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1.
Int J Esthet Dent ; 19(1): 34-44, 2024 01 29.
Artículo en Inglés | MEDLINE | ID: mdl-38284942

RESUMEN

OBJECTIVES: The present case report describes the atraumatic extraction of a primary maxillary right canine followed by immediate implant placement with a customized zirconia abutment and monolithic ultra-translucent zirconia (5Y-PSZ) crown. CLINICAL CONSIDERATIONS: A 31-year-old patient presented to the clinic with the primary concern of mobility and gingival inflammation around the maxillary right canine. After clinical evaluation, the tooth was found to be a primary retained tooth that presented grade 3 mobility and gingival inflammation. Atraumatic tooth extraction was performed, followed by immediate implant placement of a screw-retained provisional restoration with the use of a surgical guide. The soft tissue was contoured until ideal architecture was obtained. The final restoration included a customized zirconia and titanium abutment and a characterized implant-supported monolithic 5Y-PSZ crown. CONCLUSIONS: Well-planned surgical and restorative procedures including atraumatic extraction, 3D implant planning for surgical guide fabrication, implant placement, and a customized zirconia abutment with a monolithic 5Y-PSZ crown can achieve high esthetic results in replacing a primary tooth in the esthetic zone.


Asunto(s)
Implantes Dentales , Gingivitis , Circonio , Humanos , Adulto , Estética Dental , Coronas , Inflamación
3.
Phys Chem Chem Phys ; 26(5): 4541-4554, 2024 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-38241021

RESUMEN

The bottom-up prediction of thermodynamic and mechanical behaviors of polymeric materials based on molecular dynamics (MD) simulation is of critical importance in polymer physics. Although the atomistically informed coarse-grained (CG) model can access greater spatiotemporal scales and retain essential chemical specificity, the temperature-transferable CG model is still a big challenge and hinders widespread application of this technique. Herein, we use a silicone polymer, i.e., polydimethylsiloxane (PDMS), having an incredibly low chain rigidity as a model system, combined with an energy-renormalization (ER) approach, to systematically develop a temperature-transferable CG model. Specifically, by introducing temperature-dependent ER factors to renormalize the effective distance and cohesive energy parameters, the developed CG model faithfully preserved the dynamics, mechanical and conformational behaviors compared with the target all-atomistic (AA) model from glassy to melt regimes, which was further validated by experimental data. With the developed CG model featuring tremendously improved computational efficiency, we systematically explored the influences of cohesive interaction strength and temperature on the dynamical heterogeneity and mechanical response of polymers, where we observed consistent trends with other linear polymers with varying chain rigidity and monomeric structures. This study serves as an extension of our proposed ER approach of developing temperature transferable CG models with diverse segmental structures, highlighting the critical role of cohesive interaction strength on CG modeling of polymer dynamics and thermomechanical behaviors.

4.
Liver Int ; 44(1): 180-190, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37872644

RESUMEN

BACKGROUND: Porto-sinusoidal vascular disorder (PSVD) involves a group of rare vascular liver diseases of unknown aetiology that may lead to the development of portal hypertension and its life-threatening complications. Its pathophysiology is not well understood, and animal models described to date do not fully recapitulate human disease. METHODS: We developed three different PSVD rat models by either immunosensitization (repetitive intraportal LPS or intramuscular spleen extract injections) or toxic (Selfox: combination of FOLFOX and a selenium-enriched diet) treatment and characterized them at haemodynamic, histological, biochemical and transcriptional levels. We compared these results to human data. RESULTS: All three models developed significant portal hypertension, while only the LPS and the Selfox models displayed PSVD-specific and nonspecific histological alterations in the absence of cirrhosis. Transcriptional comparison between rat models and human data showed that both LPS and Selfox models recapitulate the main transcriptional alterations observed in humans, especially regarding haemostasis, oxidative phosphorylation and cell cycle regulation. Reproducibility and feasibility was higher for the Selfox model. CONCLUSIONS: The Selfox rat model faithfully reproduces the main alterations described in PSVD. Its use as a preclinical model for drug testing in progressing PSVD can be a significant step forward towards the development of new therapeutic targets for this rare condition.


Asunto(s)
Hipertensión Portal , Enfermedades Vasculares , Ratas , Humanos , Animales , Lipopolisacáridos , Reproducibilidad de los Resultados , Cirrosis Hepática/complicaciones , Perfilación de la Expresión Génica , Hígado
5.
J Chem Phys ; 159(18)2023 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-37955325

RESUMEN

Many modern anti-icing and anti-fouling coatings rely on soft, low surface energy elastomeric materials such as polydimethylsiloxane for their functionality. While the low surface energy is desirable for reducing adhesion, very little work considers the larger contribution to adhesive failure caused by the viscoelastic nature of elastomers. Here we examine several different siloxane elastomers using a JKR adhesion test, which was operated over a range of different speeds and temperatures. Additionally, we characterize the dynamic mechanical modulus over a large range of frequencies for each material. We note that surface energies of the materials are all similar, but variation in adhesion strength is clear in the data. The variation at low speeds is related to elastomer architecture but the speed dependence itself is independent of architecture. Qualitative correlations are noted between the JKR adhesion measurements and the dynamic moduli. Finally, an attempt is made to directly compare moduli and adhesion through the recent Persson-Brener model. Approximations of the model are shown to be inaccurate. The full model is found to be accurate at low speeds, although it fails to precisely capture higher speed behaviour.

6.
Sci Rep ; 13(1): 13125, 2023 08 12.
Artículo en Inglés | MEDLINE | ID: mdl-37573373

RESUMEN

The concept of "one-airway-one-disease", coined over 20 years ago, may be an over-simplification of the links between allergic diseases. Genomic studies suggest that rhinitis alone and rhinitis with asthma are operated by distinct pathways. In this MeDALL (Mechanisms of the Development of Allergy) study, we leveraged the information of the human interactome to distinguish the molecular mechanisms associated with two phenotypes of allergic rhinitis: rhinitis alone and rhinitis in multimorbidity with asthma. We observed significant differences in the topology of the interactomes and in the pathways associated to each phenotype. In rhinitis alone, identified pathways included cell cycle, cytokine signalling, developmental biology, immune system, metabolism of proteins and signal transduction. In rhinitis and asthma multimorbidity, most pathways were related to signal transduction. The remaining few were related to cytokine signalling, immune system or developmental biology. Toll-like receptors and IL-17-mediated signalling were identified in rhinitis alone, while IL-33 was identified in rhinitis in multimorbidity. On the other hand, few pathways were associated with both phenotypes, most being associated with signal transduction pathways including estrogen-stimulated signalling. The only immune system pathway was FceRI-mediated MAPK activation. In conclusion, our findings suggest that rhinitis alone and rhinitis and asthma multimorbidity should be considered as two distinct diseases.


Asunto(s)
Asma , Rinitis Alérgica , Rinitis , Humanos , Multimorbilidad , Citocinas
7.
Nat Commun ; 14(1): 4506, 2023 07 26.
Artículo en Inglés | MEDLINE | ID: mdl-37495570

RESUMEN

Ulcerative colitis and Crohn's disease are chronic inflammatory intestinal diseases with perplexing heterogeneity in disease manifestation and response to treatment. While the molecular basis for this heterogeneity remains uncharacterized, single-cell technologies allow us to explore the transcriptional states within tissues at an unprecedented resolution which could further understanding of these complex diseases. Here, we apply single-cell RNA-sequencing to human inflamed intestine and show that the largest differences among patients are present within the myeloid compartment including macrophages and neutrophils. Using spatial transcriptomics in human tissue at single-cell resolution (CosMx Spatial Molecular Imaging) we spatially localize each of the macrophage and neutrophil subsets identified by single-cell RNA-sequencing and unravel further macrophage diversity based on their tissue localization. Finally, single-cell RNA-sequencing combined with single-cell spatial analysis reveals a strong communication network involving macrophages and inflammatory fibroblasts. Our data sheds light on the cellular complexity of these diseases and points towards the myeloid and stromal compartments as important cellular subsets for understanding patient-to-patient heterogeneity.


Asunto(s)
Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Humanos , Neutrófilos , Enfermedades Inflamatorias del Intestino/genética , Enfermedad de Crohn/genética , Macrófagos , ARN
8.
Int J Mol Sci ; 24(8)2023 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-37108839

RESUMEN

This paper assesses the association of the insertion/deletion ACE (angiotensin-converting enzyme) variant (rs1799752 I/D) and the serum ACE activity with the severity of COVID-19 as well as its impact on post-COVID-19, and we compare these associations with those for patients with non-COVID-19 respiratory disorders. We studied 1252 patients with COVID-19, 104 subjects recovered from COVID-19, and 74 patients hospitalized with a respiratory disease different from COVID-19. The rs1799752 ACE variant was assessed using TaqMan® Assays. The serum ACE activity was determined using a colorimetric assay. The DD genotype was related to risk for invasive mechanical ventilation (IMV) requirement as an indicator of COVID-19 severity when compared to the frequencies of II + ID genotypes (p = 0.025, OR = 1.428, 95% CI = 1.046-1.949). In addition, this genotype was significantly higher in COVID-19 and post-COVID-19 groups than in the non-COVID-19 subjects. The serum ACE activity levels were lower in the COVID-19 group (22.30 U/L (13.84-32.23 U/L)), which was followed by the non-COVID-19 (27.94 U/L (20.32-53.36 U/L)) and post-COVID-19 subjects (50.00 U/L (42.16-62.25 U/L)). The DD genotype of the rs1799752 ACE variant was associated with the IMV requirement in patients with COVID-19, and low serum ACE activity levels could be related to patients with severe disease.


Asunto(s)
COVID-19 , Polimorfismo Genético , Humanos , COVID-19/genética , Genotipo , Peptidil-Dipeptidasa A/genética , Carboxipeptidasas/metabolismo
9.
Microbiol Spectr ; 11(3): e0458422, 2023 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-37022279

RESUMEN

We characterized five carbapenemase-producing Enterobacterales (CPE) isolates from two health care institutions in Lima, Peru. The isolates were identified as Klebsiella pneumoniae (n = 3), Citrobacter portucalensis (n = 1), and Escherichia coli (n = 1). All were identified as blaOXA-48-like gene carriers using conventional PCR. Whole-genome sequencing found the presence of the blaOXA-181 gene as the only carbapenemase gene in all isolates. Genes associated with resistance to aminoglycosides, quinolones, amphenicols, fosfomycins, macrolides, tetracyclines, sulfonamides, and trimethoprim were also found. The plasmid incompatibility group IncX3 was identified in all genomes in a truncated Tn6361 transposon flanked by ΔIS26 insertion sequences. The qnrS1 gene was also found downstream of blaOXA-181, conferring fluoroquinolone resistance to all isolates. CPE isolates harboring blaOXA-like genes are an increasing public health problem in health care settings worldwide. The IncX3 plasmid is involved in the worldwide dissemination of blaOXA-181, and its presence in these CPE isolates suggests the wide dissemination of blaOXA-181 in Peru. IMPORTANCE Reports of carbapenemase-producing Enterobacterales (CPE) isolates are increasing worldwide. Accurate detection of the ß-lactamase OXA-181 (a variant of OXA-48) is important to initiate therapy and preventive measures in the clinic. OXA-181 has been described in CPE isolates in many countries, often associated with nosocomial outbreaks. However, the circulation of this carbapenemase has yet to be reported in Peru. Here, we report the detection of five multidrug-resistant CPE clinical isolates harboring blaOXA-181 in the IncX3-type plasmid, a potential driver of dissemination in Peru.


Asunto(s)
Infecciones por Enterobacteriaceae , Enterobacteriaceae , Humanos , Enterobacteriaceae/genética , América Latina , Proteínas Bacterianas/genética , beta-Lactamasas/genética , Escherichia coli/genética , Klebsiella pneumoniae/genética , Antibacterianos/farmacología , Pruebas de Sensibilidad Microbiana , Infecciones por Enterobacteriaceae/epidemiología
10.
Lancet Glob Health ; 11 Suppl 1: S21, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36866479

RESUMEN

BACKGROUND: Mexico declared an obesity epidemic in 2000, and in response, became an early adopter of public policies in the form of natural experiments, which have not been evaluated for their effect on high BMI. We focus on children younger than 5 years due to the long-term outcomes of childhood obesity. METHODS: We used the Global Burden of Disease data to evaluate time trends in high BMI, defined as being overweight or obese based on the International Obesity Task Force standards, between 1990 and 2019. Marginalisation and poverty estimates from Mexico's Government were used to identify differences in socioeconomic groups. The time variable reflects the introduction of policies between 2006 and 2011. Our hypothesis was that poverty and marginalisation modify the effects of public policies. We tested for the change in prevalence of high BMI over time using Wald-type tests, correcting for the effect of repeated measures. We stratified the sample by gender, marginalisation index, and households under the poverty line. Ethics approval was not required. FINDINGS: Between 1990 and 2019, high BMI in children younger than 5 years increased from 23·5% (95% uncertainty interval 38·6-14·3) to 30·2% (46·0-20·4). After a period of sustained increase to 28·7% (44·8-18·6) in 2005, high BMI decreased to 27·3% (42·4-17·4; p<0·001) in 2011. Afterwards, high BMI increased constantly. We found an average gender gap of 12·2%, with a higher rate in males, in 2006, which remained constant. With respect to marginalisation and poverty, we observed a reduction in high BMI across all strata, except for the uppermost quintile of marginalisation in which high BMI remained flat. INTERPRETATION: The epidemic affected groups across different socioeconomic levels, thus weakening economic explanations for the decrease in high BMI, while gender gaps point to behavioural explanations of consumption. The observed patterns warrant investigation through more granular data and structural models to isolate the effect of the policy from secular trends in the population, including other age groups. FUNDING: Tecnológico de Monterrey Challenge-Based Research Funding Program.


Asunto(s)
Obesidad Infantil , Niño , Masculino , Humanos , Análisis de Series de Tiempo Interrumpido , Índice de Masa Corporal , México/epidemiología , Obesidad Infantil/epidemiología , Obesidad Infantil/prevención & control , Política Pública
11.
Life (Basel) ; 12(6)2022 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-35743918

RESUMEN

Coronavirus disease 2019 (COVID-19) is a pandemic respiratory disease associated with high morbidity and mortality. Although many patients recover, long-term sequelae after infection have become increasingly recognized and concerning. Among other sequelae, the available data indicate that many patients who recover from COVID-19 could develop fibrotic abnormalities over time. To understand the basic pathophysiology underlying the development of long-term pulmonary fibrosis in COVID-19, as well as the higher mortality rates in patients with pre-existing lung diseases, we compared the transcriptomic fingerprints among patients with COVID-19, idiopathic pulmonary fibrosis (IPF), and chronic obstructive pulmonary disease (COPD) using interactomic analysis. Patients who died of COVID-19 shared some of the molecular biological processes triggered in patients with IPF, such as those related to immune response, airway remodeling, and wound healing, which could explain the radiological images seen in some patients after discharge. However, other aspects of this transcriptomic profile did not resemble the profile associated with irreversible fibrotic processes in IPF. Our mathematical approach instead showed that the molecular processes that were altered in COVID-19 patients more closely resembled those observed in COPD. These data indicate that patients with COPD, who have overcome COVID-19, might experience a faster decline in lung function that will undoubtedly affect global health.

12.
PhytoKeys ; 197: 81-148, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36760671

RESUMEN

With about 70 species Virola, is the largest genus of Myristicaceae in the Neotropics, the genus ranked in the top ten genera of abundance across Amazonia. Ten new species are proposed in this striking genus, which are described based on morphology, and are illustrated. The new species were discovered thanks to herbarium specimens collected mainly in the 1980s and 1990s when field documentations were more active. The new species come from Colombia (V.calimensis sp. nov., V.cogolloi sp. nov., V.excisa sp. nov., V.tuckerae sp. nov.), Ecuador (V.alvaroperezii sp. nov., V.bombuscaroensis sp. nov., V.calimensis, V.excisa, V.yasuniana sp. nov.), Peru (V.aguarunana sp. nov., V.cumala sp. nov., V.excisa, V.parkeri sp. nov.), and Brazil (V.excisa, V.yasuniana). Additionally, a lectotype is designated for V.macrocarpa, a name used to identify some specimens of the new species here described, and V.kwatae is reported for the first time for Brazil. We provide a comparation table between the new species and the species that is morphologically close to it, a preliminary list of species for the genus, and notes of how the new species were treated in floras, checklists, or collections that need more study and herbarium specimens.

13.
Rev. enferm. Inst. Mex. Seguro Soc ; 29(3): 125-127, 04-oct-2021.
Artículo en Español | LILACS, BDENF - Enfermería | ID: biblio-1357663

RESUMEN

México enfrenta retos de salud sin precedentes y es necesario pensar en estrategias que con- tribuyan a su solución con un enfoque hacia el personal de enfermería, que es el recurso humano más numeroso. En este sentido, se desarrolló un programa de capacitación integral, el cual considera un diplomado virtual de 165 horas y componentes semipresenciales para fortalecer el conocimiento en el abordaje integral de diabetes para enfermería en el primer nivel de atención (PNA). Este programa se inscribe dentro de la Estrategia Integral para la Ampliación del Rol de Enfermería (EIARE) en el PNA. La implementación del programa educativo tendrá un pilotaje en el sur del país, donde se consideran el seguimiento y la evaluación para identificar y solventar áreas susceptibles de mejora y buscar su implementación en otros estados. El programa educativo y la EIARE permitirán el desarrollo de una nueva carrera para la enfermería en el PNA y mejoras sustantivas a la salud.


Mexico faces unprecedented health challenges, and it is necessary to think of mindful strategies to solve this, focusing on the nursing workforce, which is the most numerous human resource. In this sense, it was developed a comprehensive training program, which considers a virtual diploma program of 165 hours, and blended-learning components to strengthen knowledge in comprehensive diabetes care to nursing in the primary level of care (PLC). This training program is part of the Estrategia Integral para la Ampliación del Rol de Enfermería (Comprehensive Strategy for Amplifying the Role of Nurses­EIARE, according to its initialism in Spanish]) in PLC. The implementation of the training program will have a pilot in the southern area of Mexico, where monitoring and evaluation are considered to identify and solve areas susceptible to improvement and seek its implementation in other states of Mexico. This training program and the EIARE will allow the development of a new career for nursing in PLC and substantive improvements to health.


Asunto(s)
Humanos , Atención Primaria de Salud , Diabetes Mellitus , Educación Continua en Enfermería , Personal de Enfermería , Estrategias de Salud , México
14.
PhytoKeys ; 178: 147-170, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34140828

RESUMEN

Otoba is the third largest genus of Myristicaceae in the Neotropics with 12 species, nine of them native to Colombia. Two new species from the department of Antioquia, O. scottmorii sp. nov. and O. squamosa sp. nov., are described and illustrated. Otoba scottmorii occurs in humid, lowland forests, while O. squamosa occurs in premontane forest. Previously, Otoba scottmorii was confused with O. acuminata (which here is considered restricted to Costa Rica and Panama), while O. squamosa was confused with O. gordoniifolia. The similarities and differences between these and other species are discussed.

15.
Cien Saude Colet ; 26(suppl 1): 2471-2482, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34133627

RESUMEN

To describe a general overview of health services delivery in Mexico and geospatially analyze the current distribution and accessibility of Primary Health Care (PHC) facilities to contribute to new approaches to improve healthcare planning in Mexico. We performed a spatial analysis of official data to analyze current distances from health facilities to population, to determine the underserved areas of health services delivery in three selected states using a ranking of indicators. We estimated service area coverage of PHC facilities with road networks of three Mexican states (Chiapas, Guerrero, and Oaxaca). Our estimations provide an overview of spatial access to healthcare of the Mexican population in Mexico's three most impoverished states. We did not consider social security nor private providers. Geospatial access to health facilities is critical to achieving PHC and adequate coverage. Countries like Mexico must measure this to identify underserved areas with a lack of geospatial access to healthcare to solve it. This type of analysis provides critical information to help decision-makers decide where to build new health facilities to increase effective geospatial access to care and to achieve Universal Health Coverage.


Asunto(s)
Sistemas de Información Geográfica , Accesibilidad a los Servicios de Salud , Instituciones de Salud , Humanos , México , Cobertura Universal del Seguro de Salud
16.
Ciênc. Saúde Colet. (Impr.) ; 26(supl.1): 2471-2482, jun. 2021. tab, graf
Artículo en Inglés | LILACS | ID: biblio-1278846

RESUMEN

Abstract To describe a general overview of health services delivery in Mexico and geospatially analyze the current distribution and accessibility of Primary Health Care (PHC) facilities to contribute to new approaches to improve healthcare planning in Mexico. We performed a spatial analysis of official data to analyze current distances from health facilities to population, to determine the underserved areas of health services delivery in three selected states using a ranking of indicators. We estimated service area coverage of PHC facilities with road networks of three Mexican states (Chiapas, Guerrero, and Oaxaca). Our estimations provide an overview of spatial access to healthcare of the Mexican population in Mexico's three most impoverished states. We did not consider social security nor private providers. Geospatial access to health facilities is critical to achieving PHC and adequate coverage. Countries like Mexico must measure this to identify underserved areas with a lack of geospatial access to healthcare to solve it. This type of analysis provides critical information to help decision-makers decide where to build new health facilities to increase effective geospatial access to care and to achieve Universal Health Coverage.


Resumo Descrever uma visão geral da prestação de serviços de saúde no México e analisar geoespacialmente a atual distribuição e acessibilidade das unidades de APS para contribuir com novas abordagens para melhorar o planejamento da saúde no México. Realizamos uma análise espacial de dados oficiais para analisar as distâncias atuais das unidades de saúde à população, para determinar as áreas descobertas de prestação de serviços de saúde em 3 estados selecionados usando uma classificação de indicadores. Estimamos a cobertura da área de serviço das unidades de APS com redes viárias de 3 estados do México (Chiapas, Guerrero e Oaxaca). Nossas estimativas fornecem uma visão geral do acesso espacial à saúde da população mexicana nos três estados mais pobres do México. Não consideramos seguridade social nem prestadores privados. O acesso geoespacial às unidades de saúde é fundamental para alcançar a cobertura universal de saúde e uma cobertura eficaz. Países, como o México, devem medir isso para identificar áreas não merecidas com falta de acesso geoespacial à saúde para resolvê-lo. Os governos devem gerar políticas e mecanismos para distribuir efetivamente novas instalações de saúde para aumentar o acesso geoespacial efetivo à saúde, bem como para evitar instalações de saúde não planejadas.


Asunto(s)
Humanos , Sistemas de Información Geográfica , Accesibilidad a los Servicios de Salud , Cobertura Universal del Seguro de Salud , Instituciones de Salud , México
17.
Inflamm Bowel Dis ; 27(12): 1999-2009, 2021 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-34042156

RESUMEN

BACKGROUND: Janus kinase (JAK) inhibition shows promise for treatment of patients with moderate to severe Crohn's disease. We aimed to provide mechanistic insights into the JAK1-selective inhibitor upadacitinib through a transcriptomics substudy on biopsies from patients with Crohn's disease from CELEST. METHODS: Seventy-four patients consented to this optional substudy. Ileal and colonic biopsies were collected during endoscopy at screening and week 12 or 16. RNA isolated from 226 samples was analyzed by RNAseq, with additional qPCR analysis. Additional biopsies from patients with Crohn's disease receiving anti-tumor necrosis factor (anti-TNF; n = 34) and healthy controls (n = 10) were used for qPCR. Single-cell RNAseq public profiles were used to evaluate treatment effects on specific cellular subsets, associations with endoscopic improvement, and indirect comparisons with the anti-TNF-treated cohort. RESULTS: In involved areas of mucosa with endoscopic remission after upadacitinib treatment, 1156 and 76 protein-coding genes were significantly regulated (false discovery rate < 0.05) at week 12/16 in colonic and ileal biopsies, respectively (60 overlapped), compared with baseline. Upadacitinib did not significantly affect transcriptomes of noninvolved intestinal areas. CELEST patients (mostly anti-TNF-refractory) showed baseline differences in gene expression compared with a separate cohort of biologic-naïve patients. Notably, upadacitinib reversed overexpression of inflammatory fibroblast and interferon-γ effector signature markers. CONCLUSIONS: Upadacitinib modulates inflammatory pathways in mucosal lesions of patients with anti-TNF-refractory Crohn's disease, including inflammatory fibroblast and interferon-γ-expressing cytotoxic T cell compartments. This substudy is the first to describe the molecular response to JAK1 inhibition in inflammatory bowel disease and differential effects relative to anti-TNF treatment. (Clinical trial identifier: NCT02365649).


Asunto(s)
Enfermedad de Crohn , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Inhibidores de las Cinasas Janus , Enfermedad de Crohn/tratamiento farmacológico , Endoscopía Gastrointestinal , Humanos , Interferón gamma , Mucosa Intestinal/efectos de los fármacos , Janus Quinasa 1/antagonistas & inhibidores , Inhibidores de las Cinasas Janus/uso terapéutico , Inhibidores del Factor de Necrosis Tumoral
18.
FASEB J ; 35(3): e21396, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33583073

RESUMEN

We have recently reported that a specific pool of ceramide, located in the plasma membrane, mediated the effects of sublethal doses of the chemotherapeutic compound doxorubicin on enhancing cancer cell migration. We identified neutral sphingomyelinase 2 (nSMase2) as the enzyme responsible to generate this bioactive pool of ceramide. In this work, we explored the role of members of the protein phosphatases 1 family (PP1), and we identified protein phosphatase 1 alpha isoform (PP1 alpha) as the specific PP1 isoform to mediate this phenotype. Using a bioinformatics approach, we build a functional interaction network based on phosphoproteomics data on plasma membrane ceramide. This led to the identification of several ceramide-PP1 alpha downstream substrates. Studies on phospho mutants of ezrin (T567) and Scrib (S1378/S1508) demonstrated that their dephosphorylation is sufficient to enhance cell migration. In summary, we identified a mechanism where reduced doses of doxorubicin result in the dysregulation of cytoskeletal proteins and enhanced cell migration. This mechanism could explain the reported effects of doxorubicin worsening cancer metastasis in animal models.


Asunto(s)
Ceramidas/fisiología , Doxorrubicina/farmacología , Proteína Fosfatasa 1/fisiología , Adhesión Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Células HeLa , Humanos
19.
Environ Int ; 146: 106248, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33212358

RESUMEN

Air pollution has been associated with adverse health effects across the life-course. Although underlying mechanisms are unclear, several studies suggested pollutant-induced changes in transcriptomic profiles. In this meta-analysis of transcriptome-wide association studies of 656 children and adolescents from three European cohorts participating in the MeDALL Consortium, we found two differentially expressed transcript clusters (FDR p < 0.05) associated with exposure to particulate matter < 2.5 µm in diameter (PM2.5) at birth, one of them mapping to the MIR1296 gene. Further, by integrating gene expression with DNA methylation using Functional Epigenetic Modules algorithms, we identified 9 and 6 modules in relation to PM2.5 exposure at birth and at current address, respectively (including NR1I2, MAPK6, TAF8 and SCARA3). In conclusion, PM2.5 exposure at birth was linked to differential gene expression in children and adolescents. Importantly, we identified several significant interactome hotspots of gene modules of relevance for complex diseases in relation to PM2.5 exposure.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Adolescente , Contaminantes Atmosféricos/análisis , Contaminantes Atmosféricos/toxicidad , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Niño , Metilación de ADN , Exposición a Riesgos Ambientales/análisis , Epigenómica , Humanos , Material Particulado/análisis , Material Particulado/toxicidad
20.
Ginecol. obstet. Méx ; 89(12): 994-1001, ene. 2021. graf
Artículo en Español | LILACS-Express | LILACS | ID: biblio-1375565

RESUMEN

Resumen ANTECEDENTES: El lupus eritematoso sistémico es una enfermedad autoinmunitaria y multisistémica. El daño pericárdico es la complicación cardiaca más común y el taponamiento cardiaco es infrecuente, más aún en embarazadas y con lupus eritematoso sistémico. OBJETIVO: Exponer las características clínicas, diagnósticas, tratamiento y evolución del taponamiento cardiaco en una embarazada que inició con lupus eritematoso sistémico y valorar la información de la bibliografía a propósito de otros casos. CASO CLÍNICO: Paciente de 24 años, con 27.5 semanas de embarazo, con anasarca, disnea que evolucionó a ortopnea y dolor torácico punzante de tres semanas de evolución. La radiografía de tórax mostró cardiomegalia grado II, campos pulmonares congestivos y derrame pleural a la altura de los senos cardiofrénicos. En el ecocardiograma se encontró derrame pericárdico de 500 mL, con datos de taponamiento cardiaco. Tuvo deterioro progresivo con afectación de la capacidad pulmonar e insuficiencia renal aguda con aumentos progresivos de creatinina; se encontró hemodinámica inestable, con pulso paradójico e hipotensión. Anticuerpos antinucleares positivos y proteinuria. La biopsia renal reportó patrones histopatológicos correspondientes a nefritis lúpica. Se trató con pulsos esteroideos y ciclofosfamida por vía intravenosa. El derrame pericárdico desapareció por medio de una ventana subxifoidea y la extracción del líquido del pericardio. La evolución posterior fue satisfactoria para la madre y su hijo. CONCLUSIÓN: El taponamiento cardiaco es infrecuente en pacientes con lupus eritematoso sistémico y más raro aún durante el embarazo. Es una urgencia clínica que requiere atención multidisciplinaria porque el embarazo, en una paciente con lupus eritematoso sistémico, implica mayor riesgo de complicaciones sistémicas, como se señala en la bibliografía.


Abstract BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic, multisystemic disease of unknown etiology, whose clinical manifestations are heterogeneous. Pericardial involvement is the most common cardiac complication; however, the development of cardiac tamponade is rare, and even more so in pregnant patients presenting with SLE. OBJECTIVE: To present the clinical characteristics, diagnosis, treatment, and evolution of cardiac tamponade in a pregnant patient that presents with systemic lupus erythematosus. CLINICAL CASE: A 24-year-old patient, who is 27.5 weeks pregnant, presenting with anasarca, dyspnea that evolved to orthopnea and stabbing chest pain for three weeks. Her chest X-ray showed cardiomegaly grade II, congestive lung fields and pleural effusion at the level of cardiophrenic sinuses. The echocardiogram found a 500 mL pericardial effusion with evidence of cardiac tamponade. Progressive deterioration with compromised lung capacity, and the appearance of acute renal failure with progressive increases in creatinine; showing hemodynamic instability characterized by paradoxical pulse and hypotension. With positive Antinuclear Antibodies (ANA) and proteinuria, renal biopsy reports histopathological patterns corresponding to lupus nephritis, treated with steroid pulses and intravenous cyclophosphamide in a risk-benefit assessment, with subsequent satisfactory maternal-fetal evolution. CONCLUSION: Cardiac tamponade is not common in patients with SLE, and it is even rarer as the initial manifestation, even more so during pregnancy. It is a clinical emergency and requires multidisciplinary management since pregnancy in a patient with SLE implies an increased risk of systemic complications.

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