Molecular approaches for structural characterization of a new potassium channel blocker from Tityus stigmurus venom: cDNA cloning, homology modeling, dynamic simulations and docking

AbstractPotassium channels are involved in the maintenance of resting membrane potential, control of cardiac and neuronal excitability, neurotransmitters release, muscle contractility and hormone secretion. The Tityus stigmurus scorpion is widely distributed in Northeastern Brazil and known to cause severe human envenomations, inducing pain, hypoesthesia, edema, erythema, paresthesia, headaches and vomiting. Most potassium channel blocking peptides that have been purified from scorpion venoms contain 30–40 amino acids with three or four disulfide bridges. These peptides belong to α-KTx subfamily. On the other hand, the β-KTx subfamily is poorly characterized, though it is very representative in some scorpion venoms. A transcriptomic approach of T. stigmurus scorpions developed by our group revealed the repertoire of possible molecules present in the venom, including many toxins of the β-KTx subfamily. One of the ESTs found, named TSTI0003C has a cDNA sequence of 538bp codifying a mature protein with 47 amino acid residues, corresponding to 5299Da. This β-KTx peptide is a new member of the BmTXKβ-related toxins, and was here named TstKMK. The three-dimensional structure of this potassium channel toxin of the T. stigmurus scorpion was obtained by computational modeling and refined by molecular dynamic simulations. Furthermore, we have made docking simulations using a Shaker kV-1.2 potassium channel from rats as receptor model and proposed which amino acid residues and interactions could be involved in its blockade

Systems Biology-Based Analysis Indicates Global Transcriptional Impairment in Lead-Treated Human Neural Progenitor Cells

Lead poisoning effects are wide and include nervous system impairment, peculiarly during development, leading to neural damage. Lead interaction with calcium and zinc-containing metalloproteins broadly affects cellular metabolism since these proteins are related to intracellular ion balance, activation of signaling transduction cascades, and gene expression regulation. In spite of lead being recognized as a neurotoxin, there are gaps in knowledge about the global effect of lead in modulating the transcription of entire cellular systems in neural cells. In order to investigate the effects of lead poisoning in a systemic perspective, we applied the transcriptogram methodology in an RNA-seq dataset of human embryonic-derived neural progenitor cells (ES-NP cells) treated with 30 µM lead acetate for 26 days. We observed early downregulation of several cellular systems involved with cell differentiation, such as cytoskeleton organization, RNA, and protein biosynthesis. The downregulated cellular systems presented big and tightly connected networks. For long treatment times (12 to 26 days), it was possible to observe a massive impairment in cell transcription profile. Taking the enriched terms together, we observed interference in all layers of gene expression regulation, from chromatin remodeling to vesicle transport. Considering that ES-NP cells are progenitor cells that can originate other neural cell types, our results suggest that lead-induced gene expression disturbance might impair cells’ ability to differentiate, therefore influencing ES-NP cells’ fate

Evaluation of the use and need of dental prosthesis in a school clinic: a cross-study / Avaliação do uso e necessidade de prótese dentária numa clínica escola: um estudo transversal

Objective: This paper aims to identify the use and need of prosthesis, age and gender of users of the dental service of the school clinic of a private university in Recife. Methodology: A descriptive cross-sectional study was performed through analysis of medical records. From 2,294 records of the semesters 2016.2 and 2017.1, 790 were analyzed that met the inclusion and exclusion criteria. The study was divided into three groups according to the age of the patients (35 - 44, 45 - 64 and 65 - 74 years old) and were analyzed according to gender, prosthesis use, need of prosthesis or use and need of prosthesis. Data were tabulated in Microsoft Excel © and submitted to statistics. Results: Females were the most expressive in the search of the service (66.1%); besides that, 86.8% of the patients did not wear prosthesis and 71.1% needed to use it. Total Prosthesis was the most used (50%) and the Removable Partial Prosthesis presented the greatest need of use (74%). Conclusion: It was concluded that women from 45 – 64 years old seek more the rehabilitation service, and the need is greater in one arcade, showing an evolution to access the dentist. 

Clinical and molecular description of a high-copy IncQ1 KPC-2 plasmid harbored by the international ST15 Klebsiella pneumoniae clone

This study provides the genomic characterization and clinical description of bloodstream infections (BSI) cases due to ST15 KPC-2 producer Klebsiella pneumoniae. Six KPC-K. pneumoniae isolates were recovered in 2015 in a tertiary Brazilian hospital and were analyzed by whole-genome sequencing (WGS) (Illumina MiSeq short reads). Of these, two isolates were further analyzed by Nanopore MinION sequencing, allowing complete chromosome and plasmid circularization (hybrid assembly), using Unicycler software. The clinical analysis showed that the 30-day overall mortality for these BSI cases was high (83%). The isolates exhibited meropenem resistance (MICs, 32 to 128 mg/liter), with 3/6 isolates resistant to polymyxin B. The conjugative properties of the blaKPC-2 plasmid and its copy number were assessed by standard conjugation experiments and sequence copy number analysis. We identified in all six isolates a small (8.3-kb), high-copy-number (20 copies/cell) non-self-conjugative IncQ plasmid harboring blaKPC-2 in a non-Tn4401 transposon. This plasmid backbone was previously reported to harbor blaKPC-2 only in Brazil, and it could be comobilized at a high frequency (10−4) into Escherichia coli J53 and into several high-risk K. pneumoniae clones (ST258, ST15, and ST101) by a common IncL/M helper plasmid, suggesting the potential of international spread. This study thus identified the international K. pneumoniae ST15 clone as a carrier of blaKPC-2 in a high-copy-number IncQ1 plasmid that is easily transmissible among other common Klebsiella strains. This finding is of concern since IncQ1 plasmids are efficient antimicrobial resistance determinant carriers across Gram-negative species. The spread of such carbapenemase-encoding IncQ1 plasmids should therefore be closely monitored. IMPORTANCE In many parts of the world, carbapenem resistance is a serious public health concern. In Brazil, carbapenem resistance in Enterobacterales is mostly driven by the dissemination of KPC-2-producing K. pneumoniae clones. Despite being endemic in this country, only a few reports providing both clinical and genomic data are available in Brazil, which limit the understanding of the real clinical impact caused by the dissemination of different clones carrying blaKPC-2 in Brazilian hospitals. Although several of these KPC-2-producer K. pneumoniae isolates belong to the clonal complex 258 and carry Tn4401 transposons located on large plasmids, a concomitant emergence and silent dissemination of small high-copy-number blaKPC-2 plasmids are of importance, as described in this study. Our data identify a small high-copy-number IncQ1 KPC plasmid, its clinical relevance, and the potential for conjugative transfer into several K. pneumoniae isolates, belonging to different international lineages, such as ST258, ST101, and ST15

Tratamento farmacoterapêutico homeopático aos pacientes portadores de doenças crônicas / Homeopathic pharmacotherapeutic treatment for patients with chronic diseases

A homeopatia está se crescendo no mercado, sendo reconhecida como alternativa de tratamento e representação de saúde. Essa prática terapêutica de Samuel Hahnemann condiz em curar doentes frente aos medicamentos preparados por diluições infinitesimais que tem como capacidade produzir no indivíduo o bem-estar aos sintomas idênticos da doença. O objetivo deste estudo foi verificar na literatura vigente, a efetividade e adesão dos medicamentos na terapêutica dos pacientes. Trata-se de uma revisão integrativa da literatura, nas seguintes bases de dados: Scientific Eletronic Library Online (SCIELO); Medical Literature Analysis and Retrieval System Online (MEDLINE) e Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), utilizando os descritores em DeCS – Descritores em Ciências da Saúde – foram utilizados Homeopatia, Procedimentos terapêuticos e Enfermidades. A seleção respeitou critérios de inclusão/exclusão dos artigos disponíveis de forma completa e gratuita, entre os anos de 2015 a 2020, nos idiomas português, inglês e espanhol. Foram excluídos estudos que se mostravam inconclusos e/ou repetitivos. Foram encontrados 301 estudos dos quais 17 cumpriram os critérios previamente estabelecidos e foram incluídos na revisão. Na qual os pacientes estão obtendo resultados significativos nos tratamentos homeopáticos. É essencial entender que a Homeopatia está crescendo como alternativa terapêutica para o tratamento dos pacientes portadores de patologias crônicas. Portanto, e importante que entidades da saúde trabalhem  mais em terapias homeopáticas, fortalecendo investimento na farmacoterapia, oferecendo ao paciente  mais uma  alternativa de tratamento

A epidemiologia da cardiomiopatia de Takotsubo no Brasil e os principais fatores de risco da cardiomiopatia de Takotsubo: The epidemiology of Takotsubo cardiomyopathy in Brazil and the main risk factors for takotsubo cardiomyopathy

A Cardiomiopatia de Takotsubo (CTT) é uma disfunção cardíaca reversível, a qual está relacionada, diretamente, ao estresse físico ou emocional. Objetiva-se através dessa pesquisa evidenciar os principais fatores de risco da CT. Trata-se de uma revisão sistemática realizada no motor de busca Biblioteca Virtual em Saúde (BVS) na base de dados das “Ciências em Saúde em Geral” (Scielo, Medline, Lilacs). Percebeu-se que que a CT apresenta uma ocorrência maior em mulheres na fase de pós-menopausa, onde são atingidas pelo estresse emocional, bem como a inserção de marcapasso também pode desencadear a doença. Entretanto, a etiologia da CT ainda é marcada por controvérsias, mas há concordância acerca do surgimento da CT estar relacionado com a abundância de catecolaminas circulantes

Síndrome de DiGeorge: um relato de caso: DiGeorge's Syndrome: a case report

O presente artigo objetivou apresentar o caso clínico de uma paciente pediátrica diagnosticada com a síndrome de DiGeorge e que foi admitida no setor de Cardiologia Pediátrica para correção de malformação cardíaca. Este trabalho se trata de um estudo descritivo, do tipo relato de caso, que visou analisar as principais manifestações desse distúrbio genético, bem como suas abordagens diagnósticas e terapêuticas. A criança foi submetida à correção de defeito cardíaco característico da anomalia e evoluiu com parada cardiorrespiratória, prontamente revertida, e com crise convulsiva no pós-operatório. A anomalia possui espectro clínico diverso, com repercussões que impactam sobremaneira no equilíbrio eletrolítico e nos sistemas imunológico e cardiovascular, exigindo reconhecimento em tempo hábil e a adoção de condutas assertivas para reduzir a morbidade do portador