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During their long evolutionary history, jellyfish have faced changes in multiple environmental factors, to which they may selectively fix adaptations, allowing some species to survive and inhabit diverse environments. Previous findings have confirmed the jellyfish's ability to synthesize large ATP amounts, mainly produced by mitochondria, in response to environmental challenges. This study characterized the respiratory chain from the mitochondria of the jellyfish Stomolophus sp2 (previously misidentified as Stomolophus meleagris). The in-gel activity from isolated jellyfish mitochondria confirmed that the mitochondrial respiratory chain contains the four canonical complexes I to IV and F0F1-ATP synthase. Specific additional activity bands, immunodetection, and mass spectrometry identification confirmed the occurrence of four alternative enzymes integrated into a branched mitochondrial respiratory chain of Stomolophus sp2: an alternative oxidase and three dehydrogenases (two NADH type II enzymes and a mitochondrial glycerol-3-phosphate dehydrogenase). The analysis of each transcript sequence, their phylogenetic relationships, and each protein's predicted models confirmed the mitochondrial alternative enzymes' identity and specific characteristics. Although no statistical differences were found among the mean values of transcript abundance of each enzyme in the transcriptomes of jellyfish exposed to three different temperatures, it was confirmed that each gene was expressed at all tested conditions. These first-time reported enzymes in cnidarians suggest the adaptative ability of jellyfish's mitochondria to display rapid metabolic responses, as previously described, to maintain energetic homeostasis and face temperature variations due to climate change.
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Membranas Mitocondriais , Cifozoários , Animais , Transporte de Elétrons , Filogenia , Membranas Mitocondriais/metabolismo , Cifozoários/química , Cifozoários/metabolismo , Mitocôndrias/metabolismo , Complexo IV da Cadeia de Transporte de ElétronsRESUMO
Herein, an analysis of the optical field emerging from a topological Young's interferometer is conducted. The interferometer consists of two 3D-slit shape curves and is studied by projecting it onto a trihedral reference system. From the projection, Airy, Pearcey, and cusped-type beams emerge. The optical field of these beams is organized around its caustic region. The interference between these types of beams presents interesting physical properties, which can be derived from the interaction between the interference fringes and the caustic regions. One property of the interaction is the irradiance flow, which induces a long-distance interaction between the caustic regions. Another property is the bending of the interference fringes toward the caustic regions, which acts as a sink. Due to the adiabatic features of the caustic regions, the interaction between the fringes-caustic and caustic irradiance is studied using a predator-prey model, which leads to a logistic-type differential equation with nonlinear harvesting. The stability analysis of this equation is in good agreement with the theoretical and experimental results.
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Detecting the association of genetic variants to the response of biological therapy represents an important advance in developing a personalized therapy. The aim of this work was to study the association of polymorphisms with an optimal response to tildrakizumab in patients with psoriasis in a real-life clinical practice. Ninety patients with plaque psoriasis recruited from-Spanish hospitals receiving tildrakizumab for at least 24 weeks were genotyped for 180 polymorphisms. Optimal response to tildrakizumab was evaluated by absolute PASI ≤1 at 6 and 12 months. Polymorphisms corrected for weight and disease duration with an FDR <0.15 were included in a multiple regression model. Sixty three percent of patients achieved an absolute PASI ≤1 at 6 months, while 71% did so after 12 months. Disease duration (>27 years) and weight (>76 kg) were associated with treatment response; after correcting by these factors, no association (FDR >0.15) was found for any polymorphism and response to tildrakizumab at 6 months. The analysis at 12 months identified the genotype GG for rs610604 (TNFAIP3), CT for rs9373839 (ATG5), and delCTGT/delCTGT for rs72167053 (PDE4D) as risk factors to not achieve an optimal response (PASI ≤1), while CT for rs708567 (IL17RC) was protective, independently of weight and disease duration (FDR <0.15). The final multivariable model at 12 months showed an AUC of 0.90 (95% CI 0.82 to -0.98). We identified a set of polymorphisms that could be helpful to identify psoriatic patients with an optimal response to tildrakizumab at 12 months in real-world practice conditions.
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Anticorpos Monoclonais Humanizados , Psoríase , Humanos , Psoríase/tratamento farmacológico , Psoríase/genética , Feminino , Masculino , Pessoa de Meia-Idade , Anticorpos Monoclonais Humanizados/uso terapêutico , Adulto , Polimorfismo de Nucleotídeo Único , Resultado do Tratamento , Genótipo , Idoso , Polimorfismo GenéticoRESUMO
BACKGROUND: The coronavirus disease 2019 (COVID-19) has serious physiological and psychological consequences. The long-term (>12 weeks post-infection) impact of COVID-19 on mental health, specifically in older adults, is unclear. We longitudinally assessed the association of COVID-19 with depression symptomatology in community-dwelling older adults with metabolic syndrome within the framework of the PREDIMED-Plus cohort. METHODS: Participants (n = 5486) aged 55-75 years were included in this longitudinal cohort. COVID-19 status (positive/negative) determined by tests (e.g. polymerase chain reaction severe acute respiratory syndrome coronavirus 2, IgG) was confirmed via event adjudication (410 cases). Pre- and post-COVID-19 depressive symptomatology was ascertained from annual assessments conducted using a validated 21-item Spanish Beck Depression Inventory-II (BDI-II). Multivariable linear and logistic regression models assessed the association between COVID-19 and depression symptomatology. RESULTS: COVID-19 in older adults was associated with higher post-COVID-19 BDI-II scores measured at a median (interquartile range) of 29 (15-40) weeks post-infection [fully adjusted ß = 0.65 points, 95% confidence interval (CI) 0.15-1.15; p = 0.011]. This association was particularly prominent in women (ß = 1.38 points, 95% CI 0.44-2.33, p = 0.004). COVID-19 was associated with 62% increased odds of elevated depression risk (BDI-II ≥ 14) post-COVID-19 when adjusted for confounders (odds ratio; 95% CI 1.13-2.30, p = 0.008). CONCLUSIONS: COVID-19 was associated with long-term depression risk in older adults with overweight/obesity and metabolic syndrome, particularly in women. Thus, long-term evaluations of the impact of COVID-19 on mental health and preventive public health initiatives are warranted in older adults.
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COVID-19 , Síndrome Metabólica , Humanos , Feminino , Idoso , COVID-19/epidemiologia , Depressão/psicologia , Síndrome Metabólica/epidemiologia , Sobrepeso/epidemiologia , Obesidade/epidemiologiaRESUMO
Sleep is a factor associated with overweight/obesity risk, wherein interactions with fatty liver should be ascertained. The aim of this cross-sectional study was to analyze the possible relationships of sleep with liver health and whether this interplay is related to body adiposity distribution in children and adolescents. Anthropometric, clinical, and biochemical measurements were performed in children and adolescents (2-18 years old) with overweight/obesity (n = 854). Body fat distribution was clinically assessed, and several hepatic markers, including hepatic steatosis index, were calculated. Sleep time mediation (hours/day) in the relationship between the hepatic steatosis index and body fat distribution was investigated. Differences among diverse fatty liver disease scores were found between children with overweight or obesity (p < 0.05). Linear regression models showed associations between hepatic steatosis index and lifestyle markers (p < 0.001). Hepatic steatosis index was higher (about + 15%) in children with obesity compared to overweight (p < 0.001). Pear-shaped body fat distribution may seemingly play a more detrimental role on liver fat deposition. The association between sleep time and hepatic steatosis index was dependent on body mass index z-score. Post hoc analyses showed that 39% of the relationship of body fat distribution on hepatic steatosis index may be explained by sleep time. Conclusion: An association of sleep time in the relationship between body fat distribution and hepatic steatosis index was observed in children and adolescents with overweight/obesity, which can be relevant in the prevention and treatment of excessive adiposity between 2 and 18 years old. CLINICAL TRIAL: NCT04805762. Import: As part of a healthy lifestyle, sleep duration might be a modifiable factor in the management of fatty liver disease in children. WHAT IS KNOWN: ⢠Sleep is an influential factor of overweight and obesity in children. ⢠Excessive adiposity is associated with liver status in children and adolescents. WHAT IS NEW: ⢠Sleep time plays a role in the relationship between body fat distribution and liver disease. ⢠Monitoring sleep pattern may be beneficial in the treatment of hepatic steatosis in children with excessive body weight.
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Hepatopatia Gordurosa não Alcoólica , Obesidade Infantil , Adolescente , Criança , Pré-Escolar , Humanos , Adiposidade , Índice de Massa Corporal , Estudos Transversais , Fígado , Hepatopatia Gordurosa não Alcoólica/complicações , Sobrepeso/complicações , Obesidade Infantil/complicações , Duração do SonoRESUMO
To assess the associations between the adherence to a composite score comprised of 6 healthy lifestyle behaviors and its individual components with several cardiometabolic risk factors in Spanish preschool children. Cross-sectional analyses were conducted in 938 participants included in the CORALS cohort aged 3-6 years. Six recognized healthy lifestyle behaviors (breastfeeding, sleep duration, physical activity, screentime, adherence to the Mediterranean diet, and eating speed) were assessed in a composite score. Multiple linear and logistic regression models were fitted to assess the associations with cardiometabolic risk factors (weight status, waist circumference, fat mass index, blood pressure, fasting plasma glucose, and lipid profile). In the adjusted multiple linear and logistic regression models, compared with the reference category of adherence to the healthy lifestyle behavior composite score, those participants in the category of the highest adherence showed significant decreased prevalence risk of overweight or obesity [OR (95% CI), 0.4 (0.2, 0.6)] as well as significant lower waist circumference, fat mass index (FMI), systolic blood pressure and fasting plasma glucose concentration [ß (95% CI), - 1.4 cm (- 2.5, - 0.4); - 0.3 kg/m2 (- 0.5, - 0.1); and - 3.0 mmHg (- 5.2, - 0.9); - 1.9 mg/dL (- 3.5, - 0.4), respectively]. Slow eating speed was individually associated with most of the cardiometabolic risk factors. Conclusions: Higher adherence to the healthy lifestyle behavior composite score was associated with lower waist circumference, FMI, other cardiometabolic risk factors, and risk of overweight or obesity in Spanish preschool children. Further studies are required to confirm these associations. What is Known: ⢠Lifestyle is a well-recognized etiologic factor of obesity and its comorbidities. ⢠Certain healthy behaviors such as adhering to a healthy diet, increasing physical activity, and decreasing screentime are strategies for prevention and treatment of childhood obesity. What is New: ⢠Higher adherence to the healthy lifestyle behavior composite score to 6 healthy behaviors (breastfeeding, sleep duration, physical activity, screentime, eating speed, and adherence to the Mediterranean diet) was associated with decreased adiposity, including prevalence risk of overweight or obesity, and cardiometabolic risk in preschool children. ⢠Slow eating and greater adherence to the Mediterranean diet were mainly associated to lower fasting plasma and serum triglycerides concentration, respectively.
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Obesidade Infantil , Criança , Pré-Escolar , Humanos , Obesidade Infantil/epidemiologia , Obesidade Infantil/etiologia , Obesidade Infantil/prevenção & controle , Sobrepeso/epidemiologia , Fatores de Risco Cardiometabólico , Glicemia/análise , Estudos Transversais , Índice de Massa Corporal , Estilo de Vida Saudável , Fatores de RiscoRESUMO
AIM: The antifungal activity was studied on sessile and persister cells (PCs) of Candida tropicalis biofilms of gold nanoparticles (AuNPs) stabilized with cetyltrimethylammonium bromide (CTAB-AuNPs) and those conjugated with cysteine, in combination with Amphotericin B (AmB). MATERIALS/METHODS: The PC model was used and synergistic activity was tested by the checkerboard assay. Biofilms were studied by crystal violet and scanning electron microscopy. RESULTS/CONCLUSIONS: After the combination of both AuNPs and AmB the biofilm biomass was reduced, with significant differences in architecture being observed with a reduced biofilm matrix. In addition, the CTAB-AuNPs-AmB combination significantly reduced PCs. Understanding how these AuNPs aid in the fight against biofilms and the development of new approaches to eradicate PCs has relevance for chronic infection treatment.
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Anfotericina B , Antifúngicos , Biofilmes , Candida tropicalis , Sinergismo Farmacológico , Ouro , Nanopartículas Metálicas , Testes de Sensibilidade Microbiana , Candida tropicalis/efeitos dos fármacos , Ouro/química , Ouro/farmacologia , Biofilmes/efeitos dos fármacos , Anfotericina B/farmacologia , Anfotericina B/química , Nanopartículas Metálicas/química , Antifúngicos/farmacologia , Antifúngicos/química , Cetrimônio/química , Compostos de Cetrimônio/farmacologia , Compostos de Cetrimônio/químicaRESUMO
PURPOSE: Vitamin D deficiency has been associated with multiple chronic diseases, including metabolic disorders such as insulin resistance and type 2 diabetes (T2D). The aim of the study was to analyze the association between validated predicted serum vitamin D status and the risk of developing T2D in a large prospective cohort based on a Mediterranean population. METHODS: The SUN project is a prospective and dynamic Spanish cohort that gathers university graduates who have answered lifestyle questionnaires, including a validated Food Frequency Questionnaire. The association between predicted serum vitamin D and the risk of T2D was assessed through Cox regression models according to quartiles (Q) of predicted vitamin D at baseline. The models were adjusted for potential confounders and sensitivity analyses were performed to ensure the robustness of our findings. RESULTS: Our study included a total of 18,594 participants and after a total follow-up of 238,078 person-years (median follow-up of 13.5 years), 209 individuals were diagnosed with incident T2D. We found a significant inverse association between predicted levels of serum vitamin D and the risk of developing T2D, after adjusting for potential confounders and performing different sensitivity analyses (hazard ratio Q4 vs. Q1: 0.48, 95% CI 0.26-0.88; p for trend = 0.032). CONCLUSION: The outcomes suggest that higher levels of vitamin D at baseline may be associated with a reduced risk of developing T2D.
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OBJECTIVES: To examine the cross-sectional association between baseline depressive symptoms and the presence of type 2 diabetes (T2D), and its association with glycated hemoglobin (HbA1c) and other metabolic variables, and the prospective association of depressive symptoms and HbA1c after 1 year of follow-up. METHODS: n = 6224 Mediterranean older adults with overweight/obesity and metabolic syndrome (48% females, mean age 64.9 ± 4.9 years) were evaluated in the framework of the PREDIMED-Plus study cohort. Depressive symptoms were assessed using the Beck Depression Inventory-II and HbA1c was used to measure metabolic control. RESULTS: The presence of T2D increased the likelihood of higher levels of depressive symptoms (χ2 = 15.84, p = 0.001). Polynomial contrast revealed a positive linear relationship (χ2 = 13.49, p = 0.001), the higher the depressive symptoms levels, the higher the prevalence of T2D. Longitudinal analyses showed that the higher baseline depressive symptoms levels, the higher the likelihood of being within the HbA1c ≥ 7% at 1-year level (Wald-χ2 = 24.06, df = 3, p < .001, for the full adjusted model). Additionally, depressive levels at baseline and duration of T2D predicted higher HbA1c and body mass index, and lower physical activity and adherence to Mediterranean Diet at 1 year of follow-up. CONCLUSIONS: This study supports an association between T2D and the severity of depressive symptoms, suggesting a worse metabolic control from mild severity levels in the short-medium term, influenced by lifestyle habits related to diabetes care. Screening for depressive symptoms and a multidisciplinary integrative therapeutic approach should be ensured in patients with T2D.
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Depressão , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/psicologia , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Feminino , Masculino , Pessoa de Meia-Idade , Seguimentos , Depressão/epidemiologia , Depressão/etiologia , Idoso , Estudos Transversais , Hemoglobinas Glicadas/análise , Estudos Prospectivos , Dieta Mediterrânea , Prevalência , Índice de Massa Corporal , Obesidade/psicologia , Obesidade/epidemiologia , Obesidade/complicações , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/psicologiaRESUMO
BACKGROUND: Prediction of the response to a biological treatment in psoriasis patients would allow efficient treatment allocation. OBJECTIVE: To identify polymorphisms associated with secukinumab response in psoriasis patients in a daily practice setting. METHODS: We studied 180 SNPs in patients with moderate-to-severe plaque psoriasis recruited from 15 Spanish hospitals. Treatment effectiveness was evaluated by absolute PASI ≤3 and ≤1 at 6 and 12 months. Individuals were genotyped using a custom Taqman array. Multiple logistic regression models were generated. Sensitivity, specificity and area under the curve (AUC) were analysed. RESULTS: A total of 173 patients were studied at 6 months, (67% achieved absolute PASI ≤ 3 and 65% PASI ≤ 1) and 162 at 12 months (75% achieved absolute PASI ≤ 3 and 64% PASI ≤ 1). Multivariable analysis showed the association of different sets of SNPs with the response to secukinumab. The model of absolute PASI≤3 at 6 months showed best values of sensitivity and specificity. Four SNPs were associated with the capability of achieving absolute PASI ≤ 3 at 6 months. rs1801274 (FCGR2A), rs2431697 (miR-146a) and rs10484554 (HLCw6) were identified as risk factors for failure to achieve absolute PASI≤3, while rs1051738 (PDE4A) was protective. AUC including these genotypes, weight of patients and history of biological therapy was 0.88 (95% CI 0.83-0.94), with a sensitivity of 48.6% and specificity of 95.7% to discriminate between both phenotypes. CONCLUSION: We have identified a series of polymorphisms associated with the response to secukinumab capable of predicting the potential response/non-response to this drug in patients with plaque psoriasis.
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Anticorpos Monoclonais Humanizados , Polimorfismo de Nucleotídeo Único , Psoríase , Humanos , Psoríase/tratamento farmacológico , Psoríase/genética , Feminino , Masculino , Anticorpos Monoclonais Humanizados/uso terapêutico , Pessoa de Meia-Idade , Adulto , Fármacos Dermatológicos/uso terapêutico , MicroRNAs/genética , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
OBJECTIVE: This article aims to estimate the differences in environmental impact (greenhouse gas [GHG] emissions, land use, energy used, acidification and potential eutrophication) after one year of promoting a Mediterranean diet (MD). METHODS: Baseline and 1-year follow-up data from 5800 participants in the PREDIMED-Plus study were used. Each participant's food intake was estimated using validated semi-quantitative food frequency questionnaires, and the adherence to MD using the Dietary Score. The influence of diet on environmental impact was assessed through the EAT-Lancet Commission tables. The influence of diet on environmental impact was assessed through the EAT-Lancet Commission tables. The association between MD adherence and its environmental impact was calculated using adjusted multivariate linear regression models. RESULTS: After one year of intervention, the kcal/day consumed was significantly reduced (-125,1 kcal/day), adherence to a MD pattern was improved (+0,9) and the environmental impact due to the diet was significantly reduced (GHG: -361 g/CO2-eq; Acidification:-11,5 g SO2-eq; Eutrophication:-4,7 g PO4-eq; Energy use:-842,7 kJ; and Land use:-2,2 m2). Higher adherence to MD (high vs. low) was significantly associated with lower environmental impact both at baseline and one year follow-up. Meat products had the greatest environmental impact in all the factors analysed, both at baseline and at one-year follow-up, in spite of the reduction observed in their consumption. CONCLUSIONS: A program promoting a MD, after one year of intervention, significantly reduced the environmental impact in all the factors analysed. Meat products had the greatest environmental impact in all the dimensions analysed.
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Dieta Mediterrânea , Gases de Efeito Estufa , Humanos , Dieta , Meio Ambiente , Coleta de DadosRESUMO
BACKGROUND: This study aimed to evaluate the surgical accuracy of a new universal disposable stop system for implant drills (FCA Universal Drill Stop). MATERIAL AND METHODS: A total of 60 bovine ribs were included in this in vitro study. The ribs were randomized into three study groups (n=20 ribs per group). In each study group (Group1: drills without stop or control group, Group 2: prefabricated drills with stop or gold standard group, and Group 3: drills with FCA Universal Drill Stop) a total of 100 osteotomies were performed with implant drills in each group, following the drilling sequence for the placement of a dental implant of 10 mm length and 4 mm diameter. The accuracy of the depth of the osteotomies was quantified clinically (with periodontal probe) and radiologically, using ImageJ version 1.48v software. RESULTS: The order of highest to lowest accuracy (clinical and radiological) in the depth of osteotomies was: FCA Universal Drill Stop> prefabricated drills with a stop>drills without stop, with statistically significant differences being observed between both systems with stop with respect to the control group, although not between them. CONCLUSIONS: The new universal disposable stop system for implant drills, offers similar accuracy to prefabricated drills with stop, with both systems being much more accurate than implant drills without stop. Although this experimental evaluation showed favourable results, further clinical studies are necessary.
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Osteotomia , Costelas , Animais , Bovinos , Osteotomia/instrumentação , Osteotomia/métodos , Costelas/cirurgia , Desenho de Equipamento , Equipamentos Descartáveis , Técnicas In Vitro , Implantes Dentários , Distribuição AleatóriaRESUMO
Background and Objectives: Modern classification and categorization of individuals' health requires personalized variables such as nutrition, physical activity, lifestyle, and medical data through advanced analysis and clustering methods involving machine learning tools. The objective of this project was to categorize Mediterranean dwellers' health factors and design metabotypes to provide personalized well-being in order to develop professional implementation tools in addition to characterizing nutritional and lifestyle features in such populations. Materials and Methods: A two-phase observational study was conducted by the Pharmacists Council to identify Spanish nutritional and lifestyle characteristics. Adults over 18 years of age completed questionnaires on general lifestyle habits, dietary patterns (FFQ, MEDAS-17 p), physical activity (IPAQ), quality of life (SF-12), and validated well-being indices (LS7, MEDLIFE, HHS, MHL). Subsequently, exploratory factor, clustering, and random forest analysis methods were conducted to objectively define the metabotypes considering population determinants. Results: A total of 46.4% of the sample (n = 5496) had moderate-to-high adherence to the Mediterranean diet (>8 points), while 71% of the participants declared that they had moderate physical activity. Almost half of the volunteers had a good self-perception of health (49.9%). Regarding lifestyle index, population LS7 showed a fair cardiovascular health status (7.9 ± 1.7), as well as moderate quality of life by MEDLIFE (9.3 ± 2.6) and MHL scores (2.4 ± 0.8). In addition, five metabotype models were developed based on 26 variables: Westernized Millennial (28.6%), healthy (25.1%), active Mediterranean (16.5%), dysmetabolic/pre-morbid (11.5%), and metabolically vulnerable/pro-morbid (18.3%). Conclusions: The support of tools related to precision nutrition and lifestyle integrates well-being characteristics and contributes to reducing the impact of unhealthy lifestyle habits with practical implications for primary care. Combining lifestyle, metabolic, and quality of life traits will facilitate personalized precision interventions and the implementation of targeted public health policies.
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Dieta Mediterrânea , Exercício Físico , Estilo de Vida , Qualidade de Vida , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Dieta Mediterrânea/estatística & dados numéricos , Inquéritos e Questionários , Exercício Físico/psicologia , Algoritmos , Espanha/epidemiologia , Estudos de Coortes , Idoso , Estado NutricionalRESUMO
BACKGROUND: Ringworm is highly prevalent in our setting and is frequently observed in our routine clinical practice. Diagnostic confirmation depends on techniques that are not always accessible (PCR), with highly variable sensitivity depending on the observer (direct microscopy) or delayed results (culture, histopathology). Recently, an immunochromatography-based rapid test (Diafactory®) for the antigenic detection of dermatophytes has been developed. This diagnostic tool can help diagnose ringworm, allowing early initiation of treatment and fewer consultation visits. OBJECTIVE: To determine the sensitivity and specificity of the rapid antigen detection test compared to conventional culture. MATERIAL AND METHODS: For a full year, 333 nail samples were collected from patients with suspected onychomycosis. The rapid test and the conventional culture were simultaneously performed on each sample. Those with a positive antigenic test result began treatment early. The remaining patients had appointments for serial cultures and subsequent medical consultation to evaluate the results. RESULTS: Compared to conventional culture, the sensitivity and specificity rates of the rapid antigen detection test are 97.2% and 80.7%, respectively. CONCLUSION: The effectiveness of the rapid antigen detection test is similar to that of conventional culture for the detection of dermatophytes in nail samples. It is a quick and simple diagnostic technique that reduces the number of patient visits to the hospital, and allows early treatment start.
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The suppression of the SOS response has been shown to enhance the in vitro activity of quinolones. Furthermore, Dam-dependent base methylation has an impact on susceptibility to other antimicrobials affecting DNA synthesis. Here, we investigated the interplay between these two processes, alone and in combination, in terms of antimicrobial activity. A genetic strategy was used employing single- and double-gene mutants for the SOS response (recA gene) and the Dam methylation system (dam gene) in isogenic models of Escherichia coli both susceptible and resistant to quinolones. Regarding the bacteriostatic activity of quinolones, a synergistic sensitization effect was observed when the Dam methylation system and the recA gene were suppressed. In terms of growth, after 24 h in the presence of quinolones, the Δdam ΔrecA double mutant showed no growth or delayed growth compared to the control strain. In bactericidal terms, spot tests showed that the Δdam ΔrecA double mutant was more sensitive than the ΔrecA single mutant (about 10- to 102-fold) and the wild type (about 103- to 104-fold) in both susceptible and resistant genetic backgrounds. Differences between the wild type and the Δdam ΔrecA double mutant were confirmed by time-kill assays. The suppression of both systems, in a strain with chromosomal mechanisms of quinolone resistance, prevents the evolution of resistance. This genetic and microbiological approach demonstrated the enhanced sensitization of E. coli to quinolones by dual targeting of the recA (SOS response) and Dam methylation system genes, even in a resistant strain model.
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Proteínas de Escherichia coli , Quinolonas , Escherichia coli , Antibacterianos/farmacologia , Resposta SOS em Genética , Epigenoma , Proteínas de Escherichia coli/genética , Quinolonas/farmacologia , Mutação/genéticaRESUMO
Objectives:To evaluate human-like intravenous doses of fosfomycin (8g/Q8h) and amikacin (15mg/kg/Q24h) efficacy in monotherapy and in combination against six fosfomycin-heteroresistant Escherichia coli isolates using a hollow-fiber infection model (HFIM).Materials and methods:Six fosfomycin-heteroresistant E. coli isolates (4 with strong mutator phenotype) and the control strain E. coli ATCC 25922 were used. Mutant frequencies for rifampin (100mg/L), fosfomycin (50 and 200mg/L) and amikacin (32mg/L) were determined. Fosfomycin and amikacin MICs were assessed by agar dilution (AD), gradient strip (GSA) and broth microdilution (BMD) assays. Fosfomycin and amikacin synergies were studied by checkerboard and time-kill assays at different concentrations. Fosfomycin (8g/Q8h) and amikacin (15mg/kg/Q24h) efficacy alone and in combination were assessed using a HFIM.Results:Five isolates were resistant to fosfomycin by AD and BMD, but all susceptible by GSA. All isolates were considered susceptible to amikacin. Antibiotic combinations were synergistic in two isolates and no antagonism was detected. In time-kill assays, all isolates survived under fosfomycin at 64mg/L, although, at 307mg/L, only the normomutators and two hypermutators survived. Four isolates survived under 16mg/L amikacin and none at 45mg/L. No growth was detected under combination conditions. In HFIM, fosfomycin and amikacin monotherapies failed to sterilise bacterial cultures, however, fosfomycin and amikacin combination showed a rapid eradication.Conclusions.There may be a risk of treatment failure of fosfomycin-heteroresistant E. coli isolates using either amikacin or fosfomycin in monotherapy. These results support that the combination amikacin-fosfomycin can rapidly decrease bacterial burden and prevent the emergence of resistant subpopulations against fosfomycin-heteroresistant strains.
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BACKGROUND: Water intake and hydration status have been suggested to impact cognition; however, longitudinal evidence is limited and often inconsistent. This study aimed to longitudinally assess the association between hydration status and water intake based on current recommendations, with changes in cognition in an older Spanish population at high cardiovascular disease risk. METHODS: A prospective analysis was conducted of a cohort of 1957 adults (aged 55-75) with overweight/obesity (BMI between ≥ 27 and < 40 kg/m2) and metabolic syndrome from the PREDIMED-Plus study. Participants had completed bloodwork and validated, semiquantitative beverage and food frequency questionnaires at baseline, as well as an extensive neuropsychological battery of 8 validated tests at baseline and 2 years of follow-up. Hydration status was determined by serum osmolarity calculation and categorized as < 295 mmol/L (hydrated), 295-299.9 mmol/L (impending dehydration), and ≥ 300 mmol/L (dehydrated). Water intake was assessed as total drinking water intake and total water intake from food and beverages and according to EFSA recommendations. Global cognitive function was determined as a composite z-score summarizing individual participant results from all neuropsychological tests. Multivariable linear regression models were fitted to assess the associations between baseline hydration status and fluid intake, continuously and categorically, with 2-year changes in cognitive performance. RESULTS: The mean baseline daily total water intake was 2871 ± 676 mL/day (2889 ± 677 mL/day in men; 2854 ± 674 mL/day in women), and 80.2% of participants met the ESFA reference values for an adequate intake. Serum osmolarity (mean 298 ± 24 mmol/L, range 263 to 347 mmol/L) indicated that 56% of participants were physiologically dehydrated. Lower physiological hydration status (i.e., greater serum osmolarity) was associated with a greater decline in global cognitive function z-score over a 2-year period (ß: - 0.010; 95% CI - 0.017 to - 0.004, p-value = 0.002). No significant associations were observed between water intake from beverages and/or foods with 2-year changes in global cognitive function. CONCLUSIONS: Reduced physiological hydration status was associated with greater reductions in global cognitive function over a 2-year period in older adults with metabolic syndrome and overweight or obesity. Future research assessing the impact of hydration on cognitive performance over a longer duration is needed. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Registry, ISRCTN89898870. Retrospectively registered on 24 July 2014.
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Ingestão de Líquidos , Síndrome Metabólica , Masculino , Humanos , Feminino , Idoso , Sobrepeso , Estudos Prospectivos , Cognição , Obesidade/epidemiologiaRESUMO
BACKGROUND: Cross-sectionally, older age and obesity are associated with increased coronavirus disease-2019 (COVID-19) risk. We assessed the longitudinal associations of baseline and changes in adiposity parameters with COVID-19 incidence in older adults at high cardiovascular risk. METHODS: This analysis included 6874 men and women (aged 55-75 years) with overweight/obesity and metabolic syndrome in the PREDIMED-Plus lifestyle intervention trial for cardiovascular risk reduction. Body weight, body-mass-index (BMI), waist circumference, waist-to-height ratio (WHtR), and a body shape index (ABSI) were measured at baseline and annual follow-up visits. COVID-19 was ascertained by an independent Event Committee until 31 December 2021. Cox regression models were fitted to evaluate the risk of COVID-19 incidence based on baseline adiposity parameters measured 5-6 years before the pandemic and their changes at the visit prior to censoring. RESULTS: At the time of censoring, 653 incident COVID-19 cases occurred. Higher baseline body weight, BMI, waist circumference, and WHtR were associated with increased COVID-19 risk. During the follow-up, every unit increase in body weight (HRadj (95%CI): 1.01 (1.00, 1.03)) and BMI (HRadj: 1.04 (1.003, 1.08)) was associated with increased COVID-19 risk. CONCLUSIONS: In older adults with overweight/obesity, clinically significant weight loss may protect against COVID-19. TRIAL REGISTRATION: This study is registered at the International Standard Randomized Controlled Trial (ISRCT; http://www.isrctn.com/ISRCTN89898870 ).
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COVID-19 , Síndrome Metabólica , Idoso , Feminino , Humanos , Masculino , Adiposidade , Índice de Massa Corporal , Peso Corporal , COVID-19/epidemiologia , COVID-19/complicações , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/complicações , Obesidade/complicações , Obesidade/epidemiologia , Obesidade/metabolismo , Sobrepeso/complicações , Sobrepeso/epidemiologia , Fatores de Risco , Circunferência da Cintura , Pessoa de Meia-IdadeRESUMO
BACKGROUND/OBJECTIVES: Some individuals with overweight/obesity may be relatively metabolically healthy (MHO) and have a lower risk of cardiovascular disease than those with metabolically unhealthy overweight/obesity (MUO). We aimed to compare changes in body weight and cardiometabolic risk factors and type 2 diabetes incidence during a lifestyle intervention between individuals with MHO vs MUO. METHODS: This post-hoc analysis included 1012 participants with MHO and 1153 participants with MUO at baseline in the randomized trial PREVIEW. Participants underwent an eight-week low-energy diet phase followed by a 148-week lifestyle-based weight-maintenance intervention. Adjusted linear mixed models and Cox proportional hazards regression models were used. RESULTS: There were no statistically significant differences in weight loss (%) between participants with MHO vs MUO over 156 weeks. At the end of the study, weight loss was 2.7% (95% CI, 1.7%-3.6%) in participants with MHO and 3.0% (2.1%-4.0%) in those with MUO. After the low-energy diet phase, participants with MHO had smaller decreases in triglyceride (mean difference between MHO vs MUO 0.08 mmol·L-1 [95% CI, 0.04-0.12]; P < 0.001) but similar reductions in fasting glucose and HOMA-IR than those with MUO. However, at the end of weight maintenance, those with MHO had greater reductions in triglyceride (mean difference -0.08 mmol·L-1 [-0.12--0.04]; P < 0.001), fasting glucose, 2-hour glucose (difference -0.28 mmol·L-1 [-0.41--0.16]; P < 0.001), and HOMA-IR than those with MUO. Participants with MHO had smaller decreases in diastolic blood pressure and HbA1c and greater decreases in HDL cholesterol after weight loss than those with MUO, whereas the statistically significant differences disappeared at the end of weight maintenance. Participants with MHO had lower 3-year type 2 diabetes incidence than those with MUO (adjusted hazard ratio 0.37 [0.20-0.66]; P < 0.001). CONCLUSIONS: Individuals with MUO had greater improvements in some cardiometabolic risk factors during the low-energy diet phase, but had smaller improvements during long-term lifestyle intervention than those with MHO.
Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Síndrome Metabólica , Humanos , Índice de Massa Corporal , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/prevenção & controle , Glucose , Incidência , Síndrome Metabólica/epidemiologia , Obesidade/complicações , Obesidade/epidemiologia , Obesidade/terapia , Sobrepeso , Fenótipo , Fatores de Risco , TriglicerídeosRESUMO
OBJECTIVE: To assess the associations between eating speed, adiposity, cardiometabolic risk factors, and diet quality in a cohort of Spanish preschool-children. STUDY DESIGN: A cross-sectional study in 1371 preschool age children (49% girls; mean age, 4.8 ± 1.0 years) from the Childhood Obesity Risk Assessment Longitudinal Study (CORALS) cohort was conducted. After exclusions, 956 participants were included in the analyses. The eating speed was estimated by summing the total minutes used in each of the 3 main meals and then categorized into slow, moderate, or fast. Multiple linear and logistic regression models were fitted to assess the ß-coefficient, or OR and 95% CI, between eating speed and body mass index, waist circumference, fat mass index (FMI), blood pressure, fasting plasma glucose, and lipid profile. RESULTS: Compared with participants in the slow-eating category, those in the fast-eating category had a higher prevalence risk of overweight/obesity (OR, 2.9; 95% CI, 1.8-4.4; P < .01); larger waist circumference (ß, 2.6 cm; 95% CI, 1.5-3.8 cm); and greater FMI (ß, 0.3 kg/m2; 95% CI, 0.1-0.5 kg/m2), systolic blood pressure (ß, 2.8 mmHg; 95% CI, 0.6-4.9 mmHg), and fasting plasma glucose levels (ß, 2.7 mg/dL, 95% CI, 1.2-4.2 mg/dL) but lower adherence to the Mediterranean diet (ß, -0.5 points; 95% CI, -0.9 to -0.1 points). CONCLUSIONS: Eating fast is associated with higher adiposity, certain cardiometabolic risk factors, and lower adherence to a Mediterranean diet. Further long-term and interventional studies are warranted to confirm these associations.