acids induces an increase in RGS2 protein expression, which has been associated with decreased basal metabolism in mice; however, the above has not yet been analyzed in humans. For this reason, in the present study, we examined the association between RGS2 expression and insulin resistance state. The incubation with palmitic acid (PA), which inhibits insulin-mediated Akt Ser473 phosphorylation, resulted in the increased RGS2 expression in human umbilical vein endothelial-CS (HUVEC-CS) cells. The RGS2 overexpression without PA was enough to inhibit insulin-mediated Akt Ser473 phosphorylation in HUVEC-CS cells. Remarkably, the platelet RGS2 expression levels were higher in type 2 diabetes mellitus (T2DM) patients than in healthy donors. Moreover, an unbiased principal component analysis (PCA) revealed that RGS2 expression level positively correlated with glycated hemoglobin (HbA1c) and negatively with age and high-density lipoprotein cholesterol (HDL) in T2DM patients. Furthermore, PCA showed that healthy subjects segregated from T2DM patients by having lower levels of HbA1c and RGS2. These results demonstrate that RGS2 overexpression leads to decreased insulin signaling in a human endothelial cell line and is associated with poorly controlled diabetes.

First-principles study of Mn3 adsorbed on Au(111) and Cu(111) surfaces.

A theoretical study of the Mn trimer adsorbed on the noble metal surfaces Au(111) and Cu(111) is reported. The calculations were performed using first-principles methods within the density functional theory and the generalized gradient approximation in the collinear and non-collinear magnetic phases. The system was modeled by considering a surface unit cell of 25 atoms to improve the trimer's isolation on the surface. We evaluated the trimer as a linear chain and forming triangular structures. The triangular trimer can be adsorbed in two possible configurations, above an empty surface triangle site (Δ) or on a triangle with a surface atom at the center in a hexagonal structure (H). The difference is the coordination of the Mn with surface atoms. We studied the antiferromagnetic (AF), ferromagnetic (FM), and non-collinear (NC) magnetic cases. As a result, the lowest energy configuration on both metals is the AFΔ configuration, which has an isosceles triangle shape. In comparison, the NC and the FM configurations adopt an equilateral geometry. The same trend was observed for the H configurations, but they are less bonded. The results are supported by calculating the spin-polarized electronic structure and the electronic charge transfer. Finally, we computed the energy barriers that inhibit the transformation of the linear chain to a delta Mn trimer on both substrates.

Perineurioma versus meningioma. A multi-institutional immunohistochemical and ultrastructural studY.

The differential diagnosis between perineurioma (PN) and meningioma (MEN) can be difficult by histology and immunohistochemistry (IHC) because the perineurium and arachnoid have the same embryological origin. However, there are no comparative studies determining conclusive parameters for the differential diagnosis. The aim of this study is to compare IHC of PN and MEN and their ultra-structural characteristics to elucidate which are the useful data that allow differentiate both entities. Thirty-five MEN were analyzed, and 15 PN, (11 skin and soft tissues and four oral cavity). IHC for epithelial membrane antigen (EMA), Claudin-1, GLUT-1, somatostatin-2 receptor (SSTR-2), and progesterone receptor (RP) was performed. Ultrastructural studies were performed on 8 MEN and 15 PN. Only in PN Claudin-1 was positive in 9/11 (90%) cases and GLUT-1 in 7/11 (63%) cases. In MEN, the progesterone receptor was expressed in 21/35 (60%) cases and no case expressed Claudin-1 and GLUT-1; EMA was expressed in all MEN cases and 93% of PN. SSTR-2 was expressed weakly in six cases of MEN (17%), and it was not considered useful for differential diagnosis. On ultrastructure, PN showed thin and parallel processes, some caveolae, and lacked cell junctions. The cellular processes were surrounded by a collagenous stroma in 94% of the cases. MEN were characterized by curved cytoplasmic cell processes showing desmosomes in 75% of cases. Ultrastructural findings aid in the differential diagnosis between PN and MEN, especially if molecular studies are not available.