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1.
J Antimicrob Chemother ; 77(12): 3340-3348, 2022 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-36173394

RESUMO

BACKGROUND: Typing of staphylococcal cassette chromosome mec (SCCmec) elements is commonly used for studies on the molecular epidemiology of MRSA. OBJECTIVES: To perform an investigation centred on uncovering the reasons for misclassification of MRSA clonal complex 5 (CC5) SCCmec type II clinical isolates in our laboratory. METHODS: MRSA isolates from CC5 were subjected to WGS and SCCmec typing. RESULTS: This investigation led to the discovery that the classification failure was due to an insertion of IS1272 carrying the fabI gene on a transposable element (TnSha1) that confers increased MIC to the biocide triclosan. Genomic analysis revealed that fabI was present in 25% of the CC5 MRSA isolates sampled. The frequency of TnSha1 in our collection was much higher than that observed among publicly available genomes (0.8%; n = 24/3142 CC5 genomes). Phylogenetic analyses revealed that genomes in different CC5 clades carry TnSha1 inserted in different integration sites, suggesting that this transposon has entered CC5 MRSA genomes on multiple occasions. In at least two genotypes, ST5-SCCmecII-t539 and ST5-SCCmecII-t2666, TnSha1 seems to have entered prior to their divergence. CONCLUSIONS: Our work highlights an important misclassification problem of SCCmecII in isolates harbouring TnSha1 when Boye's method is used for typing, which could have important implications for molecular epidemiology of MRSA. The importance of increased-MIC phenotype is still a matter of controversy that deserves more study given the widespread use of triclosan in many countries. Our results suggest expanding prevalence that may indicate strong selection for this phenotype.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Triclosan , Humanos , Infecções Estafilocócicas/epidemiologia , Triclosan/farmacologia , Testes de Sensibilidade Microbiana , Filogenia , DNA Bacteriano/genética , Cromossomos
2.
BMC Psychiatry ; 20(1): 385, 2020 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-32703170

RESUMO

BACKGROUND: Patients with somatoform, depressive or anxiety disorders often don't respond well to medical treatment and experience many side effects. It is thus of clinical relevance to identify alternative, scientifically based, treatments. Our approach is based on the recent evidence that urbanicity has been shown to be associated with an increased risk for mental disorders. Conversely, green and blue environments show a dose-dependent beneficial impact on mental health. METHODS: Here we evaluate the effect of viewing stimuli of individuals in an alpine environment on emotional analytics in 183 patients with psychiatric disorders (mostly somatoform, depressive and anxiety disorders) and 315 healthy controls (HC). Emotional analytics (valence: unhappy vs happy, arousal: calm vs excited, dominance: controlled vs in control) were assessed using the Self-Assessment Manikin. Further parameters related to mental health and physical activity were recorded. RESULTS: Emotional analytics of patients indicated that they felt less happy, less in control and had higher levels of arousal than HC when viewing neutral stimuli. The comparison alpine>neutral stimuli showed a significant positive effect of alpine stimuli on emotional analytics in both groups. Patients and HC both felt attracted to the scenes displayed in the alpine stimuli. Emotional analytics correlated positively with resilience and inversely with perceived stress. CONCLUSIONS: Preventive and therapeutic programs for patients with somatoform, depressive and anxiety disorders should consider taking the benefits of natural outdoor environments, such as alpine environments, into account. Organizational barriers which are preventing the implementation of such programs in clinical practice need to be identified and addressed.


Assuntos
Transtornos de Ansiedade , Emoções , Nível de Alerta , Exercício Físico , Humanos , Transtornos Somatoformes
3.
Eur Arch Psychiatry Clin Neurosci ; 269(5): 543-553, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30046989

RESUMO

OBJECTIVE: Physical activity (PA) in an outdoor environment has been shown to exert positive effects on mental well-being beyond those found for PA indoors. The specific effect of an alpine environment has not been investigated so far. Here we evaluate the association of PA in an alpine environment with resilience and quality of life (QOL) in patients with psychosomatic disorders and controls. METHODS: 194 patients with psychosomatic disorders (mostly somatoform disorder and major depressive syndrome) and 326 healthy controls were included in this web-based cross-sectional study. PA was scored using an adapted version of the Global Physical Activity Questionnaire including the environmental aspect (indoor, outdoor, alpine environment). Resilience was assessed using the Resilience Scale-13, QOL using the WHOQOL-BREF. Group comparisons, correlation and mediation analyses were performed. RESULTS: Patients showed significantly lower levels of resilience (p < 0.001) and QOL (p < 0.001) compared to controls. PA in an alpine environment was associated with resilience (patients: r = 0.35, p < 0.001; controls r = 0.18, p < 0.001). There were no significant associations between PA in other environments (outdoor or indoor) and resilience. PA in all three environments correlated with subcategories of QOL. The effect of PA in an alpine environment on QOL was partly mediated by resilience in patients (68% of total effect mediated, p < 0.001) and controls (49% mediated, p = 0.006). CONCLUSION: There is a positive effect of PA in an alpine environment on mental health beyond that of physical activity itself. Preventive and therapeutic programs should thus include physical activity, but also take additional benefits of natural environments into account.


Assuntos
Meio Ambiente , Exercício Físico/psicologia , Transtornos Psicofisiológicos/psicologia , Qualidade de Vida/psicologia , Resiliência Psicológica , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Adulto Jovem
4.
Cogn Process ; 20(1): 125-131, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30377871

RESUMO

Studies indicate that a brief period of wakeful rest after learning supports memory retention, whereas distraction weakens it. It is open for investigation whether advanced age has a significant effect on the impact of post-learning wakeful rest on memory retention for verbal information when compared to a cognitively demanding distraction task. In this study, we examined (1) whether post-learning rest promotes verbal memory retention in younger and older adults and (2) whether the magnitude of the rest benefit changes with increasing age. Younger adults and older adults learned and immediately recalled two consecutive word lists. After one word list, participants rested wakefully for 8 min; after the other list, they solved matrices. Memory performance was again tested in a surprise free recall test at the end of the experimental session. We found that, overall, younger adults outperformed older adults. Also, memory retention was higher following a wakeful rest phase compared to distraction. A detailed analysis revealed that this wakeful rest benefit was significant for the older adults group, whereas the younger adults group retained a similar amount of information in both post-encoding conditions. We assume that older adults can profit more from a wakeful rest phase after learning and are more prone to distraction than younger adults. With increasing age, a short break immediately after information uptake may help better retain the previously learned information, while distraction after learning tends to weaken memory retention.


Assuntos
Memória/fisiologia , Descanso/psicologia , Vigília/fisiologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Aprendizagem , Rememoração Mental , Pessoa de Meia-Idade , Distribuição Aleatória , Adulto Jovem
5.
BMC Cancer ; 17(1): 599, 2017 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-28854893

RESUMO

BACKGROUND: Cancer survivorship is of increasing importance in post-treatment care. Sexual health (SH) and femininity can be crucial issues for women surviving cancer. We aimed to determine a more complete understanding of the contribution that a breast cancer (BC) diagnosis and its treatment exert on patients' follow-up SH. For this purpose, self-reported levels and predictors of SH in breast cancer survivors (BCS) were compared with those of women with no previous or current BC (WNBC). METHODS: BCS and WNBC underwent a comprehensive, cross-sectional patient-reported outcome (PRO) assessment. Validated PRO instruments were used to measure SH, body image, anxiety and depression and menopausal symptoms. Assessments were performed within the routine clinical setting. Instruments used were the Sexual Interest and Desire Inventory - Female, Sexual Activity Questionnaire, Body Image Scale, Hospital Anxiety and Depression Scale and the Menopause-Specific Quality of Life Questionnaire. RESULTS: One hundred five BCS (average time since diagnosis of 3 years) and 97 WNBC with a mean age of 49 years completed the assessment. SH was significantly worse in BCS compared to WNBC (p = 0.005; BCS SIDI-F mean = 24.9 vs. WNBC mean = 29.8). 68.8% of BCS and 58.8% of WNBC met criteria of a hypo-active sexual desire disorder. Higher depressive symptoms, higher age and lower partnership satisfaction were predictive for poorer SH in BCS. CONCLUSION: SH problems are apparent in BCS and differ significantly from those seen in the general population. Consequently, BC survivorship care should include interventions to ameliorate sexual dysfunction and provide help with depressive symptoms and partnership problems, which are associated with poor BCS SH.


Assuntos
Neoplasias da Mama/fisiopatologia , Neoplasias da Mama/psicologia , Sobreviventes de Câncer/psicologia , Adulto , Ansiedade/fisiopatologia , Ansiedade/psicologia , Imagem Corporal/psicologia , Estudos Transversais , Depressão/fisiopatologia , Depressão/psicologia , Feminino , Humanos , Pessoa de Meia-Idade , Autorrelato , Comportamento Sexual/fisiologia , Comportamento Sexual/psicologia , Disfunções Sexuais Fisiológicas/fisiopatologia , Disfunções Sexuais Psicogênicas/psicologia , Saúde Sexual , Inquéritos e Questionários
6.
Value Health ; 20(4): 610-617, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28408003

RESUMO

BACKGROUND: Currently there is little knowledge on real-life sustainability of routine patient-reported outcome (PRO) measurement and the representativeness of collected data. OBJECTIVES: The investigation of routine PRO with regard to noncompletion bias and long-term adher- ence, considering the potential impact of mode of assessment (MOA) (paper-pencil vs. electronic PRO [ePRO]) and patient characteristics. METHODS: At our department, routine PRO measurement in oncological patients is being done since 2005 using different MOA (paper-pencil assessment until 2011 and ePRO assessment from 2011 onward). We analyzed two different patient groups: patients eligible in both periods (both-MOA group) and patients eligible in only one period (one-MOA group). The primary outcome was PRO noncompletion (100% missing questionnaires). The secondary outcome was poor PRO adherence (>20% missing questionnaires). Multivariate logistic regression models were developed, testing the impact of MOA and patient characteristics on the outcomes in the different patient groups. RESULTS: Data from 1484 eligible patients were included in the analyses. Most of the patients could be included in PRO assessment at least once. PRO noncompletion rates were clearly higher during paper-pencil assessment (odds ratios between 2.72 and 4.31), as were poor PRO adherence rates (odd ratio 2.23). Analyses of potential bias by patient characteristics showed that male patients had a higher risk of poor adherence. Other factors with significant impact were age, country, and cancer diagnosis, but results were indecisive. CONCLUSIONS: ePRO increased the feasibility of our clinical routine PRO data for retrospective analyses by increasing completion rates. In general, potential completion bias regarding certain patient characteristics requires attention before generalizing results to the respective populations.


Assuntos
Computadores de Mão , Indicadores Básicos de Saúde , Neoplasias/radioterapia , Cooperação do Paciente , Medidas de Resultados Relatados pelo Paciente , Inquéritos e Questionários , Adulto , Idoso , Viés , Estudos de Viabilidade , Feminino , Nível de Saúde , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias/diagnóstico , Razão de Chances , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Software , Fatores de Tempo , Resultado do Tratamento
7.
J Dairy Res ; 84(2): 202-205, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28290267

RESUMO

This Regional Research Communication describes the characterisation of ampicillin, penicillin and tetracycline resistance in Staphylococcus aureus isolated from bovine subclinical mastitis in Minas Gerais State, Brazil. Ninety S. aureus isolates from bovine mastitis exhibiting phenotypic resistance to ampicillin, penicillin and/or tetracycline were selected for this study. The minimum inhibitory concentration (MIC) of each antibiotic was determined using the E-Test® and the production of beta-lactamase was determined by cefinase disks. The resistance genes blaZ, tet(K), tet(L), tet(M), and tet(O) were investigated by PCR in all of the isolates. The MIC results classified 77, 83 and 71% of the isolates as resistant to ampicillin, penicillin and tetracycline, respectively. The MIC50 and MIC90 were, respectively, 1 and 2 µg/ml for ampicillin, 0·5 and 1 µg/ml for penicillin and 32 and 64 µg/ml for tetracycline. Eighty-six per cent of beta-lactamase producing isolates were detected. Of the 90 isolates investigated, 97% amplified blaZ, 84% amplified tet(K), 9% amplified tet(L), 2% amplified tet(M) and 1% amplified tet(O). Seventy-nine isolates (88%) showed blaZ together with at least one tet gene. S. aureus isolates showed high MIC50 and MIC90 values for the three antimicrobials. The blaZ and tet(K) genes were widespread in the herds studied, and most of the isolates harboured blaZ and tet(K) concomitantly.


Assuntos
Mastite Bovina/microbiologia , Leite/microbiologia , Resistência às Penicilinas , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/isolamento & purificação , Resistência a Tetraciclina , Ampicilina/administração & dosagem , Animais , Brasil , Bovinos , Feminino , Testes de Sensibilidade Microbiana , Resistência às Penicilinas/genética , Penicilinas/administração & dosagem , Reação em Cadeia da Polimerase/veterinária , Staphylococcus aureus/genética , Tetraciclina/administração & dosagem , Resistência a Tetraciclina/genética , beta-Lactamases/biossíntese
8.
Health Qual Life Outcomes ; 14(1): 127, 2016 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-27614762

RESUMO

BACKGROUND: Gastroenteropancreatic neuroendocrine tumours (GEP-NET) are often slow-growing and patients may live for years with metastasised disease. Hence, along with increasing overall and progression-free survival, treatments aim at preserving patients' well-being and health-related quality of life (HRQoL). However, studies on systematic HRQoL assessment in patients with GEP-NET are scarce. Therefore, the purpose of the current review is to systematically evaluate the methodological quality of the identified studies. METHODS: A targeted database search was performed in PubMed, EMBASE, and CENTRAL. Data extraction was conducted by two independent researchers according to predefined criteria. For study evaluation, the Minimum Standard Checklist for Evaluating HRQoL Outcomes in Cancer Clinical Trials and the CONSORT Patient-Reported Outcome extension were adapted. RESULTS: The database search yielded 48 eligible studies. We found the awareness for the need of HRQoL measurement to be growing and application of cancer-specific instruments gaining acceptance. Overall, studies were too heterogeneous in terms of patient characteristics and treatment interventions to draw clear conclusions for clinical practice. More importantly, a range of methodological shortcomings has been identified which were mainly related to the assessment and statistical analysis, as well as the reporting and interpretation of HRQoL data. CONCLUSION: Despite an increasing interest in HRQoL in GEP-NET patients, there is still a lack of knowledge on this issue. A transfer of HRQoL results into clinical practice is hindered not only by the scarceness of studies, but also by the often limited quality of HRQoL processing and reporting.


Assuntos
Neoplasias Intestinais/psicologia , Tumores Neuroendócrinos/psicologia , Neoplasias Pancreáticas/psicologia , Qualidade de Vida/psicologia , Neoplasias Gástricas/psicologia , Intervalo Livre de Doença , Nível de Saúde , Humanos , Avaliação de Resultados em Cuidados de Saúde , Anos de Vida Ajustados por Qualidade de Vida
9.
J Clin Epidemiol ; 162: 1-9, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37517504

RESUMO

OBJECTIVES: This review addresses the common problem of missing patient-reported outcome (PRO) data in clinical trials by assessing the current practice of their statistical handling as reported in publications of randomized controlled trials (RCTs) in patients with breast cancer. STUDY DESIGN AND SETTING: We searched PubMed to identify RCTs evaluating biomedical treatments in breast cancer patients with at least one PRO endpoint published between January 2019 and February 2022. Two reviewers independently assessed the eligibility of the publications for this scoping review and extracted prespecified information on missing PRO data and related statistical practices. RESULTS: Of 1,598 publications identified, 118 trials met the inclusion criteria. Eighty-eight (74.6%) trials reported the extent of missing data, with 11 (9.3%) not containing any missing PRO data. Twenty-one (19.6%) trials explicitly stated the statistical approach for handling missing data, with a preference for single imputation over multiple imputation approaches (57.2%/19.0%). Only six (5.6%) trials reported a sensitivity analysis to examine the extent to the results being affected by changes in assumptions made about missing PRO data. CONCLUSION: International efforts to raise awareness of the importance of accurately reporting state-of-the-art handling of missing PRO data are not yet fully reflected in the current literature of breast cancer RCTs.


Assuntos
Neoplasias da Mama , Medidas de Resultados Relatados pelo Paciente , Humanos , Feminino , Neoplasias da Mama/terapia
10.
Antibiotics (Basel) ; 12(10)2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37887231

RESUMO

Streptococcus pyogenes is known to be associated with a variety of infections, from pharyngitis to necrotizing fasciitis (flesh-eating disease). S. pyogenes of the ST62/emm87 lineage is recognized as one of the most frequently isolated lineages of invasive infections caused by this bacterium, which may be involved in hospital outbreaks and cluster infections. Despite this, comparative genomic and phylogenomic studies have not yet been carried out for this lineage. Thus, its virulence and antimicrobial susceptibility profiles are mostly unknown, as are the genetic relationships and evolutionary traits involving this lineage. Previously, a strain of S. pyogenes ST62/emm87 (37-97) was characterized in our lab for its ability to generate antibiotic-persistent cells, and therapeutic failure in severe invasive infections caused by this bacterial species is well-reported in the scientific literature. In this work, we analyzed genomic and phylogenomic characteristics and evaluated the virulence and resistance profiles of ST62/emm87 S. pyogenes from Brazil and international sources. Here we show that strains that form this lineage (ST62/emm87) are internationally spread, involved in invasive outbreaks, and share important virulence profiles with the most common emm types of S. pyogenes, such as emm1, emm3, emm12, and emm69, which are associated with most invasive infections caused by this bacterial species in the USA and Europe. Accordingly, the continued increase of ST62/emm87 in severe S. pyogenes diseases should not be underestimated.

11.
Antibiotics (Basel) ; 11(9)2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36139996

RESUMO

Multidrug resistance is commonly acquired by transferring DNA from one bacterium to another. However, the mechanisms that enhance the acquisitions of foreign genes are poorly understood, as well as the dynamics of their transmission between hosts in different environments. Here, genomic approaches were applied to evaluate the enrichment of the S. aureus chromosome with resistance traits in groups of genomes with or without anti-restriction genes and to analyze some evolutionary aspects of these acquisitions. Furthermore, the role played by an anti-restriction gene in improving multiresistance in MRSA was investigated by molecular cloning. A strong association was observed between the presence of anti-restriction gene homologs and patterns of multidrug resistance. Human isolates, mainly ST239-SCCmecIII, carry ardA-H1, and from animal sources, mainly CC398, carry ardA-H2. Increased DNA transfer was observed for clones that express the ardA-H1 allele, corroborating its role in promoting gene transfer. In addition, ardA-H1 was expressed in the dsDNA format in the BMB9393 strain. The evolution of successful multidrug-resistant MRSA lineages of the ST239 and ST398 was initiated not only by the entry of the mec cassette but also by the acquisition of anti-restriction gene homologs. Understanding the mechanisms that affect DNA transfer may provide new tools to control the spread of drug resistance.

12.
Braz J Vet Med ; 43: e001820, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35749062

RESUMO

Peritoneopericardial diaphragmatic hernia (PPDH) is a communication between the abdomen and the pericardial sac generated by congenital anomalies triggered during diaphragmatic and pericardial development. This report aimed to present the case of an adult, mixed-breed cat, affected by PPDH, focusing on the period from diagnosis to successful surgical correction. The patient had a capricious appetite and weight loss for about four months and started, at the end of this period, a state of apathy. On abdominal ultrasound, the gallbladder (GB) was close to the heart, suggesting diaphragmatic discontinuity. On thoracic radiography, there were changes suggestive of PPDH, pericardial efusion or cardiomegaly with probable dilated cardiomyopathy. Based on these findings, an echocardiogram was performed, highlighting the hepatic lobe and GB internally to the pericardium, causing cardiac compression, although without severe cardiac changes. During surgery, a diaphragmatic defect of 4 cm in diameter was observed with the congested right medial hepatic lobe and hyperemic GB in the pericardial sac. The defect was sutured using the sultan pattern in separate stitches and polyamide threads. The feline returned to feeding with greater interest soon after the surgery, and after 15 days it was fed with dry food and had normal behavior. PPDH can be diagnosed in healthy adult cats, even if there are no apparent respiratory, gastrointestinal, or cardiac signs. The echocardiogram is relevant in the definitive diagnosis, in addition to excluding differential diagnoses, and simple surgical treatment with polyamide thread and sultan suture is successful.


A hérnia periotônio-pericárdica diafragmática (HPPD) comunica o abdome e o saco pericárdico, é gerada por anomalias congênitas deflagradas no desenvolvimento diafragmático e pericárdico. O objetivo deste relato é apresentar o caso de uma gata adulta, mestiça, acometida por HPPD, destacando do diagnóstico à correção cirúrgica bem sucedida. A paciente exibia apetite caprichoso e emagrecimento há cerca de 4 meses, iniciando ao final deste período, apatia. Na ultrassonografia abdominal a vesícula biliar (VB) estava próxima ao coração sugerindo ruptura diafragmática. Na radiografia torácica evidenciou-se alterações sugestivas de HPPD ou cardiomegalia com provável miocardiopatia dilatada. Devido tais achados realizou-se ecocardiograma destacando o lobo hepático e a VB no pericárdio comprimindo o coração sem comprometer sua função. Na cirurgia observou-se defeito diafragmático (4 cm), passagem do lobo hepático medial direito e da VB para o pericárdio. Suturou-se o defeito com padrão sultan e fio poliamida 3.0. A felina voltou a se alimentar com maior interesse logo após a cirurgia. A HPPD pode ser diagnosticada em felinos adultos saudáveis, mesmo que não haja sinais respiratórios, gastrointestinais ou cardíacos aparentes. O ecocardiograma é relevante no diagnóstico definitivo, além de excluir diagnósticos diferenciais, sendo o simples tratamento cirúrgico com fio poliamida e sutura sultan bem sucedido.

13.
Front Microbiol ; 12: 716628, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34621249

RESUMO

Streptococcus pyogenes (group A Streptococcus-GAS) is an important pathogen for humans. GAS has been associated with severe and invasive diseases. Despite the fact that these bacteria remain universally susceptible to penicillin, therapeutic failures have been reported in some GAS infections. Many hypotheses have been proposed to explain these antibiotic-unresponsive infections; however, none of them have fully elucidated this phenomenon. In this study, we show that GAS strains have the ability to form antimicrobial persisters when inoculated on abiotic surfaces to form a film of bacterial agglomerates (biofilm-like environment). Our data suggest that efflux pumps were possibly involved in this phenomenon. In fact, gene expression assays by real-time qRT-PCR showed upregulation of some genes associated with efflux pumps in persisters arising in the presence of penicillin. Phenotypic reversion assay and whole-genome sequencing indicated that this event was due to non-inherited resistance mechanisms. The persister cells showed downregulation of genes associated with protein biosynthesis and cell growth, as demonstrated by gene expression assays. Moreover, the proteomic analysis revealed that susceptible cells express higher levels of ribosome proteins. It is remarkable that previous studies have reported the recovery of S. pyogenes viable cells from tissue biopsies of patients presented with GAS invasive infections and submitted to therapy with antibiotics. The persistence phenomenon described herein brings new insights into the origin of therapeutic failures in S. pyogenes infections. Multifactorial mechanisms involving protein synthesis inhibition, cell growth impairment and efflux pumps seem to play roles in the formation of antimicrobial persisters in S. pyogenes.

14.
Biomolecules ; 10(12)2020 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-33266015

RESUMO

Insulin receptor (IR) and IR-related signaling defects have been shown to trigger insulin-resistance in insulin-dependent cells and ultimately to give rise to type 2 diabetes in mammalian organisms. IR expression is ubiquitous in mammalian tissues, and its over-expression is also a common finding in cancerous cells. This latter finding has been shown to associate with both a relative and absolute increase in IR isoform-A (IR-A) expression, missing 12 aa in its EC subunit corresponding to exon 11. Since IR-A is a high-affinity transducer of Insulin-like Growth Factor-II (IGF-II) signals, a growth factor is often secreted by cancer cells; such event offers a direct molecular link between IR-A/IR-B increased ratio in insulin resistance states (obesity and type 2 diabetes) and the malignant advantage provided by IGF-II to solid tumors. Nonetheless, recent findings on the biological role of isoforms for cellular signaling components suggest that the preferential expression of IR isoform-A may be part of a wider contextual isoform-expression switch in downstream regulatory factors, potentially enhancing IR-dependent oncogenic effects. The present review focuses on the role of isoform- and paralog-dependent variability in the IR and downstream cellular components playing a potential role in the modulation of the IR-A signaling related to the changes induced by insulin-resistance-linked conditions as well as to their relationship with the benign versus malignant transition in underlying solid tumors.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Neoplasias/metabolismo , Receptor de Insulina/metabolismo , Animais , Humanos , Isoformas de Proteínas , Transdução de Sinais
15.
Sci Rep ; 10(1): 17976, 2020 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-33087750

RESUMO

Similar to sleeping after learning, a brief period of wakeful resting after encoding new information supports memory retention in contrast to task-related cognition. Recent evidence suggests that working memory capacity (WMC) is related to sleep-dependent declarative memory consolidation. We tested whether WMC moderates the effect of a brief period of wakeful resting compared to performing a distractor task subsequent to encoding a word list. Participants encoded and immediately recalled a word list followed by either an 8 min wakeful resting period (eyes closed, relaxed) or by performing an adapted version of the d2 test of attention for 8 min. At the end of the experimental session (after 12-24 min) and again, after 7 days, participants were required to complete a surprise free recall test of both word lists. Our results show that interindividual differences in WMC are a central moderating factor for the effect of post-learning activity on memory retention. The difference in word retention between a brief period of wakeful resting versus performing a selective attention task subsequent to encoding increased in higher WMC individuals over a retention interval of 12-24 min, as well as over 7 days. This effect was reversed in lower WMC individuals. Our results extend findings showing that WMC seems not only to moderate sleep-related but also wakeful resting-related memory consolidation.


Assuntos
Aprendizagem/fisiologia , Consolidação da Memória/fisiologia , Memória de Curto Prazo/fisiologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Descanso/fisiologia , Fatores de Tempo , Vigília/fisiologia , Testes de Associação de Palavras , Adulto Jovem
16.
J Med Microbiol ; 69(4): 576-586, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32125264

RESUMO

Introduction. In some species, the population structure of pathogenic bacteria is clonal. However, the mechanisms that determine the predominance and persistence of specific bacterial lineages of group C Streptococcus remain poorly understood. In Brazil, a previous study revealed the predominance of two main lineages of Streptococcus dysgalactiae subsp. equisimilis (SDSE).Aim. The aim of this study was to assess the virulence and fitness advantages that might explain the predominance of these SDSE lineages for a long period of time.Methodology. emm typing was determined by DNA sequencing. Adhesion and invasion tests were performed using human bronchial epithelial cells (16HBE14o-). Biofilm formation was tested on glass surfaces and the presence of virulence genes was assessed by PCR. Additionally, virulence was studied using Caenorhabditis elegans models and competitive fitness was analysed in murine models.Results. The predominant lineages A and B were mostly typed as emm stC839 and stC6979, respectively. Notably, these lineages exhibited a superior ability to adhere and invade airway cells. Furthermore, the dominant lineages were more prone to induce aversive olfactory learning and more likely to kill C. elegans. In the competitive fitness assays, they also showed increased adaptability. Consistent with the increased virulence observed in the ex vivo and in vivo models, the predominant lineages A and B showed a higher number of virulence-associated genes and a superior ability to accumulate biofilm.Conclusion. These results suggest strongly that this predominance did not occur randomly but rather was due to adaptive mechanisms that culminated in increased colonization and other bacterial properties that might confer increased bacteria-host adaptability to cause disease.


Assuntos
Biodiversidade , Infecções Estreptocócicas/microbiologia , Streptococcus/patogenicidade , Animais , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Brasil , Caenorhabditis elegans , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Streptococcus/classificação , Streptococcus/genética , Streptococcus/isolamento & purificação , Virulência
17.
Br J Dev Psychol ; 37(2): 199-210, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30255941

RESUMO

Evidence primarily exists in adults that engaging in task-related mental activity after new learning results in increased forgetting of learned information, compared with quietly resting in the minutes that follow learning, where less forgetting is observed. The current study investigated whether the beneficial effect of post-encoding rest can be observed in children aged 13-14 years. Each child (N = 102) encoded two word lists. After the presentation and immediate recall of one word list, children wakefully rested for 10 min (resting condition), after presentation and immediate recall of the other word list, they solved visuo-spatial problems for 10 min (problem-solving condition). Seven days later, a surprise free recall test for the two word lists took place. Our results showed that children retained more words over 7 days in the resting condition than with the problem-solving condition. Post-hoc analyses revealed that the resting effect was a function of the number of words recollected during the immediate recall. Specifically, those children who recalled fewest words (≤ 13/30 words) in the immediate recall showed a significant resting effect. There was no resting effect in those who recalled a mid-range (14-16/30 words) or a high number (>16/30 words) of words. These results provide new insights into the factors that influence memory in children, and suggest that a few minutes of wakeful rest benefits memory, relative to engaging in an ongoing task. Statement of contribution What is already known on this subject? Task-related mental activity after encoding weakens memory retention more than wakeful resting. Beneficial effect of resting after encoding was found primarily in younger and older adults. What does this study add? We investigated children at the age of 13-14 years. 8-min post-encoding wakeful resting supports memory retention over 7 days. Individuals differ in the impact of a brief period of wakeful resting after learning. Only children with lower immediate memory performances profited from wakeful resting.


Assuntos
Aprendizagem/fisiologia , Rememoração Mental/fisiologia , Descanso/fisiologia , Vigília/fisiologia , Adolescente , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Resolução de Problemas/fisiologia
18.
J Patient Rep Outcomes ; 3(1): 7, 2019 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-30694417

RESUMO

OBJECTIVE: Computer-adaptive tests (CAT) use individualised sets of questions to assess patient-reported health states, whereas static (conventional) questionnaires present the same questions to all patients. CAT has been shown to increase measurement precision and reduce assessment length. In our study, we investigated if patients perceive CAT questions as more appropriate than static questionnaires, a claim that is frequently associated with CAT measures. METHODS: We compared the static European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) against its corresponding CAT measures focusing on two domains: Physical Functioning (PF) and Emotional Functioning (EF). Cancer patients completed the questionnaires and participated in a cognitive interview to assess how appropriate they perceive the QLQ-C30 and the CAT questions for their current health state. RESULTS: Forty-four cancer patients (mean age = 54.6; 56.8% female) were assessed. For the PF domain, patients considered the CAT items more appropriate (p = 0.002) than the QLQ-C30 items (56.8% vs. 15.9%; 27.2% indifferent). For the EF domain, patients were in favour of the QLQ-C30 items (p < 0.001), with 54.5% considering the QLQ-C30, and 4.5% considering the CAT items to be more appropriate; 40.9% were indifferent. Most patients (N = 36) commented on the preference for the CAT (PF), mentioning better matching of the questions and the health state (38.6%) and better item wording (15.9%). CONCLUSION: For the PF domain the CAT measure better matched the score distribution in the patient sample than the QLQ-C30 PF scale and was consequently considered more appropriate by patients. For the EF domain, the CAT measure did not show better fit than the QLQ-C30 and hence no such preference in terms of appropriateness was observed.

19.
J Patient Rep Outcomes ; 3(1): 13, 2019 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-30783818

RESUMO

Following publication of the original article [1], the authors reported three of their given name have been erroneously tagged as their family names. The correct names are: give name Caroline family name Martini, give name Irene family name Virgolini, give name Bernhard family name Holzner.

20.
J Nucl Med ; 59(10): 1566-1573, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30042164

RESUMO

In patients with metastatic gastroenteropancreatic neuroendocrine tumors (NETs), we evaluated health-related quality of life (HRQoL) from the first peptide receptor radionuclide therapy (PRRT) to the first restaging and compared the scores with general-population (GP) norms. Methods: The data were from routine HRQoL monitoring using the core quality-of-life questionnaire of the European Organization for Research and Treatment of Cancer (EORTC QLQ-C30). Patients received 4-6 cycles of 177Lu-DOTATATE or 90Y-DOTATOC. To be eligible for analysis, patients had to have at least one HRQoL assessment before PRRT and at least one HRQoL assessment at the end of or after treatment completion. Linear mixed models were used to consider HRQoL changes over time. Results: In total, 61 gastroenteropancreatic NET patients (small-intestine NETs, n = 37; pancreatic NETs, n = 24) were eligible for analysis. Clear improvements from baseline to the first restaging were found for diarrhea in small-intestine NET patients, showing a decrease of 16 points, which represents a moderately large change. We observed a clinically relevant decrease in appetite loss (17 points), but for female small-intestine NET patients only. Other HRQoL changes were also restricted to sociodemographic or clinical subgroups and mainly reflected improvements, except for physical and social functioning, which showed decreasing scores in older small-intestine NET patients. Compared with HRQoL GP norms, patients had impairments consisting of diarrhea; fatigue; appetite loss; reduced physical, social, and role functioning; and reduced global HRQoL. Except for diarrhea and appetite loss, patient scores at the first restaging did not reach GP levels. Conclusion: Our analyses support previous findings of overall stable HRQoL under PRRT. Yet, significant HRQoL impairments compared with the GP and potentially specific subgroup patterns need to be considered.


Assuntos
Neoplasias Intestinais/patologia , Neoplasias Intestinais/radioterapia , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/radioterapia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/radioterapia , Qualidade de Vida , Receptores de Peptídeos/uso terapêutico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Inquéritos e Questionários , Resultado do Tratamento
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