RESUMO

BACKGROUND: Atrial fibrillation (AF) is the most common sustained arrythmia, but still underdiagnosed especially among asymptomatic patients. OBJECTIVES: To evaluate a simple strategy to optimize the identification of AF. METHODS: Asymptomatic patients aged 65 years or older, with hypertension or heart failure (HF), were included. Data were inserted into the REDCap software platform. Patients were assessed for the risk for AF using the Stroke Risk Analysis (SRA) mathematical algorithm, which was applied on a one-hour electrocardiogram (ECG). All patients at high risk for AF were instructed to follow a home ECG protocol for seven days using a portable Kardia 6 (OMRON, AliveCor®). The Kolmogorov-test was used to test the normality of quantitative variables; those with normal distribution were expressed as mean and standard deviation. A p<0.05 was set as statistically significant. RESULTS: A total of 423 patients were assessed; 15 were excluded due to absence of SRA, yielding a sample of 408 patients. In 13 (3.2%), AF was identified, 120 (29.4%) were considered at high risk and 275 (67.4%) without increased risk for AF. Of the 120 high-risk patients, 111 successfully completed the seven-day protocol with Kardia; at least one episode of AF was identified in 43 patients. CONCLUSION: The strategy adopted in the RITMO study was shown to be effective in identifying AF in asymptomatic elderly patients with hypertension or HF, with an incidence of 13.7% (56/408).

FUNDAMENTO: A fibrilação atrial (FA) é a arritmia cardíaca sustentada mais frequente, mas ainda é subdiagnosticada especialmente em pacientes assintomáticos. OBJETIVO: Avaliar uma estratégia simples para otimizar a identificação da FA. MÉTODOS: Avaliados indivíduos assintomáticos com 65 anos ou mais, portadores de hipertensão arterial (HA) ou insuficiência cardíaca (IC). Os dados foram inseridos e armazenados em plataforma REDCap. Inicialmente foram realizadas análise de risco de FA com o algoritmo matemático Stroke Risk Analysis (SRA) aplicado em eletrocardiograma (ECG) de 1 hora. Todos os pacientes de alto risco de FA foram orientados a realizar o protocolo de ECG domiciliar por sete dias com o equipamento portátil Kardia 6L OMRON, AliveCor®. O teste de Kolmogorov-Smirnov foi usado para verificar a normalidade da distribuição das variáveis quantitativas; aquelas com distribuição normal foram expressas em média e desvio-padrão. Adotou-se como significativo o valor de p<0,05. RESULTADOS: Foram avaliados 423 pacientes; 15 foram excluídos por não terem realizado o SRA, resultando em uma amostra de 408 pacientes. A avaliação evidenciou que 13 (3,2%) pacientes apresentaram FA, 120 (29,4%) foram considerados de alto risco para FA e 275 (67,4%) sem risco aumentado. Dos 120 pacientes de alto risco, 111 realizaram adequadamente o protocolo de sete dias com o Kardia, tendo sido identificados um ou mais registros de FA em 43 pacientes. CONCLUSÃO: A estratégia adotada no estudo RITMO mostrou-se eficaz para identificar, com uma incidência de 13,7% (56/408), episódios de FA em pacientes idosos assintomáticos e portadores de HA ou IC.

Assuntos

RESUMO

Retinitis pigmentosa (RP) is a Mendelian disease characterized by gradual loss of vision, due to the progressive degeneration of retinal cells. Genetically, it is highly heterogeneous, with pathogenic variants identified in more than 100 genes so far. Following a large-scale sequencing screening, we identified five individuals (four families) with recessive and non-syndromic RP, carrying as well bi-allelic DNA changes in COQ8B, a gene involved in the biosynthesis of coenzyme Q10. Specifically, we detected compound heterozygous assortments of five disease-causing variants (c.187C>T [p.Arg63Trp], c.566G>A [p.Trp189Ter], c.1156G>A [p.Asp386Asn], c.1324G>A [p.Val442Met], and c.1560G>A [p.Trp520Ter]), all segregating with disease according to a recessive pattern of inheritance. Cell-based analysis of recombinant proteins deriving from these genotypes, performed by target engagement assays, showed in all cases a significant decrease in ligand-protein interaction compared to the wild type. Our results indicate that variants in COQ8B lead to recessive non-syndromic RP, possibly by impairing the biosynthesis of coenzyme Q10, a key component of oxidative phosphorylation in the mitochondria.

RESUMO

BACKGROUND: The current work aimed to describe and compare the cortisol and insulin concentrations behavior and rate of perceived exertion (RPE) during a 115 km ultramarathon race. METHODS: Nine ultrarunners (eight males) were evaluated six times (0, 37, 60, 76, 89 and 115 km). At each moment, saliva samples (for cortisol and insulin assessment) and RPE (CR10 scale) were collected. Statistical analysis included correlation, one-way repeated measure ANOVA, and Statistical Parametric Mapping to define discrete and continues changes and compare cortisol, insulin and RPE profiles. RESULTS: Our main findings revealed an early peak in cortisol and RPE, accompanied by a decline in insulin responses (402±49 min of the race, P<0.05). Cortisol and insulin only showed magnitude differences with inverse behaviors until ~6% (7 km) of the ultramarathon duration. Cortisol and RPE presented similar behaviors, rising from the beginning of the race and remaining elevated throughout the race (η2=0.91 and η2=1.0, P<0.001). Insulin levels decreased when the race started, remaining below 60% of baseline values from the midpoint to the end of the race (P=0.04). CONCLUSIONS: The study showed an imbalance in the catabolic/anabolic hormone profile during an ultramarathon race, with a prominence in catabolic state. It should be considered in the ultramarathon races preparation and participation due to its possible detrimental effect on the athlete's health.

RESUMO

BACKGROUND: The coexistence of neuromyelitis optica spectrum disorders (NMOSD) with other autoimmune diseases (AID) has been increasingly reported. The prevalence and significance of this association are not fully understood. OBJECTIVES: This study aimed to compare the clinical and laboratory characteristics in NMOSD patients with and without AID. METHODS: Retrospective cross-sectional observational study was conducted involving adults meeting NMOSD criteria followed in a neuroimmunology clinic at a tertiary center. Descriptive analysis of clinical/paraclinical/treatment/outcome data collected from the medical records was compared between NMOSD patients with AID (polyautoimmunity) and those without AID. RESULTS: From a cohort of 46 NMOSD patients, 16 (34.8 %) patients, mostly women around 40 years of age, presented with polyautoimmunity: 10 anti-AQP4 positive, 4 anti-MOG positive, and 2 seronegative. Five different organ -specific AID, and six systemic AID were identified in the polyautoimmunity patients group, in addition to 6 cases of multiple autoimmune syndrome. The AID manifestation preceded NMOSD in 10 (62.5 %) patients, with a median interval of 7 years. The NMOSD with polyautoimmunity and NMOSD without AID groups had similar initial clinical manifestations with optic neuritis and/or myelitis being most frequent. Inflammatory CSF, namely elevated proteins, was more common in the polyautoimmunity group (13.0 % in NMOSD vs. 31.3 % in NMOSD+AID, p = 0.003). After a 10±6 years follow-up period, more patients with polyautoimmunity had a relapsing disease (75.0 % in NMOSD vs. 46.7 % in NMOSD+AID, p = 0.012) but no difference in the functional outcome evaluated by the EDSS score was identified. CONCLUSIONS: Polyautoimmunity was common in AQP4 positive NMOSD patients leading to a significantly higher risk of disease recorrence. The presence of polyautoimmunity and multiple autoimmune syndrome in NMOSD patients suggests the existence of common susceptibility factors or pathophysiological mechanisms, emphasizing the importance of a multidisciplinary approach to those patients.

Assuntos

RESUMO

OBJECTIVES: Vestibular migraine is a neurological disorder characterized by the association of vertigo and headache, affecting up to 1% of the population. Among its differential diagnoses is endolymphatic hydrops. The aim of this study was to investigate the role of cervical vestibular-evoked myogenic potential and electrocochleography in the diagnosis of vestibular migraine. METHOD: Thirteen women with clinical diagnosis of vestibular migraine (mean age 44 years) and 13 healthy volunteers without auditory and/or vestibular complaints matched for sex and age were evaluated by performing hydrops examinations of cervical vestibular-evoked myogenic potential and electrocochleography. RESULTS: The presence of vertigo and headache was reported by all members of the group with vestibular migraine, associated with symptoms such as nausea, photophobia, and phonophobia. Tinnitus was the most frequent auditory complaint. A significant increase in P1 and N1 latencies was observed in the test group. There was no significant difference in the occurrence of asymmetry and decreased amplitude of the cervical vestibular-evoked myogenic potential. Electrocochleography showed an increase in amplitude of the summation potential. The altered SP/AP ratio was double in the group with vestibular migration, without statistical significance. CONCLUSIONS: Changes in latency increase of cervical vestibular-evoked myogenic potential suggests a central lesion. Patients with vestibular migraine may present electrocochleography compatible with endolymphatic hydrops. LEVEL OF EVIDENCE: Level 4.

RESUMO

Bone tissue regeneration remains a significant challenge in clinical settings due to the complexity of replicating the mechanical and biological properties of bone environment. This study addresses this challenge by proposing a hybrid scaffold designed to enhance both bioactivity and physical stability for bone tissue regeneration. This research is the fisrt to develop a rigid 3D structure composed of polycaprolactone (PCL) and hydroxyapatite nanoparticles (nHA) integrated with a bioink containing human dental pulp stem/stromal cells (hDPSCs), alginate, nHA and collagen (Col). The biofabricated constructs were extensively characterized through cytocompatibility tests, osteogenic differentiation assessment, and biocompatibility evaluation in a rat model. In vitro results demontrated that the hybrid scaffolds presented significantly higher cell viability after 168 h compared to the control group. Furthermore, the hybrid scaffolds showed increased osteogenic differentiation relative to other groups. In vivo evaluation indicated good biocompatibility, characterized by minimal inflammatory response and successful tissue integration. These findings highlight the scaffold's potential to support bone tissue regeneration by combining the mechanical strength of PCL and nHA with the biological activity of the alginate-nHA-Col and hDPSCs bioink. The current study provides a promising foundation for the development of biomaterials aimed at improving clinical outcomes in bone repair and regeneration, particulary for the treatment of critical-size bone defects, targeted drug administration, and three-dimensional models for bone tissue engineering.

RESUMO

Miranda donkeys are an endangered autochthonous breed of Portugal. The HemoCue WBC DIFF and HemoCue Hb 201 portable analyzers, developed as a simplified alternative method for total and differential WBC count and hemoglobin measurement, respectively, may be relevant tools in veterinary practice. This study aimed to validate these instruments using Miranda donkey blood samples. For the HemoCue WBC DIFF, most parameters showed acceptable intra- and inter-assay precision with coefficients of variation (CV) below 5%, except for monocytes and eosinophils with higher CVs. The HemoCue Hb 201 showed CVs of 1.98% and 4.07%. Linearity correlation coefficients (r) ranged from 0.53 to 0.99 for HemoCue WBC DIFF and 0.99 for HemoCue Hb 201. Significant levels for neutrophils, lymphocytes, monocytes, eosinophils, and Hb measurements varied. Comparisons with ProCyte Dx showed an excellent correlation for WBC (rs = 0.96), neutrophils (rs = 0.91), lymphocytes (rs = 0.94), and eosinophils (rs = 0.90) but a poor correlation for monocytes and basophils. The HemoCue Hb 201 showed a correlation of rs = 0.96 with ProCyte Dx. In conclusion, both analyzers provided reliable results and are suitable for use in Miranda's donkey breed for WBC counts and Hb measurements.

RESUMO

Background/Objectives: A comprehensive and up-to-date review on cardiovascular disease (CVD) risk in patients with COPD is needed. Therefore, we aimed to systematically review the risk of a range of CVD in patients with COPD. Methods: We searched three databases (Pubmed, Web of Science, SCOPUS) from inception to September 2023 using terms related to COPD and CVD. Observational studies were included if they (1) were conducted in adults with a diagnosis of COPD based on the GOLD criteria, spirometry, physician diagnosis, or review of electronic health records; (2) reported the risk of CVD, namely of myocardial infarction (MI), ischaemic heart disease (IHD), atrial fibrillation (AF), heart failure, cerebrovascular disease, pulmonary hypertension, and peripheral vascular disease, compared with a control population using a measure of risk. A narrative synthesis was used. Results: Twenty-four studies from 2015 to 2023, mainly from Europe (n = 17), were included. A total of 3,485,392 patients with COPD (43.5-76.0% male; 63.9-73.5 yrs) and 31,480,333 (40.0-55.4% male, 49.3-70.0 yrs) controls were included. A higher risk of CVD in patients with COPD was evident regarding overall CVD, MI, IHD, heart failure, and angina. Higher risks of arrhythmia and AF, stroke, sudden cardiac death/arrest, pulmonary embolism, pulmonary hypertension, and peripheral vascular disease were also found, although based on a small amount of evidence. Conclusions: Patients with COPD have a higher risk of CVD than the general population or matched controls. This review underscores the need for vigilant and close monitoring of cardiovascular risk in individuals with COPD to inform more precise preventive strategies and targeted interventions to enhance their overall management.

RESUMO

Background: Since the seminal publication of the TCGA consortium in 2013, the molecular classification of endometrial cancer has been widely accepted as a new and powerful tool to better understand the natural history of this malignancy. Adoption of routine molecular classification around the world has been limited. We sought to demonstrate our initial experience in incorporating the four molecular subtypes for endometrioid carcinomas. Methods: This was a retrospective analysis at a single center in Portugal. Molecular classification was determined using immunohistochemical staining for MMR and p53 and Sanger Sequencing to determine POLE mutation status as per published PROMISE method. Descriptive statistics were reported. Results: 20 patients with endometrioid histology were included. Median age of the cohort was 64 years (range 45-76). Median Body Mass Index (kg/m2) was 29.81 (range 21.3-43.1). In terms of tumor grading, 16 (80%) of the endometrial carcinomas of the cohort were low-grade (either grade 1 or grade 2). 16 (80%) of the cases were FIGO stage I. Regarding the molecular classification the tumors were classified as: MMRd [n = 6 (30%)]; p53 abn [n = 2 (10%)]; NSMP (n = 10 (50%)), POLE ultramut [n = 2 (10%)]. Conclusion: Despite the small sample size, we were able to show that molecular classification is feasible. To our knowledge this is the first cohort of endometroid endometrial carcinomas fully characterized according to the TCGA classification in Portugal, from one single center.

Assuntos

RESUMO

Healthcare waste management is a critical aspect of public health and environmental protection, particularly in establishments such as dental clinics. This study examined the dental clinic waste (DCW) management processes in clinics within the city of Belo Horizonte, Brazil. Utilizing data from Healthcare Waste Management Plans (HCWMP) provided by the Urban Cleaning Superintendence, the study investigated waste generation, segregation, storage, collection, treatment, and final disposal practices. The results revealed that hazardous DCW represented a significant portion (26.5 %) of waste generated in dental clinics, exceeding the World Health Organization's recommended threshold. Biological waste (22.9 %), mainly consisting of cotton, gauze, and gloves contaminated with blood or body fluids, was the most generated hazardous waste group, followed by chemical (2.2 %) and sharps waste (1.3 %). Incineration was the predominant treatment method for hazardous DCW, raising concerns about environmental impacts and greenhouse gas emissions. Non-hazardous waste, primarily destined for landfills, had limited recycling rates (2.4 %), emphasizing the need for improved waste management strategies to minimize environmental impacts and increase circular economy. Challenges in DCW management included inadequate segregation practices, limited recycling initiatives, and incomplete HCWMPs lacking descriptions of waste management beyond establishment boundaries. Addressing these challenges requires comprehensive training programs, strengthened regulations, and increased environmental awareness among healthcare professionals. In conclusion, improving DCW management in dental clinics is crucial for mitigating occupational and environmental risks. Collective efforts are needed to enhance waste segregation, promote recycling, and ensure compliance with regulations, ultimately safeguarding public health and the environment.

Assuntos

RESUMO

BACKGROUND: Central nervous system dysfunction is common in longstanding hereditary transthyretin amyloidosis (ATTRv) caused by the V30M (p.V50M) mutation. Neuropathology studies show leptomeningeal amyloid deposition and cerebral amyloid angiopathy (CAA). Brain MRI is widely used in the assessment of Aß associated CAA but there are no systematic studies with brain MRI in ATTRv amyloidosis. METHODS: we performed 3 T brain MRIs in 16 patients with longstanding (>14 years) ATTRV30M. We additionally retrospectively reviewed 48 brain MRIs from patients followed at our clinic. CNS symptoms and signs were systematically accessed, and MRIs were blindly reviewed for ischaemic and haemorrhagic lesions. RESULTS: in the prospective cohort, we found white matter hyperintensities in 8/16 patients (50%, Fazekas score> =1). There were no relevant microbleeds, large ischaemic or haemorrhagic lesions or superficial siderosis. In the retrospective cohort, microbleeds were found in 5/48 patients (10,4%), two of which with > =20 microbleeds. White matter hyperintensities were found in 20/48 cases (41.7%). White matter lesions, microbleeds and cortical atrophy were not associated with disease duration. CONCLUSIONS: white matter hyperintensities are common in ATTRV30M, irrespective of disease duration. Haemorrhagic lesions are rare, even in patients with longstanding disease, suggesting the existence of other risk factors.

RESUMO

BACKGROUND: Brazil has a high prevalence of toxoplasmosis. However, there is a gap in comparing seroprevalence for Toxoplasma gondii across different environments, particularly among pregnant residents of rural and urban areas. METHODS: The prevalence of IgG and IgM for T. gondii was compared among pregnant residents of the urban, peri-urban, and rural settlement areas in a municipality in southeastern Brazil. Information regarding age and area of residence was compiled from January 2015 to December 2022. Logistic regression analysis was used to assess the age and area of residence as risk factors. RESULTS: A total of 1614 examinations were recorded, revealing 54.0% seropositivity, which was highest in the rural settlement (61.1%), followed by the peri-urban area (55.9%), and lowest in the urban area (49.2%). CONCLUSIONS: The high prevalence of IgG and presence of IgM in pregnant residents of rural, peri-urban, and urban areas highlights the significance of the results obtained for strengthening maternal health programs aimed at preventing toxoplasmosis, regardless of their residence.

RESUMO

Genome analysis of individuals affected by retinitis pigmentosa (RP) identified two rare nucleotide substitutions at the same genomic location on chromosome 11 (g.61392563 [GRCh38]), 69 base pairs upstream of the start codon of the ciliopathy gene TMEM216 (c.-69G>A, c.-69G>T [GenBank: NM_001173991.3]), in individuals of South Asian and African ancestry, respectively. Genotypes included 71 homozygotes and 3 mixed heterozygotes in trans with a predicted loss-of-function allele. Haplotype analysis showed single-nucleotide variants (SNVs) common across families, suggesting ancestral alleles within the two distinct ethnic populations. Clinical phenotype analysis of 62 available individuals from 49 families indicated a similar clinical presentation with night blindness in the first decade and progressive peripheral field loss thereafter. No evident systemic ciliopathy features were noted. Functional characterization of these variants by luciferase reporter gene assay showed reduced promotor activity. Nanopore sequencing confirmed the lower transcription of the TMEM216 c.-69G>T allele in blood-derived RNA from a heterozygous carrier, and reduced expression was further recapitulated by qPCR, using both leukocytes-derived RNA of c.-69G>T homozygotes and total RNA from genome-edited hTERT-RPE1 cells carrying homozygous TMEM216 c.-69G>A. In conclusion, these variants explain a significant proportion of unsolved cases, specifically in individuals of African ancestry, suggesting that reduced TMEM216 expression might lead to abnormal ciliogenesis and photoreceptor degeneration.

Assuntos

RESUMO

INTRODUCTION: Neuromyelitis optica spectrum disorders (NMOSD) and MOG-associated disease (MOGAD) are an increasingly recognized group of demyelinating disorders of the central nervous system. Previous studies suggest that prognosis is predicted by older age at onset, number of relapses, the severity of the first attack and autoantibody status. OBJECTIVE: To study prognostic factors associated with disability progression and additional relapses in the 3-year follow-up of a national NMOSD/MOGAD cohort. RESULTS: Out of 180 of the initial Portuguese cohort, data on 82 patients was available at the end of the follow-up period (2019-2022). Two patients died. Twenty (24.4%) patients had one or more attack in this period (25 attacks in total), mostly transverse myelitis (TM) (56.0%) or optic neuritis (32.0%). MOGAD was significantly associated with a monophasic disease course (p = 0.03), with milder attacks (p = 0.01), while AQP4 + NMOSD was associated with relapses (p = 0.03). The most common treatment modalities were azathioprine (38.8%) and rituximab (18.8%). AQP4 + NMOSD more frequently required chronic immunosuppressive treatment, particularly rituximab (p = 0.01). Eighteen (22.5%) had an EDSS ≥6 at the end of the follow-up. AQP4 + NMOSD (p < 0.01) and the occurrence of transverse myelitis (TM) during disease (p = 0.04) correlated with an EDSS≥6 at the end of the follow-up period. MOGAD was significantly associated with an EDSS<6 (p < 0.01), and MOG+ cases that reached an EDSS>6 were significantly older (64.0 ± 2.8 versus 31.0 ± 17.1, p = 0.017). A bivariate logistic regression model including the serostatus and TM attacks during disease history successfully predicted 72.2% of patients that progressed to an EDSS≥6. CONCLUSION: This study highlights that myelitis predict increased disability (EDSS≥6) in NMOSD/MOGAG and AQP4 positivity is associated with increased disability.

Assuntos

RESUMO

Introduction: Ischemic stroke is a significant global health concern, with reperfusion therapies playing a vital role in patient management. Neuron-specific enolase (NSE) has been suggested as a potential biomarker for assessing stroke severity and prognosis, however, the role of NSE in predicting long-term outcomes in patients undergoing reperfusion therapies is still scarce. Aim: To investigate the association between serum NSE levels at admission and 48 h after reperfusion therapies, and functional outcomes at 90 days in ischemic stroke patients. Methods: This study conducted a prospective cross-sectional analysis on consecutive acute ischemic stroke patients undergoing intravenous fibrinolysis and/or endovascular thrombectomy. Functional outcomes were assessed using the modified Rankin Scale (mRS) at 90 days post-stroke and two groups were defined according to having unfavorable (mRS3-6) or favorable (mRS0-2) outcome. Demographic, clinical, radiological, and laboratory data were collected, including NSE levels at admission and 48 h. Spearman's coefficient evaluated the correlation between analyzed variables. Logistic regression analysis was performed to verify which variables were independently associated with unfavorable outcome. Two ROC curves determined the cut-off points for NSE at admission and 48 h, being compared by Delong test. Results: Analysis of 79 patients undergoing reperfusion treatment following acute stroke revealed that patients with mRS 3-6 had higher NIHSS at admission (p < 0.0001), higher NIHSS at 24 h (p < 0.0001), and higher NSE levels at 48 h (p = 0.008) when compared to those with mRS 0-2. Optimal cut-off values for NSE0 (>14.2 ng/mL) and NSE48h (>26.3 ng/mL) were identified, showing associations with worse clinical outcomes. Adjusted analyses demonstrated that patients with NSE48h > 26.3 ng/mL had a 13.5 times higher risk of unfavorable outcome, while each unit increase in NIHSS24h score was associated with a 22% increase in unfavorable outcome. Receiver operating characteristic analysis indicated similar predictive abilities of NSE levels at admission and 48 h (p = 0.298). Additionally, a strong positive correlation was observed between NSE48h levels and mRS at 90 days (r = 0.400 and p < 0.0001), suggesting that higher NSE levels indicate worse neurological disability post-stroke. Conclusion: Serum NSE levels at 48 h post-reperfusion therapies are associated with functional outcomes in ischemic stroke patients, serving as potential tool for patient long-term prognosis.

RESUMO

PURPOSE: Asthma is a clinical syndrome with various underlying pathomechanisms and clinical phenotypes. Genetic, ethnic, and geographic factors may influence the differences in clinical presentation, severity, and prognosis. We compared the characteristics of asthma based on the geographical background by analyzing representative cohorts from the United States, Europe, South America, and Asia using the Severe Asthma Research Program (SARP), Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED), Program for Control of Asthma in Bahia (ProAR), and Cohort for Reality and Evolution of Adult Asthma in Korea (COREA), respectively. METHODS: The clinical characteristics and medications for the SARP (n = 669), U-BIOPRED (n = 509), ProAR (n = 996), and COREA (n = 3,748) were analyzed. Subgroup analysis was performed for severe asthma. RESULTS: The mean age was highest and lowest in the COREA and SARP, respectively. The asthma onset age was lowest in the ProAR. The mean body mass index was highest and lowest in the SARP and COREA, respectively. Baseline pulmonary function was lowest and highest in the U-BIOPRED and COREA, respectively. The number of patients with acute exacerbation in the previous year was highest in U-BIOPRED. The mean blood eosinophil count was highest in COREA. The total immunoglobulin E was highest in the ProAR. The frequency of atopy was highest in the SARP. The principal component analysis plot revealed differences among all cohorts. CONCLUSIONS: The cohorts from 4 different continents exhibited different clinical and physiological characteristics, probably resulting from the interplay between genetic susceptibility and geographical factors.

RESUMO

Depression currently affects about 280 million people worldwide and its prevalence has been increasing dramatically, especially among the young and people of reproductive age, which consequently leads to an increase in antidepressant consumption. Antidepressants are associated with sexual dysfunction in both men and women; however, their role in male fertility has been scarcely studied. Fluoxetine and sertraline, two serotonin reuptake inhibitors (SSRIs), are among the most prescribed antidepressants worldwide. To determine their possible effects, human sperm cells were exposed to either sertraline or fluoxetine at concentrations previously found in blood and seminal fluid of patients undergoing treatment. Spermatozoa were incubated for up to 24 h at 37°C and 5% CO2, and important functional parameters such as sperm motility, viability, mitochondrial membrane potential, cellular reactive oxygen species (ROS) production, chromatin/DNA integrity, acrosome status, and tyrosine phosphorylation were assessed. At low levels, fluoxetine consistently decreased progressive motility throughout time while promoting fluctuations in ROS levels and sperm capacitation. Nevertheless, it did not affect viability, mitochondrial membrane potential, acrosome reaction nor chromatin/DNA integrity. Sertraline, on the other hand, had little to nonsignificant impact at low doses, but affected almost all tested parameters at supratherapeutic concentrations. Altogether, our results suggest that both antidepressants may impair sperm function, possibly through different mechanisms of action, but fluoxetine is the only exhibiting mild negative effects at doses found in vivo.

RESUMO

In the original publication [...].

RESUMO

The aim of the study was to assess glucocorticoid sensitivity in survivors of childhood acute lymphoblastic leukemia using in vivo and in vitro tests. Thirty leukemia survivors of both sexes aged ≥18 years participated in the study and at least two years after therapy withdrawal. In vivo tests comprised: a) a very low dose intravenous dexamethasone suppression test for measurement of serum cortisol before, after, and % suppression, compared with 32 age-matched controls; and b) 0.25 mg overnight oral dexamethasone suppression test for assessment of salivary cortisol before, after, and % suppression. In vitro methods comprised: c) glucocorticoid receptor polymorphisms: BcI1-NR3C1 and A3669G; and d) splicing variant of glucocorticoid receptor GR-α mRNA by real-time quantitative polymerase chain reaction, compared with 32 controls. There was a reduction in salivary cortisol, and 73.3% of leukemia survivors showed high sensitivity according to % suppression after oral dexamethasone (p<0.05). Serum cortisol at baseline, after the test, % suppression after intravenous dexamethasone, and the percentage of high sensitivity were reduced in the leukemia group (%F=36.7; p<0.05). The BcI1-NR3C1 and A3669G polymorphisms were present in 11/30 (36.7%) and 5/30 (16.7%) patients, respectively. GR-α mRNA levels were lower in the leukemia group than in the controls (p<0.05). Survivors of acute lymphoblastic leukemia presented with reduced glucocorticoid sensitivity. Glucocorticoid sensitivity allows individualized treatment to avoid adverse effects and may be involved in cardiovascular disease risk among this particular group of cancer survivors.

Assuntos

RESUMO

Research on personal adornments depends on the reliable characterisation of materials to trace provenance and model complex social networks. However, many analytical techniques require the transfer of materials from the museum to the laboratory, involving high insurance costs and limiting the number of items that can be analysed, making the process of empirical data collection a complicated, expensive and time-consuming routine. In this study, we compiled the largest geochemical dataset of Iberian personal adornments (n = 1243 samples) by coupling X-ray fluorescence compositional data with their respective X-ray diffraction mineral labels. This allowed us to develop a machine learning-based framework for the prediction of bead-forming minerals by training and benchmarking 13 of the most widely used supervised algorithms. As a proof of concept, we developed a multiclass model and evaluated its performance on two assemblages from different Portuguese sites with current mineralogical characterisation: Cova das Lapas (n = 15 samples) and Gruta da Marmota (n = 10 samples). Our results showed that decisión-tres based classifiers outperformed other classification logics given the discriminative importance of some chemical elements in determining the mineral phase, which fits particularly well with the decision-making process of this type of model. The comparison of results between the different validation sets and the proof-of-concept has highlighted the risk of using synthetic data to handle imbalance and the main limitation of the framework: its restrictive class system. We conclude that the presented approach can successfully assist in the mineral classification workflow when specific analyses are not available, saving time and allowing a transparent and straightforward assessment of model predictions. Furthermore, we propose a workflow for the interpretation of predictions using the model outputs as compound responses enabling an uncertainty reduction approach currently used by our team. The Python-based framework is packaged in a public repository and includes all the necessary resources for its reusability without the need for any installation.

Assuntos