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1.
Nature ; 608(7924): 757-765, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35948641

RESUMO

The notion that mobile units of nucleic acid known as transposable elements can operate as genomic controlling elements was put forward over six decades ago1,2. However, it was not until the advancement of genomic sequencing technologies that the abundance and repertoire of transposable elements were revealed, and they are now known to constitute up to two-thirds of mammalian genomes3,4. The presence of DNA regulatory regions including promoters, enhancers and transcription-factor-binding sites within transposable elements5-8 has led to the hypothesis that transposable elements have been co-opted to regulate mammalian gene expression and cell phenotype8-14. Mammalian transposable elements include recent acquisitions and ancient transposable elements that have been maintained in the genome over evolutionary time. The presence of ancient conserved transposable elements correlates positively with the likelihood of a regulatory function, but functional validation remains an essential step to identify transposable element insertions that have a positive effect on fitness. Here we show that CRISPR-Cas9-mediated deletion of a transposable element-namely the LINE-1 retrotransposon Lx9c11-in mice results in an exaggerated and lethal immune response to virus infection. Lx9c11 is critical for the neogenesis of a non-coding RNA (Lx9c11-RegoS) that regulates genes of the Schlafen family, reduces the hyperinflammatory phenotype and rescues lethality in virus-infected Lx9c11-/- mice. These findings provide evidence that a transposable element can control the immune system to favour host survival during virus infection.


Assuntos
Elementos de DNA Transponíveis , Interações entre Hospedeiro e Microrganismos , Imunidade , Retroelementos , Viroses , Animais , Sistemas CRISPR-Cas/genética , Elementos de DNA Transponíveis/genética , Elementos de DNA Transponíveis/imunologia , Evolução Molecular , Interações entre Hospedeiro e Microrganismos/genética , Interações entre Hospedeiro e Microrganismos/imunologia , Imunidade/genética , Camundongos , RNA não Traduzido/genética , Sequências Reguladoras de Ácido Nucleico/genética , Retroelementos/genética , Retroelementos/imunologia , Viroses/genética , Viroses/imunologia
2.
EMBO J ; 39(6): e102513, 2020 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-32073171

RESUMO

Various species of non-coding RNAs (ncRNAs) are enriched in specific subcellular compartments, but the mechanisms orchestrating their localization and their local functions remain largely unknown. We investigated both aspects using the elongating retinal ganglion cell axon and its tip, the growth cone, as models. We reveal that specific endogenous precursor microRNAs (pre-miRNAs) are actively trafficked to distal axons by hitchhiking primarily on late endosomes/lysosomes. Upon exposure to the axon guidance cue semaphorin 3A (Sema3A), pre-miRNAs are processed specifically within axons into newly generated miRNAs, one of which, in turn, silences the basal translation of tubulin beta 3 class III (TUBB3), but not amyloid beta precursor protein (APP). At the organismal level, these mature miRNAs are required for growth cone steering and a fully functional visual system. Overall, our results uncover a novel mode of ncRNA transport from one cytosolic compartment to another within polarized cells. They also reveal that newly generated miRNAs are critical components of a ncRNA-based signaling pathway that transduces environmental signals into the structural remodeling of subcellular compartments.


Assuntos
MicroRNAs/genética , RNA não Traduzido/genética , Transdução de Sinais , Animais , Axônios/fisiologia , Transporte Biológico , Endossomos/metabolismo , Feminino , Cones de Crescimento/fisiologia , Camundongos Endogâmicos C57BL , Precursores de RNA/genética , Células Ganglionares da Retina/fisiologia , Xenopus laevis
3.
Exp Physiol ; 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38687158

RESUMO

Limb immobilization causes rapid declines in muscle strength and mass. Given the role of the nervous system in immobilization-induced weakness, targeted interventions may be able to preserve muscle strength, but not mass, and vice versa. The purpose of this study was to assess the effects of two distinct interventions during 1 week of knee joint immobilization on muscle strength (isometric and concentric isokinetic peak torque), mass (bioimpedance spectroscopy and ultrasonography), and neuromuscular function (transcranial magnetic stimulation and interpolated twitch technique). Thirty-nine healthy, college-aged adults (21 males, 18 females) were randomized into one of four groups: immobilization only (n = 9), immobilization + action observation/mental imagery (AOMI) (n = 10), immobilization + neuromuscular electrical stimulation (NMES) (n = 12), or control group (n = 8). The AOMI group performed daily video observation and mental imagery of knee extensions. The NMES group performed twice daily stimulation of the quadriceps femoris. Based on observed effect sizes, it appears that AOMI shows promise as a means of preserving voluntary strength, which may be modulated by neural adaptations. Strength increased from PRE to POST in the AOMI group, with +7.2% (Cohen's d = 1.018) increase in concentric isokinetic peak torque at 30°/s. However, NMES did not preserve muscle mass. Though preliminary, our findings highlight the specific nature of clinical interventions and suggest that muscle strength can be independently targeted during rehabilitation. This study was prospectively registered: ClinicalTrials.gov NCT05072652.

4.
J Electrocardiol ; 82: 141-146, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38141487

RESUMO

BACKGROUND: The detection of atrial electrical activity is extremely valuable in recognizing complex cardiac arrhythmias. However, P-wave detection on a surface electrocardiogram (S-ECG) can sometimes be challenging. The intracardiac electrocardiogram (IC-ECG), recorded by a central venous catheter loaded with saline solution, has proven to be a safe and effective method for amplifying atrial electrical activity. We aim to compare the P-wave amplitude recorded in the S-ECG and the IC-ECG in different venous accesses, catheters, heart rhythms, and atrial dimensions. METHODS: We compared the P wave amplitude obtained by the IC-ECG and the S-ECG recordings from cardiac intensive care unit patients. RESULTS: In 109 nonconsecutive patients, a total of 166 IC-ECG were collected. The median amplitude of the P wave was 0.1 (0.083-0.3) mV in the S-ECG and 0.4 (0.25-2.4) mV in the IC-ECG; p < 0.001. This difference remained significant regardless of the patient's heart rhythm, left atrial dimension, and catheter or vascular access used. CONCLUSION: The IC-ECG acquired using central venous catheters significantly increases atrial electrical activity signals. This technique might help identify complex cardiac arrhythmias.


Assuntos
Cateterismo Venoso Central , Cateteres Venosos Centrais , Humanos , Cateterismo Venoso Central/métodos , Eletrocardiografia/métodos , Arritmias Cardíacas/diagnóstico , Átrios do Coração
5.
Exp Eye Res ; 234: 109602, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37488007

RESUMO

Glaucoma is the leading cause of irreversible blindness worldwide and its most prevalent subtype is primary open angle glaucoma (POAG). One pathological change in POAG is loss of cells in the trabecular meshwork (TM), which is thought to contribute to ocular hypertension and has thus motivated development of cell-based therapies to refunctionalize the TM. TM cell therapy has shown promise in intraocular pressure (IOP) control, but existing cell delivery techniques suffer from poor delivery efficiency. We employed a novel magnetic delivery technique to reduce the unwanted side effects of off-target cell delivery. Mesenchymal stem cells (MSCs) were labeled with superparamagnetic iron oxide nanoparticles (SPIONs) and after intracameral injection were magnetically steered towards the TM using a focused magnetic apparatus ("point magnet"). This technique delivered the cells significantly closer to the TM at higher quantities and with more circumferential uniformity compared to either unlabeled cells or those delivered using a "ring magnet" technique. We conclude that our point magnet cell delivery technique can improve the efficiency of TM cell therapy and in doing so, potentially increase the therapeutic benefits and lower the risk of complications such as tumorigenicity and immunogenicity.


Assuntos
Glaucoma de Ângulo Aberto , Glaucoma , Animais , Camundongos , Malha Trabecular/patologia , Glaucoma de Ângulo Aberto/patologia , Glaucoma/patologia , Pressão Intraocular , Fenômenos Magnéticos
6.
Biomacromolecules ; 24(9): 4042-4050, 2023 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-37605889

RESUMO

Biomineralization of fish otoliths is regulated by macromolecules, such as proteins, whose presence is crucial for the functionality and properties of these mineralized structures. Special regulatory effects are exerted by intrinsically disordered proteins, such as the polyanionic Starmaker-like protein from medaka, a homolog of zebrafish Starmaker. In this study, we employed a set of bioinspired mineralization experiments with a single diffusion system to investigate the effect of the Starmaker-like protein on calcium carbonate biominerals with regards to the prior exposition of the protein to calcium or carbonate ions. Interestingly, the bioinspired minerals grown in the presence of the Starmaker-like protein in calcium- or carbonate-type experiments differ significantly in terms of morphology and protein distribution within the crystals. Our deeper analysis shows that the Starmaker-like protein action is a result of the environmental conditions to which it is exposed. These findings may be of special interest in the areas of biomineralization process pathways and biomaterial sciences.


Assuntos
Carbonato de Cálcio , Cálcio , Animais , Peixe-Zebra , Materiais Biocompatíveis , Íons
7.
Med Vet Entomol ; 37(2): 316-329, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36543747

RESUMO

Triatoma maculata (Hemiptera, Reduviidae, Triatominae) occurs across dry-to-semiarid ecoregions of northern South America, where it transmits Trypanosoma cruzi, causative agent of Chagas disease. Using 207 field-caught specimens from throughout the species' range, mitochondrial(mt) DNA sequence data, and cytogenetics, we investigated inter-population genetic diversity and the phylogenetic affinities of T. maculata. Mitochondrial DNA sequence analyses (cytb and nd4) disclosed a monophyletic T. maculata clade encompassing three distinct geographic groups: Roraima formation (Guiana shield), Orinoco basin, and Magdalena basin (trans-Andean). Between-group cytb distances (11.0-12.8%) were larger than the ~7.5% expected for sister Triatoma species; the most recent common ancestor of these T. maculata groups may date back to the late Miocene. C-heterochromatin distribution and the sex-chromosome location of 45S ribosomal DNA clusters both distinguished Roraima bugs from Orinoco and Magdalena specimens. Cytb genealogies reinforced that T. maculata is not sister to Triatoma pseudomaculata and probably represents an early (middle-late Miocene) offshoot of the 'South American Triatomini lineage'. In sum, we report extensive genetic diversity and deep phylogeographic structuring in T. maculata, suggesting that it may consist of a complex of at least three sibling taxa. These findings have implications for the systematics, population biology, and perhaps medical relevance of T. maculata sensu lato.


Assuntos
Doença de Chagas , Triatoma , Trypanosoma cruzi , Animais , Triatoma/genética , Filogenia , Doença de Chagas/veterinária , Trypanosoma cruzi/genética , DNA Mitocondrial/genética , Análise Citogenética/veterinária
8.
Nucleic Acids Res ; 49(12): 7164-7178, 2021 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-34139012

RESUMO

The rnlAB toxin-antitoxin operon from Escherichia coli functions as an anti-phage defense system. RnlA was identified as a member of the HEPN (Higher Eukaryotes and Prokaryotes Nucleotide-binding domain) superfamily of ribonucleases. The activity of the toxin RnlA requires tight regulation by the antitoxin RnlB, the mechanism of which remains unknown. Here we show that RnlA exists in an equilibrium between two different homodimer states: an inactive resting state and an active canonical HEPN dimer. Mutants interfering with the transition between states show that canonical HEPN dimerization via the highly conserved RX4-6H motif is required for activity. The antitoxin RnlB binds the canonical HEPN dimer conformation, inhibiting RnlA by blocking access to its active site. Single-alanine substitutions mutants of the highly conserved R255, E258, R318 and H323 show that these residues are involved in catalysis and substrate binding and locate the catalytic site near the dimer interface of the canonical HEPN dimer rather than in a groove located between the HEPN domain and the preceding TBP-like domain. Overall, these findings elucidate the structural basis of the activity and inhibition of RnlA and highlight the crucial role of conformational heterogeneity in protein function.


Assuntos
Proteínas de Escherichia coli/química , Ribonucleases/química , Dimerização , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Modelos Moleculares , Mutação , Conformação Proteica , Domínios Proteicos , Multimerização Proteica , Ribonucleases/genética , Ribonucleases/metabolismo , Especificidade por Substrato
9.
J Emerg Nurs ; 49(4): 611-630, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37178091

RESUMO

INTRODUCTION: Seniors are often accompanied by a family member to the emergency department. Families advocate for their needs and contribute to the continuity of care. However, they often feel excluded from care. To improve the quality and safety of care for seniors, it is necessary to consider the experience of families in the emergency department. The aim was to identify and synthesize the available scientific literature dealing with the experience of families accompanying a senior to the emergency department. To identify and synthesize the available scientific literature dealing with the experience of families accompanying a senior to the emergency department. METHODS: A scoping review was conducted using the Arksey and O'Malley framework. Six databases were targeted. A description of the identified scientific literature and an inductive content analysis were performed. RESULTS: Of the 3082 articles retrieved, 19 met the inclusion criteria. Most articles (89%) were published since 2010, were from nursing (63%), and used a qualitative research design (79%). The content analysis identified 4 main categories related to the experience of families accompanying a senior to the emergency department: (1) process leading to the emergency department, families feel uncertainty and ambiguity with the decision to go to the emergency department; (2) staying in the emergency department, families' experiences are influenced by the triage, the ED environment, and the interactions with ED personnel; (3) discharge from the emergency department, families consider that they should be part of the discharge planning; and (4) recommendations and possible solutions, there is a paucity of recommendations specifically focused on families. DISCUSSION: The experience of families of seniors in the emergency department is multifactorial and part of a trajectory of care and health services.


Assuntos
Serviço Hospitalar de Emergência , Triagem , Humanos , Alta do Paciente , Incerteza
10.
Exp Brain Res ; 240(6): 1801-1810, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35488129

RESUMO

Muscle weakness is a critical problem facing many older adults. Interventions targeting nervous system plasticity may show promise in enhancing strength. The purpose of this study was to examine the acute effects of action observation on muscular strength characteristics and corticospinal excitability in older adults. Isometric wrist flexion strength characteristics and corticospinal excitability of the first dorsal interosseous (FDI) were measured in 14 older adults (mean age = 73 years) in response to observation of (1) STRONG contractions of the hand/wrist, (2) WEAK contractions of the hand/wrist, and (3) a CONTROL condition. Results from repeated measures analyses of variance (ANOVAs) indicated that rate of torque development at 200 ms (RTD200) significantly decreased from PRE to POST observation for CONTROL and WEAK, but not STRONG. No other ANOVAs were significant. However, effect sizes indicated that maximal voluntary contraction (MVC) peak torque showed moderate declines following WEAK (d = - 0.571) and CONTROL (d = - 0.636), but not STRONG (d = 0.024). Similarly, rate of torque development at 30 (RTD30), 50 (RTD50), and 200 (RTD200) ms showed large declines from PRE to POST after WEAK and CONTROL, but small changes following STRONG. FDI motor-evoked potential (MEP) amplitude tended to increase over time, but these results were variable. There was a pronounced effect from PRE to 8MIN (d = 0.954) during all conditions. Action observation of strong contractions may exert a preservatory effect on muscular strength. More work is needed to determine whether this is modulated by increased corticospinal excitability. The study was prospectively registered (ClinicalTrials.gov Identifier: NCT03946709).


Assuntos
Contração Isométrica , Tratos Piramidais , Idoso , Eletromiografia , Potencial Evocado Motor/fisiologia , Humanos , Contração Isométrica/fisiologia , Força Muscular/fisiologia , Debilidade Muscular , Músculo Esquelético/fisiologia , Tratos Piramidais/fisiologia , Estimulação Magnética Transcraniana/métodos
11.
Clin Nephrol ; 98(6): 288-295, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36331021

RESUMO

BACKGROUND: The following cell cycle arrest urinary biomarkers, tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP-7), have been used for early detection of acute kidney injury (AKI) in critically ill patients. The purpose of this study is to validate the use of these urinary biomarkers in patients undergoing open heart surgery. MATERIALS AND METHODS: In a single-center prospective observational study, urine samples were collected in 108 consecutive patients who underwent open heart surgery immediately after separation from cardiopulmonary bypass and on postoperative day 1, and were sent for the biomarker [TIMP-2]*[IGFBP7] analysis. Acute kidney injury was defined based on KDIGO criteria, and levels of [TIMP-2]*[IGFBP7] were analyzed for the ability to predict AKI. RESULTS: Of the 108 patients, 19 (17.6%) patients developed postoperative AKI within 48 hours of surgery. At the threshold of > 0.3 (ng/mL)2/1,000, post-cardiopulmonary bypass [TIMP-2]*[IGFBP-7] had a sensitivity of 13% and specificity of 82% for predicting postoperative AKI. Postoperative day-1 [TIMP-2]*[IGFBP-7] had a sensitivity of 47% and a specificity of 59% for predicting postoperative AKI. There were no differences in [TIMP-2]*[IGFBP-7] values at either timepoint between patients who developed postoperative AKI as compared to those who did not. CONCLUSION: Urinary [TIMP-2]*[IGFBP7] was not predictive of the risk of AKI after cardiac surgery in this single-center study population.


Assuntos
Injúria Renal Aguda , Procedimentos Cirúrgicos Cardíacos , Humanos , Inibidor Tecidual de Metaloproteinase-2/urina , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/urina , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Biomarcadores/urina
12.
Mem Inst Oswaldo Cruz ; 116: e210259, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35137904

RESUMO

BACKGROUND: Panstrongylus rufotuberculatus (Hemiptera-Reduviidae) is a triatomine species with a wide geographic distribution and a broad phenotypic variability. In some countries, this species is found infesting and colonising domiciliary ecotopes representing an epidemiological risk factor as a vector of Trypanosoma cruzi, etiological agent of Chagas disease. In spite of this, little is known about P. rufotuberculatus genetic diversity. METHODS: Cytogenetic studies and DNA sequence analyses of one nuclear (ITS-2) and two mitochondrial DNA sequences (cyt b and coI) were carried out in P. rufotuberculatus individuals collected in Bolivia, Colombia, Ecuador and Mexico. Moreover, a geometric morphometrics study was applied to Bolivian, Colombian, Ecuadorian and French Guiana samples. OBJECTIVES: To explore the genetic and phenetic diversity of P. rufotuberculatus from different countries, combining chromosomal studies, DNA sequence analyses and geometric morphometric comparisons. FINDINGS: We found two chromosomal groups differentiated by the number of X chromosomes and the chromosomal position of the ribosomal DNA clusters. In concordance, two main morphometric profiles were detected, clearly separating the Bolivian sample from the other ones. Phylogenetic DNA analyses showed that both chromosomal groups were closely related to each other and clearly separated from the remaining Panstrongylus species. High nucleotide divergence of cyt b and coI fragments were observed among P. rufotuberculatus samples from Bolivia, Colombia, Ecuador and Mexico (Kimura 2-parameter distances higher than 9%). MAIN CONCLUSIONS: Chromosomal and molecular analyses supported that the two chromosomal groups could represent different closely related species. We propose that Bolivian individuals constitute a new Panstrongylus species, being necessary a detailed morphological study for its formal description. The clear morphometric discrimination based on the wing venation pattern suggests such morphological description might be conclusive.


Assuntos
Doença de Chagas , Heterópteros , Panstrongylus , Triatoma , Animais , Humanos , Insetos Vetores/genética , Panstrongylus/genética , Filogenia
13.
Rev Panam Salud Publica ; 46: e133, 2022.
Artigo em Espanhol | MEDLINE | ID: mdl-36245907

RESUMO

The Virtual Campus for Public Health (VCPH) is the educational platform of the Pan American Health Organization, conceived as a tool for technical cooperation.The objectives of this article are to: characterize the training offered at the VCPH, identifying its virtual courses; characterize course participants; describe technological updating processes and the advances made in terms of accessibility; and identify the VCPH's relationship with the main lines of cooperation of the Pan American Health Organization.The VCPH has developed 210 tutored courses and 226 self-learning courses since 2007, related to the Organization's policies. Heterogeneous use of the campus was observed in the different areas of cooperation. The number of self-learning courses conducted during the pandemic surpassed the total figure accumulated in previous years.Participants are mainly from Latin America; 67.5% are women between 26 and 45 years of age; 57.1% have a university education, mainly in nursing or medicine; half of them work in hospitals and 35.8% at the first level of care.More than 90% of the participants had a favorable opinion of the topics addressed, the learning resources offered, and the characteristics of the virtual classroom. Among difficulties, they indicated little available time and poor internet access; among advantages, they emphasized independent schedules and access to various sources of information. The available assessment tools are not sufficient to determine the impact of VCPH educational programs.The challenges are to deepen the accessibility and quality of education offered, strengthen links with areas of cooperation, and improve course evaluations and knowledge about VCPH users.


O Campus Virtual de Saúde Pública é a plataforma educacional da Organização Pan-Americana da Saúde, concebida como uma ferramenta de cooperação técnica.Os objetivos deste artigo são caracterizar os treinamentos oferecidos pelo Campus Virtual de Saúde Pública, identificando as propostas de cursos virtuais; caracterizar os participantes desses cursos; descrever os processos de atualização tecnológica e seu progresso em termos de acessibilidade; e identificar sua relação com as principais linhas de cooperação da Organização Pan-Americana da Saúde.Desde 2007, o Campus Virtual de Saúde Pública desenvolveu 210 cursos com orientação e 226 cursos de autoaprendizagem relacionados às políticas da Organização. Houve um uso heterogêneo do campus em relação aos diferentes temas de cooperação. O número de cursos de autoaprendizagem realizados durante a pandemia excedeu o número total acumulado nos anos anteriores.Os participantes são oriundos principalmente da América Latina. No total, 67,5% são mulheres, com idade entre 26 e 45 anos, e 57,1% têm formação universitária, principalmente em enfermagem ou medicina. Metade trabalha em hospitais e 35,8% na atenção primária.Mais de 90% dos participantes fizeram uma avaliação favorável dos tópicos abordados, recursos de conhecimento e características da sala de aula virtual. Como dificuldades, destacam-se a pouca disponibilidade de tempo e o acesso limitado à Internet. As vantagens incluem a autonomia de horários e o acesso a várias fontes de informação. As ferramentas de avaliação disponíveis não são suficientes para reconhecer o impacto dos programas educacionais.Os desafios são aprofundar a acessibilidade e a qualidade das propostas educacionais, fortalecer sua relação com os temas de cooperação e melhorar a avaliação dos cursos e o conhecimento dos usuários.

14.
Molecules ; 27(6)2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35335253

RESUMO

Circulating levels of 2-hydroxybutyrate (2HB) are highly related to glycemic status in different metabolomic studies. According to recent evidence, 2HB is an early biomarker of the future development of dysglycemia and type 2 diabetes mellitus and may be causally related to the progression of normal subjects to impaired fasting glucose or insulin resistance. In the present study, we developed and validated a simple, specific and sensitive gas chromatography-mass spectrometry (GC-MS) method specifically intended to quantify serum levels of 2HB. Liquid-liquid extraction with ethyl acetate was followed by 2 min of microwave-assisted derivatization. The method presented acceptable accuracy, precision and recovery, and the limit of quantification was 5 µM. Levels of 2HB were found to be stable in serum after three freeze-thaw cycles, and at ambient temperature and at a temperature of 4 °C for up to 24 h. Extracts derivatized under microwave irradiation were stable for up to 96 h. No differences were found in 2HB concentrations measured in serum or plasma EDTA samples. In summary, the method is useful for a rapid, precise and accurate quantification of 2HB in serum samples assessed for the evaluation of dysglycemia and diabetes mellitus.


Assuntos
Diabetes Mellitus Tipo 2 , Micro-Ondas , Biomarcadores , Diabetes Mellitus Tipo 2/diagnóstico , Cromatografia Gasosa-Espectrometria de Massas/métodos , Humanos , Hidroxibutiratos
15.
Dev Biol ; 457(2): 206-214, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-30796893

RESUMO

The choriocapillaris is an exceptionally high density, two-dimensional, sheet-like capillary network, characterized by the highest exchange rate of nutrients for waste products per area in the organism. These unique morphological and physiological features are critical for supporting the extreme metabolic requirements of the outer retina needed for vision. The developmental mechanisms and processes responsible for generating this unique vascular network remain, however, poorly understood. Here we take advantage of the zebrafish as a model organism for gaining novel insights into the cellular dynamics and molecular signaling mechanisms involved in the development of the choriocapillaris. We show for the first time that zebrafish have a choriocapillaris highly similar to that in mammals, and that it is initially formed by a novel process of synchronized vasculogenesis occurring simultaneously across the entire outer retina. This initial vascular network expands by un-inhibited sprouting angiogenesis whereby all endothelial cells adopt tip-cell characteristics, a process which is sustained throughout embryonic and early post-natal development, even after the choriocapillaris becomes perfused. Ubiquitous sprouting was maintained by continuous VEGF-VEGFR2 signaling in endothelial cells delaying maturation until immediately before stages where vision becomes important for survival, leading to the unparalleled high density and lobular structure of this vasculature. Sprouting was throughout development limited to two dimensions by Bruch's membrane and the sclera at the anterior and posterior surfaces respectively. These novel cellular and molecular mechanisms underlying choriocapillaris development were recapitulated in mice. In conclusion, our findings reveal novel mechanisms underlying the development of the choriocapillaris during zebrafish and mouse development. These results may explain the uniquely high density and sheet-like organization of this vasculature.


Assuntos
Corioide/irrigação sanguínea , Corioide/embriologia , Neovascularização Fisiológica/fisiologia , Retina/embriologia , Animais , Diferenciação Celular/fisiologia , Camundongos , Camundongos Endogâmicos BALB C , Transdução de Sinais/fisiologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Peixe-Zebra , Proteínas de Peixe-Zebra/metabolismo
16.
Proc Biol Sci ; 288(1954): 20210922, 2021 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-34255999

RESUMO

Animals across phyla can detect early cues of infection in conspecifics, thereby reducing the risk of contamination. It is unknown, however, if humans can detect cues of sickness in people belonging to communities with whom they have limited or no experience. To test this, we presented Western faces photographed 2 h after the experimental induction of an acute immune response to one Western and five non-Western communities, including small-scale hunter-gatherer and large urban-dwelling communities. All communities could detect sick individuals. There were group differences in performance but Western participants, who observed faces from their own community, were not systematically better than all non-Western participants. At odds with the common belief that sickness detection of an out-group member should be biased to err on the side of caution, the majority of non-Western communities were unbiased. Our results show that subtle cues of a general immune response are recognized across cultures and may aid in detecting infectious threats.


Assuntos
Sinais (Psicologia) , Humanos
17.
J Pediatr Psychol ; 46(7): 844-855, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34015114

RESUMO

OBJECTIVE: This study examined the feasibility and initial outcome of a time-limited and intensive format of Parent-Child Interaction Therapy (PCIT) for families of young children who have sustained a traumatic brain injury (TBI). METHODS: The nonrandomized open trial included 15 families with a child aged 2-5 years who had sustained a TBI and displayed clinically elevated levels of externalizing behavior problems. Families received clinic-based PCIT twice per week over an average of 6 weeks, with the exception of two families that received the same intensity and format of PCIT in the home. RESULTS: Ten of the 14 families who completed the baseline assessment (71%) completed the intervention and post and follow-up assessments. On average, caregivers completed homework practice on 52% of the days in between sessions. Caregivers reported high acceptability and satisfaction following the intervention, as well as decreases in child externalizing and internalizing behavior problems at the post-assessment and 2-month follow-up. CONCLUSIONS: Results of this open trial provide preliminary support for the feasibility of a time-limited and intensive format of PCIT for families of young children who have sustained a TBI and have elevated levels of behavior problems. This study highlights a promising intervention approach for improving domains commonly affected by early childhood TBI and preventing the development of more severe and persistent problems.


Assuntos
Lesões Encefálicas Traumáticas , Comportamento Problema , Terapia Comportamental , Lesões Encefálicas Traumáticas/terapia , Pré-Escolar , Estudos de Viabilidade , Humanos , Relações Pais-Filho
18.
Australas J Dermatol ; 62(3): e366-e372, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33608878

RESUMO

BACKGROUND/OBJECTIVE: Psoriatic arthritis (PsA) is a chronic inflammatory illness. Approximately, 15% of psoriasis patients have undiagnosed PsA. In Mexico, we found no related studies. Our objective was to investigate the clinical-epidemiological characteristics of PsA in psoriasis patients in western Mexico. METHODS: A cross-sectional study including Mexican patients with clinical and histopathological diagnosis of psoriasis. Physical examination, rheumatoid factor analysis and radiographies of axial and peripheral skeleton were performed. The prevalence of PsA using the CASPAR criteria, age, sex; clinical variants of PsA, psoriasis type and the Psoriasis Area and Severity Index (PASI), were assessed. Descriptive and inferential statistics were used. RESULTS: Of 90 patients with psoriasis, 48 met the criteria for PsA, with a prevalence of 53%, and average age of 50 ± 15 years. Predominating were, the female sex in 29 (60%), the axial variant of PsA in 24 (50%), and psoriasis plaques in 40 (83%). The average PASI was 12 ± 11. All cases were rheumatoid factor negative. These variables were not significantly different when comparing subjects with and without PsA, except for the female sex (60% vs. 7%; P < 0.001). CONCLUSIONS: Patients with psoriasis should intentionally be evaluated jointly Dermatologists and Rheumatologists searching joint involvement given the high prevalence of PsA previously undiagnosed.


Assuntos
Artrite Psoriásica/diagnóstico , Artrite Psoriásica/epidemiologia , Índice de Gravidade de Doença , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , México , Pessoa de Meia-Idade , Psoríase/diagnóstico , Psoríase/epidemiologia
19.
Prev Sci ; 22(3): 269-283, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33586056

RESUMO

Health agencies call for the immediate mobilization of existing interventions in response to numerous child and family mental health concerns that have arisen as result of the COVID-19 pandemic. Answering this call, this pilot study describes the rapid, full-scale change from a primarily clinic-based Parent-Child Interaction Therapy (PCIT) model to a virtual service model (i.e., I-PCIT) in an academic and community-based program in Miami, Florida. First, we describe the virtual service training model our program developed and its implementation with 17 therapists (MAge = 32.35, 88.2% female, 47.1% Hispanic) to enable our clinic to shift from providing virtual services to a small portion of the families served (29.1%) to all of the families served. Second, we examine the effect of I-PCIT on child and caregiver outcomes during the 2-month stay-at-home period between March 16, 2020, and May 16, 2020, in 86 families (MChildAge = 4.75, 71% Hispanic). Due to the rapid nature of the current study, all active participants were transferred to virtual services, and therefore there was no comparison or control group, and outcomes represent the most recently available scores and not treatment completion. Results reveal that I-PCIT reduced child externalizing and internalizing problems and caregiver stress, and increased parenting skills and child compliance with medium to large effects even in the midst of the COVID-19 pandemic. Finally, the study examined components of our virtual service training model associated with the greatest improvements in child and caregiver outcomes. Preliminary findings revealed that locally and collaboratively developed strategies (e.g., online communities of practice, training videos and guides) had the strongest association with child and caregiver outcomes. Implications for virtual service delivery, implementation, and practice in the midst of the COVID-19 pandemic are discussed.


Assuntos
Terapia Comportamental/métodos , COVID-19/epidemiologia , Transtornos do Comportamento Infantil/psicologia , Transtornos do Comportamento Infantil/terapia , Relações Pais-Filho , Telemedicina , Adulto , Criança , Feminino , Florida , Humanos , Masculino , Pandemias , Projetos Piloto , SARS-CoV-2
20.
Gac Med Mex ; 157(4): 343-349, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35133336

RESUMO

INTRODUCTION: Sarcoplasmic reticulum Ca2+ ATPases (SERCA) enzymes are essential for intracellular Ca2+ homeostasis. SERCA genes (ATP2A1-3) encode for different functional isoforms of the protein, whose expression or function is altered in several types of cancer, such as gastric and oral, as well as colon, breast, lung, thyroid, liver, and prostate cancer, among others. However, the role played by SERCA pumps in carcinogenesis is unknown. METHODS: Techniques such as real-time polymerase chain reaction, optical microscopy, proliferation and cell death assays, as well as bioinformatic analyses were used. OBJECTIVES: To evaluate the expression levels of the ATP2A2 and ATP2A3 genes in cell lines representative of different subtypes of breast cancer. RESULTS: The results show that the MDA-MB-231 cell line expresses lower mRNA levels for the ATP2A3 gene in comparison with MCF-7 cells. The use of the phytoestrogen resveratrol induces ATP2A3 expression, decreases proliferation, and induces apoptosis in both cell types. CONCLUSIONS: SERCA expression might function as a tool to differentiate breast cancer subtypes, which have different treatment requirements.


INTRODUCCIÓN: Las enzimas SERCA son esenciales para la homeostasis intracelular de Ca2+. Los genes SERCA (ATP2A1-3) codifican para distintas isoformas funcionales de la proteína, cuya expresión o función se encuentra alterada en diversos tipos de cáncer, como el gástrico y el oral, así como de colon, mama, pulmón, tiroides, hígado y próstata, entre otros. Sin embargo, se desconoce el papel de las bombas SERCA en la carcinogénesis. MÉTODOS: Se utilizaron estudios como reacción en cadena de la polimerasa en tiempo real, microscopia óptica, ensayos de proliferación y muerte celular, así como análisis bioinformáticos. OBJETIVOS: Evaluar los niveles de expresión de los genes ATP2A2 y ATP2A3 en líneas celulares que representan diferentes subtipos de cáncer de mama. RESULTADOS: La línea celular MDA-MB-231 expresa niveles más bajos del ARNm para el gen ATP2A3, en comparación con las células MCF-7. El uso del fitoestrógeno resveratrol induce la expresión de ATP2A3, disminuye la proliferación e induce apoptosis en ambos tipos de células. CONCLUSIONES: La expresión de SERCA puede funcionar como una herramienta para diferenciar los subtipos de cáncer de mama, los cuales tienen distintas necesidades de tratamiento.


Assuntos
Neoplasias da Mama , Apoptose , Neoplasias da Mama/genética , Cálcio/metabolismo , Feminino , Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Retículo Sarcoplasmático/metabolismo
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