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1.
Artículo en Inglés | MEDLINE | ID: mdl-39250735

RESUMEN

OBJECTIVES: Patients with systemic sclerosis present with severe gastroesophageal reflux disease, often refractory to proton-pump inhibitors (PPI) treatment. The aim of the present study was to identify factors associated with PPI-refractory esophagitis. METHODS: We performed a cross-sectional study in a single-center cohort of patients diagnosed with systemic sclerosis. We included patients who underwent an esophagogastroduodenoscopy while on PPI treatment. Patients with PPI-refractory erosive esophagitis were compared with those with endoscopically normal esophageal mucosa. RESULTS: A total of 69 patients were included, from these, 23 patients (33%) had PPI-refractory esophagitis (Grade A, n = 11; Grade B, n = 7; Grade C, n = 2; Grade D, n = 3) and 46 (67%) had an endoscopically normal esophageal mucosa. On univariate analysis, patients with PPI-refractory esophagitis were more frequently diffuse SSc subset (43% vs 17%; p= 0.041). Evaluating gastrointestinal motility tests, neither absent esophageal contractility (39% vs 25%, p= 0.292) nor hypotensive lower esophageal sphincter (47% vs 44%, p= 0.980) were significantly associated with PPI-refractory esophagitis. Gastrointestinal dysmotility, defined as abnormal gastric emptying and/or small bowel dilated loops, was significantly associated with PPI-refractory esophagitis (66 vs 8%, p = <0.001). On a multivariate regression model to evaluate the association between motility test results adjusted for the diffuse subset, gastrointestinal dysmotility (ß = 0.751, p= 0.010) was independently associated with PPI-refractory esophagitis, while absent esophageal contractility (ß = 0.044, p= 0.886) or a hypotensive LES were not (ß=-0.131, p= 0.663). CONCLUSIONS: Our findings suggest that gastric and small intestinal motor dysfunction may be an important contributor to the development of PPI-refractory esophagitis in patients with systemic sclerosis.

2.
Lupus ; : 9612033241283551, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39259025

RESUMEN

OBJECTIVES: To identify the predictive factors of first hospitalization and associated variables to the main causes of hospitalizations in lupus patients from a Latin American cohort. METHODS: The first hospitalization after entry into the cohort during these patients' follow-up due to either lupus disease activity and/or infection was examined. Clinical and therapeutic variables were those occurring prior to the first hospitalization. Descriptive statistical tests, multivariable logistic, and Cox regression models were performed. RESULTS: 1341 individuals were included in this analysis; 1200 (89.5%) were women. Their median and interquartile range (IQR) age at diagnosis were 27 (20-37) years and their median and IQR follow up time were 27.5 (4.7-62.2) months. A total of 456 (34.0%) patients were hospitalized; 344 (75.4%), 85 (18.6%) and 27 (5.9%) for disease activity, infections, or both, respectively. The predictors of the first hospitalization regardless of its cause were: medium (HR 2.03(1.27-3.24); p = 0.0028) and low (HR 2.42(1.55-3.79); p < 0.0001) socioeconomic status, serosal (HR 1.32(1.07-1.62); p = 0.0074) and renal (HR 1.50(1.23-1.82); p < 0.0001) involvement. Antimalarial (AM) use (HR 0.61(0.50-0.74); p < 0.0001) and achieving remission (HR 0.80(0.65-0.97); p = 0.0300) were negative predictors. CONCLUSIONS: The first hospitalization was associated with worse socioeconomic status and serosal and renal involvement. Conversely, AM use and achieving remission were associated with a lower risk of hospitalizations.

3.
Ecol Evol ; 14(9): e70236, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39238570

RESUMEN

An ongoing challenge in evolutionary and ecological research focuses on testing biogeographic hypotheses for the understanding of both species' distributional patterns and of the factors influencing range limits. In this study, we described the climatic niches of Neotropical humid montane forest birds through the analysis of factors driving their evolution at inter- and intraspecific levels; and tested for differences among allopatric lineages within Aulacorhynchus, Chlorospingus, Cardellina, and Eupherusa. We employed ecological niche models (ENMs) along with an ordination approach with kernel smoothing to perform niche overlap analyses and test hypotheses of niche equivalence/similarity among lineages. In addition, we described the potential distributions of each lineage during the Late Pleistocene climate fluctuations, identifying historical range expansions, connectivity, and stability. Overall, we observed differences in environmental variables influencing climatic requirements and distributional patterns for our selected species. We detected the highest values of niche overlap mainly between Eupherusa and some Chlorospingus lineages. At both interspecific and intraspecific levels, sister lineages showed non-identical environmental niches. Our results offer weak support to a moist forest model, in which populations followed the expansion and contraction cycles of montane forests, leading to a lack of niche conservatism among lineages (they tend to occupy not identical climatic environments) throughout Mesoamerica. Therefore, historical climatic conditions may act as ecological barriers determining the distributional ranges of these species.

4.
Am J Trop Med Hyg ; 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39288760

RESUMEN

The New World screwworm, Cochliomyia hominivorax Coquerel (Diptera: Calliphoridae), was officially eliminated from Costa Rica in 2000, but it was reintroduced in 2023. A myiasis by C. hominivorax in a 71-year-old man with a 4-month history of foot hyperkeratosis and interdigital ulcers is reported. The myiasis was detected before sampling for bacterial culture. Approximately 160 first- and second-instar larvae were recovered and identified as C. hominivorax. Morphological identification was based mainly on characteristics of the cephalopharyngeal skeleton, spiracles, and pigmented dorsal tracheal trunks. Sequencing of a cytochrome c oxidase subunit I gene fragment confirmed the identity. The ulcers healed after extraction of the larvae and ciprofloxacin treatment of a concurrent Staphylococcus aureus and Pseudomonas aeruginosa infection. Given the reintroduction of C. hominivorax in Costa Rica and the risk of northward expansion, this report highlights its impact on public health and calls for awareness among clinicians and healthcare practitioners.

5.
Front Public Health ; 12: 1461630, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39234092

RESUMEN

In most self-determination theory (SDT) research, improving (de)motivating teaching styles provides numerous benefits for students and teachers, although there is less evidence of the latter. Although the recent circumplex model provides a fine-grained picture of the different (de)motivating teaching styles (i.e., autonomy support, structure, control, and chaos) that physical education (PE) teachers can use in their lessons, no previous motivational training programs have been based on this model. Moreover, all SDT-training programs have been implemented through different group sessions, but individual sessions have not been delivered. This study outlines the protocol of a motivational training program, derived from the circumplex model, designed to enhance motivating teaching styles (and prevent or decrease demotivating teaching styles) among PE teachers. Consequently, this program seeks to improve motivational variables and influence (mal)adaptive outcomes in both teachers and students. A randomised controlled trial design with a mixed-method approach. At least 16 secondary PE teachers will be assigned to either an experimental group or a control group, together with some of their students. The training program comprises four face-to-face group sessions and two follow-up sessions (one individual and one group session). PE teachers will learn how to support autonomy and provide structure, as well as to be less controlling and chaotic towards students. Over approximately five months, teachers will implement these motivational strategies during their PE classes. Different (de)motivating teaching styles, motivational variables, and (mal)adaptive outcomes will be assessed in both PE teachers and their students at three distinct points: before the training program (T1), during the intervention (T2), and at the end of the intervention (T3). Additionally, two discussion groups involving all experimental PE teachers will be held (one following the training program and another at the end of the intervention). The results from this study could be useful for developing motivational training programs for in-service PE teachers. Clinical trial registration: ClinicalTrials.gov, identifier [NTC06479369].


Asunto(s)
Motivación , Educación y Entrenamiento Físico , Maestros , Humanos , Maestros/psicología , Autonomía Personal , Estudiantes/psicología , Masculino , Femenino , Adulto , Formación del Profesorado
6.
Hum Genomics ; 18(1): 94, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39227859

RESUMEN

BACKGROUND: The architecture and dynamics of T cell populations are critical in orchestrating the immune response to SARS-CoV-2. In our study, we used T Cell Receptor sequencing (TCRseq) to investigate TCR repertoires in 173 post-infection COVID-19 patients. METHODS: The cohort included 98 mild and 75 severe cases with a median age of 53. We amplified and sequenced the TCR ß chain Complementary Determining Region 3 (CDR3b) and performed bioinformatic analyses to assess repertoire diversity, clonality, and V/J allelic usage between age, sex and severity groups. CDR3b amino acid sequence inference was performed by clustering structural motifs and filtering validated reactive CDR3b to COVID-19. RESULTS: Our results revealed a pronounced decrease in diversity and an increase in clonal expansion in the TCR repertoires of severe COVID-19 patients younger than 55 years old. These results reflect the observed trends in patients older than 55 years old (both mild and severe). In addition, we identified a significant reduction in the usage of key V alleles (TRBV14, TRBV19, TRBV15 and TRBV6-4) associated with disease severity. Notably, severe patients under 55 years old had allelic patterns that resemble those over 55 years old, accompanied by a skewed frequency of COVID-19-related motifs. CONCLUSIONS: Present results suggest that severe patients younger than 55 may have a compromised TCR repertoire contributing to a worse disease outcome.


Asunto(s)
COVID-19 , Regiones Determinantes de Complementariedad , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Humanos , COVID-19/genética , COVID-19/inmunología , COVID-19/virología , Masculino , Persona de Mediana Edad , Femenino , SARS-CoV-2/inmunología , SARS-CoV-2/genética , SARS-CoV-2/patogenicidad , Adulto , Anciano , Regiones Determinantes de Complementariedad/genética , Regiones Determinantes de Complementariedad/inmunología , España , Linfocitos T/inmunología , Receptores de Antígenos de Linfocitos T alfa-beta/genética , Receptores de Antígenos de Linfocitos T alfa-beta/inmunología , Receptores de Antígenos de Linfocitos T/genética , Receptores de Antígenos de Linfocitos T/inmunología , Alelos
8.
J Cyst Fibros ; 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39327194

RESUMEN

Interdisciplinary teams care for people with cystic fibrosis (pwCF) at specialized treatment centers. These teams have laid the foundation for the cystic fibrosis (CF) care model responsible for gains in health outcomes and quality of life within the CF community. However, the landscape of CF care is transforming, invigorated by new technologies, accessibility of cystic fibrosis transmembrane conductance regulator (CFTR) therapies, and increased utilization of telemedicine. In light of these advances, it is appropriate to re-evaluate the CF care team structure. This position paper offers guidance for the structure of a CF care center designed to meet the evolving needs of the CF community. Fundamental to the proposed center structure is recognition of pwCF and their families as integral members of their care teams, underpinning the necessity for shared decision making, awareness of social determinants of health, and active partnership between all healthcare professionals involved in the care of pwCF.

9.
J Leukoc Biol ; 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39327799

RESUMEN

Viral RNA and miRNAs released by immune cells contribute to inflammation in COVID-19 patients. Here, we investigated the role of SARS-CoV2 RNA and host miRNAs carried within extracellular vesicles (EVs) in modulating inflammation. EVs were classified as positive or negative depending on their viral RNA cargo. To assess the function of viral RNA, EVs, and LPS were used to stimulate whole blood samples from healthy subjects, and the secretion of 27 serum analytes was measured. EVs alone did not induce cytokines, chemokines, or growth factors. However, under LPS stimulation, (SARS-CoV2+) EVs increased IL-12 and decreased IL-13 secretion, while (SARS-CoV2-) EVs increased MIP-1α and IL-1ß secretion. Host miR-19a-3p, -192-5p, -let-7c-5p, and -92b-3a were differentially expressed in association with viral RNA. EVs from COVID-19 patients exhibited differences in viral RNA and miRNA expression profiles that modulate LPS responses. This knowledge sheds light on the immunopathology of COVID-19.

10.
Int J Mol Sci ; 25(17)2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39273702

RESUMEN

This study aimed to elucidate the genetic causes underlying the juvenile parkinsonism (JP) diagnosed in a girl with several family members diagnosed with spinocerebellar ataxia type 2 (SCA2). To achieve this, whole-exome sequencing, analysis of CAG repeats, RNA sequencing analysis on fibroblasts, and metabolite identification were performed. As a result, a homozygous missense mutation SNP T>C (rs2254562) in synaptojamin 1 (SYNJ1), which has been implicated in the regulation of membrane trafficking in the synaptic vesicles, was identified. Additionally, we observed overexpression of L1 cell adhesion molecule (L1CAM), Cdc37, GPX1, and GPX4 and lower expression of ceruloplasmin in the patient compared to the control. We also found changes in sphingolipid, inositol, and inositol phosphate metabolism. These findings help to clarify the mechanisms of JP and suggest that the etiology of JP in the patient may be multifactorial. This is the first report of the rs2254562 mutation in the SYNJ gene identified in a JP patient with seizures and cognitive impairment.


Asunto(s)
Trastornos Parkinsonianos , Humanos , Femenino , Trastornos Parkinsonianos/genética , Mutación Missense , Secuenciación del Exoma , Linaje , Polimorfismo de Nucleótido Simple , Proteínas del Tejido Nervioso/genética , Niño , Multiómica
11.
Biomedicines ; 12(9)2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39335610

RESUMEN

Conditioned pain modulation (CPM) and temporal summation (TS) tests can measure the ability to inhibit pain in fibromyalgia syndrome (FMS) patients and its level of pain sensitization, respectively. However, their clinical validity is still unclear. We studied the association between changes in the CPM and TS tests and the clinical improvement of FMS patients who received therapeutic intervention. We systematically searched for FMS randomized clinical trials with data on therapeutic interventions comparing clinical improvement (pain intensity and symptom severity reduction), CPM, and TS changes relative to control interventions. To study the relationship between TS/CPM and clinical measures, we performed a meta-regression analysis to calculate odds ratios. We included nine studies (484 participants). We found no significant changes in TS or CPM by studying all the interventions together. Our findings show that this lack of difference is likely because pharmacological and non-pharmacological interventions resulted in contrary effects. Non-pharmacological interventions, such as non-invasive neuromodulation, showed the largest effects normalizing CPM/TS. Meta-regression was significantly associated with pain reduction and symptom severity improvement with normalization of TS and CPM. We demonstrate an association between clinical improvement and TS/CPM normalization in FMS patients. Thus, the TS and CPM tests could be surrogate biomarkers in FMS management. Recovering defective endogenous pain modulation mechanisms by targeted non-pharmacological interventions may help establish long-term clinical recovery in FMS patients.

12.
Cells ; 13(18)2024 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-39329772

RESUMEN

Nuclear bodies are structures in eukaryotic cells that lack a plasma membrane and are considered protein condensates, DNA, or RNA molecules. Known nuclear bodies include the nucleolus, Cajal bodies, and promyelocytic leukemia nuclear bodies. These bodies are involved in the concentration, exclusion, sequestration, assembly, modification, and recycling of specific components involved in the regulation of ribosome biogenesis, RNA transcription, and RNA processing. Additionally, nuclear bodies have been shown to participate in cellular processes such as the regulation of transcription of the cell cycle, mitosis, apoptosis, and the cellular stress response. The dynamics and functions of these bodies depend on the state of the cell. It is now known that both DNA and RNA viruses can direct their proteins to nuclear bodies, causing alterations in their composition, dynamics, and functions. Although many of these mechanisms are still under investigation, it is well known that the interaction between viral and nuclear body proteins is necessary for the success of the viral infection cycle. In this review, we concisely describe the interaction between viral and nuclear body proteins. Furthermore, we focus on the role of the nucleolus in RNA virus infections. Finally, we discuss the possible implications of the interaction of viral proteins on cellular transcription and the formation/degradation of non-coding RNAs.


Asunto(s)
Nucléolo Celular , Proteínas Virales , Nucléolo Celular/metabolismo , Nucléolo Celular/virología , Humanos , Proteínas Virales/metabolismo , Animales
13.
Artículo en Inglés | MEDLINE | ID: mdl-39297205

RESUMEN

BACKGROUND: Arteriovenous fistulae (AVFs) are the preferred vascular access for hemodialysis in patients with end-stage kidney disease. Chronic kidney disease (CKD) is associated with endothelial injury, impaired AVF maturation, and reduced patency, as well as utilization. Because CKD is characterized by multiple pathophysiological processes that induce endothelial-to-mesenchymal transition (EndMT), we hypothesized that CKD promotes EndMT during venous remodeling and that disruption of endothelial TGF (transforming growth factor)-ß signaling inhibits EndMT to prevent AVF failure even in the end-stage kidney disease environment. METHODS: The mouse 5/6 nephrectomy and aortocaval fistula models were used. CKD was created via 5/6 nephrectomy, with controls of no (0/6) or partial (3/6) nephrectomy in C57BL/6J mice. AVFs were created in mice with knockdown of TGF-ßR1/R2 (TGF-ß receptors type 1/2) in either smooth muscle cells or endothelial cells. AVF diameters and patency were measured and confirmed by serial ultrasound examination. AVF, both murine and human, were examined using Western blot, histology, and immunofluorescence. Human and mouse endothelial cells were used for in vitro experiments. RESULTS: CKD accelerates TGF-ß activation and promotes EndMT that is associated with increased AVF wall thickness and reduced patency in mice. Inhibition of TGF-ß signaling in both endothelial cells and smooth muscle cells decreased smooth muscle cell proliferation in the AVF wall, attenuated EndMT, and was associated with reduced wall thickness, increased outward remodeling, and improved AVF patency. Human AVF also showed increased TGF-ß signaling and EndMT. CONCLUSIONS: CKD promotes EndMT and reduces AVF patency. Inhibition of TGF-ß signaling, especially disruption of endothelial cell-specific TGF-ß signaling, attenuates EndMT and improves AVF patency in mouse AVF. Inhibition of EndMT may be a therapeutic approach of translational significance to improve AVF patency in human patients with CKD.

14.
J Breast Imaging ; 6(5): 502-512, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39162574

RESUMEN

OBJECTIVE: To evaluate the clinical performance and financial costs of breast-specific gamma imaging (BSGI) as a biopsy-reducing problem-solving strategy in patients with inconclusive diagnostic imaging findings. METHODS: A retrospective analysis of all patients for whom BSGI was utilized for inconclusive imaging findings following complete diagnostic mammographic and sonographic evaluation between January 2013 and December 2018 was performed. Positive BSGI findings were correlated and biopsied with either US or stereotactic technique with confirmation by clip location and pathology. After a negative BSGI result, patients were followed for a minimum of 24 months or considered lost to follow-up and excluded (22 patients). Results of further imaging studies, biopsies, and pathology results were analyzed. Net savings of avoided biopsies were calculated based on average Medicare charges. RESULTS: Four hundred and forty female patients from 30 to 95 years (mean 55 years) of age were included in our study. BSGI demonstrated a negative predictive value (NPV) of 98.4% (314/319) and a positive predictive value for biopsy of 35.5% (43/121). The overall sensitivity was 89.6% (43/48), and the specificity was 80.1% (314/392). In total, 78 false positive but only 5 false negative BSGI findings were identified. Six hundred and twenty-one inconclusive imaging findings were analyzed with BSGI and a total of 309 biopsies were avoided. Estimated net financial savings from avoided biopsies were $646 897. CONCLUSION: In the management of patients with inconclusive imaging findings on mammography or ultrasonography, BSGI is a problem-solving imaging modality with high NPV that helps avoid costs of image-guided biopsies.


Asunto(s)
Neoplasias de la Mama , Mamografía , Ultrasonografía Mamaria , Humanos , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Neoplasias de la Mama/patología , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/economía , Mamografía/economía , Mamografía/métodos , Adulto , Ultrasonografía Mamaria/economía , Ultrasonografía Mamaria/métodos , Anciano de 80 o más Años , Mama/diagnóstico por imagen , Mama/patología , Biopsia/economía , Biopsia/métodos , Sensibilidad y Especificidad , Cintigrafía/métodos , Cintigrafía/economía , Valor Predictivo de las Pruebas , Solución de Problemas
16.
Plant Physiol Biochem ; 215: 109066, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39186850

RESUMEN

The study aims to explore the natural variation in the metabolome of different populations of the invasive plant Carpobrotus from different genetic clusters and geographical origins to enhance our comprehension of its involvement in the adaptation process and phenotypic diversity. The metabolomic profile of shoots was analysed in four populations from two different genetic clusters (Cluster A: Cádiz and A Lanzada; Cluster B: La Marina and Samil) and two different biogeographical regions in Spain (Atlantic: Samil and A Lanzada; Mediterranean: Cádiz and La Marina), collected in the field and subsequently grown in the greenhouse. In addition, climatic, and physiological parameters were analysed. The Mediterranean populations (Cádiz and La Marina) showed lower initial weight and length measurements in morphological parameters than the Atlantic populations. On the contrary, only root parameters showed significant differences in growth parameters among populations. The analysis of ion levels revealed a consistent pattern of higher concentrations in shoots compared to roots, with significant differences among populations, particularly in sodium (Na+) and chlorides (Cl-) levels. Regarding metabolomic analysis, clear correlations between the metabolome, genetic and climatic conditions of Carpobrotus sp.pl populations are described. Pairwise comparisons using t-tests and Principal Component Analysis (PCA) indicated that the differences in metabolomic profile between the Samil and La Marina populations, which correspond to the same genetic cluster (cluster B), were smaller than in the rest of the comparisons indicating that populations from the same genetic cluster were more similar metabolically than those from the same climatic region. The study identified key metabolites representative of each cluster, with significant differences in amino acids, organic acids, and sugars contributing to the variation among populations. Pathway analysis highlighted the impact of climatic conditions on metabolic pathways, particularly in populations from Cluster A. In conclusion, the different populations were more similar according to the genetic cluster than to the climatic region of origin when studied at the metabolomic level. Consequently, the metabolites more representative of each cluster were also identified.


Asunto(s)
Especies Introducidas , Ambiente , Metaboloma , España
17.
J Proteomics ; 307: 105269, 2024 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-39098729

RESUMEN

Quantitative phosphoproteomic data has mostly been reported from experiments comparing relative phosphopeptides intensities in two or more different conditions, while the ideal parameter to compare is phosphopeptides occupancies. This term is scarcely used and therefore barely implemented in phosphoproteomics studies, and this should be of concern for the scientific journals. In order to demonstrate the relevance of this issue, here we show how the method of choice affects the interpretation of the data. The phosphoproteomic profile modulated in two AML cell lines after CK2 inhibition with CIGB-300 or CX-4945 is shown. Following the downstream action of CK2 the phosphosite intensity and occupancy results were compared to validate the best approach for quantitative phosphoproteomic studies. Even when the total number of quantified phosphopeptides was higher by using the intensity calculation, in all the cases the percent of CK2 consensus sequences which were down-regulated in response to CK2 inhibition was higher using the phosphosite occupancy quantification. To note, a high number of CK2 consensus sequences was found down-regulated with at least a 10% or 15% of phosphosite occupancy variation illustrating that low thresholds of occupancy modulation might be indicative of biological effect. Additionally, several biological processes only appear significantly over-represented in the phosphoproteome quantified by occupancy. The functional enrichment analysis per ranges of occupancy variations also illustrated clear differences among AML cell lines subjected to CK2 inhibition by CX-4945. A low overlap between the phosphoproteomes quantified by intensity and occupancy was obtained illustrating that new developments in proteomics techniques are needed to improve the performance of the occupancy approach. Even in such context, results indicate that occupancy quantification performs better than phosphorylation quantification based on intensity reinforcing the importance of such quantification approach to describe phosphoproteomic data.


Asunto(s)
Quinasa de la Caseína II , Fosfopéptidos , Proteómica , Quinasa de la Caseína II/metabolismo , Quinasa de la Caseína II/antagonistas & inhibidores , Humanos , Fosfopéptidos/análisis , Fosfopéptidos/metabolismo , Proteómica/métodos , Línea Celular Tumoral , Fosfoproteínas/metabolismo , Fosfoproteínas/análisis , Fosforilación , Naftiridinas/farmacología , Fenazinas , Proteoma/análisis , Proteoma/metabolismo , Leucemia Mieloide Aguda/metabolismo
18.
J Thromb Haemost ; 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39173878

RESUMEN

BACKGROUND: Anticoagulation and antiplatelet therapy effectively inhibit neointimal hyperplasia (NIH) in both arterial and venous systems but not in arteriovenous fistulae (AVF). The main site of AVF failure is the juxta-anastomotic area that is characterized by disturbed flow compared with laminar flow in the arterial inflow and the venous outflow. OBJECTIVES: We hypothesized that early thrombus formation is required for eccentric and heterogeneous NIH in the presence of disturbed flow. METHODS: Needle puncture and sutured AVF were created in C57BL/6 mice, in PF4-Cre × mT/mG reporter mice, and in Wistar rats. Human AVF samples were second-stage basilic vein transpositions. The tissues were examined by histology, immunofluorescence, immunohistochemistry, and en face staining. RESULTS: In the presence of disturbed flow, both mouse and human AVF showed eccentric and heterogeneous NIH. Maladapted vein wall was characterized by eccentric and heterogeneous neointima that was composed of a different abundance of thrombus and smooth muscle cells. PF4-cre × mT/mG reporter mice AVF showed that green fluorescent protein-labeled platelets deposit on the wall directly facing the fistula exit with endothelial cell loss and continue to accumulate in the presence of disturbed flow. Neither disturbed flow with limited endothelial cell loss nor nondisturbed flow induced heterogeneous neointima in different animal models. CONCLUSION: Early thrombus contributes to late heterogeneous NIH in the presence of disturbed flow. Disturbed flow, large area of endothelial cell loss, and thrombus formation are critical to form eccentric and heterogeneous NIH. Categorization of adapted or maladapted walls may be helpful for therapy targeting heterogeneous NIH.

19.
Emerg Microbes Infect ; 13(1): 2386136, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39148308

RESUMEN

Babesiosis, caused by protozoan parasites of the genus Babesia, is an emerging tick-borne disease of significance for both human and animal health. Babesia parasites infect erythrocytes of vertebrate hosts where they develop and multiply rapidly to cause the pathological symptoms associated with the disease. The identification of new Babesia species underscores the ongoing risk of zoonotic pathogens capable of infecting humans, a concern amplified by anthropogenic activities and environmental changes. One such pathogen, Babesia MO1, previously implicated in severe cases of human babesiosis in the United States, was initially considered a subspecies of B. divergens, the predominant agent of human babesiosis in Europe. Here we report comparative multiomics analyses of B. divergens and B. MO1 that offer insight into their biology and evolution. Our analysis shows that despite their highly similar genomic sequences, substantial genetic and genomic divergence occurred throughout their evolution resulting in major differences in gene functions, expression and regulation, replication rates and susceptibility to antiparasitic drugs. Furthermore, both pathogens have evolved distinct classes of multigene families, crucial for their pathogenicity and adaptation to specific mammalian hosts. Leveraging genomic information for B. MO1, B. divergens, and other members of the Babesiidae family within Apicomplexa provides valuable insights into the evolution, diversity, and virulence of these parasites. This knowledge serves as a critical tool in preemptively addressing the emergence and rapid transmission of more virulent strains.


Asunto(s)
Babesia , Babesiosis , Genoma de Protozoos , Babesia/genética , Babesia/clasificación , Babesia/patogenicidad , Babesiosis/parasitología , Animales , Humanos , Virulencia , Filogenia , Evolución Molecular , Genómica , Especiación Genética , Familia de Multigenes , Multiómica
20.
J Craniofac Surg ; 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39212303

RESUMEN

ABSTRACT: Disk perforation can result in degenerative changes within the joint structures. While discectomy has demonstrated enduring benefits, it has traditionally been described using an open approach, with the disadvantages inherent to this method. This study aims to present a series of patients who underwent arthroscopic discectomy technique and to report the outcomes. METHODS: Patients diagnosed with internal disorders of the temporomandibular joint underwent arthroscopic arthroscopic discectomy technique. Surgical outcomes were assessed by changes in pain using a visual analog scale and the maximum incisal opening. RESULTS: One hundred seventy-eight joints from 106 patients who underwent arthroscopic surgery were included. Discectomy was performed on 22 joints. Prior to surgery, patients reported an average visual analog scale pain score of 6.5, which decreased to an average of 0.5 at 6 months postsurgery (P<0.001). Before surgery, the average maximum incisal opening was 30 mm, which increased to 41 mm at 6 months postsurgery (P<0.001). CONCLUSIONS: The described technique represents an excellent alternative for managing patients with disk perforations.

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