BRAF and TERT mutations in papillary thyroid cancer patients of Latino ancestry.

Papillary thyroid cancer (PTC) is the second most commonly diagnosed malignancy in U.S. Latinas and in Colombian women. Studies in non-Latinos indicate that BRAF and TERT mutations are PTC prognostic markers. This study aimed to determine the prevalence and clinical associations of BRAF and TERT mutations in PTC Latino patients from Colombia. We analyzed mutations of BRAF (V600E) and TERT promoter (C228T, C250T) in tumor DNA from 141 patients (75 with classical variant PTC, CVPTC; 66 with follicular variant PTC, FVPTC) recruited through a multi-center study. Associations between mutations and clinical variables were evaluated with Fisher exact tests. Survival was evaluated with Kaplan-Meier plots. Double-mutant tumors (BRAF+/TERT+, n = 14 patients) were more common in CVPTC (P = 0.02). Relative to patients without mutations (n = 48), double mutations were more common in patients with large tumors (P = 0.03), lymph node metastasis (P = 0.01), extra-thyroid extension (P = 0.03), and advanced stage (P = 6.0 × 10-5). In older patients, TERT mutations were more frequent (mean age 51 years vs 45 years for wild type TERT, P = 0.04) and survival was lower (HR = 1.20; P = 0.017); however, given the small sample size, the decrease in survival was not statically significant between genotypes. Comparisons with published data in US whites revealed that Colombian patients had a higher prevalence of severe pathological features and of double-mutant tumors (10 vs 6%, P = 0.001). Mutations in both oncogenes show prognostic associations in Latinos from Colombia. Our study is important to advance Latino PTC precision medicine and replicates previous prognostic associations between BRAF and TERT in this population

The HABP2 G534E polymorphism does not increase nonmedullary thyroid cancer risk in Hispanics.

Familial nonmedullary thyroid cancer (NMTC) has not been clearly linked to causal germline variants, despite the large role that genetic factors play in risk. Recently, HABP2 G534E (rs7080536A) has been implicated as a causal variant in NMTC. We have previously shown that the HABP2 G534E variant is not associated with TC risk in patients from the British Isles. Hispanics are the largest and the youngest minority in the United States and NMTC is now the second most common malignancy in women from this population. In order to determine if the HABP2 G534E variant played a role in NMTC risk among Hispanic populations, we analyzed 281 cases and 1105 population-matched controls from a multicenter study in Colombia, evaluating the association through logistic regression. We found that the HABP2 G534E variant was not significantly associated with NMTC risk (P=0.843) in this Hispanic group. We also stratified available clinical data by multiple available clinicopathological variables and further analyzed the effect of HABP2 on NMTC presentation. However, we failed to detect associations between HABP2 G534E and NMTC risk, regardless of disease presentation (P≥0.273 for all cases). Therefore, without any significant associations between the HABP2 G534E variant and NMTC risk, we conclude that the variant is not causal of NMTC in this Hispanic population

Clinical factors associated with discontinuation of ts/bDMARDs in rheumatic patients from the BIOBADASER III registry

Altres ajuts: Spanish Agency of Medicines and Medical Devices (AEMPS); Biogen; Bristol Myers-Squibb (BMS); Celltrion Healthcare; Lilly; Merck; Novartis; Pfizer; Regeneron Pharmaceuticals; Samsung Bioepis.Biologic and targeted synthetic disease-modifying antirheumatic drugs (ts/bDMARDs) play a pivotal role in the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). Persistence of therapy provides an index of a drug's overall effectiveness. The objective of the study was to identify factors associated with discontinuation of ts/bDMARDs in a real-world dataset. The study population comprised patients diagnosed with RA, PsA, and AS included in the BIOBADASER registry for whom follow-up data were available until November 2019. Patient features and treatment data were included in the analysis. The Kaplan-Meier method was used to study survival of the different drugs according to the reason for discontinuation. Factors associated with discontinuation were studied using Cox regression models and bivariate and multivariate analyses. P values of less than 0.05 were regarded as statistically significant. The study population comprised 4,752 patients who received a total of 8,377 drugs, of which 4,411 (52.65%) were discontinued. The Kaplan-Meier curves showed that survival for first-line treatment was greater in all 3 groups (p < 0.001). Patients with RA had a greater risk of discontinuation if they were younger (HR, 0.99; 95% CI 0.99-1.00), if they were receiving anti-TNFα agents (HR, 0.61; 95% CI 0.54-0.70), and if they had more comorbid conditions (HR, 1.09; 95% CI 1.00-1.17). Patients with PsA had a higher risk if they were women (HR, 1.36; 95% CI 1.15-1.62) and if they were receiving other ts/bDMARDs (HR, 1.29; 95% CI 1.05-1.59). In patients with AS, risk increased with age (HR, 1.01; 95% CI 1.00-1.02), as did the number of comorbid conditions (HR, 1.27; 95% CI 1.12-1.45). The factors that most affected discontinuation of ts/bDMARDs were line of treatment, age, type of drug, sex, comorbidity and the year of initiation of treatment. The association with these factors differed with each disease, except for first-line treatment, which was associated with a lower risk of discontinuation in all 3 diseases

Perfil clínico de los pacientes que ingresan al programa de atención domiciliaria de Essalud en el sur de Lima Metropolitana

Objetivo: Conocer el perfil clínico-epidemiológico de los pacientes que ingresan al programa de atención domiciliaria (Padomi) de Essalud en la zona sur de Lima. Material y métodos: Estudio descriptivo, transversal realizado durante el periodo marzo-mayo 2009 en pacientes mayores de 60 años que ingresaron al Padomi. Se recogió información sociodemográfica, motivo de referencia, enfermedades, estado funcional, fármacos, síndromesproblemas geriátricos y cuidador principal. Resultados: Ingresaron al Padomi 185 pacientes, mujeres (63,2%) y mayores de 80 años (62,2%). Se encontró que los casados eran en su mayoría de sexo masculino y los viudos de sexo femenino (p &lt; 0,01). El 80,5% fue referido por alta comorbilidad y el 88,1% de los establecimientos de Essalud. Las enfermedades más frecuentes fueron las cardiovasculares, demencia y musculoesqueléticas que correlacionaron con los fármacos más usados. El 86,1% tuvo algún nivel de dependencia funcional y el 80,5%, deterioro cognitivo, a predominio de las mujeres y los mayores de 80 años (p &lt; 0,05). Hubo mayor depresión en mujeres (32,6%) que en varones (8,3%) (p &lt; 0,01). Los síndromes y problemas geriátricos más frecuentes fueron polifarmacia, caídas, deterioro visual y deterioro auditivo. El 94,6% de los pacientes tomaba algún tipo de fármaco y el 60% de pacientes tenía riesgo social moderado o alto. El 89,7% tenía un cuidador a cargo, que fue mujer en 92,2%, como hijas (44,2%) o esposas (24%). Conclusión: Los pacientes que ingresaron al Padomi presentaron alta morbilidad, nivel funcional disminuido, problema social importante, deterioro cognitivo y síndromes-problemas geriátricos diversos

Health status and labor force participation : evidence for urban low and middle income individuals in Colombia

This paper analyzes the relationship between individual health status and labor force participation using the first wave of the Colombian Longitudinal Survey. The empirical modeling strategy accounts for the presence of potential endogeneity between these two variables. The results show that there is a positive relationship between health and labor force participation in both directions, indicating that better health is likely to lead to a higher probability of participation in the labor market, but also that individuals who participate in the labor market are more likely to report better health. Interesting differences are uncovered when comparing the results by gender and/or age groups. For instance, for younger females, health status and higher education positively affect the probability of labor participation, whereas having children under the age of 5 and being married reduce their probability of participation. Our findings also highlight the importance of public policy to guarantee good health conditions of the population which could also have a positive impact on labor productivity and consequently on long-run economic growth.info:eu-repo/semantics/publishedVersio

Regulation of cell death receptor S-nitrosylation and apoptotic signaling by Sorafenib in hepatoblastoma cells

Nitric oxide (NO) plays a relevant role during cell death regulation in tumor cells. The overexpression of nitric oxide synthase type III (NOS-3) induces oxidative and nitrosative stress, p53 and cell death receptor expression and apoptosis in hepatoblastoma cells. S-nitrosylation of cell death receptor modulates apoptosis. Sorafenib is the unique recommended molecular-targeted drug for the treatment of patients with advanced hepatocellular carcinoma. The present study was addressed to elucidate the potential role of NO during Sorafenib-induced cell death in HepG2 cells. We determined the intra- and extracellular NO concentration, cell death receptor expression and their S-nitrosylation modifications, and apoptotic signaling in Sorafenib-treated HepG2 cells. The effect of NO donors on above parameters has also been determined. Sorafenib induced apoptosis in HepG2 cells. However, low concentration of the drug (10nM) increased cell death receptor expression, as well as caspase-8 and -9 activation, but without activation of downstream apoptotic markers. In contrast, Sorafenib (10 µM) reduced upstream apoptotic parameters but increased caspase-3 activation and DNA fragmentation in HepG2 cells. The shift of cell death signaling pathway was associated with a reduction of S-nitrosylation of cell death receptors in Sorafenib-treated cells. The administration of NO donors increased S-nitrosylation of cell death receptors and overall induction of cell death markers in control and Sorafenib-treated cells. In conclusion, Sorafenib induced alteration of cell death receptor S-nitrosylation status which may have a relevant repercussion on cell death signaling in hepatoblastoma cells.Instituto de Salud Carlos III PI13/00021Ministerio de Economía y Competitividad BFU2012-32056Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía BIO-0216Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía CTS-6264Consejería de Salud, Junta de Andalucía PI13/ 0002

Heart Rate Variability Dynamics for the Prognosis of Cardiovascular Risk

Statistical, spectral, multi-resolution and non-linear methods were applied to heart rate variability (HRV) series linked with classification schemes for the prognosis of cardiovascular risk. A total of 90 HRV records were analyzed: 45 from healthy subjects and 45 from cardiovascular risk patients. A total of 52 features from all the analysis methods were evaluated using standard two-sample Kolmogorov-Smirnov test (KS-test). The results of the statistical procedure provided input to multi-layer perceptron (MLP) neural networks, radial basis function (RBF) neural networks and support vector machines (SVM) for data classification. These schemes showed high performances with both training and test sets and many combinations of features (with a maximum accuracy of 96.67%). Additionally, there was a strong consideration for breathing frequency as a relevant feature in the HRV analysis

Heart Rate Variability Dynamics for the Prognosis of Cardiovascular Risk

Statistical, spectral, multi-resolution and non-linear methods were applied to heart rate variability (HRV) series linked with classification schemes for the prognosis of cardiovascular risk. A total of 90 HRV records were analyzed: 45 from healthy subjects and 45 from cardiovascular risk patients. A total of 52 features from all the analysis methods were evaluated using standard two-sample Kolmogorov-Smirnov test (KS-test). The results of the statistical procedure provided input to multi-layer perceptron (MLP) neural networks, radial basis function (RBF) neural networks and support vector machines (SVM) for data classification. These schemes showed high performances with both training and test sets and many combinations of features (with a maximum accuracy of 96.67%). Additionally, there was a strong consideration for breathing frequency as a relevant feature in the HRV analysis

Associated factors to serious infections in a large cohort of juvenile-onset systemic lupus erythematosus from Lupus Registry (RELESSER).

Objective: To assess the incidence of serious infection (SI) and associated factors in a large juvenile-onset systemic lupus erythematosus (jSLE) retrospective cohort. Methods: All patients in the Spanish Rheumatology Society Lupus Registry (RELESSER) who meet =4 ACR-97 SLE criteria and disease onset <18 years old (jSLE), were retrospectively investigated for SI (defined as either the need for hospitalization with antibacterial therapy for a potentially fatal infection or death caused by the infection). Standardized SI rate was calculated per 100 patient years. Patients with and without SI were compared. Bivariate and multivariate logistic and Cox regression models were built to calculate associated factors to SI and relative risks. Results: A total of 353 jSLE patients were included: 88.7% female, 14.3 years (± 2.9) of age at diagnosis, 16.0 years (± 9.3) of disease duration and 31.5 years (±10.5) at end of follow-up. A total of 104 (29.5%) patients suffered 205 SI (1, 55.8%; 2-5, 38.4%; and =6, 5.8%). Incidence rate was 3.7 (95%CI: 3.2–4.2) SI per 100 patient years. Respiratory location and bacterial infections were the most frequent. Higher number of SLE classification criteria, SLICC/ACR DI score and immunosuppressants use were associated to the presence of SI. Associated factors to shorter time to first infection were higher number of SLE criteria, splenectomy and immunosuppressants use. Conclusions: The risk of SI in jSLE patients is significant and higher than aSLE. It is associated to higher number of SLE criteria, damage accrual, some immunosuppressants and splenectomy

Stochastic Resonance Modulates Neural Synchronization within and between Cortical Sources

Neural synchronization is a mechanism whereby functionally specific brain regions establish transient networks for perception, cognition, and action. Direct addition of weak noise (fast random fluctuations) to various neural systems enhances synchronization through the mechanism of stochastic resonance (SR). Moreover, SR also occurs in human perception, cognition, and action. Perception, cognition, and action are closely correlated with, and may depend upon, synchronized oscillations within specialized brain networks. We tested the hypothesis that SR-mediated neural synchronization occurs within and between functionally relevant brain areas and thus could be responsible for behavioral SR. We measured the 40-Hz transient response of the human auditory cortex to brief pure tones. This response arises when the ongoing, random-phase, 40-Hz activity of a group of tuned neurons in the auditory cortex becomes synchronized in response to the onset of an above-threshold sound at its “preferred” frequency. We presented a stream of near-threshold standard sounds in various levels of added broadband noise and measured subjects' 40-Hz response to the standards in a deviant-detection paradigm using high-density EEG. We used independent component analysis and dipole fitting to locate neural sources of the 40-Hz response in bilateral auditory cortex, left posterior cingulate cortex and left superior frontal gyrus. We found that added noise enhanced the 40-Hz response in all these areas. Moreover, added noise also increased the synchronization between these regions in alpha and gamma frequency bands both during and after the 40-Hz response. Our results demonstrate neural SR in several functionally specific brain regions, including areas not traditionally thought to contribute to the auditory 40-Hz transient response. In addition, we demonstrated SR in the synchronization between these brain regions. Thus, both intra- and inter-regional synchronization of neural activity are facilitated by the addition of moderate amounts of random noise. Because the noise levels in the brain fluctuate with arousal system activity, particularly across sleep-wake cycles, optimal neural noise levels, and thus SR, could be involved in optimizing the formation of task-relevant brain networks at several scales under normal conditions