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1.
BMC Biol ; 22(1): 47, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38413947

RESUMO

BACKGROUND: Crocodilians are one of the oldest extant vertebrate lineages, exhibiting a combination of evolutionary success and morphological resilience that has persisted throughout the history of life on Earth. This ability to endure over such a long geological time span is of great evolutionary importance. Here, we have utilized the combination of genomic and chromosomal data to identify and compare the full catalogs of satellite DNA families (satDNAs, i.e., the satellitomes) of 5 out of the 8 extant Alligatoridae species. As crocodilian genomes reveal ancestral patterns of evolution, by employing this multispecies data collection, we can investigate and assess how satDNA families evolve over time. RESULTS: Alligators and caimans displayed a small number of satDNA families, ranging from 3 to 13 satDNAs in A. sinensis and C. latirostris, respectively. Together with little variation both within and between species it highlighted long-term conservation of satDNA elements throughout evolution. Furthermore, we traced the origin of the ancestral forms of all satDNAs belonging to the common ancestor of Caimaninae and Alligatorinae. Fluorescence in situ experiments showed distinct hybridization patterns for identical orthologous satDNAs, indicating their dynamic genomic placement. CONCLUSIONS: Alligators and caimans possess one of the smallest satDNA libraries ever reported, comprising only four sets of satDNAs that are shared by all species. Besides, our findings indicated limited intraspecific variation in satellite DNA, suggesting that the majority of new satellite sequences likely evolved from pre-existing ones.


Assuntos
Jacarés e Crocodilos , DNA Satélite , Animais , DNA Satélite/genética , Jacarés e Crocodilos/genética , Cromossomos , Genômica , Evolução Molecular
2.
Plant Mol Biol ; 114(1): 8, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38291213

RESUMO

In bread wheat (Triticum aestivum L.), chromosome associations during meiosis are extremely regulated and initiate at the telomeres and subtelomeres, which are enriched in satellite DNA (satDNA). We present the study and characterization of the bread wheat satellitome to shed light on the molecular organization of wheat subtelomeres. Our results revealed that the 2.53% of bread wheat genome is composed by satDNA and subtelomeres are particularly enriched in such DNA sequences. Thirty-four satellite DNA (21 for the first time in this work) have been identified, analyzed and cytogenetically validated. Many of the satDNAs were specifically found at particular subtelomeric chromosome regions revealing the asymmetry in subtelomere organisation among the wheat subgenomes, which might play a role in proper homologous recognition and pairing during meiosis. An integrated physical map of the wheat satellitome was also constructed. To the best of our knowledge, our results show that the combination of both cytogenetics and genome research allowed the first comprehensive analysis of the wheat satellitome, shedding light on the complex wheat genome organization, especially on the polymorphic nature of subtelomeres and their putative implication in chromosome recognition and pairing during meiosis.


Assuntos
Genoma de Planta , Triticum , Triticum/genética , DNA Satélite , Pão , Sequência de Bases
3.
Ann Rheum Dis ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594056

RESUMO

OBJECTIVES: To compare the safety of Janus kinase inhibitors (JAKi) with that of tumour necrosis factor inhibitors (TNFi) and determine drug persistence among patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA). METHODS: We analysed data from patients included in BIOBADASER 3.0 and treated with JAKi or TNFi from 2015 to 2023 and estimated the incidence rate ratio (IRR) of adverse events and persistence. RESULTS: A total of 6826 patients were included. Of these, 52% had RA, 25% psoriatic arthritis and 23% axial SpA. Treatment was with TNFi in 86%. The mean duration of treatment was 2.2±2.0 years with TNFi versus 1.8±1.5 with JAKi. JAKis were prescribed in older patients with longer term disease, greater comorbidity and later treatment lines and more frequently as monotherapy. The IRR of all infections and gastrointestinal events was higher among patients with RA treated with JAKi. Drug persistence at 1, 2 and 3 years was 69%, 55% and 45% for TNFi and 68%, 54% and 45% for JAKi. Multivariate regression models showed a lower probability of discontinuation for JAKi (HR=0.85; 95% CI 0.78-0.92) and concomitant conventional synthetic disease-modifying antirheumatic drugs (HR=0.90; 95% CI 0.84-0.96). The risk of discontinuation increased with glucocorticoids, comorbidities, greater disease activity and later treatment lines. CONCLUSIONS: Infections, herpes zoster and gastrointestinal adverse events in patients with RA tended to be more frequent with JAKi. However, prognosis was poor in patients receiving JAKi. Persistence was similar for TNFi and JAKi, although factors associated with discontinuation differed by diagnostic group.

4.
Eur J Clin Invest ; 54(2): e14095, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37715584

RESUMO

OBJECTIVE: The persistence of biologic (b) and targeted synthetic (ts) disease-modifying antirheumatic drugs(DMARDs) in monotherapy versus in combination with conventional synthetic (cs) DMARDs is still a controversial topic in rheumatic diseases. To clarify this issue, the retention of the initial treatment strategy of b/tsDMARD in combination with csDMARD versus monotherapy in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) patients under real-life conditions was evaluated. Factors associated with maintenance of the initial strategy were analysed. METHODS: Nested cohort study within the Spanish BIOBADASER III registry. Bivariate comparisons and multivariate Cox proportional hazards models were used for the analyses. RESULTS: A total of 2521 patients were included in the study. In the multivariate model, the initial strategy of combination therapy was associated with shorter persistence in patients with RA (hazard ratio [HR] 1.58;95% confidence interval [CI] 1.00-2.50; p = .049), PsA (HR 2.48; 95% CI 1.65-3.72) and AS (HR 16.77; 95% CI 7.37-38.16; p < .001), regardless of sex, time of disease progression, baseline disease activity, glucocorticoid use or type of b/tsDMARD. Overall, the combination strategy was associated with an increased incidence of adverse events (incidence rate ratio [IRR] 1.13; 95% CI 1.05-1.21). CONCLUSIONS: In this real-life study, the strategy of combining a b/tsDMARD with a csDMARD is associated with lower persistence and worse safety profile compared to monotherapy in RA and especially in PsA and AS, suggesting that combination therapy should be rethought as first choice in RA patients, but especially in PsA and AS patients.


Assuntos
Antirreumáticos , Artrite Psoriásica , Artrite Reumatoide , Espondilite Anquilosante , Humanos , Artrite Psoriásica/tratamento farmacológico , Estudos de Coortes , Artrite Reumatoide/tratamento farmacológico , Antirreumáticos/uso terapêutico , Espondilite Anquilosante/tratamento farmacológico , Quimioterapia Combinada
5.
Breast Cancer Res Treat ; 201(2): 151-159, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37338729

RESUMO

PURPOSE: The monarchE trial showed that the addition of abemaciclib improves efficacy in patients with high-risk early breast cancer (EBC). We analyzed the long-term outcomes of a population similar to the monarchE trial to put into context the potential benefit of abemaciclib. METHODS: HR-positive/HER2-negative EBC patients eligible for the monarchE study were selected from 3 adjuvant clinical trials and a breast cancer registry. Patients with ≥ 4 positive axillary lymph nodes (N +) or 1-3 N + with tumor size ≥ 5 cm and/or histologic grade 3 and/or Ki67 ≥ 20%, who had undergone surgery with curative intent and had received anthracyclines ± taxanes and endocrine therapy in the neoadjuvant and /or adjuvant setting were included. We performed analysis of Invasive Disease-Free Survival (iDFS), Distant Disease-Free Survival (dDFS) and Overall Survival (OS) at 5 and 10 years, as well as yearly (up to 10) of Invasive Relapse Rate (IRR), Distant Relapse Rate (DRR) and Death Rate (DR). RESULTS: A total of 1,617 patients were analyzed from the GEICAM-9906 (312), GEICAM-2003-10 (210), and GEICAM-2006-10 (160) trials plus 935 from El Álamo IV. With a median follow-up of 10.1 years, the 5 and 10 years iDFS rates were 75.2% and 57.0%, respectively. The dDFS and OS rates at 5 years were 77.4% and 88.8% and the respective figures at 10 years were 59.7% and 70.9%. CONCLUSIONS: This data points out the need for new therapies for those patients. A longer follow-up of the monarchE study to see the real final benefit with abemaciclib is warranted. TRIAL REGISTRATION: ClinTrials.gov: GEICAM/9906: NCT00129922; GEICAM/ 2003-10: NCT00129935 and GEICAM/ 2006-10: NCT00543127.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Quimioterapia Adjuvante , Recidiva Local de Neoplasia/tratamento farmacológico , Aminopiridinas/uso terapêutico , Intervalo Livre de Doença , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Receptor ErbB-2/genética
6.
BMC Biol ; 20(1): 36, 2022 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-35130900

RESUMO

BACKGROUND: The full catalog of satellite DNA (satDNA) within a same genome constitutes the satellitome. The Library Hypothesis predicts that satDNA in relative species reflects that in their common ancestor, but the evolutionary mechanisms and pathways of satDNA evolution have never been analyzed for full satellitomes. We compare here the satellitomes of two Oedipodine grasshoppers (Locusta migratoria and Oedaleus decorus) which shared their most recent common ancestor about 22.8 Ma ago. RESULTS: We found that about one third of their satDNA families (near 60 in every species) showed sequence homology and were grouped into 12 orthologous superfamilies. The turnover rate of consensus sequences was extremely variable among the 20 orthologous family pairs analyzed in both species. The satDNAs shared by both species showed poor association with sequence signatures and motives frequently argued as functional, except for short inverted repeats allowing short dyad symmetries and non-B DNA conformations. Orthologous satDNAs frequently showed different FISH patterns at both intra- and interspecific levels. We defined indices of homogenization and degeneration and quantified the level of incomplete library sorting between species. CONCLUSIONS: Our analyses revealed that satDNA degenerates through point mutation and homogenizes through partial turnovers caused by massive tandem duplications (the so-called satDNA amplification). Remarkably, satDNA amplification increases homogenization, at intragenomic level, and diversification between species, thus constituting the basis for concerted evolution. We suggest a model of satDNA evolution by means of recursive cycles of amplification and degeneration, leading to mostly contingent evolutionary pathways where concerted evolution emerges promptly after lineages split.


Assuntos
DNA Satélite , Gafanhotos , Animais , DNA Satélite/genética , Evolução Molecular , Biblioteca Gênica , Gafanhotos/genética , Humanos , Filogenia
7.
Genome ; 65(2): 95-103, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34555288

RESUMO

Vandenboschia speciosa is an endangered tetraploid fern species with a large genome (10.5 Gb). Its geographical distribution is characterized by disjoined tertiary flora refuges, with relict populations that survived past climate crises. Here, we analyzed the transposable elements (TEs) and found that they comprise approximately 76% of the V. speciosa genome, thus being the most abundant type of DNA sequence in this gigantic genome. The V. speciosa genome is composed of 51% and 5.6% of Class I and Class II elements, respectively. LTR retrotransposons were the most abundant TEs in this species (at least 42% of the genome), followed by non-LTR retrotransposons, which constituted at least 8.7% of the genome of this species. We introduce an additional analysis to identify the nature of non-annotated elements (19% of the genome). A BLAST search of the non-annotated contigs against the V. speciosa TE database allowed for the identification of almost half of them, which were most likely diverged sequence variants of the annotated TEs. In general, the TE composition in V. speciosa resembles the TE composition in seed plants. In addition, repeat landscapes revealed three episodes of amplification for all TEs, most likely due to demographic changes associated with past climate crises.


Assuntos
Gleiquênias , Elementos de DNA Transponíveis/genética , Evolução Molecular , Gleiquênias/genética , Genoma de Planta , Retroelementos
8.
Prog Mol Subcell Biol ; 60: 103-143, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34386874

RESUMO

The twenty-first century began with a certain indifference to the research of satellite DNA (satDNA). Neither genome sequencing projects were able to accurately encompass the study of satDNA nor classic methodologies were able to go further in undertaking a better comprehensive study of the whole set of satDNA sequences of a genome. Nonetheless, knowledge of satDNA has progressively advanced during this century with the advent of new analytical techniques. The enormous advantages that genome-wide approaches have brought to its analysis have now stimulated a renewed interest in the study of satDNA. At this point, we can look back and try to assess more accurately many of the key questions that were left unsolved in the past about this enigmatic and important component of the genome. I review here the understanding gathered on plant satDNAs over the last few decades with an eye on the near future.


Assuntos
DNA Satélite , Evolução Molecular , Mapeamento Cromossômico , DNA de Plantas/genética , DNA Satélite/genética , Genômica
9.
Br J Cancer ; 125(8): 1168-1176, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34483338

RESUMO

BACKGROUND: Whether there are lifetime points of greater sensitivity to the deleterious effects of alcohol intake on the breasts remains inconclusive. OBJECTIVE: To compare the influence of distinctive trajectories of alcohol consumption throughout a woman's life on development of breast cancer (BC). METHODS: 1278 confirmed invasive BC cases and matched (by age and residence) controls from the Epi-GEICAM study (Spain) were used. The novel group-based trajectory modelling was used to identify different alcohol consumption trajectories throughout women's lifetime. RESULTS: Four alcohol trajectories were identified. The first comprised women (45%) with low alcohol consumption (<5 g/day) throughout their life. The second included those (33%) who gradually moved from a low alcohol consumption in adolescence to a moderate in adulthood (5 to <15 g/day), never having a high consumption; and oppositely, women in the third trajectory (16%) moved from moderate consumption in adolescence, to a lower consumption in adulthood. Women in the fourth (6%) moved from a moderate alcohol consumption in adolescence to the highest consumption in adulthood (≥15 g/day), never having a low alcohol consumption. Comparing with the first trajectory, the fourth doubled BC risk (OR 2.19; 95% CI 1.27, 3.77), followed by the third (OR 1.44; 0.96, 2.16) and ultimately by the second trajectory (OR 1.17; 0.86, 1.58). The magnitude of BC risk was greater in postmenopausal women, especially in those with underweight or normal weight. When alcohol consumption was independently examined at each life stage, ≥15 g/day of alcohol consumption in adolescence was strongly associated with BC risk followed by consumption in adulthood. CONCLUSIONS: The greater the alcohol consumption accumulated throughout life, the greater the risk of BC, especially in postmenopausal women. Alcohol consumption during adolescence may particularly influence BC risk.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Neoplasias da Mama/epidemiologia , Adolescente , Adulto , Consumo de Bebidas Alcoólicas/efeitos adversos , Neoplasias da Mama/etiologia , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Pós-Menopausa , Pré-Menopausa , Fatores de Risco , Espanha/epidemiologia , Inquéritos e Questionários , Adulto Jovem
10.
Basic Res Cardiol ; 116(1): 4, 2021 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-33495853

RESUMO

Remote ischemic conditioning (RIC) and the GLP-1 analog exenatide activate different cardioprotective pathways and may have additive effects on infarct size (IS). Here, we aimed to assess the efficacy of RIC as compared with sham procedure, and of exenatide, as compared with placebo, and the interaction between both, to reduce IS in humans. We designed a two-by-two factorial, randomized controlled, blinded, multicenter, clinical trial. Patients with ST-segment elevation myocardial infarction receiving primary percutaneous coronary intervention (PPCI) within 6 h of symptoms were randomized to RIC or sham procedure and exenatide or matching placebo. The primary outcome was IS measured by late gadolinium enhancement in cardiac magnetic resonance performed 3-7 days after PPCI. The secondary outcomes were myocardial salvage index, transmurality index, left ventricular ejection fraction and relative microvascular obstruction volume. A total of 378 patients were randomly allocated, and after applying exclusion criteria, 222 patients were available for analysis. There were no significant interactions between the two randomization factors on the primary or secondary outcomes. IS was similar between groups for the RIC (24 ± 11.8% in the RIC group vs 23.7 ± 10.9% in the sham group, P = 0.827) and the exenatide hypotheses (25.1 ± 11.5% in the exenatide group vs 22.5 ± 10.9% in the placebo group, P = 0.092). There were no effects with either RIC or exenatide on the secondary outcomes. Unexpected adverse events or side effects of RIC and exenatide were not observed. In conclusion, neither RIC nor exenatide, or its combination, were able to reduce IS in STEMI patients when administered as an adjunct to PPCI.


Assuntos
Braço/irrigação sanguínea , Exenatida/uso terapêutico , Incretinas/uso terapêutico , Precondicionamento Isquêmico , Miocárdio/patologia , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Idoso , Terapia Combinada , Método Duplo-Cego , Exenatida/efeitos adversos , Feminino , Humanos , Incretinas/efeitos adversos , Imagem Cinética por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Estudos Prospectivos , Fluxo Sanguíneo Regional , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/patologia , Infarto do Miocárdio com Supradesnível do Segmento ST/fisiopatologia , Espanha , Fatores de Tempo , Resultado do Tratamento , Função Ventricular Esquerda
11.
Rheumatology (Oxford) ; 59(12): 3906-3916, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33068439

RESUMO

OBJECTIVE: To assess the efficacy of abatacept (ABA) in RA patients with interstitial lung disease (ILD) (RA-ILD). METHODS: This was an observational, multicentre study of RA-ILD patients treated with at least one dose of ABA. ILD was diagnosed by high-resolution CT (HRCT). We analysed the following variables at baseline (ABA initiation), 12 months and at the end of the follow-up: Modified Medical Research Council (MMRC) scale (1-point change), forced vital capacity (FVC) or diffusion lung capacity for carbon monoxide (DLCO) (improvement or worsening ≥10%), HRCT, DAS on 28 joints evaluated using the ESR (DAS28ESR) and CS-sparing effect. RESULTS: We studied 263 RA-ILD patients [150 women/113 men; mean (s.d.) age 64.6 (10) years]. At baseline, they had a median duration of ILD of 1 (interquartile range 0.25-3.44) years, moderate or severe degree of dyspnoea (MMRC grade 2, 3 or 4) (40.3%), FVC (% of the predicted) mean (s.d.) 85.9 (21.8)%, DLCO (% of the predicted) 65.7 (18.3) and DAS28ESR 4.5 (1.5). The ILD patterns were: usual interstitial pneumonia (UIP) (40.3%), non-specific interstitial pneumonia (NSIP) (31.9%) and others (27.8%). ABA was prescribed at standard dose, i.v. (25.5%) or s.c. (74.5%). After a median follow-up of 12 (6-36) months the following variables did not show worsening: dyspnoea (MMRC) (91.9%); FVC (87.7%); DLCO (90.6%); and chest HRCT (76.6%). A significant improvement of DAS28ESR from 4.5 (1.5) to 3.1 (1.3) at the end of follow-up (P < 0.001) and a CS-sparing effect from a median 7.5 (5-10) to 5 (2.5-7.5) mg/day at the end of follow-up (P < 0.001) was also observed. ABA was withdrawn in 62 (23.6%) patients due to adverse events (n = 30), articular inefficacy (n = 27), ILD worsening (n = 3) and other causes (n = 2). CONCLUSION: ABA may be an effective and safe treatment for patients with RA-ILD.


Assuntos
Abatacepte/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/complicações , Doenças Pulmonares Intersticiais/tratamento farmacológico , Abatacepte/efeitos adversos , Antirreumáticos/efeitos adversos , Feminino , Humanos , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/etiologia , Masculino , Tomografia Computadorizada por Raios X , Resultado do Tratamento
12.
Prostaglandins Other Lipid Mediat ; 147: 106404, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31838198

RESUMO

Obesity is considered a global epidemic and is mainly associated with the development of diabetes, cardiovascular diseases and Non-Alcoholic Fatty Liver (NAFLD). The pathogenesis between obesity and hepatic steatosis is partially known, but could involve differentiated or tissue-specific participation of the expression of Cd36 mRNA that codes for a receptor which is a transporter of free fatty acids (FFA) in different tissues, favoring the lipids storage. This relative expression was evaluated in adipose and liver tissue in rats with steatosis after consumption of sucrose for 30 and 40 weeks. Ten Wistar rats were divided into two experimental groups (St-30 and St-40), which received a standard diet plus 30 % sucrose in their water intake. These rats showed a significant increase in abdominal fat, serum biochemical determinations, HOMA-IR; as well as, changes in adipocytes size and mild portal hepatitis and grade 2 hepatic steatosis. The relative expression of Cd36 mRNA increased in liver tissue after 30 (4.5-fold) and 40 (8.5-fold) weeks of sucrose ingestión but no in adipose tissue; with respect to control group (P < 0.05). This expression was associated with a significant increase in the levles of sCD36 in serum, which is indicator of the presence of the FFA transporter in the hepatocyte membrane causing lipids accumulation. The above shows the link between the adipose and hepatic tissue for the accumulation of steatotic fat in the liver through time, mediated by the relative expression of cd36 mRNA that encodes for the FFA transporter.


Assuntos
Tecido Adiposo/patologia , Antígenos CD36/metabolismo , Fígado Gorduroso/patologia , Lipídeos/análise , Fígado/patologia , Obesidade/complicações , Sacarose/toxicidade , Tecido Adiposo/metabolismo , Animais , Modelos Animais de Doenças , Fígado Gorduroso/etiologia , Fígado Gorduroso/metabolismo , Fígado/metabolismo , Masculino , Obesidade/induzido quimicamente , Obesidade/metabolismo , Ratos , Ratos Wistar , Edulcorantes/toxicidade
13.
Clin Exp Rheumatol ; 38(4): 662-669, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31694752

RESUMO

OBJECTIVES: To assess the plasma apolipoprotein B/apolipoprotein A1 ratio and its potential association with cardiovascular events (CVE) in patients with rheumatoid arthritis (RA). METHODS: A baseline analysis was made of the CARdiovascular in rheuMAtology Project (CARMA), a 10-year prospective study evaluating the presence of at least one CVE in 775 Spanish patients with RA. Of them, 29 had already experienced CVE prior to the inclusion in the study. We assessed the association between the elevation of the apoB/apoA1 ratio with the presence of CVE according to a logistic regression model for possible confounding factors. We also analysed the main parameters of activity of RA and parameters related to lipid metabolism. RA patients were classified according to treatment: patients treated with disease-modifying anti-rheumatic drugs without biologics and those undergoing biologic therapy (anti-TNF-α, anti-IL-6 receptor, and other biologic agents). RESULTS: The apoB/apoA1 ratio of patients who had experienced CVE was higher than that of patients without previous CVE (0.65 vs. 0.60). However, the difference between both subgroups did not reach statistical significance (p=0.197). It was also the case after the multivariate analysis [OR: 1.48 (95% CI: 0.15-14.4); p=0.735]. RA patients from the group with CVE were more commonly receiving lipid-lowering treatment with statins than those without CVE history (41.4% vs. 20%, p=0.005). High HAQ and high atherogenic index were significantly associated with the presence of CVE. There was no statistical association between the type of biologic therapy used in RA and the presence of CVE. CONCLUSIONS: No association between ApoB/apoA1 ratio and CVE was found at the baseline visit of patients with RA from the CARMA study.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Doenças Cardiovasculares , Apolipoproteína A-I , Apolipoproteínas B , Humanos , Estudos Prospectivos , Fator de Necrose Tumoral alfa/uso terapêutico
14.
Breast Cancer Res Treat ; 177(1): 115-125, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31152327

RESUMO

PURPOSE: GEICAM/2006-10 compared anastrozole (A) versus fulvestrant plus anastrozole (A + F) to test the hypothesis of whether a complete oestrogen blockade is superior to aromatase inhibitors alone in breast cancer patients receiving hormone adjuvant therapy. METHODS: Multicenter, open label, phase III study. HR+/HER2- EBC postmenopausal patients were randomized 1:1 to adjuvant A (5 years [year]) or A + F (A plus F 250 mg/4 weeks for 3 year followed by 2 year of A). Stratification factors: prior chemotherapy (yes/no); number of positive lymph nodes (0/1-3/≥ 4); HR status (both positive/one positive) and site. PRIMARY OBJECTIVE: disease-free survival (DFS). Planned sample size: 2852 patients. RESULTS: The study has an early stop due to the financer decision with 870 patients (437 randomized to A and 433 to A + F). Patient characteristics were well balanced. After a median follow-up of 6.24y and 111 DFS events (62 in A and 49 in A + F) the Hazard Ratio for DFS (combination vs. anastrozole) was 0.84 (95% CI 0.58-1.22; p = 0.352). The proportion of patients disease-free in arms A and A + F at 5 year and 7 year were 90.8% versus 91% and 83.6% versus 86.7%, respectively. Most relevant G2-4 toxicities (≥ 5% in either arm) with A versus A + F were joint pain (14.7%; 13.7%), fatigue (2.5%; 7.2%), bone pain (3%; 6.5%), hot flushes (3.5%; 5%) and muscle pain (2.8%; 5.1%). CONCLUSIONS: The GEICAM/2006-10 study did not show a statistically significant increase in DFS by adding adjuvant F to A, though no firm conclusions can be drawn because of the limited sample size due to the early stop of the trial. ClinicalTrials.gov: NCT00543127.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Anastrozol/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Terapia Combinada , Intervalo Livre de Doença , Feminino , Fulvestranto/administração & dosagem , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Pós-Menopausa , Resultado do Tratamento
15.
Org Biomol Chem ; 17(12): 3249-3257, 2019 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-30843907

RESUMO

Despite their importance in biology and medicinal chemistry, structural and functional studies of membrane proteins present major challenges. To study diverse membrane proteins, it is crucial to have the correct detergent to efficiently extract and stabilize the proteins from the native membranes for biochemical/biophysical downstream analyses. But many membrane proteins, particularly eukaryotic ones, are recalcitrant to stabilization and/or crystallization with currently available detergents and thus there are major efforts to develop novel detergents with enhanced properties. Here, a novel class of trehalose-cored amphiphiles are introduced, with multiple alkyl chains and carbohydrates projecting from the trehalose core unit are introduced. A few members displayed enhanced protein stabilization behavior compared to the benchmark conventional detergent, n-dodecyl-ß-d-maltoside (DDM), for multiple tested membrane proteins: (i) a bacterial leucine transporter (LeuT), (ii) the R. capsulatus photosynthetic superassembly, and (iii) the human ß2 adrenergic receptor (ß2AR). Due to synthetic convenience and their favourable behaviors for a range of membrane proteins, these agents have potential for membrane protein research. In addition, the detergent property-efficacy relationship discussed here will guide future design of novel detergents.


Assuntos
Detergentes/química , Glucosídeos/química , Micelas , Receptores Acoplados a Proteínas G/química , Tensoativos/química , Trealose/química , Humanos , Estrutura Molecular , Tamanho da Partícula , Estabilidade Proteica
16.
Org Biomol Chem ; 17(19): 4919-4920, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31062815

RESUMO

Correction for 'Trehalose-cored amphiphiles for membrane protein stabilization: importance of the detergent micelle size in GPCR stability' by Manabendra Das et al., Org. Biomol. Chem., 2019, 17, 3249-3257.

17.
Health Qual Life Outcomes ; 17(1): 143, 2019 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-31420041

RESUMO

PURPOSE: Because the currently available questionnaires to evaluate sexual changes on breast cancer women only address the sexual sphere with a few questions our purpose was to develop a questionnaire that assesses changes in sexual dysfunction and satisfaction in women treated for breast cancer. METHODS: A sample was selected of women aged between 18 and 65 who had had surgery for breast cancer, completed neoadjuvant/adjuvant chemotherapy treatment and could be receiving adjuvant hormonal treatment, with an active sex life at least 3 months before starting treatment. Metastatic disease was excluded. A questionnaire structured in 4 dimensions was developed. The MOS SF-12 and QLQ-BR23 questionnaires were also provided. The following metric properties were evaluated: item analysis; internal consistency; temporal stability; construct validity; concurrent, convergent and divergent validity; and feasibility. RESULTS: Three samples were recruited: a pilot sample of 20; a reduction sample of 152; and a validation sample of 148. The presence of 6 dimensions was confirmed: 1) Loss of sex drive; 2) worsening of body image; 3) psychological coping; 4) discomfort during intercourse; 5) satisfaction with sexual relations; and 6) satisfaction with breast reconstruction. Good goodness-of-fit statistics were obtained (χ2/df = 1.5, GFI = 0.9, AGFI = 0.84, CFI = 0.959, RMSEA = 0.062). Reliability was good (α = 0.855), as was test-retest stability (r = 0.838). The correlation with the convergent questionnaires proved to be higher than that obtained with generic measurements. CONCLUSIONS: We were able to develop a short questionnaire (17 items) capable of measuring sexual satisfaction in women with breast cancer with good metric properties.


Assuntos
Neoplasias da Mama/psicologia , Orgasmo , Qualidade de Vida , Inquéritos e Questionários/normas , Adaptação Psicológica , Adulto , Idoso , Imagem Corporal/psicologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes
18.
J Plant Res ; 132(1): 3-17, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30552526

RESUMO

We provide here the first full chloroplast genome sequence, i.e., the plastome, for a species belonging to the fern order Hymenophyllales. The phylogenetic position of this order within leptosporangiate ferns, together with the general scarcity of information about fern plastomes, places this research as a valuable study on the analysis of the diversity of plastomes throughout fern evolution. Gene content of V. speciosa plastome was similar to that in most ferns, although there were some characteristic gene losses and lineage-specific differences. In addition, an important number of genes required U to C RNA editing for proper protein translation and two genes showed start codons alternative to the canonical AUG (AUA). Concerning gene order, V. speciosa shared the specific 30-kb inversion of euphyllophytes plastomes and the 3.3-kb inversion of fern plastomes, keeping the ancestral gene order shared by eusporangiate and early leptosporangiate ferns. Conversely, V. speciosa has expanded IR regions comprising the rps7, rps12, ndhB and trnL genes in addition to rRNA and other tRNA genes, a condition shared with several eusporangiate ferns, lycophytes and hornworts, as well as most seed plants.


Assuntos
Evolução Molecular , Gleiquênias/genética , Genoma de Cloroplastos , Genoma de Planta , Filogenia , Análise de Sequência de DNA
19.
Rheumatol Int ; 39(12): 2119-2127, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31535169

RESUMO

The objective of our study was to standardize magnetic resonance imaging (MRI) assessment of spine and sacroiliac joints in patients with axial spondyloarthritis (axSpA) and/or inflammatory spinal pain, by creating checklists and templates based on the opinions of rheumatologists and radiologists. A scientific committee developed a series of questionnaires with multiple items regarding MRI in patients with axial inflammatory pain and/or axSpA. Then an expert panel of rheumatologists and radiologists rated all items in a 9-point Likert scale. Finally, the scientific committee and the expert panel met to create the definitive documents. Several definitive checklists and templates were generated for rheumatologist-requested MRI and for radiologist-requested MRI reports of sacroiliac joint and spinal examinations. A technical requirement protocol was also agreed on. Our results could be useful in increasing understanding between rheumatologists and radiologists regarding MRI in axSpA diagnosis and follow-up.


Assuntos
Lista de Checagem , Imageamento por Ressonância Magnética , Articulação Sacroilíaca/diagnóstico por imagem , Coluna Vertebral/diagnóstico por imagem , Espondilartrite/diagnóstico por imagem , Humanos , Sacroileíte/diagnóstico por imagem , Inquéritos e Questionários
20.
BMC Nephrol ; 20(1): 8, 2019 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-30626347

RESUMO

BACKGROUND: Most people who make the transition to renal replacement therapy (RRT) are treated with a fixed dose thrice-weekly hemodialysis réegimen, without considering their residual kidney function (RKF). Recent papers inform us that incremental hemodialysis is associated with preservation of RKF, whenever compared with conventional hemodialysis. The objective of the present controlled randomized trial (RCT) is to determine if start HD with one sessions per week (1-Wk/HD), it is associated with better patient survival and other safety parameters. METHODS/DESIGN: IHDIP is a multicenter RCT experimental open trial. It is randomized in a 1:1 ratio and controlled through usual clinical practice, with a low intervention level and non-commercial. It includes 152 incident patients older than 18 years, with a RRF of ≥4 ml/min/1.73 m2, measured by renal clearance of urea (KrU). The intervention group includes 76 patients who will start with incremental HD (1-Wk/HD). The control group includes 76 patients who will start with thrice-weekly hemodialysis régimen. The primary outcome is assessing the survival rate, while the secondary outcomes are the morbidity rate, the clinical parameters, the quality of life and the efficiency. DISCUSSION: This study will enable to know the number of sessions a patient should receive when starting HD, depending on his RRF. The potentially important clinical and financial implications of incremental hemodialysis warrant this RCT. TRIAL REGISTRATION: U.S. National Institutes of Health, ClinicalTrials.gov . Number: NCT03239808 , completed 13/04/2017. SPONSOR: Foundation for Training and Research of Health Professionals of Extremadura.


Assuntos
Rim/fisiopatologia , Estudos Multicêntricos como Assunto/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Diálise Renal/métodos , Creatinina/urina , Humanos , Avaliação de Resultados em Cuidados de Saúde , Estudos Prospectivos , Diálise Renal/efeitos adversos , Ureia/metabolismo
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