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1.
Front Pediatr ; 12: 1423958, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39350793

RESUMEN

Kawasaki Disease (KD) affects young children less than five years old with severe blood vessel inflammation. Despite being treatable, the causes and mechanisms remain elusive. This study conducted a meta-analysis of RNA sequencing (RNA-seq) data from human and animal models to explore KD's transcriptomic profile and evaluate animal models. We retrieved bulk and single-cell RNA-seq data from Gene Expression Omnibus, with blood and coronary artery samples from KD patients, aorta samples from KD mouse models (Lactobacillus casei cell wall extract-injected mice), and their controls. Upon consistent quality control, we applied Fisher's exact test to assess differential gene expression, followed by an enrichment analysis of overlapping genes. These studies identified 400 differentially expressed genes in blood samples of KD patients compared to controls and 413 genes in coronary artery samples. The data from KD blood and KD coronary artery samples shared only 16 differentially expressed genes. Eighty-one genes overlapped between KD human coronary arteries and KD mouse aortas, and 67 of these 81 genes were regulated in parallel in both humans and mice: 30 genes were up-regulated, and 37 were down-regulated. These included previously identified KD-upregulated genes: CD74, SFRP4, ITGA4, and IKZF1. Gene enrichment analysis revealed significant alterations in the cardiomyopathy pathway. Single-cell RNAseq showed a few significant markers, with known KD markers like S100A9, S100A8, CD74, CD14, IFITM2, and IFITM3, being overexpressed in KD cohorts. Gene profiles obtained from KD human coronary artery are more compatible with data from aorta samples of KD mice than blood samples of KD humans, validating KD animal models for identifying therapeutic targets. Although blood samples can be utilized to discover novel biomarkers, more comprehensive single-cell sequencing is required to detail gene expression in different blood cell populations. This study identifies critical genes from human and mouse tissues to help develop new treatment strategies for KD.

2.
Sci Total Environ ; 954: 176555, 2024 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-39349198

RESUMEN

Human activities provide wildlife with highly abundant and predictable food subsidies, which can affect population dynamics and have wide-ranging ecological impacts. A key ecological question is how species adapt their foraging behaviour to capitalize on these new feeding opportunities. We investigate habitat use by Audouin's Gulls (Ichthyaetus audouinii) off the Western Mediterranean Sea, an opportunistic seabird that has recently expanded to diverse breeding colonies subjected to varying degrees of human influence. By combining GPS tracking, remote sensing, and GIS, we assessed the resource selection and habitat preferences of gulls from five colonies across their breeding latitudinal range, including interactions with industrial fisheries. Overall, the use of terrestrial habitats was slightly higher (57 % of total positions) compared to the marine environment (42 %), with individuals preferentially feeding on urban and related areas or fishing ports. However, habitat utilization varied among studied colonies, likely in response to contrasting food availability and accessibility of human related food resources on land (e.g., agriculture and livestock areas, landfills or rice fields). At sea, individuals largely distributed over highly productive and persistent marine areas with intense fishing pressure. Individuals also adapted their daily activity patterns to match food availability: gulls preferentially feed on the marine environment during the night, while the use of terrestrial habitats increases during daylight hours. Individuals' daily activity patterns also matched that for the two main fishing gears operating in the area: diurnal trawlers and nocturnal purse-seiners. Our findings offer perspectives on the reliance of opportunistic seabird species on anthropogenic food subsidies and inform on potential implications for the conservation and management of these under changes in fishing policies (EU discard ban). Broadly, we provide further insights on how this species can adapt to changing environments.

3.
PLoS One ; 19(8): e0308975, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39172921

RESUMEN

This study aims to describe a protocol for a systematic review and meta-analysis that assesses the detection and concentration of pharmaceutical products, drugs, and personal care products in European waters. This study protocol was developed following the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA-P) statement and the Cochrane Handbook of Systematic Reviews of Interventions. We will include studies conducted on European waters of various origins (watersheds, aquifers, rivers, seas, springs, wastewaters, and drinking water). A comprehensive search strategy will be implemented in the following databases: PubMed (Medline), EMBASE, Scopus, and Web of Science. Two independent reviewers will conduct all study selection procedures, data extraction, and methodological evaluation. Any disagreements will be referred to a third reviewer. If the studies are sufficiently homogeneous, we will conduct a meta-analysis to summarize the data. We will use the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) to assess the certainty of the evidence. The systematic review and meta-analysis will provide valuable information about the presence and concentration of these types of contaminants in water, aiding in the development of public policies regarding prevention and decontamination measures to enhancing water quality in Europe.


Asunto(s)
Metaanálisis como Asunto , Revisiones Sistemáticas como Asunto , Europa (Continente) , Preparaciones Farmacéuticas/análisis , Contaminantes Químicos del Agua/análisis , Humanos , Cosméticos/análisis , Cosméticos/química , Calidad del Agua
4.
Sci Total Environ ; 948: 174752, 2024 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-39004360

RESUMEN

Global warming has significantly altered fish distribution patterns in the ocean, shifting towards higher latitudes and deeper waters. This is particularly relevant in high-latitude marine ecosystems, where climate-driven environmental changes are occurring at higher rates than the global average. Species Distribution Models (SDMs) are increasingly being used for predicting distributional shifts in habitat suitability for marine species as a response to climate change. Here, we used SDMs to project habitat suitability changes for a range of high-latitude, pelagic and benthopelagic commercial fish species and crustaceans (10 species); from 1850 to two future climate change scenarios (SSP1-2.6: low climate forcing; and SSP5-8.5: high climate forcing). The study includes 11 Large Marine Ecosystems (LME) spanning South America, Southern Africa, Australia, and New Zealand. We identified declining and southward-shifting patterns in suitable habitat areas for most species, particularly under the SSP5-8.5 scenario and for some species such as Argentine hake (Merluccius hubbsi) in South America, or snoek (Thyrsites atun) off Southern Africa. Geographical constraints will likely result in species from Southern Africa, Australia, and New Zealand facing the most pronounced habitat losses due to rising sea surface temperatures (SST). In contrast, South American species might encounter greater opportunities for migrating southward. Additionally, the SSP5-8.5 scenario predicts that South America will be more environmentally stable compared to other regions. Overall, our findings suggest that the Patagonian shelf could serve as a climate refuge, due to higher environmental stability highlighting the importance of proactive management strategies in this area for species conservation. This study significantly contributes to fisheries and conservation management, providing valuable insights for future protection efforts in the Southern Hemisphere.


Asunto(s)
Cambio Climático , Ecosistema , Peces , Animales , Nueva Zelanda , América del Sur , Australia , Explotaciones Pesqueras , África Austral , Calentamiento Global
5.
Sensors (Basel) ; 24(13)2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-39001083

RESUMEN

Estimating the pose of a large set of fixed indoor cameras is a requirement for certain applications in augmented reality, autonomous navigation, video surveillance, and logistics. However, accurately mapping the positions of these cameras remains an unsolved problem. While providing partial solutions, existing alternatives are limited by their dependence on distinct environmental features, the requirement for large overlapping camera views, and specific conditions. This paper introduces a novel approach to estimating the pose of a large set of cameras using a small subset of fiducial markers printed on regular pieces of paper. By placing the markers in areas visible to multiple cameras, we can obtain an initial estimation of the pair-wise spatial relationship between them. The markers can be moved throughout the environment to obtain the relationship between all cameras, thus creating a graph connecting all cameras. In the final step, our method performs a full optimization, minimizing the reprojection errors of the observed markers and enforcing physical constraints, such as camera and marker coplanarity and control points. We validated our approach using novel artificial and real datasets with varying levels of complexity. Our experiments demonstrated superior performance over existing state-of-the-art techniques and increased effectiveness in real-world applications. Accompanying this paper, we provide the research community with access to our code, tutorials, and an application framework to support the deployment of our methodology.

6.
Diabetologia ; 67(9): 1998-2011, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38898303

RESUMEN

AIMS/HYPOTHESIS: Individuals with diabetes are at high risk of cardiovascular complications, which significantly increase morbidity/mortality. Coronary microvascular disease (CMD) is recognised as a critical contributor to the increased cardiac mortality observed in people with diabetes. Therefore, there is an urgent need for treatments that are specific to CMD. eNAMPT (extracellular nicotinamide phosphoribosyltransferase) is a damage-associated molecular pattern and TLR4 ligand, whose plasma levels are elevated in people with diabetes. This study was thus designed to investigate the pathogenic role of intracellular nicotinamide phosphoribosyltransferase (iNAMPT) and eNAMPT in promoting the development of CMD in a preclinical murine model of type 2 diabetes. METHODS: An inducible type 2 diabetic mouse model was generated by a single injection of low-dose streptozocin (75 mg/kg, i.p.) combined with a high-fat diet for 16 weeks. The in vivo effects of i/eNAMPT inhibition on cardiac endothelial cell (CEC) function were evaluated by using Nampt+/- heterozygous mice, chronic administration of eNAMPT-neutralising monoclonal antibody (mAb) or use of an NAMPT enzymatic inhibitor (FK866). RESULTS: As expected, diabetic wild-type mice exhibited significantly lower coronary flow velocity reserve (CFVR), a determinant of coronary microvascular function, compared with control wild-type mice. eNAMPT plasma levels or expression in CECs were significantly greater in diabetic mice than in control mice. Furthermore, in comparison with diabetic wild-type mice, diabetic Nampt+/- heterozygous mice showed markedly improved CFVR, accompanied by increased left ventricular capillary density and augmented endothelium-dependent relaxation (EDR) in the coronary artery. NAMPT inhibition by FK866 or an eNAMPT-neutralising mAb significantly increased CFVR in diabetic mice. Furthermore, administration of the eNAMPT mAb upregulated expression of angiogenesis- and EDR-related genes in CECs from diabetic mice. Treatment with either eNAMPT or NAD+ significantly decreased CEC migration and reduced EDR in coronary arteries, partly linked to increased production of mitochondrial reactive oxygen species. CONCLUSIONS/INTERPRETATION: These data indicate that increased i/eNAMPT expression contributes to the development of diabetic coronary microvascular dysfunction, and provide compelling support for eNAMPT inhibition as a novel and effective therapeutic strategy for CMD in diabetes.


Asunto(s)
Diabetes Mellitus Tipo 2 , Nicotinamida Fosforribosiltransferasa , Animales , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Ratones , Nicotinamida Fosforribosiltransferasa/metabolismo , Masculino , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/tratamiento farmacológico , Ratones Endogámicos C57BL , Citocinas/metabolismo , Células Endoteliales/metabolismo , Células Endoteliales/efectos de los fármacos , Vasos Coronarios/metabolismo , Vasos Coronarios/efectos de los fármacos
7.
J Psychopharmacol ; 38(7): 647-660, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38888086

RESUMEN

BACKGROUND: The orexin (OX) system has received increasing interest as a potential target for treating substance use disorder. OX transmission in the posterior paraventricular nucleus of the thalamus (pPVT), an area activated by highly salient stimuli that are both reinforcing and aversive, mediates cue- and stress-induced reinstatement of reward-seeking behavior. Oral administration of suvorexant (SUV), a dual OX receptor (OXR) antagonist (DORA), selectively reduced conditioned reinstatement of oxycodone-seeking behavior and stress-induced reinstatement of alcohol-seeking behavior in dependent rats. AIMS: This study tested whether OXR blockade in the pPVT with SUV reduces oxycodone or sweetened condensed milk (SCM) seeking elicited by conditioned cues or stress. METHODS: Male Wistar rats were trained to self-administer oxycodone (0.15 mg/kg, i.v., 8 h/day) or SCM (0.1 ml, 2:1 dilution [v/v], 30 min/day). After extinction, we tested the ability of intra-pPVT SUV (15 µg/0.5 µl) to prevent reinstatement of oxycodone or SCM seeking elicited by conditioned cues or footshock stress. RESULTS: The rats acquired oxycodone and SCM self-administration, and oxycodone intake correlated with signs of physical opioid withdrawal, confirming dependence. Following extinction, the presentation of conditioned cues or footshock elicited reinstatement of oxycodone- and SCM-seeking behavior. Intra-pPVT SUV blocked stress-induced reinstatement of oxycodone seeking but not conditioned reinstatement of oxycodone or SCM seeking or stress-induced reinstatement of SCM seeking. CONCLUSIONS: The results indicate that OXR signaling in the pPVT is critical for stress-induced reinstatement of oxycodone seeking, further corroborating OXRs as treatment targets for opioid use disorder.


Asunto(s)
Comportamiento de Búsqueda de Drogas , Antagonistas de los Receptores de Orexina , Orexinas , Oxicodona , Ratas Wistar , Autoadministración , Estrés Psicológico , Animales , Oxicodona/farmacología , Oxicodona/administración & dosificación , Masculino , Ratas , Comportamiento de Búsqueda de Drogas/efectos de los fármacos , Estrés Psicológico/metabolismo , Orexinas/metabolismo , Antagonistas de los Receptores de Orexina/farmacología , Antagonistas de los Receptores de Orexina/administración & dosificación , Señales (Psicología) , Transducción de Señal/efectos de los fármacos , Extinción Psicológica/efectos de los fármacos , Receptores de Orexina/metabolismo , Receptores de Orexina/efectos de los fármacos , Recompensa , Trastornos Relacionados con Opioides/metabolismo , Núcleos Talámicos de la Línea Media/efectos de los fármacos , Núcleos Talámicos de la Línea Media/metabolismo
8.
Arch Environ Contam Toxicol ; 86(4): 363-374, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38762667

RESUMEN

Mercury (Hg) is an environmental contaminant that can negatively impact the health of humans and wildlife. Albatrosses and large petrels show some of the highest levels of Hg contamination among birds, with potential repercussions for reproduction and survival. Here, body feather total Hg (THg) concentrations were determined in breeding adults of five species of albatrosses and large petrels in the foraging guild at South Georgia during the mid-2010s. We tested the effects of species, sex and trophic ecology (inferred from stable isotopes) on THg concentrations and compared our results with published values from past decades. Feather THg concentrations differed significantly among species (range: 1.9-49.6 µg g-1 dw), and were highest in wandering albatrosses Diomedea exulans, intermediate in black-browed albatrosses Thalassarche melanophris and northern giant petrels Macronectes halli, and lowest in southern giant petrels M. giganteus and white-chinned petrels Procellaria aequinoctialis. Females were more contaminated than males in all species, potentially due to differences in distributions and diet composition. Across species, THg concentrations were not correlated with feather δ13C or δ15N values, implying that species effects (e.g., breeding and moulting frequencies) may be more important than trophic effects in explaining feather THg concentrations in this foraging guild. Within species, the only significant correlation was between THg and δ13C in wandering albatrosses, which could reflect higher Hg exposure in subtropical waters. Comparisons with THg concentrations from past studies, which reflect contamination from 10 to > 60 years ago, revealed considerable annual variation and some evidence for increases over time for wandering and black-browed albatrosses since before 1950 and from the late 1980s, respectively.


Asunto(s)
Aves , Monitoreo del Ambiente , Plumas , Mercurio , Plumas/química , Animales , Mercurio/análisis , Femenino , Masculino , Contaminantes Ambientales/análisis , Contaminantes Ambientales/metabolismo
9.
J Mater Chem A Mater ; 12(18): 10773-10783, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38725523

RESUMEN

Compliance with good research data management practices means trust in the integrity of the data, and it is achievable by full control of the data gathering process. In this work, we demonstrate tooling which bridges these two aspects, and illustrate its use in a case study of automated battery cycling. We successfully interface off-the-shelf battery cycling hardware with the computational workflow management software AiiDA, allowing us to control experiments, while ensuring trust in the data by tracking its provenance. We design user interfaces compatible with this tooling, which span the inventory, experiment design, and result analysis stages. Other features, including monitoring of workflows and import of externally generated and legacy data are also implemented. Finally, the full software stack required for this work is made available in a set of open-source packages.

10.
Nurs Rep ; 14(2): 1170-1183, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38804422

RESUMEN

BACKGROUND: Wound healing competence is implied in the nursing profession, but there is no standardized content regulation for wound care in university curricula. The primary objective of this study was to identify the barriers to the acquisition of knowledge about skin integrity impairment. METHODS: A quasi-experimental pre-test and post-test study with an ad hoc questionnaire involved 304 students (control: 165; intervention: 139) from June to July 2023. A 10-h educational intervention focused on skin integrity assessment and treatment was conducted. RESULTS: The control group, scoring 17 ± 0.22 out of a maximum of 61, achieved a significantly lower final test score (p < 0.001) compared to the wound care educational intervention group, with the pre-test group scoring 30 ± 0.76 and the post-test group scoring 43 ± 0.61. The educational intervention in wound care program improved nursing students' knowledge of prevention, assessment/diagnosis, treatment, lower limb wounds, and wound bed preparation by replacing the number of "Don't know" answers in the post-test group with correct answers. CONCLUSIONS: The barriers identified to the acquisition of knowledge about skin integrity impairment in nursing studies are the following: the transversality of teaching, the teaching and evaluation system, and the variability in the training of professionals and teachers in charge of their education. The educational intervention can be used to consolidate knowledge and to enhance students' self-confidence in caring for patients with wounds.

11.
PLoS One ; 19(3): e0282386, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38530775

RESUMEN

There is currently a growing interest in the so-called emerging pollutants, such as pesticides, pharmaceuticals, personal hygiene care products, drugs, etc., whose presence in natural ecosystems is not necessarily recent, but the development in latest years of new and more sensitive methods of analysis has allowed their detection. They can be present in the natural environment, food, and many products of everyday origin, which suggests that human exposure to them is massive and universal. Therefore, the study of this type of substances is becoming one of the priority lines of research of the main agencies dedicated to the protection of public and environmental health, such as the World Health Organization (WHO), United States Environmental Protection Agency (USEPA) or European Union (EU). In this sense, it is of vital importance to know the nature and quantity of this type of contaminants, to establish preventive mechanisms that minimize its presence in aquatic systems, with special requirements for human consumption. This study aimed to describe a protocol for a systematic review and meta-analysis to assess the status of pesticides in European waters. We will search for original studies in the PubMed/Medline, Scopus, Web of Science, EMBASE, ScienceDirect databases. Prevalence studies of emerging contaminants (pesticides) in water resources (watersheds, aquifers, rivers, marine and springs), wastewaters (influent and effluent), and drinking water should be included. Two reviewers will independently screen and assess the included studies, with any disagreements being resolved by a third reviewer. We will summarize the findings using a narrative approach and, if possible, conduct a quantitative synthesis (meta-analysis). We will conduct the protocol following the Preferred Reporting Items for Systematic Review and Meta-Analyses Protocols (PRISMA-P) guidelines. The review will summarize the current evidence on the presence of pesticides in European waters such as glyphosate, chlorpyrifos, pyrethroid pesticides, neonicotinoid pesticides, and/or fungicides, in samples of different water resources like wastewaters and drinking water. We expect that this systematic review will establish preventive mechanisms that minimize the presence of pesticides in water in the environment.


Asunto(s)
Metaanálisis como Asunto , Plaguicidas , Revisiones Sistemáticas como Asunto , Contaminantes Químicos del Agua , Plaguicidas/análisis , Contaminantes Químicos del Agua/análisis , Europa (Continente) , Humanos , Monitoreo del Ambiente/métodos , Aguas Residuales/análisis , Aguas Residuales/química
12.
Clin Gastroenterol Hepatol ; 22(8): 1596-1604.e4, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38513982

RESUMEN

BACKGROUND & AIMS: Endoscopic Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) detection is invasive and expensive. Nonendoscopic BE/EAC detection tools are guideline-endorsed alternatives. We previously described a 5-methylated DNA marker (MDM) panel assayed on encapsulated sponge cell collection device (CCD) specimens. We aimed to train a new algorithm using a 3-MDM panel and test its performance in an independent cohort. METHODS: Algorithm training and test samples were from 2 prospective multicenter cohorts. All BE cases had esophageal intestinal metaplasia (with or without dysplasia/EAC); control subjects had no endoscopic evidence of BE. The CCD procedure was followed by endoscopy. From CCD cell lysates, DNA was extracted, bisulfite treated, and MDMs were blindly assayed. The algorithm was set and locked using cross-validated logistic regression (training set) and its performance was assessed in an independent test set. RESULTS: Training (N = 352) and test (N = 125) set clinical characteristics were comparable. The final panel included 3 MDMs (NDRG4, VAV3, ZNF682). Overall sensitivity was 82% (95% CI, 68%-94%) at 90% (79%-98%) specificity and 88% (78%-94%) sensitivity at 84% (70%-93%) specificity in training and test sets, respectively. Sensitivity was 90% and 68% for all long- and short-segment BE, respectively. Sensitivity for BE with high-grade dysplasia and EAC was 100% in training and test sets. Overall sensitivity for nondysplastic BE was 82%. Areas under the receiver operating characteristic curves for BE detection were 0.92 and 0.94 in the training and test sets, respectively. CONCLUSIONS: A locked 3-MDM panel algorithm for BE/EAC detection using a nonendoscopic CCD demonstrated excellent sensitivity for high-risk BE cases in independent validation samples. (Clinical trials.gov: NCT02560623, NCT03060642.).


Asunto(s)
Algoritmos , Esófago de Barrett , Humanos , Esófago de Barrett/diagnóstico , Esófago de Barrett/patología , Estudios Prospectivos , Femenino , Masculino , Persona de Mediana Edad , Anciano , Sensibilidad y Especificidad , Adulto , Metilación de ADN , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/patología , Adenocarcinoma/diagnóstico , Adenocarcinoma/patología
13.
Nat Commun ; 15(1): 2126, 2024 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-38459105

RESUMEN

Ocean warming and acidification, decreases in dissolved oxygen concentrations, and changes in primary production are causing an unprecedented global redistribution of marine life. The identification of underlying ecological processes underpinning marine species turnover, particularly the prevalence of increases of warm-water species or declines of cold-water species, has been recently debated in the context of ocean warming. Here, we track changes in the mean thermal affinity of marine communities across European seas by calculating the Community Temperature Index for 65 biodiversity time series collected over four decades and containing 1,817 species from different communities (zooplankton, coastal benthos, pelagic and demersal invertebrates and fish). We show that most communities and sites have clearly responded to ongoing ocean warming via abundance increases of warm-water species (tropicalization, 54%) and decreases of cold-water species (deborealization, 18%). Tropicalization dominated Atlantic sites compared to semi-enclosed basins such as the Mediterranean and Baltic Seas, probably due to physical barrier constraints to connectivity and species colonization. Semi-enclosed basins appeared to be particularly vulnerable to ocean warming, experiencing the fastest rates of warming and biodiversity loss through deborealization.


Asunto(s)
Biodiversidad , Invertebrados , Animales , Océanos y Mares , Peces , Temperatura , Agua , Ecosistema , Calentamiento Global
14.
Sci Rep ; 14(1): 5804, 2024 03 09.
Artículo en Inglés | MEDLINE | ID: mdl-38461355

RESUMEN

Alcohol use disorder (AUD) remains a major public health concern. The dynorphin (DYN)/κ-opioid receptor (KOP) system is involved in actions of alcohol, particularly its withdrawal-associated negative affective states. This study tested the ability of LY2444296, a selective, short-acting, KOP antagonist, to decrease alcohol self-administration in dependent male and female Wistar rats at 8 h abstinence. Animals were trained to orally self-administer 10% alcohol (30 min/day for 21 sessions) and were made dependent via chronic intermittent alcohol vapor exposure for 6 weeks or exposed to air (nondependent). After 6 weeks, the effect of LY2444296 (0, 3, and 10 mg/kg, p.o.) was tested on alcohol self-administration at 8 h of abstinence. A separate cohort of rats was prepared in parallel, and their somatic withdrawal signs and alcohol self-administration were measured after LY2444296 administration at 8 h, 2 weeks, and 4 weeks abstinence. LY2444296 at 3 and 10 mg/kg significantly reduced physical signs of withdrawal in dependent rats at 8 h abstinence, only. Furthermore, 3 and 10 mg/kg selectively decreased alcohol self-administration in dependent rats at only 8 h abstinence. These results highlight the DYN/KOP system in actions of alcohol during acute abstinence, suggesting KOP antagonism could be beneficial for mitigating acute withdrawal signs and, in turn, significantly reduce excessive alcohol consumption associated with AUD.


Asunto(s)
Alcoholismo , Síndrome de Abstinencia a Sustancias , Humanos , Ratas , Masculino , Femenino , Animales , Alcoholismo/tratamiento farmacológico , Alcoholismo/psicología , Antagonistas de Narcóticos/farmacología , Antagonistas de Narcóticos/uso terapéutico , Ratas Wistar , Receptores Opioides kappa , Síndrome de Abstinencia a Sustancias/tratamiento farmacológico , Síndrome de Abstinencia a Sustancias/psicología , Etanol , Consumo de Bebidas Alcohólicas , Dinorfinas , Autoadministración
15.
Biol Psychiatry Glob Open Sci ; 4(1): 240-251, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38298791

RESUMEN

Background: Ketamine (KET) is administered to manage major depression in adolescent patients. However, the long-term effects of juvenile KET exposure on memory-related tasks have not been thoroughly assessed. We examined whether exposure to KET, psychological stress, or both results in long-lasting alterations in spatial memory in C57BL/6 mice. Furthermore, we evaluated how KET and/or psychological stress history influenced hippocampal protein kinase B-mechanistic target of rapamycin (AKT-mTOR)-related signaling. Methods: On postnatal day 35, male and female mice underwent vicarious defeat stress (VDS), a form of psychological stress that reduces sociability in both sexes, with or without KET exposure (20 mg/kg/day, postnatal days 35-44). In adulthood (postnatal day 70), mice were assessed for spatial memory performance on a water maze task or euthanized for hippocampal tissue collection. Results: Juvenile pre-exposure to KET or VDS individually increased the latency (seconds) to locate the escape platform in adult male, but not female, mice. However, juvenile history of concomitant KET and VDS prevented memory impairment. Furthermore, individual KET or VDS pre-exposure, unlike their combined history, decreased hippocampal AKT-mTOR signaling in adult male mice. Conversely, KET pre-exposure alone increased AKT-mTOR in the hippocampus of adult female mice. Lastly, rapamycin-induced decreases of mTOR in naïve adult female mice induced spatial memory retrieval deficits, mimicking adult male mice with a history of exposure to VDS or KET. Conclusions: Our preclinical model shows how KET treatment for the management of adolescent psychological stress-induced sequelae does not impair spatial memory later in life. However, juvenile recreational KET misuse, like psychological stress history, results in long-term spatial memory deficits and hippocampal AKT-mTOR signaling changes in a sex-specific manner.

16.
Glob Chang Biol ; 30(1): e17143, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38273518

RESUMEN

As charismatic and iconic species, penguins can act as "ambassadors" or flagship species to promote the conservation of marine habitats in the Southern Hemisphere. Unfortunately, there is a lack of reliable, comprehensive, and systematic analysis aimed at compiling spatially explicit assessments of the multiple impacts that the world's 18 species of penguin are facing. We provide such an assessment by combining the available penguin occurrence information from Global Biodiversity Information Facility (>800,000 occurrences) with three main stressors: climate-driven environmental changes at sea, industrial fisheries, and human disturbances on land. Our analyses provide a quantitative assessment of how these impacts are unevenly distributed spatially within species' distribution ranges. Consequently, contrasting pressures are expected among species, and populations within species. The areas coinciding with the greatest impacts for penguins are the coast of Perú, the Patagonian Shelf, the Benguela upwelling region, and the Australian and New Zealand coasts. When weighting these potential stressors with species-specific vulnerabilities, Humboldt (Spheniscus humboldti), African (Spheniscus demersus), and Chinstrap penguin (Pygoscelis antarcticus) emerge as the species under the most pressure. Our approach explicitly differentiates between climate and human stressors, since the more achievable management of local anthropogenic stressors (e.g., fisheries and land-based threats) may provide a suitable means for facilitating cumulative impacts on penguins, especially where they may remain resilient to global processes such as climate change. Moreover, our study highlights some poorly represented species such as the Northern Rockhopper (Eudyptes moseleyi), Snares (Eudyptes robustus), and Erect-crested penguin (Eudyptes sclateri) that need internationally coordinated efforts for data acquisition and data sharing to understand their spatial distribution properly.


Asunto(s)
Spheniscidae , Animales , Humanos , Australia , Ecosistema , Biodiversidad , Explotaciones Pesqueras
17.
Am J Gastroenterol ; 119(4): 662-670, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-37795907

RESUMEN

INTRODUCTION: Endoscopic eradication therapy (EET) is standard of care for T1a esophageal adenocarcinoma (EAC). However, data on outcomes in high-risk T1a EAC are limited. We assessed and compared outcomes after EET of low-risk and high-risk T1a EAC, including intraluminal EAC recurrence, extraesophageal metastases, and overall survival. METHODS: Patients who underwent EET for T1a EAC at 3 referral Barrett's esophagus endotherapy units between 1996 and 2022 were included. Patients with submucosal invasion, positive deep margins, or metastases at initial diagnosis were excluded. High-risk T1a EAC was defined as T1a EAC with poor differentiation and/or lymphovascular invasion, with low-risk disease being defined without these features. All pathology was systematically assessed by expert gastrointestinal pathologists. Baseline and follow-up endoscopy and pathology data were abstracted. Time-to-event analyses were performed to compare outcomes between groups. RESULTS: One hundred eighty-eight patients with T1a EAC were included (high risk, n = 45; low risk, n = 143) with a median age of 70 years, and 84% were men. Groups were comparable for age, sex, Barrett's esophagus length, lesion size, and EET technique. Rates of delayed extraesophageal metastases (11.1% vs 1.4%) were significantly higher in the high-risk group ( P = 0.02). There was no significant difference in the rates of intraluminal EAC recurrence ( P = 0.79) and overall survival ( P = 0.73) between the 2 groups. DISCUSSION: Patients with high-risk T1a EAC undergoing successful EET had a substantially higher rate of extraesophageal metastases compared with those with low-risk T1a EAC on long-term follow-up. These data should be factored into discussions with patients while selecting treatment approaches. Additional prospective data in this area are critical.


Asunto(s)
Adenocarcinoma , Esófago de Barrett , Neoplasias Esofágicas , Masculino , Humanos , Anciano , Femenino , Esófago de Barrett/cirugía , Esófago de Barrett/patología , Estudios Prospectivos , Neoplasias Esofágicas/patología , Adenocarcinoma/patología , Endoscopía Gastrointestinal
18.
J Immunol Methods ; 524: 113586, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38040191

RESUMEN

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19) global pandemic. Rapid and sensitive detection of the virus soon after infection is important for the treatment and prevention of transmission of COVID-19, and detection of antibodies is important for epidemiology, assessment of vaccine immunogenicity, and identification of the natural reservoir and intermediate host(s). Patient nasal or oropharyngeal swabs or saliva used in conjunction with polymerase chain reaction (PCR) detect SARS-CoV-2 RNA, whereas lateral flow immunoassays (LFI) detect SARS-CoV-2 proteins. Enzyme-linked immunosorbent assays (ELISA) detect anti-SARS-CoV-2 antibodies in blood. Although effective, these assays have poor sensitivity (e.g., LFI) or are labor intensive and time consuming (PCR and ELISA). Here we describe the development of rapid, automated ELISA-based immunoassays to detect SARS-CoV-2 antigens and antibodies against the virus. The Simple Plex™ platform uses rapid microfluidic reaction kinetics for sensitive analyte detection with small sample volumes. We developed three sensitive <90-min Simple Plex immunoassays that measure either the SARS-CoV-2 antigens or the immune response to SARS-CoV-2, including neutralizing antibodies, in serum from COVID-19 patients.


Asunto(s)
COVID-19 , Humanos , COVID-19/diagnóstico , SARS-CoV-2 , Prueba de COVID-19 , ARN Viral , Microfluídica , Inmunoglobulina G , Inmunoensayo , Anticuerpos Antivirales , Sensibilidad y Especificidad
19.
Environ Pollut ; 343: 123159, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38104761

RESUMEN

Mercury (Hg) is a global pollutant known for its significant bioaccumulation and biomagnification capabilities, posing a particular threat to marine environments. Seabirds have been recognized as effective bioindicators of marine pollution, and, among them, penguins present a unique opportunity to serve as a single taxonomic group (Sphenisciformes) for monitoring Hg across distinct marine ecosystems in the Southern Hemisphere. In this study, we conducted a comprehensive systematic review of Hg concentrations, and performed a meta-analysis that took into account the various sources of uncertainty associated with Hg contamination in penguins. Beyond intrinsic species-specific factors shaping Hg levels, our results showed that the penguin community effectively reflects spatial patterns of Hg bioavailability. We identified geographic Hg hotspots in Australia, the Indian Ocean, and Tierra del Fuego, as well as coldspots in Perú and the South Atlantic. Furthermore, specific penguin species, namely the Southern Rockhopper (Eudyptes chrysocome) and Macaroni penguin (Eudyptes chrysolophus), are highlighted as particularly vulnerable to the toxic effects of Hg. Additionally, we identified knowledge gaps in geographic areas such as the Galápagos Islands, South Africa, and the coast of Chile, as well as in species including Fiordland (Eudyptes pachyrhynchus), Snares (Eudyptes robustus), Erect-crested (Eudyptes sclateri), Royal (Eudyptes schlegeli), Yellow-eyed (Megadyptes antipodes), and Galápagos (Spheniscus mendiculus) penguins. Overall, our study contributes to the growing body of literature emphasizing the role of penguins as bioindicators of Hg pollution, but it also highlights areas where further research and data collection are needed for a more comprehensive understanding of Hg contamination in marine ecosystems in the Southern Hemisphere.


Asunto(s)
Ecosistema , Monitoreo del Ambiente , Mercurio , Spheniscidae , Contaminantes Químicos del Agua , Animales , Spheniscidae/metabolismo , Mercurio/análisis , Mercurio/metabolismo , Monitoreo del Ambiente/métodos , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/metabolismo , Australia , Océano Índico
20.
Animals (Basel) ; 13(23)2023 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-38067066

RESUMEN

This work aimed to determine the presence of bacterial pathogens in fish with a clinical picture suggestive of infectious disease in Nile tilapia reared in Chiapas, Mexico. Blood and viscera samples were taken from healthy and diseased animals from commercial farms. Clinical and pathological examinations of each individual were performed and samples were collected for bacteriological studies. The bacterial isolates were identified and characterized by culture, biochemical tests, antibiogram, challenge tests and 16S rRNA sequencing. Staphylococcus haemolyticus and Providencia vermicola were isolated from various diseased organisms. The clinical picture caused by Staphylococcus haemolyticus was characterized by appetite disorders, neurological signs, nodulation or ulceration in different areas and congestion or enlargement of internal organs. Providenciosis in juvenile specimens caused a characteristic picture of hemorrhagic septicemia. Challenge tests performed in healthy organisms revealed that both infections caused higher mortality rates in fish (p < 0.05) compared with non-infected specimens, with 100% survival. There was 100% mortality for animals infected with P. vermicola after three days post infection and 45% for those infected with S. haemolyticus. The isolation and identification of two pathogens involved in an infection process were achieved and cataloged as potential causal agents of disease outbreaks in tilapia farming in Mexico. This is the first report of possible bacterial infection caused by S. haemolyticus and P. vermicola in tilapia farms, which are two uncommon but potentially emerging pathogens for the species.

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