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Kidney Blood Press Res ; : 1-9, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31683270


BACKGROUND: There is limited evidence on the etiology and outcomes of renal infarction. A provoking factor is identified only in one- to two-thirds of patients. METHODS: This is a retrospective observational study. The clinical characteristics and outcomes of patients with acute renal infarction were studied; the sample was divided into two groups according to the presence of at least one provoking factor at the time of diagnosis (atrial fibrillation, flutter, major thrombophilia, or renal artery malformations). RESULTS: The study comprised 59 patients with a mean age of 63 (±16.7) years and a follow-up period of 3.1 (±2.8) years. An identifiable provoking factor was found for 59.3% of the renal infarctions at the time of diagnosis, and atrial fibrillation was the most frequent one (in 49.2% of all patients). Renal impairment was found in 49.2% of the patients at diagnosis and in 50.8% of the patients 6 months after the event (p = 0.525). When compared with the idiopathic group, the patients with provoked infarction were older (69.8 vs. 57.9 years, p = 0.014) and had a higher rate of recurrence of arterial thrombosis during follow-up (18.8 vs. 0%, p = 0.028), but there were no differences in the rest of the baseline characteristics or in mortality rates. Six patients (10.2%) in the idiopathic group were diagnosed with atrial fibrillation during follow-up. CONCLUSIONS: Atrial fibrillation, both at diagnosis and at follow-up, is the most common identifiable cause of renal infarction; however, a significant number of patients are idiopathic, and these are younger, but they have a similar burden of cardiovascular disease and a lower risk of arterial recurrence.

Genet Med ; 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31578471


PURPOSE: Lamb-Shaffer syndrome (LAMSHF) is a neurodevelopmental disorder described in just over two dozen patients with heterozygous genetic alterations involving SOX5, a gene encoding a transcription factor regulating cell fate and differentiation in neurogenesis and other discrete developmental processes. The genetic alterations described so far are mainly microdeletions. The present study was aimed at increasing our understanding of LAMSHF, its clinical and genetic spectrum, and the pathophysiological mechanisms involved. METHODS: Clinical and genetic data were collected through GeneMatcher and clinical or genetic networks for 41 novel patients harboring various types ofSOX5 alterations. Functional consequences of selected substitutions were investigated. RESULTS: Microdeletions and truncating variants occurred throughout SOX5. In contrast, most missense variants clustered in the pivotal SOX-specific high-mobility-group domain. The latter variants prevented SOX5 from binding DNA and promoting transactivation in vitro, whereas missense variants located outside the high-mobility-group domain did not. Clinical manifestations and severity varied among patients. No clear genotype-phenotype correlations were found, except that missense variants outside the high-mobility-group domain were generally better tolerated. CONCLUSIONS: This study extends the clinical and genetic spectrum associated with LAMSHF and consolidates evidence that SOX5 haploinsufficiency leads to variable degrees of intellectual disability, language delay, and other clinical features.

Am J Hum Genet ; 105(2): 302-316, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31256877


Members of a paralogous gene family in which variation in one gene is known to cause disease are eight times more likely to also be associated with human disease. Recent studies have elucidated DHX30 and DDX3X as genes for which pathogenic variant alleles are involved in neurodevelopmental disorders. We hypothesized that variants in paralogous genes encoding members of the DExD/H-box RNA helicase superfamily might also underlie developmental delay and/or intellectual disability (DD and/or ID) disease phenotypes. Here we describe 15 unrelated individuals who have DD and/or ID, central nervous system (CNS) dysfunction, vertebral anomalies, and dysmorphic features and were found to have probably damaging variants in DExD/H-box RNA helicase genes. In addition, these individuals exhibit a variety of other tissue and organ system involvement including ocular, outer ear, hearing, cardiac, and kidney tissues. Five individuals with homozygous (one), compound-heterozygous (two), or de novo (two) missense variants in DHX37 were identified by exome sequencing. We identified ten total individuals with missense variants in three other DDX/DHX paralogs: DHX16 (four individuals), DDX54 (three individuals), and DHX34 (three individuals). Most identified variants are rare, predicted to be damaging, and occur at conserved amino acid residues. Taken together, these 15 individuals implicate the DExD/H-box helicases in both dominantly and recessively inherited neurodevelopmental phenotypes and highlight the potential for more than one disease mechanism underlying these disorders.

Int J Biol Macromol ; 136: 625-631, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31220501


Ribotoxins are fungal proteins that serve as weapons against parasites and insects. They are strongly toxic due to their ability to enter host cells and inactivate ribosomes. Ageritin is the prototype of a new ribotoxin-like protein family present in basidiomycetes. We demonstrate that this enzyme has peculiar binding and enzymatic features. Different from other ribotoxins, its ribonucleolytic activity requires the presence of divalent cations, with a maximum activation in the presence of zinc ions, for which Ageritin exhibits the strongest affinity of binding. We modeled the catalytic metal binding site of Ageritin, made of the putative triad Asp68, Asp70 and His77. This report highlights that Ageritin has the structure and function of an RNase but a Mg2+/Zn2+-dependent mechanism of action, a new finding for ribotoxins. As a zinc-dependent toxin, Ageritin can be classified among the arsenal of zinc-binding proteins involved in fungal virulence.

Int J Antimicrob Agents ; 54(2): 189-196, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31075401


Carbapenems are considered the treatment of choice for extended-spectrum ß-lactamase (ESBL)- or AmpC ß-lactamase-producing Enterobacteriaceae bacteraemia. Data on the effectiveness of non-intravenous carbapenem-sparing antibiotic options are limited. This study compared the 30-day mortality and clinical failure associated with the use of carbapenems versus alternative non-intravenous antibiotics for the definitive treatment of ESBL/AmpC-positive Enterobacteriaceae bacteraemia. This 12-year retrospective study (2004-2015) included all patients with bacteraemia due to ESBL/AmpC-producing Enterobacteriaceae at a Spanish hospital. Given the lack of randomisation of initial therapies, a propensity score for receiving carbapenems was calculated. There were 1115 patients with a first episode of bacteraemia due to Escherichia coli or Klebsiella pneumoniae, of which 123 (11.0%) were ESBL/AmpC-positive. There were 101 eligible patients: 59 in the carbapenem group and 42 in the alternative treatment group (trimethoprim/sulfamethoxazole 59.5%, quinolones 21.4%). The most frequent sources of infection were urinary (63%) and biliary (15%). Compared with the carbapenem group, patients treated with an alternative regimen had a shorter hospital stay [median (IQR) 7 (5-10) days vs. 12 (9-18) days; P < 0.001]. Use of an alternative non-intravenous therapy did not increase mortality (OR = 0.27, 95% CI 0.05-1.61; P = 0.15). After controlling for confounding factors with the propensity score, the adjusted OR of carbapenem treatment was 4.95 (95% CI 0.94-26.01; P = 0.059). Alternative non-intravenous carbapenem-sparing antibiotics could have a role in the definitive treatment of ESBL/AmpC-positive Enterobacteriaceae bacteraemia, allowing a reduction in carbapenem use. Use of trimethoprim/sulfamethoxazole in this series showed favourable results.

Molecules ; 24(1)2019 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-30621310


Sustained pacemaker function is a challenge in biological pacemaker engineering. Human cardiomyocyte progenitor cells (CMPCs) have exhibited extended survival in the heart after transplantation. We studied whether lentivirally transduced CMPCs that express the pacemaker current If (encoded by HCN4) can be used as functional gene delivery vehicle in biological pacing. Human CMPCs were isolated from fetal hearts using magnetic beads coated with Sca-1 antibody, cultured in nondifferentiating conditions, and transduced with a green fluorescent protein (GFP)- or HCN4-GFP-expressing lentivirus. A patch-clamp analysis showed a large hyperpolarization-activated, time-dependent inward current (-20 pA/pF at -140 mV, n = 14) with properties typical of If in HCN4-GFP-expressing CMPCs. Gap-junctional coupling between CMPCs and neonatal rat ventricular myocytes (NRVMs) was demonstrated by efficient dye transfer and changes in spontaneous beating activity. In organ explant cultures, the number of preparations showing spontaneous beating activity increased from 6.3% in CMPC/GFP-injected preparations to 68.2% in CMPC/HCN4-GFP-injected preparations (P < 0.05). Furthermore, in CMPC/HCN4-GFP-injected preparations, isoproterenol induced a significant reduction in cycle lengths from 648 ± 169 to 392 ± 71 ms (P < 0.05). In sum, CMPCs expressing HCN4-GFP functionally couple to NRVMs and induce physiologically controlled pacemaker activity and may therefore provide an attractive delivery platform for sustained pacemaker function.

Técnicas de Transferência de Genes , Ventrículos do Coração/transplante , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/genética , Proteínas Musculares/genética , Miócitos Cardíacos/transplante , Canais de Potássio/genética , Células-Tronco/citologia , Animais , Terapia Genética/métodos , Proteínas de Fluorescência Verde/química , Ventrículos do Coração/patologia , Humanos , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/uso terapêutico , Proteínas Musculares/uso terapêutico , Técnicas de Patch-Clamp , Canais de Potássio/uso terapêutico , Ratos , Transplante de Células-Tronco
Biochim Biophys Acta Gen Subj ; 1862(12): 2888-2894, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30262416


Ageritin has been recently described as the first ribotoxin-like from Basidiomycota division (mushroom Agrocybe aegerita) with known antitumor activity (BBA 2017, 1861: 1113-1121). By investigating structural, catalytic and binding properties, we demonstrate that Ageritin is a unique ribotoxin-like protein. Indeed, typical of the ribotoxin family, it shows the specific ribonucleolytic activity against the ribosomal Sarcin-Ricin Loop in a rabbit reticulocytes assay. However, it displays several elements of novelty, as this activity is strongly metal-dependent and completely suppressed in the presence of EDTA, different from other representative members of the ribotoxin family. Consistently, we prove that Ageritin is able to bind magnesium ions with low micromolar affinity. We also show that Ageritin is significantly more stable than other ribotoxins in thermal and chemical denaturation experiments. These peculiar features make Ageritin the prototype of a new ribotoxin-like family present in basidiomycetes. Finally, given its high stability, this enzyme is a promising candidate as a new tool in immunoconjugates and nanoconstructs.

Av. enferm ; 36(2): 209-219, maio-ago. 2018. tab, graf
Artigo em Espanhol | LILACS-Express | ID: biblio-973965


Resumen Objetivo: El propósito de esta revisión es conocer la evidencia científica existente de la relación entre la violencia contra la mujer (VCM) y su índice de masa corporal (IMC) (alto y bajo). Síntesis del contenido: Se realizó una revisión integradora de las publicaciones científicas que abordaron y relacionaran la VCM y el IMC en diferentes bases de datos. Se consideraron los siete pasos de Cooper. Se analizaron por título, año de publicación, autores y fuente; finalmente, se estudiaron los aspectos metodológicos. Se identificaron 85 artículos y se excluyeron 67 por no cumplir con los criterios de inclusión; seis de los artículos incluidos en la revisión, reportaron correlación positiva y significativa entre la VCM con el IMC alto (sobrepeso/obesidad). Asimismo, siete de los artículos refieren una relación significativa entre la VCM y el IMC bajo, de tal manera que a mayor violencia contra la mujer, se presenta un IMC más bajo en las mujeres. Conclusión: Los resultados encontrados muestran la existencia escasa de literatura científica que aborde la temática de la VCM y el IMC. Algunos estudios muestran la relación entre la VCM y el IMC alto y bajo. Los resultados no son concluyentes, por lo que se requiere generar líneas de acción y atención a las mujeres receptoras de los diferentes tipos de violencia.

Resumo Objetivo: O objetivo desta revisão é conhecer as evidências científicas existentes sobre a relação entre violencia contra mulheres (VCM) e seu índice de massa corporal (IMC) (baixo peso, sobrepeso/obesidade). Síntese do conteúdo: Uma revisão integrativa das publicações científicas que abordam e relacionam a vcm e o IMC em diferentes bases de dados. Os sete passos de Cooper foram considerados. Foram analisados por título, ano de publicação, autores e fonte; finalmente, os aspectos metodológicos foram estudados. Identificaram-se 85 artigos, 67 artigos foram excluídos porque não atendiam aos criterios de inclusão; seis dos artigos incluídos na revisão relataram uma correlação positiva e significativa entre a VMC com o IMC alto (sobrepeso/obesidade). Da mesma forma, sete dos artigos referem-se a uma relação significativa entre VMC e baixo IMC, ou seja, quanto maior a violência, um imc mais baixo é relatado. Conclusão: Os resultados mostram a existência de literatura científica escassa abordando a questão da VMC e IMC. Alguns estudos mostram a relação entre a violência contra as mulheres e o alto e baixo IMC. Os resultados não são conclusivos, por isso é necessário gerar linhas de ação e atenção às mulheres que recebem os diferentes tipos de violência.

Abstract Objective: The objective of this review is to know the existing scientific evidence of the relation between violence against women and their body mass index (BMI) (underweight, overweight/obese). Content synthesis: An integrative review of the scientific publications that approached and related violence against women and BMI in different databases. Cooper's seven steps were considered. They were analyzed by title, year of publication, authors and source; and, finally, by methodological aspects. It was possible to identify 85 articles, -67 articles were excluded because they did not meet the inclusion criteria-. Six of the articles included in the review reported a positive and significant correlation between violence against women with high BMI (overweight/obesity). In other words, the higher the violence, a high BMI is reported. Likewise, seven of the articles referred to a significant relation between violence against women and low BMI, such a way to greater violence against women, a lower women's BMI is found. Conclusion: The results show the existence of scarce scientific literature that addresses the issue of violence against women and BMI. Some studies expose the relation between violence against women and high and low BMI. The results are inconclusive, so it is necessary to generate lines of action and attention to women who suffer different types of violence.

Index enferm ; 27(1/2): 52-56, ene.-jun. 2018. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-175350


El incremento en el uso de los métodos anticonceptivos para la prevención de embarazos no planeados es una prioridad a nivel mundial, para los profesionales de enfermería es muy importante prevenir problemas reproductivos a través de teorizaciones aplicadas a la práctica de enfermería. Objetivo: Desarrollar una teoría de situación específica de enfermería de la conducta anticonceptiva en mujeres a partir de una teoría de rango medio. Método: Técnica de derivación de teoría de Walker y Avant. Resultados: el modelo de conducta anticonceptiva en mujeres incluye factores personales, interpersonales, sociales, que pueden ser medibles y aplicables a la práctica de enfermería y se derivan del cuerpo de conocimientos propios de enfermería. Conclusiones: la teoría de situación específica ofrece un sustento teórico para la investigación, la práctica y el desarrollo de la profesión, así mismo permite el desarrollo de intervenciones efectivas en salud

The increase in the use of contraceptive methods for the prevention of unplanned pregnancies is a priority at the global level, it is very important for nurses to prevent reproductive problems through theories applied to nursing practice. Objective: To develop a theory of the specific situation of nursing contraceptive behavior in women based on a theory of midrange. Method: Walker and Avant theory derivation technique. Results: the model of contraceptive behavior in women includes personal, interpersonal, and social factors, which can be measured and applicable to nursing practice and are derived from the nursing body of knowledge. Conclusions: specific situation theory offers a theoretical basis for the research, practice and development of the profession, as well as the development of effective interventions in health

Humanos , Feminino , Adulto Jovem , Comportamento Contraceptivo , Modelos de Enfermagem , Promoção da Saúde , Saúde Materna , Mulheres
Hisp Health Care Int ; 16(2): 56-61, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29781292


INTRODUCTION: The Contraceptive Behavior Scale requires adaptation for use by health professionals among Mexican heterosexual populations of reproductive age. METHODS: Cross-sectional, descriptive, correlational design assessed adaptation of the Contraceptive Behavior Scale. RESULTS: Six hundred Mexican men and women of reproductive age (18-35 years) were recruited from a second-level health care unit in a metropolitan area in Mexico. Exploratory factor analysis identified two factors with an explanatory variance of 69.238%. Confirmatory factor analysis identified acceptable index values. Cronbach alpha of .729 obtained for the scale was acceptable. Significant correlation ( p = .007) was observed between Contraceptive Conduct and participant gender. Component 1 constituted Items 1, 2, and 4, while Component 2 consisted of Items 3 and 5. No items were eliminated as adequate factorial saturation was present. CONCLUSIONS: The Contraceptive Conduct Scale is a reliable assessment tool for Mexican men and women of reproductive age. This scale is potentially useful for health professionals to assess contraceptive behavior in heterosexual couples of reproductive age. Clinicians may use the tool to obtain information for development of strategies responding to sexual and reproductive health needs of both men and women.

Anaerobe ; 2018 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-29698754


Clostridioides difficile (CD), previously known as Clostridium difficile, is an anaerobic Gram-positive rod-shaped bacterium that causes mild to severe diarrhea mainly in hospitalized patients. The bacteria are easily spread between patients and can persist in hospital wards due to its ability to form spores. An outbreak of CD causes great sufferings for patients and is in many aspects very expensive for the health care organization. Continuously monitoring circulating CD isolates in the hospital as well as being able to detect possible spread between patients at an early phase would be of great benefit. Recently a new method was published by Rizzardi et al. (2015) where CD can be typed to a High Molecular Weight (HMW)-profile using Matrix-Assisted Laser Desorption Ionization -Time of Flight Mass Spectrometry (MALDI-TOF MS). We analyzed 1000 isolates of toxin-positive CD with this method and compared the frequency of profiles within different hospitals as well as between two counties in the south-east part of Sweden. During the study period we could detect three outbreaks of CD in three different hospitals. One was an outbreak of CD with ribotype 027, resulting in severe consequences. The method was easily implemented at the clinical microbiology routine diagnostic laboratory and in collaboration with the hospitals Infection Control Units it is a very useful and cost-effective tool to detect outbreaks of CD at an early stage.

Artigo em Inglês | MEDLINE | ID: mdl-29162653


Using whole-exome sequencing, we identified seven unrelated individuals with global developmental delay, hypotonia, dysmorphic facial features, and an increased frequency of short stature, ataxia, and autism with de novo heterozygous frameshift, nonsense, splice, and missense variants in the Early B-cell Transcription Factor Family Member 3 (EBF3) gene. EBF3 is a member of the collier/olfactory-1/early B-cell factor (COE) family of proteins, which are required for central nervous system (CNS) development. COE proteins are highly evolutionarily conserved and regulate neuronal specification, migration, axon guidance, and dendritogenesis during development and are essential for maintaining neuronal identity in adult neurons. Haploinsufficiency of EBF3 may affect brain development and function, resulting in developmental delay, intellectual disability, and behavioral differences observed in individuals with a deleterious variant in EBF3.

Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Adolescente , Sequência de Aminoácidos/genética , Ataxia/genética , Transtorno Autístico/genética , Criança , Pré-Escolar , Sequência Conservada/genética , Deficiências do Desenvolvimento/genética , Exoma , Feminino , Humanos , Lactente , Deficiência Intelectual , Masculino , Hipotonia Muscular/genética , Mutação , Transtornos do Neurodesenvolvimento/genética , Síndrome de Prader-Willi/genética , Sequenciamento Completo do Exoma/métodos , Adulto Jovem