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1.
Int J Obes (Lond) ; 46(12): 2163-2167, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36008680

RESUMEN

Despite its cardiometabolic benefits, bariatric surgery has historically been underused in patients with obesity and diabetes, but contemporary data are lacking. Among 1,520,182 patients evaluated from 2013 to 2019 within a multicenter, longitudinal, US registry of outpatients with diabetes, we found that 462,033 (30%) met eligibility for bariatric surgery. After a median follow-up of 854 days, 6310/384,859 patients (1.6%) underwent primary bariatric surgery, with a slight increase over time (0.38% per year [2013] to 0.68% per year [2018]). Patients who underwent bariatric surgery were more likely to be female (63% vs. 56%), white (87% vs. 82%), have higher body mass indices (42.1 ± 6.9 vs. 40.6 ± 5.9 kg/m2), and depression (23% vs. 14%; p < 0.001 for all). Over a median (IQR) follow-up after surgery of 722 days (364-993), patients who underwent bariatric surgery had lost an average of 11.8 ± 18.5 kg (23% of excess body weight), 10.2% were on fewer glucose-lowering medications, and 8.4% were on fewer antihypertensives. Despite bariatric surgery being safer and more accessible over the past two decades, less than one in fifty eligible patients with diabetes receive this therapy.


Asunto(s)
Cirugía Bariátrica , Diabetes Mellitus Tipo 2 , Diabetes Mellitus , Obesidad Mórbida , Humanos , Femenino , Masculino , Pérdida de Peso , Cirugía Bariátrica/efectos adversos , Obesidad/complicaciones , Obesidad/epidemiología , Obesidad/cirugía , Sistema de Registros , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/cirugía , Obesidad Mórbida/complicaciones , Obesidad Mórbida/epidemiología , Obesidad Mórbida/cirugía , Estudios Retrospectivos
2.
Development ; 140(9): 2027-38, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23536569

RESUMEN

Adult Drosophila walk using six multi-jointed legs, each controlled by ∼50 leg motoneurons (MNs). Although MNs have stereotyped morphologies, little is known about how they are specified. Here, we describe the function of Hox genes and homothorax (hth), which encodes a Hox co-factor, in Drosophila leg MN development. Removing either Hox or Hth function from a single neuroblast (NB) lineage results in MN apoptosis. A single Hox gene, Antennapedia (Antp), is primarily responsible for MN survival in all three thoracic segments. When cell death is blocked, partially penetrant axon branching errors are observed in Hox mutant MNs. When single MNs are mutant, errors in both dendritic and axon arborizations are observed. Our data also suggest that Antp levels in post-mitotic MNs are important for specifying their identities. Thus, in addition to being essential for survival, Hox and hth are required to specify accurate MN morphologies in a level-dependent manner.


Asunto(s)
Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Extremidades/crecimiento & desarrollo , Genes de Insecto , Proteínas de Homeodominio/metabolismo , Neuronas Motoras/metabolismo , Animales , Proteína con Homeodominio Antennapedia/genética , Proteína con Homeodominio Antennapedia/metabolismo , Apoptosis , Axones/metabolismo , Linaje de la Célula , Supervivencia Celular , Células Dendríticas/citología , Células Dendríticas/metabolismo , Proteínas de Drosophila/genética , Drosophila melanogaster/embriología , Drosophila melanogaster/genética , Embrión no Mamífero/citología , Embrión no Mamífero/metabolismo , Regulación del Desarrollo de la Expresión Génica , Proteínas de Homeodominio/genética , Inmunohistoquímica , Mitosis , Neuronas Motoras/citología , Fenotipo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
3.
Am Heart J ; 178: 65-73, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-27502853

RESUMEN

BACKGROUND: Little is known about the relationship between ejection fraction (EF) and clinical outcomes among older patients with myocardial infarction in contemporary clinical practice. METHODS: Data on 82,558 patients 65 years or older with ST-elevation myocardial infarction or non-ST-elevation myocardial infarction who survived to hospital discharge in the ACTION Registry-GWTG (2007-2011) were linked to Medicare data. Multivariable Cox proportional hazard modeling was used to assess the association between EF reported during hospitalization and 1-year mortality, using EF as a categorical variable (≤35%, >35% and ≤45%, >45% and <55%, and ≥55%) and as a continuous variable. Secondary outcomes of interest were 1-year all-cause, cardiovascular, and heart failure readmissions. RESULTS: The risk of 1-year mortality was 29.0% in patients with EF ≤ 35%, compared with 13.0% in patients in the reference group, EF ≥ 55% (adjusted hazard ratio [HR] 1.58, 95% CI 1.51-1.66). Relative to patients with EF ≥ 55%, patients with EF ≤ 35% had an increased risk of 1-year all-cause readmission (adjusted HR 1.20, 95% CI 1.17-1.24), cardiovascular readmission (adjusted HR 1.36, 95% CI 1.31-1.41), and heart failure readmission (adjusted HR 2.43, 95% CI 2.28-2.60). For patients with EF ≤ 40%, the hazard of mortality increased by 26% for every 5% decrease in EF, a finding that remained after risk adjustment (adjusted HR 1.11, 95% CI 1.09-1.12). CONCLUSIONS: Low EF after MI remains an important risk factor for postdischarge mortality and hospital readmission, even after adjustment for patient and hospital characteristics.


Asunto(s)
Mortalidad , Infarto del Miocardio sin Elevación del ST/fisiopatología , Sistema de Registros , Infarto del Miocardio con Elevación del ST/fisiopatología , Volumen Sistólico , Disfunción Ventricular Izquierda/fisiopatología , Anciano , Anciano de 80 o más Años , Causas de Muerte , Bases de Datos Factuales , Femenino , Hospitalización , Humanos , Almacenamiento y Recuperación de la Información , Masculino , Medicare , Infarto del Miocardio sin Elevación del ST/complicaciones , Infarto del Miocardio sin Elevación del ST/terapia , Readmisión del Paciente/estadística & datos numéricos , Pronóstico , Modelos de Riesgos Proporcionales , Factores de Riesgo , Infarto del Miocardio con Elevación del ST/complicaciones , Infarto del Miocardio con Elevación del ST/terapia , Estados Unidos , Disfunción Ventricular Izquierda/etiología , Disfunción Ventricular Izquierda/terapia
4.
Development ; 139(19): 3572-82, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22949613

RESUMEN

The LIM-homeodomain transcription factor Tailup/Islet1 (Tup) is a key component of cardiogenesis in Drosophila and vertebrates. We report here an additional major role for Drosophila Tup in specifying dorsal muscles. Tup is expressed in the four dorsal muscle progenitors (PCs) and tup-null embryos display a severely disorganized dorsal musculature, including a transformation of the dorsal DA2 into dorsolateral DA3 muscle. This transformation is reciprocal to the DA3 to DA2 transformation observed in collier (col) mutants. The DA2 PC, which gives rise to the DA2 muscle and to an adult muscle precursor, is selected from a cluster of myoblasts transiently expressing both Tinman (Tin) and Col. The activation of tup by Tin in the DA2 PC is required to repress col transcription and establish DA2 identity. The transient, partial overlap between Tin and Col expression provides a window of opportunity to distinguish between DA2 and DA3 muscle identities. The function of Tup in the DA2 PC illustrates how single cell precision can be reached in cell specification when temporal dynamics are combined with positional information. The contributions of Tin, Tup and Col to patterning Drosophila dorsal muscles bring novel parallels with chordate pharyngeal muscle development.


Asunto(s)
Proteínas de Drosophila/fisiología , Drosophila/embriología , Drosophila/genética , Músculos/embriología , Organogénesis/genética , Factores de Transcripción/fisiología , Animales , Animales Modificados Genéticamente , Linaje de la Célula/genética , Drosophila/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Embrión no Mamífero , Regulación del Desarrollo de la Expresión Génica , Modelos Biológicos , Músculos/metabolismo , Especificidad de Órganos/genética , Organogénesis/fisiología , Factores de Tiempo , Distribución Tisular , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
5.
Am Heart J ; 170(1): 173-9, 179.e1, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-26093879

RESUMEN

BACKGROUND: Understanding risk factor burden and control as well as perceived risk prior to acute myocardial infarction (MI) presentation may identify gaps in contemporary systems of care. METHODS: Patients presenting with MI in the National Cardiovascular Data Registry Acute Coronary Treatment and Intervention Outcomes Network Registry--Get With the Guidelines between January 2007 and November 2013 (N = 443,117) were stratified into 5 mutually exclusive risk categories: Framingham Risk Score (FRS) <10% 74,990 (16.9%), FRS 10% to 20% 90,429 (20.4%), FRS >20% 25,701 (5.8%), diabetes without cardiovascular disease (CVD) 67,779 (15.3%), and prior CVD 184,218 (41.6%). Low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol (non-HDL-C) goals and statin eligibility were determined based on the Third Adult Treatment Panel. RESULTS: At presentation, 66.3% met the low-density lipoprotein cholesterol goal, 66.8% met the non-HDL-C goal, 63.7% were nonsmokers, and 65.1% of patients with prior CVD were on aspirin. Only 36.1% of patients met all assessed risk factor control metrics. Overall statin eligibility prior to MI was 60.8%, and 61.1% of statin-eligible patients reported statin use. CONCLUSION: Risk factor control prior to MI was suboptimal, with the majority of individuals failing to meet at least 1 risk factor control metric. More effective system-based interventions are needed to promote adherence to prevention targets.


Asunto(s)
Diabetes Mellitus/epidemiología , Dislipidemias/epidemiología , Adhesión a Directriz/estadística & datos numéricos , Hospitalización , Infarto del Miocardio/epidemiología , Guías de Práctica Clínica como Asunto , Fumar/epidemiología , Anciano , Aspirina/uso terapéutico , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/epidemiología , Dislipidemias/tratamiento farmacológico , Femenino , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/uso terapéutico , Factores de Riesgo , Estados Unidos/epidemiología
6.
Expert Rev Cardiovasc Ther ; 22(1-3): 111-120, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38284754

RESUMEN

BACKGROUND: Mechanical complications (MC) are rare but significant sequelae of acute myocardial infarction (AMI). Current data on sex differences in AMI with MC is limited. METHODS: We queried the National Inpatient Sample database to identify adult patients with the primary diagnosis of AMI and MC. The main outcome of interest was sex difference in-hospital mortality. Secondary outcomes were sex differences in the incidence of acute kidney injury (AKI), major bleeding, use of inotropes, permanent pacemaker implantation (PPMI), performance of percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), surgery (VSD repair and MV surgery), pericardiocentesis, use of mechanical circulatory support (MCS), ischemic stroke, and mechanical ventilation. RESULTS: Among AMI-MC cohort, in-hospital mortality was higher among females compared to males (41.24% vs 28.13%: aOR 1.39. 95% CI 1.079-1.798; p = 0.01). Among those who had VSD, females also had higher in-hospital mortality compared to males (56.7% vs 43.1%: aOR 1.74, 95% CI 1.12-2.69; p = 0.01). Females were less likely to receive CABG compared to males (12.03% vs 20%: aOR 0.49 95% CI 0.345-0.690; p < 0.001). CONCLUSION: Despite the decreasing trend in AMI admission, females had higher risk of MC and associated mortality. Significant sex disparities still exist in AMI treatment.


Asunto(s)
Infarto del Miocardio , Intervención Coronaria Percutánea , Adulto , Humanos , Femenino , Masculino , Estados Unidos , Caracteres Sexuales , Factores de Riesgo , Infarto del Miocardio/diagnóstico , Puente de Arteria Coronaria , Mortalidad Hospitalaria , Resultado del Tratamiento
7.
Dev Biol ; 363(1): 27-39, 2012 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-22200594

RESUMEN

The diversity of Drosophila muscles correlates with the expression of combinations of identity transcription factors (iTFs) in muscle progenitors. Here, we address the question of when and how a combinatorial code is translated into muscle specific properties, by studying the roles of the Collier and Nautilus iTFs that are expressed in partly overlapping subsets of muscle progenitors. We show that the three dorso-lateral (DL) progenitors which express Nautilus and Collier are specified in a fixed temporal sequence and that each expresses additionally other, distinct iTFs. Removal of Collier leads to changes in expression of some of these iTFs and mis-orientation of several DL muscles, including the dorsal acute DA3 muscle which adopts a DA2 morphology. Detailed analysis of this transformation revealed the existence of two steps in the attachment of elongating muscles to specific tendon cells: transient attachment to alternate tendon cells, followed by a resolution step selecting the final sites. The multiple cases of triangular-shaped muscles observed in col mutant embryos indicate that transient binding of elongating muscle to exploratory sites could be a general feature of the developing musculature. In nau mutants, the DA3 muscle randomly adopts the attachment sites of the DA3 or DO5 muscles that derive from the same progenitor, resulting in a DA3, DO5-like or bifid DA3-DO5 orientation. In addition, nau mutant embryos display thinner muscle fibres. Together, our data show that the sequence of expression and combinatorial activities of Col and Nau control the pattern and morphology of DL muscles.


Asunto(s)
Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Proteínas Musculares/metabolismo , Músculos/metabolismo , Factores de Transcripción/metabolismo , Animales , Animales Modificados Genéticamente , Tipificación del Cuerpo/genética , Proteínas de Drosophila/genética , Drosophila melanogaster/embriología , Drosophila melanogaster/genética , Embrión no Mamífero/embriología , Embrión no Mamífero/metabolismo , Embrión no Mamífero/ultraestructura , Regulación del Desarrollo de la Expresión Génica , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Inmunohistoquímica , Microscopía Electrónica de Rastreo , Modelos Biológicos , Proteínas Musculares/genética , Músculos/embriología , Músculos/ultraestructura , Mutación , Factores de Tiempo , Factores de Transcripción/genética
8.
Development ; 137(3): 457-66, 2010 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-20056681

RESUMEN

Hox transcription factors control many aspects of animal morphogenetic diversity. The segmental pattern of Drosophila larval muscles shows stereotyped variations along the anteroposterior body axis. Each muscle is seeded by a founder cell and the properties specific to each muscle reflect the expression by each founder cell of a specific combination of 'identity' transcription factors. Founder cells originate from asymmetric division of progenitor cells specified at fixed positions. Using the dorsal DA3 muscle lineage as a paradigm, we show here that Hox proteins play a decisive role in establishing the pattern of Drosophila muscles by controlling the expression of identity transcription factors, such as Nautilus and Collier (Col), at the progenitor stage. High-resolution analysis, using newly designed intron-containing reporter genes to detect primary transcripts, shows that the progenitor stage is the key step at which segment-specific information carried by Hox proteins is superimposed on intrasegmental positional information. Differential control of col transcription by the Antennapedia and Ultrabithorax/Abdominal-A paralogs is mediated by separate cis-regulatory modules (CRMs). Hox proteins also control the segment-specific number of myoblasts allocated to the DA3 muscle. We conclude that Hox proteins both regulate and contribute to the combinatorial code of transcription factors that specify muscle identity and act at several steps during the muscle-specification process to generate muscle diversity.


Asunto(s)
Proteínas de Homeodominio/fisiología , Músculos/embriología , Animales , Tipificación del Cuerpo , Drosophila/embriología , Embrión no Mamífero , Desarrollo Embrionario , Morfogénesis , Músculos/citología , Células Madre/citología , Factores de Transcripción/fisiología
9.
Am Heart J ; 165(1): 43-9, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23237132

RESUMEN

BACKGROUND: Although chronic lung disease (CLD) is common among patients with myocardial infarction (MI), little is known about the influence of CLD on patient management and outcomes following MI. METHODS: Using the National Cardiovascular Data Registry's ACTION Registry-GWTG, demographics, clinical characteristics, treatments, processes of care, and in-hospital adverse events after acute MI were compared between patients with (n = 22,624) and without (n = 136,266) CLD. Multivariable adjustment was performed to determine the independent association of CLD with treatments and adverse events. RESULTS: CLD (17.0% of non-ST-elevation MI [NSTEMI] and 10.1% of ST-elevation MI [STEMI] patients) was associated with older age, female sex, and a greater burden of comorbidities. Among NSTEMI patients, those with CLD were less likely to undergo cardiac catheterization, percutaneous coronary intervention, and coronary artery bypass graft compared to those without; in contrast, no differences were seen in invasive therapies for STEMI patients with or without CLD. Multivariable-adjusted risk of major bleeding was significantly increased in CLD patients with NSTEMI (13.0% vs 8.1%, OR(adj) = 1.27, 95% CI = 1.20-1.34, P < .001) and STEMI (16.0% vs 10.5%, OR(adj) = 1.19, 95% CI = 1.10-1.29, P < .001). In NSTEMI, CLD was associated with a higher risk of inhospital mortality (OR(adj) = 1.21, 95% CI = 1.11-1.33); in STEMI no association between CLD and mortality was seen (OR(adj) = 1.05, 95% CI = 0.95-1.17). CONCLUSIONS: CLD is common among patients with MI and is independently associated with an increased risk for major bleeding. In NSTEMI, CLD is also associated with receiving less revascularization and with increased in-hospital mortality. Special attention should be given to this high-risk subgroup for the prevention and management of complications after MI.


Asunto(s)
Puente de Arteria Coronaria/efectos adversos , Enfermedades Pulmonares/epidemiología , Infarto del Miocardio/epidemiología , Intervención Coronaria Percutánea/efectos adversos , Anciano , Enfermedad Crónica , Puente de Arteria Coronaria/mortalidad , Femenino , Mortalidad Hospitalaria , Humanos , Enfermedades Pulmonares/tratamiento farmacológico , Enfermedades Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/cirugía , Intervención Coronaria Percutánea/mortalidad , Factores de Riesgo , Resultado del Tratamiento
10.
Am Heart J ; 166(4): 709-15, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24093851

RESUMEN

BACKGROUND: Aldosterone antagonists (AldA) improve survival after myocardial infarction (MI) in patients with left ventricular systolic dysfunction (ejection fraction [EF] <40%) concomitant with either clinical heart failure (HF) or diabetes mellitus (DM). Although current American College of Cardiology/American Heart Association guidelines provide a class I recommendation for AldA therapy in such patients, how US practice reflects these recommendations is unclear. METHODS: Using data from the National Cardiovascular Data Registry ACTION Registry-GWTG, we describe contemporary discharge AldA prescription patterns among 202,213 patients discharged after acute MI from 526 US sites participating in ACTION Registry-GWTG between January 2007 and March 2011. RESULTS: Overall, 10.0% of patients were eligible for AldA without documented contraindication, with only 14.5% of eligible patients receiving AldA at discharge. Among the subset of AldA-eligible patients discharged on otherwise optimal medical therapy (68.9%), AldAs were prescribed to 16.1%. Aldosterone antagonist use was higher in patients with EF <40% and clinical HF with or without DM (17.7% and 16.6%, respectively), compared with patients with EF <40% and DM without clinical HF (7.8%, P < .001 for each). Fewer than 2% of participating centers used AldA in ≥50% of eligible patients. CONCLUSIONS: Despite clinical outcome evidence and class I guideline recommendations, AldAs are underused in the United States, with only 1 in 7 eligible patients prescribed AldA at discharge after MI. This contrasts with high use of other evidence-based post-MI medications and identifies a specific gap in translation of evidence into clinical practice.


Asunto(s)
Adhesión a Directriz , Antagonistas de Receptores de Mineralocorticoides/uso terapéutico , Infarto del Miocardio/tratamiento farmacológico , Alta del Paciente , Sistema de Registros , Anciano , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/mortalidad , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia/tendencias , Resultado del Tratamiento , Estados Unidos/epidemiología
11.
STAR Protoc ; 4(2): 102316, 2023 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-37195867

RESUMEN

Techniques allowing the precise quantification of mRNA at the cellular level are essential for understanding biological processes. Here, we present a semi-automated smiFISH (single-molecule inexpensive FISH) pipeline enabling quantification of mRNA in a small number of cells (∼40) in fixed whole mount tissue. We describe steps for sample preparation, hybridization, image acquisition, cell segmentation, and mRNA quantification. Although the protocol was developed in Drosophila, it can be optimized for use in other organisms. For complete details on the use and execution of this protocol, please refer to Guan et al.1.

12.
JAMA Netw Open ; 6(4): e237699, 2023 04 03.
Artículo en Inglés | MEDLINE | ID: mdl-37043202

RESUMEN

Importance: High-risk medical devices approved by the US Food and Drug Administration (FDA) can undergo modifications to their original premarket approval (PMA) via 1 of 5 types of supplements. Only panel track supplements (approximately 1%) require clinical data for approval. The association between device modifications and risk to patient safety has not previously been analyzed. Objective: To determine the association between PMA supplements and the risk of any device recall and high-risk (class 1) recall. Design, Setting, and Participants: In this cohort study, the FDA database was queried for original devices approved via PMA from January 1, 2008, through December 31, 2019. Supplement and recall data were obtained for these devices from January 1, 2008, through December 31, 2021, giving a minimum 2-year follow-up after initial approval. Data were analyzed from July 6 to August 6, 2022. Retrospective, time-to-event analysis investigated the association between the number and type of supplements and risk of recall. Exposures: Supplements submitted by manufacturers for FDA approval to modify devices. Main Outcomes and Measures: A mixed-effects Cox proportional hazards regression model with frailty terms was used, modeling device recall as an outcome variable during the observation period. A second model was performed for class 1 (high-risk) recall. Explanatory variables are the number of supplements, number of panel track supplements, and cardiovascular devices. Multivariable analysis was performed to identify independent risk factors for recall with hazard ratios (HRs) as the main end point. Results: A total of 373 original PMA devices with 10 776 associated supplements were included in the analysis. A median 2.5 (IQR, 1.2-5.0) supplements per device were approved annually. Cardiovascular devices contributed 138 supplements (37.0%), followed by microbiology with 45 (12.1%). No other specialty contributed more than 10%. Multivariable analysis demonstrated that each increase of 1 supplement per year was associated with increased risk of recall (HR, 1.28 [95% CI, 1.15-1.44]; P < .001). For class 1 recall, increased number of supplements (HR, 1.32 [95% CI, 1.06-1.64]; P = .01) and cardiovascular vsnoncardiovascular classification of devices (HR, 3.51 [95% CI, 1.15-10.72]; P = .03) were significantly associated with an increased risk of recall. Conclusions and Relevance: The findings of this cohort study suggest that PMA supplements are associated with an approximately 30% increased risk of any recall and class 1 recall. The FDA processes for approving modifications to high-risk medical devices should be reevaluated to optimize patient safety and public health.


Asunto(s)
Vigilancia de Productos Comercializados , Estados Unidos , Humanos , United States Food and Drug Administration , Estudios Retrospectivos , Estudios de Cohortes , Factores de Riesgo
13.
Cell Rep ; 39(13): 110992, 2022 06 28.
Artículo en Inglés | MEDLINE | ID: mdl-35767953

RESUMEN

How the vast array of neuronal diversity is generated remains an unsolved problem. Here, we investigate how 29 morphologically distinct leg motoneurons are generated from a single stem cell in Drosophila. We identify 19 transcription factor (TF) codes expressed in immature motoneurons just before their morphological differentiation. Using genetic manipulations and a computational tool, we demonstrate that the TF codes are progressively established in immature motoneurons according to their birth order. Comparing RNA and protein expression patterns of multiple TFs reveals that post-transcriptional regulation plays an essential role in shaping these TF codes. Two RNA-binding proteins, Imp and Syp, expressed in opposing gradients in immature motoneurons, control the translation of multiple TFs. The varying sensitivity of TF mRNAs to the opposing gradients of Imp and Syp in immature motoneurons decrypts these gradients into distinct TF codes, establishing the connectome between motoneuron axons and their target muscles.


Asunto(s)
Proteínas de Drosophila , Células-Madre Neurales , Animales , Drosophila/genética , Drosophila/metabolismo , Proteínas de Drosophila/metabolismo , Neuronas Motoras/metabolismo , Células-Madre Neurales/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
14.
Med Sci (Paris) ; 36 Hors série n° 2: 13-16, 2020 Dec.
Artículo en Francés | MEDLINE | ID: mdl-33427630

RESUMEN

Diseases of the locomotor system are at the origin of disabilities with severe social and economic consequences. The study of the neuromuscular system development and maintenance has become a key challenge for the scientific community in order to design efficient therapies. My thesis project aims to elucidate the mechanisms at the origin of the communication between motoneuron axons and their muscle targets in order to understand how specific innervations are generated during development and maintained during adulthood. The first part of the project will address the understanding of the mechanisms controlling the specific muscle-axon recognition during development. I will perform live imaging and fixed tissues experiments to visualize and understand the development of myoblasts and motoneurons at the same time. Then, I will perform transcriptomic experiments to discover molecules playing a role in the specific axon-muscle recognition. The second part of the project is meant to elucidate the mechanism controlling the system maintenance in the adult. To answer this question I will study the function of morphological transcription factors in adulthood, which are known as transcription factors controlling the morphology of motoneurons during development. To conclude, this project will lead to novel biological concepts that will increase our fundamental knowledge on developmental biology. Understanding the mechanisms that specify the muscle innervation will allow to find efficient ways to tackle neuromuscular diseases.


Asunto(s)
Músculo Esquelético/crecimiento & desarrollo , Músculo Esquelético/fisiología , Regeneración/fisiología , Adulto , Animales , Axones/fisiología , Sistemas CRISPR-Cas , Regulación del Desarrollo de la Expresión Génica , Genómica/métodos , Humanos , Neuronas Motoras/fisiología , Músculo Esquelético/inervación , RNA-Seq , Regeneración/genética
15.
Clin Cardiol ; 42(3): 352-357, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30597584

RESUMEN

BACKGROUND: Little is known about how differences in out of hospital cardiac arrest patient volume affect in-hospital myocardial infarction (MI) mortality. HYPOTHESIS: Hospitals accepting cardiac arrest transfers will have increased hospital MI mortality. METHODS: MI patients (ST elevation MI [STEMI] and non-ST elevation MI [NSTEMI]) in the Acute Coronary Treatment Intervention Outcomes Network Registry were included. Hospital variation of cardiac arrest and temporal trend of the proportion of cardiac arrest MI patients were explored. Hospitals were divided into tertiles based on the proportion of cardiac arrest MI patients, and association between in-hospital mortality and hospital tertiles of cardiac arrest was compared using logistic regression adjusting for case mix. RESULTS: A total of 252 882 patients from 224 hospitals were included, of whom 9682 (3.8%) had cardiac arrest (1.6% of NSTEMI and 7.5% of STEMI patients). The proportion of MI patients who had cardiac arrest admitted to each hospital was relatively low (median 3.7% [25th, 75th percentiles: 3.0%, 4.5%]).with a range of 4.2% to 12.4% in the high-volume tertiles. Unadjusted in-hospital mortality increased with tertile: low 3.8%, intermediate 4.6%, and high 4.7% (P < 0.001); this was no longer significantly different after adjustment (intermediate vs high tertile odds ratio (OR) = 1.02; 95% confidence interval [0.90-1.16], low vs high tertile OR = 0.93 [0.83, 1.05]). CONCLUSIONS: The proportion of MI patients who have cardiac arrest is low. In-hospital mortality among all MI patients did not differ significantly between hospitals that had increased proportions of cardiac arrest MI patients. For most hospitals, overall MI mortality is unlikely to be adversely affected by treating cardiac arrest patients with MI.


Asunto(s)
Paro Cardíaco/etiología , Hospitalización/estadística & datos numéricos , Hospitales/estadística & datos numéricos , Infarto del Miocardio/complicaciones , Intervención Coronaria Percutánea/métodos , Sistema de Registros , Medición de Riesgo/métodos , Anciano , Colombia Británica/epidemiología , Causas de Muerte/tendencias , Electrocardiografía , Femenino , Paro Cardíaco/epidemiología , Mortalidad Hospitalaria/tendencias , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/cirugía , Factores de Riesgo , Estados Unidos/epidemiología
16.
J Am Heart Assoc ; 8(17): e012929, 2019 09 03.
Artículo en Inglés | MEDLINE | ID: mdl-31462138

RESUMEN

Background Little is known regarding use of cardiac therapies and clinical outcomes among older myocardial infarction (MI) patients with cognitive impairment. Methods and Results Patients ≥65 years old with MI in the NCDR (National Cardiovascular Data Registry) Chest Pain-MI Registry between January 2015 and December 2016 were categorized by presence and degree of chart-documented cognitive impairment. We evaluated whether cognitive impairment was associated with all-cause in-hospital mortality after adjusting for known prognosticators. Among 43 812 ST-segment-elevation myocardial infarction (STEMI) patients, 3.9% had mild and 2.0% had moderate/severe cognitive impairment; among 90 904 non-ST-segment-elevation myocardial infarction (NSTEMI patients, 5.7% had mild and 2.6% had moderate/severe cognitive impairment. A statistically significant but numerically small difference in the use of primary percutaneous coronary intervention was observed between patients with STEMI with and without cognitive impairment (none, 92.1% versus mild, 92.8% versus moderate/severe, 90.4%; P=0.03); use of fibrinolysis was lower among patients with cognitive impairment (none, 40.9% versus mild, 27.4% versus moderate/severe, 24.2%; P<0.001). Compared with NSTEMI patients without cognitive impairment, rates of angiography, percutaneous coronary intervention, and coronary artery bypass grafting were significantly lower among patients with NSTEMI with mild (41%, 45%, and 70% lower, respectively) and moderate/severe cognitive impairment (71%, 74%, and 93% lower, respectively). After adjustment, compared with no cognitive impairment, presence of moderate/severe (STEMI: odds ratio, 2.2, 95% CI, 1.8-2.7; NSTEMI: odds ratio, 1.7, 95% CI, 1.4-2.0) and mild cognitive impairment (STEMI: OR, 1.3, 95% CI, 1.1-1.5; NSTEMI: odds ratio, 1.3, 95% CI, 1.2-1.5) was associated with higher in-hospital mortality. Conclusions Patients with NSTEMI with cognitive impairment are substantially less likely to receive invasive cardiac care, while patients with STEMI with cognitive impairment receive similar primary percutaneous coronary intervention but less fibrinolysis. Presence and degree of cognitive impairment was independently associated with increased in-hospital mortality. Approaching clinical decision making for older patients with MI with cognitive impairment requires further study.


Asunto(s)
Cognición , Disfunción Cognitiva/epidemiología , Puente de Arteria Coronaria/tendencias , Disparidades en Atención de Salud/tendencias , Infarto del Miocardio sin Elevación del ST/terapia , Intervención Coronaria Percutánea/tendencias , Pautas de la Práctica en Medicina/tendencias , Infarto del Miocardio con Elevación del ST/terapia , Terapia Trombolítica/tendencias , Factores de Edad , Anciano , Anciano de 80 o más Años , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/mortalidad , Disfunción Cognitiva/psicología , Angiografía Coronaria/tendencias , Puente de Arteria Coronaria/efectos adversos , Puente de Arteria Coronaria/mortalidad , Femenino , Investigación sobre Servicios de Salud , Mortalidad Hospitalaria , Humanos , Masculino , Infarto del Miocardio sin Elevación del ST/diagnóstico , Infarto del Miocardio sin Elevación del ST/mortalidad , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/mortalidad , Prevalencia , Sistema de Registros , Medición de Riesgo , Factores de Riesgo , Infarto del Miocardio con Elevación del ST/diagnóstico , Infarto del Miocardio con Elevación del ST/mortalidad , Índice de Severidad de la Enfermedad , Terapia Trombolítica/efectos adversos , Terapia Trombolítica/mortalidad , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos/epidemiología
17.
Gend Med ; 5(1): 53-61, 2008 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-18420166

RESUMEN

BACKGROUND: Women have worse morbidity, mortality, and health-related quality-of-life outcomes associated with coronary artery disease (CAD) compared with men. This may be related to underutilization of drug therapies, such as aspirin, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, or statins. No studies have sought to describe the relationship of gender with adverse reactions to drug therapy (ADRs) for CAD in clinical practice. OBJECTIVE: The aim of this study was to determine the prevalence of ADRs associated with common CAD drug therapies in women and men in clinical practice. METHODS: In a cohort of consecutive outpatients with CAD, detailed chart abstraction was performed to determine the use of aspirin, beta-blocker, ACE inhibitor, and statin therapy, as well as the ADRs reported for these treatments. Baseline clinical characteristics were also determined to identify the independent association of gender with use of standard drug treatments for CAD. RESULTS: Consecutive patients with CAD (153 men, 151 women) were included in the study. Women and men were observed to have a similar prevalence of cardiac risk factors and comorbidities, except that men had significantly higher prevalence of atrial fibrillation (30 [19.6%] men vs 15 [9.9%] women; P = 0.03) and significantly lower mean (SD) high-density lipoprotein cholesterol concentrations (45 [16] mg/dL for men vs 55 [19] mg/dL for women; P < 0.001). No significant differences were observed between the sexes in the prevalence of ADRs; however, significantly fewer women than men were treated with statins (118 [78.1%] vs 139 [90.8%], respectively; P = 0.003). After adjusting for clinical characteristics, women were also found to be less likely than men to receive aspirin (odds ratio [OR] = 0.164; 95% CI, 0.083-0.322; P = 0.001) and beta-blockers (OR = 0.184; 95% CI, 0.096-0.351; P = 0.001). CONCLUSIONS: Women and men experienced a similar prevalence of ADRs in the treatment of CAD; however, women were significantly less likely to be treated with aspirin, beta-blockers, and statins than were their male counterparts. To optimize care for women with CAD, further study is needed to identify the cause of this gender disparity in therapeutic drug use.


Asunto(s)
Antagonistas Adrenérgicos beta/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Aspirina/uso terapéutico , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Factores Sexuales , Resultado del Tratamiento
18.
Cureus ; 10(3): e2261, 2018 Mar 02.
Artículo en Inglés | MEDLINE | ID: mdl-29725564

RESUMEN

Cardiac metastasis is much more common than primary cardiac tumors. Lung cancer is one of the most common primary malignancies to metastasize to the heart. It is not common for metastasis in the heart to present as a cavitary mass. To our knowledge, four cases have been reported in the literature showing metastatic lung cancer to the heart, presenting as a right ventricular mass.

19.
Cureus ; 10(5): e2632, 2018 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-30034954

RESUMEN

Streptococcus agalactiae (S.agalactiae) is known to cause invasive infections in pregnant women, newborns, and immunosuppressed patients. It is an uncommon but life-threatening case of infective endocarditis in middle-aged otherwise healthy adults. We present a case of a patient with life-threatening infective endocaritis caused by Streptococcus agalactiae, who passed away despite medical treatment.

20.
J Vis Exp ; (140)2018 10 30.
Artículo en Inglés | MEDLINE | ID: mdl-30451217

RESUMEN

The majority of work on the neuronal specification has been carried out in genetically and physiologically tractable models such as C. elegans, Drosophila larvae, and fish, which all engage in undulatory movements (like crawling or swimming) as their primary mode of locomotion. However, a more sophisticated understanding of the individual motor neuron (MN) specification-at least in terms of informing disease therapies-demands an equally tractable system that better models the complex appendage-based locomotion schemes of vertebrates. The adult Drosophila locomotor system in charge of walking meets all of these criteria with ease, since in this model it is possible to study the specification of a small number of easily distinguished leg MNs (approximately 50 MNs per leg) both using a vast array of powerful genetic tools, and in the physiological context of an appendage-based locomotion scheme. Here we describe a protocol to visualize the leg muscle innervation in an adult fly.


Asunto(s)
Axones/fisiología , Drosophila/fisiología , Locomoción/fisiología , Neuronas Motoras/fisiología , Animales , Drosophila/citología , Proteínas de Drosophila/genética , Extremidades/inervación , Locomoción/genética , Músculo Esquelético/inervación
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