Gr\"obner bases in the mod 22 cohomology of oriented Grassmann manifolds G~2t,3\widetilde G_{2^t,3}

For $n$ a power of two, we give a complete description of the cohomology algebra $H^*(\widetilde G_{n,3};\mathbb Z_2)$ of the Grassmann manifold $\widetilde G_{n,3}$ of oriented $3$-planes in $\mathbb R^n$. We do this by finding a reduced Gr\"obner basis for an ideal closely related to this cohomology algebra. Using this Gr\"obner basis we also present an additive basis for $H^*(\widetilde G_{n,3};\mathbb Z_2)$

Reversal of FLT3 Mutational Status and Sustained Expression of NPM1 Mutation in Paired Presentation, and Relapse Samples in a Patient with Acute Myeloid Leukemia

We report a case of de novo acute myeloid leukemia (AML) with unstable FLT3 gene mutations and stable NPM1 mutation. FLT3/D835 and NPM1 (Type A) mutations were detected upon diagnosis. During the relapse, the FLT3/D835 mutation changed to an FLT3/ITD mutation while the NPM1 (Type A) mutation was retained. Cytogenetic analyses showed the normal karyotype at diagnosis and relapse. Our findings raise interesting questions about the significance of these mutations in the leukemogenic process, about their stability during the evolution of the disease, and regarding the selection of appropriate molecular markers for the monitoring of minimal residual disease

Acute Myeloid Leukemia Associated With Near-Tetraploid Karyotype and Mutations in the FLT3 Gene

Tetraploidy and near-tetraploidy are rare in acute myeloid leukemia (AML), contrary to other hematological disease. In this paper we describe a case of a 52-year-old male with AML associated with tetraploidy, mutation in tyrosine kinase receptor FLT3, and very short survival. At presentation maculopapular rash with crustae, lymphadenopathy, and hepatosplenomegaly was diagnosed. The blasts comprised 80% of marrow nucleated cells (POX negative and PAS finely granular positive). Immunophenotyping done on marrow cells was (CD34, HLA DR, CD14, CD64, CD33, CD11b, and CD15) and correlated with the acute monoblastic leukemia. Detection of FLT3 mutation was done by polymerase chain reaction (PCR). Cytogenetic analysis show: 85-93. XXYY,inc(cp5)/46,XY. Based on these considerations, we suggest the detection of FLT3 mutations as a diagnostic procedure for all AML patients

Cholinesterase inhibitors for vascular dementia and other vascular cognitive impairments:A network meta-analysis

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the benefits and harms of each cholinesterase inhibitor in the treatment of adults with VCI. To compare cholinesterase inhibitors for efficacy and safety in people with VCI

Cholinesterase inhibitors for vascular dementia and other vascular cognitive impairments:a network meta-analysis (Review)

BACKGROUND: Vascular cognitive impairment (VCI) describes a broad spectrum of cognitive impairments caused by cerebrovascular disease, ranging from mild cognitive impairment to dementia. There are currently no pharmacological treatments recommended for improving either cognition or function in people with VCI. Three cholinesterase inhibitors (donepezil, galantamine, and rivastigmine) are licenced for the treatment of dementia due to Alzheimer's disease. They are thought to work by compensating for reduced cholinergic neurotransmission, which is also a feature of VCI. Through pairwise comparisons with placebo and a network meta‐analysis, we sought to determine whether these medications are effective in VCI and whether there are differences between them with regard to efficacy or adverse events. OBJECTIVES: (1) To assess the efficacy and safety of cholinesterase inhibitors in the treatment of adults with vascular dementia and other VCI. (2) To compare the effects of different cholinesterase inhibitors on cognition and adverse events, using network meta‐analysis. SEARCH METHODS: We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group's register, MEDLINE (OvidSP), Embase (OvidSP), PsycINFO (OvidSP), CINAHL (EBSCOhost), Web of Science Core Collection (ISI Web of Science), LILACS (BIREME), ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform on 19 August 2020. SELECTION CRITERIA: We included randomised controlled trials in which donepezil, galantamine, or rivastigmine was compared with placebo or in which the drugs were compared with each other in adults with vascular dementia or other VCI (excluding cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)). We included all drug doses and routes of administration. DATA COLLECTION AND ANALYSIS: Two review authors independently identified eligible trials, extracted data, assessed risk of bias, and applied the GRADE approach to assess the certainty of the evidence. The primary outcomes were cognition, clinical global impression, function (performance of activities of daily living), and adverse events. Secondary outcomes were serious adverse events, incidence of development of new dementia, behavioural disturbance, carer burden, institutionalisation, quality of life and death. For the pairwise analyses, we pooled outcome data at similar time points using random‐effects methods. We also performed a network meta‐analysis using Bayesian methods. MAIN RESULTS: We included eight trials (4373 participants) in the review. Three trials studied donepezil 5 mg or 10 mg daily (n= 2193); three trials studied rivastigmine at a maximum daily dose of 3 to 12 mg (n= 800); and two trials studied galantamine at a maximum daily dose of 16 to 24 mg (n= 1380). The trials included participants with possible or probable vascular dementia or cognitive impairment following stroke. Mean ages were between 72.2 and 73.9 years. All of the trials were at low or unclear risk of bias in all domains, and the evidence ranged from very low to high level of certainty. For cognition, the results showed that donepezil 5 mg improves cognition slightly, although the size of the effect is unlikely to be clinically important (mean difference (MD) −0.92 Alzheimer's Disease Assessment Scale‐Cognitive Subscale (ADAS‐Cog) points (range 0 to 70), 95% confidence interval (CI) −1.44 to −0.40; high‐certainty evidence). Donepezil 10 mg (MD −2.21 ADAS‐Cog points, 95% CI −3.07 to −1.35; moderate‐certainty evidence) and galantamine 16 to 24 mg (MD −2.01 ADAS‐Cog point, 95%CI −3.18 to −0.85; moderate‐certainty evidence) probably also improve cognition, although the larger effect estimates still may not be clinically important. With low certainty, there may be little to no effect of rivastigmine 3 to 12 mg daily on cognition (MD 0.03 ADAS‐Cog points, 95% CI −3.04 to 3.10; low‐certainty evidence). Adverse events reported in the studies included nausea and/or vomiting, diarrhoea, dizziness, headache, and hypertension. The results showed that there was probably little to no difference between donepezil 5 mg and placebo in the number of adverse events (odds ratio (OR) 1.22, 95% CI 0.94 to 1.58; moderate‐certainty evidence), but there were slightly more adverse events with donepezil 10 mg than with placebo (OR 1.95, 95% CI 1.20 to 3.15; high‐certainty evidence). The effect of rivastigmine 3 to 12 mg on adverse events was very uncertain (OR 3.21, 95% CI 0.36 to 28.88; very low‐certainty evidence). Galantamine 16 to 24 mg is probably associated with a slight excess of adverse events over placebo (OR 1.57, 95% CI 1.02 to 2.43; moderate‐certainty evidence). In the network meta‐analysis (NMA), we included cognition to represent benefit, and adverse events to represent harm. All drugs ranked above placebo for cognition and below placebo for adverse events. We found donepezil 10 mg to rank first in terms of benefit, but third in terms of harms, when considering the network estimates and quality of evidence. Galantamine was ranked second in terms of both benefit and harm. Rivastigmine had the lowest ranking of the cholinesterase inhibitors in both benefit and harm NMA estimates, but this may reflect possibly inadequate doses received by some trial participants and small trial sample sizes. AUTHORS' CONCLUSIONS: We found moderate‐ to high‐certainty evidence that donepezil 5 mg, donepezil 10 mg, and galantamine have a slight beneficial effect on cognition in people with VCI, although the size of the change is unlikely to be clinically important. Donepezil 10 mg and galantamine 16 to 24 mg are probably associated with more adverse events than placebo. The evidence for rivastigmine was less certain. The data suggest that donepezil 10 mg has the greatest effect on cognition, but at the cost of adverse effects. The effect is modest, but in the absence of any other treatments, people living with VCI may still wish to consider the use of these agents. Further research into rivastigmine is needed, including the use of transdermal patches

Nirmatrelvir/ritonavir in COVID-19 patients with haematological malignancies:a report from the EPICOVIDEHA registry

Background: Nirmatrelvir/ritonavir treatment decreases the hospitalisation rate in immunocompetent patients with COVID-19, but data on efficacy in patients with haematological malignancy are scarce. Here, we describe the outcome of nirmatrelvir/ritonavir treatment in a large cohort of the latter patients. Methods: This is a retrospective cohort study from the multicentre EPICOVIDEHA registry (NCT04733729) on patients with haematological malignancy, who were diagnosed with COVID-19 between January and September 2022. Patients receiving nirmatrelvir/ritonavir were compared to those who did not. A logistic regression was run to determine factors associated with nirmatrelvir/ritonavir administration in our sample. Mortality between treatment groups was assessed with Kaplan–Meier survival plots after matching all the patients with a propensity score. Additionally, a Cox regression was modelled to detect factors associated with mortality in patients receiving nirmatrelvir/ritonavir. Findings: A total of 1859 patients were analysed, 117 (6%) were treated with nirmatrelvir/ritonavir, 1742 (94%) were treated otherwise. Of 117 patients receiving nirmatrelvir/ritonavir, 80% had received ≥1 anti-SARS-CoV-2 vaccine dose before COVID-19 onset, 13% of which received a 2nd vaccine booster. 5% were admitted to ICU. Nirmatrelvir/ritonavir treatment was associated with the presence of extrapulmonary symptoms at COVID-19 onset, for example anosmia, fever, rhinitis, or sinusitis (aOR 2.509, 95%CI 1.448–4.347) and 2nd vaccine booster (aOR 3.624, 95%CI 1.619–8.109). Chronic pulmonary disease (aOR 0.261, 95%CI 0.093–0.732) and obesity (aOR 0.105, 95%CI 0.014–0.776) were not associated with nirmatrelvir/ritonavir use. After propensity score matching, day-30 mortality rate in patients treated with nirmatrelvir/ritonavir was 2%, significantly lower than in patients with SARS-CoV-2 directed treatment other than nirmatrelvir/ritonavir (11%, p = 0.036). No factor was observed explaining the mortality difference in patients after nirmatrelvir/ritonavir administration. Interpretation: Haematological malignancy patients were more likely to receive nirmatrelvir/ritonavir when reporting extrapulmonary symptoms or 2nd vaccine booster at COVID-19 onset, as opposed to chronic pulmonary disease and obesity. The mortality rate in patients treated with nirmatrelvir/ritonavir was lower than in patients with targeted drugs other than nirmatrelvir/ritonavir. Funding: EPICOVIDEHA has received funds from Optics COMMIT (COVID-19 Unmet Medical Needs and Associated Research Extension) COVID-19 RFP program by GILEAD Science, United States (Project 2020-8223).</p

Nirmatrelvir/ritonavir in COVID-19 patients with haematological malignancies: a report from the EPICOVIDEHA registry

Background: Nirmatrelvir/ritonavir treatment decreases the hospitalisation rate in immunocompetent patients with COVID-19, but data on efficacy in patients with haematological malignancy are scarce. Here, we describe the outcome of nirmatrelvir/ritonavir treatment in a large cohort of the latter patients. Methods: This is a retrospective cohort study from the multicentre EPICOVIDEHA registry (NCT04733729) on patients with haematological malignancy, who were diagnosed with COVID-19 between January and September 2022. Patients receiving nirmatrelvir/ritonavir were compared to those who did not. A logistic regression was run to determine factors associated with nirmatrelvir/ritonavir administration in our sample. Mortality between treatment groups was assessed with Kaplan-Meier survival plots after matching all the patients with a propensity score. Additionally, a Cox regression was modelled to detect factors associated with mortality in patients receiving nirmatrelvir/ritonavir. Findings: A total of 1859 patients were analysed, 117 (6%) were treated with nirmatrelvir/ritonavir, 1742 (94%) were treated otherwise. Of 117 patients receiving nirmatrelvir/ritonavir, 80% had received ≥1 anti-SARS-CoV-2 vaccine dose before COVID-19 onset, 13% of which received a 2nd vaccine booster. 5% were admitted to ICU. Nirmatrelvir/ritonavir treatment was associated with the presence of extrapulmonary symptoms at COVID-19 onset, for example anosmia, fever, rhinitis, or sinusitis (aOR 2.509, 95%CI 1.448-4.347) and 2nd vaccine booster (aOR 3.624, 95%CI 1.619-8.109). Chronic pulmonary disease (aOR 0.261, 95%CI 0.093-0.732) and obesity (aOR 0.105, 95%CI 0.014-0.776) were not associated with nirmatrelvir/ritonavir use. After propensity score matching, day-30 mortality rate in patients treated with nirmatrelvir/ritonavir was 2%, significantly lower than in patients with SARS-CoV-2 directed treatment other than nirmatrelvir/ritonavir (11%, p&nbsp;=&nbsp;0.036). No factor was observed explaining the mortality difference in patients after nirmatrelvir/ritonavir administration. Interpretation: Haematological malignancy patients were more likely to receive nirmatrelvir/ritonavir when reporting extrapulmonary symptoms or 2nd vaccine booster at COVID-19 onset, as opposed to chronic pulmonary disease and obesity. The mortality rate in patients treated with nirmatrelvir/ritonavir was lower than in patients with targeted drugs other than nirmatrelvir/ritonavir. Funding: EPICOVIDEHA has received funds from Optics COMMIT (COVID-19 Unmet Medical Needs and Associated Research Extension) COVID-19 RFP program by GILEAD Science, United States (Project 2020-8223)

The P-type ATPase inhibiting potential of polyoxotungstates.

Polyoxometalates (POMs) are transition metal complexes that exhibit a broad diversity of structures and properties rendering them promising for biological purposes. POMs are able to inhibit a series of biologically important enzymes, including phosphatases, and thus are able to affect many biochemical processes. In the present study, we analyzed and compared the inhibitory effects of nine different polyoxotungstates (POTs) on two P-type ATPases, Ca2+-ATPase from skeletal muscle and Na+/K+-ATPase from basal membrane of skin epithelia. For Ca2+-ATPase inhibition, an in vitro study was performed and the strongest inhibitors were determined to be the large heteropolytungstate K9(C2H8N)5[H10Se2W29O103] (Se2W29) and the Dawson-type POT K6[α-P2W18O62] (P2W18) exhibiting IC50 values of 0.3 and 0.6 μM, respectively. Promising results were also shown for the Keggin-based POTs K6H2[CoW11TiO40] (CoW11Ti, IC50 = 4 μM) and Na10[α-SiW9O34] (SiW9, IC50 = 16 μM), K14[As2W19O67(H2O)] (As2W19, IC50 = 28 μM) and the lacunary Dawson K12[α-H2P2W12O48] (P2W12, IC50 = 11 μM), whereas low inhibitory potencies were observed for the isopolytungstate Na12[H4W22O74] (W22, IC50 = 68 μM) and the Anderson-type Na6[TeW6O24] (TeW6, IC50 = 200 μM). Regarding the inhibition of Na+/K+-ATPase activity, for the first time an ex vivo study was conducted using the opercular epithelium of killifish in order to investigate the effects of POTs on the epithelial chloride secretion. Interestingly, 1 μM of the most potent Ca2+-ATPase inhibitor, Se2W29, showed only a minor inhibitory effect (14% inhibition) on Na+/K+-ATPase activity, whereas almost total inhibition (99% inhibition) was achieved using P2W18. The remaining POTs exhibited similar inhibition rates on both ATPases. These results reveal the high potential of some POTs to act as P-type ATPase inhibitors, with Se2W29 showing high selectivity towards Ca2+-ATPase.info:eu-repo/semantics/submittedVersio

Contextualização no ensino de estatística: uma proposta para os anos finais do ensino fundamental

Acompanha: Sequência de ensino contemplando a estatística nos anos finais do ensino fundamental segundo pressupostos da contextualizaçãoThe present study aimed to examine the contributions that a sequence of teaching based on assumptions of contextualization can bring to the teaching of statistics in the final years of basic school. The literature review concerning the teaching of statistics relies on Cazorla (2002), Lopes (2003, 2008, 2010a, 2010b), Silva (2007), Andrade (2008), Cazorla, Kataoka and Silva (2010), Jacobini et al. (2010), Campos, Wodewotzki and Jacobini (2011), among others. As for context, the literature review supported by Brazil (1998b, 1999), Tufano (2001), Pais (2002, 2010), Ramos (2004), (2005), Sadovsky (2007), Luccas (2011), among others. With the intention of achieving the proposed goal, was developed in the year 2011 a applied research, interpretive analysis and qualitative, descriptive in a batch of students of 7° year of basic school to a State public College of the city of Ponta Grossa, Paraná. The review of literature pertaining to the search features based on Gil (1991, 2006), Chizzotti (2003, 2008), Silva and Menezes (2005), Moreira and Caleffe (2008), Alves-Mazzotti (2011), Sarmento (2011), Teixeira (2011), among others. First was conducted an analysis of previous performance of the students on the basic content of statistics, based on a diagnostic instrument called pre-test. Then it was applied a sequence of teaching directed to basic statistical content, through the use of data collected in their own class, i.e. through contextualization. It emerged during the implementation of education, a greater interest and motivation of students to classes, as well as greater involvement of learners with the contents. The results of the analysis of the performance of the students after teaching sequence showed that this contributed to a significant gain on the acquisition of basic statistical content by students of the final years basic school. It is considered that the activities undertaken with learners, contributed to the development of the skills of reasoning, thinking, and statistical literacy of those forming the necessary basis for that in the future these students can reach the level of statistical literacy that contemporary society requires. As the final product of this work was to elaborate a courseware to support teacher education sequence containing a contextualized on basic statistical content aimed at the basic school, which is attached to this dissertation.O presente trabalho teve como objetivo analisar as contribuições que uma sequência de ensino pautada nos pressupostos da contextualização poderá trazer para o ensino e aprendizagem de Estatística nos anos finais do Ensino Fundamental. A revisão de literatura referente ao ensino de Estatística apoia-se em Cazorla (2002), Lopes (2003, 2008, 2010a, 2010b), Silva (2007), Andrade (2008), Cazorla, Kataoka e Silva (2010), Jacobini et al. (2010), Campos, Wodewotzki e Jacobini (2011), dentre outros. Quanto a contextualização, a revisão de literatura apoia-se em Brasil (1998b, 1999), Tufano (2001), Pais (2002, 2010), Ramos (2004), Mello (2005), Sadovsky (2007), Luccas (2011), além de outros. Com a intenção de alcançar o objetivo proposto, foi desenvolvida no ano de 2011 uma pesquisa aplicada, qualitativa com análise interpretativa e, descritiva em uma turma de alunos do 7° ano do Ensino Fundamental de um colégio público estadual do município de Ponta Grossa, Paraná. A revisão de literatura referente às características da pesquisa fundamenta-se em Gil (1991, 2006), Chizzotti (2003, 2008), Silva e Menezes (2005), Moreira e Caleffe (2008), Alves-Mazzotti (2011), Sarmento (2011), Teixeira (2011), dentre outros. Primeiramente foi realizada uma análise do desempenho prévio dos alunos em relação a conteúdos básicos de Estatística, tendo como base um instrumento diagnóstico chamado pré – teste. Depois foi aplicada uma sequência de ensino direcionada a conteúdos básicos de Estatística, por meio da utilização de dados coletados na própria turma, ou seja, por meio da contextualização. Verificou-se durante a aplicação da sequência de ensino, um maior interesse e motivação dos alunos para as aulas, além de um maior envolvimento dos educandos com os conteúdos estudados. Os resultados da análise do desempenho dos alunos após a aplicação da sequência de ensino mostraram que essa contribuiu para que houvesse um ganho significativo quanto à aquisição de conteúdos básicos de Estatística por parte de educandos dos anos finais do Ensino Fundamental. Considera-se que as atividades realizadas com os educandos, contribuíram para o desenvolvimento das competências de raciocínio, pensamento e, letramento estatísticos desses, formando a base necessária para que futuramente esses alunos possam atingir o nível de letramento estatístico que a sociedade contemporânea exige. Como produto final deste trabalho foi elaborado um material didático de apoio ao professor contendo uma sequência de ensino contextualizada sobre conteúdos básicos de Estatística voltada ao Ensino Fundamental, o qual se encontra anexado a esta dissertação