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1.
Nucleic Acids Res ; 52(1): 4-21, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-37993417

RESUMO

Several cancer core regulatory circuitries (CRCs) depend on the sustained generation of DNA accessibility by SWI/SNF chromatin remodelers. However, the window when SWI/SNF is acutely essential in these settings has not been identified. Here we used neuroblastoma (NB) cells to model and dissect the relationship between cell-cycle progression and SWI/SNF ATPase activity. We find that SWI/SNF inactivation impairs coordinated occupancy of non-pioneer CRC members at enhancers within 1 hour, rapidly breaking their autoregulation. By precisely timing inhibitor treatment following synchronization, we show that SWI/SNF is dispensable for survival in S and G2/M, but becomes acutely essential only during G1 phase. We furthermore developed a new approach to analyze the oscillating patterns of genome-wide DNA accessibility across the cell cycle, which revealed that SWI/SNF-dependent CRC binding sites are enriched at enhancers with peak accessibility during G1 phase, where they activate genes involved in cell-cycle progression. SWI/SNF inhibition strongly impairs G1-S transition and potentiates the ability of retinoids used clinically to induce cell-cycle exit. Similar cell-cycle effects in diverse SWI/SNF-addicted settings highlight G1-S transition as a common cause of SWI/SNF dependency. Our results illustrate that deeper knowledge of the temporal patterns of enhancer-related dependencies may aid the rational targeting of addicted cancers.


Cancer cells driven by runaway transcription factor networks frequently depend on the cellular machinery that promotes DNA accessibility. For this reason, recently developed small molecules that impair SWI/SNF (or BAF) chromatin remodeling activity have been under active evaluation as anti-cancer agents. However, exactly when SWI/SNF activity is essential in dependent cancers has remained unknown. By combining live-cell imaging and genome-wide profiling in neuroblastoma cells, Cermakova et al. discover that SWI/SNF activity is needed for survival only during G1 phase of the cell cycle. The authors reveal that in several cancer settings, dependency on SWI/SNF arises from the need to reactivate factors involved in G1-S transition. Because of this role, authors find that SWI/SNF inhibition potentiates cell-cycle exit by retinoic acid.


Assuntos
Fase G1 , Neoplasias , Fatores de Transcrição , Humanos , Ciclo Celular , Cromatina/genética , Montagem e Desmontagem da Cromatina , DNA , Sequências Reguladoras de Ácido Nucleico , Fatores de Transcrição/metabolismo , Elementos Facilitadores Genéticos
2.
An Acad Bras Cienc ; 92(2): e20180766, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32520217

RESUMO

Two dimensions of the ecological niche (diet and habitat) of a snake assemblage from an endemic rich area in east-central Argentina, the Sierras de Ventania mountain chain, were analyzed. Field data collection was performed in 15-week study periods between 2010 and 2014. Snakes were hand-captured using transect surveys. Field observations on diet were analyzed together with stomach content data from museum specimens. Our results supported the partitioning of the snake assemblage by both habitat use and diet into at least three functional groups: species restricted to microhabitats under rocks and with a diet composed exclusively of ants (Epictia australis); species found mostly in stream microhabitats and feeding mainly upon anurans (Erythrolamprus poecilogyrus and Lygophis elegantissimus); and species found mostly in grassland microhabitats, with specialized diets of terrestrial prey items (Philodryas patagoniensis and Bothrops alternatus). Consistent with previous work, diet was more important than habitat in explaining ecological niche partitioning of this snake assemblage. Our results showed that high overlap values of microhabitat use were compensated by low overlap values of the trophic niche dimension, thus matching the traditional complementary niches hypothesis.


Assuntos
Comportamento Alimentar/fisiologia , Conteúdo Gastrointestinal , Serpentes/fisiologia , Animais , Argentina , Estações do Ano , Serpentes/classificação
3.
Europace ; 21(1): 147-153, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30016418

RESUMO

AIMS: Left ventricular (LV) outflow tract ventricular arrhythmias (OTVA) are associated with hypertension (HT), older age, and LV dysfunction, suggesting that LV overload plays a role in the aetiopathogenesis. We hypothesized that anatomical modifications of the LV outflow tract (LVOT) could predict left vs. right OTVA site of origin (SOO). METHODS AND RESULTS: Fifty-six (32 men, 53 ± 18 years old) consecutive patients referred for OTVA ablation were included. Cardiac multidetector computed tomography was performed before ablation and then imported to the CARTO system to aid the mapping and ablation procedure. Anatomical characteristics of the aortic root as well as aortopulmonary valvular planar angulation (APVPA) were analysed. The LV was the OTVA SOO (LVOT-VA) in 32 (57%) patients. These patients were more frequently male (78% vs. 22%, P = 0.001), older (57 ± 18 vs. 47 ± 18 years, P = 0.055), and more likely to have HT (59% vs. 21%, P = 0.004), compared to right OTVA patients. Aortopulmonary valvular planar angulation was higher in LVOT-VA patients (68 ± 5° vs. 55 ± 6°, respectively; P < 0.001). Absolute size of all aortic root diameters was associated with LVOT origin. However, after indexing by body surface area, only sinotubular junction diameter maintained a significant association (P = 0.049). Multivariable analysis showed that APVPA was an independent predictor of LVOT origin. Aortopulmonary valvular planar angulation ≥62° reached 94% sensitivity and 83% specificity (area under the curve 0.95) for predicting LVOT origin. CONCLUSIONS: The measurement of APVPA as a marker of chronic LV overload is useful for the prediction of left vs. right ventricular OTVA origin.


Assuntos
Ventrículos do Coração/diagnóstico por imagem , Tomografia Computadorizada Multidetectores , Disfunção Ventricular Esquerda/diagnóstico por imagem , Função Ventricular Esquerda , Função Ventricular Direita , Complexos Ventriculares Prematuros/etiologia , Remodelação Ventricular , Potenciais de Ação , Adulto , Idoso , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/fisiopatologia , Ablação por Cateter , Técnicas Eletrofisiológicas Cardíacas , Feminino , Frequência Cardíaca , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Valva Pulmonar/diagnóstico por imagem , Valva Pulmonar/fisiopatologia , Fatores de Risco , Disfunção Ventricular Esquerda/complicações , Disfunção Ventricular Esquerda/fisiopatologia , Complexos Ventriculares Prematuros/diagnóstico , Complexos Ventriculares Prematuros/fisiopatologia , Complexos Ventriculares Prematuros/cirurgia
4.
Europace ; 20(2): 337-346, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-28017938

RESUMO

Aims: Identification of local abnormal electrograms (EGMs) during ventricular tachycardia substrate ablation (VTSA) is challenging when they are hidden within the far-field signal. This study analyses whether the response to a double ventricular extrastimulus during substrate mapping could identify slow conducting areas that are hidden during sinus rhythm. Methods and results: Consecutive patients (n = 37) undergoing VTSA were prospectively included. Bipolar EGMs with >3 deflections and duration <133 ms were considered as potential hidden slow conduction EGMs (HSC-EGM) if located within/surrounding the scar area. Whenever a potential HSC-EGM was identified, a double ventricular extrastimulus was delivered. If the local potential delayed, it was annotated as HSC-EGM. The incidence of HSC-EGM in core, border-zone, and normal-voltage regions was determined. Ablation was delivered at conducting channel entrances and HSC-EGMs. VT inducibility after VTSA obtained was compared with data from a historic control group. 2417 EGMs were analyzed. 575 (23.7%) qualified as potential HSC-EGM, and 198 of them were tagged as HSC-EGMs. Scars in patients with HSC-EGMs (n = 21, 56.7%) were smaller (35.424.7 vs 67.639.1 cm2; P = 0.006) and more heterogeneous (core/scar area ratio 0.250.2 vs 0.450.19; P = 0.02). 28.8% of HSC-EGMs were located in normal-voltage tissue; 81.3% were targeted for ablation. Patients undergoing VTSA incorporating HSC analysis needed less radiofrequency time (17.411 vs 2310.7 minutes; P = 0.016) and had a lower rate of VT inducibility after VTSA than the historic controls (24.3% vs 50%; P = 0.018). Conclusion: Ventricular tachycardia substrate ablation incorporating HSC analysis allowed further arrhythmic substrate identification (especially in normal-voltage areas) and reduced RF time and VT inducibility after VTSA.


Assuntos
Estimulação Cardíaca Artificial , Técnicas Eletrofisiológicas Cardíacas , Sistema de Condução Cardíaco/fisiopatologia , Frequência Cardíaca , Taquicardia Ventricular/diagnóstico , Potenciais de Ação , Idoso , Ablação por Cateter , Feminino , Sistema de Condução Cardíaco/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Valor Preditivo dos Testes , Estudos Prospectivos , Taquicardia Ventricular/fisiopatologia , Taquicardia Ventricular/cirurgia , Fatores de Tempo , Resultado do Tratamento
5.
Europace ; 20(3): 512-519, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-28069835

RESUMO

Aims: Ventricular tachycardia (VT) substrate ablation is based on detailed electroanatomical maps (EAM). This study analyses whether high-density multielectrode mapping (MEM) is superior to conventional point-by-point mapping (PPM) in guiding VT substrate ablation procedures. Methods and results: This was a randomized controlled study (NCT02083016). Twenty consecutive ischemic patients undergoing VT substrate ablation were randomized to either group A [n = 10; substrate mapping performed first by PPM (Navistar) and secondly by MEM (PentaRay) ablation guided by PPM] or group B [n = 10; substrate mapping performed first by MEM and second by PPM ablation guided by MEM]. Ablation was performed according to the scar-dechanneling technique. Late potential (LP) pairs were defined as a Navistar-LP and a PentaRay-LP located within a three-dimensional distance of ≤ 3 mm. Data obtained from EAM, procedure time, radiofrequency time, and post-ablation VT inducibility were compared between groups. Larger bipolar scar areas were obtained with MEM (55.7±31.7 vs. 50.5±26.6 cm2; P = 0.017). Substrate mapping time was similar with MEM (19.7±7.9 minutes) and PPM (25±9.2 minutes); P = 0.222. No differences were observed in the number of LPs identified within the scar by MEM vs. PPM (73±50 vs. 76±52 LPs per patient, respectively; P = 0.965). A total of 1104 LP pairs were analysed. Using PentaRay, far-field/LP ratio was significantly lower (0.58±0.4 vs. 1.64±1.1; P = 0.01) and radiofrequency time was shorter [median (interquartile range) 12 (7-20) vs. 22 (17-33) minutes; P = 0.023]. No differences were observed in VT inducibility after procedure. Conclusion: MEM with PentaRay catheter provided better discrimination of LPs due to a lower sensitivity for far-field signals. Ablation guided by MEM was associated with a shorter radiofrequency time.


Assuntos
Cateterismo Cardíaco/métodos , Ablação por Cateter/métodos , Técnicas Eletrofisiológicas Cardíacas , Sistema de Condução Cardíaco/cirurgia , Taquicardia Ventricular/cirurgia , Potenciais de Ação , Idoso , Idoso de 80 Anos ou mais , Cateterismo Cardíaco/efeitos adversos , Cateterismo Cardíaco/instrumentação , Cateteres Cardíacos , Ablação por Cateter/efeitos adversos , Ablação por Cateter/instrumentação , Técnicas Eletrofisiológicas Cardíacas/instrumentação , Feminino , Sistema de Condução Cardíaco/fisiopatologia , Frequência Cardíaca , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Projetos Piloto , Valor Preditivo dos Testes , Espanha , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/fisiopatologia , Fatores de Tempo , Resultado do Tratamento
6.
BMC Genet ; 18(1): 40, 2017 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-28499390

RESUMO

BACKGROUND: Two key questions in understanding the genetic control of behaviors are: what genes are involved and how these genes interact. To answer these questions at a systems level, we conducted high-content profiling of Drosophila larval locomotor behaviors for over 100 genotypes. RESULTS: We studied 69 genes whose C. elegans orthologs were neuronal signalling genes with significant locomotor phenotypes, and conducted RNAi with ubiquitous, pan-neuronal, or motor-neuronal Gal4 drivers. Inactivation of 42 genes, including the nicotinic acetylcholine receptors nAChRα1 and nAChRα3, in the neurons caused significant movement defects. Bioinformatic analysis suggested 81 interactions among these genes based on phenotypic pattern similarities. Comparing the worm and fly data sets, we found that these genes were highly conserved in having neuronal expressions and locomotor phenotypes. However, the genetic interactions were not conserved for ubiquitous profiles, and may be mildly conserved for the neuronal profiles. Unexpectedly, our data also revealed a possible motor-neuronal control of body size, because inactivation of Rdl and Gαo in the motor neurons reduced the larval body size. Overall, these data established a framework for further exploring the genetic control of Drosophila larval locomotion. CONCLUSIONS: High content, quantitative phenotyping of larval locomotor behaviours provides a framework for system-level understanding of the gene networks underlying such behaviours.


Assuntos
Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Redes Reguladoras de Genes , Neurônios/metabolismo , Animais , Comportamento Animal , Drosophila melanogaster/crescimento & desenvolvimento , Epistasia Genética , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Larva/genética , Larva/crescimento & desenvolvimento , Locomoção , Masculino , Neurônios/citologia , Interferência de RNA , Transdução de Sinais
7.
Europace ; 19(6): 976-982, 2017 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-27353322

RESUMO

AIMS: This study assessed the benefit of peri-implantable cardioverter-defibrillator implant ventricular tachycardia (VT)-substrate ablation in patients with structural heart disease (SHD). METHODS AND RESULTS: Patients with SHD and indication for secondary prevention ICD implant were prospectively included. Patients presenting with incessant and/or slow VT or frequent (≥2) VT episodes who underwent peri-ICD VT-substrate ablation (the scar dechannelling technique) were compared with those who received ICD alone and did not meet ablation criteria. The primary endpoint was any sustained VT/ICD therapy during follow-up. Of 206 patients included (43.2% non-ischaemic), 70 were assigned to ablation and 136 received ICD implant alone. During a mean follow-up of 45.6 ± 24.7 months, the primary endpoint was more frequent in the non-ablation group (47.1 vs. 22.9%; P< 0.0001). Higher VT recurrence-free survival rate [log-rank P= 0.001; HR = 0.42 (0.24-0.73), P= 0.002] and ICD shock-free survival rate [log-rank P= 0.007; HR = 0.36 (0.17-0.78); P = 0.01] were observed in the ablation group. Higher relative risk reduction was observed in ischaemic [HR = 0.38 (0.18-0.83); P = 0.015] vs. non-ischaemic patients [HR = 0.49 (0.23-1.01); P = 0.08]. Patients with left ventricular ejection fraction (LVEF) <35% showed no differences in VT recurrence between treatment groups (log-rank P = 0.213) although VT burden during follow-up was lower in the ablation group [median (interquartile range) 1 (1-3) vs. 4 (1-10) VT episodes; P = 0.05]. CONCLUSION: First-line peri-ICD implant VT-substrate ablation was associated with decreased VT recurrence and ICD shocks during long-term follow-up in patients with SHD and indication for secondary prevention ICD implant, especially in ischaemic patients. In patients with LVEF <35%, no benefit was observed in terms of VT recurrence-free survival, although VT burden during follow-up was lower in the ablation group.


Assuntos
Ablação por Cateter , Desfibriladores Implantáveis , Cardioversão Elétrica/instrumentação , Prevenção Secundária/instrumentação , Taquicardia Ventricular/terapia , Idoso , Ablação por Cateter/efeitos adversos , Distribuição de Qui-Quadrado , Terapia Combinada , Intervalo Livre de Doença , Cardioversão Elétrica/efeitos adversos , Cardioversão Elétrica/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Estudos Prospectivos , Recidiva , Fatores de Risco , Volume Sistólico , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/mortalidade , Taquicardia Ventricular/fisiopatologia , Fatores de Tempo , Resultado do Tratamento , Função Ventricular Esquerda
8.
Ann Hepatol ; 14(3): 425-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25864226

RESUMO

We report the case of a 37-year-old woman with no relevant medical history. She was admitted to the hospital for epigastric pain related with food intake for 4 days; the pain did not improve with symptomatic management. A laparoscopic cholecystectomy due to acute lithiasic cholecystitis was performed. However, after 4 days, postoperative painless jaundice was evident; thus, endoscopic retrograde cholangiopancreatography was performed, which revealed an amputation of intrapancreatic common bile duct, as well as secondary intra- and extrahepatic bile duct dilatation. Brushing of the distal portion of the common bile duct revealed a well-differentiated adenocarcinoma. Therefore, a Whipple procedure with pylorus preservation was performed. Pathologic diagnosis of a papillary in situ adenocarcinoma with two microscopic foci of microinvasion was established. The pathologic Tumor-Node-Metastasis (TNM) stage was pT1, pN0, pM0, R0. The patient is asymptomatic and disease-free 24 months after surgery. In general, adenocarcinomas of the extrahepatic bile ducts are uncommon and have a poor prognosis. However, symptomatic patients with early disease stages are even rarer and can be cured surgically.


Assuntos
Adenocarcinoma Papilar/diagnóstico , Neoplasias dos Ductos Biliares/diagnóstico , Carcinoma in Situ/diagnóstico , Colangiopancreatografia Retrógrada Endoscópica/métodos , Colecistectomia Laparoscópica/métodos , Ducto Colédoco , Adenocarcinoma Papilar/cirurgia , Adulto , Neoplasias dos Ductos Biliares/cirurgia , Carcinoma in Situ/cirurgia , Feminino , Humanos
9.
JCO Glob Oncol ; 10: e2300343, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38603656

RESUMO

Head and neck squamous cell carcinoma (HNSCC) is well known as a serious health problem worldwide, especially in low-income countries or those with limited resources, such as most countries in Latin America. International guidelines cannot always be applied to a population from a large region with specific conditions. This study established a Latin American guideline for care of patients with head and neck cancer and presented evidence of HNSCC management considering availability and oncologic benefit. A panel composed of 41 head and neck cancer experts systematically worked according to a modified Delphi process on (1) document compilation of evidence-based answers to different questions contextualized by resource availability and oncologic benefit regarding Latin America (region of limited resources and/or without access to all necessary health care system infrastructure), (2) revision of the answers and the classification of levels of evidence and degrees of recommendations of all recommendations, (3) validation of the consensus through two rounds of online surveys, and (4) manuscript composition. The consensus consists of 12 sections: Head and neck cancer staging, Histopathologic evaluation of head and neck cancer, Head and neck surgery-oral cavity, Clinical oncology-oral cavity, Head and neck surgery-oropharynx, Clinical oncology-oropharynx, Head and neck surgery-larynx, Head and neck surgery-larynx/hypopharynx, Clinical oncology-larynx/hypopharynx, Clinical oncology-recurrent and metastatic head and neck cancer, Head and neck surgery-reconstruction and rehabilitation, and Radiation therapy. The present consensus established 48 recommendations on HNSCC patient care considering the availability of resources and focusing on oncologic benefit. These recommendations could also be used to formulate strategies in other regions like Latin America countries.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , América Latina/epidemiologia , Consenso , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Neoplasias de Cabeça e Pescoço/terapia
10.
Cancer Res ; 83(7): 983-996, 2023 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-36662812

RESUMO

In acute myeloid leukemia (AML), SWI/SNF chromatin remodeling complexes sustain leukemic identity by driving high levels of MYC. Previous studies have implicated the hematopoietic transcription factor PU.1 (SPI1) as an important target of SWI/SNF inhibition, but PU.1 is widely regarded to have pioneer-like activity. As a result, many questions have remained regarding the interplay between PU.1 and SWI/SNF in AML as well as normal hematopoiesis. Here we found that PU.1 binds to most of its targets in a SWI/SNF-independent manner and recruits SWI/SNF to promote accessibility for other AML core regulatory factors, including RUNX1, LMO2, and MEIS1. SWI/SNF inhibition in AML cells reduced DNA accessibility and binding of these factors at PU.1 sites and redistributed PU.1 to promoters. Analysis of nontumor hematopoietic cells revealed that similar effects also impair PU.1-dependent B-cell and monocyte populations. Nevertheless, SWI/SNF inhibition induced profound therapeutic response in an immunocompetent AML mouse model as well as in primary human AML samples. In vivo, SWI/SNF inhibition promoted leukemic differentiation and reduced the leukemic stem cell burden in bone marrow but also induced leukopenia. These results reveal a variable therapeutic window for SWI/SNF blockade in AML and highlight important off-tumor effects of such therapies in immunocompetent settings. SIGNIFICANCE: Disruption of PU.1-directed enhancer programs upon SWI/SNF inhibition causes differentiation of AML cells and induces leukopenia of PU.1-dependent B cells and monocytes, revealing the on- and off-tumor effects of SWI/SNF blockade.


Assuntos
Leucemia Mieloide Aguda , Leucopenia , Animais , Camundongos , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Medula Óssea/patologia , Regiões Promotoras Genéticas , Diferenciação Celular , Leucopenia/genética
11.
Curr Biol ; 31(12): 2603-2618.e9, 2021 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-34048707

RESUMO

Host genetic landscapes can shape microbiome assembly in the animal gut by contributing to the establishment of distinct physiological environments. However, the genetic determinants contributing to the stability and variation of these microbiome types remain largely undefined. Here, we use the free-living nematode Caenorhabditis elegans to identify natural genetic variation among wild strains of C. elegans that drives assembly of distinct microbiomes. To achieve this, we first established a diverse model microbiome that represents the strain-level phylogenetic diversity naturally encountered by C. elegans in the wild. Using this community, we show that C. elegans utilizes immune, xenobiotic, and metabolic signaling pathways to favor the assembly of different microbiome types. Variations in these pathways were associated with enrichment for specific commensals, including the Alphaproteobacteria Ochrobactrum. Using RNAi and mutant strains, we showed that host selection for Ochrobactrum is mediated specifically by host insulin signaling pathways. Ochrobactrum recruitment is blunted in the absence of DAF-2/IGFR and modulated by the competitive action of insulin signaling transcription factors DAF-16/FOXO and PQM-1/SALL2. Further, the ability of C. elegans to enrich for Ochrobactrum as adults is correlated with faster animal growth rates and larger body size at the end of development. These results highlight a new role for the highly conserved insulin signaling pathways in the regulation of gut microbiome composition in C. elegans.


Assuntos
Caenorhabditis elegans/microbiologia , Variação Genética , Microbiota/genética , Microbiota/fisiologia , Animais , Proteínas de Caenorhabditis elegans/metabolismo , Insulina/metabolismo , Filogenia , Transdução de Sinais , Fatores de Transcrição/metabolismo
12.
Methods Mol Biol ; 2144: 131-144, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32410031

RESUMO

The gut microbiome is an important driver of host physiology and development. Altered abundance or membership of this microbe community can influence host health and disease progression, including the determination of host lifespan and healthspan. Here, we describe a robust pipeline to measure microbiome abundance and composition in the C. elegans gut that can be applied to examine the role of the microbiome on host aging or other physiologic processes.


Assuntos
Envelhecimento/genética , Caenorhabditis elegans/microbiologia , Microbioma Gastrointestinal/genética , Ensaios de Triagem em Larga Escala/métodos , Animais , Caenorhabditis elegans/crescimento & desenvolvimento , Longevidade/genética
13.
Sensors (Basel) ; 9(7): 5477-92, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-22346709

RESUMO

In this paper, we propose a low-cost contact-free measurement system for both 3-D data acquisition and fast surface parameter registration by digitized points. Despite the fact that during the last decade several approaches for both contact-free measurement techniques aimed at carrying out object surface recognition and 3-D object recognition have been proposed, they often still require complex and expensive equipment. Therefore, alternative low cost solutions are in great demand. Here, two low-cost solutions to the above-mentioned problem are presented. These are two examples of practical applications of the novel passive optical scanning system presented in this paper.

14.
Heart Rhythm ; 15(6): 814-821, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29427821

RESUMO

BACKGROUND: Patients with transmural myocardial infarction (MI) who undergo endocardial-only substrate ablation are at increased risk for ventricular tachycardia recurrence. Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) can be used to assess infarct transmurality (IT). However, the degree of IT associated with an epicardial arrhythmogenic substrate (AS) has not been determined. OBJECTIVE: The purpose of this study was to determine the degree of IT observed by LGE-CMR and multidetector computed tomography (MDCT) that predicts the presence of epicardial AS. METHODS: The study included 38 post-MI patients. Ten patients with a subendocardial infarction underwent endocardial-only mapping, and 28 with a classic transmural MI (C-TMI), defined as hyperenhancement ≥75% of myocardial wall thickness (WT), underwent endo-epicardial mapping. LGE-CMR/MDCT data were registered to high-density endocardial or epicardial maps to be analyzed for the presence of AS. RESULTS: Of the 28 post-MI patients with C-TMI, 18 had epicardial AS (64%) and 10 (36%) did not. An epicardial scar area ≥14 cm2 on LGE-CMR identified patients with epicardial AS (sensitivity 1, specificity 1). Mean WT in the epicardial scar area in these patients was lower than in patients without epicardial AS (3.14 ± 1.16 mm vs 5.54 ± 1.78 mm; P = .008). A mean WT cutoff value ≤3.59 mm identified patients with epicardial AS (sensitivity 0.91, specificity 0.93). CONCLUSION: An epicardial scar area ≥14 cm2 on LGE-CMR and mean CT-WT ≤3.59 mm predict epicardial AS in post-MI patients.


Assuntos
Mapeamento Epicárdico/métodos , Frequência Cardíaca/fisiologia , Infarto do Miocárdio/complicações , Taquicardia Ventricular/diagnóstico , Idoso , Feminino , Seguimentos , Humanos , Imageamento Tridimensional , Imagem Cinética por Ressonância Magnética , Masculino , Tomografia Computadorizada Multidetectores , Infarto do Miocárdio/diagnóstico , Reprodutibilidade dos Testes , Estudos Retrospectivos , Taquicardia Ventricular/etiologia , Taquicardia Ventricular/fisiopatologia
15.
Heart Rhythm ; 14(12): 1864-1870, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28756100

RESUMO

BACKGROUND: Frequent premature ventricular complexes (PVCs) can induce or worsen left ventricular (LV) systolic dysfunction. OBJECTIVE: The purpose of this study was to identify the clinical pattern of patients having a "pure PVC-induced" cardiomyopathy at presentation. METHODS: This prospective multicenter study included 155 consecutive patients (age 55 ± 12 years, 96 men [62%], 23% ±12% mean PVC burden) with LV dysfunction and frequent PVCs submitted for ablation and followed up for at least 12 months. Patients with a previously diagnosed structural heart disease (50 [32%]) and those without complete PVC abolition during follow-up who did not normalize LV ejection fraction (LVEF) (24 [15%]) were excluded from the analysis. RESULTS: Of the remaining 81 patients, 41 (51%) had a successful sustained ablation, did not have normalized LVEF, and were classified as having PVC-worsened nonischemic cardiomyopathy, and 40 (49%) who had normalized LVEF were considered as having pure PVC-induced cardiomyopathy. The latter group had higher baseline PVC burden (27% ± 12% vs 12% ± 8%; P <.001), smaller LV end-diastolic diameter (58 ± 5 mm vs 60 ± 6 mm; P = .05), and shorter intrinsic QRS (105 ± 12 vs 129 ± 24 ms; P <.001). Any of the following baseline characteristics accurately identified patients who will not normalize LVEF after PVC ablation (85% sensitivity, 98% specificity): intrinsic QRS >130 ms, baseline PVC burden <17%, and LV end-diastolic diameter >63 mm. CONCLUSION: Almost half of patients with frequent PVCs and low LVEF of unknown origin normalize LVEF after sustained PVC abolition, and these patients can be identified before ablation.


Assuntos
Cardiomiopatias/etiologia , Ablação por Cateter/métodos , Volume Sistólico/fisiologia , Função Ventricular Esquerda/fisiologia , Complexos Ventriculares Prematuros/complicações , Cardiomiopatias/fisiopatologia , Eletrocardiografia Ambulatorial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Complexos Ventriculares Prematuros/fisiopatologia , Complexos Ventriculares Prematuros/cirurgia
16.
Genetics ; 206(3): 1469-1478, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28495959

RESUMO

It is crucial for animal survival to detect dangers such as predators. A good indicator of dangers is injury of conspecifics. Here we show that fluids released from injured conspecifics invoke acute avoidance in both free-living and parasitic nematodes. Caenorhabditis elegans avoids extracts from closely related nematode species but not fruit fly larvae. The worm extracts have no impact on animal lifespan, suggesting that the worm extract may function as an alarm instead of inflicting physical harm. Avoidance of the worm extract requires the function of a cGMP signaling pathway that includes the cGMP-gated channel TAX-2/TAX-4 in the amphid sensory neurons ASI and ASK. Genetic evidence indicates that the avoidance behavior is modulated by the neurotransmitters GABA and serotonin, two common targets of anxiolytic drugs. Together, these data support a model that nematodes use a nematode-specific alarm pheromone to detect conspecific injury.


Assuntos
Caenorhabditis elegans/metabolismo , Quimiotaxia , Reação de Fuga , Feromônios/metabolismo , Animais , Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/genética , Caenorhabditis elegans/fisiologia , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Canais Iônicos/genética , Canais Iônicos/metabolismo , Feromônios/farmacologia , Células Receptoras Sensoriais/metabolismo , Serotonina/metabolismo , Ácido gama-Aminobutírico/metabolismo
17.
Heart Rhythm ; 13(8): 1589-95, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27180621

RESUMO

BACKGROUND: The role and optimal sequence of ventricular tachycardia (VT) induction, mapping, and ablation when combined with substrate modification is unclear. OBJECTIVE: The purpose of this study was to test the benefits of starting the scar-related VT ablation procedure with substrate modification vs the standard protocol of VT induction, mapping, and ablation as the first step. METHODS: Forty-eight consecutive patients with structural heart disease and clinical VTs were randomized to simplified substrate ablation procedure with scar dechanneling as the first step (group 1, n = 24) or standard procedure with VT induction, mapping, and ablation followed by scar dechanneling (group 2, n = 24). Procedure and fluoroscopy times, the need for external cardioversion, acute results, and VT recurrence during follow-up were compared between groups. RESULTS: Thirty-seven patients had ischemic cardiomyopathy, 10 nonischemic cardiomyopathy, and 1 arrhythmogenic cardiomyopathy. Before substrate ablation, 32 VTs were induced and targeted for ablation in 23 patients of group 2. Procedure time (209 ± 70 minutes vs 262 ± 63 minutes; P = .009), fluoroscopy time (14 ± 6 minutes vs 21± 9 minutes; P = .005), and electrical cardioversion (25% vs 54%; P = .039) were lower in group 1. After substrate ablation, 16 patients (66%) of group 1 and 12 patients (50%) of group 2 were noninducible (P = .242). End-procedure success (after residual inducible VT ablation) was achieved in 87.5% and 70.8% of patients, respectively (P = .155). There were no differences in VT recurrence rate between groups during a mean follow-up of 22 ± 14 months (log rank, P = .557). CONCLUSION: VT induction and mapping before substrate ablation prolongs the procedure, radiation exposure, and the need for electrical cardioversion without improving acute results and long-term ablation outcomes.


Assuntos
Mapeamento Potencial de Superfície Corporal/métodos , Ablação por Cateter/métodos , Taquicardia Ventricular/cirurgia , Idoso , Feminino , Seguimentos , Humanos , Masculino , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/fisiopatologia , Resultado do Tratamento
18.
Podium (Pinar Río) ; 15(3): 518-533, sept.-dic. 2020. tab, graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1143461

RESUMO

Resumen El análisis sobre la técnica de los movimientos deportivos desde el estudio de la variabilidad del movimiento es un nuevo acercamiento a la evaluación, diagnóstico y control de las técnicas deportivas. Se conoció de la existencia de diversas investigaciones sobre la técnica del lanzamiento del disco, sin embargo, estas no han enfocado sus análisis desde la variabilidad, ni han ofrecido procedimientos para hacer el análisis desde esta perspectiva. El objetivo de esta investigación es establecer un procedimiento para el estudio de la variabilidad de la técnica en el Lanzamiento de Disco. El estudio se centró en un caso del sexo masculino que cuenta con 15 años y que entrena lanzamiento del disco en la Escuela de Iniciación Deportiva Escolar (Eide) de Villa Clara. Cuba. En la investigación se utilizaron métodos del nivel teórico y empírico tales como el estudio de casos, el estudio biomecánico y el análisis estadístico-matemático. Se logra comprobar que solo dos parámetros mostraron alta variabilidad en los nueve lanzamientos efectuados, mientras que el resto si logra una desviación estándar menor y por tanto poca variabilidad en los movimientos, además, existió una alta satisfacción de los usuarios con el procedimiento utilizado. El índice obtenido al aplicar la técnica IADOV indica que existe satisfacción de los usuarios introductores con los indicadores determinados.


Resumo A análise da técnica dos movimentos esportivos a partir do estudo da variabilidade do movimento é uma nova abordagem para a avaliação, diagnóstico e controle das técnicas esportivas. Sabia-se da existência de várias investigações sobre a técnica do lançamento de disco, porém, estas não focalizaram sua análise a partir da variabilidade, nem ofereceram procedimentos para fazer a análise nesta perspectiva. O objetivo desta pesquisa é estabelecer um procedimento para o estudo da variabilidade da técnica de Lançamento de Disco. O estudo teve como foco um jovem de 15 anos que treina lançamento de disco na Escola de Iniciação ao Esporte Escolar (Eide), em Villa Clara. Cuba. A pesquisa utilizou métodos de nível teórico e empírico como o estudo de caso, o estudo biomecânico e a análise estatística-matemática. É possível verificar que apenas dois parâmetros apresentaram alta variabilidade nos 9 arremessos realizados, enquanto os demais obtiveram menor desvio padrão e, portanto, pouca variabilidade nos movimentos, além disso, houve alta satisfação dos usuários com o procedimento utilizado. O índice obtido pela aplicação da técnica IADOV indica que há satisfação dos usuários introdutores com os indicadores determinados.


Abstract The analysis on the technique of the sport movements from the study of the variability of the movement is a new approach to the evaluation, diagnosis and control of the sport techniques. It was known of the existence of diverse investigations on the technique of the Launching of the Disk, however these they have not focused their analyses from the variability; neither they have offered procedures to make the analysis from this perspective. The objective of this paper is: to establish a procedure for the study of the variability of the technique in the Launching of Disk. The study was centered in a case of the masculine sex that has 15 years and that it trains Launching of the Disk in the School of Initiation Sport Scholar of Villa Clara. Cuba. As the research methods of the theoretical and empiric level were used as the study of cases, the study of the Biomechanics and the statistical-mathematical analysis. it is possible to verify that single two parameters showed high variability in the 9 made launchings, while the rest if it achieves a deviation standard smaller and therefore little variability in the movements, also, a high satisfaction of the users existed with the used procedure. The index obtained when applying the technical IADOV indicates that the introductory users' satisfaction exists with the certain indicators.

19.
Heart Rhythm ; 12(12): 2434-42, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26385530

RESUMO

BACKGROUND: Premature ventricular complex (PVC) ablation has been shown to improve left ventricular ejection fraction (LVEF) and New York Heart Association functional class in patients with left ventricular dysfunction. Both are considered key variables in predicting risk of sudden cardiac death. OBJECTIVE: The objective of this study was to assess whether ablation might remove the primary prevention (PP) implantable cardioverter-defibrillator (ICD) indication in patients with frequent PVC. METHODS: Sixty-six consecutive patients with PP-ICD indication and frequent PVC [33 (50%) men; mean age 53 ± 13 years; 11 (17%) with ischemic heart disease] underwent PVC ablation. The ICD was withheld and the indication was reevaluated at 6 and 12 months. RESULTS: LVEF progressively improved from 28% ± 4% at baseline to 42% ± 12% at 12 months (P < .001). New York Heart Association functional class improved from 2 patients with NYHA functional class I (3%) at baseline to 35 (53%) at 12 months (P < .001). The brain natriuretic peptide level decreased from 246 ± 187 to 176 ± 380 pg/mL (P = .004). The PP-ICD indication was removed in 42 patients (64%) during follow-up, from 38 (92%) of them at 6 months, showing an independent association with baseline PVC burden and successful sustained ablation. In patients with successful sustained ablation, a cutoff value of 13% PVC burden had a sensitivity of 100% and a specificity of 93% (area under the curve 99%) for removing ICD indication postablation. No sudden cardiac deaths or malignant ventricular arrhythmias were observed. CONCLUSION: In patients with frequent PVC and PP-ICD indication, ablation improves LVEF and, in most cases, allows removal of the indication. Withholding the ICD and reevaluating within 6 months of ablation seems to be a safe and appropriate strategy.


Assuntos
Ablação por Cateter , Desfibriladores Implantáveis , Prevenção Primária , Complexos Ventriculares Prematuros/terapia , Suspensão de Tratamento , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Estudos Prospectivos , Volume Sistólico , Resultado do Tratamento , Complexos Ventriculares Prematuros/etiologia , Complexos Ventriculares Prematuros/fisiopatologia , Complexos Ventriculares Prematuros/prevenção & controle
20.
Rev Colomb Psiquiatr ; 42(4): 324-32, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26573117

RESUMO

INTRODUCTION: Most of the studies that have examined cognitive and executive functions in conduct disorders (CD) have been conducted on institutionalized male adolescents. In this research the cognitive and executive functions of non-institutionalized Colombian school children with CD were compared with normal school children, all between 6 and 12 years-old. MATERIALS AND METHODS: We used a case-control design. The cases were participants who met the diagnostic criteria for CD (n=39) and controls who did not meet these criteria (n=39), according to reports of a professional of the participants' institution, and a structured interview for childhood psychiatric syndromes. The two groups were selected from educational institutions, and there were no differences in age, school grade, or socioeconomic level. The IQ was reviewed, as well as the presence of other mental disorders, serious physical illnesses, and more serious neurological signs. The cognitive and executive functions were evaluated using a child neuropsychological test battery. RESULTS: We found that participants with CD had significantly lower scores in construction abilities, perceptual abilities (tactile, visual and auditory), differed in verbal memory, differed in visual memory, language (repetition, expression and understanding), meta-linguistic abilities, spatial abilities, visual and auditory attention, conceptual abilities, verbal and graphic fluency, and cognitive flexibility. The same differences were found between males, except in repetition, whereas girls showed fewer differences, thus the cognitive and executive performance was poorer in males with CD than in females, especially in verbal and linguistic-related functions. CONCLUSIONS: Children with CD could show generalized cognitive and executive deficits. These deficits seem to be more frequent in boys than in girls with CD.

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