Front-line treatment of acute promyelocytic leukaemia (APL) consists of all-
trans
retinoic acid (ATRA) and anthracycline-based chemotherapy. In this setting, a comparison of idarubicin and ...daunorubicin has never been carried out. Two similar clinical trials using ATRA and chemotherapy for newly diagnosed APL were compared using matched-pair analysis. One was conducted by the PETHEMA/HOVON group with idarubicin and the other by the International Consortium on APL (IC-APL) using daunorubicin. Three hundred and fifty patients from the PETHEMA/HOVON cohort were matched with 175 patients in the IC-APL cohort, adjusting for the significantly unbalanced presenting features of the two entire cohorts. Complete remission (CR) rate was significantly higher in the PETHEMA/HOVON (94 %) than in the IC-APL cohort (85 %) (
P
= 0.002). The distribution of causes of induction failure and the time to achieve CR were similar in both cohorts. Patients who achieved CR had comparable cumulative incidence of relapse and disease-free survival rates, but lower overall and event-free survivals were observed in the IC-APL cohort, which was mainly due to a higher death rate during induction therapy. A higher death rate during consolidation therapy was also observed in the IC-APL. These results show that daunorubicin and idarubicin have similar antileukaemic efficacy in terms of primary resistance, molecular persistence, as well as molecular and haematological relapse rates when combined with ATRA in treatment of APL. However, a higher toxic death rate during induction and consolidation therapy was observed in the IC-APL cohort. This trial was registered at
www.clinicaltrials.gov
as #NCT00408278 ClinicalTrials.gov.
Background
Research shows that personnel working in mental health facilities may share some of the societal prejudices towards mental illness. This might result in stigmatizing behaviours towards ...people suffering from mental disorders, undermining the quality of their care.
Aims
To describe and compare attitudes towards mental illness across a sample of professionals working in a wide range of mental health facilities in Spain, Portugal and Italy.
Method
We administered a survey to personnel including two questionnaires related to stigmatizing attitudes: The Community Attitudes toward the Mentally Ill (CAMI) and the Attribution Questionnaire (AQ-27). Data were compared according to professional category, work setting and country.
Results
34.06% (1525) professionals of the surveyed population responded adequately. Psychologists and social therapists had the most positive attitudes, and nursing assistants the most negative, on most factors of CAMI and AQ-27. Community staff had more positive attitudes than hospital-based professionals in most factors on CAMI and in discriminatory responses on AQ-27.
Conclusions
Globally, mental health professionals showed a positive attitude towards mental illness, but also a relative support to coercive treatments. There are differences in attitudes modulated by professional category and setting. Results can guide preventive strategies, particularly for the hospital-based and nursing staff.
The prevalence of anxiety and depression in young students is associated with biosocial factors and scholastic stress. However, few studies have evaluated emotional-affective symptoms that are ...related to the immune system and antioxidant parameters in young individuals without diagnoses of affective disorders.
This study aims to assess the relationship between emotional-affective symptoms and glutathione concentrations and CD4 and CD8 lymphocyte counts in college students.
College students (
= 177) completed standardized psychometric instruments, including the Perceived Stress Scale, Hamilton Anxiety Scale, Beck Depression Inventory, Familiar Social and Friends Support Scale, and Rosenberg Scale. Blood samples were biochemically analyzed. Analyses of variance were conducted between four groups according to symptom severity.
A considerable prevalence of stress, anxiety, and depression symptoms was observed and negatively correlated with self-esteem and socio-familiar support. Perceived stress was sexually dimorphic. Although biochemical parameters were within reference ranges, glutathione, CD4, and CD8 tended to be lower in participants with anxiety and depression symptoms, which may be of predictive value.
The relationship between antioxidant/immune parameters and socio-affective scores is latent in undiagnosed college students who might develop affective disorders. The findings suggest that during the initial development of affective disorders, stress management strategies should be implemented to help college students cope with the academic load and monitor negative changes in their physiological state.
Idiopathic inflammatory myopathies are a heterogeneous group of rare autoimmune disorders characterized by progressive muscle weakness and the histopathologic findings of inflammatory infiltrates in ...muscle tissue. Although their pathogenesis remains indefinite, the association of autoantibodies with clinical manifestations and the evidence of high effectiveness of depleting therapies suggest that B cells could be implicated. Therefore, we explored the landscape of peripheral B cells in this disease by multiparametric flow cytometry, finding significant numerical decreases in memory and double negative subsets, as well as an expansion of the naïve compartment relative to healthy controls, that contribute to defining disease-associated B cell subset signatures and correlating with different clinical features of patients. Additionally, we determined the potential value of these subsets as diagnostic biomarkers, thus positioning B cells as neglected key elements possibly participating in idiopathic inflammatory myopathies onset or development.
Latino populations have one of the highest prevalences of type 2 diabetes worldwide.
To investigate the association between rare protein-coding genetic variants and prevalence of type 2 diabetes in a ...large Latino population and to explore potential molecular and physiological mechanisms for the observed relationships.
Whole-exome sequencing was performed on DNA samples from 3756 Mexican and US Latino individuals (1794 with type 2 diabetes and 1962 without diabetes) recruited from 1993 to 2013. One variant was further tested for allele frequency and association with type 2 diabetes in large multiethnic data sets of 14,276 participants and characterized in experimental assays.
Prevalence of type 2 diabetes. Secondary outcomes included age of onset, body mass index, and effect on protein function.
A single rare missense variant (c.1522G>A p.E508K) was associated with type 2 diabetes prevalence (odds ratio OR, 5.48; 95% CI, 2.83-10.61; P = 4.4 × 10(-7)) in hepatocyte nuclear factor 1-α (HNF1A), the gene responsible for maturity onset diabetes of the young type 3 (MODY3). This variant was observed in 0.36% of participants without type 2 diabetes and 2.1% of participants with it. In multiethnic replication data sets, the p.E508K variant was seen only in Latino patients (n = 1443 with type 2 diabetes and 1673 without it) and was associated with type 2 diabetes (OR, 4.16; 95% CI, 1.75-9.92; P = .0013). In experimental assays, HNF-1A protein encoding the p.E508K mutant demonstrated reduced transactivation activity of its target promoter compared with a wild-type protein. In our data, carriers and noncarriers of the p.E508K mutation with type 2 diabetes had no significant differences in compared clinical characteristics, including age at onset. The mean (SD) age for carriers was 45.3 years (11.2) vs 47.5 years (11.5) for noncarriers (P = .49) and the mean (SD) BMI for carriers was 28.2 (5.5) vs 29.3 (5.3) for noncarriers (P = .19).
Using whole-exome sequencing, we identified a single low-frequency variant in the MODY3-causing gene HNF1A that is associated with type 2 diabetes in Latino populations and may affect protein function. This finding may have implications for screening and therapeutic modification in this population, but additional studies are required.
The objective of this research was to isolate, characterize, and determine the effects of kafirins and procyanidins of brown sorghum, against different concentrations of superoxide anion radical ...(O2•−) chemically generated in an aprotic polar medium. Likewise (-)-epicatechin, which represents the most abundant monomer of sorghum procyanidins was included as a reference system. Studies in this context are scarce and are considered relevant due to the abundance of such compounds and their potential application as drugs or functional ingredients in foods. By the effect of the hydrophobicity of the kafirins, these were better inhibitors of O2•− in the aprotic polar medium (DMSO) in which they were analyzed, compared to procyanidins and (-)-epicatechin that have a hydrophilic character. This result is important since procyanidins are considered one of the bioactive compounds with the highest antioxidant ability against a considerable number of free radicals.
The primary aim of our study was to investigate the association between intubation timing and hospital mortality in critically ill patients with coronavirus disease 2019 (COVID-19)-associated ...respiratory failure. We also analysed both the impact of such timing throughout the first four pandemic waves and the influence of prior noninvasive respiratory support on outcomes.
This is a secondary analysis of a multicentre, observational and prospective cohort study that included all consecutive patients undergoing invasive mechanical ventilation due to COVID-19 from across 58 Spanish intensive care units (ICUs) participating in the CIBERESUCICOVID project. The study period was between 29 February 2020 and 31 August 2021. Early intubation was defined as that occurring within the first 24 h of ICU admission. Propensity score matching was used to achieve a balance across baseline variables between the early intubation cohort and those patients who were intubated after the first 24 h of ICU admission. Differences in outcomes between early and delayed intubation were also assessed. We performed sensitivity analyses to consider a different time-point (48 h from ICU admission) for early and delayed intubation.
Of the 2725 patients who received invasive mechanical ventilation, a total of 614 matched patients were included in the analysis (307 for each group). In the unmatched population, there were no differences in mortality between the early and delayed groups. After propensity score matching, patients with delayed intubation presented higher hospital mortality (27.3%
37.1%; p=0.01), ICU mortality (25.7%
36.1%; p=0.007) and 90-day mortality (30.9%
40.2%; p=0.02) compared with the early intubation group. Very similar findings were observed when we used a 48-h time-point for early or delayed intubation. The use of early intubation decreased after the first wave of the pandemic (72%, 49%, 46% and 45% in the first, second, third and fourth waves, respectively; first
second, third and fourth waves p<0.001). In both the main and sensitivity analyses, hospital mortality was lower in patients receiving high-flow nasal cannula (HFNC) (n=294) who were intubated earlier. The subgroup of patients undergoing noninvasive ventilation (n=214) before intubation showed higher mortality when delayed intubation was set as that occurring after 48 h from ICU admission, but not when after 24 h.
In patients with COVID-19 requiring invasive mechanical ventilation, delayed intubation was associated with a higher risk of hospital mortality. The use of early intubation significantly decreased throughout the course of the pandemic. Benefits of such an approach occurred more notably in patients who had received HFNC.
The objective of this paper is to compare and evaluate statistically the behavior of two vaccines against cysticercus in a sample of female rabbits. The two vaccines under discussion are 1) ...S3Pvac-Papaya12 mg and 2) Wild Type (WT) or S3P Wild and also 3) Saline Solution. The challenge is to show that the developed vaccine, S3Pvac-Papaya, produces more antibodies and with better stability than the other vaccine and saline solution. With the aim of proving this conjecture, an analysis of variance (ANOVA) and multiple Fisher comparisons at 95% confidence were performed. The vaccine of interest, S3Pvac-Papaya, revealed in the box diagram at T2 that the development of antibodies was high and showed little dispersion, which implies that the vaccine S3Pvac Papaya is statistically efficient in the production of antibodies. Finally, the mathematical contribution centers on highlighting the low use of inferential statistical techniques, comparing means of generated antibodies by a set of vaccines in order to determine which one is more efficient and reliable. Tacitly, a methodology both statistical and procedural has been proposed along this work, to apply when contrasting other kinds of vaccines in both animals and humans for diverse conditions.
Resumo Fundamento A ecocardiografia é essencial para o diagnóstico e a quantificação da insuficiência aórtica (IA). A integral velocidade-tempo (IVT) do fluxo da IA pode estar relacionada à gravidade ...da IA. Objetivo Este estudo tem por objetivo avaliar se a IVT é um marcador ecocardiográfico de gravidade da IA. Métodos Foram incluídos todos os pacientes com IA nativa moderada ou grave e ritmo sinusal que visitaram o nosso laboratório de imagem entre janeiro e outubro de 2016. Todos os indivíduos foram submetidos a um ecocardiograma completo com medição da IVT da IA. A associação entre a IVT e a gravidade da IA foi analisada por regressão logística e modelos de regressão multivariada. Valores p<0,05 foram considerados estatisticamente significativos. Resultados Entre os 62 pacientes incluídos (68,5±14,9 anos; 64,5%: IA moderada; 35,5%: IA grave), a IVT foi maior em indivíduos com IA moderada em comparação àqueles com IA grave (2,2±0,5 m versus 1,9±0,5 m, p=0,01). Pacientes com IA grave apresentaram valores maiores de diâmetro diastólico final do ventrículo esquerdo (DDFVE) (56,1±7,1 mm versus 47,3±9,6 mm, p=0,001), volume diastólico final do ventrículo esquerdo (VDFVE) (171±36,5 mL versus 106±46,6 mL, p<0,001), orifício regurgitante efetivo (0,44±0,1 cm2 versus 0,18±0,1 cm2, p=0,002) e volume regurgitante (71,3±25,7 mL versus 42,5±10,9 mL, p=0,05), assim como menor fração de ejeção do ventrículo esquerdo (FEVE) (54,1±11,2% versus 63,2±13,3%, p=0,012). A IVT mostrou ser um marcador de gravidade da IA, independentemente do DDFVE, VDFVE e FEVE ( odds ratio 0,160, p=0,032) e da frequência cardíaca e pressão arterial diastólica (PAD) ( odds ratio 0,232, p=0,044). Conclusões A IVT do fluxo da IA apresentou associação inversa com a gravidade da IA, independentemente do diâmetro e volume do ventrículo esquerdo, frequência cardíaca, PAD e FEVE. A IVT pode ser um marcador de gravidade da IA em pacientes com IA nativa e ritmo sinusal. (Arq Bras Cardiol. 2020; online.ahead print, PP.0-0)
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