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1.
AIDS Res Ther ; 21(1): 52, 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39113038

RESUMEN

BACKGROUND: Anemia is common and associated with increased morbidity among people with HIV (PWH). Classification of anemia using the mean corpuscular volume (MCV) can help investigate the underlying causative factors of anemia. We characterize anemia using MCV among PWH receiving antiretroviral therapy (ART), and identify the risk factors for normocytic, macrocytic, and microcytic anemias. METHODS: Including PWH with anemia (hemoglobin measure < 12.9 g/dL among men and < 11.9 g/dL among women) in the NA-ACCORD from 01/01/2007 to 12/31/2017, we estimated the annual distribution of normocytic (80-100 femtolitre (fL)), macrocytic (> 100 fL) or microcytic (< 80 fL) anemia based on the lowest hemoglobin within each year. Poisson regression models with robust variance and general estimating equations were used to estimate crude and adjusted prevalence ratios and 95% confidence intervals for risk factors for macrocytic (vs. normocytic) and microcytic (vs. normocytic) anemia stratified by sex. RESULTS: Among 37,984 hemoglobin measurements that identified anemia in 14,590 PWH, 27,909 (74%) were normocytic, 4257 (11%) were microcytic, and 5818 (15%) were macrocytic. Of the anemic PWH included over the study period, 1910 (13%) experienced at least one measure of microcytic anemia and 3208 (22%) at least one measure of macrocytic anemia. Normocytic anemia was most common among both males and females, followed by microcytic among females and macrocytic among males. Over time, the proportion of anemic PWH who have macrocytosis decreased while microcytosis increased. Macrocytic (vs. normocytic) anemia is associated with increasing age and comorbidities. With increasing age, microcytic anemia decreased among females but not males. A greater proportion of PWH with normocytic anemia had CD4 counts ≤ 200 cells/mm3 and had recently initiated ART. CONCLUSION: In anemic PWH, normocytic anemia was most common. Over time macrocytic anemia decreased, and microcytic anemia increased irrespective of sex. Normocytic anemia is often due to chronic disease and may explain the greater risk for normocytic anemia among those with lower CD4 counts or recent ART initiation. Identified risk factors for type-specific anemias including sex, age, comorbidities, and HIV factors, can help inform targeted investigation into the underlying causes.


Asunto(s)
Anemia , Índices de Eritrocitos , Infecciones por VIH , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Infecciones por VIH/complicaciones , Infecciones por VIH/sangre , Masculino , Femenino , Anemia/epidemiología , Anemia/sangre , Adulto , Persona de Mediana Edad , Factores de Riesgo , América del Norte/epidemiología , Prevalencia , Hemoglobinas/análisis , Fármacos Anti-VIH/uso terapéutico , Recuento de Linfocito CD4
2.
J Am Chem Soc ; 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39137318

RESUMEN

The newly discovered series of layered monophosphate tungsten bronzes (L-MPTB) [Ba(PO4)2]WmO3m-3 consist of m-layer-thick slabs of WO6 octahedra separated by barium-phosphate spacers. They display a 2D metallic behavior confined in the central part of the perovskite slabs. Here, we report the missing m = 2 member of this series, containing the rather uncommon W5+ oxidation state. We have analyzed its structure-property relationships in relation to the other members of the L-MPTB family. In particular, we have determined its crystal structure by means of single-crystal X-ray and electron diffraction and investigated its physical properties from resistivity, Seebeck-coefficient and heat-capacity measurements combined with first-principles calculations. All the L-MPTB compounds show metallic behavior down to 1.8 K without any clear charge-density-wave (CDW) order. The m = 2 member, however, displays an increased influence of the spacer that translates into anisotropic negative thermal expansion, reversed thermopower and reversed crystal-field splitting of the tungsten t2g orbitals. Our analysis of the full [Ba(PO4)2]WmO3m-3 series reveals a systematic and significant W off-centering in their octahedral coordination. We identify the resulting anti-polar character of these W displacements as the crucial aspect behind the 2D metallicity of these systems: It leads to the presence of bound charges whose screening determines the distribution of mobile charges, tending to accumulate at the center of the [WmO3-m] block. We argue that this mechanism is analogous to enhanced conductivity observed for charged domain walls in ferroelectrics, thus providing a general design rule to promote 2D metallicity in layered systems.

3.
Aging Dis ; 2024 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-39122449

RESUMEN

Cognitive decline has been reported as a short-term sequela in patients hospitalized for coronavirus disease-19 (COVID-19). Whether COVID-19 is associated with late cognitive impairment in older free-living individuals with high cardiovascular risk, a group at greater risk of cognitive decline, is unknown. We determined this association of COVID-19 through a longitudinal evaluation of post-COVID-19 cognitive performance and impairment as post hoc analysis in 5,179 older adults (48% female) with mean (SD) age 68.5 (5.0) years, body mass index 31.7 (3.7) kg/m2, harboring ≥ 3 criteria for metabolic syndrome (e.g., hypertension, hyperlipidemia, hyperglycemia etc.) enrolled in PREDIMED-Plus trial. Pre- and post-COVID-19 cognitive performance was ascertained from scheduled assessments conducted using a battery of neuropsychological tests, including 5 domains: Global Cognitive Function, General Cognitive Function, Execution Function, Verbal Fluency and Attention domains, which were standardized for the cohort. Cognitive impairment was defined as the bottom 10 percentile of the sample. Multivariable linear and logistic regression models assessed the association of COVID-19 with cognitive decline and impairment, respectively. After a mean 50-week follow-up, no significant associations were observed between COVID-19 status and post-COVID-19 scores of all tapped neuropsychological domains, except Global Cognitive Function (GCF). When fully adjusted, COVID-19 was marginally associated with higher (better) post-pandemic GCF score (ßadj (95% CI): 0.06 (0.00, 0.13) p=.05). However, the odds for post-COVID-19 cognitive impairment in GCF domain were not associated with the disease (ORadj (95% CI): 0.90 (0.53, 1.51) p=.68). In the PREDIMED-Plus cohort, COVID-19 status and cognitive impairment determined 50 weeks post-infection showed no association in older adults at high cardiovascular risk. This suggests that cognitive changes observed shortly after COVID-19 revert over time. However, cautious interpretation is warranted as these data were obtained within the framework of a clinical trial encouraging a healthy lifestyle.

4.
Artículo en Inglés | MEDLINE | ID: mdl-39118208

RESUMEN

BACKGROUND: Anemia is an independent predictor of mortality, which may be utilized as a signal of deteriorating health. We estimated the association between anemia severity categories and mortality following the initiation of antiretroviral therapy (ART) among people with HIV (PWH) in North America. METHODS: Within the NA-ACCORD, annual median hemoglobin measurements between 01/01/2007-12/31/2016 were categorized using World Health Organization criteria into mild (11.0-12.9g/dL men, 11.0-11.9g/dL women), moderate (8.0-10.9g/dL men/women) and severe (<8.0g/dL men/women) anemia. Discrete time-to-event analyses using complementary log-log link models estimated mortality hazards ratios adjusted for demographics, comorbidities, and HIV clinical markers with 95% confidence intervals for the association between anemia and mortality. RESULTS: Among 67,228 PWH contributing a total of 320,261 annual median hemoglobin measurements, 257,293 (80%) demonstrated no anemia, 44,041 (14%) mild, 18,259 (6%) moderate, and 668 (0.2%) severe anemia during follow-up. Mortality risk was 5.6-fold higher among PWH with (vs. without) anemia. The association was greater among males (aHR=5.8 [5.4, 6.2]) versus females (aHR=4.1 [3.2, 5.4]). Mortality risk was 3.8-fold higher among PWH with mild anemia, 13.7-fold higher with moderate anemia, and 34.5-fold higher with severe anemia (vs. no anemia). Median hemoglobin levels significantly declined within 4 years prior to death, with the maximum decrease the year prior to death. Macrocytic anemia was associated with an increased and microcytic anemia a decreased mortality risk (vs. normocytic anemia). CONCLUSIONS: Anemia among PWH who have initiated ART is an important predictive marker for mortality with macrocytic anemia having an increased and microcytic anemia a decreased association with mortality compared with normocytic anemia.

5.
Anal Chim Acta ; 1318: 342942, 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39067921

RESUMEN

BACKGROUND: In reversed-phase liquid chromatography, solute retention is primarily influenced by interactions between a nonpolar stationary phase and a moderately polar hydro-organic mobile phase, based on the solute lipophilicity. However, challenges regarding retention and peak tailing can arise due to ionic interactions between positively charged analytes and free silanols present on silica-based stationary phases. To address these challenges, incorporating surfactants and ionic liquids (ILs) into the mobile phase offers an effective solution. These additives synergistically enhance chromatographic performance through electrostatic and lipophilic interactions, which enable fine-tuning of selectivity and improved separation efficiency. RESULTS: This study explores the chromatographic behaviour of several basic compounds in aqueous mixtures containing the anionic surfactant sodium dodecyl sulphate (SDS), above its critical micellar concentration, combined with various 1-alkyl-3-methylimidazolium-based ionic liquids (ILs) featuring chloride, tetrafluoroborate, and hexafluorophosphate anions, all without the addition of organic solvents. Specifically, this research investigates the influence of different anion types within the ILs and considers the impact of the IL cations. Analysis of solute peak profiles reveals narrow and symmetrical peaks. By introducing tetrafluoroborate and hexafluorophosphate IL anions into a mobile phase that contains an anionic surfactant, the study sheds light on the interactions occurring within the chromatographic column. This enhanced understanding of the combined effects of surfactants and ILs contributes to refining chromatographic methodologies. SIGNIFICANCE: This research highlights the importance of carefully selecting the appropriate IL when incorporating it into a micellar mobile phase alongside SDS. This combination results in practical retention times that surpass the performance achieved with either the surfactant or IL alone in the mobile phase. The study particularly emphasises the impact of the IL anion, especially in the absence of SDS and organic solvents. This unveils interactions that are otherwise obscured in micellar and hydro-organic media, providing new insights into chromatographic dynamics.

6.
Nutrients ; 16(13)2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38999747

RESUMEN

BACKGROUND: The COVID-19 lockdown represented an immense impact on human health, which was characterized by lifestyle and dietary changes, social distancing and isolation at home. Some evidence suggests that these consequences mainly affected women and altered relevant ongoing clinical trials. The aim of this study was to evaluate the status and changes in diet, physical activity (PA), sleep and self-reported health status (SRH) as perceived by older adult men and women with metabolic syndrome during the COVID-19 lockdown. METHODS: We analyzed data from 4681 Spanish adults with metabolic syndrome. We carried out a telephone survey during May and June 2020 to collect information on demographics, dietary habits, PA, sleep, SRH and anthropometric data. RESULTS: The mean age of participants was 64.9 years at recruitment, and 52% of participants were men. Most participants (64.1%) perceived a decrease in their PA during confinement. Regarding gender-specific differences, a higher proportion of women than men perceived a decrease in their PA (67.5% vs. 61.1%), Mediterranean diet adherence (20.9% vs. 16.8%), sleep hours (30.3% vs. 19.1%), sleep quality (31.6% vs. 18.2%) and SRH (25.9% vs. 11.9%) (all p < 0.001). CONCLUSIONS: The COVID-19 lockdown affected women more negatively, particularly their self-reported diet, PA, sleep and health status.


Asunto(s)
COVID-19 , Ejercicio Físico , Estado de Salud , Estilo de Vida , Síndrome Metabólico , Autoinforme , Humanos , Masculino , Femenino , COVID-19/epidemiología , COVID-19/prevención & control , Persona de Mediana Edad , Anciano , España/epidemiología , Síndrome Metabólico/epidemiología , Factores Sexuales , Factores de Riesgo Cardiometabólico , SARS-CoV-2 , Cuarentena , Dieta Mediterránea/estadística & datos numéricos , Sueño , Dieta
7.
Artículo en Inglés | MEDLINE | ID: mdl-38971932

RESUMEN

Psychedelics produce lasting therapeutic responses in neuropsychiatric diseases suggesting they may disrupt entrenched associations and catalyze learning. Here, we examine psychedelic 5-HT2A/2C agonist, DOI, effects on dopamine signaling in the nucleus accumbens (NAc) core, a region extensively linked to reward learning, motivation, and drug-seeking. We measure phasic dopamine transients following acute DOI administration in rats during well learned Pavlovian tasks in which sequential cues predict rewards. We find that DOI (0.0-1.2 mg/kg, i.p.) increases dopamine signals, photometrically measured using GRABDA optical sensor, to rewards and proximal reward cues, but not to the distal cues that predict these events. We determine that the elevated dopamine produced by DOI to reward cues occurs independently of DOI-induced changes in reward value. The increased dopamine associated with predictable reward cues and rewards supports DOI-induced increases in prediction error signaling. These findings lay a foundation for developing psychedelic strategies aimed at engaging error-driven learning mechanisms to disrupt entrenched associations or produce new associations.

8.
Plant Physiol Biochem ; 214: 108923, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39002308

RESUMEN

Jasmonates are growth regulators that play a key role in flower development, fruit ripening, root growth, and plant defence. The study explores the coordination of floral organ maturation to ensure proper flower opening for pollination and fertilization. A new mutant (jar1b) was discovered, lacking petal elongation and flower opening but showing normal pistil and stamen development, leading to parthenocarpic fruit development. The mutation also enhanced the elongation of roots while reducing the formation of root hairs. BSA sequencing showed that jar1b is a missense mutation in the gene CpJAR1B, which encodes the enzyme that catalyzes the conjugation between JA and the amino acid isoleucine. The loss of function mutation in CpJAR1B produced a deficiency in biologically active (+) -7-iso-jasmonoyl-L-isoleucine (JA-Ile), which was not complemented by the paralogous gene CpJAR1A or any other redundant gene. Exogenous application of methyl jasmonate (MeJA) demonstrated that jar1b is partially insensitive to JA in both flowers and roots. Further experimentation involving the combination of JA-Ile deficient and ethylene-deficient, and ET insensitive mutations in double mutants revealed that CpJAR1B mediated ET action in female petal maturation and flower opening, but JA and ET have independent additive effects as negative regulators of the set and development of squash fruits. CpJAR1B also regulated the aperture of male flowers in an ethylene-independent manner. The root phenotype of jar1b and effects of external MeJA treatments indicated that CpJAR1B has a dual role in root development, inhibiting the elongation of primary and secondary roots, but promoting the formation of root hairs.


Asunto(s)
Cucurbita , Ciclopentanos , Flores , Frutas , Oxilipinas , Proteínas de Plantas , Ciclopentanos/farmacología , Ciclopentanos/metabolismo , Oxilipinas/farmacología , Oxilipinas/metabolismo , Flores/genética , Flores/crecimiento & desarrollo , Flores/efectos de los fármacos , Cucurbita/genética , Cucurbita/crecimiento & desarrollo , Frutas/genética , Frutas/crecimiento & desarrollo , Frutas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Isoleucina/farmacología , Isoleucina/metabolismo , Isoleucina/análogos & derivados , Mutación , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Acetatos/farmacología , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/genética , Raíces de Plantas/metabolismo , Raíces de Plantas/efectos de los fármacos , Reguladores del Crecimiento de las Plantas/metabolismo , Reguladores del Crecimiento de las Plantas/farmacología
9.
Appl Environ Microbiol ; 90(7): e0052824, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-38916293

RESUMEN

Xenorhabdus nematophila is a symbiotic Gammaproteobacterium that produces diverse natural products that facilitate mutualistic and pathogenic interactions in their nematode and insect hosts, respectively. The interplay between X. nematophila secondary metabolism and symbiosis stage is tuned by various global regulators. An example of such a regulator is the LysR-type protein transcription factor LrhA, which regulates amino acid metabolism and is necessary for virulence in insects and normal nematode progeny production. Here, we utilized comparative metabolomics and molecular networking to identify small molecule factors regulated by LrhA and characterized a rare γ-ketoacid (GKA) and two new N-acyl amides, GKA-Arg (1) and GKA-Pro (2) which harbor a γ-keto acyl appendage. A lrhA null mutant produced elevated levels of compound 1 and reduced levels of compound 2 relative to wild type. N-acyl amides 1 and 2 were shown to be selective agonists for the human G-protein-coupled receptors (GPCRs) C3AR1 and CHRM2, respectively. The CHRM2 agonist 2 deleteriously affected the hatch rate and length of Steinernema nematodes. This work further highlights the utility of exploiting regulators of host-bacteria interactions for the identification of the bioactive small molecule signals that they control. IMPORTANCE: Xenorhabdus bacteria are of interest due to their symbiotic relationship with Steinernema nematodes and their ability to produce a variety of natural bioactive compounds. Despite their importance, the regulatory hierarchy connecting specific natural products and their regulators is poorly understood. In this study, comparative metabolomic profiling was utilized to identify the secondary metabolites modulated by the X. nematophila global regulator LrhA. This analysis led to the discovery of three metabolites, including an N-acyl amide that inhibited the egg hatching rate and length of Steinernema carpocapsae nematodes. These findings support the notion that X. nematophila LrhA influences the symbiosis between X. nematophila and S. carpocapsae through N-acyl amide signaling. A deeper understanding of the regulatory hierarchy of these natural products could contribute to a better comprehension of the symbiotic relationship between X. nematophila and S. carpocapsae.


Asunto(s)
Amidas , Proteínas Bacterianas , Simbiosis , Factores de Transcripción , Xenorhabdus , Xenorhabdus/genética , Xenorhabdus/metabolismo , Xenorhabdus/fisiología , Animales , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Amidas/farmacología , Amidas/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Regulación Bacteriana de la Expresión Génica , Humanos , Nematodos/microbiología
10.
Int J Mol Sci ; 25(12)2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38927995

RESUMEN

Neural precursor cells (NPCs) that persist in the postnatal/adult subventricular zone (SVZ) express connexins that form hemichannels and gap junctions. Gap junctional communication plays a role in NPC proliferation and differentiation during development, but its relevance on postnatal age remains to be elucidated. In this work we aimed to evaluate the effect of the blockade of gap junctional communication on proliferation and cell fate of NPCs obtained from the SVZ of postnatal rats. NPCs were isolated and expanded in culture as neurospheres. Electron microscopy revealed the existence of gap junctions among neurosphere cells. Treatment of cultures with octanol, a broad-spectrum gap junction blocker, or with Gap27, a specific blocker for gap junctions formed by connexin43, produced a significant decrease in bromodeoxyuridine incorporation. Octanol treatment also exerted a dose-dependent antiproliferative effect on glioblastoma cells. To analyze possible actions on NPC fate, cells were seeded in the absence of mitogens. Treatment with octanol led to an increase in the percentage of astrocytes and oligodendrocyte precursors, whereas the percentage of neurons remained unchanged. Gap27 treatment, in contrast, did not modify the differentiation pattern of SVZ NPCs. Our results indicate that general blockade of gap junctions with octanol induces significant effects on the behavior of postnatal SVZ NPCs, by reducing proliferation and promoting glial differentiation.


Asunto(s)
Diferenciación Celular , Proliferación Celular , Uniones Comunicantes , Células-Madre Neurales , Neuroglía , Octanoles , Animales , Uniones Comunicantes/efectos de los fármacos , Uniones Comunicantes/metabolismo , Células-Madre Neurales/efectos de los fármacos , Células-Madre Neurales/metabolismo , Células-Madre Neurales/citología , Proliferación Celular/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Ratas , Octanoles/farmacología , Neuroglía/efectos de los fármacos , Neuroglía/metabolismo , Neuroglía/citología , Células Cultivadas , Ventrículos Laterales/citología , Ventrículos Laterales/metabolismo , Ventrículos Laterales/efectos de los fármacos , Conexina 43/metabolismo , Ratas Wistar , Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Astrocitos/citología , Animales Recién Nacidos , Humanos
11.
Spinal Cord ; 62(8): 454-467, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38898145

RESUMEN

STUDY DESIGN: Double-blind, randomized, placebo-controlled, parallel-group multicentric phase IIA clinical trial. OBJECTIVE: To assess the safety and tolerability of oral administration of NFX-88 in subjects with chronic spinal cord injury (SCI) and explore its efficacy in pain control. SETTING: A total of 7 spinal cord injury rehabilitation units in Spain. METHODS: A total of 61 adult with traumatic complete or incomplete spinal cord injury (C4-T12 level), were randomised 1:1:1:1 to a placebo, NFX88 1.05 g, 2.1 g, 4.2 g/day for up to 12 weeks. The placebo or NFX-88 was administered as add-on therapy to pre-existing pregabalin (150-300 mg per day). Safety and tolerability were evaluated, and the Visual Analogue Scale (VAS) was the primary measure to explore the efficacy of NFX-88 in pain control. RESULTS: No severe treatment-related adverse effects were reported for any of the four study groups. 44 SCI individuals completed the study and were analysed. The data obtained from the VAS analysis and the PainDETECT Questionnaire (PD-Q) suggested that the combination of NFX88 with pregabalin is more effective than pregabalin with placebo at reducing neuropathic pain (NP) in individuals with SCI and that the dose 2.10 g/day causes the most dramatic pain relief. CONCLUSIONS: NFX88 treatment was found to be highly safe and well tolerated, with the dose of 2.10 g/day being the most effective at causing pain relief. Thus, the promising efficacy of this first-in-class lipid mediator deserves further consideration in future clinical trials.


Asunto(s)
Neuralgia , Traumatismos de la Médula Espinal , Humanos , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/tratamiento farmacológico , Neuralgia/tratamiento farmacológico , Neuralgia/etiología , Método Doble Ciego , Masculino , Femenino , Persona de Mediana Edad , Adulto , Administración Oral , Analgésicos/administración & dosificación , Pregabalina/administración & dosificación , Resultado del Tratamiento , Dimensión del Dolor , Anciano , Adulto Joven
12.
Clin Cancer Res ; 30(16): 3578-3591, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38864848

RESUMEN

PURPOSE: Retinoblastoma is the most common intraocular malignancy in children. Although new chemotherapeutic approaches have improved ocular salvage rates, novel therapies are required for patients with refractory intraocular and metastatic disease. Chimeric antigen receptor (CAR) T cells targeting glypican-2 (GPC2) are a potential new therapeutic strategy. EXPERIMENTAL DESIGN: GPC2 expression and its regulation by the E2F1 transcription factor were studied in retinoblastoma patient samples and cellular models. In vitro, we performed functional studies comparing GPC2 CAR T cells with different costimulatory domains (4-1BB and CD28). In vivo, the efficacy of local and systemic administration of GPC2 CAR T cells was evaluated in intraocular and leptomeningeal human retinoblastoma xenograft models. RESULTS: Retinoblastoma tumors, but not healthy retinal tissues, expressed cell surface GPC2, and this tumor-specific expression was driven by E2F1. GPC2-directed CARs with 4-1BB costimulation (GPC2.BBz) were superior to CARs with CD28 stimulatory domains (GPC2.28z), efficiently inducing retinoblastoma cell cytotoxicity and enhancing T-cell proliferation and polyfunctionality. In vivo, GPC2.BBz CARs had enhanced persistence, which led to significant tumor regression compared with either control CD19 or GPC2.28z CARs. In intraocular models, GPC2.BBz CAR T cells efficiently trafficked to tumor-bearing eyes after intravitreal or systemic infusions, significantly prolonging ocular survival. In central nervous system (CNS) retinoblastoma models, intraventricular or systemically administered GPC2.BBz CAR T cells were activated in retinoblastoma-involved CNS tissues, resulting in robust tumor regression with substantially extended overall mouse survival. CONCLUSIONS: GPC2-directed CAR T cells are effective against intraocular and CNS metastatic retinoblastomas.


Asunto(s)
Glipicanos , Inmunoterapia Adoptiva , Receptores Quiméricos de Antígenos , Retinoblastoma , Linfocitos T , Ensayos Antitumor por Modelo de Xenoinjerto , Humanos , Animales , Retinoblastoma/inmunología , Retinoblastoma/patología , Retinoblastoma/terapia , Ratones , Receptores Quiméricos de Antígenos/inmunología , Glipicanos/inmunología , Glipicanos/antagonistas & inhibidores , Inmunoterapia Adoptiva/métodos , Linfocitos T/inmunología , Linfocitos T/metabolismo , Línea Celular Tumoral , Neoplasias del Sistema Nervioso Central/terapia , Neoplasias del Sistema Nervioso Central/inmunología , Neoplasias del Sistema Nervioso Central/secundario , Neoplasias del Sistema Nervioso Central/patología , Modelos Animales de Enfermedad , Femenino
13.
Biotechnol Biofuels Bioprod ; 17(1): 77, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38835059

RESUMEN

Plastic consumption has increased globally, and environmental issues associated with it have only gotten more severe; as a result, the search for environmentally friendly alternatives has intensified. Polyhydroxyalkanoates (PHA), as biopolymers produced by microalgae, might be an excellent option; however, large-scale production is a relevant barrier that hinders their application. Recently, innovative materials such as carbon dots (CDs) have been explored to enhance PHA production sustainably. This study added green synthesized multi-doped CDs to Scenedesmus sp. microalgae cultures to improve PHA production. Prickly pear was selected as the carbon precursor for the hydrothermally synthesized CDs doped with nitrogen, phosphorous, and nitrogen-phosphorous elements. CDs were characterized by different techniques, such as FTIR, SEM, ζ potential, UV-Vis, and XRD. They exhibited a semi-crystalline structure with high concentrations of carboxylic groups on their surface and other elements, such as copper and phosphorus. A medium without nitrogen and phosphorous was used as a control to compare CDs-enriched mediums. Cultures regarding biomass growth, carbohydrates, lipids, proteins, and PHA content were analyzed. The obtained results demonstrated that CDs-enriched cultures produced higher content of biomass and PHA; CDs-enriched cultures presented an increase of 26.9% in PHA concentration and an increase of 32% in terms of cell growth compared to the standard cultures.

14.
Int J Mol Sci ; 25(11)2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38892351

RESUMEN

Pulmonary arteriovenous malformations (PAVMs) are vascular anomalies resulting in abnormal connections between pulmonary arteries and veins. In 80% of cases, PAVMs are present from birth, but clinical manifestations are rarely seen in childhood. These congenital malformations are typically associated with Hereditary Hemorrhagic Telangiectasia (HHT), a rare disease that affects 1 in 5000/8000 individuals. HHT disease is frequently caused by mutations in genes involved in the TGF-ß pathway. However, approximately 15% of patients do not have a genetic diagnosis and, among the genetically diagnosed, more than 33% do not meet the Curaçao criteria. This makes clinical diagnosis even more challenging in the pediatric age group. Here, we introduce an 8-year-old patient bearing a severe phenotype of multiple diffuse PAVMs caused by an unknown mutation which ended in lung transplantation. Phenotypically, the case under study follows a molecular pattern which is HHT-like. Therefore, molecular- biological and cellular-functional analyses have been performed in primary endothelial cells (ECs) isolated from the explanted lung. The findings revealed a loss of functionality in lung endothelial tissue and a stimulation of endothelial-to-mesenchymal transition. Understanding the molecular basis of this transition could potentially offer new therapeutic strategies to delay lung transplantation in severe cases.


Asunto(s)
Células Endoteliales , Arteria Pulmonar , Venas Pulmonares , Telangiectasia Hemorrágica Hereditaria , Humanos , Telangiectasia Hemorrágica Hereditaria/genética , Telangiectasia Hemorrágica Hereditaria/patología , Niño , Arteria Pulmonar/anomalías , Arteria Pulmonar/patología , Venas Pulmonares/anomalías , Venas Pulmonares/patología , Células Endoteliales/metabolismo , Células Endoteliales/patología , Masculino , Mutación , Malformaciones Arteriovenosas/genética , Malformaciones Arteriovenosas/patología , Malformaciones Arteriovenosas/metabolismo , Transición Epitelial-Mesenquimal/genética , Trasplante de Pulmón , Fístula Arteriovenosa/patología , Fístula Arteriovenosa/genética , Pulmón/patología , Pulmón/irrigación sanguínea , Femenino
15.
Artículo en Inglés | MEDLINE | ID: mdl-38841841

RESUMEN

INTRODUCTION: Intimate partner violence (IPV) involves an individual committing acts intended to harm or intimidate a current or former romantic partner. The COVID-19 pandemic and subsequent stay-at-home orders often trapped victims with perpetrators and intensified IPV. Although sexual and gender diverse people disproportionately experience IPV compared to cisgender, heterosexual people, their experiences are not well documented in the Canadian context. This study aimed to explore the experiences of Two-Spirit, lesbian, gay, bisexual, transgender, queer, intersex, asexual, and other sexual and gender diverse (2S/LGBTQIA+) people with IPV in Ontario and how the COVID-19 pandemic affected their IPV experiences. METHODS: We conducted in-depth, semi-structured interviews with self-identified 2S/LGBTQIA+ people who experienced IPV on/after March 15, 2020. We audio-recorded and transcribed all interviews and coded the transcripts for content and themes using inductive and deductive techniques. RESULTS: Our 20 participants experienced physical, psychological, sexual, and financial abuse. Technology-facilitated violence extended abuse geographically and temporally. IPV experiences were associated with negative mental health outcomes that were intensified by the COVID-19 pandemic. Participants struggled to see themselves as legitimate victims of IPV. Although participants regretted being victims of violence, many saw their abusive relationship(s) as a learning experience to inform future relationships. DISCUSSION: Our findings suggest that 2S/LGBTQIA+ people may experience unique forms of identity abuse and may have difficulty recognizing their IPV experiences as abuse. Ensuring that comprehensive sexual health education is trauma-informed, anti-oppressive, and includes information about healthy relationship dynamics, 2S/LGBTQIA+ relationships, and IPV is critical.

17.
Environ Pollut ; 356: 124284, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38821342

RESUMEN

Prior reviews have highlighted that nature exposure was a valuable coping strategy enhancing mental health during the COVID-19 pandemic. However, no existing reviews have determined the quality of evidence and risk of bias of the empirical studies supporting this claim. To address this gap, we employed a Navigation Guide systematic review and meta-analysis approach to investigate associations between nature exposure and mental health during the pandemic. Searches in PubMed, Web of Science, Scopus, CINAHL, and PsycInfo retrieved relevant articles published between January 1, 2020, and March 4, 2024. We used the Navigation Guide methodology to assess the risk of bias and Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) assessments to evaluate the overall quality of evidence. Our search retrieved 113 studies that met the inclusion criteria and reported diverse types of exposure, including nature availability, nature visit frequency, green space accessibility, and green space type, alongside associations with 12 mental health outcomes. Meta-analyses found access to gardens was associated with lower odds of depression [(Pooled odds ratio [OR] = 0.71, 95%CI = 0.61, 0.82), I2 = 0%, n = 3] and anxiety [(Pooled OR = 0.73, 95%CI = 0.63, 0.84), I2 = 0%, n = 3]. Increased time in green spaces was associated with lower level of stress [(Pooled Corr = -0.11, 95%CI = -0.17, -0.05), I2 = 0%, n = 2]. Higher frequency of visits to nature was associated with improved mental well-being [(Pooled standardized beta = 0.10, 95%CI = 0.07, 0.14), I2 = 0%, n = 2] and general mental health [(Pooled standardized beta = 0.11, 95%CI = 0.03-0.38), I2 = 82%, n = 2]. However, the number of pooled studies was small and the overall quality of evidence was "very low" for all outcomes, and high levels of bias were observed (26% of studies had high, 71% probably high). Nonetheless, given the trends in the results, nature-based solutions emphasizing exposure to gardens and green spaces near the home may have promoted psychological resilience during this public health crisis.


Asunto(s)
COVID-19 , Salud Mental , COVID-19/epidemiología , COVID-19/psicología , Humanos , SARS-CoV-2 , Ansiedad/epidemiología , Depresión/epidemiología , Naturaleza , Pandemias , Jardines
18.
New Phytol ; 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38725409

RESUMEN

In angiosperms, wound-derived signals travel through the vasculature to systemically activate defence responses throughout the plant. In Arabidopsis thaliana, activity of vasculature-specific Clade 3 glutamate receptor-like (GLR) channels is required for the transmission of electrical signals and cytosolic Ca2+ ([Ca2+]cyt) waves from wounded leaves to distal tissues, triggering activation of oxylipin-dependent defences. Whether nonvascular plants mount systemic responses upon wounding remains unknown. To explore the evolution of systemic defence responses, we investigated electrical and calcium signalling in the nonvascular plant Marchantia polymorpha. We found that electrical signals and [Ca2+]cyt waves are generated in response to mechanical wounding and propagated to nondamaged distal tissues in M. polymorpha. Functional analysis of MpGLR, the only GLR encoded in the genome of M. polymorpha, indicates that its activity is necessary for the systemic transmission of wound-induced electrical signals and [Ca2+]cyt waves, similar to vascular plants. However, spread of these signals is neither coupled to systemic accumulation of oxylipins nor to a transcriptional defence response in the distal tissues of wounded M. polymorpha plants. Our results suggest that lack of vasculature prevents translocation of additional signalling factors that, together with electrical signals and [Ca2+]cyt waves, contribute to systemic activation of defences in tracheophytes.

19.
Digit Health ; 10: 20552076241253739, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38736733

RESUMEN

Introduction: There are very few scholastic studies applying a theory-driven methodology to analyse the employment of teledentistry in clinical practice by the Saudi dental community. The objective of this research was to predict the employment of teledentistry in clinical practice by the Saudi dental community using the UTAUT (Unified Theory of Acceptance and Use of Technology) model. Methods: A countrywide survey was executed from November 2022 to April 2023 among the dental community (pre-graduate students, graduates, post-graduate students, general dentists, and specialist dentists) involved in clinical practice. The survey employed the UTAUT model, which has four fundamental constructs: performance expectancy (PE), effort expectancy (EE), social influence (SI) and facilitating conditions (FC). These constructs are known to impact the user's behavioural intention (BI). The four fundamental constructs were independent, and BI was the dependent variable. A Likert scale with five scores was used to record each variable. Descriptive statistics were used to describe all the constructs. Cronbach's alpha scores were used to measure the inner consistency of the Likert scale. Simple linear regression and multiple linear regression were used to determine the correlation between all the constructs and the overall model's prediction. The Statistical Package for the Social Sciences was applied for analysis. The study had 80% power and an alpha threshold of .05. Results: The electronic survey was sent to 3000 participants, out of whom 2143 responded (response rate = 71.43%). PE (R2= 26%, p < .01) was the most significant predictor of the Saudi dental community BI to employ teledentistry in clinical practice, followed by SI (R2= 24%, p < .01), EE (R2= 19%, p < .01) and FC (R2= 6%, p < .01). With statistically significant predictive power, the UTAUT model explained 32% of the variance in the BI (R2= 0.32, p < .01). Conclusions: Each UTAUT construct and the entire model were significantly correlated with the employment of teledentistry in clinical practice by the Saudi dental community. PE had the most salient correlation, followed by SI, EE and FC. The participants have perceived the benefits of teledentistry, increasing the future likelihood of its utilisation. The Saudi government could consider the UTAUT constructs to promote teledentistry in tandem with Vision 2030.

20.
Heliyon ; 10(10): e31435, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38818196

RESUMEN

Background: Previous cross-sectional studies have found a beneficial relationship between greenspace and children's behaviour. Nevertheless, evidence on the mechanisms underlying this association remains scant. We examined whether the availability of greenspace was related to fewer behavioural problems in Polish children and investigated potential mechanisms. Methods: Data were obtained from the case-control NeuroSmog study, in which children with and without attention deficit hyperactivity disorder (ADHD) were tested from October 2020 to September 2022. The analytic sample comprised 679 children aged 10-13 years. Parents reported internalizing, externalizing, and total behavioural problems using the Child Behaviour Check List (CBCL), as well as information about the presence of a domestic garden and potential mediators: greenspace perception, neighbourhood social cohesion, and physical activity. Tree and grass covers were extracted in 500 m and 1 km buffers around lifelong residences. Structural equation modelling (SEM) was used to examine the psychosocial pathways linking the greenspace metrics to behavioural problems. Results: Greenspace was only indirectly related to fewer behavioural problems. Specifically, tree cover was related to greater levels of physical activity which, in turn, was related to fewer internalizing and total behavioural problems. Tree cover and presence of garden were related to greenspace perception which, in turn, was associated with higher neighbourhood social cohesion which, in turn, was linked to fewer behavioural problems. The patterns of associations in children without ADHD were very similar to those in the full sample except that the associations from garden to greenspace perception and from physical activity to total behavioural problems were no longer significant. The only association persisted among girls was from neighbourhood social cohesion to behavioural problems and among boys were from tree cover to physical activity and tree cover and garden to greenspace perception. Conclusion: Trees and garden, but not grass, are linked to fewer behavioural problems through greenspace perception, neighbourhood social cohesion, and physical activity in Polish children.

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