Insecticidal activity of two organic extracts from Libidibia coriaria (Jacq.) Schltdl. fruits against Spodoptera frugiperda J. E. Smith.

This study describes the chemical characterisation of two extracts (ethyl acetate, EtOAc-E and hexanic, Hx-E) from Libidibia coriaria fruits and their insecticidal properties on Spodoptera frugiperda. The HPLC analysis in EtOAct-E revealed the presence of ellagic acid and phenolic compounds. The CG-MS analysis in Hx-E revealed the presence of Hexadecanoic acid, 11-Methylheptacosane, Dodecanoic acid and Nonacosane as major compounds. The application of both extracts was performed on the dorsal part of each larva via aspersion. The larval mortality, relative growth and emergence percentage of adults were evaluated. The Hx-E caused a 93.33% mortality at 100 mg/mL at 24 h post-application. A minor relative growth with both EtOAc-E (12.64 mg) and Hx-E (7.90 mg) was observed compared with their respective negative controls (methanol = 25.05 mg and tween20 = 24.53 mg). The lowest emergence percentage of adults with the Hx-E (25%) at 50 mg/mL was observed. Libidibia coriaria fruits exhibit insecticidal properties against S. frugiperda.

Prevalence of anterior uveitis in cases of systemic inflammatory response syndrome in dogs and cats.

OBJECTIVE: To determine the prevalence of anterior uveitis in dogs and cats hospitalized with a diagnosis of systemic inflammatory response syndrome (SIRS). ANIMALS STUDIED: Dogs and cats hospitalized between May 2020 and January 2021 were prospectively included. PROCEDURES: Patients were categorized into two different groups: The first group included patients diagnosed with SIRS, and the second group included patients hospitalized without SIRS as a control group. Daily physical and ophthalmological examinations were conducted during hospitalization. Diagnosis of anterior uveitis was made based on the presence of aqueous flare, low intraocular pressure, and other associated ocular signs such as episcleral injection and miosis. A multinomial logistic regression analysis was conducted to investigate factors associated with SIRS and anterior uveitis development. RESULTS: The study comprised 42 patients with SIRS and 26 patients without SIRS. Among those with SIRS, 38% developed anterior uveitis, whereas only 7.7% of patients without SIRS showed signs of anterior uveitis. The prevalence of uveitis was significantly higher in animals with SIRS compared to those without SIRS (p < .05). CONCLUSION: Anterior uveitis is more prevalent in patients with SIRS than patients without SIRS. Therefore, complete ophthalmic examination is recommended in all patients presenting with this syndrome.

Serum GFAP levels correlate with astrocyte reactivity, post-mortem brain atrophy and neurofibrillary tangles.

Glial fibrillary acidic protein (GFAP), a proxy of astrocyte reactivity, has been proposed as biomarker of Alzheimer's disease. However, there is limited information about the correlation between blood biomarkers and post-mortem neuropathology. In a single-centre prospective clinicopathological cohort of 139 dementia patients, for which the time-frame between GFAP level determination and neuropathological assessment was exceptionally short (on average 139 days), we analysed this biomarker, measured at three time points, in relation to proxies of disease progression such as cognitive decline and brain weight. Most importantly, we investigated the use of blood GFAP to detect the neuropathological hallmarks of Alzheimer's disease, while accounting for potential influences of the most frequent brain co-pathologies. The main findings demonstrated an association between serum GFAP level and post-mortem tau pathology (ß = 12.85; P < 0.001) that was independent of amyloid deposits (ß = 13.23; P = 0.02). A mediation analysis provided additional support for the role of astrocytic activation as a link between amyloid and tau pathology in Alzheimer's disease. Furthermore, a negative correlation was observed between pre-mortem serum GFAP and brain weight at post-mortem (r = -0.35; P < 0.001). This finding, together with evidence of a negative correlation with cognitive assessments (r = -0.27; P = 0.005), supports the role of GFAP as a biomarker for disease monitoring, even in the late phases of Alzheimer's disease. Moreover, the diagnostic performance of GFAP in advanced dementia patients was explored, and its discriminative power (area under the receiver operator characteristic curve at baseline = 0.91) in differentiating neuropathologically-confirmed Alzheimer's disease dementias from non-Alzheimer's disease dementias was determined, despite the challenging scenario of advanced age and frequent co-pathologies in these patients. Independently of Alzheimer's disease, serum GFAP levels were shown to be associated with two other pathologies targeting the temporal lobes-hippocampal sclerosis (ß = 3.64; P = 0.03) and argyrophilic grain disease (ß = -6.11; P = 0.02). Finally, serum GFAP levels were revealed to be correlated with astrocyte reactivity, using the brain GFAP-immunostained area as a proxy (ρ = 0.21; P = 0.02). Our results contribute to increasing evidence suggesting a role for blood GFAP as an Alzheimer's disease biomarker, and the findings offer mechanistic insights into the relationship between blood GFAP and Alzheimer's disease neuropathology, highlighting its ties with tau burden. Moreover, the data highlighting an independent association between serum GFAP levels and other neuropathological lesions provide information for clinicians to consider when interpreting test results. The longitudinal design and correlation with post-mortem data reinforce the robustness of our findings. However, studies correlating blood biomarkers and neuropathological assessments are still scant, and further research is needed to replicate and validate these results in diverse populations.

Plasma Cell-free RNA Signatures of Inflammatory Syndromes in Children.

Inflammatory syndromes, including those caused by infection, are a major cause of hospital admissions among children and are often misdiagnosed because of a lack of advanced molecular diagnostic tools. In this study, we explored the utility of circulating cell-free RNA (cfRNA) in plasma as an analyte for the differential diagnosis and characterization of pediatric inflammatory syndromes. We profiled cfRNA in 370 plasma samples from pediatric patients with a range of inflammatory conditions, including Kawasaki disease (KD), Multisystem Inflammatory Syndrome in Children (MIS-C), viral infections and bacterial infections. We developed machine learning models based on these cfRNA profiles, which effectively differentiated KD from MIS-C - two conditions presenting with overlapping symptoms - with high performance (Test Area Under the Curve (AUC) = 0.97). We further extended this methodology into a multiclass machine learning framework that achieved 81% accuracy in distinguishing among KD, MIS-C, viral, and bacterial infections. We further demonstrated that cfRNA profiles can be used to quantify injury to specific tissues and organs, including the liver, heart, endothelium, nervous system, and the upper respiratory tract. Overall, this study identified cfRNA as a versatile analyte for the differential diagnosis and characterization of a wide range of pediatric inflammatory syndromes.

Melatonin and Its Role in the Epithelial-to-Mesenchymal Transition (EMT) in Cancer.

The epithelial-to-mesenchymal transition (EMT) is a cell-biological program that occurs during the progression of several physiological processes and that can also take place during pathological situations such as carcinogenesis. The EMT program consists of the sequential activation of a number of intracellular signaling pathways aimed at driving epithelial cells toward the acquisition of a series of intermediate phenotypic states arrayed along the epithelial-mesenchymal axis. These phenotypic features include changes in the motility, conformation, polarity and functionality of cancer cells, ultimately leading cells to stemness, increased invasiveness, chemo- and radioresistance and the formation of cancer metastasis. Amongst the different existing types of the EMT, type 3 is directly involved in carcinogenesis. A type 3 EMT occurs in neoplastic cells that have previously acquired genetic and epigenetic alterations, specifically affecting genes involved in promoting clonal outgrowth and invasion. Markers such as E-cadherin; N-cadherin; vimentin; and transcription factors (TFs) like Twist, Snail and ZEB are considered key molecules in the transition. The EMT process is also regulated by microRNA expression. Many miRNAs have been reported to repress EMT-TFs. Thus, Snail 1 is repressed by miR-29, miR-30a and miR-34a; miR-200b downregulates Slug; and ZEB1 and ZEB2 are repressed by miR-200 and miR-205, respectively. Occasionally, some microRNA target genes act downstream of the EMT master TFs; thus, Twist1 upregulates the levels of miR-10b. Melatonin is an endogenously produced hormone released mainly by the pineal gland. It is widely accepted that melatonin exerts oncostatic actions in a large variety of tumors, inhibiting the initiation, progression and invasion phases of tumorigenesis. The molecular mechanisms underlying these inhibitory actions are complex and involve a great number of processes. In this review, we will focus our attention on the ability of melatonin to regulate some key EMT-related markers, transcription factors and micro-RNAs, summarizing the multiple ways by which this hormone can regulate the EMT. Since melatonin has no known toxic side effects and is also known to help overcome drug resistance, it is a good candidate to be considered as an adjuvant drug to conventional cancer therapies.

Crinoidea y Asteroidea (Echinodermata) del talud de la península de Yucatán, de la Colección Nacional de Equinodermos de México / Crinoidea and Asteroidea (Echinodermata) from the slope of the Yucatan Peninsula, Colección Nacional de Equinodermos, Mexico

Resumen Introducción: Las especies de las clases Crinoidea y Asteroidea se distribuyen en gran variedad de hábitats en todos los océanos desde la zona intermareal hasta grandes profundidades, existen pocos registros en aguas mexicanas, a profundidades superiores a los 200 m, los escasos registros existentes datan de documentos históricos de la literatura especializada y los ejemplares se resguardan en colecciones científicas extranjeras. Objetivo: Contribuir a la recopilación de información de los ejemplares resguardados en la Colección Nacional de Equinodermos (CNE) del Instituto de Ciencias del Mar y Limnología (ICML), UNAM y proveer un inventario de las especies de crinoideos y asteroideos que habitan en zonas profundas del talud de la Península de Yucatán, México. Métodos: Del año 2005 al 2014 se recolectaron ejemplares de crinoideos y asteriodeos en cuatro cruceros en el B/O "Justo Sierra" BIOREPES 1 y 2 y COBERPES 2 y 6. Se realizaron arrastres con red camaronera en 80 estaciones de muestreo. Resultados: El listado taxonómico comprende 1146 ejemplares, de los cuales 204 son crinoideos del orden Comatulida, distribuidos en tres familias tres géneros y tres especies y 942 asteroideos distribuidos en seis órdenes, 11 familias, 21 géneros y 28 especies. Se obtuvieron los registros nuevos para la CNE: Democrinus rawsonii y Atelecrinus balanoides en crinoideos. Astropecten alligator, Hymenaster modestus, Calyptraster personatus, Pteraster militarioides militarioides, Sclerasterias contorta en asteroideos. Con esta información se incrementan los registros de crinoideos y asteroideos (de profundidad mayor a 200 m) para los estados de Yucatán (16) y Quintana Roo (16).

Abstract Introduction: The species of the Crinoidea and Asteroidea classes are distributed in a wide variety of habitats in all oceans from the intertidal zone to great depths, there are few Mexican records in depths greater than 200 m, the few existing records date from historical documents in the specialized literature and the specimens are kept in foreign scientific collections. Objective: Contribute to the collection of information on the specimens kept in the Colección Nacional de Equinodermos (CNE) of Instituto de Ciencias del Mar y Limnología (ICML), UNAM and provide an inventory of the species of crinoids and asteroids that inhabit deep areas of the slope of the Yucatan Peninsula, Mexico. Methods: From 2005 to 2014, specimens of crinoids and asterioids were collected through four cruises in the B/O "Justo Sierra" BIOREPES 1 and 2 and COBERPES 2 and 6, shrimp net trawls were carried out at 80 sampling stations. Results: The taxonomic list includes 1146 specimens, of which 204 crinoids are of the order Comatulida, distributed in three families, three genera and three species and 942 asteroids distributed in six orders, 11 families, 21 genera and 28 species. New records were obtained for CNE: Democrinus rawsonii and Atelecrinus balanoides in crinoids. Astropecten alligator, Hymenaster modestus, Calyptraster personatus, Pteraster militarioides militarioides, Sclerasterias contorta in asteroids. With this information, the records of crinoids and asteroids (deeper than 200 m) increase for the states of Yucatan (16) and Quintana Roo (16).

Assessment of Interprofessional Competence of Leadership Education in Neurodevelopmental and Related Disabilities Trainees through a Virtual Standardized Patient Encounter.

INTRODUCTION: Leadership Education in Neurodevelopmental and Related Disabilities (LEND) programs have an emphasis on developing skills in providing family-centered and interdisciplinary care. Due to Coronavirus pandemic-related restrictions, opportunities for interdisciplinary education were limited for the 2020-2021 LEND Trainee cohort at The Ohio State University Nisonger Center. Standardized Patient (SP) encounters can be a mechanism for instruction and assessment of interprofessional competence. METHODS: An SP encounter was developed for the The Ohio State University 2020-2021 LEND Cohort. Prior to the activity, participants (N = 11) were given clinic notes to review from their respective disciplines. During the activity, participants met virtually to develop collaborative recommendations which were then delivered to the SP who portrayed the mother of a young child receiving a new diagnosis of autism spectrum disorder. Following the encounter, 4 LEND faculty observers completed the Modified McMaster-Ottawa Team Rating Scale and participants completed the Interprofessional Collaboration Competency Attainment Scale-Revised (ICCAS-R). RESULTS: Eleven LEND trainees completed the ICCAS-R with an overall increase in the mean score from 3.86 to 4.12. Four LEND faculty members completed the Modified McMaster-Ottawa Team Rating Scale, with the Communication domain demonstrating the highest level of competence. DISCUSSION: This activity was well-received by both faculty and LEND trainees. Although delivered in virtual format, it could easily be transitioned to an in-person encounter for future LEND trainees. The success of this activity further supports that standardized patient encounters can be a feasible mechanism for instruction and assessment of interprofessional competencies and serve as a training mechanism for LEND programs.

Neo-functionalization in Saccharomyces cerevisiae: a novel Nrg1-Rtg3 chimeric transcriptional modulator is essential to maintain mitochondrial DNA integrity.

In Saccharomyces cerevisiae, the transcriptional repressor Nrg1 (Negative Regulator of Glucose-repressed genes) and the ß-Zip transcription factor Rtg3 (ReTroGrade regulation) mediate glucose repression and signalling from the mitochondria to the nucleus, respectively. Here, we show a novel function of these two proteins, in which alanine promotes the formation of a chimeric Nrg1/Rtg3 regulator that represses the ALT2 gene (encoding an alanine transaminase paralog of unknown function). An NRG1/NRG2 paralogous pair, resulting from a post-wide genome small-scale duplication event, is present in the Saccharomyces genus. Neo-functionalization of only one paralog resulted in the ability of Nrg1 to interact with Rtg3. Both nrg1Δ and rtg3Δ single mutant strains were unable to use ethanol and showed a typical petite (small) phenotype on glucose. Neither of the wild-type genes complemented the petite phenotype, suggesting irreversible mitochondrial DNA damage in these mutants. Neither nrg1Δ nor rtg3Δ mutant strains expressed genes encoded by any of the five polycistronic units transcribed from mitochondrial DNA in S. cerevisiae. This, and the direct measurement of the mitochondrial DNA gene complement, confirmed that irreversible damage of the mitochondrial DNA occurred in both mutant strains, which is consistent with the essential role of the chimeric Nrg1/Rtg3 regulator in mitochondrial DNA maintenance.

Previous exposure to Spike-providing parental strains confers neutralizing immunity to XBB lineage and other SARS-CoV-2 recombinants in the context of vaccination.

The emergence of SARS-CoV-2 recombinants is of particular concern as they can result in a sudden increase in immune evasion due to antigenic shift. Recent recombinants XBB and XBB.1.5 have higher transmissibility than previous recombinants such as "Deltacron." We hypothesized that immunity to a SARS-CoV-2 recombinant depends on prior exposure to its parental strains. To test this hypothesis, we examined whether Delta or Omicron (BA.1 or BA.2) immunity conferred through infection, vaccination, or breakthrough infection could neutralize Deltacron and XBB/XBB.1.5 recombinants. We found that Delta, BA.1, or BA.2 breakthrough infections provided better immune protection against Deltacron and its parental strains than did the vaccine booster. None of the sera were effective at neutralizing the XBB lineage or its parent BA.2.75.2, except for the sera from the BA.2 breakthrough group. These results support our hypothesis. In turn, our findings underscore the importance of multivalent vaccines that correspond to the antigenic profile of circulating variants of concern and of variant-specific diagnostics that may guide public health and individual decisions in response to emerging SARS-CoV-2 recombinants.

Systematic profiling of subtelomeric silencing factors in budding yeast.

Subtelomeric gene silencing is the negative transcriptional regulation of genes located close to telomeres. This phenomenon occurs in a variety of eukaryotes with salient physiological implications, such as cell adherence, virulence, immune-system escape, and ageing. The process has been widely studied in the budding yeast Saccharomyces cerevisiae, where genes involved in this process have been identified mostly on a gene-by-gene basis. Here, we introduce a quantitative approach to study gene silencing, that couples the classical URA3 reporter with GFP monitoring, amenable to high-throughput flow cytometry analysis. This dual silencing reporter was integrated into several subtelomeric loci in the genome, where it showed a gradual range of silencing effects. By crossing strains with this dual reporter at the COS12 and YFR057W subtelomeric query loci with gene-deletion mutants, we carried out a large-scale forward screen for potential silencing factors. The approach was replicable and allowed accurate detection of expression changes. Results of our comprehensive screen suggest that the main players influencing subtelomeric silencing were previously known, but additional potential factors underlying chromatin conformation are involved. We validate and report the novel silencing factor LGE1, a protein with unknown molecular function required for histone H2B ubiquitination. Our strategy can be readily combined with other reporters and gene perturbation collections, making it a versatile tool to study gene silencing at a genome-wide scale.

Impact of the COVID-19 Pandemic in Spain in the Successive Pandemic Waves on Hemodialysis Patients and Healthcare Personnel.

(1) Background: The impact of SARS-CoV-2 has been variable over the time course of the pandemic and in different populations. The aim was to analyze the impact of COVID-19 infection in a known population of hemodialysis (HD) patients and professionals in Spain at different times of the pandemic. (2) Methods: We conducted an observational, descriptive study with a follow-up from 3 March 2020 to 23 April 2022 (776 days), using in average of 414 professionals and 1381 patients from 18 HD units in Spain. The data from the positive PCR or the rapid antigen detection test (RADT) subject were analyzed and segmented into six periods (waves). (3) Results: Of 703 positive COVID-19 tests, 524 were HD patients (74.5%), and 179 were HD professionals (25.5%). Overall, 38% of staff and 43% of patients were affected. Differences were observed in regard to incidence (21% vs. 13%), mortality (3.5% vs. 0%), and symptomatology between the patients and professionals and throughout the pandemic. (4) Conclusions: COVID-19 severity varied during different pandemic waves, with a greater impact seen in the first wave. HD professionals and patients had similar infection rates, but patients had higher mortality rates. Community transmission was the primary route of infection.

Nucleic acid biomarkers of immune response and cell and tissue damage in children with COVID-19 and MIS-C.

Differential host responses in coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome in children (MIS-C) remain poorly characterized. Here, we use next-generation sequencing to longitudinally analyze blood samples from pediatric patients with COVID-19 or MIS-C across three hospitals. Profiling of plasma cell-free nucleic acids uncovers distinct signatures of cell injury and death between COVID-19 and MIS-C, with increased multiorgan involvement in MIS-C encompassing diverse cell types, including endothelial and neuronal cells, and an enrichment of pyroptosis-related genes. Whole-blood RNA profiling reveals upregulation of similar pro-inflammatory pathways in COVID-19 and MIS-C but also MIS-C-specific downregulation of T cell-associated pathways. Profiling of plasma cell-free RNA and whole-blood RNA in paired samples yields different but complementary signatures for each disease state. Our work provides a systems-level view of immune responses and tissue damage in COVID-19 and MIS-C and informs future development of new disease biomarkers.

The ß Form in PVDF Nanocomposites with Carbon Nanotubes: Structural Features and Properties.

Different amounts of carbon nanotubes (CNT) have been incorporated in materials based on poly(vinylidene fluoride) (PVDF) by solvent blending followed by their further precipitation. Final processing was performed by compression molding. The morphological aspects and crystalline characteristics have been examined, additionally exploring in these nanocomposites the common routes described in the pristine PVDF to induce the ß polymorph. This polar ß phase has been found to be promoted by the simple inclusion of CNT. Therefore, coexistence of the α and ß lattices occurs for the analyzed materials. The real-time variable-temperature X-ray diffraction measurements with synchrotron radiation at a wide angle have undoubtedly allowed us to observe the presence of the two polymorphs and determine the melting temperature of both crystalline modifications. Furthermore, the CNT plays a nucleating role in the PVDF crystallization, and also acts as reinforcement, increasing the stiffness of the nanocomposites. Moreover, the mobility within the amorphous and crystalline PVDF regions is found to change with the CNT content. Finally, the presence of CNT leads to a very remarkable increase in the conductivity parameter, in such a way that the transition from insulator to electrical conductor is reached in these nanocomposites at a percolation threshold ranging from 1 to 2 wt.%, leading to the excellent value of conductivity of 0.05 S/cm in the material with the highest content in CNT (8 wt.%).

Adeno-associated virus type 2 in US children with acute severe hepatitis.

As of August 2022, clusters of acute severe hepatitis of unknown aetiology in children have been reported from 35 countries, including the USA1,2. Previous studies have found human adenoviruses (HAdVs) in the blood from patients in Europe and the USA3-7, although it is unclear whether this virus is causative. Here we used PCR testing, viral enrichment-based sequencing and agnostic metagenomic sequencing to analyse samples from 16 HAdV-positive cases from 1 October 2021 to 22 May 2022, in parallel with 113 controls. In blood from 14 cases, adeno-associated virus type 2 (AAV2) sequences were detected in 93% (13 of 14), compared to 4 (3.5%) of 113 controls (P < 0.001) and to 0 of 30 patients with hepatitis of defined aetiology (P < 0.001). In controls, HAdV type 41 was detected in blood from 9 (39.1%) of the 23 patients with acute gastroenteritis (without hepatitis), including 8 of 9 patients with positive stool HAdV testing, but co-infection with AAV2 was observed in only 3 (13.0%) of these 23 patients versus 93% of cases (P < 0.001). Co-infections by Epstein-Barr virus, human herpesvirus 6 and/or enterovirus A71 were also detected in 12 (85.7%) of 14 cases, with higher herpesvirus detection in cases versus controls (P < 0.001). Our findings suggest that the severity of the disease is related to co-infections involving AAV2 and one or more helper viruses.

Longitudinal comparison of the developing gut virome in infants and their mothers.

The human gut virome and its early life development are poorly understood. Prior studies have captured single-point assessments with the evolution of the infant virome remaining largely unexplored. We performed viral metagenomic sequencing on stool samples collected longitudinally from a cohort of 53 infants from age 2 weeks to 3 years (80.7 billion reads), and from their mothers (9.8 billion reads) to examine and compare viromes. The asymptomatic infant virome consisted of bacteriophages, nonhuman dietary/environmental viruses, and human-host viruses, predominantly picornaviruses. In contrast, human-host viruses were largely absent from the maternal virome. Previously undescribed, sequence-divergent vertebrate viruses were detected in the maternal but not infant virome. As infants aged, the phage component evolved to resemble the maternal virome, but by age 3, the human-host component remained dissimilar from the maternal virome. Thus, early life virome development is determined predominantly by dietary, infectious, and environmental factors rather than direct maternal acquisition.

Vascular anatomy of the breast and its implications in the breast-sharing reconstruction technique.

The most frequently described breast-sharing procedure consists in a pedicled technique where the transferred lower breast pole is based on the lower perforators of the internal mammary (IM) artery. The current article investigates the vascular supply of the breast and its surgical implications in breast-sharing reconstruction. Contrast-enhanced magnetic resonance images of 55 patients (110 breasts) were retrospectively examined. A total of 473 branches of the IM, lateral thoracic (LT) and anterior intercostal (AI) arteries with a diameter greater than 0.5 mm were traced throughout their course in the breast. Distinct connections between the vessels were equally recorded. Although any vessel could vascularise any quadrant in the individual patient, blood supply to the lower quadrants came fundamentally from the AI arteries (76.2% of all the perforators). Lower IM branches (4th-5th) were seen to reach both lower quadrants in only 6.4% of the breasts, whereas LT branches did in 15.5%. In 86.4% of the breasts, at least a distinct AI perforator was seen to perfuse both lower quadrants. Well-defined connections between the IM and the LT arteries were observed in 41.8% of the breasts, always at or above the nipple-areola level. Other connections were far less common. Our study strongly indicates that the breast-sharing technique based on 4th-5th contralateral branches of the IM or LT arteries is unreliable in most patients. Given the unpredictable vascularization pattern in the lower breast pole, a preoperative imaging study is mandatory when the use of the contralateral breast is considered. Due to its accuracy, availability, and anatomical reliability, contrast-enhanced magnetic resonance is the best technique in the preoperative evaluation of the breast-sharing reconstruction.

Reduced expression of Basigin gene products in response to chronic inflammation may contribute to vision loss.

Chronic inflammation of the retina, like that of diabetic retinopathy, disrupts the blood-retina barrier (BRB). Disruption of the BRB increases vascular permeability and leads to vision loss. Basigin gene products, cell-adhesion molecules and members of the immunoglobulin superfamily, are expressed on endothelial cells, photoreceptor cells and Müller glial cells. Basigin variant-1 on photoreceptors interacts with Basigin variant-2 on Müller glial cells and to rod-derived cone viability factor (RdCVF) to form metabolic support mechanisms necessary for the survival of photoreceptor neurons. The goal of the current study was to determine the gene expression changes of Basigin gene products in ex vivo neonatal, adolescent, and adult retina when exposed to an inflammatory insult in acute and chronic phases. Retinas extracted from mice at postnatal day (P) 7, 30, and 180 were incubated with either phosphate-buffered saline (PBS), as a control, or lipopolysaccharide (LPS), an endotoxin, for 3, 6, 12, or 24 h. RNA was then extracted and Basigin gene products were quantified by qPCR. Analyses indicate both gene products are influenced by LPS exposure in a time and age dependent manner. Specifically, P180 retinas exposed to LPS showed significant decreases in both Basigin gene products, suggesting older retinas may be susceptible to chronic inflammation and subsequent vision loss.

Magnetic resonance in patients with cardiovascular devices. SEC-GT CRMTC/SEC-Heart Rhythm Association/SERAM/SEICAT consensus document.

Magnetic resonance has become a first-line imaging modality in various clinical scenarios. The number of patients with different cardiovascular devices, including cardiac implantable electronic devices, has increased exponentially. Although there have been reports of risks associated with exposure to magnetic resonance in these patients, the clinical evidence now supports the safety of performing these studies under specific conditions and following recommendations to minimize possible risks. This document was written by the Working Group on Cardiac Magnetic Resonance Imaging and Cardiac Computed Tomography of the Spanish Society of Cardiology (SEC-GT CRMTC), the Heart Rhythm Association of the Spanish Society of Cardiology (SEC-Heart Rhythm Association), the Spanish Society of Medical Radiology (SERAM), and the Spanish Society of Cardiothoracic Imaging (SEICAT). The document reviews the clinical evidence available in this field and establishes a series of recommendations so that patients with cardiovascular devices can safely access this diagnostic tool.

TRIM25 mutation (p.C168*), coding for an E3 ubiquitin ligase, is a cause of early-onset autosomal dominant dementia with amyloid load and parkinsonism.

INTRODUCTION: Patients with familial early-onset dementia (EOD) pose a unique opportunity for gene identification studies. METHODS: We present the phenotype and whole-exome sequencing (WES) study of an autosomal dominant EOD family. Candidate genes were examined in a set of dementia cases and controls (n = 3712). Western blotting was conducted of the wild-type and mutant protein of the final candidate. RESULTS: Age at disease onset was 60 years (range 56 to 63). The phenotype comprised mixed amnestic and behavioral features, and parkinsonism. Cerebrospinal fluid and plasma biomarkers, and a positron emission tomography amyloid study suggested Alzheimer's disease. WES and the segregation pattern pointed to a nonsense mutation in the TRIM25 gene (p.C168*), coding for an E3 ubiquitin ligase, which was absent in the cohorts studied. Protein studies supported a loss-of-function mechanism. DISCUSSION: This study supports a new physiopathological mechanism for brain amyloidosis. Furthermore, it extends the role of E3 ubiquitin ligases dysfunction in the development of neurodegenerative diseases. HIGHLIGHTS: A TRIM25 nonsense mutation (p.C168*) is associated with autosomal dominant early-onset dementia and parkinsonism with biomarkers suggestive of Alzheimer's disease. TRIM25 protein studies support that the mutation exerts its effect through loss of function. TRIM25, an E3 ubiquitin ligase, is known for its role in the innate immune response but this is the first report of association with neurodegeneration. The role of TRIM25 dysfunction in development of amyloidosis and neurodegeneration merits a new line of research.

Development of in vitro and in vivo tools to evaluate the antiangiogenic potential of melatonin to neutralize the angiogenic effects of VEGF and breast cancer cells: CAM assay and 3D endothelial cell spheroids.

Melatonin is a molecule with different antitumor actions in breast cancer and has been described as an inhibitor of vascular endothelial growth factor (VEGF). Despite the recognition of the key role exerted by VEGF in tumor angiogenesis, limitations arise when developing models to test new antiangiogenic molecules. Thus, the aim of this study was to develop rapid, economic, high capacity and easy handling angiogenesis assays to test the antiangiogenic effects of melatonin and demonstrate its most effective dose to neutralize and interfere with the angiogenic sprouting effect induced by VEGF and MCF-7. To perform this, 3D endothelial cell (HUVEC) spheroids and a chicken embryo chorioallantoic membrane (CAM) assay were used. The results showed that VEGF and MCF-7 were able to stimulate the sprouting of the new vessels in 3D endothelial spheroids and the CAM assay, and that melatonin had an inhibitory effect on angiogenesis. Specifically, as the 1 mM pharmacological dose was the only effective dose able to inhibit the formation of ramifications around the alginate in the CAM assay model, this inhibition was shown to occur in a dose-dependent manner. Taken together, these techniques represent novel tools for the development of antiangiogenic molecules such as melatonin, with possible implications for the therapy of breast cancer.