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1.
Allergy Asthma Proc ; 45(1): 37-43, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-37993116

RESUMO

Background: Hereditary angioedema (HAE) is characterized by recurrent and unpredictable episodes of subcutaneous and/or submucosal swelling. Objective: To characterize the real-world treatment burden associated with existing on-demand therapies, we analyzed administration-site adverse drug reactions (ADR) associated with approved on-demand HAE therapies reported in the U.S. Food and Drug Administration's (FDA) Adverse Event Reporting System (FAERS). Methods: We searched the FAERS database from October 1, 2009, to March 31, 2022, for reports of all FDA-approved on-demand therapies for HAE: plasma-derived C1-inhibitor (pdC1-INH), ecallantide, icatibant, and recombinant C1-inhibitor (rhC1-INH). ADRs in which the drug was listed as the "primary suspect" were recorded for each drug. ADR preferred terms were grouped into 18 ADR domains based on semantic and/or clinical similarity, and the number of reports for each drug was calculated per year from the time of approval through March 2022, and descriptive results were presented. Preferred terms associated with administration-site ADRs identified from clinical trials and denoted on approved HAE drug U.S. package inserts were examined in a complementary analysis. Results: The highest reported rates of administration-site ADRs per year were site pain (17.9 reports per year), site erythema (7.4 per year), and site swelling (6.7 per year). RhC1-INH was the only drug for which access-site complications and/or malfunctions were reported (9.5 per year). PdC1-INH had the highest rate of incorrect route of product administration (3.7 per year). PdC1-INH showed statistically significant elevated reporting rate of injection-site reactions (reporting odds ratio [ROR] 3.59 [2.36-5.46]; empirical Bayesian geometric mean [EBGM] 1.97 [1.39]). Icatibant and rhC1-INH showed a statistical trend toward an increased reporting rate of administration-site reactions. Conclusion: Real-world data from FAERS were generally consistent with adverse events reported in clinical trials and suggest that patients experience substantial treatment burden associated with FDA-approved parenteral on-demand therapies for HAE attacks. It should be noted that ADR rates are not exposure adjusted and are based on spontaneous reporting.


Assuntos
Angioedemas Hereditários , Humanos , Angioedemas Hereditários/tratamento farmacológico , Teorema de Bayes , Resultado do Tratamento , Proteína Inibidora do Complemento C1/efeitos adversos , Plasma
2.
Nurse Educ Pract ; 79: 104037, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38968822

RESUMO

AIM: The aim of this study is to understand the significance of a disaster-related competence framework for Portuguese general nurses and identify from ICN - Core Competencies in Disaster Nursing version 2.0 core competencies description, those that are considered crucial for a competent preparedness and response in disaster scenarios. BACKGROUND: Research suggests that the occurrence of disasters will be more recurrent, requiring that nurses, pillars of any health system, have knowledge, skills and preparedness to face these events. DESIGN: An exploratory, cross-sectional qualitative study was carried out. Delphi method was used for data collection. METHODS: The study group consisted of technical-scientific council's presidents or coordinators/directors of nursing courses, nurses integrated in the Portuguese Council of Nurses and National Nursing Specialty Colleges and nurses with experience in the field of disasters. RESULTS: Findings revealed that there is consensus on sixteen competencies, considered relevant for developing general nurse knowledge and competence, both at a national or international level, in the field of disasters. CONCLUSIONS: The development of these competencies which establishes practice standards, building nurses skills and knowledge and ultimately, influencing nursing level-entry curricula's, conferring professional autonomy and self-regulation, in the field of disaster are fundamental. Furthermore, this study may serve as a reference for future alignment of competency frameworks between European Union countries or others.

3.
Med Mycol ; 50(2): 136-42, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21838617

RESUMO

We have compared multilocus sequence typing (MLST) and fluconazole susceptibility profiles of Candida glabrata bloodstream isolates obtained during active, population-based surveillance to those obtained from non-sterile sites of individuals with no evidence of fungal disease (i.e., non-invasive isolates) in the same US city during an overlapping time period. In each of the two populations, different proportions of the same six major sequence types (STs) encompassed 82% of the isolates. One ST was more prevalent in the candidemia population and two other STs were more prevalent in the non-invasive population, but the overall allelic frequencies within the groups suggested little, if any, genotypic diversity between them. Fluconazole susceptibility profiles of isolates from the patients in the two groups were not significantly different and were not associated with a particular sequence type. Our results support the hypothesis that C. glabrata strains causing bloodstream infections are genetically indistinguishable from those normally residing in/on the host, suggesting that relative pathogenicity may be closely tied to commensalism.


Assuntos
Antifúngicos/farmacologia , Candida glabrata/genética , Candida glabrata/isolamento & purificação , Candidemia/microbiologia , Candidíase/microbiologia , Fluconazol/farmacologia , Análise de Variância , Candida glabrata/efeitos dos fármacos , Candida glabrata/patogenicidade , Farmacorresistência Fúngica , Humanos , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Análise de Componente Principal
4.
Children (Basel) ; 9(9)2022 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-36138605

RESUMO

This paper presents a case report of a child with Neonatal Brachial Plexus Palsy on the right arm, with C5, C6, and C7 nerve injuries. The symptoms presented at birth and at the time of diagnosis were absence of movement in the right arm but with mobility of the fingers; internal rotation of the injured limb with elbow extension; active flexion of the wrist and fingers; and ulnar deviation of the hand. The rehabilitation plan followed the conservative approach and included different intervention strategies (passive and active mobilisation, kinesio tape, use of splints, bimanual stimulation, etc.) carried out by the occupational therapist and the physical therapist. The rehabilitation allowed the child to have a functional limb for daily activities, with bimanual motor integration and coordination; passive and active range of motion in the different joints except for pronation, sensibility, and maintained strength. In conclusion, it can be said that this case report describes a set of rehabilitation strategies that were used in the conservative treatment of a child with NBPP and the functional gains they allowed. Early intervention, parental involvement in the rehabilitation process, and continuous follow-up of the child favoured the prognosis and allowed the prevention of functional sequelae of the limb.

5.
Clin Infect Dis ; 52(4): e94-8, 2011 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-21220771

RESUMO

BACKGROUND: This article describes transmission of Cryptococcus neoformans by solid organ transplantation. METHODS: We reviewed medical records and performed molecular genotyping of isolates to determine potential for donor transmission of Cryptococcus. RESULTS: Cryptococcosis was diagnosed in 3 recipients of organs from a common donor with an undifferentiated neurologic condition at the time of death. Cryptococcal meningoencephalitis was later diagnosed in the donor at autopsy. The liver and 1 kidney recipient developed cryptococcemia and pneumonia and the other kidney recipient developed cryptococcemia and meningitis; 2 patients recovered with prolonged antifungal therapy. We tested 4 recipient isolates with multilocus sequence typing and found they had identical alleles. CONCLUSIONS: Our investigation documents the transmission of Cryptococcus neoformans by organ transplantation. Evaluation for cryptococcosis in donors with unexplained neurologic symptoms should be strongly considered.


Assuntos
Criptococose/transmissão , Cryptococcus neoformans/isolamento & purificação , Transplante de Órgãos/efeitos adversos , Idoso , Criptococose/microbiologia , Cryptococcus neoformans/genética , Feminino , Genótipo , Humanos , Doença Iatrogênica , Masculino , Pessoa de Meia-Idade , Tipagem Molecular , Técnicas de Tipagem Micológica
6.
Antimicrob Agents Chemother ; 55(9): 4465-8, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21690285

RESUMO

We surveyed 497 isolates of Aspergillus fumigatus collected from 2008 to 2009 as part of the ARTEMIS global surveillance study for elevated MIC values to itraconazole, voriconazole, and posaconazole. Sequencing of the cyp51A gene revealed that 8/29 isolates with elevated MIC values to one or more triazoles, all originating in China, contained the TR/L98H mutation associated with resistant European isolates of A. fumigatus. This is the first time the TR/L98H mutation has been identified outside Europe.


Assuntos
Antifúngicos/farmacologia , Aspergillus fumigatus/efeitos dos fármacos , Aspergillus fumigatus/genética , Sistema Enzimático do Citocromo P-450/genética , Proteínas Fúngicas/genética , Farmacorresistência Fúngica/genética , Itraconazol/farmacologia , Testes de Sensibilidade Microbiana , Mutação
7.
Eukaryot Cell ; 9(4): 619-25, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20190071

RESUMO

The human commensal yeast Candida glabrata is becoming increasingly important as an agent of nosocomial bloodstream infection. However, relatively little is known concerning the genetics and population structure of this species. We have analyzed 230 incident bloodstream isolates from previous and current population-based surveillance studies by using multilocus sequence typing (MLST). Our results show that in the U.S. cities of Atlanta, GA; Baltimore, MD; and San Francisco, CA during three time periods spanning 1992 to 2009, five populations of C. glabrata bloodstream isolates are defined by a relatively small number of sequence types. There is little genetic differentiation in the different C. glabrata populations. We also show that there has been a significant temporal shift in the prevalence of one major subtype in Atlanta. Our results support the concept that both recombination and clonality play a role in the population structure of this species.


Assuntos
Candida glabrata/genética , Candida glabrata/metabolismo , Candidíase , Vigilância da População , Recombinação Genética , Análise de Sequência de DNA , Técnicas de Tipagem Bacteriana , Baltimore/epidemiologia , Candida glabrata/classificação , Candidíase/sangue , Candidíase/epidemiologia , Candidíase/genética , Infecção Hospitalar/sangue , Infecção Hospitalar/genética , Infecção Hospitalar/microbiologia , Genética Populacional , Genótipo , Georgia/epidemiologia , Humanos , Filogenia , São Francisco/epidemiologia
8.
Mycoses ; 54(4): e154-62, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20337936

RESUMO

Candida spp. biofilms can be established on a wide range of materials, including implanted medical devices, and can display a resistant phenotype to antifungal drugs. Several factors, including host and surface properties, may influence the establishment and the development of Candida albicans biofilms on biotic and abiotic surfaces. We therefore selected a collection of C. albicans clinical isolates to evaluate the effect of surface and serum on biofilm attachment and development. Disc coupons from the CDC biofilm reactor were used in a well plate assay to study biofilm production on six different surfaces with or without the addition of serum: polycarbonate, polystyrene, stainless steel, Teflon, polyvinyl chloride or hydroxyapatite. Our results showed that serum increases in vitro C. albicans biofilm formation on a wide range of distinct surfaces including metallic and non-metallic materials, and that roughness and hydrophobicity can modulate C. albicans biofilm formation. These findings were also confirmed by scanning electron microscopy and it revealed the deposition of extracellular material on hyphae attached to a solid surface. Interestingly, adhesion can be significantly increased in the early stages of colonisation when serum is provided as a conditioning film in a surface-dependent manner.


Assuntos
Biofilmes/crescimento & desenvolvimento , Candida albicans/fisiologia , Microbiologia Ambiental , Soro/metabolismo , Propriedades de Superfície , Candida albicans/crescimento & desenvolvimento , Humanos , Hifas/crescimento & desenvolvimento , Hifas/fisiologia
9.
BMJ Case Rep ; 14(11)2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34753723

RESUMO

Helcococcus kunzii is a Gram-positive anaerobic facultative coccus that colonises the skin. Human infection is rare, with very few cases being described in the literature. The authors present the case of a 17-year-old man, with a history of cholesteatoma, diagnosed with mastoiditis complicated by intracranial empyema. After urgent surgical drainage, Gram staining revealed a Gram-negative bacillus and a Gram-positive coccus. The latter exhibited fastidious growth, presented as small grey colonies in blood agar, and was afterwards identified as H. kunzii The patient was started on intravenous antibiotics, switched to oral route after 8 weeks and fully recovered. To the best of our knowledge, this is the third case of an intracranial infection in which H. kunzii is involved, two of them occurring in patients with cholesteatoma.


Assuntos
Empiema , Infecções por Bactérias Gram-Positivas , Cocos Gram-Positivos , Adolescente , Firmicutes , Infecções por Bactérias Gram-Positivas/complicações , Infecções por Bactérias Gram-Positivas/diagnóstico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Humanos , Masculino
10.
J Clin Med ; 10(19)2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34640486

RESUMO

Confinement of the population has been one of the measures implemented by different governments to address the COVID-19 health crisis, and it has led to social isolation together with a disruption of daily activities. The aim of the study is to analyze psychological distress during the COVID-19 pandemic in Portugal. During the quarantine, a cross-sectional study was carried out on a sample of 2120 subjects over 18 years of age, resident and born in Portugal. Data were collected using a self-developed questionnaire that considered socio-demographic variables, physical symptoms, health conditions, and history of contact with COVID-19, as well as psychological alterations. The General Health Questionnaire (GHQ-12) was also included. Univariate and bivariate statistical analyses were performed. Predictive capacity was studied using logistic regression models. The results showed a higher percentage of individuals presenting psychological distress (57.2.0%), with a higher percentage identified among women (79.0%), and in people with a higher educational level (bachelor's + master's and doctorate) (75.8%). The predictor variables with the greatest weight were sex, educational level (graduation, master's, and doctorate), living with children or under 16 years of age, presence of symptoms, and quarantine in the last 14 days for having symptoms. Good self-assessment of health and working at home appear to be protective against psychological distress. These results highlight the impact of the COVID-19 pandemic on psychological distress and provide an opportunity to consider the need to implement specific multidisciplinary public health and mental health interventions in this pandemic situation.

11.
Pulmonology ; 27(2): 116-123, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33408043

RESUMO

INTRODUCTION: AGXT gene codes for the enzyme alanine glyoxylate aminotransferase, which is involved in hepatic peroxisomal metabolism of platinum-based chemotherapeutic agents. The association of genetic variant AGXT rs34116584 on the clinical outcome and response to chemotherapy of patients with non-small cell lung cancer (NSCLC) remains to be established. Our aim was to evaluate the association of functional AGXT gene polymorphism in NSCLC progression, considering as primary and secondary endpoint, progression free survival (PFS) and overall survival (OS), respectively. METHODS: Genotyping of theAGXT rs34116584 genetic polymorphism was performed by mass spectrometry on 168 DNA samples from patients with NSCLC (stages IIIA-IVB). Univariate survival analysis included the study of Kaplan-Meier curves with the Log-Rank test, while Cox regression was used as a multivariate analysis. RESULTS: Multivariate analysis showed shorter PFS for T carriers [HR=2.0, 95% CI, 1.4-3.0, p<0.0001] and shorter OS [HR=1.8, 95% CI, 1.1-3.0, p=0.017] globally, as well as in a subgroup of patients (n=144) treated with first line platinum-based chemotherapy [HR=2.0, 95% CI, 1.3-3.1, p=0.001] and [HR=1.8, 95% CI, 1.1-3.1, p=0.026], respectively. CONCLUSION: This polymorphism seems to have an impact on NSCLC progression, opening new perspectives for its inclusion as a pharmacogenetic predictor of response to platinum-based chemotherapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Farmacogenética/métodos , Transaminases/genética , Idoso , Antineoplásicos/uso terapêutico , Carboplatina/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Cisplatino/uso terapêutico , Progressão da Doença , Feminino , Genótipo , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Polimorfismo Genético/genética , Valor Preditivo dos Testes , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Índice de Gravidade de Doença , Transaminases/metabolismo
12.
J Clin Microbiol ; 48(9): 3062-7, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20592158

RESUMO

Prospective population surveillance has been conducted for candidemia in Brazil (A. L. Colombo, M. Nucci, B. J. Park, et al., J. Clin. Microbiol. 44:2816-2823, 2006). In the present study, a total of 63 isolates from 61 patients, representing 11 medical centers from nine geographic regions, were characterized by multilocus sequence typing (MLST). A total of 48 unique profiles or diploid sequence types (DSTs) were observed, with nine new sequence types (STs) and 32 new DSTs. There were no apparent correlations between center/region and DST patterns. Subtypes were compared to those in a known characterized reference set, including a large database of strains obtained worldwide. Significantly, only one C. albicans group 2 isolate was found in our collection, although isolates from this particular group are commonly found worldwide. These data, combined with information from other previously reported studies, establish a statistically significant diminishment of group 2 strains in Central and South America, including Mexico and portions of the Southwestern United States.


Assuntos
Candida/classificação , Candida/genética , Candidíase/epidemiologia , Impressões Digitais de DNA , Fungemia/epidemiologia , Técnicas de Tipagem Micológica , Brasil/epidemiologia , Candida/isolamento & purificação , DNA Fúngico/química , DNA Fúngico/genética , Geografia , Humanos , Epidemiologia Molecular , Análise de Sequência de DNA
13.
Med Mycol ; 48(5): 757-62, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20105100

RESUMO

Multilocus sequence typing (MLST) is a useful tool to explore the phylogenetics and epidemiology of Candida albicans isolates recovered from cases of invasive candidiasis. The goal of this study was to determine whether the same or different strains were responsible for persistent or recurrent fungemia through the use of MLST and ABC typing on sequential C. albicans isolates from the same patient. We applied both typing methods to 21 C. albicans strains recovered from 8 patients with persistent or recurrent candidemia. The isolates were collected during a multicenter surveillance study in four public tertiary care hospitals in Brazil. Persistent candidemia was defined as two or more blood cultures positive for C. albicans on 2 or more separate days. Recurrent candidemia was defined as an episode of candidemia occurring at least 1 month after the apparent complete resolution of an infectious episode caused by Candida species. We observed that, except for one patient, all strains from the first and second samples of the same patient showed the same MLST diploid sequence type (DST), ABC type and susceptibility profile to antifungals. Three distinct strains, well discriminated by MLST, were found in the seven samples collected sequentially over 10 days from one patient. The strains from the first four samples were indistinguishable, the fifth and sixth were also indistinguishable but different from the first four and seventh samples. Significantly, the seventh strain was the only C. albicans clade 2 isolate found in our total collection involving 61 patients, although clade 2 is commonly found worldwide. To the best of our knowledge, this is the first study describing the recovery of three distinct C. albicans strains in the same patient with a persistent blood stream infection within a short period of time.


Assuntos
Candida albicans/classificação , Candida albicans/genética , Candidíase/microbiologia , Impressões Digitais de DNA , Fungemia/microbiologia , Técnicas de Tipagem Micológica , Brasil , Candida albicans/isolamento & purificação , DNA Fúngico/química , DNA Fúngico/genética , Genótipo , Hospitais , Humanos , Epidemiologia Molecular , Recidiva , Análise de Sequência de DNA
14.
Diabetol Metab Syndr ; 12(1): 107, 2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33292447

RESUMO

INTRODUCTION: Adult-onset autoimmune diabetes (AID) has two different phenotypes: classic type 1 diabetes mellitus (T1DM), with insulin requirement just after diagnosis, and latent autoimmune diabetes in adults (LADA). The purpose of this study is to characterize patients with AID followed on a tertiary centre, comparing classic T1DM and LADA. METHODS: We collected data from patients with diabetes and positive islet autoantibodies, aged 30 years old and over at diagnosis. Patients who started insulin in the first 6 months were classified as T1DM and patients with no insulin requirements in the first 6 months were classified as LADA. Data regarding clinical presentation, autoantibodies, A1C and C-peptide at diagnosis, pharmacologic treatment and complications were analysed. RESULTS: We included 92 patients, 46 with classic T1DM and 46 with LADA. The percentage of females was 50% in T1DM group and 52.1% in LADA group. The median age at diagnosis was 38 years (IQR-15) for T1DM and 42 years (IQR-15) for LADA (p = 0.057). The median time between diagnosis of diabetes and diagnosis of autoimmune aetiology was 0 months in T1DM group and 60 months in LADA group (p < 0.001). The mean BMI at diagnosis was 24.1 kg/m2 in T1DM group and 26.1 kg/m2 in LADA group (p = 0.042). In T1DM group, 67.4% of the patients had more than one positive autoantibody, comparing to 41.3% of LADA patients (p = 0.012). There was no statistical difference in what concerns to title of GAD autoantibodies, A1C and C-peptide at diagnosis of autoimmune aetiology. The presence of symptoms at diagnosis was associated with T1DM group (p < 0.001). The median daily insulin dose was 40 IU for T1DM (0.58 IU/kg) and 33.5 IU for LADA (0.57 IU/kg), with no statistical difference. LADA patients were more often under non-insulin antidiabetic drugs (p = 0.001). At 10 years follow up, 21.1% of T1DM patients and 63.3% of LADA patients had microvascular complications (p = 0.004). Diabetic nephropathy was present in 23.5% of T1DM patients and 53.3% of LADA patients (p = 0.047). At the last evaluation, 55.6% of T1DM and 82.6% of LADA patients had metabolic syndrome and this difference was independent of diabetes duration. CONCLUSION: Patients with classic T1DM presented more often with symptoms, lower BMI and higher number of autoantibodies, which may be related to a more aggressive autoimmune process. Patients with LADA developed more frequently microvascular complications for the same disease duration, namely diabetic nephropathy, and had more often metabolic syndrome.

15.
Vaccine ; 38(5): 1211-1215, 2020 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-31767464

RESUMO

The present study aims to contribute to the evaluation of the serological impact of vaccination against mumps in Portugal, measuring anti-mumps IgG (MuIgG) levels in cord sera and the corresponding proportions of seropositive newborns, and their association with potential predictive variables. The data from this study came from 198 umbilical cord sera. Detailed vaccination records were available for all mothers. MuIgG were measured in the sera, using a commercial immunoassay. The geometric mean concentration (GMC) of MuIgG was 31.7 RU/ml. Seropositive/immune sera (concentration ≥16 RU/ml) were 75.3%. While 49 mothers were "unsure" about ever having had mumps, 46 said they had had the disease and 103 said they had not had it. Eighty eight women did not receive a single dose of MMR while the other received 1 or 2 doses, with different combinations of vaccine strains. This study found that recalling mumps was predictive of higher MuIgG GMC and seropositivity. Maternal age and vaccination status were not associated with GMC or seropositivity. Nevertheless, in the small subset of newborns from vaccinated mothers not recalling mumps, receiving two doses was predictive of higher GMC than just receiving one. Maternal recall of mumps is highly predictive of seropositivity while not recalling the disease results in numerous false-negatives. This is consistent with other studies and with the fact that infection with mumps virus can result in a wide range of clinical manifestations. We agree on the need for further research to support a recommendation of a three (or more)-dose MMR strategy but we also believe that evidence is fast accumulating in favour of a higher dose strategy. The issue of waning immunity due to vaccines when vaccination succeeds in controlling (and nationally eliminating) target diseases like measles and mumps must be urgently taken into account.


Assuntos
Anticorpos Antivirais/sangue , Sangue Fetal/imunologia , Caxumba , Vacinação , Feminino , Humanos , Imunoglobulina G/sangue , Recém-Nascido , Rememoração Mental , Mães , Caxumba/imunologia , Caxumba/prevenção & controle , Portugal
16.
Nat Commun ; 11(1): 5445, 2020 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-33116115

RESUMO

Single-cell RNA sequencing studies on gene co-expression patterns could yield important regulatory and functional insights, but have so far been limited by the confounding effects of differentiation and cell cycle. We apply a tailored experimental design that eliminates these confounders, and report thousands of intrinsically covarying gene pairs in mouse embryonic stem cells. These covariations form a network with biological properties, outlining known and novel gene interactions. We provide the first evidence that miRNAs naturally induce transcriptome-wide covariations and compare the relative importance of nuclear organization, transcriptional and post-transcriptional regulation in defining covariations. We find that nuclear organization has the greatest impact, and that genes encoding for physically interacting proteins specifically tend to covary, suggesting importance for protein complex formation. Our results lend support to the concept of post-transcriptional RNA operons, but we further present evidence that nuclear proximity of genes may provide substantial functional regulation in mammalian single cells.


Assuntos
Núcleo Celular/genética , Redes Reguladoras de Genes , Mapas de Interação de Proteínas , Animais , Linhagem Celular , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Técnicas de Inativação de Genes , Variação Genética , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Células-Tronco Embrionárias Murinas/citologia , Células-Tronco Embrionárias Murinas/metabolismo , RNA-Seq , Ribonuclease III/deficiência , Ribonuclease III/genética , Ribonuclease III/metabolismo , Análise de Célula Única , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Transcriptoma
17.
Cancers (Basel) ; 12(12)2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33353148

RESUMO

INTRODUCTION: The renin-angiotensin system (RAS) is involved in cell proliferation, immunoinflammatory response, hypoxia and angiogenesis, which are critical biological processes in lung cancer. Our aim was to study the association of putatively functional genetic polymorphisms in genes coding for proteins involved in RAS, hypoxia and angiogenesis with non-small cell lung cancer (NSCLC) prognosis. METHODS: Genotyping of 52 germline variants from genes of the RAS and hypoxic/angiogenic factors/receptors was performed using MassARRAY iPLEX Gold in a retrospective cohort (n = 167) of advanced NSCLC patients. Validation of the resulting genetic markers was conducted in an independent group (n = 190), matched by clinicopathological characteristics. RESULTS: Multivariate analysis on the discovery set revealed that MME rs701109 C carriers were protected from disease progression in comparison with homozygous T (hazard ratio (HR) = 0.5, 95% confidence interval (CI) = 0.2-0.8, p = 0.010). Homozygous A and T genotypes for KDR rs1870377 were at increased risk for disease progression and death compared to heterozygous (HR = 1.7, 95% CI = 1.2-2.5, p = 0.005 and HR = 2.1, 95% CI = 1.2-3.4, p = 0.006, respectively). Carriers of homozygous genotypes for ACE2 rs908004 presented increased risk for disease progression, only in the subgroup of patients without tumour actionable driver mutations (HR = 2.9, 95% CI = 1.3-6.3, p = 0.010). Importantly, the association of homozygous genotypes in MME rs701109 with risk for disease progression was confirmed after multivariate analysis in the validation set. CONCLUSION: This study provides evidence that MME polymorphism, which encodes neprilysin, may modulate progression-free survival in advanced NSCLC. Present genetic variation findings will foster basic, translational, and clinical research on their role in NSCLC.

18.
Rev Paul Pediatr ; 39: e2019372, 2020.
Artigo em Inglês, Português | MEDLINE | ID: mdl-33206841

RESUMO

OBJECTIVE: To construct a scale of adolescents' attitudes towards sexuality and to determine their psychometric characteristics. METHODS: Methodological study conducted with 394 students from the 8th to 12th grades of a school in central Portugal. They answered a questionnaire consisting of the Adolescent Students' Attitude Scale for Sexuality (E3AS) and socio-demographic and academic data. The project received a favorable opinion from the National Data Protection Commission (authorization No. 10421/2017). Construct validity analysis was performed through exploratory factor analysis and internal consistency was performed through Cronbach's alpha. A maximum error probability of 5% was considered. RESULTS: The mean age of the sample was 14.9±1.4 years, with 53.3% being female. The instrument consisted of 34 items distributed into five factors: F1. Family planning and sex education (α=0.826); F2. First sexual relationship (α=0.819); F3. Violation of sexual rights and who to turn to in the event of unplanned pregnancies (α=0.695); F4. Gender expression and identity (α=0.542), and F5. Unplanned pregnancy and parenting (α= 0.761), with a total alpha value of 0.766, accounting for 45.3% of total variance. CONCLUSIONS: The psychometric adequacy of the E3AS for the Portuguese population allows us to affirm that it is a valid and reliable instrument that can be used in future studies to assess the attitudes of adolescent students towards sexuality.


Assuntos
Comportamento Sexual/psicologia , Inquéritos e Questionários/normas , Adolescente , Atitude , Análise Fatorial , Feminino , Humanos , Masculino , Portugal , Reprodutibilidade dos Testes
19.
Sci Adv ; 5(10): eaax4199, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31663024

RESUMO

Cells with high ploidy content are common in mammalian extraembryonic and adult tissues. Cell-to-cell fusion generates polyploid cells during mammalian development and tissue regeneration. However, whether increased ploidy can be occasionally tolerated in embryonic lineages still remains largely unknown. Here, we show that pluripotent, fusion-derived tetraploid cells, when injected in a recipient mouse blastocyst, can generate diploid cells upon ploidy reduction. The generated diploid cells form part of the adult tissues in mouse chimeras. Parental chromosomes in pluripotent tetraploid cells are segregated through tripolar mitosis both randomly and nonrandomly and without aneuploidy. Tetraploid-derived diploid cells show a differentiated phenotype. Overall, we discovered an unexpected process of controlled genome reduction in pluripotent tetraploid cells. This mechanism can ultimately generate diploid cells during mouse embryo development and should also be considered for cell fusion-mediated tissue regeneration approaches.


Assuntos
Embrião de Mamíferos/fisiologia , Desenvolvimento Embrionário/fisiologia , Animais , Blastocisto/fisiologia , Linhagem Celular , Linhagem da Célula/genética , Linhagem da Célula/fisiologia , Quimera/genética , Quimera/fisiologia , Cromossomos/genética , Diploide , Genoma/genética , Camundongos , Ploidias
20.
J Burn Care Res ; 40(1): 112-119, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30481299

RESUMO

Sepsis is the main cause of death in burns. Early institution of antimicrobial therapy is crucial to optimize outcomes but superfluous therapy increases adverse events, microbial resistance, and costs. Blood cultures are the gold standard for diagnosis but can take 48 to 72 hours. Biomarkers are used to help sepsis diagnosis and distinction between Gram-negative and Gram-positive bacterial cause. The aim of this work is to evaluate procalcitonin (PCT) accuracy for this distinction in burn patients. Retrospective observational study of adult septic burn patients with ≥15% total burn surface area admitted from January 2011 to December 2014 at a Burn Unit in Portugal. A statistical analysis was done, evaluating the correlation between PCT levels on the day of the first positive blood culture and microbiological data for Gram-negative and Grand-positive bacteria. Patients with mixed bacterial and/or fungal blood cultures were excluded. Data were summarized by quartiles statistics. Blood cultures were positive in 189 patients: 75 (39.7%) showed growth for Gram-negative and 114 (60.3%) for Gram-positive bacteria. Patients with Gram-negative bacteria have significantly higher PCT levels. Receiver operating characteristic curve analysis showed accuracy for Gram-negative discrimination with area under the curve = 0.687. Most elevated levels were related to nonfermentative Gram-negative bacteria and by Klebsiella pneumoniae and other Enterobacteriaceae. PCT levels were significantly higher in burn patients with Gram-negative sepsis comparing to patients with Gram-positive sepsis and controls. The determination of PCT levels may help the choice of empirical antimicrobial therapy while microbiological culture results are not available, despite not fully ensuring the desirable degree of precision.


Assuntos
Queimaduras/microbiologia , Infecções por Bactérias Gram-Negativas/sangue , Infecções por Bactérias Gram-Positivas/diagnóstico , Pró-Calcitonina/sangue , Sepse/microbiologia , Idoso , Biomarcadores/sangue , Hemocultura , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Portugal , Estudos Retrospectivos
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