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1.
ESC Heart Fail ; 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32059081

RESUMO

AIMS: The objective of the present study is to assess the prognostic value of acute kidney injury (AKI) in the evolution of patients with heart failure (HF) using real-world data. METHODS AND RESULTS: Patients with a diagnosis of HF and with serial measurements of renal function collected throughout the study period were included. Estimated glomerular filtration rate (GFR) was calculated with the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration). AKI was defined when a sudden drop in creatinine with posterior recovery was recorded. According to the Risk, Injury, Failure, Loss, and End-Stage Renal Disease (RIFLE) scale, AKI severity was graded in three categories: risk [1.5-fold increase in serum creatinine (sCr)], injury (2.0-fold increase in sCr), and failure (3.0-fold increase in sCr or sCr > 4.0 mg/dL). AKI incidence and risk of hospitalization and mortality after the first episode were calculated by adjusting for potential confounders. A total of 30 529 patients with HF were included. During an average follow-up of 3.2 years, 5294 AKI episodes in 3970 patients (13.0%) and incidence of 3.3/100 HF patients/year were recorded. One episode was observed in 3161 (10.4%), two in 537 (1.8%), and three or more in 272 (0.9%). They were more frequent in women with diabetes and hypertension. The incidence increases across the GFR levels (Stages 1 to 4: risk 7.6%, 6.8%, 11.3%, and 12.5%; injury 2.1%, 2.0%, 3.3%, and 5.5%; and failure 0.9%, 0.6%. 1.4%, and 8.0%). A total of 3817 patients with acute HF admission were recorded during the follow-up, with incidence of 38.4/100 HF patients/year, 3101 (81.2%) patients without AKI, 545 (14.3%) patients with one episode, and 171 (4.5%) patients with two or more. The number of AKI episodes [one hazard ratio (HR) 1.05 (0.98-1.13); two or more HR 2.01 (1.79-2.25)] and severity [risk HR 1.05 (0.97-1.04); injury HR 1.41 (1.24-1.60); and failure HR 1.90 (1.64-2.20)] increases the risk of hospitalization. A total of 10 560 deaths were recorded, with incidence of 9.3/100 HF patients/year, 8951 (33.7%) of subjects without AKI episodes, 1180 (11.17%) of subjects with one episode, and 429 (4.06%) with two or more episodes. The number of episodes [one HR 1.05 (0.98-1.13); two or more HR 2.01 (1.79-2.25)] and severity [risk 1.05 confidence interval (CI) (0.97-1.14), injury 1.41 (CI 1.24-1.60), and failure 1.90 (CI 1.64-2.20)] increases mortality risk. CONCLUSIONS: The study demonstrated the worse prognostic value of sudden renal function decline in HF patients and pointed to those with more future risk who require review of treatment and closer follow-up.

3.
Am J Hosp Palliat Care ; : 1049909119901133, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31968989

RESUMO

OBJECTIVE: The use of chemotherapy near the end of life is not advisable. There are scarce data in Europe but shows signs of aggressiveness. We designed this study to analyze the proportion of onco-hematological patients receiving chemotherapy within their last 2 weeks of life as well as starting a new chemotherapy regimen in the 30 days prior to death. METHODS: A retrospective observational study was conducted in a tertiary hospital. Adults who died of an onco-hematological neoplasia while hospitalized between April 2017 and March 2018 were included. We assessed the use of chemotherapy over the course of the last 14 days of life, defined as the administration of at least one dose of chemotherapy. We also examined the proportion of patients starting a new chemotherapy regimen in the last 30 days of life. RESULTS: A total of 298 inpatients died in the Hematology and Oncology units. During the last 14 days, 28.2% (n = 11) of hematological and 26.3% (n = 68) of oncological patients received chemotherapy; the overall rate was 26.5% (n = 79). Furthermore, the proportion of patients starting a new chemotherapy regimen in the last 30 days of life was high (20.5% and 20.8%, respectively). Female gender (odds ratio [OR] = 1.99, 95% confidence interval [CI] = 1.18-3.35) and age <45 (OR = 2.68, 95% CI = 1.05-6.88) were associated with higher rates of chemotherapy. CONCLUSION: The proportion of patients receiving chemotherapy in the last 14 days of life was high, as well as the proportion of patients starting a new regimen in their last 30 days. This was indicative of excessive aggressiveness at the end-of-life care.

4.
Sci Adv ; 6(3): eaax7467, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31998838

RESUMO

Our nearest neighbor, Proxima Centauri, hosts a temperate terrestrial planet. We detected in radial velocities evidence of a possible second planet with minimum mass m c sin i c = 5.8 ± 1.9M ⊕ and orbital period P c = 5.21 - 0.22 + 0.26 years. The analysis of photometric data and spectro-scopic activity diagnostics does not explain the signal in terms of a stellar activity cycle, but follow-up is required in the coming years for confirming its planetary origin. We show that the existence of the planet can be ascertained, and its true mass can be determined with high accuracy, by combining Gaia astrometry and radial velocities. Proxima c could become a prime target for follow-up and characterization with next-generation direct imaging instrumentation due to the large maximum angular separation of ~1 arc second from the parent star. The candidate planet represents a challenge for the models of super-Earth formation and evolution.

5.
RNA ; 26(2): 186-198, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31694875

RESUMO

The 3'X domain of hepatitis C virus has been reported to control viral replication and translation by modulating the exposure of a nucleotide segment involved in a distal base-pairing interaction with an upstream 5BSL3.2 domain. To study the mechanism of this molecular switch, we have analyzed the structure of 3'X mutants that favor one of the two previously proposed conformations comprising either two or three stem-loops. Only the two-stem conformation was found to be stable and to allow the establishment of the distal contact with 5BSL3.2, and also the formation of 3'X domain homodimers by means of a universally conserved palindromic sequence. Nucleotide changes disturbing the two-stem conformation resulted in poorer replication and translation levels, explaining the high degree of conservation detected for this sequence. The switch function attributed to the 3'X domain does not occur as a result of a transition between two- and three-stem conformations, but likely through the sequestration of the 5BSL3.2-binding sequence by formation of 3'X homodimers.

6.
Arch. prev. riesgos labor. (Ed. impr.) ; 22(4): 176-177, oct.-dic. 2019.
Artigo em Espanhol | IBECS-Express | ID: ibc-FGT-2500

RESUMO

En los últimos años se viene observando un aumento de la prevalencia de asma siendo la exposición laboral uno de los factores condicionantes. Se llama asma laboral al que es inducido por la exposición a una sustancia en el lugar de trabajo y asma agravada por el trabajo a la que existe previamente y se exacerba en el trabajo. Para realizar un diagnóstico correcto es necesario una alta sospecha y relacionar temporalmente los síntomas y el trabajo. Un diagnóstico incorrecto produce consecuencias socio-económicas para el paciente. En el Real Decreto 1299/2006 de 10 noviembre (modificado el 4 de mayo de 2018) se establecen criterios para su clasificación y registro. Ante un proceso alérgico debe contemplarse la etiología laboral y los médicos del trabajo de los servicios de prevención de riesgos laborales hospitalarios pueden actuar como consultores para orientar y manejar estos casos. En este caso que se presenta se estableció una asociación entre la exposición laboral y el asma sufrido por la paciente, lo cual llevó, mediante una serie de procesos, a establecer su patología como enfermedad profesional


Currently there is an increase in the prevalence of asthma and it seems that occupational exposure is one of the factors contributing to this increase. "Occupational asthma" refers to new onset asthma induced by exposure to a substance in the workplace, whereas "work-aggravated asthma" refers to pre-existing asthma that is then exacerbated in the workplace. A correct diagnosis requires a high index of suspicion and establishing a temporal relationship between symptoms and work. An in-correct diagnosis can lead to important socioeconomic consequences for the worker. In Spain, Royal Order 1299/2006 on 10 November (amended on May 4, 2018) establishes the criteria for its classification and official recognition. In the context of an allergic process, an occupational etiology should be considered and occupational physicians in an occupational health service can serve as consultants to guide and manage these cases. In this case report we established an association between an occupational exposure and asthma in a worker which led to a series of steps resulting in its acceptance as an occupational disease

7.
Cancers (Basel) ; 11(12)2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31766351

RESUMO

T-cell prolymphocytic leukemia (T-PLL) is a rare and poor-prognostic mature T-cell leukemia. Recent studies detected genomic aberrations affecting JAK and STAT genes in T-PLL. Due to the limited number of primary patient samples available, genomic analyses of the JAK/STAT pathway have been performed in rather small cohorts. Therefore, we conducted-via a primary-data based pipeline-a meta-analysis that re-evaluated the genomic landscape of T-PLL. It included all available data sets with sequence information on JAK or STAT gene loci in 275 T-PLL. We eliminated overlapping cases and determined a cumulative rate of 62.1% of cases with mutated JAK or STAT genes. Most frequently, JAK1 (6.3%), JAK3 (36.4%), and STAT5B (18.8%) carried somatic single-nucleotide variants (SNVs), with missense mutations in the SH2 or pseudokinase domains as most prevalent. Importantly, these lesions were predominantly subclonal. We did not detect any strong association between mutations of a JAK or STAT gene with clinical characteristics. Irrespective of the presence of gain-of-function (GOF) SNVs, basal phosphorylation of STAT5B was elevated in all analyzed T-PLL. Fittingly, a significant proportion of genes encoding for potential negative regulators of STAT5B showed genomic losses (in 71.4% of T-PLL in total, in 68.4% of T-PLL without any JAK or STAT mutations). They included DUSP4, CD45, TCPTP, SHP1, SOCS1, SOCS3, and HDAC9. Overall, considering such losses of negative regulators and the GOF mutations in JAK and STAT genes, a total of 89.8% of T-PLL revealed a genomic aberration potentially explaining enhanced STAT5B activity. In essence, we present a comprehensive meta-analysis on the highly prevalent genomic lesions that affect genes encoding JAK/STAT signaling components. This provides an overview of possible modes of activation of this pathway in a large cohort of T-PLL. In light of new advances in JAK/STAT inhibitor development, we also outline translational contexts for harnessing active JAK/STAT signaling, which has emerged as a 'secondary' hallmark of T-PLL.

8.
Blood Cancer J ; 9(12): 91, 2019 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-31748534

RESUMO

MYC is the most altered oncogene in human cancer, and belongs to a large family of genes, including MYCN and MYCL. Recently, while assessing the degree of correlation between MYC gene rearrangement and MYC protein expression in aggressive B-cell lymphomas, we observed few Burkitt lymphoma (BL) cases lacking MYC protein expression despite the translocation involving the MYC gene. Therefore, in the present study we aimed to better characterize such cases. Our results identified two sub-groups of MYC protein negative BL: one lacking detectable MYC protein expression but presenting MYCN mRNA and protein expression; the second characterized by the lack of both MYC and MYCN proteins but showing MYC mRNA. Interestingly, the two sub-groups presented a different pattern of SNVs affecting MYC gene family members that may induce the switch from MYC to MYCN. Particulary, MYCN-expressing cases show MYCN SNVs at interaction interface that stabilize the protein associated with loss-of-function of MYC. This finding highlights MYCN as a reliable diagnostic marker in such cases. Nevertheless, due to the overlapping clinic, morphology and immunohistochemistry (apart for MYC versus MYCN protein expression) of both sub-groups, the described cases represent bona fide BL according to the current criteria of the World Health Organization.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31677197

RESUMO

T-cell prolymphocytic leukemia (T-PLL) is an aggressive tumor with leukemic presentation of mature T-lymphocytes. Here, we aimed at characterizing the initial events in the molecular pathogenesis of T-PLL and particularly, at determining the point in T-cell differentiation when the hallmark oncogenic events, that is, inv(14)(q11q32)/t(14;14)(q11;q32) and t(X;14)(q28;q11) occur. To this end, we mined whole genome and transcriptome sequencing data of 17 and 11 T-PLL cases, respectively. Mapping of the 14q32.1 locus breakpoints identified only TCL1A, which was moreover significantly overexpressed in T-PLL as compared to benign CD4+ and CD8+ T-cells, as the only common oncogenic target of aberrations. In cases with t(14;14), the breakpoints mapped telomeric and in cases with inv(14) centromeric or in the 3'-untranslated region of TCL1A. Regarding the T-cell receptor alpha (TRA) locus-TCL1A breakpoint junctions, all 17 breakpoints involved recombination signal sequences and 15 junctions contained nontemplated (N-) nucleotides. All T-PLL cases studied carried in-frame TRA rearrangements on the intact allele, which skewed significantly toward usage of distal/central TRAV/TRAJ gene segments as compared to the illegitimate TRA rearrangements. Our findings suggest that the oncogenic TRA-TCL1A/MTCP1 rearrangements in T-PLL occur during opening of the TRA locus, that is, during the progression from CD4+ immature single positive to early double positive thymocyte stage, just before physiologic TCL1A expression is silenced. The cell carrying such an oncogenic event continues maturation and rearranges the second TRA allele to achieve a functional T-cell receptor. Thereafter, it switches off RAG and DNTT expression in line with the mature T-cell phenotype at presentation of T-PLL.

10.
Arch Prev Riesgos Labor ; 22(4): 176-177, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-31633891

RESUMO

Currently there is an increase in the prevalence of asthma and it seems that occupational exposure is one of the factors contributing to this increase. "Occupational asthma" refers to new onset asthma induced by exposure to a substance in the workplace, whereas "workaggravated asthma" refers to pre-existing asthma that is then exacerbated in the workplace. A correct diagnosis requires a high index of suspicion and establishing a temporal relationship between symptoms and work. An incorrect diagnosis can lead to important socioeconomic consequences for the worker. In Spain, Royal Order 1299/2006 on 10 November (amended on May 4, 2018) establishes the criteria for its classification and official recognition. In the context of an allergic process, an occupational etiology should be considered and occupational physicians in an occupational healht service can serve as consultants to guide and manage these cases. In this case report we established an association between an occupational exposure and asthma in a worker which led to a series of steps resulting in its acceptance as an occupational disease.

11.
Br J Haematol ; 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31573078

RESUMO

Rituximab is a standard treatment for non-Hodgkin diffuse large B-cell (DLBCL) and follicular (FL) lymphomas. A subcutaneous formulation was developed to improve the resource use of intravenous rituximab, with comparable efficacy and safety profiles except for increased administration-related reactions (ARRs). MabRella was a phase IIIb trial to assess the safety of switching from intravenous to subcutaneous administration of rituximab during first-line induction/maintenance for DLBCL or FL, focusing on ARRs. Efficacy, satisfaction and quality of life were also assessed. Patients received subcutaneous rituximab plus standard induction chemotherapy for DLBCL or FL for 4-7 cycles, and/or every 2 months maintenance monotherapy for FL for 6-12 cycles. The study included 140 patients: DLBCL, n = 29; FL, n = 111. Ninety-five percent of patients experienced adverse events, reaching grade ≥3 in 38·6% and were serious in 30·0%. AARs occurred in 48·6%, mostly (84·9%) at the injection site, with only 2·1% of patients reaching grade 3. The end-of-induction complete/unconfirmed complete response rate was 69·6%. After a median follow-up of 33·5 months, median disease-/event-/progression-free and overall survivals were not attained. The Rituximab Administration Satisfaction Questionnaire showed improvements in overall satisfaction and the EuroQoL-5D a good quality-of-life perception at induction/maintenance end. Therefore, switching to subcutaneous rituximab showed no new safety issues and maintained efficacy with improved satisfaction and quality of life.

13.
Neurocirugia (Astur) ; 2019 Aug 07.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31401052

RESUMO

Choroid plexus papilloma is an uncommon tumour of the central nervous system, accounting for less than 1% of all intracranial neoplasm. The usual locations are the lateral ventricle in infants and children and the fourth ventricle in adults. The third ventricle is a rare location, with few cases reported in the literature. We describe the case of a 3-month-old boy who was admitted to our centre with signs of raised intracranial pressure. Neuroimaging studies showed a third ventricular mass with associated hydrocephalus. The patient underwent complete tumour removal through a transfrontal approach and ventriculo-peritoneal shunt surgery. Postoperative course of the child was uneventful and follow-up magnetic resonance imaging revealed no residual tumour. Histopathology of the resected lesion confirmed the diagnosis of choroid plexus papilloma. We discuss the clinical, radiological and histological features of this infrequent type of tumours.

14.
Waste Manag ; 97: 149-163, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31447022

RESUMO

The focus of this study is the pyrolysis and gasification of Refuse Derived Fuel (RDF) and fine fractions recovered from the excavation of landfill waste, with an emphasize on the characterization of the reactivity and kinetics of the char-steam gasification. The results from the pyrolysis tests demonstrated that CO and CO2 are the main produced gases during the pyrolysis of the finer fraction of landfill waste. This might be caused by the accumulation of degraded organic materials. The oil products from the pyrolysis of landfill waste were dominated by the derivative products of plastics such as styrene, toluene, and ethylbenzene. The chars obtained from the pyrolysis process were gasified under steam and steam/air atmospheres at temperatures between 800 and 900 °C by using thermogravimetry. The results from the gasification tests demonstrated that the char reactivity was mainly affected by the amount ratio between catalytic elements (K, Ca, Na, Mg, and Fe) over the inhibitor elements (Si, Al, and Cl), as well as the ash amount in the char. The results showed that char from the fine fraction of landfill waste has a higher reactivity than the RDF fraction, due to the high content of catalytic metal elements. These results suggest the use of a smaller sieve opening size for landfill waste separation processes may produce waste fuels with a high reactivity during gasification. Further, based on the thermogravimetric data, the kinetic parameters of landfill waste char gasification were calculated to have activation energies ranging from 54 to 128 kJ/mol.


Assuntos
Pirólise , Vapor , Atmosfera , Biomassa , Cinética
15.
Gigascience ; 8(8)2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31430368

RESUMO

BACKGROUND: We present the draft genome sequence of Dysdera silvatica, a nocturnal ground-dwelling spider from a genus that has undergone a remarkable adaptive radiation in the Canary Islands. RESULTS: The draft assembly was obtained using short (Illumina) and long (PaciBio and Nanopore) sequencing reads. Our de novo assembly (1.36 Gb), which represents 80% of the genome size estimated by flow cytometry (1.7 Gb), is constituted by a high fraction of interspersed repetitive elements (53.8%). The assembly completeness, using BUSCO and core eukaryotic genes, ranges from 90% to 96%. Functional annotations based on both ab initio and evidence-based information (including D. silvatica RNA sequencing) yielded a total of 48,619 protein-coding sequences, of which 36,398 (74.9%) have the molecular hallmark of known protein domains, or sequence similarity with Swiss-Prot sequences. The D. silvatica assembly is the first representative of the superfamily Dysderoidea, and just the second available genome of Synspermiata, one of the major evolutionary lineages of the "true spiders" (Araneomorphae). CONCLUSIONS: Dysderoids, which are known for their numerous instances of adaptation to underground environments, include some of the few examples of trophic specialization within spiders and are excellent models for the study of cryptic female choice. This resource will be therefore useful as a starting point to study fundamental evolutionary and functional questions, including the molecular bases of the adaptation to extreme environments and ecological shifts, as well of the origin and evolution of relevant spider traits, such as the venom and silk.

16.
Behav Ther ; 50(5): 910-923, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31422847

RESUMO

While evidence-based interventions can help the substantial number of veterans diagnosed with comorbid PTSD and depression, an emerging literature has identified sleep disturbances as predictors of treatment nonresponse. More specifically, predicting effects of residual insomnia and nightmares on postintervention PTSD and depressive symptoms among veterans with comorbid PTSD and depression has remained unclear. The present study used data from a clinical trial of Behavioral Activation and Therapeutic Exposure (BA-TE), a combined approach to address comorbid PTSD and depression, administered to veterans (N = 232) to evaluate whether residual insomnia and nightmare symptoms remained after treatment completion and, if so, whether these residual insomnia and nightmare symptoms were associated with higher levels of comorbid PTSD and depression at the end of treatment. Participants (ages 21 to 77 years old; 47.0% Black; 61.6% married) completed demographic questions, symptom assessments, and engagement-related surveys. Hierarchical multiple linear regression models demonstrated that residual insomnia was a significant predictor of PTSD and depression symptom reduction above and beyond the influence of demographic and engagement factors (e.g., therapy satisfaction). Consistent with previous research, greater residual insomnia symptoms were predictive of smaller treatment gains. Findings illustrate the potential significance of insomnia during the course of transdiagnostic treatment (e.g., PTSD and depression), leading to several important clinical assessment and treatment implications.


Assuntos
Depressão/complicações , Distúrbios do Início e da Manutenção do Sono/complicações , Transtornos do Sono-Vigília/complicações , Transtornos de Estresse Pós-Traumáticos/complicações , Veteranos/psicologia , Adulto , Idoso , Depressão/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Distúrbios do Início e da Manutenção do Sono/psicologia , Transtornos do Sono-Vigília/psicologia , Transtornos de Estresse Pós-Traumáticos/terapia , Veteranos/estatística & dados numéricos , Adulto Jovem
17.
J Commun Disord ; 82: 105924, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31446201

RESUMO

BACKGROUND: Research on comprehension of wh-dependencies in Broca's aphasia has resulted in discrepant findings, suggesting that structurally different languages may involve different comprehension patterns. AIMS: In the present study, we investigated whether Spanish speakers with Broca's aphasia rely on a language-specific cue that might facilitate comprehension of object wh-dependencies - the preposition a. Since the preposition a in Spanish indicates animate objects, reliance on this cue would facilitate comprehension of more demanding object wh-dependencies, cancelling out processing differences between structures with subject and object extractions. METHODS: We studied comprehension of subject vs. object quién ("who") and qué ("which") direct and embedded questions, and relative clauses introduced by que in seven speakers with aphasia (SWA): six with Broca's and one with mixed aphasia. Control data were obtained from ten neurologically intact elderly Spanish speakers. RESULTS: Mann-Whitney test revealed that compared to healthy controls, SWA had preserved comprehension of both subject and object who direct questions, object which direct questions, and object relative clauses. However, they exhibited considerably worse comprehension of subject which direct questions, all embedded questions regardless of the extraction site (subject, object) or type of wh-word (who, which), and subject relative clauses. Individual comprehension profiles obtained in a modified t-test and revised standardized difference test, while containing some variability, largely support lack of subject-object asymmetry and objects-better patterns. Furthermore, in direct questions, comprehension of who questions was better than the comprehension of which questions, while the opposite was found in embedded questions. CONCLUSIONS: The lack of significant subject-object asymmetry in most conditions, together with better comprehension of object than subject extractions in direct questions, indicates that Spanish SWA rely on the preposition a in the comprehension of object wh-dependencies. However, this strategy fails in more complex conditions (embedded questions), because the processing costs outweigh the facilitating effects of this cue, unless additional cues to the object are present (object relatives). The present findings have implications for the accounts of wh-dependencies in Broca's aphasia involving Discourse-linking, the Intervener hypothesis, and the Competition model.

18.
BMC Med Genomics ; 12(1): 112, 2019 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-31351478

RESUMO

BACKGROUND: Synthetic lethal interactions (SLIs) that occur between gene pairs are exploited for cancer therapeutics. Studies in the model eukaryote yeast have identified ~ 550,000 negative genetic interactions that have been extensively studied, leading to characterization of novel pathways and gene functions. This resource can be used to predict SLIs that can be relevant to cancer therapeutics. METHODS: We used patient data to identify genes that are down-regulated in breast cancer. InParanoid orthology mapping was performed to identify yeast orthologs of the down-regulated genes and predict their corresponding SLIs in humans. The predicted network graphs were drawn with Cytoscape. CancerRXgene database was used to predict drug response. RESULTS: Harnessing the vast available knowledge of yeast genetics, we generated a Humanized Yeast Genetic Interaction Network (HYGIN) for 1009 human genes with 10,419 interactions. Through the addition of patient-data from The Cancer Genome Atlas (TCGA), we generated a breast cancer specific subnetwork. Specifically, by comparing 1009 genes in HYGIN to genes that were down-regulated in breast cancer, we identified 15 breast cancer genes with 130 potential SLIs. Interestingly, 32 of the 130 predicted SLIs occurred with FBXW7, a well-known tumor suppressor that functions as a substrate-recognition protein within a SKP/CUL1/F-Box ubiquitin ligase complex for proteasome degradation. Efforts to validate these SLIs using chemical genetic data predicted that patients with loss of FBXW7 may respond to treatment with drugs like Selumitinib or Cabozantinib. CONCLUSIONS: This study provides a patient-data driven interpretation of yeast SLI data. HYGIN represents a novel strategy to uncover therapeutically relevant cancer drug targets and the yeast SLI data offers a major opportunity to mine these interactions.


Assuntos
Neoplasias da Mama/genética , Epistasia Genética , Proteína 7 com Repetições F-Box-WD/genética , Leveduras/genética , Redes Reguladoras de Genes , Humanos
19.
Ann Surg Oncol ; 26(12): 3883-3891, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31346895

RESUMO

BACKGROUND: Breast surgery is considered a clean surgery. However, surgical-site infection (SSI) rates are currently higher than predicted. Postoperative drains remain in situ for several days, with inevitable bacterial colonization and increased SSI risk. METHODS: This randomized controlled trial from October 2016 to January 2018 analyzed patients undergoing breast cancer surgery. The patients were randomized to either the standard drain care group or the antiseptic dressing group (3M® Tegaderm® CHG). Drain samples taken on postoperative days (PODs) 7 and 14 were cultured as standardized in the laboratory. Colonization rates and SSI were compared between the two groups. RESULTS: The study enrolled 104 patients with 167 surgical drains. The patients' clinical characteristics were similar in the two groups, with no statistically significant differences. Bulb fluid cultures at postoperative week (POW) 1 were positive for 42.9% of the control group and 28.9% of the antiseptic group (p = 0.06). Cultures from the POW 2 assessment were positive for 79.7% of the control group versus 54.9% of the antiseptic group (p = 0.001). Cultures from drain tubes were positive for 79.8% of the control group and 50.7% of the antiseptic group (p = < 0.001). In 11 patients, an SSI developed, 3 (5.8%) from the intervention and 8 (15.4%) from the control procedure (p = 0.11). CONCLUSION: The study findings demonstrated that the use of antiseptics at the drain exit site significantly reduced bacterial colonization of the closed drainage system in breast cancer surgery. Semi-permeable occlusive chlorhexidine-impregnated dressings provide an opportunity to test simple, safe, and low-cost interventions that may reduce drain bacterial colonization and SSI after breast surgery.

20.
Rev Esp Salud Publica ; 932019 Jul 19.
Artigo em Espanhol | MEDLINE | ID: mdl-31313755

RESUMO

OBJECTIVE: The literature points to the possibility of carrying out an intervention, from primary prevention to rehabilitation after a cardiac event, towards decreasing the incidence of such cardiac events and facilitating the return to daily life. The objective was to determine the effect of a cardiac rehabilitation intervention over perceived selfefficacy for patients who have suffered a cardiac event. METHODS: A community clinical trial, open, controlled, and randomised, was designed, and performed in primary care. To determine the sample size, the research team used the General Self-Efficacy Scale by Baessler and Schwarzer. The mean difference between groups considered of clinical relevance was of at least 6 points in the aforementioned General Self-Efficacy Scale. A precision of 95% and a test power of 80% were accepted. The result proposed a sample of 44 subjects in each group. Over 12 months, all subjects of legal age (N = 104), both sexes, that had concluded phase II in the cardiac rehabilitation unit of the university Hospital Puerta del Mar (Cadiz) were offered to participate in the study. The patients were informed about the study development, asking for their participation and providing them with a written informed consent. The subjects were randomly assigned to the intervention or control group through blind allocation (in a sealed envelope to the researcher), on a pre-set 2:1 ratio (two patients assigned to the intervention group to one assigned to the control group). A non-response or rejection to participate in the study record was made for the non-response analysis. RESULTS: A total of 89 subjects were included in the statistical analysis (response rate of 85.57%), with an average age of 63.01 years (SD: 8.75). The main dependent variable was the scores difference between groups, comparing means before and after the intervention, through the General Self-Efficacy Scale by Baessler & Schwarner. A mean difference of 6.0972 points was obtained between the intervention and the control groups (p<0.0053; 95% CI -4.1950 to -10.29), as a result of a 3.3750 mean points increase (standard deviation: 7.01) in the intervention group and a 3.3750 mean points decrease (standard deviation: 7.19) in the control group. In relation to the possible changes to be detected through the Hamilton anxiety scale and the Beck's depression inventory, after finishing the intervention, an estimate and contrast of population means was made between groups for the scores difference in the Hamilton scale, determined on the final visit, with no significant differences found (t-student 0.1211; p <0.9 43). Similarly, no significant differences were found between the groups for the means obtained in the variable "Beck's depression inventory scores difference" (t-student -0.1281; p<0.8987). CONCLUSIONS: The inclusion in cardiac rehabilitation programmes carried out in primary care improves the general perceived self-efficacy of patients who have suffered cardiac events.


Assuntos
Reabilitação Cardíaca/métodos , Serviços de Saúde Comunitária/organização & administração , Cardiopatias/reabilitação , Atenção Primária à Saúde/métodos , Autoeficácia , Centros Médicos Acadêmicos , Idoso , Atenção , Depressão/diagnóstico , Feminino , Cardiopatias/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Participação do Paciente , Escalas de Graduação Psiquiátrica , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Espanha/epidemiologia
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