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1.
Proc Natl Acad Sci U S A ; 120(33): e2302661120, 2023 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-37549288

RESUMO

Polycystic Echinococcosis (PE), a neglected life-threatening zoonotic disease caused by the cestode Echinococcus vogeli, is endemic in the Amazon. Despite being treatable, PE reaches a case fatality rate of around 29% due to late or missed diagnosis. PE is sustained in Pan-Amazonia by a complex sylvatic cycle. The hunting of its infected intermediate hosts (especially the lowland paca Cuniculus paca) enables the disease to further transmit to humans, when their viscera are improperly handled. In this study, we compiled a unique dataset of host occurrences (~86000 records) and disease infections (~400 cases) covering the entire Pan-Amazonia and employed different modeling and statistical tools to unveil the spatial distribution of PE's key animal hosts. Subsequently, we derived a set of ecological, environmental, climatic, and hunting covariates that potentially act as transmission risk factors and used them as predictors of two independent Maximum Entropy models, one for animal infections and one for human infections. Our findings indicate that temperature stability promotes the sylvatic circulation of the disease. Additionally, we show how El Niño-Southern Oscillation (ENSO) extreme events disrupt hunting patterns throughout Pan-Amazonia, ultimately affecting the probability of spillover. In a scenario where climate extremes are projected to intensify, climate change at regional level appears to be indirectly driving the spillover of E. vogeli. These results hold substantial implications for a wide range of zoonoses acquired at the wildlife-human interface for which transmission is related to the manipulation and consumption of wild meat, underscoring the pressing need for enhanced awareness and intervention strategies.


Assuntos
Equinococose , Echinococcus , Animais , Humanos , Hotspot de Doença , Equinococose/epidemiologia , Zoonoses/epidemiologia , Fatores de Risco , El Niño Oscilação Sul
2.
Artigo em Inglês | MEDLINE | ID: mdl-35544312

RESUMO

An actinobacterium, designated strain EGI L10124T, was isolated from saline lake sediment collected in Xinjiang province, PR China. The taxonomic position of the isolate was determined based on polyphasic taxonomic and phylogenomic analyses. Phylogenetic analysis and 16S rRNA gene sequence similarities indicated that strain EGI L10124T formed a distinct clade with Rhabdothermincola sediminis SYSU G02662T, with a shared sequence identity of 95.2 %. The novel isolate could be distinguished from species in the genus Rhabdothermincola by its distinct phenotypic, physiological and genotypic characteristics. The cells of strain EGI L10124T were aerobic, Gram-stain-positive and short rod-shaped. Optimal growth conditions of strain EGI L10124T on marine agar 2216 were registered at pH 8.0 at 37 °C. In addition, meso-diaminopimelic acid was the diagnostic diamino acid in the cell-wall peptidoglycan. The major respiratory quinone was MK-9 (H8), while the major fatty acids were iso-C16 : 0, C17 : 0 and C16 : 0. The polar lipids included diphosphatidylglycerol, phosphatidylinositol mannoside and phosphatidylinositol. Based on the genome sequence of strain EGI L10124T, it appears that the G+C content of the novel isolate was 71.8 mol%. According to our data, strain EGI L10124T represents a new species of the genus Rhabdothermincola, for which the name Rhabdothermincola salaria sp. nov. is proposed. The type strain of the proposed novel isolate is EGI L10124T (=CGMCC 1.19113T=KCTC 49679T).


Assuntos
Actinobacteria , Perciformes , Animais , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/química , Lagos , Fosfolipídeos/química , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
3.
Arch Microbiol ; 204(5): 277, 2022 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-35460374

RESUMO

An actinobacterium, designated strain EGI L100131T, was isolated from saline lake sediment in Xinjiang Province, China. The taxonomic position of the isolate was determined using analysis based on the polyphasic taxonomy and phylogenomics. Phylogenetic analysis and 16S rRNA gene sequence similarities indicated that strain EGI L100131T formed a distinct clade with Ornithinimicrobium murale DSM 22056T and Ornithinimicrobium cavernae CFH 30183T, and shared sequence identities of 97.8% and 97.0%, respectively. The novel isolate could be distinguished from other species of the genus Ornithinimicrobium by its distinct phenotypic, physiological, and genotypic characteristics. Cells of strain EGI L100131T were aerobic, Gram-staining positive, and coccoid to rod-shaped. Optimal growing conditions of strain EGI L100131T occurred at pH 8.0 and 28 ºC. Ornithine was the diagnostic diamino acid in the cell-wall peptidoglycan. The respiratory quinone was MK-8 (H4), while the major fatty acids (> 10%) were C17:1 ω8c, C17:0, iso-C16:0, and iso-C15:0. The detected polar lipids included diphosphatidylglycerol, phosphatidylinositol, phosphatidylglycerol, and a glycophospholipid. The G + C content based on genomic DNA was 71.5%. According to the phenotypic, physiological, genotypic, and phylogenetic data, strain EGI L100131T represents a new species of the genus Ornithinimicrobium, for which the name Ornithinimicrobium sediminis sp. nov. is proposed. The type strain is EGI L100131T (= KCTC 49716 T = CGMCC 1.19241T).


Assuntos
Actinomycetales , Lagos , Técnicas de Tipagem Bacteriana , China , DNA Bacteriano/genética , Ácidos Graxos/química , Fosfolipídeos/química , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
4.
Port J Card Thorac Vasc Surg ; 28(4): 69, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-35334169

RESUMO

A 67-year-old man with fatigue and dyspnea, in NYHA class IV, was admitted to our hospital. His evaluation, physical examination, and other investigations were carried out. An atypical finding was found and he was referred for cardiac surgery.


Assuntos
Insuficiência Cardíaca , Neoplasias , Idoso , Dispneia/diagnóstico , Fadiga/diagnóstico , Insuficiência Cardíaca/diagnóstico , Hospitalização , Humanos , Masculino
5.
Port J Card Thorac Vasc Surg ; 28(3): 51-52, 2021 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-35333468

RESUMO

Supravalvular aortic stenosis is a rare congenital anomaly (less than 0.05% of all congenital heart defects). This aortic root anomaly consists in a narrow aortic lumen immediately above the aortic valve and represents the least common form of left ventricular outflow tract obstruction. Clinical presentation is usually in the first decades of life. In most cases, the aortic valve leaflets are morphologically normal. However, aortic insufficiency due the high systolic pressure proximal to the sinotubular junction is the most commonly abnormality described. There are very few cases described in the literature with concomitant valvular and supra-valvular aortic stenosis.


Assuntos
Estenose Aórtica Supravalvular , Insuficiência da Valva Aórtica , Estenose da Valva Aórtica , Cardiopatias Congênitas , Estenose Aórtica Supravalvular/diagnóstico por imagem , Valva Aórtica/diagnóstico por imagem , Insuficiência da Valva Aórtica/complicações , Estenose da Valva Aórtica/complicações , Cardiopatias Congênitas/complicações , Humanos
7.
Anesth Analg ; 131(5): 1520-1528, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33079875

RESUMO

BACKGROUND: Cerebral blood flow (CBF) is maintained over a range of blood pressures through cerebral autoregulation (CA). Blood pressure outside the range of CA, or impaired autoregulation, is associated with adverse patient outcomes. Regional oxygen saturation (rSO2) derived from near-infrared spectroscopy (NIRS) can be used as a surrogate CBF for determining CA, but existing methods require a long period of time to calculate CA metrics. We have developed a novel method to determine CA using cotrending of mean arterial pressure (MAP) with rSO2that aims to provide an indication of CA state within 1 minute. We sought to determine the performance of the cotrending method by comparing its CA metrics to data derived from transcranial Doppler (TCD) methods. METHODS: Retrospective data collected from 69 patients undergoing cardiac surgery with cardiopulmonary bypass were used to develop a reference lower limit of CA. TCD-MAP data were plotted to determine the reference lower limit of CA. The investigated method to evaluate CA state is based on the assessment of the instantaneous cotrending relationship between MAP and rSO2 signals. The lower limit of autoregulation (LLA) from the cotrending method was compared to the manual reference derived from TCD. Reliability of the cotrending method was assessed as uptime (defined as the percentage of time that the state of autoregulation could be measured) and time to first post. RESULTS: The proposed method demonstrated minimal mean bias (0.22 mmHg) when compared to the TCD reference. The corresponding limits of agreement were found to be 10.79 mmHg (95% confidence interval [CI], 10.09-11.49) and -10.35 mmHg (95% CI, -9.65 to -11.05). Mean uptime was 99.40% (95% CI, 99.34-99.46) and the mean time to first post was 63 seconds (95% CI, 58-71). CONCLUSIONS: The reported cotrending method rapidly provides metrics associated with CA state for patients undergoing cardiac surgery. A major strength of the proposed method is its near real-time feedback on patient CA state, thus allowing for prompt corrective action to be taken by the clinician.


Assuntos
Circulação Cerebrovascular , Homeostase , Monitorização Neurofisiológica Intraoperatória/métodos , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Pressão Arterial , Pressão Sanguínea , Ponte Cardiopulmonar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Estudos Retrospectivos , Ultrassonografia Doppler Transcraniana
8.
Rev. Ciênc. Méd. Biol. (Impr.) ; 19(2): 305-310, set 24, 2020. tab
Artigo em Inglês | LILACS | ID: biblio-1358273

RESUMO

Introduction: breast cancer (BC) is the most common tumor and the leading cause of cancer-related death among the female population worldwide. Polymorphisms genetics of ABCB1 gene contributed to breast cancer susceptibility and interindividual differences in chemotherapy response. Objectives: to evaluate the association between the ABCB1 C3435T gene polymorphism (SNPs) with the response to neoadjuvant chemotherapy in women with breast cancer. Methodology: this study included 32 female patients who received neoadjuvant chemotherapy. The polymorphisms were genotyped through real-time allele-specific polymerase chain reaction (PCR). The statistical analysis was performed using the Fisher's exact test or Pearson's chi-square test in the Statistical Package for Social Sciences (SPSS) version 20.0 software. Results: the genotypes found for the C3435T polymorphism were in Hardy-Weinberg equilibrium and their genotypic distributions were CC= 10 (31.1%), CT= 14 (43.8%), and TT= 08 (25.0%) with χ2: 0.86 and p-value > 0.05. Allele frequencies were C = 0.54 and T = 0.46. There were no significant statistical differences between genotypes considering the response to neoadjuvant chemotherapy and immunohistochemistry; the presence of the T allele was associated with worsen axillary status response to neoadjuvant chemotherapy. Conclusion: no definite association between the presence of C3435T polymorphism and the response to neoadjuvant chemotherapy was observed. Further studies in Brazil involving larger samples will contribute to validating the results of this study.


Introdução: o câncer de mama (CM) é o tumor mais comum e a principal causa de morte relacionada ao câncer na população feminina em todo o mundo. Polimorfismos genéticos do gene ABCB1 contribuem para a suscetibilidade ao câncer de mama e diferenças interindividuais na resposta à quimioterapia. Objetivos: avaliar a associação entre o polimorfismo (SNPs) do gene ABCB1 C3435T com a resposta à quimioterapia neoadjuvante em mulheres com câncer de mama. Metodologia: estudo com 32 pacientes do sexo feminino, que utilizaram quimioterapia neoadjuvante. A genotipagem dos polimorfismos foi feita por reação da polimerase em cadeia (PCR) em tempo real alelo específica. A análise estatística foi realizada mediante o teste exato de Fisher ou Qui-quadrado de Pearson, utilizando o software SPSS (Statistical Package for the Social Sciences) vs20.0. Resultados: os genótipos encontrados para o polimorfismo C3435T estavam em equilíbrio de Hardy-Weinberg e suas distribuições genotípicas foram respectivamente CC= 10 (31,1%), CT= 14 (43,8%), TT= 08 (25,0%) sendo, X2: 0.86 e p-value> 0,05. As frequências alélicas foram de C= 0,54 e T= 0,46. Não ocorreram diferenças estatísticas entre os genótipos, considerando a resposta a quimioterapia neoadjuvante e a imunohistoquímica, sendo a presença do alelo T associada a pior resposta do status axilar à quimioterapia neoadjuvante. Conclusão: não foi possível correlacionar a presença do polimorfismo C3435T com a resposta à quimioterapia neoadjuvante, sendo necessária a realização de novos estudos no Brasil envolvendo casuísticas maiores para a validação dos resultados.


Assuntos
Humanos , Feminino , Polimorfismo Genético , Neoplasias da Mama , Tratamento Farmacológico , Estudos Prospectivos , Estudo Observacional
9.
Microb Biotechnol ; 13(4): 844-887, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32406115

RESUMO

We have recently argued that, because microbes have pervasive - often vital - influences on our lives, and that therefore their roles must be taken into account in many of the decisions we face, society must become microbiology-literate, through the introduction of relevant microbiology topics in school curricula (Timmis et al. 2019. Environ Microbiol 21: 1513-1528). The current coronavirus pandemic is a stark example of why microbiology literacy is such a crucial enabler of informed policy decisions, particularly those involving preparedness of public-health systems for disease outbreaks and pandemics. However, a significant barrier to attaining widespread appreciation of microbial contributions to our well-being and that of the planet is the fact that microbes are seldom visible: most people are only peripherally aware of them, except when they fall ill with an infection. And it is disease, rather than all of the positive activities mediated by microbes, that colours public perception of 'germs' and endows them with their poor image. It is imperative to render microbes visible, to give them life and form for children (and adults), and to counter prevalent misconceptions, through exposure to imagination-capturing images of microbes and examples of their beneficial outputs, accompanied by a balanced narrative. This will engender automatic mental associations between everyday information inputs, as well as visual, olfactory and tactile experiences, on the one hand, and the responsible microbes/microbial communities, on the other hand. Such associations, in turn, will promote awareness of microbes and of the many positive and vital consequences of their actions, and facilitate and encourage incorporation of such consequences into relevant decision-making processes. While teaching microbiology topics in primary and secondary school is key to this objective, a strategic programme to expose children directly and personally to natural and managed microbial processes, and the results of their actions, through carefully planned class excursions to local venues, can be instrumental in bringing microbes to life for children and, collaterally, their families. In order to encourage the embedding of microbiology-centric class excursions in current curricula, we suggest and illustrate here some possibilities relating to the topics of food (a favourite pre-occupation of most children), agriculture (together with horticulture and aquaculture), health and medicine, the environment and biotechnology. And, although not all of the microbially relevant infrastructure will be within reach of schools, there is usually access to a market, local food store, wastewater treatment plant, farm, surface water body, etc., all of which can provide opportunities to explore microbiology in action. If children sometimes consider the present to be mundane, even boring, they are usually excited with both the past and the future so, where possible, visits to local museums (the past) and research institutions advancing knowledge frontiers (the future) are strongly recommended, as is a tapping into the natural enthusiasm of local researchers to leverage the educational value of excursions and virtual excursions. Children are also fascinated by the unknown, so, paradoxically, the invisibility of microbes makes them especially fascinating objects for visualization and exploration. In outlining some of the options for microbiology excursions, providing suggestions for discussion topics and considering their educational value, we strive to extend the vistas of current class excursions and to: (i) inspire teachers and school managers to incorporate more microbiology excursions into curricula; (ii) encourage microbiologists to support school excursions and generally get involved in bringing microbes to life for children; (iii) urge leaders of organizations (biopharma, food industries, universities, etc.) to give school outreach activities a more prominent place in their mission portfolios, and (iv) convey to policymakers the benefits of providing schools with funds, materials and flexibility for educational endeavours beyond the classroom.


Assuntos
Amiloidose , Pré-Albumina , Adulto , Benzoxazóis , Criança , Humanos
10.
Brain ; 142(8): 2402-2416, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31243443

RESUMO

Ever since its introduction 40 years ago l-3,4-dihydroxyphenylalanine (l-DOPA) therapy has retained its role as the leading standard medication for patients with Parkinson's disease. With time, however, the shortcomings of oral l-DOPA treatment have become apparent, particularly the motor fluctuations and troublesome dyskinetic side effects. These side effects, which are caused by the excessive swings in striatal dopamine caused by intermittent oral delivery, can be avoided by delivering l-DOPA in a more continuous manner. Local gene delivery of the l-DOPA synthesizing enzymes, tyrosine hydroxylase and guanosine-tri-phosphate-cyclohydrolase-1, offers a new approach to a more refined dopaminergic therapy where l-DOPA is delivered continuously at the site where it is needed i.e. the striatum. In this study we have explored the therapeutic efficacy of adeno-associated viral vector-mediated l-DOPA delivery to the putamen in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated rhesus monkeys, the standard non-human primate model of Parkinson's disease. Viral vector delivery of the two enzymes, tyrosine hydroxylase and guanosine-5'-tri-phosphate-cyclohydrolase-1, bilaterally into the dopamine-depleted putamen, induced a significant, dose-dependent improvement of motor behaviour up to a level identical to that obtained with the optimal dose of peripheral l-DOPA. Importantly, this improvement in motor function was obtained without any adverse dyskinetic effects. These results provide proof-of-principle for continuous vector-mediated l-DOPA synthesis as a novel therapeutic strategy for Parkinson's disease. The constant, local supply of l-DOPA obtained with this approach holds promise as an efficient one-time treatment that can provide long-lasting clinical improvement and at the same time prevent the appearance of motor fluctuations and dyskinetic side effects associated with standard oral dopaminergic medication.


Assuntos
Antiparkinsonianos/administração & dosagem , GTP Cicloidrolase/administração & dosagem , Vetores Genéticos/uso terapêutico , Levodopa/biossíntese , Transtornos Parkinsonianos/terapia , Putamen/metabolismo , Tirosina 3-Mono-Oxigenase/administração & dosagem , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/efeitos adversos , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/análogos & derivados , Animais , Antiparkinsonianos/uso terapêutico , Dependovirus/genética , Avaliação Pré-Clínica de Medicamentos , Feminino , GTP Cicloidrolase/análise , GTP Cicloidrolase/genética , GTP Cicloidrolase/metabolismo , Genes Reporter , Genes Sintéticos , Vetores Genéticos/administração & dosagem , Humanos , Macaca mulatta , Masculino , Atividade Motora/efeitos dos fármacos , Transtornos Parkinsonianos/induzido quimicamente , Parte Compacta da Substância Negra/química , Parte Compacta da Substância Negra/patologia , Estudo de Prova de Conceito , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/análise , Proteínas Recombinantes/uso terapêutico , Tirosina 3-Mono-Oxigenase/análise , Tirosina 3-Mono-Oxigenase/genética , Tirosina 3-Mono-Oxigenase/metabolismo
11.
Rev Med Suisse ; 14(622): 1806-1809, 2018 Oct 10.
Artigo em Francês | MEDLINE | ID: mdl-30307141

RESUMO

Extraspinal tuberculous arthritis is a rare entity in developed countries, mostly found in populations of migrants. We describe a case of foot osteoarthritis in a young migrant, with an arduous diagnostic process. The sequence of the diagnostic studies (imaging, articular tap, bone biopsy together with cultures and molecular biology) must follow a logic based on clinical suspicion and on the knowledge of the diagnostic values of different tests. The diagnosis of tuberculous arthritis, a slowly progressing infection with a low bacteriologic burden, is difficult. The reported case emphases the need for perseverance. It shows the value of diagnostic procedures, their limits and the need for their integration to the clinical judgement.


L'arthrite tuberculeuse non rachidienne est rare dans les pays occidentaux où elle touche avant tout les populations de migrants. Nous décrivons un cas d'ostéoarthrite du pied, dont le processus diagnostique s'est révélé ardu. La succession des examens pratiqués (radiologie, ponction puis biopsie avec les cultures et la biologie moléculaire) doit s'inscrire dans une logique dictée par la suspicion clinique et la connaissance des performances diagnostiques des différents tests. Le diagnostic d'arthrite tuberculeuse, une infection d'évolution lente, pauvre en charge bactérienne, est difficile. Le cas présenté révèle le besoin de persévérer et permet de discuter la valeur des procédures diagnostiques, leurs limites et leur intégration dans le raisonnement clinique.


Assuntos
Artrite , Tuberculose Osteoarticular , Artrite/diagnóstico , Artrite/microbiologia , Humanos , Tuberculose Osteoarticular/diagnóstico
12.
Arq. bras. cardiol ; 111(2): 151-159, Aug. 2018. tab, graf
Artigo em Inglês | LILACS | ID: biblio-950206

RESUMO

Abstract Background: The dissatisfaction of health professionals in emergency services has a negative influence on both the quality of care provided for acute myocardial infarction (AMI) patients and the retention of those professionals. Objective: To assess physicians' satisfaction with the structure of care and diagnosis at the emergency services in the Northern Region of Minas Gerais before the implementation of the AMI system of care. Methods: This cross-sectional study included physicians from the emergency units of the ambulance service (SAMU) and level II, III and IV regional hospitals. Satisfaction was assessed by using the CARDIOSATIS-Team scale. The median score for each item, the overall scale and the domains were calculated and then compared by groups using the non-parametric Mann-Whitney test. Correlation between time since graduation and satisfaction level was assessed using Spearman correlation. A p value < 0.05 was considered significant. Results: Of the 137 physicians included in the study, 46% worked at SAMU. Most of the interviewees showed overall dissatisfaction with the structure of care, and the median score for the overall scale was 2.0 [interquartile range (IQR) 2.0-4.0]. Most SAMU physicians expressed their dissatisfaction with the care provided (54%), the structure for managing cardiovascular diseases (52%), and the technology available for diagnosis (54%). The evaluation of the overall satisfaction evidenced that the dissatisfaction of SAMU physicians was lower when compared to that of hospital emergency physicians. Level III/IV hospital physicians expressed greater overall satisfaction when compared to level II hospital physicians. Conclusion: This study showed the overall dissatisfaction of the emergency physicians in the region assessed with the structure of care for cardiovascular emergencies.


Resumo Fundamentos: A insatisfação dos profissionais de saúde dos serviços de urgência tem influência negativa na qualidade do cuidado ao infarto agudo do miocárdio (IAM) e na fixação desses profissionais. Objetivo: Avaliar a satisfação de médicos com a estrutura de atendimento e diagnóstico de serviços públicos de urgência na Região Ampliada Norte de Minas Gerais, previamente à implantação da linha de cuidado ao IAM. Métodos: Estudo transversal, que incluiu médicos das unidades de emergência do SAMU e de hospitais regionais nível II, III e IV. Foi avaliada a satisfação usando a escala CARDIOSATIS-Team. O escore mediano para cada item, a escala global e os domínios foram calculados e então comparados por grupos, utilizando o teste não paramétrico de Mann-Whitney. Foi avaliada a correlação entre tempo de formação e nível de satisfação com o método de Spearman. Um valor-p < 0,05 foi considerado significativo. Resultados: De 137 médicos incluídos, 46% trabalhavam no SAMU. A maior parte dos entrevistados demonstrou insatisfação geral com a estrutura de atendimento, cuja mediana da escala global foi 2,0 (intervalo interquartil [IQ] 2,0-4,0). A maioria dos médicos do SAMU demonstrou-se insatisfeita quanto a atendimento prestado (54%), estrutura para condução das doenças cardiovasculares (52%) e tecnologia disponível para diagnóstico (54%). Na avaliação da satisfação global, evidenciou-se que a insatisfação dos médicos do SAMU foi menor quando comparada à dos médicos de urgência hospitalar. Os médicos de hospitais nível III/IV demonstraram maior satisfação global quando comparados aos de hospitais nível II. Conclusão: Este estudo demonstrou insatisfação geral dos médicos dos serviços de urgência na região em relação à estrutura de atendimento às emergências cardiovasculares.


Assuntos
Humanos , Masculino , Feminino , Serviços Médicos de Emergência/estatística & dados numéricos , Medicina de Emergência/estatística & dados numéricos , Satisfação no Emprego , Corpo Clínico Hospitalar/estatística & dados numéricos , Infarto do Miocárdio/terapia , Estudos Transversais , Inquéritos e Questionários
13.
Brain ; 141(7): 2014-2031, 2018 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-29788236

RESUMO

Recombinant adeno-associated viruses (AAVs) are popular in vivo gene transfer vehicles. However, vector doses needed to achieve therapeutic effect are high and some target tissues in the central nervous system remain difficult to transduce. Gene therapy trials using AAV for the treatment of neurological disorders have seldom led to demonstrated clinical efficacy. Important contributing factors are low transduction rates and inefficient distribution of the vector. To overcome these hurdles, a variety of capsid engineering methods have been utilized to generate capsids with improved transduction properties. Here we describe an alternative approach to capsid engineering, which draws on the natural evolution of the virus and aims to yield capsids that are better suited to infect human tissues. We generated an AAV capsid to include amino acids that are conserved among natural AAV2 isolates and tested its biodistribution properties in mice and rats. Intriguingly, this novel variant, AAV-TT, demonstrates strong neurotropism in rodents and displays significantly improved distribution throughout the central nervous system as compared to AAV2. Additionally, sub-retinal injections in mice revealed markedly enhanced transduction of photoreceptor cells when compared to AAV2. Importantly, AAV-TT exceeds the distribution abilities of benchmark neurotropic serotypes AAV9 and AAVrh10 in the central nervous system of mice, and is the only virus, when administered at low dose, that is able to correct the neurological phenotype in a mouse model of mucopolysaccharidosis IIIC, a transmembrane enzyme lysosomal storage disease, which requires delivery to every cell for biochemical correction. These data represent unprecedented correction of a lysosomal transmembrane enzyme deficiency in mice and suggest that AAV-TT-based gene therapies may be suitable for treatment of human neurological diseases such as mucopolysaccharidosis IIIC, which is characterized by global neuropathology.


Assuntos
Capsídeo/fisiologia , Terapia Genética/métodos , Engenharia de Proteínas/métodos , Animais , Dependovirus/genética , Feminino , Vetores Genéticos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mucopolissacaridose III/genética , Mucopolissacaridose III/terapia , Células Fotorreceptoras/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Retina/fisiologia , Distribuição Tecidual , Transdução Genética
14.
Dermatol Ther (Heidelb) ; 8(2): 203-216, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29214505

RESUMO

INTRODUCTION: Cutaneous warts are common skin lesions, caused by human papillomavirus. For years, liquid nitrogen is the cryogen of choice for wart treatment. Alternatively, several cryogenic devices for home treatment are commercially available. The present trial assessed efficacy and safety of a novel nitrous oxide-based cryogenic device for home use (EndWarts Freeze® in Europe, Compound W® Nitro-Freeze in the USA). METHODS: This investigator-blinded, controlled, randomized study compared the nitrous oxide device (test product) with a dimethylether propane-based product (Wartner®; comparator 1). Subjects with common or plantar warts (50/50 ratio) were randomized into two groups (n = 58, test product; n = 40, comparator 1). Sequentially, an extra treatment arm (n = 40) was added to compare with a dimethylether-based product with metal nib (Wortie®; comparator 2). Main objective implied comparison of the percentage cured subjects after one to maximum three treatments. Efficacy and safety was evaluated by a blinded investigator. RESULTS: After a maximum of three applications, a significantly (p = 0.001) higher cure rate of 70.7% (Intention-to-Treat analysis) was observed with test product versus 46.2% (comparator 1) and 47.5% (comparator 2). Almost three times more subjects were cured after 1 test product application (29.3%), versus comparator 1 (10.4%) and comparator 2 (12.5%). Reported side effects were transient and typical of cryotherapy. All treatments were well-tolerated. CONCLUSION: The superior cure rates for the test product versus two comparators can be explained by its design. Combination of nitrous oxide (cooling agent), the specific activation method (holding the liquid coolant in the cap), and skin-conforming polyurethane foam, results in higher cooling efficiency (- 80 °C) and more effective wart freezing. This trial demonstrated that the nitrous oxide device is a safe, user-friendly and effective wart treatment for home use, comparing favourably to dimethylether (propane) devices with higher freezing temperature, regardless of the applicator type. FUNDING: Oystershell Laboratories. TRIAL REGISTRATION: Clinicaltrials.gov identifier, NCT03129373.

15.
Rev. méd. Minas Gerais ; 27: [1-7], jan.-dez. 2017.
Artigo em Português | LILACS | ID: biblio-979673

RESUMO

O objetivo deste artigo é relatar a experiência exitosa da Rede de Teleassistência de Minas Gerais (RTMG), um serviço público de telessaúde em larga escala. A RTMG foi constituída pela parceria entre seis universidades públicas do estado de Minas Gerais (MG). Recursos públicos e de agências de pesquisa financiaram suas atividades. A telecardiologia foi o foco inicial da Rede com realização de eletrocardiograma (ECG) e plantões de cardiologia, posteriormente, um sistema de teleconsultoria em especialidades foi incorporado. A RTMG atualmente abrange 780 municípios com 1.000 pontos de telessaúde em MG. De junho de 2006 a março de 2016, 2,538,592 ECGs e 75,866 teleconsultorias foram realizados e mais de 8.000 profissionais foram treinados. As atividades da RTMG possibilitam o acesso de pacientes de municípios remotos ao cuidado especializado, qualifica os encaminhamentos e contribui para a melhoria do cuidado. Atualmente, os serviços de telessaúde foram integrados ao sistema de saúde em MG. (AU)


The purpose of this article is to report the successful experience of The Telehealth Network of Minas Gerais (TNMG), a public service of telehealth on a large scale. The TNMG was formed through a partnership among six public universities at the Minas Gerais (MG) state. Public funding and research agencies support their activities. The telecardiology was the initial focus providing tele-electrocardiography, later teleconsulting in specialties was incorporated. The TNMG currently covers 780 municipalities in MG with 1,000 points in telehealth. From June 2006 to March 2016, a total of 2,538,592 and 75.866 teleconsultation were done and more than 8,000 professionals were trained. The activities of TNMG allow access of patients from remote municipalities to specialized healthcare, qualify referrals and contribute to the improvement of care. Currently, telehealth services were integrated into to the health system in MG. (AU)


Assuntos
Atenção Primária à Saúde , Telemedicina , Universidades , Sistemas de Saúde , Consulta Remota
16.
Rev Port Cir Cardiotorac Vasc ; 24(3-4): 119, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29701351

RESUMO

INTRODUCTION: The management of induction and maintenance immunosuppression therapy after heart transplantation (HT) remains a controversial issue. The dosage and the timing has been a changing target. We aimed at evaluate the incidence of acute cellular rejection (ACR) [≥1R grade], major infection and survival in first year after HT in patients receiving two different induction immunosuppression regimes and with a reduction in intensity of triple maintenance immunosuppression dose. METHODS: From November-2003 to June-2016, 317 patients were submitted to HT. After excluding those with pediatric age (n=8), those with previous renal or hepatic transplantation (n=2), those submitted to retransplantation (n=2), patients with early death without endomiocardial biopsy (n=10) and those in a transition maintenance regime (n=26), the study population resulted in 269 patients. These patients were divided in two groups: patients receiving the previous regime of two doses of basiliximab (group A, n=211) and those receiving a single dose of basiliximab (group B, n=58). All the patients were treated with a maintenance standard triple immunosuppressive regimen of corticosteroids, an inhibitor of calcineurin and mycophenolate mofetil but more immunosuppressive load in group A. RESULTS: Mean age of the recipients (group A vs. group B) was 54.6±10.6vs.55.0±9.8 years (p=0.808); 77.3%vs.75.9% were male (p=0.861); 28.4%vs.28.1% were diabetic (p=0.957); and ischemic etiology was present in 39.8%vs 41.0% of the patients (p=0.798), respectively. No differences were found, at first year, between the two groups concerning global ACR incidence (55.0%vs.56.9%, p=0.882, respectively) but major ACR (≥2R grade) was slightly superior in group B (16.6%vs.27.6%, p=0.080, respectively). Time-free from major ACR at 3rd, 6th and 12th months was, respectively 91.0±2.0%vs.84.5%±4.8%; 86.7±2.3%vs.74.1±5.7%; and 83.4±2.6%vs.72.4±5.9% (p=0.048). Time-free from major infection at 3rd, 6th and 12th months was, respectively 89.6±2.1%vs.82.8±5.0%; 87.7±2.3%vs.79.3±5.3%; and 84.4±2.5%vs.79.3±5.3% (p=0.253). No differences were found concerning survival at 3rd, 6th and 12th months (94.3±1.6%vs.94.8±2.9%; 92.4±1.8%vs.93.1±3.3%; and 90.0±2.1%vs.91.4±3.7%, (p=0.771) respectively). CONCLUSION: With this study, we verified that lowering doses of induction and maintenance therapy was responsible for increase cases of major ACR at first year of heart transplant. However, no differences were found concerning the incidence of major infection and early survival. Hence, effective immunosuppression induction regimen can apparently be done safely with a single dose regime without compromising survival at first year after HT.


Assuntos
Transplante de Coração , Imunossupressores , Adulto , Feminino , Rejeição de Enxerto , Humanos , Imunossupressores/uso terapêutico , Masculino
17.
Rev Port Cir Cardiotorac Vasc ; 24(3-4): 158, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29701389

RESUMO

INTRODUCTION: Coronary allograft vasculopathy (CAV) is still a serious long-term complication after cardiac transplantation. PURPOSE: To evaluate the prevalence of CAV in a single institution, its impact on survival and to explore associated risk factors. METHODS: From November-2003 through June-2016, 316 patients were submitted to cardiac transplantation. After excluding those with paediatric age (n=8), those with previous renal or hepatic transplantation (n=2) and those who didn't survive the first year after cardiac transplantation (n=40), the study population resulted in 266 patients. Forty two patients (15.8%) with CAV, diagnosed by a new >50% coronary artery stenosis in any vessel during follow-up, were compared with a non-CAV group. RESULTS: Both groups share de same median age (54+10years). Recipient male sex predominated in the CAV group (93% vs. 74%), as did ischemic etiology (52% vs. 37%). Although not reaching statistical significance, CAV patients also had more dyslipidemia (60% vs. 50%), history of smoking (52% vs. 44%) and peripheral vascular disease (45% vs. 29%). The incidence of celular acute rejection 1R is more frequent in CAV group (69% vs. 60%) such as 2R or 3R (29% vs. 27%). Prolonged use of inotropic support and mechanical assistance after cardiac transplantation were comparable between both groups. The survival of this patients, who were submitted to cardiac transplantation and had lived at least 1 year, between CAV and non-CAV group was comparable at 5-year (91% vs. 85%), but tended to be lower for CAV patients in 10-year interval (52% vs. 73%). CONCLUSION: This data confirms CAV as a common long-term complication following cardiac transplantation. Although short to mid-term survival seems not to be affected by CAV, long-term survival appears lower, hence a longer follow-up is needed.


Assuntos
Aloenxertos , Doença da Artéria Coronariana , Transplante de Coração , Adulto , Idoso , Aloenxertos/patologia , Criança , Angiografia Coronária , Doença da Artéria Coronariana/cirurgia , Transplante de Coração/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Fatores de Risco
18.
Rev. Soc. Bras. Med. Trop ; 49(6): 713-720, Dec. 2016. tab, graf
Artigo em Inglês | LILACS | ID: biblio-829676

RESUMO

Abstract: INTRODUCTION: Chagas disease currently affects 5.7 million people in Latin America and is emerging in non-endemic countries. There is no consensus concerning the efficacy of trypanocidal therapy for patients with the chronic form of the disease. We evaluated cardiac function and sociodemographic, clinical, and serologic characteristics of a group of asymptomatic Trypanosoma cruzi-seropositive former blood donors, and compared the effects of benznidazole treatment applied for different lengths of time. METHODS: Blood donors who screened positive for T. cruzi between 1998 and 2002 were recruited 10 years later for follow-up (n = 244); 46 individuals had received treatment. Three subjects had terminated treatment prematurely. The remaining 43 individuals were divided into two groups: individuals who had received benznidazole therapy for 50-60 days (n = 28; BT ≤60 group) or more than 60 days (n = 15; BT >60). Serologic assays, biochemical tests, electrocardiographic, echocardiographic, and clinical examinations were performed on all participants. Parasite loads were determined by qualitative and quantitative polymerase chain reaction. RESULTS: Parasitemia was significantly reduced in the BT ≤60 and BT >60 groups compared with the untreated group. There were no differences in epidemiologic profiles or clinical, biochemical, electrocardiographic, or echocardiographic data between any of the groups. CONCLUSIONS: Despite elimination or significant reduction in parasitemia in patients with chronic Chagas disease who received benznidazole, there was no clinical difference between those who were treated for >60 days and those treated for a shorter duration. Furthermore, the adverse effects of benznidazole appear to be less severe than previous reports would suggest.


Assuntos
Humanos , Masculino , Feminino , Adulto , Tripanossomicidas/administração & dosagem , Doadores de Sangue , Doença de Chagas/tratamento farmacológico , Parasitemia/parasitologia , Nitroimidazóis/administração & dosagem , Fatores de Tempo , Protocolos Clínicos , Reação em Cadeia da Polimerase , Doença Crônica , Estudos Transversais , Resultado do Tratamento , Doença de Chagas/parasitologia , Infecções Assintomáticas , Carga Parasitária , Pessoa de Meia-Idade
19.
Arq. bras. cardiol ; 107(2): 106-115, Aug. 2016. tab, graf
Artigo em Inglês | LILACS | ID: lil-794559

RESUMO

Abstract Background: Coronary artery disease is the main cause of death in Brazil. In the Brazilian public health system, the in-hospital mortality associated with acute myocardial infarction is high. The Minas Telecardio 2 Project (Projeto Minas Telecardio 2) aims at implementing a myocardial infarction system of care in the Northern Region of Minas Gerais (MG) to decrease hospital morbidity and mortality. The aim of this study was to describe the profile of the patients with acute coronary syndrome (ACS) cared for in the period that preceded the implementation of the system of care. Methods: Observational, prospective study of patients with ACS admitted between June 2013 and March 2014 to six emergency departments in Montes Claros, MG, and followed up until hospital discharge. Results: During the study period, 593 patients were admitted with a diagnosis of ACS (mean age 63 ± 12 years, 67.6% men), including 306 (51.6%) cases of unstable angina, 214 (36.0%) of ST-elevation myocardial infarction (STEMI), and 73 (12.3%) of non-ST-elevation myocardial infarction (NSTEMI). The total STEMI mortality was 21%, and the in-hospital mortality was 17.2%. In the STEMI patients, 46,0% underwent reperfusion therapy, including primary angioplasty in 88 and thrombolysis in six. Overall, aspirin was administered to 95.1% of the patients within 24 hours and to 93.5% at discharge, a P2Y12 inhibitor was administered to 88.7% participants within 24 hours and to 75.1% at discharge. A total of 73.1% patients received heparin within 24 hours. Conclusion: We observed a low reperfusion rate in patients with STEMI and limited adherence to the recommended ACS treatment in the Northern Region of MG. These observations enable opportunities to improve health care.


Resumo Fundamento: A doença coronariana é a principal causa de morte no Brasil. No sistema público de saúde brasileiro, a mortalidade hospitalar por infarto agudo do miocárdio é elevada. O Projeto Minas Telecardio 2 tem o objetivo de implantar a linha de cuidado do infarto na Região Ampliada Norte de Minas Gerais (MG), com vistas à redução da morbimortalidade hospitalar. O objetivo deste estudo foi descrever o perfil dos casos de síndrome coronariana aguda (SCA) atendidos no período que precedeu à implantação do programa. Métodos: Estudo prospectivo observacional dos pacientes com SCA admitidos entre junho de 2013 e março de 2014 nas seis portas de entrada de urgência de Montes Claros e acompanhados até a alta hospitalar. Resultados: No período do estudo, 593 pacientes foram admitidos com SCA (idade média 63 ± 12 anos, 67,6% homens), com 306 (51,6%) casos de angina instável, 214 (36,0%) de infarto com supradesnivelamento do ST (IAMCSST) e 73 (12,3%) com infarto sem supradesnivelamento do ST (IAMSSST). A mortalidade total para IAMCSST foi 21% e a intra-hospitalar foi de 17,2%. Nos pacientes com IAMCSST, 46,0% foram submetidos a terapia de reperfusão, com 88 angioplastias primárias e seis trombólises. AAS foi administrado a 95,1% dos pacientes nas primeiras 24 horas e a 93,5% na alta, inibidores do P2Y12 foram administrados a 88,7% dos participantes nas primeiras 24 horas e a 75,1% na alta. Ao todo, 73,1% receberam heparina nas primeiras 24 horas. Conclusão: Foram observadas baixa taxa de reperfusão em pacientes com IAMCSST e adesão limitada aos tratamentos preconizados para abordagem da SCA na Região Ampliada Norte de MG. Estas observações possibilitam oportunidades para melhoria do cuidado em saúde.


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Indicadores de Qualidade em Assistência à Saúde/estatística & dados numéricos , Síndrome Coronariana Aguda/epidemiologia , Fatores de Tempo , Brasil/epidemiologia , Reperfusão Miocárdica/estatística & dados numéricos , Aspirina/administração & dosagem , Demografia/estatística & dados numéricos , Estudos Prospectivos , Mortalidade Hospitalar , Fidelidade a Diretrizes/estatística & dados numéricos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Hospitalização
20.
Rev. méd. Minas Gerais ; 24(1)jan.-mar. 2014.
Artigo em Português | LILACS | ID: lil-720009

RESUMO

Introdução: os distúrbios hipertensivos representam as intercorrências mais frequentes e graves do ciclo grávido-puerperal. Achados anormais no doppler de artérias uterinas, como valores alterados do índice de pulsatilidade médio e persistência da incisura protodiastólica, têm sido propostos como testes de rastreamento adequados para a predição da pré-eclâmpsia. Objetivos: avaliar a capacidade de predizer a ocorrência depré-eclâmpsia pelo doppler das artérias uterinas em grupo de risco clínico e epidemiológico para o seu desenvolvimento. Pacientes e métodos: foram selecionadas 81 gestantes, todas portadoras de fatores de risco para pré-eclâmpsia. As avaliações do índice de pulsatilidade médio foram realizadas nos intervalos gestacionais compreendidos entre 16+0 e 19+6 semanas e 24+0 e 27+6 semanas. Neste último intervalo, foi também avaliada apersistência da incisura protodiastólica bilateral. Resultados: a incisura protodiastólica bilateral entre 24+0 e 27+6 semanas de gestação foi capaz de predizer o diagnóstico de pré-eclâmpsia com 75% de sensibilidade, 82% de especificidade, valor preditivo positivo de 50% e valor preditivo negativo de 93%. A análise dos dados obtidos entre 16+0 e 19+6 semanas de gestação e entre 24+0 e 27+6 semanas de gestação demonstrou que elevados valores de índice de pulsatilidade médio foram encontrados no grupo de pacientes acometidas pela pré-eclâmpsia quando comparado aos encontrados no grupo de pacientes normotensas. Conclusão: as gestações complicadas pela pré-eclâmpsia mostraram prevalência significativamente maior de incisura bilateral e medidas de índice de pulsatilidade médio maiores em cada um dos intervalos estudados. Como nenhum tratamento específico está atualmente disponível, a possibilidade de se predizer a doença, com início ainda na primeira metade da gestação, pode facilitar a monitorização precoce, a instituição de medidas de suporte e a intervenção em momento apropriado para reduzir a morbimortalidade materno-fetal observada na pré-eclâmpsia.


Introduction: Hypertensive disorders represent the most frequent and serious complications of pregnancy and childbirth. Abnormal findings upon uterine artery Doppler, including altered values of pulsatility index and average persistence of bilateral diastolic notch, have been proposed as suitable predictors of preeclampsia in screening tests. Objectives: To evaluate the usefulness of uterine artery Doppler in predicting the occurrence of preeclampsia in a group of women at clinical and epidemiological risk for its development. Patients and methods: 81 pregnant women, all of which with risk factors for developing preeclampsia were selected. The average pulsatility index exams were performed on gestational intervals of 16+0 and 19+6 weeks and 24+0 and 27+6 weeks. In the latter range, the persistence of bilateral diastolic notch was also assessed. Results: Bilateral diastolic notch between 24+0 and 27+6 weeks of gestation could predict the diagnosis of preeclampsia with 75% sensitivity, 82% specificity, positive predictive value of 50% and negative predictive value of 93%. The analysis of data obtained between 16+0 and 19+6 weeks and between 24+0 and 27+6 weeks demonstrated that high values of mean pulsatility index were found in patients affected by preeclampsia compared with those found in the group of normotensivepatients. Conclusion: pregnancies complicated by preeclampsia had significantly higher prevalence of bilateral notches and higher mean pulsatility indexes in each of the ranges studied. Since no specific treatment is currently available, the ability to predict the disease at its onset,in the first half of pregnancy, can facilitate early monitoring, increased support, and the ability to intervene at the appropriate time so as to reduce the maternal-fetal morbidity and mortality observed in preeclampsia.


Assuntos
Humanos , Feminino , Gravidez , Fatores de Risco , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/prevenção & controle , Ultrassonografia Doppler
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