4940 research outputs found
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Coronary Microvascular Dysfunction in Hypertrophic Cardiomyopathy
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Coronary Microvascular Adaptation in Athlete's Heart
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The Role of MiRNAs in the Diagnosis of Stable Atherosclerosis of Different Arterial Territories: a Critical Review
No full textAtherosclerotic disease is a major cause of morbidity and mortality worldwide. Atherosclerosis may be present in different arterial territories and as a single- or multi-territorial disease. The different phenotypes of atherosclerosis are attributable only in part to acquired cardiovascular risk factors and genetic Mendelian inheritance. miRNAs, which regulate the gene expression at the post-transcriptional level, may also contribute to such heterogeneity. Numerous miRNAs participate in the pathophysiology of atherosclerosis by modulating endothelial function, smooth vascular cell function, vascular inflammation, and cholesterol homeostasis in the vessel, among other biological processes. Moreover, miRNAs are present in peripheral blood with high stability and have the potential to be used as non-invasive biomarkers for the diagnosis of atherosclerosis. However, the circulating miRNA profile may vary according to the involved arterial territory, considering that atherosclerosis expression, including the associated molecular phenotype, varies according to the affected arterial territory. In this review, we discuss the specific circulating miRNA profiles associated with atherosclerosis of different arterial territories, the common circulating miRNA profile of stable atherosclerosis irrespective of the involved arterial territory, and the circulating miRNA signature of multi-territorial atherosclerosis. miRNAs may consist of a simple non-invasive method for discriminating atherosclerosis of different arterial sites. The limitations of miRNA profiling for such clinical application are also discussed.info:eu-repo/semantics/publishedVersio
Disclosing Azole Resistance Mechanisms in Resistant Candida Glabrata Strains Encoding Wild-Type or Gain-of-Function CgPDR1 Alleles Through Comparative Genomics and Transcriptomics
No full textThe pathogenic yeast Candida glabrata is intrinsically resilient to azoles and rapidly acquires resistance to these antifungals, in vitro and in vivo. In most cases azole-resistant C. glabrata clinical strains encode hyperactive CgPdr1 variants, however, resistant strains encoding wild-type CgPDR1 alleles have also been isolated, although remaining to be disclosed the underlying resistance mechanism. In this study, we scrutinized the mechanisms underlying resistance to azoles of 8 resistant clinical C. glabrata strains, identified along the course of epidemiological surveys undertaken in Portugal. Seven of the strains were found to encode CgPdr1 gain-of-function variants (I392M, E555K, G558C, and I803T) with the substitutions I392M and I803T being herein characterized as hyper-activating mutations for the first time. While cells expressing the wild-type CgPDR1 allele required the mediator subunit Gal11A to enhance tolerance to fluconazole, this was dispensable for cells expressing the I803T variant indicating that the CgPdr1 interactome is shaped by different gain-of-function substitutions. Genomic and transcriptomic profiling of the sole azole-resistant C. glabrata isolate encoding a wild-type CgPDR1 allele (ISTB218) revealed that under fluconazole stress this strain over-expresses various genes described to provide protection against this antifungal, while also showing reduced expression of genes described to increase sensitivity to these drugs. The overall role in driving the azole-resistance phenotype of the ISTB218 C. glabrata isolate played by these changes in the transcriptome and genome of the ISTB218 isolate are discussed shedding light into mechanisms of resistance that go beyond the CgPdr1-signalling pathway and that may alone, or in combination, pave the way for the acquisition of resistance to azoles in vivo.info:eu-repo/semantics/publishedVersio
Miringoplastia em População Pediátrica – Análise Retrospetiva de 5 Anos
No full textObjetivos: As miringoplastias são cirurgias frequentemente realizadas em idade pediátrica, existindo controvérsia quanto à melhor técnica cirúrgica e fatores que influenciam o seu sucesso. O objetivo deste estudo é caracterizar uma população de doentes pediátricos submetidos a miringoplastia e avaliar como
desfechos: o encerramento da perfuração, resultado audiométrico e existência de fatores determinantes de sucesso cirúrgico.
Desenho do Estudo: Estudo retrospetivo descritivo
Material e Métodos: Foram avaliados 56 doentes (57 ouvidos) com média de idades de 10,4±3,2 anos (6-17 anos) num período de 5 anos (2016-2020)
Resultados: A maioria das perfurações ocorreu após colocação de tubo de ventilação transtimpânico. A técnica cirúrgica mais utilizada foi a abordagem retroauricular com colocação de fascia temporalis underlay obtendo-se uma taxa de sucesso de 74% após 30 meses de seguimento médio. O limiar tonal médio da via aérea melhorou significativamente após o procedimento. A presença de malformações craniofaciais relacionou-se com um menor encerramento do Rinne audiométrico. Conclusões: As miringoplastias em idade pediátrica têm uma elevada taxa de sucesso.info:eu-repo/semantics/publishedVersio
Tumor Burden Score and Serum Alpha-fetoprotein Subclassify Intermediate-Stage Hepatocellular Carcinoma
No full textBackground: Resection of Barcelona Clinic Liver Cancer (BCLC) intermediate-stage hepatocellular carcinoma (HCC) remains controversial. While not recommended by the BCLC algorithm, some patients may indeed benefit from hepatectomy. We sought to identify that subset of patients who might derive long-term survival benefit from resection.
Methods: Intermediate-stage HCC patients who underwent curative-intent resection were identified from an international multi-institutional database. Factors associated with long-term prognosis were identified using multivariate analysis and a risk score was developed and assessed.
Results: Among 194 patients, most individuals had two tumors (n = 123, 63.4%) with a median size of 6.0 cm (IQR, 4.0-8.4) for a median tumor burden score (TBS) of 6.5 (IQR, 5.0-9.1); median alpha-fetoprotein (AFP) was 23.9 ng/mL (IQR, 5.0-503.2), and median overall survival (OS) was 69 months (IAR, 60.7-77.3). Factors associated with OS included AFP (referent ≤ 20 ng/mL, > 20 ng/mL: HR 1.78 95%CI, 1.09-2.89) and TBS (referent TBS ≤ 8.0, TBS > 8.0: HR 1.72 95%CI, 1.07-2.75). While 71 (36.6%) patients had neither risk factor, 79 (40.7%) and 44 (22.7%) had 1 or 2, respectively. A simplified score stratified patients relative to recurrence-free survival (RFS) (0: 33.6% vs. 1: 18.0% vs. 2: 14.7%) (AUC 0.60) and recurrence time (i.e., < 6 months after surgery) (0: 21.3% vs. 1: 43.1% vs. 2: 68.6%) (AUC 0.69) (both p < 0.001). Of note, a higher score was also associated with incrementally worse 5-year OS (0: 68.1% vs. 1: 61.0% vs. 2: 29.9%) (AUC 0.62) (p < 0.001).
Conclusion: Long-term OS and RFS outcomes varied considerably. Using a simple risk score, patients with low AFP and low TBS were identified as the subset of individuals most likely to benefit from resection.info:eu-repo/semantics/publishedVersio
Long-Term Outcome of Prostatic Artery Embolization for Patients with Benign Prostatic Hyperplasia: Single-Centre Retrospective Study in 1072 Patients Over a 10-Year Period.
No full textPurpose: Assess long-term outcomes of prostatic artery embolization (PAE) for patients with benign prostatic hyperplasia (BPH).
Materials and methods: Single centre retrospective study from 2009-2019 including 1072 patients who received PAE and had available follow-up. Patients were evaluated yearly at 1-10 years post PAE using the International Prostate Symptom Score (IPSS) and quality of life (QoL), prostate volume (PV), prostate-specific antigen (PSA), peak urinary flow rate (Qmax) and postvoid residual (PVR) volume. The need for prostatic medication, re-intervention rates, repeat PAE and prostatectomy rates were assessed with Kaplan-Meier survival analysis and compared between different embolic agents using Cox regression analysis.
Results: Mean follow-up time was 4.39 ± 2.37 years. At last follow-up visit, mean IPSS and QoL improvements were - 10.14 ± 8.34 (p < .0001) and - 1.87 ± 1.48 (p < .0001) points, mean PV reduction was - 6.82 ± 41.11 cm3 (p = 0.7779), mean PSA reduction was - 1.12 ± 4.60 ng/mL (p = 0.9713), mean Qmax increase was 2.72 ± 6.38 mL/s (p = 0.0005), mean PVR reduction was - 8.35 ± 135.75 mL (p = 0.6786). There were 335 patients (31.3%) needing prostatic medication after PAE. Re-intervention rates were 3.4% at 1 year, 21.1% at 5 years and 58.1% at 10 years. Repeat-PAE rates were 2.3% at 1 year, 9.5% at 5 years and 23.1% at 10 years. Prostatectomy rates were 1.1% at 1 year, 11.6% at 5 years and 35.0% at 10 years. No significant differences were found between polyvinyl alcohol particles, Bead Block, Embospheres and Embozenes.
Conclusion: PAE induces durable long-term LUTS relief, with re-intervention rates of 20% in the first 5 years and 30%-60% > 5 years post-PAE
Isolated Salter-Harris Type IV Distal Ulna Fracture: a Case Report
No full textinfo:eu-repo/semantics/publishedVersio