Nemaline Myopathy in Brazilian Patients: Molecular and Clinical Characterization

Nemaline myopathy (NM), a structural congenital myopathy, presents a significant clinical and genetic heterogeneity. Here, we compiled molecular and clinical data of 30 Brazilian patients from 25 unrelated families. Next-generation sequencing was able to genetically classify all patients: sixteen families (64%) with mutation in NEB, five (20%) in ACTA1, two (8%) in KLHL40, and one in TPM2 (4%) and TPM3 (4%). In the NEB-related families, 25 different variants, 11 of them novel, were identified; splice site (10/25) and frame shift (9/25) mutations were the most common. Mutation c.24579 G>C was recurrent in three unrelated patients from the same region, suggesting a common ancestor. Clinically, the “typical” form was the more frequent and caused by mutations in the different NM genes. Phenotypic heterogeneity was observed among patients with mutations in the same gene. Respiratory involvement was very common and often out of proportion with limb weakness. Muscle MRI patterns showed variability within the forms and genes, which was related to the severity of the weakness. Considering the high frequency of NEB mutations and the complexity of this gene, NGS tools should be combined with CNV identification, especially in patients with a likely non-identified second mutation

Nemaline Myopathy in Brazilian Patients: Molecular and Clinical Characterization

Nemaline myopathy (NM), a structural congenital myopathy, presents a significant clinical and genetic heterogeneity. Here, we compiled molecular and clinical data of 30 Brazilian patients from 25 unrelated families. Next-generation sequencing was able to genetically classify all patients: sixteen families (64%) with mutation in NEB, five (20%) in ACTA1, two (8%) in KLHL40, and one in TPM2 (4%) and TPM3 (4%). In the NEB-related families, 25 different variants, 11 of them novel, were identified; splice site (10/25) and frame shift (9/25) mutations were the most common. Mutation c.24579 G>C was recurrent in three unrelated patients from the same region, suggesting a common ancestor. Clinically, the “typical” form was the more frequent and caused by mutations in the different NM genes. Phenotypic heterogeneity was observed among patients with mutations in the same gene. Respiratory involvement was very common and often out of proportion with limb weakness. Muscle MRI patterns showed variability within the forms and genes, which was related to the severity of the weakness. Considering the high frequency of NEB mutations and the complexity of this gene, NGS tools should be combined with CNV identification, especially in patients with a likely non-identified second mutation

Butanol production in a sugarcane biorefinery using ethanol as feedstock. Part II: Integration to a second generation sugarcane distillery

Production of second generation ethanol and other added value chemicals from sugarcane bagasse and straw integrated to first generation sugarcane biorefineries presents large potential for industrial implementation, since part of the infrastructure where first generation ethanol is produced may be shared between both plants. In this context, butanol from renewable resources has attracted increasing interest, mostly for its use as a drop in liquid biofuel for transportation, since its energy density is greater than that of ethanol, but also for its use as feedstock in the chemical industry. In this paper, vapor-phase catalytic production of butanol from first and second generation ethanol in a sugarcane biorefinery was assessed, using data available from the literature. The objective is to evaluate the potential of butanol either as fuel or feedstock for industry, taking into account economical/environmental issues through computer simulation. The results obtained show that, although promising, butanol sold as chemical has a limited market and as fuel presents economic constraints. In addition, investments on the butanol conversion plant could be an obstacle to its practical implementation. Nevertheless, environmental assessment pointed out advantages of its use as fuel for road transportation, if compared with gasoline in terms of global environmental impacts such as global warming92814521462CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP476168/2013-92011/19396-6; 2010/17139-3; 2012/15192-

Butanol production in a sugarcane biorefinery using ethanol as feedstock. Part I: Integration to a first generation sugarcane distillery

Butanol production from renewable resources has been increasingly investigated over the past decade, mostly for its use as a liquid biofuel for road transportation, since its energy density is higher than that of ethanol and it may be used in gasoline driven engines with practically no changes, but also for use as a feedstock in the chemical industry. Most of the research concerning butanol production focuses on the ABE process (fermentation of sugars into a mixture of acetone, butanol and ethanol), which has several drawbacks regarding microorganism performance and product inhibition. An alternative to ABE fermentation, ethanol catalytic conversion to butanol can produce a higher quality product with less retrofitting than ABE in existing ethanol producing facilities. There are different types of catalysts for the chemical conversion of ethanol to butanol being developed in laboratory scale, but their actual use in a sugarcane processing plant has never before been assessed. Butanol production from ethanol in a sugarcane biorefinery, using data from the literature, was assessed in this study; different technological alternatives (catalytic routes) were evaluated through computer simulation in Aspen Plus (including production of electricity, sugar, ethanol and other products) and economic and environmental impacts were assessed. Results indicate that vapor-phase catalysis presents higher potential for industrial implementation, and commercialization of butanol for use as a chemical feedstock has an economic performance similar to that of current, optimized first generation sugarcane distilleries, but can potentially contribute to cost reduction that will allow commercialization of butanol as a fuel in the future92814411451CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP476168/2013-92011/19396-6; 2012/15192-0; 2010/17139-

An accurate and linear-scaling method for calculating charge-transfer excitation energies and diabatic couplings

Quantum–mechanical methods that are both computationally fast and accurate are not yet available for electronic excitations having charge transfer character. In this work, we present a significant step forward towards this goal for those charge transfer excitations that take place between non-covalently bound molecules. In particular, we present a method that scales linearly with the number of non-covalently bound molecules in the system and is based on a two-pronged approach: The molecular electronic structure of broken-symmetry charge-localized states is obtained with the frozen density embedding formulation of subsystem density-functional theory; subsequently, in a post-SCF calculation, the full-electron Hamiltonian and overlap matrix elements among the charge-localized states are evaluated with an algorithm which takes full advantage of the subsystem DFT density partitioning technique. The method is benchmarked against coupled-cluster calculations and achieves chemical accuracy for the systems considered for intermolecular separations ranging from hydrogen-bond distances to tens of Ångstroms. Numerical examples are provided for molecular clusters comprised of up to 56 non-covalently bound molecules

Nemaline Myopathy in Brazilian Patients: Molecular and Clinical Characterization

Nemaline myopathy (NM), a structural congenital myopathy, presents a significant clinical and genetic heterogeneity. Here, we compiled molecular and clinical data of 30 Brazilian patients from 25 unrelated families. Next-generation sequencing was able to genetically classify all patients: sixteen families (64%) with mutation in NEB, five (20%) in ACTA1, two (8%) in KLHL40, and one in TPM2 (4%) and TPM3 (4%). In the NEB-related families, 25 different variants, 11 of them novel, were identified; splice site (10/25) and frame shift (9/25) mutations were the most common. Mutation c.24579 G>C was recurrent in three unrelated patients from the same region, suggesting a common ancestor. Clinically, the "typical" form was the more frequent and caused by mutations in the different NM genes. Phenotypic heterogeneity was observed among patients with mutations in the same gene. Respiratory involvement was very common and often out of proportion with limb weakness. Muscle MRI patterns showed variability within the forms and genes, which was related to the severity of the weakness. Considering the high frequency of NEB mutations and the complexity of this gene, NGS tools should be combined with CNV identification, especially in patients with a likely non-identified second mutation

Primary results of the brazilian registry of atherothrombotic disease (NEAT)

Abstract There is limited contemporary prospective real-world evidence of patients with chronic arterial disease in Latin America. The Network to control atherothrombosis (NEAT) registry is a national prospective observational study of patients with known coronary (CAD) and/or peripheral arterial disease (PAD) in Brazil. A total of 2,005 patients were enrolled among 25 sites from September 2020 to March 2022. Patient characteristics, medications and laboratorial data were collected. Primary objective was to assess the proportion of patients who, at the initial visit, were in accordance with good medical practices (domains) for reducing cardiovascular risk in atherothrombotic disease. From the total of patients enrolled, 2 were excluded since they did not meet eligibility criteria. Among the 2,003 subjects included in the analysis, 55.6% had isolated CAD, 28.7% exclusive PAD and 15.7% had both diagnoses. Overall mean age was 66.3 (± 10.5) years and 65.7% were male patients. Regarding evidence-based therapies (EBTs), 4% were not using any antithrombotic drug and only 1.5% were using vascular dose of rivaroxaban (2.5 mg bid). Only 0.3% of the patients satisfied all the domains of secondary prevention, including prescription of EBTs and targets of body-mass index, blood pressure, LDL-cholesterol, and adherence of lifestyle recommendations. The main barrier for prescription of EBTs was medical judgement. Our findings highlight that the contemporary practice does not reflect a comprehensive approach for secondary prevention and had very low incorporation of new therapies in Brazil. Large-scale populational interventions addressing these gaps are warranted to improve the use of evidence-based therapies and reduce the burden of atherothrombotic disease. ClinicalTrials.gov NCT0467772