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1.
Environ Sci Pollut Res Int ; 31(43): 55169-55186, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39222230

RESUMEN

In recent years, pelagic Sargassum has invaded the Caribbean coasts, and anaerobic digestion has been proposed as a sustainable management option. However, the complex composition of these macroalgae acts as a barrier to microbial degradation, thereby limiting methane production. Microbial adaptation is a promising strategy to improve substrate utilization and stress tolerance. This study aimed to investigate the adaptation of a microbial consortium to enhance methane production from the pelagic Sargassum. Microbial adaptation was performed in a fed-batch mode for 100 days by progressive feeding of Sargassum. The evolution of the microbial community was analyzed by high-throughput sequencing of 16S rRNA amplicons. Additionally, 16S rRNA data were used to predict functional profiles using the iVikodak platform. The results showed that, after adaptation, the consortium was dominated by the bacterial phyla Bacteroidota, Firmicutes, and Atribacterota, as well as methanogens of the families Methanotrichaceae and Methanoregulaceae. The abundance of predicted genes related to different metabolic functions was affected during the adaptation stage when Sargassum concentration was increased. At the end of the adaptation stage, the abundance of the predicted genes increased again. The adapted microbial consortium demonstrated a 60% increase in both biomethane potential and biodegradability index. This work offers valuable insights into the development of treatment technologies and the effective management of pelagic Sargassum in coastal regions, emphasizing the importance of microbial adaptation in this context.


Asunto(s)
Metano , Consorcios Microbianos , ARN Ribosómico 16S , Sargassum , Metano/metabolismo , ARN Ribosómico 16S/genética , Bacterias/metabolismo , Bacterias/clasificación , Bacterias/genética
2.
J Infect Dis ; 230(Supplement_1): S40-S50, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39140723

RESUMEN

BACKGROUND: Postinfectious Lyme arthritis (LA) is associated with dysregulated immunity and autoreactive T- and B-cell responses in joints. Here we explored the role of host genetic variation in this outcome. METHODS: The frequency of 253 702 single-nucleotide polymorphisms (SNPs) was determined in 147 patients with LA (87 with postinfectious LA and 60 with antibiotic-responsive LA), and for comparison in 90 patients with erythema migrans or the general population (n = 2504). Functional outcome of candidate SNPs was assessed by evaluating their impact on clinical outcome and on immune responses in blood and synovial fluid in patients with LA. RESULTS: Six SNPs associated with late cornified envelope (LCE3) genes were present at greater frequency in patients with postinfectious LA compared to those with antibiotic-responsive LA (70% vs 30%; odds ratio, 2; P < .01). These SNPs were associated with heightened levels of inflammatory Th17 cytokines in serum but lower levels of interleukin 27, a regulatory cytokine, implying that they may contribute to dysregulated Th17 immunity in blood. Moreover, in patients with postinfectious LA, the levels of these Th17 mediators correlated directly with autoantibody responses in synovial fluid, providing a possible link between LCE3 SNPs, maladaptive systemic Th17 immunity, and autoreactive responses in joints. CONCLUSIONS: Variation in the LCE3 locus, a known genetic risk factor in psoriasis and psoriatic arthritis, is associated with dysregulated systemic Th17 immunity and heightened autoantibody responses in joints. These findings underscore the importance of host genetic predisposition and systemic Th17 immunity in the pathogenesis of postinfectious (antibiotic-refractory) Lyme arthritis.


Asunto(s)
Enfermedad de Lyme , Polimorfismo de Nucleótido Simple , Células Th17 , Humanos , Enfermedad de Lyme/genética , Enfermedad de Lyme/inmunología , Células Th17/inmunología , Masculino , Femenino , Adulto , Persona de Mediana Edad , Líquido Sinovial/inmunología , Anciano , Citocinas/genética , Citocinas/metabolismo , Artritis Infecciosa/genética , Artritis Infecciosa/inmunología , Adulto Joven
3.
Cells ; 13(16)2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39195214

RESUMEN

Following spinal cord injury (SCI), the regenerative capacity of the central nervous system (CNS) is severely limited by the failure of axonal regeneration. The regeneration of CNS axons has been shown to occur by grafting predegenerated peripheral nerves (PPNs) and to be promoted by the transplantation of neural precursor cells (NPCs). The introduction of a combinatorial treatment of PPNs and NPCs after SCI has to address the additional problem of glial scar formation, which prevents regenerating axons from leaving the implant and making functional connections. Previously, we discovered that the synthetic sulfoglycolipid Tol-51 inhibits astrogliosis. The objective was to evaluate axonal regeneration and locomotor function improvement after SCI in rats treated with a combination of PPN, NPC, and Tol-51. One month after SCI, the scar tissue was removed and replaced with segments of PPN or PPN+Tol-51; PPN+NPC+Tol-51. The transplantation of a PPN segment favors regenerative axonal growth; in combination with Tol-51 and NPC, 30% of the labeled descending corticospinal axons were able to grow through the PPN and penetrate the caudal spinal cord. The animals treated with PPN showed significantly better motor function. Our data demonstrate that PPN implants plus NPC and Tol-51 allow successful axonal regeneration in the CNS.


Asunto(s)
Regeneración Nerviosa , Células-Madre Neurales , Nervios Periféricos , Traumatismos de la Médula Espinal , Animales , Traumatismos de la Médula Espinal/fisiopatología , Traumatismos de la Médula Espinal/terapia , Traumatismos de la Médula Espinal/patología , Ratas , Regeneración Nerviosa/efectos de los fármacos , Células-Madre Neurales/efectos de los fármacos , Células-Madre Neurales/trasplante , Células-Madre Neurales/citología , Nervios Periféricos/efectos de los fármacos , Nervios Periféricos/patología , Femenino , Axones/efectos de los fármacos , Glucolípidos/farmacología , Recuperación de la Función/efectos de los fármacos
4.
Differentiation ; : 100800, 2024 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-38987088

RESUMEN

Retinoblastoma protein is central in signaling networks of fundamental cell decisions such as proliferation and differentiation in all metazoans and cancer development. Immunostaining and biochemical evidence demonstrated that during interphase retinoblastoma protein is in the nucleus and is hypophosphorylated, and during mitosis is in the cytoplasm and is hyperphosphorylated. The purpose of this study was to visualize in vivo in a non-diseased tissue, the dynamic spatial and temporal nuclear exit toward the cytoplasm of this protein during mitosis and its return to the nucleus to obtain insights into its potential cytosolic functions. Using high-resolution time-lapse images from confocal microscopy, we tracked in vivo the ortholog in plants the RETINOBLASTOMA RELATED (RBR) protein tagged with Green Fluorescent Protein (GFP) in Arabidopsis thaliana's root. RBR protein exits from dense aggregates in the nucleus before chromosomes are in prophase in less than 2 min, spreading outwards as smaller particles projected throughout the cytosol during mitosis like a diffusive yet controlled event until telophase, when the daughter's nuclei form; RBR returns to the nuclei in coordination with decondensing chromosomal DNA forming new aggregates again in punctuated larger structures in each corresponding nuclei. We propose RBR diffused particles in the cytoplasm may function as a cytosolic sensor of incoming signals, thus coordinating re-aggregation with DNA is a mechanism by which any new incoming signals encountered by RBR may lead to a reconfiguration of the nuclear transcriptomic context. The small RBR diffused particles in the cytoplasm may preserve topologic-like properties allowing them to aggregate and restore their nuclear location, they may also be part of transient cytoplasmic storage of the cellular pre-mitotic transcriptional context, that once inside the nuclei may execute both the pre mitosis transcriptional context as well as new transcriptional instructions.

5.
Int J Mol Sci ; 25(14)2024 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-39063176

RESUMEN

Gastric cancer (GC) remains a significant global health challenge, with high mortality rates, especially in developing countries. Current treatments are invasive and have considerable risks, necessitating the exploration of safer alternatives. Quercetin (QRC), a flavonoid present in various plants and foods, has demonstrated multiple health benefits, including anticancer properties. This study investigated the therapeutic potential of QRC in the treatment of GC. We utilized advanced molecular techniques to assess the impact of QRC on GC cells, examining its effects on cellular pathways and gene expression. Our findings indicate that QRC significantly inhibits GC cell proliferation and induces apoptosis, suggesting its potential as a safer therapeutic option for GC treatment. Further research is required to validate these results and explore the clinical applications of QRC in cancer therapy.


Asunto(s)
Apoptosis , Proliferación Celular , Biología Computacional , Quercetina , Neoplasias Gástricas , Quercetina/farmacología , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Humanos , Proliferación Celular/efectos de los fármacos , Línea Celular Tumoral , Apoptosis/efectos de los fármacos , Biología Computacional/métodos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos
6.
J Extracell Biol ; 3(6): e157, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38947172

RESUMEN

Chemoresistance is a common problem in ovarian cancer (OvCa) treatment, where resistant cells, in response to chemotherapy, secrete small extracellular vesicles (sEVs), known as chemo-sEVs, that transfer resistance to recipient cells. sEVs are formed as intraluminal vesicles (ILVs) within multivesicular endosomes (MVEs), whose trafficking is regulated by Ras-associated binding (RAB) GTPases that mediate sEVs secretion or lysosomal degradation. A decrease in lysosomal function can promote sEVs secretion, but the relationship between MVEs trafficking pathways and sEVs secretion in OvCa chemoresistance is unclear. Here, we show that A2780cis cisplatin (CCDP) resistant OvCa cells had an increased number of MVEs and ILVs structures, higher levels of Endosomal Sorting Complex Required for Transport (ESCRTs) machinery components, and RAB27A compared to A2780 CDDP-sensitive OvCa cells. CDDP promoted the secretion of chemo-sEVs in A2780cis cells, enriched in DNA damage response proteins. A2780cis cells exhibited poor lysosomal function with reduced levels of RAB7, essential in MVEs-Lysosomal trafficking. The silencing of RAB27A in A2780cis cells prevents the Chemo-EVs secretion, reduces its chemoresistance and restores lysosomal function and levels of RAB7, switching them into an A2780-like cellular phenotype. Enhancing lysosomal function with rapamycin reduced chemo-sEVs secretion. Our results suggest that adjusting the balance between secretory MVEs and lysosomal MVEs trafficking could be a promising strategy for overcoming CDDP chemoresistance in OvCa.

7.
Microbiol Resour Announc ; 13(7): e0018824, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-38860796

RESUMEN

To understand microbial metabolism in horticultural soils exposed to pesticides, genome sequencing of Bacillus subtilis sp. strain UAMC was performed. A total of 7,892 genes distributed across 40 contigs were identified. Among these, those related to the degradation of endosulfan such as FMNH2 monooxygenase, or cytochrome p450 stand out.

8.
Angew Chem Int Ed Engl ; 63(34): e202405823, 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-38856634

RESUMEN

Invasive fungal disease accounts for about 3.8 million deaths annually, an unacceptable rate that urgently prompts the discovery of new knowledge-driven treatments. We report the use of camelid single-domain nanobodies (Nbs) against fungal ß-1,3-glucanosyltransferases (Gel) involved in ß-1,3-glucan transglycosylation. Crystal structures of two Nbs with Gel4 from Aspergillus fumigatus revealed binding to a dissimilar CBM43 domain and a highly conserved catalytic domain across fungal species, respectively. Anti-Gel4 active site Nb3 showed significant antifungal efficacy in vitro and in vivo prophylactically and therapeutically against different A. fumigatus and Cryptococcus neoformans isolates, reducing the fungal burden and disease severity, thus significantly improving immunocompromised animal survival. Notably, C. deneoformans (serotype D) strains were more susceptible to Nb3 and genetic Gel deletion than C. neoformans (serotype A) strains, indicating a key role for ß-1,3-glucan remodelling in C. deneoformans survival. These findings add new insight about the role of ß-1,3-glucan in fungal biology and demonstrate the potential of nanobodies in targeting fungal enzymes to combat invasive fungal diseases.


Asunto(s)
Aspergillus fumigatus , Dominio Catalítico , Anticuerpos de Dominio Único , Anticuerpos de Dominio Único/química , Anticuerpos de Dominio Único/inmunología , Anticuerpos de Dominio Único/farmacología , Aspergillus fumigatus/inmunología , Aspergillus fumigatus/enzimología , Cryptococcus neoformans/enzimología , Cryptococcus neoformans/inmunología , Antifúngicos/química , Antifúngicos/farmacología , Animales , Ratones , Glucano Endo-1,3-beta-D-Glucosidasa
9.
SLAS Technol ; 29(3): 100143, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38740284

RESUMEN

Within a growing drug discovery company, scientists acquire (either through in house synthesis or purchase) then store, retrieve, and ship solid compound samples daily between multiple locations. The efficient management and tracking of this entire process to support drug discovery is a significant challenge. This article describes a decentralized and cost-effective inventory facility that simplifies the solid compound storage and retrieval process. Standardized storage cabinets from the market are utilized, providing a cost-effective physical infrastructure. The cabinets can be distributed across storage rooms at multiple sites and arranged into spaces with a variety of dimensions, allowing the system to be retrofitted into existing facilities and scaled up easily. We can provide storage close to work areas at each location, minimizing both unnecessary movement of staff and transportation of substances. We have applied a systematic barcoding method to the compound batch identifier that correlates with its compound location. This simplifies the compound registration process as well as the process of finding and returning compounds. Additionally, a centralized electronic platform has been employed to store, update and track solid compound information, such as properties, location and quantity. Compound shipment may be initiated from different sites, and a centralized electronic platform assists the information retrieval process, ensuring each location possesses up-to-date information. The electronic platform we present streamlines the management of compound registration, location tracking, weight updates and shipment information, facilitating seamless record sharing among all stakeholders. Every step of the process can be tracked in real time by the project team. The platform can be flexibly configured to adapt to an evolving set of storage locations, with all information and processes being audited.


Asunto(s)
Descubrimiento de Drogas , Almacenaje de Medicamentos , Industria Farmacéutica
10.
Materials (Basel) ; 17(10)2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38793334

RESUMEN

The global presence of pharmaceutical pollutants in water sources represents a burgeoning public health concern. Recent studies underscore the urgency of addressing this class of emerging contaminants. In this context, our work focuses on synthesizing a composite material, FexOy/MAF-32, through a streamlined one-pot reaction process, as an adsorbent for diclofenac, an emerging environmental contaminant frequently found in freshwater environments and linked to potential toxicity towards several organisms such as fish and mussels. A thorough characterization was performed to elucidate the structural composition of the composite. The material presents magnetic properties attributed to its superparamagnetic behavior, which facilitates the recovery efficiency of the composite post-diclofenac adsorption. Our study further involves a comparative analysis between the FexOy/MAF-32 and a non-magnetic counterpart, comprised solely of 2-ethylimidazolate zinc polymer. This comparison aims to discern the relative advantages and disadvantages of incorporating magnetic iron oxide nanoparticles in the contaminant removal process facilitated by a coordination polymer. Our findings reveal that even a minimal incorporation of iron oxide nanoparticles substantially enhanced the composite's overall performance in pollutant adsorption.

11.
Radiat Oncol ; 19(1): 54, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38702761

RESUMEN

BACKGROUND: Stereotactic ablative body radiotherapy (SABR) is an emerging treatment alternative for patients with localized low and intermediate risk prostate cancer patients. As already explored by some authors in the context of conventional moderate hypofractionated radiotherapy, focal boost of the index lesion defined by magnetic resonance imaging (MRI) is associated with an improved biochemical outcome. The objective of this phase II trial is to determine the effectiveness (in terms of biochemical, morphological and functional control), the safety and impact on quality of life, of prostate SABR with MRI guided focal dose intensification in males with intermediate and high-risk localized prostate cancer. METHODS: Patients with intermediate and high-risk prostate cancer according to NCCN definition will be treated with SABR 36.25 Gy in 5 fractions to the whole prostate gland with MRI guided simultaneous integrated focal boost (SIB) to the index lesion (IL) up to 50 Gy in 5 fractions, using a protocol of bladder trigone and urethra sparing. Intra-fractional motion will be monitored with daily cone beam computed tomography (CBCT) and intra-fractional tracking with intraprostatic gold fiducials. Androgen deprivation therapy (ADT) will be allowed. The primary endpoint will be efficacy in terms of biochemical and local control assessed by Phoenix criteria and post-treatment MRI respectively. The secondary endpoints will encompass acute and late toxicity, quality of life (QoL) and progression-free survival. Finally, the subgroup of high-risk patients will be involved in a prospective study focused on immuno-phenotyping. DISCUSSION: To the best of our knowledge, this is the first trial to evaluate the impact of post-treatment MRI on local control among patients with intermediate and high-risk prostate cancer undergoing SABR and MRI guided focal intensification. The results of this trial will enhance our understanding of treatment focal intensification through the employment of the SABR technique within this specific patient subgroup, particularly among those with high-risk disease, and will help to clarify the significance of MRI in monitoring local responses. Hopefully will also help to design more personalized biomarker-based phase III trials in this specific context. Additionally, this trial is expected to be incorporated into a prospective radiomics study focused on localized prostate cancer treated with radiotherapy. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT05919524; Registered 17 July 2023. TRIAL SPONSOR: IRAD/SEOR (Instituto de Investigación de Oncología Radioterápica / Sociedad Española de Oncología Radioterápica). STUDY SETTING: Clinicaltrials.gov identifier: NCT05919524; Registered 17 July 2023. TRIAL STATUS: Protocol version number and date: v. 5/ 17 May-2023. Date of recruitment start: August 8, 2023. Date of recruitment completion: July 1, 2024.


Asunto(s)
Neoplasias de la Próstata , Radiocirugia , Radioterapia Guiada por Imagen , Anciano , Humanos , Masculino , Persona de Mediana Edad , Imagen por Resonancia Magnética/métodos , Tratamientos Conservadores del Órgano/métodos , Órganos en Riesgo/efectos de la radiación , Estudios Prospectivos , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/cirugía , Neoplasias de la Próstata/patología , Calidad de Vida , Radiocirugia/métodos , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia Guiada por Imagen/métodos , Vejiga Urinaria/efectos de la radiación , Ensayos Clínicos Fase II como Asunto
12.
Rev Alerg Mex ; 71(1): 47-51, 2024 Feb 01.
Artículo en Español | MEDLINE | ID: mdl-38683069

RESUMEN

BACKGROUND: Loxoscelism is a toxic clinical condition caused by the bite of spiders of the genus Loxosceles, with wide distribution throughout the world.1 Phospholipase D is responsible for dermonecrosis, inflammation, platelet aggregation, hemolysis, alteration of vascular permeability, cytotoxicity, nephrotoxicity, acute renal failure, among other symptoms involved with this protein. CASE REPORT: 27-year-old male patient, who began with a sudden episode of intense pain in the right hand, in the metacarpus and metacarpophalangeal joints. On clinical examination, the upper extremity was noted to have increased volume, extensive edema, hyperemia, and increased local temperature; The lesion progressed to extensive necrosis. Fasciotomies were performed, from distal to proximal, and release of the second and third finger compartment through longitudinal radial and ulnar incisions. A skin autograft was placed, obtained from the anterior surface of the right thigh. Opioid analgesics, non-steroidal anti-inflammatory drugs, corticosteroids, and antibiotics were administered. The skin biopsy reported: inflammatory infiltrate with neutrophils, ulceration, and bacterial colonies. After 27 days he had a favorable evolution, so he was discharged to his home, with follow-up by staff from the Outpatient Service. CONCLUSION: Cutaneous loxoscelism, as a cause of acute compartment syndrome of the hand, is rare, but should be considered in an area endemic for Loxosceles spp. Surgical decompression of the affected compartments represents a decisive factor in the treatment of patients.


ANTECEDENTES: El loxoscelismo es un cuadro clínico tóxico provocado por la mordedura de arañas del género Loxosceles, con amplia distribución en todo el mundo.1 La fosfolipasa D es la responsable de la dermonecrosis, inflamación, agregación plaquetaria, hemólisis, alteración de la permeabilidad vascular, citotoxicidad, nefrotoxicidad, insuficiencia renal aguda, entre otros síntomas implicados con esta proteína. REPORTE DE CASO: Paciente masculino de 27 años, que inició con un cuadro repentino de dolor intenso en la mano derecha, en el metacarpo y las articulaciones metacarpofalángicas. Al examen clínico, la extremidad superior se percibió con aumento de volumen, edema extenso, hiperemia y aumento de la temperatura local; la lesión progresó a necrosis extensa. Se realizaron fasciotomías, de distal a proximal, y liberación del compartimento del segundo y tercer dedo a través de incisiones longitudinales radiales y cubitales. Se colocó un autoinjerto de piel, obtenido de la superficie anterior del muslo derecho. Se administraron analgésicos opioides, antiinflamatorios no esteroides, corticosteroides y antibióticos. La biopsia de piel reporto: infiltrado inflamatorio con neutrófilos, ulceración y colonias bacterianas. Luego de 27 días tuvo evolución favorable, por lo que se dio alta a su domicilio, con seguimiento por personal del servicio de Consulta externa. CONCLUSIÓN: El loxoscelismo cutáneo, como causa de síndrome compartimental agudo de la mano, es poco común, pero debe considerarse en un área endémica para Loxosceles spp. La descompresión quirúrgica de los compartimentos afectados representa un factor decisivo en el tratamiento de los pacientes.


Asunto(s)
Picaduras de Arañas , Humanos , Masculino , Adulto , Picaduras de Arañas/complicaciones , Enfermedad Aguda , Síndromes Compartimentales/etiología
13.
BMC Health Serv Res ; 24(1): 507, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38659025

RESUMEN

BACKGROUND: Hospitalizations for ambulatory care sensitive conditions (ACSC) incur substantial costs on the health system that could be partially avoided with adequate outpatient care. Complications of chronic diseases, such as diabetes mellitus (DM), are considered ACSC. Previous studies have shown that hospitalizations due to diabetes have a significant financial burden. In Mexico, DM is a major health concern and a leading cause of death, but there is limited evidence available. This study aimed to estimate the direct costs of hospitalizations by DM-related ACSC in the Mexican public health system. METHODS: We selected three hospitals from each of Mexico's main public institutions: the Mexican Social Security Institute (IMSS), the Ministry of Health (MoH), and the Institute of Social Security and Services for State Workers (ISSSTE). We employed a bottom-up microcosting approach from the healthcare provider perspective to estimate the total direct costs of hospitalizations for DM-related ACSC. Input data regarding length of stay (LoS), consultations, medications, colloid/crystalloid solutions, procedures, and laboratory/medical imaging studies were obtained from clinical records of a random sample of 532 hospitalizations out of a total of 1,803 DM-related ACSC (ICD-10 codes) discharges during 2016. RESULTS: The average cost per DM-related ACSC hospitalization varies among institutions, ranging from $1,427 in the MoH to $1,677 in the IMSS and $1,754 in the ISSSTE. The three institutions' largest expenses are LoS and procedures. Peripheral circulatory and renal complications were the major drivers of hospitalization costs for patients with DM-related ACSC. Direct costs due to hospitalizations for DM-related ACSC in these three institutions represent 1% of the gross domestic product (GDP) dedicated to health and social services and 2% of total hospital care expenses. CONCLUSIONS: The direct costs of hospitalizations for DM-related ACSC vary considerably across institutions. Disparities in such costs for the same ACSC among different institutions suggest potential disparities in care quality across primary and hospital settings (processes and resource utilization), which should be further investigated to ensure optimal supply utilization. Prioritizing preventive measures for peripheral circulatory and renal complications in DM patients could be highly beneficial.


Asunto(s)
Atención Ambulatoria , Diabetes Mellitus , Hospitalización , Humanos , México , Diabetes Mellitus/terapia , Diabetes Mellitus/economía , Atención Ambulatoria/economía , Masculino , Femenino , Persona de Mediana Edad , Hospitalización/economía , Hospitalización/estadística & datos numéricos , Adulto , Costos de Hospital/estadística & datos numéricos , Anciano , Tiempo de Internación/economía , Tiempo de Internación/estadística & datos numéricos , Adolescente , Adulto Joven
14.
IUCrJ ; 11(Pt 3): 374-383, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38656310

RESUMEN

The large Bunyavirales order includes several families of viruses with a segmented ambisense (-) RNA genome and a cytoplasmic life cycle that starts by synthesizing viral mRNA. The initiation of transcription, which is common to all members, relies on an endonuclease activity that is responsible for cap-snatching. In La Crosse virus, an orthobunyavirus, it has previously been shown that the cap-snatching endonuclease resides in the N-terminal domain of the L protein. Orthobunyaviruses are transmitted by arthropods and cause diseases in cattle. However, California encephalitis virus, La Crosse virus and Jamestown Canyon virus are North American species that can cause encephalitis in humans. No vaccines or antiviral drugs are available. In this study, three known Influenza virus endonuclease inhibitors (DPBA, L-742,001 and baloxavir) were repurposed on the La Crosse virus endonuclease. Their inhibition was evaluated by fluorescence resonance energy transfer and their mode of binding was then assessed by differential scanning fluorimetry and microscale thermophoresis. Finally, two crystallographic structures were obtained in complex with L-742,001 and baloxavir, providing access to the structural determinants of inhibition and offering key information for the further development of Bunyavirales endonuclease inhibitors.


Asunto(s)
Antivirales , Endonucleasas , Virus La Crosse , Triazinas , Virus La Crosse/efectos de los fármacos , Virus La Crosse/enzimología , Antivirales/farmacología , Antivirales/química , Endonucleasas/antagonistas & inhibidores , Endonucleasas/metabolismo , Endonucleasas/química , Dibenzotiepinas , Morfolinas/farmacología , Morfolinas/química , Piridonas/farmacología , Piridonas/química , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Transferencia Resonante de Energía de Fluorescencia , Humanos , Animales , Proteínas Virales/antagonistas & inhibidores , Proteínas Virales/química , Proteínas Virales/metabolismo
15.
Brain Sci ; 14(4)2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38671958

RESUMEN

Epilepsy is a neurological disease with one of the highest rates of incidence worldwide. Although EEG is a crucial tool for its diagnosis, the manual detection of epileptic seizures is time consuming. Automated methods are needed to streamline this process; although there are already several works that have achieved this, the process by which it is executed remains a black box that prevents understanding of the ways in which machine learning algorithms make their decisions. A state-of-the-art deep learning model for seizure detection and three EEG databases were chosen for this study. The developed models were trained and evaluated under different conditions (i.e., three distinct levels of overlap among the chosen EEG data windows). The classifiers with the best performance were selected, then Shapley Additive Explanations (SHAPs) and Local Interpretable Model-Agnostic Explanations (LIMEs) were employed to estimate the importance value of each EEG channel and the Spearman's rank correlation coefficient was computed between the EEG features of epileptic signals and the importance values. The results show that the database and training conditions may affect a classifier's performance. The most significant accuracy rates were 0.84, 0.73, and 0.64 for the CHB-MIT, Siena, and TUSZ EEG datasets, respectively. In addition, most EEG features displayed negligible or low correlation with the importance values. Finally, it was concluded that a correlation between the EEG features and the importance values (generated by SHAP and LIME) may have been absent even for the high-performance models.

16.
Rev. esp. salud pública ; 98: e202403021, Mar. 2024. tab
Artículo en Español | IBECS | ID: ibc-231919

RESUMEN

Fundamentos: la periodontitis es la sexta complicación de la diabetes tipo 2 (dt2); dependiendo de su severidad puede causar dolor, incomodidad o hasta pérdida dental. El objetivo del estudio fue evaluar el impacto del estado periodontal autorreportado en la calidad de vida relacionada con la salud oral (cvrso) en personas con dt2. Métodos: se realizó un estudio transversal que incluyó a setenta y nueve adultos con dt2 atendidos en la clínica de síndrome metabólico del instituto nacional de enfermedades respiratorias cosío villegas en la ciudad de méxico, entre agosto y noviembre de 2010. La cvrso se evaluó con el cuestionario perfil de impacto en la salud bucal acortado (ohip-ee14). La periodontitis se evaluó por autorreporte, profundidad al sondeo (ps) y pérdida de inserción clínica (pic). La asociación entre estado periodontal autorreportado y cvrso se evaluó con modelos de regresión binomial negativa. Resultados: la edad promedio fue de 60,4 años (de=9,6); la duración de diabetes de 10,1 años (de=6,6). La cvrso se asoció con la autopercepción de mal aliento (rr=1,58, p=0,025), autopercepción de mala salud de las encías (rr=1,66, p=0,016), insatisfacción de la habilidad para masticar (rr=2,22, p≤0,001), pérdida de algún diente con movilidad previa (rr=1,74, p=0,019) y 20 dientes presentes o menos (rr=1,57, p=0,045). Conclusiones: la cvrso se asocia con el autorreporte de mal aliento, mala salud de las encías e insatisfacción de la habilidad para masticar en personas con dt2; esto sugiere que las condiciones bucales autopercibidas representan signos y síntomas de deterioro funcional y psicológico relacionados con la periodontitis severa.(AU)


Background: periodontitis ranks sixth as a type 2 diabetes (t2d) complication. According to its severity, it may cause pain, discomfort and tooth loss. The aim of this study was to evaluate the impact of self-reported periodontal status on the oral health related quality of life (ohrqol) of people with t2d.methods: a cross-sectional study was conducted involving seventy-nine adults with t2d who visited the metabolic syndrome clinic at the cosío villegas national institute of respiratory diseases in mexico city between august and november 2010. The ohrqol was evaluated with the shortened oral health impact profile (ohip-ee14). Periodontitis was measured by self-report, probing depth (pd), and clinical attachment loss (cal). The association between self-reported periodontal status and ohrqol was evaluated with binomial regression models.results: mean age of the participants was 60,4 years (sd=9,6); diabetes duration was 10,1 years (sd=6,6). The ohrqol was associated with self-perception of bad breath (rr=1,58; p=0,025), self-perception of poor gum health (rr=1,66; p=0,016), dissatisfaction with chewing ability (rr=2,22; p≤0,001), tooth loss due to mobility (rr=1,74; p=0,019), and presence of 20 teeth or less (rr=1,57; p=0,045). Conclusions: ohrqol is associated with self-report of bad breath, poor gum health and dissatisfaction with chewing ability in people with t2d, which suggests that self-perceived oral conditions represent signs and symptoms of functional and psychological impairment related to severe periodontitis.(AU)


Asunto(s)
Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Diabetes Mellitus , Salud Bucal , Enfermedades Periodontales , Calidad de Vida , Periodontitis , Estudios Transversales , Salud Pública , México , Encuestas y Cuestionarios
17.
PLoS One ; 19(3): e0301283, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38547155

RESUMEN

OBJECTIVE: To study the white matter connections between anterior cingulate cortex, anterior insula and amygdala as key regions of the frontal-limbic network that have been related to meditation. DESIGN: Twenty experienced practitioners of Sahaja Yoga Meditation and twenty nonmeditators matched on age, gender and education level, were scanned using Diffusion Weighted Imaging, using a 3T scanner, and their white matter connectivity was compared using diffusion tensor imaging analyses. RESULTS: There were five white matter fiber paths in which meditators showed a larger number of tracts, two of them connecting the same area in both hemispheres: the left and right amygdalae and the left and right anterior insula; and the other three connecting left anterior cingulate with the right anterior insula, the right amygdala and the left amygdala. On the other hand, non-meditators showed larger number of tracts in two paths connecting the left anterior insula with the left amygdala, and the left anterior insula with the left anterior cingulate. CONCLUSIONS: The study shows that long-term practice of Sahaja Yoga Meditation is associated with larger white matter tracts strengthening interhemispheric connections between limbic regions and connections between cingulo-amygdalar and cingulo-insular brain regions related to top-down attentional and emotional processes as well as between top-down control functions that could potentially be related to the witness state perceived through the state of mental silence promoted with this meditation. On the other hand, reduced connectivity strength in left anterior insula in the meditation group could be associated to reduced emotional processing affecting top-down processes.


Asunto(s)
Meditación , Sustancia Blanca , Yoga , Humanos , Meditación/psicología , Yoga/psicología , Giro del Cíngulo/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagen , Imagen de Difusión Tensora , Amígdala del Cerebelo/diagnóstico por imagen , Encéfalo , Imagen por Resonancia Magnética/métodos
18.
Rev Esp Salud Publica ; 982024 Mar 14.
Artículo en Español | MEDLINE | ID: mdl-38516881

RESUMEN

OBJECTIVE: Periodontitis ranks sixth as a type 2 diabetes (T2D) complication. According to its severity, it may cause pain, discomfort and tooth loss. The aim of this study was to evaluate the impact of self-reported periodontal status on the Oral Health Related Quality of Life (OHRQoL) of people with T2D. METHODS: A cross-sectional study was conducted involving seventy-nine adults with T2D who visited the Metabolic Syndrome clinic at the Cosío Villegas National Institute of Respiratory Diseases in Mexico City between August and November 2010. The OHRQoL was evaluated with the shortened Oral Health Impact Profile (OHIP-EE14). Periodontitis was measured by self-report, probing depth (PD), and clinical attachment loss (CAL). The association between self-reported periodontal status and OHRQoL was evaluated with binomial regression models. RESULTS: Mean age of the participants was 60,4 years (SD=9,6); diabetes duration was 10,1 years (SD=6,6). The OHRQoL was associated with self-perception of bad breath (RR=1,58; p=0,025), self-perception of poor gum health (RR=1,66; p=0,016), dissatisfaction with chewing ability (RR=2,22; p≤0,001), tooth loss due to mobility (RR=1,74; p=0,019), and presence of 20 teeth or less (RR=1,57; p=0,045). CONCLUSIONS: OHRQoL is associated with self-report of bad breath, poor gum health and dissatisfaction with chewing ability in people with T2D, which suggests that self-perceived oral conditions represent signs and symptoms of functional and psychological impairment related to severe periodontitis.


OBJECTIVE: La periodontitis es la sexta complicación de la diabetes tipo 2 (DT2); dependiendo de su severidad puede causar dolor, incomodidad o hasta pérdida dental. El objetivo del estudio fue evaluar el impacto del estado periodontal autorreportado en la Calidad de Vida Relacionada con la Salud Oral (CVRSO) en personas con DT2. METHODS: Se realizó un estudio transversal que incluyó a setenta y nueve adultos con DT2 atendidos en la Clínica de Síndrome Metabólico del Instituto Nacional de Enfermedades Respiratorias Cosío Villegas en la Ciudad de México, entre agosto y noviembre de 2010. La CVRSO se evaluó con el cuestionario Perfil de Impacto en la Salud Bucal acortado (OHIP-EE14). La periodontitis se evaluó por autorreporte, profundidad al sondeo (PS) y pérdida de inserción clínica (PIC). La asociación entre estado periodontal autorreportado y CVRSO se evaluó con modelos de regresión binomial negativa. RESULTS: La edad promedio fue de 60,4 años (DE=9,6); la duración de diabetes de 10,1 años (DE=6,6). La CVRSO se asoció con la autopercepción de mal aliento (RR=1,58, p=0,025), autopercepción de mala salud de las encías (RR=1,66, p=0,016), insatisfacción de la habilidad para masticar (RR=2,22, p≤0,001), pérdida de algún diente con movilidad previa (RR=1,74, p=0,019) y 20 dientes presentes o menos (RR=1,57, p=0,045). CONCLUSIONS: La CVRSO se asocia con el autorreporte de mal aliento, mala salud de las encías e insatisfacción de la habilidad para masticar en personas con DT2; esto sugiere que las condiciones bucales autopercibidas representan signos y síntomas de deterioro funcional y psicológico relacionados con la periodontitis severa.


Asunto(s)
Diabetes Mellitus Tipo 2 , Periodontitis , Pérdida de Diente , Adulto , Humanos , Calidad de Vida/psicología , Diabetes Mellitus Tipo 2/complicaciones , Autoinforme , Pérdida de Diente/epidemiología , Estudios Transversales , México/epidemiología , Salud Bucal , España , Periodontitis/complicaciones , Periodontitis/epidemiología , Encuestas y Cuestionarios
20.
Nutrients ; 16(4)2024 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-38398890

RESUMEN

The utilization of food as a therapeutic measure for various ailments has been a prevalent practice throughout history and across different cultures. This is exemplified in societies where substances like Hibiscus sabdariffa have been employed to manage health conditions like hypertension and elevated blood glucose levels. The inherent bioactive compounds found in this plant, namely, delphinidin-3-sambubioside (DS3), quercetin (QRC), and hibiscus acid (HA), have been linked to various health benefits. Despite receiving individual attention, the specific molecular targets for these compounds remain unclear. In this study, computational analysis was conducted using bioinformatics tools such as Swiss Target Prediction, ShinnyGo 0.77, KEGG, and Stringdb to identify the molecular targets, pathways, and hub genes. Supplementary results were obtained through a thorough literature search in PubMed. DS3 analysis revealed potential genetic alterations related to the metabolism of nitrogen and glucose, inflammation, angiogenesis, and cell proliferation, particularly impacting the PI3K-AKT signaling pathway. QRC analysis demonstrated interconnected targets spanning multiple pathways, with some overlap with DS3 analysis and a particular focus on pathways related to cancer. HA analysis revealed distinct targets, especially those associated with pathways related to the nervous system. These findings emphasize the necessity for focused research on the molecular effects of DS3, QRC, and HA, thereby providing valuable insights into potential therapeutic pathways.


Asunto(s)
Antocianinas , Citratos , Hibiscus , Quercetina , Humanos , Extractos Vegetales/farmacología , Extractos Vegetales/análisis , Fosfatidilinositol 3-Quinasas
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