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Immune thrombocytopenia (ITP) is characterized by low platelet counts (PLTs) and an increased risk of bleeding. Fostamatinib, a spleen tyrosine kinase inhibitor, has been approved as a second-line treatment for ITP. Real-world data on fostamatinib are lacking. This observational, retrospective, multicentre study, conducted in the Andalusia region of Spain, evaluated 44 adult primary ITP patients (47.7% female; median age 58 years; newly diagnosed ITP 6.8%; persistent 13.6%; chronic 79.5%; median four prior treatments) after ≥ 4 weeks of fostamatinib therapy. The median PLT at the initiation of fostamatinib was 15 × 109/L. Common reasons for starting fostamatinib were refractoriness or intolerance to prior therapy, oral medication preference, history of thrombosis and cardiovascular risk. Dosing was individualized based on efficacy and tolerance. After 2 weeks, global response rate was 56.8% (response and complete response). Response rates were 70.5%, 62.5% and 64% at 4 weeks, 12 weeks and at the end of the study respectively. Adverse events were mild, and no patients discontinued as a result. This real-world study demonstrated a response rate similar to fostamatinib as seen in the pivotal clinical trials while including newly diagnosed patients and allowing for individualized dosing.
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Aminopiridinas , Morfolinas , Púrpura Trombocitopênica Idiopática , Piridinas , Humanos , Pessoa de Meia-Idade , Feminino , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Masculino , Espanha , Aminopiridinas/uso terapêutico , Aminopiridinas/efeitos adversos , Idoso , Morfolinas/uso terapêutico , Morfolinas/efeitos adversos , Estudos Retrospectivos , Adulto , Piridinas/uso terapêutico , Piridinas/efeitos adversos , Oxazinas/uso terapêutico , Oxazinas/efeitos adversos , Pirimidinas/uso terapêutico , Pirimidinas/efeitos adversos , Resultado do Tratamento , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/efeitos adversos , Idoso de 80 Anos ou maisRESUMO
INTRODUCTION: Despite advancements in the treatment of benign prostatic hyperplasia (BPH), the mechanisms underlying BPH development and progression remain elusive and lacks a one-size-fits-all therapeutic solution. Prostatic inflammation contributes to BPH and lower urinary tract symptoms (LUTS), but the initial trigger remains unknown. Current research suggests dysbiosis of the urinary microbiome as a potential culprit. This systematic review explores the emerging field of the male urinary and prostatic microbiome and its relationship with BPH/LUTS. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. A systematic search in the Pubmed and Scopus databases was performed using specific terms. Inclusion criteria considered male non-neurogenic patients with LUTS due to BPH with analyses of urinary microbiome, concerning evaluation of English-language publications with relevance. RESULTS: Among seven articles involving 542 patients, there was an association between male LUTS/BPH and the urinary microbiome. Findings indicate a correlation between urinary microbiome dysbiosis and LUTS severity, with specific bacterial genera such as Streptococcus and Haemophilus linked to higher International Prostate Symptom Score (IPSS) scores and PSA levels. The fecal microbiome may be associated with LUTS, although contradictory findings are reported. The review also highlights methodological inconsistencies, small sample sizes, few negative controls and a lack of comprehensive clinical data as major limitations. CONCLUSIONS: While there is an undeniable correlation between the microbiome and LUTS/BPH, future research should aim to standardize sampling techniques and expand the score to include functional microbiome characterization, potentially leading to novel, microbiome-targeted therapeutic strategies for BPH.
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INTRODUCTION: In this article, we offer an overview of the Capdroits participatory research approach, initially focusing on the controversy surrounding Article 12 of the International Convention of Persons with Disabilities, “Recognition of legal personality under conditions of equality.” Its objective is to encourage the participation of the people concerned by Article 12. It brings together academic researchers, experts in support relationships, and people directly concerned by impediment situations. PURPOSE OF THE STUDY: In this contribution, we present our participatory research approach, the methodology of “public problem-solving” and the ways in which it was deployed. We will show how productions and evaluations have been made accessible, while identifying the tensions at work. RESULTS: Two phases of research have been developed and deployed since 2015, based on an experimental “public problem-solving” methodology. Several collaborative productions have been developed, intended for various types of reception and made possible thanks to accessibility practices. They nevertheless highlight the tensions produced in the participatory processes. CONCLUSIONS: The epistemology that we have been collectively developing since 2015 radically aims to reduce social and cognitive inequalities by promoting experiential knowledge while perpetuating inequalities. Our ability to dialogue [14] is the basis for co-constructing a radical epistemology, which, while imperfect, is profoundly purposeful.
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Pessoas com Deficiência , Humanos , Direitos HumanosRESUMO
This study presents for the first time an analysis of the content and chemical composition of the cuticular waxes and cutin in the leaves of the widespread and important tropical species Terminalia catappa. The leaves were collected in the equatorial Atlantic islands of São Tomé and Príncipe, in the Gulf of Guinea. The epicuticular and intracuticular waxes were determined via dichloromethane extraction and their chemical composition via GC-MS analysis, and the content and monomeric composition of cutin were determined after depolymerization via methanolysis. The leaves contained an epidermal cuticular coverage of 52.8 µg cm-2 of the cuticular waxes (1.4% of mass) and 63.3 µg cm-2 (1.5% of mass) of cutin. Cuticular waxes include mainly n-alkanols and fatty acids, with a substantial proportion of terpenes in the more easily solubilized fraction, and sterols in the more embedded waxes. Cutin is mostly constituted by C16 fatty acids and dihydroxyacids, also including aromatic monomers, suggesting a largely linear macromolecular arrangement. The high proportion of triacontanol, α-amyrin, ß-amyrin, germanicol, and lupeol in the easily solubilized cuticular fraction may explain the bioactive properties attributed to the T. catappa leaves via the popular medicine, which allows us to consider them as a potential source for the extraction of these compounds.
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Terminalia , São Tomé e Príncipe , Folhas de Planta , Ácidos GraxosRESUMO
Exposure to heavy metals may cause the overproduction of reactive oxygen species, generating oxidative stress and consequently, various harms to human health. The soil surrounding the Ventanas Industrial Complex, in Puchuncaví and Quintero municipal districts on the central Chilean coast, contains heavy metal concentrations (As, Cu, Pb, Zn, among others) that far exceed the maximum permissible levels established by Italian soil standards (used as a reference). This study aimed to investigate the potential association between heavy metal exposure in humans and the levels of oxidative stress biomarkers in inhabitants of these locations. We took blood samples from 140 adults living in sites with high concentrations of heavy metals in the soil and compared them with blood samples from 140 adults living in areas with normal heavy metal concentrations. We assessed lipid peroxidation, damage to genetic material, and Total Antioxidant Capacity in these blood samples. Our results indicate an association between oxidative damage and heavy metal exposure, where the inhabitants living in exposed areas have a higher level of DNA damage compared with those living in control areas. Given that DNA damage is one of the main factors in carcinogenesis, these results are of interest, both for public health and for public policies aimed at limiting human exposure to environmental pollution.
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Metais Pesados , Poluentes do Solo , Adulto , Humanos , Chile , Monitoramento Ambiental/métodos , Metais Pesados/toxicidade , Metais Pesados/análise , Estresse Oxidativo , Solo , Poluentes do Solo/toxicidade , Poluentes do Solo/análise , Medição de Risco , ChinaRESUMO
OBJECTIVE: Activated prothrombin complex concentrate (aPCC) is a bypassing agent indicated to treat bleeds in patients with acquired hemophilia A (AHA). Nevertheless, its efficacy and safety in the real-world setting have not often been addressed. METHODS: We report the experience of Spanish reference centers for coagulation disorders and from acquired hemophilia Spanish Registry (AHASR) from August 2012 to February 2021. Follow-up period of 30 days after aPCC withdrawal. RESULTS: Thirty patients with a median age of 70 years old, suffering from 51 bleeds treated with aPCC were finally evaluated. As first-line treatment, aPCC stopped bleeding in 13 of 14 (92.9%) cases. aPCC as the second line after recombinant factor VIIa failure, stopped bleeding in all cases. In 17 patients, aPCC was used far from initial bleed control as prophylaxis of rebleeding with 94% effectiveness. No thromboembolic episodes were communicated. One patient developed hypofibrinogenemia, which did not prevent aPCC from halting bleeding. No other serious adverse events possibly or probably associated with aPCC were reported. CONCLUSIONS: This data support aPCC as hemostatic treatment in AHA with high effectiveness and excellent safety profile in acute bleeds and as extended use to prevent rebleedings, even in aging people with high cardiovascular risk.
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Hemofilia A , Idoso , Humanos , Fatores de Coagulação Sanguínea/uso terapêutico , Análise Custo-Benefício , Fator IX/uso terapêutico , Fator VIII/uso terapêutico , Hemofilia A/complicações , Hemofilia A/tratamento farmacológico , Hemorragia/etiologia , Hemorragia/tratamento farmacológico , Proteínas Recombinantes/uso terapêuticoRESUMO
OBJECTIVES: (1) To describe the incidence, clinical characteristics, treatment and outcome of Aspergillus Endocarditis (AE) in a nationwide multicentric cohort (GAMES). (2) To compare the AE cases of the GAMES cohort, with the AE cases reported in the literature since 2010. (3) To identify variables related to mortality. METHODS: We recruited 10 AE cases included in the GAMES cohort (January 2008-December 2018) and 51 cases from the literature published from January 2010 to July 2019. RESULTS: 4528 patients with infectious endocarditis (IE) were included in the GAMES cohort, of them 10 (0.2%) were AE. After comparing our 10 cases with the 51 of the literature, no differences were found. Analysing the 61 AE cases together, 55.7% were male, median age 45 years. Their main underlying conditions were as follows: prosthetic valve surgery (34.4%) and solid organ transplant (SOT) (19.7%). Mainly affecting mitral (36.1%) and aortic valve (29.5%). Main isolated species were as follows: Aspergillus fumigatus (47.5%) and Aspergillus flavus (24.6%). Embolisms occurred in 54%. Patients were treated with antifungals (90.2%), heart surgery (85.2%) or both (78.7%). Overall, 52.5% died. A greater mortality was observed in immunosuppressed patients (59.4% vs. 24.1%, OR = 4.09, 95%CI = 1.26-13.19, p = .02), and lower mortality was associated with undergoing cardiac surgery plus azole therapy (28.1% vs. 65.5%, OR = 0.22, 95%CI = 0.07-0.72, p = .01). CONCLUSIONS: AE accounts for 0.2% of all IE episodes of a national multicentric cohort, mainly affecting patients with previous valvular surgery or SOT recipients. Mortality remains high especially in immunosuppressed hosts and azole-based treatment combined with surgical resection are related to a better outcome.
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Aspergilose , Endocardite , Antifúngicos/uso terapêutico , Aspergilose/tratamento farmacológico , Aspergillus , Aspergillus fumigatus , Endocardite/tratamento farmacológico , Endocardite/terapia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: Cutin is a biopolyester involved in waterproofing aerial plant organs, including leaves. Cutin quantification and compositional profiling require depolymerisation, namely by methanolysis, but specific protocols are not available. OBJECTIVES: Investigate how different methanolysis conditions regarding catalyst concentration effect cutin depolymerisation and monomer release, to better define protocols for cutin content determination and composition profiling. MATERIAL AND METHODS: Cork oak (Quercus suber) dewaxed leaves were reacted with five sodium methoxide (NaOMe) concentrations. Extracts were analysed: glycerol by high-performance liquid chromatography (HPLC) and long-chain lipids by gas chromatography-mass spectrometry (GC-MS). RESULTS: Cutin was completely removed by 3% NaOMe (8.4% of dewaxed leaves), while mild 0.1% and 0.01% NaOMe methanolysis only depolymerised 14% of total cutin. Reactivity of cutin ester bonds is not homogeneous and glyceridic ester bonds are more easily cleaved, releasing the existing glycerol already under the mildest conditions (0.53% with 0.01% NaOMe and 0.41% with 3% NaOMe). The composition of cutin extracts varies with depolymerisation extent, with easier release of alkanoic acids and alkanols, respectively, 34.9% and 8.8% of total monomers at 0.1% NaOMe, while ω-hydroxyacids (49.3% of total monomers) and α,ω-diacids (9.0% of the monomers) are solubilised under more intensive reactive conditions. CONCLUSION: Cutin of Quercus suber leaves is confirmed as a glyceridic polyester of ω-hydroxyacids and alkanoic acids, with minor content of α,ω-diacids, and including coumarate moieties. The protocol for the determination of cutin content and compositional profiling was established regarding catalyst concentration. The molar composition of cutin suggests a macromolecular assembly based on glycerol linked to lipid oligomeric chains with moderate cross-linking.
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Quercus , Ésteres , Lipídeos de Membrana , Folhas de PlantaRESUMO
Infections are one of the well-known precipitating factors for relapses in patients with immune thrombocytopenia (ITP). Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection can sometimes lead to or be associated with thrombocytopenia due to an increase in peripheral platelet destruction from inflammatory hyperactivation. Currently, we do not know if SARS-CoV-2 infection modifies the natural evolution of chronic or persistent ITP or if previous immunosuppression of patients with ITP influences the incidence and severity of coronavirus disease 2019 (COVID-19) in this group. The present study was an observational, multicentre, national series of 32 adult patients with pre-existing ITP and subsequent SARS-CoV-2 infection, collected by the Spanish ITP Group [Grupo Español de Trombocitopenia Inmune (GEPTI)].
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COVID-19/epidemiologia , Púrpura Trombocitopênica Idiopática/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/diagnóstico , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/isolamento & purificação , Espanha/epidemiologiaRESUMO
BACKGROUND: Gastric dysbiosis has been hinted as a potential cause of gastric cancer. However, changes in microbiome throughout the major stages of gastric carcinogenesis remain mostly unknown. OBJECTIVE: To describe gastric microbiome at different stages, analysing for the first time dysbiosis specifically in patients with early gastric cancer (EGC). METHODS: Cross-sectional study including patients (n = 77) with endoscopically and histologically confirmed normal stomachs (controls; n = 25), advanced atrophic gastritis with intestinal metaplasia (IM; n = 18) and EGC (n = 34). Endoscopic biopsies from antrum and corpus (n = 154) were analyzed. Next-generation sequencing was performed characterizing microbial communities down to the species level based on full-length 16SrRNA gene profiling. RESULTS: Significant differences were found in the microbiome profile between the groups. Firmicutes were more frequent (p = .012) and Proteobacteria were less frequent (p = .04) both in the IM and EGC when comparing to controls. Relative frequency of Helicobacter pylori, when present, was much higher in the controls (83%) when comparing to the other groups (IM 1%, EGC 27%; p = .006), being the dominant bacteria only in the controls. Dysbiosis was present already and more significantly at the IM stage, with two bacteria progressively increasing from controls to IM then to cancer: Gemella from 1.48 to 3.9% (p = .014); and Streptococcus from 19.3 to 33.7% (p = .04), being the EGC dominant bacteria. CONCLUSIONS: Our results confirm Helicobacter pylori dominancy in non-atrophic stomachs and progressive dysbiosis throughout gastric carcinogenesis. Gemella but particularly Streptococcus is significantly increased in patients with EGC. Specific modulation of these bacteria may change gastric cancer risk.
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Gastrite Atrófica , Microbioma Gastrointestinal , Infecções por Helicobacter , Helicobacter pylori , Helicobacter , Neoplasias Gástricas , Carcinogênese , Estudos Transversais , Mucosa Gástrica , Humanos , Metaplasia , EstômagoRESUMO
OBJECTIVE: Given the lack of information on the psychological impact of COVID-19 on people aged ≥60, we aimed to describe their psychological responses to this pandemic and lockdown situation and compare them with those under 60 years of age. METHODS: Secondary analysis of a larger online cross-sectional study designed to determine the psychological impact of the COVID-19 pandemic and lockdown across Spain. We analyzed a total of 1690 respondents aged ≥60 years and compared them with 13,363 respondents under 60 years of age. We employed the Depression, Anxiety, and Stress Scale and the Impact of Event Scale to evaluate psychological responses. RESULTS: In all, 52.6% of women and 34.3% of men were found to be probable cases of any emotional distress (p < 0.001). In both sexes, the most common psychological response was avoidance behavior (34.7% and 23.8%, respectively), followed by depression (28.5 and 14.2%). Older women and men were considered probable cases of any emotional distress less often than younger ones (women: 52.6% vs. 72.3%, p < 0.001; men: 34.3% vs. 50.6%, p < 0.001). Finally, the results of the binary logistic regression showed that only depressive and stress responses are psychological factors associated with age group [age ≥ 60 years, O.R. = 0.617 (95% CI = 0.501 - 0.759) and 0.437 (95% CI = 0.334 - 0.573), respectively]. CONCLUSION: Contrary to our hypothesis and despite the high percentage of emotional distress we found in older adults, especially women, they are actually at lower risk of developing depressive and stress consequences from COVID-19 and lockdown than those under 60 years of age. That said, we believe our results highlight the need for expert guidance in this age group, especially older women living alone.
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COVID-19 , Pandemias , Idoso , Ansiedade , Controle de Doenças Transmissíveis , Estudos Transversais , Depressão , Feminino , Humanos , Masculino , SARS-CoV-2 , Espanha , Estresse PsicológicoRESUMO
Brain damage related to alcohol consumption is associated with impairments in cognitive functions, among which memory and verbal learning stand out. The main objective is to evaluate memory and verbal learning in a sample of 111 patients with alcohol use disorder (AUD) versus 78 with major depressive disorder (MDD) and 100 healthy controls. The evaluation included sociodemographic and clinical variables, the Hamilton Depression Scale (HDRS) and the California Verbal Learning Test (CVLT). One-way ANOVA was used for comparisons between the 3 groups and two-way ANCOVAS including different covariates. The one-way ANOVA shows that patients with AUD and MDD had scores similar to each other and lower than those of the control group (p <0.001), with the exception of the Cued CVLT (worse scores in MDD vs AUD, p <0.001). After including age, sex and years of completed studies as covariates, the differences between the AUD and MDD groups persisted compared to the control group (p ≤ 0.003) in all indices except for the Immediate Free CVLT and the Cued CVLT (worse performance in MDD vs AUD, p = 0.022 and p = 0.035, respectively). In the second ANCOVA, after controlling for depression severity, differences were only detected between AUD patients and healthy controls (p ≤ 0.007). Patients with AUD present a significant impairment in learning and verbal memory when compared with patients with MDD and with healthy people.
El daño cerebral relacionado con el consumo de alcohol se asocia a alteraciones de las funciones cognitivas, entre las que destacan memoria y aprendizaje verbal. El objetivo principal es evaluar memoria y aprendizaje verbal en una muestra de 111 pacientes con trastorno por consumo de alcohol (TCA) versus 78 con trastorno de depresión mayor (TDM) y 100 controles sanos. La evaluación incluyó variables sociodemográficas y clínicas, la Escala de Hamilton para la Depresión (HDRS) y el Test de Aprendizaje Verbal de California (CVLT). Se utilizó ANOVA de un factor para comparaciones entre los 3 grupos y ANCOVAS bidireccionales incluyendo diferentes covariables. El ANOVA de un factor muestra que los pacientes con TCA y TDM obtienen puntuaciones similares entre sí e inferiores a las del grupo control (p < 0,001), con excepción del CVLT Guiado (peores puntuaciones en TDM vs TCA, p < 0,001). Tras incluir como covariables la edad, sexo y los años de estudios completados, persisten las diferencias entre los grupos de TCA y TDM frente al grupo control (p ≤ 0,003) en todos los índices con excepción del CVLT Libre Inmediato y del CVLT Guiado (peor rendimiento en TDM vs TCA, p = 0,022 y p = 0,035, respectivamente). En el segundo ANCOVA, tras controlar por gravedad de la depresión, únicamente se detectan diferencias entre los pacientes con TCA y los controles sanos (p ≤ 0,007). Los pacientes con TCA presentan una importante alteración en aprendizaje y memoria verbal al compararlos con pacientes con TDM y con personas sanas.
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Five Candida krusei isolates (susceptible and resistant) recovered from the urine of a kidney transplant patient treated with voriconazole (VRC) 200 mg twice daily for 20 days were studied. Eight unrelated clinical isolates of C. krusei were exposed in vitro to VRC 0.001 µg/ml for 30 days. Development of VRC transient resistance occurred in vivo, and induction of permanent resistance occurred in vitro Mostly, ABC1 and ERG11 genes were overexpressed, and a homozygous T418C mutation in the ERG11 gene was found.
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Adaptação Fisiológica/efeitos dos fármacos , Antifúngicos/farmacologia , Farmacorresistência Fúngica/genética , Micoses/tratamento farmacológico , Pichia/efeitos dos fármacos , Voriconazol/farmacologia , Transportadores de Cassetes de Ligação de ATP/genética , Sistema Enzimático do Citocromo P-450/genética , Feminino , Humanos , Transplante de Rim/efeitos adversos , Testes de Sensibilidade Microbiana , Micoses/microbiologia , Pichia/genética , Pichia/isolamento & purificação , Adulto JovemRESUMO
The role of epicardial adipose tissue (EAT) in the pathophysiology of coronary artery disease (CAD) remains unclear. The present systematic review aimed at compiling dysregulated proteins/genes from different studies to dissect the potential role of EAT in CAD pathophysiology. Exhaustive literature research was performed using the keywords "epicardial adipose tissue and coronary artery disease", to highlight a group of proteins that were consistently regulated among all studies. Reactome, a pathway analysis database, was used to clarify the function of the selected proteins and their intertwined association. SignalP/SecretomeP was used to clarify the endocrine function of the selected proteins. Overall, 1886 proteins/genes were identified from 44 eligible studies. The proteins were separated according to the control used in each study (EAT non-CAD or subcutaneous adipose tissue (SAT) CAD) and by their regulation (up- or downregulated). Using a Venn diagram, we selected the proteins that were upregulated and downregulated (identified as 27 and 19, respectively) in EAT CAD for both comparisons. The analysis of these proteins revealed the main pathways altered in the EAT and how they could communicate with the heart, potentially contributing to CAD development. In summary, in this study, the identified dysregulated proteins highlight the importance of inflammatory processes to modulate the local environment and the progression of CAD, by cellular and metabolic adaptations of epicardial fat that facilitate the formation and progression of atherogenesis of coronaries.
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Tecido Adiposo/metabolismo , Doença da Artéria Coronariana/genética , Vasos Coronários/metabolismo , Pericárdio/metabolismo , Doença da Artéria Coronariana/metabolismo , Doença da Artéria Coronariana/patologia , Vasos Coronários/patologia , Humanos , Pericárdio/patologia , Proteoma/genética , RNA Mensageiro/genéticaRESUMO
Candida glabrata is an emerging fungal pathogen. Its increased prevalence is associated with its ability to rapidly develop antifungal drug resistance, particularly to azoles. In order to unravel new molecular mechanisms behind azole resistance, a transcriptomics analysis of the evolution of a C. glabrata clinical isolate (isolate 044) from azole susceptibility to posaconazole resistance (21st day), clotrimazole resistance (31st day), and fluconazole and voriconazole resistance (45th day), induced by longstanding incubation with fluconazole, was carried out. All the evolved strains were found to accumulate lower concentrations of azole drugs than the parental strain, while the ergosterol concentration remained mostly constant. However, only the population displaying resistance to all azoles was found to have a gain-of-function mutation in the C. glabrataPDR1 gene, leading to the upregulation of genes encoding multidrug resistance transporters. Intermediate strains, exhibiting posaconazole/clotrimazole resistance and increased fluconazole/voriconazole MIC levels, were found to display alternative ways to resist azole drugs. Particularly, posaconazole/clotrimazole resistance after 31 days was correlated with increased expression of adhesin genes. This finding led us to identify the Epa3 adhesin as a new determinant of azole resistance. Besides being required for biofilm formation, Epa3 expression was found to decrease the intracellular accumulation of azole antifungal drugs. Altogether, this work provides a glimpse of the transcriptomics evolution of a C. glabrata population toward multiazole resistance, highlighting the multifactorial nature of the acquisition of azole resistance and pointing out a new player in azole resistance.
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Antifúngicos/farmacologia , Azóis/farmacologia , Candida glabrata/efeitos dos fármacos , Candida glabrata/genética , Farmacorresistência Fúngica/genética , Candida glabrata/isolamento & purificação , Clotrimazol/farmacologia , Ergosterol/metabolismo , Fluconazol/farmacologia , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Humanos , Proteínas de Membrana Transportadoras/genética , Testes de Sensibilidade Microbiana , Fatores de Transcrição/genética , Transcriptoma/genética , Triazóis/farmacologia , Voriconazol/farmacologiaRESUMO
The immediate immune response developed by the keratinocytes against Malassezia yeasts has been addressed yielding conflicting results. This study aims the assessment of cytokines and antimicrobial peptides gene expression elicited by M. sympodialis and M. furfur once in contact with a reconstructed human epidermis. A yeast suspension was prepared in RPMI 1640 medium (Sigma-Aldrich, St. Louis, MO) supplemented with Tween 60 and oleic acid to obtain approximately 1 × 106 cells in a volume of 100 µL. Clinical isolates of M. sympodialis (from pityriasis versicolor) and M. furfur (from seborrhoeic dermatitis) were inoculated, separately, onto a reconstructed human epidermis. A distinct expression pattern was found between the two tested species, with a tendency for overexpression of pro-inflammatory cytokines very soon after infection, whereas no significant expression or gene downregulation was often noticed following 24 and 48 h of incubation. A possible Malassezia species-dependent immune response pattern is highlighted.
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Epiderme/imunologia , Epiderme/microbiologia , Interações Hospedeiro-Patógeno , Queratinócitos/imunologia , Queratinócitos/microbiologia , Malassezia/crescimento & desenvolvimento , Malassezia/imunologia , Peptídeos Catiônicos Antimicrobianos/análise , Citocinas/análise , Dermatomicoses/microbiologia , Dermatomicoses/patologia , Humanos , Modelos TeóricosRESUMO
BACKGROUND: Biofilm formation represents a major microbial virulence attribute especially at epithelial surfaces such as the skin. Malassezia biofilm formation at the skin surface has not yet been addressed. OBJECTIVE: The present study aimed to evaluate Malassezia colonisation pattern on a reconstructed human epidermis (RhE) by imaging techniques. METHODS: Malassezia clinical isolates were previously isolated from volunteers with pityriasis versicolor and seborrhoeic dermatitis. Yeast of two strains of M furfur and M sympodialis were inoculated onto the SkinEthic™ RHE. The tissues were processed for light microscopy, wide-field fluorescence microscopy and scanning electron microscopy. RESULTS: Colonisation of the RhE surface with aggregates of Malassezia yeast entrapped in a multilayer sheet with variable amount of extracellular matrix was unveiled by imaging techniques following 24, 48, 72 and 96 hours of incubation. Whenever yeast were suspended in RPMI medium supplemented with lipids, the biofilm substantially increased with a dense extracellular matrix in which the yeast cells were embedded. Slight differences were found in the biofilm architectural structure between the two tested species with an apparently higher entrapment and viscosity in M furfur biofilm. CONCLUSION: Skin isolates of M furfur and M sympodialis were capable of forming biofilm in vitro at the epidermal surface simulating in vivo conditions. Following 24 hours of incubation, without added lipids, rudimental matrix was barely visible, conversely to the reported at plastic surfaces. The amount of biofilm apparently increased progressively from 48 to 96 hours. A structural heterogeneity of biofilm between species was found.
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Biofilmes , Epiderme/microbiologia , Processamento de Imagem Assistida por Computador , Malassezia/isolamento & purificação , Pele Artificial/microbiologia , Dermatite Seborreica/microbiologia , Humanos , Malassezia/ultraestrutura , Microscopia Eletrônica de Varredura , Tinha Versicolor/microbiologiaRESUMO
BACKGROUND: Data on associations between cannabis use and psychopathology, cognition and functional impairment in schizophrenia spectrum disorders (SSD) is controversial. OBJECTIVES: To examine the effect of cannabis on psychopathology, cognition and real-world functioning in SSD patients. METHOD: Naturalistic cross-sectional study, 123 clinically stable SSD outpatients. ASSESSMENT: demographic and clinical data, psychometric evaluation: Positive and Negative Syndrome, Hamilton Depression Rating, Clinical Global Impression (CGI), Personal and Social Performance and Screen for Cognitive Impairment in Psychiatry (SCIP) scales. Patients were classified as cannabis user patients (CUP) and non cannabis user patients (NCUP) according to self-report, both lifetime and last year. STATISTICAL ANALYSIS: chi-square, Student t test, ANOVA (Duncan post hoc), and general linear model analysis for adjusting for antipsychotic doses. RESULTS: Mean age 40.75, 66.7% male, single (66.7%), prior hospital admissions 2.75, mean length of illness 13.85 years. 53.7% were lifetime cannabis users and 8.9% last year users. Lifetime CUP had more hospitalizations (p = 0.013) at a younger age (p = 0.002), and showed better cognitive functioning globally (CGI-C: p = 0.045) and on working memory and processing speed (SCIP-2: p = 0.039; SCIP-5: p = 0.033) and worse functioning in socially useful activities (p = 0.014) than NCUP. All these differences remained after adjusting for antipsychotic doses. Last year cannabis users had worse mood (Hamilton Depression Rating Scale 9.66 vs. 5.64; p = 0.002), but this difference disappears when adjusting for antipsychotic doses. CONCLUSIONS: Lifetime cannabis use is associated with better working memory and processing speed and worse real-world functioning in the area of socially useful activities in patients with schizophrenia-related disorders. Clinicians should, therefore, be aware of it to provide patient-centred care in their daily clinical practice.
Assuntos
Cannabis , Cognição/fisiologia , Abuso de Maconha/complicações , Esquizofrenia/complicações , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Abuso de Maconha/psicologia , Testes NeuropsicológicosRESUMO
Smoking and depression are related in a bidirectional way: smoking is the primary avoidable cause of illness and death in patients with depression, and depression is one of the most consistent risk factors for smoking. The main objective of this study is to investigate the relationship between smoking and depression, analyzing sociodemographic and clinical variables such as severity of symptoms, subtype of affective disorder, and its impact on suicidal behavior in the clinical population.A sample of 201 patients, over 18 years of age [mean age (SD) = 53.76 (10.36) years; women = 132 (65.7%)], with a history of depressive episode (unipolar or bipolar) or dysthymia (ICD 10 criteria) was studied.Current smoking prevalence was 43.2% and life-time prevalence 61.2%. No statistically significant differences in smoking prevalence between men and women were found (X2 = 3.896, p = 0.143). The average age of onset was 17.81 (5.60) years. There was a tendency towards a linear association between number of cigarettes/day consumed and severity of depression according to the Hamilton Depression Scale (HDRS) in current smokers (Pearson's R = 0.298, p = 0.050). Multinomial logistic regression analysis showed that current tobacco consumption was associated with higher HDRS scores, with each additional point on the HDRS increasing the likelihood of smoking by 0.062 [p = 0.032; OR (95% CI) = 1.064 (1.005-1.125)].Our results showed that depressed patients present higher prevalence of current smoking than the general population, also suggesting a relationship between severity of consumption and severity of depressive symptoms.
Tabaquismo y depresión se relacionan de forma bidireccional: el tabaquismo es la primera causa evitable de enfermedad y muerte en pacientes con depresión, y la depresión constituye uno de los factores de riesgo de tabaquismo más consistentes. El principal objetivo del presente trabajo es profundizar en la relación entre tabaquismo y depresión, analizando variables socio-demográficas y clínicas como la gravedad de los síntomas, el subtipo de trastorno afectivo, y su impacto en las conductas suicidas en población clínica.Se estudió una muestra de 201 pacientes, mayores de 18 años [edad media (SD) = 53,76 (10,36) años; mujeres = 132 (65,7%)], con historia de episodio depresivo (unipolar o bipolar) o distimia (criterios CIE 10).La prevalencia de tabaquismo actual fue 43,2% y la prevalencia vida 61,2%, no existiendo diferencias estadísticamente significativas entre hombres y mujeres (X2 = 3,896; p = 0,143). La edad media de inicio fue 17,81 (5,60) años. Se observó tendencia a asociación lineal entre número de cigarrillos/día consumidos y gravedad de la depresión según la Escala de Hamilton para la Depresión (HDRS) en los consumidores actuales de tabaco (R de Pearson = 0,298; p = 0,050). El análisis de regresión logística multinomial puso de manifiesto que el consumo actual de tabaco se asocia con puntuaciones más elevadas en la HDRS, de modo que cada incremento de un punto en dicha escala, la posibilidad de fumar aumenta en 0,062 [p = 0,032; OR (95% CI) = 1,064 (1,005-1,125)].Nuestros resultados muestran que los pacientes deprimidos presentan mayor prevalencia de consumo actual de tabaco que la población general, sugiriendo además una relación entre gravedad de consumo y gravedad de los síntomas de depresión.
Assuntos
Transtorno Depressivo/epidemiologia , Transtorno Depressivo/psicologia , Fumar/efeitos adversos , Adulto , Comorbidade , Estudos Transversais , Transtorno Depressivo/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Índice de Gravidade de Doença , Fumar/epidemiologia , Fatores Socioeconômicos , Ideação Suicida , Uso de Tabaco/epidemiologia , Uso de Tabaco/psicologia , Tabagismo/psicologiaRESUMO
A flow cytometry test was developed to identify carbapenemase production by Enterobacteriaceae and to discriminate between the different types of carbapenemases (classes A, B, and D). It is based on the detection of meropenem activity against bacteria, coupled with different carbapenemase inhibitors, which is assessed by flow cytometry. It represents a convenient, fast, and reliable approach (100% sensitivity and 100% specificity) for the detection and characterization of different carbapenemases.