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1.
Biochem J ; 480(3): 225-241, 2023 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-36734208

RESUMEN

Carcinoma-associated fibroblasts (CAFs) play an important role in the progression of multiple malignancies. Secretion of cytokines and growth factors underlies the pro-tumoral effect of CAFs. Although this paracrine function has been extensively documented, the molecular mechanisms controlling the expression of these factors remain elusive. In this study, we provide evidence of a novel CAF transcriptional axis regulating the expression of SDF1, a major driver of cancer cell migration, involving the transcription factor GLI1 and histone acetyltransferase p300. We demonstrate that conditioned media from CAFs overexpressing GLI1 induce the migration of pancreatic cancer cells, and this effect is impaired by an SDF1-neutralizing antibody. Using a combination of co-immunoprecipitation, proximity ligation assay and chromatin immunoprecipitation assay, we further demonstrate that GLI1 and p300 physically interact in CAFs to co-occupy and drive SDF1 promoter activity. Mapping experiments highlight the requirement of GLI1 N-terminal for the interaction with p300. Importantly, knockdowns of both GLI1 and p300 reduce SDF1 expression. Further analysis shows that knockdown of GLI1 decreases SDF1 promoter activity, p300 recruitment, and levels of its associated histone marks (H4ac, H3K27ac, and H3K14ac). Finally, we show that the integrity of two GLI binding sites in the SDF1 promoter is required for p300 recruitment. Our findings define a new role for the p300-GLI1 complex in the regulation of SDF1, providing new mechanistic insight into the molecular events controlling pancreatic cancer cells migration.


Asunto(s)
Fibroblastos Asociados al Cáncer , Neoplasias Pancreáticas , Humanos , Fibroblastos Asociados al Cáncer/metabolismo , Fibroblastos Asociados al Cáncer/patología , Línea Celular Tumoral , Movimiento Celular , Inmunoprecipitación de Cromatina , Neoplasias Pancreáticas/patología , Transducción de Señal , Proteína con Dedos de Zinc GLI1/genética , Proteína con Dedos de Zinc GLI1/metabolismo , Quimiocina CXCL12/metabolismo , Neoplasias Pancreáticas
2.
J Biosoc Sci ; : 1-16, 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38646721

RESUMEN

Existing research on human growth in Mexico is regionally focused, creating a gap in the understanding of growth patterns of children and adolescents at national level and regional variation. The objective of the present study was to characterize the height growth curve of the Mexican population by geographic area and to cluster the states of the Mexican Republic according to their somatic maturation characteristics, based on a national representative sample of boys. Data on age, height, socioeconomic level, and geographic area of 18,219 boys were obtained from the National Health and Nutrition Survey 2012 (ENSANUT) and ENSANUT 2018, carried out in 32 Mexican states. Both surveys had representative samples. Preece-Baines 1 model was applied to fit height growth curves. Biological parameters were estimated; principal component analysis and cluster analysis were performed to group Mexican states based on these biological parameters. The estimated age at peak height velocity (PHV) was 12.3 years in the sample. Significant regional differences in the timing and tempo of PHV among Mexican boys were observed. Boys in the northern region experienced PHV at an earlier age and had a shorter duration of growth compared with boys in the central and southern regions. Boys in the central region had a longer duration of growth and a later age of PHV compared with the boys in the southern region. The cluster that included the southern states of the country showed estimated lower adult height and earlier somatic maturation. A lower height was found in the low and low-middle socioeconomic levels compared with the medium-high and high socioeconomic levels. Future research in Mexico should focus on longitudinal studies to analyse the timing and tempo of growth and maturation, considering the impacts of environmental and genetic factors. Public health strategies should account for geographic variations.

3.
Int J Mol Sci ; 25(11)2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38892397

RESUMEN

Pathogenic bacteria have several mechanisms to evade the host's immune response and achieve an efficient infection. Bacterial extracellular vesicles (EVs) are a relevant cellular communication mechanism, since they can interact with other bacterial cells and with host cells. In this review, we focus on the EVs produced by some World Health Organization (WHO) priority Gram-negative and Gram-positive pathogenic bacteria; by spore-producing bacteria; by Mycobacterium tuberculosis (a bacteria with a complex cell wall); and by Treponema pallidum (a bacteria without lipopolysaccharide). We describe the classification and the general properties of bacterial EVs, their role during bacterial infections and their effects on the host immune response. Bacterial EVs contain pathogen-associated molecular patterns that activate innate immune receptors, which leads to cytokine production and inflammation, but they also contain antigens that induce the activation of B and T cell responses. Understanding the many effects of bacterial EVs on the host's immune response can yield new insights on the pathogenesis of clinically important infections, but it can also lead to the development of EV-based diagnostic and therapeutic strategies. In addition, since EVs are efficient activators of both the innate and the adaptive immune responses, they constitute a promising platform for vaccine development.


Asunto(s)
Vesículas Extracelulares , Vesículas Extracelulares/inmunología , Vesículas Extracelulares/metabolismo , Humanos , Animales , Inmunidad Innata , Interacciones Huésped-Patógeno/inmunología , Infecciones Bacterianas/inmunología , Infecciones Bacterianas/microbiología , Bacterias/inmunología
4.
Am J Psychother ; 77(2): 79-87, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38487817

RESUMEN

Clinical decision making by psychiatrists and informed consent by patients require knowledge of evidence-based psychotherapies (EBPs) and their indications. However, many mental health professionals are not versed in the empirical literature on EBPs or the consensus guideline recommendations derived from this literature. The authors compared rigorous national consensus guidelines for EBP treatment of DSM-defined adult psychiatric disorders-derived from well-conducted randomized controlled trials and meta-analyses and from expert opinions from the United States, United Kingdom, and Canada-to create the Psychotherapies-at-a-Glance tool. Recommended EBPs are cognitive-behavioral therapy, family therapy, contingency management, dialectical behavior therapy, eye movement desensitization reprocessing, interpersonal psychotherapy, mentalization-based treatment, motivational interviewing, peer support, problem-solving therapy, psychoeducation, short-term psychodynamic psychotherapy, and 12-step facilitation. The Psychotherapies-at-a-Glance tool summarizes the indications, rationales, and therapeutic tasks that characterize these differing psychotherapies and psychosocial treatments. The tool is intended for use in clinical teaching, treatment planning, and patient communications.


Asunto(s)
Trastornos Mentales , Guías de Práctica Clínica como Asunto , Psicoterapia , Humanos , Trastornos Mentales/terapia , Psicoterapia/métodos , Psicoterapia/normas , Adulto , Consenso , Estados Unidos , Medicina Basada en la Evidencia
5.
J Sex Marital Ther ; 49(8): 869-885, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37218825

RESUMEN

Sexual difficulties can have negative intrapersonal and interpersonal consequences on both members of a couple, but little is known about how communication in a relationship relates to men's experience of sexual difficulties. We explored the associations among components of intimate communication, men's sexual difficulties, relationship satisfaction, and sexual satisfaction in a sample of men in mixed-gender and same-gender relationships (n = 341). Among all components of intimate communication, sexual communication was most consistently related to indicators of sexual difficulties, relationship satisfaction, and sexual satisfaction. Results generally remained consistent across mixed-gender and same-gender couples, with some exceptions relevant to sexual difficulties.


Asunto(s)
Conducta Sexual , Parejas Sexuales , Masculino , Humanos , Hombres , Identidad de Género , Comunicación , Relaciones Interpersonales
6.
Appl Opt ; 62(31): 8357-8365, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-38037940

RESUMEN

The use of polarization measurements has become more common in recent years, as it gives more information than pure intensity measurements. Polarimetric components such as fixed or variable retarders and polarizers must be included in optical systems to obtain the polarization parameters required, and in many cases the optical system also includes other components such as relay and/or imaging optical systems. In this work we present a simple and robust method for the polarimetric characterization of non-depolarizing polarization components and other optical elements in the system, which does not require a full polarimeter. Since there is no depolarization, we represent the components as pure retarders with diattenuation and find their parameters (transmittance for the polarization components, angle of orientation of the fast axis, and retardance), from which we can retrieve their Mueller matrix. Our results show that the proposed method is accurate when compared with results obtained with a Mueller matrix dual-rotating retarder polarimeter calibrated using the eigenvalue calibration method, considered in this work as the gold standard, and is comparatively easier than the latter to implement, particularly for imaging polarimeters.

7.
J Vasc Bras ; 22: e20220073, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37576727

RESUMEN

Venous aneurysms are rare and have a prevalence of 0.1 to 0.2% in the reported series. Typically, patients do not present any symptoms, but are prone to develop deep venous thrombosis (DVT) and the most feared complication, pulmonary embolism (PE). We present the case of a previously healthy 36-year-old man who presented at the emergency department with tachycardia, dyspnea, and pleuritic pain. A thoracic computed tomography angiography (CTA) confirmed the diagnosis of acute pulmonary embolism. He was treated with systemic thrombolysis and anticoagulation. In the further workup of the cause of the embolism, computed tomography revealed a fusiform dilation of the left popliteal vein measuring 3 by 3 centimeters (cm) with an incomplete filling defect because of thrombus presence. The patient underwent open surgical repair. At one month follow-up, he was asymptomatic, and an ultrasound revealed complete patency of the popliteal vein without dilatation or thrombus.


Aneurismas venosos são raros, tendo uma prevalência de 0,1 a 0,2% nas séries relatadas. Os pacientes não costumam manifestar sintomas; entretanto, são propensos a desenvolver trombose venosa profunda e a complicação mais temida, embolia pulmonar. Apresentamos o caso de um homem de 36 anos previamente hígido que chegou ao serviço de emergência queixando-se de taquicardia, dispneia e dor pleurítica. Uma angiotomografia computadorizada confirmou o diagnóstico de embolia pulmonar aguda. O paciente foi tratado com trombólise sistêmica e anticoagulantes. Em exames posteriores para investigar a causa da embolia, uma tomografia computadorizada revelou dilatação fusiforme da veia poplítea esquerda medindo 3x3 cm, com enchimento incompleto devido à presença de um trombo. O paciente foi submetido a reparo cirúrgico aberto. No seguimento de 1 mês, ele estava assintomático, e uma ultrassonografia revelou a patência completa da veia poplítea, sem dilatação ou trombo.

8.
Nutr Health ; : 2601060221127115, 2022 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-36221976

RESUMEN

OBJECTIVE: Our aim was to identify changes in population habits induced by COVID-19 confinement in Argentina. METHODS: An internet-based cross-sectional survey was conducted among adults in Argentina on December 2020, requesting possible changes occurring during the COVID-19 outbreak. It included 26 questions regarding general information (age, gender, location), eating habits, desire/anxiety for food or to eat between meals, weight gain, physical activity, and hours of sleep. We ran a descriptive statistical analysis of changes in habits and lifestyle during the confinement, followed by a logistic regression analysis to explore the relation between these changes and weight gain. Results: Out of 1536 survey participants, 57.1% were female, aged 38.8 ± 13.1 years. Data showed that during the outbreak, people experienced significant changes in food intake, physical activity, nutritional supplement consumption, anxiety, and sleeping disorders. These changes in behavior resulted in an elevated percentage of people (39.7%) that gained weight (average 4.8 ± 2.8 kg). Weight gain was associated with more food consumption (OR: 9.398), increased snacking between meals (OR: 1.536), anxiety about food (OR: 3.180), less practice of physical activity (OR: 0.586) and less consumption of nutritional supplements (OR: 0.762). Conclusions: COVID-19 outbreak was associated with unhealthy lifestyle changes and body weight increase. These adverse side effects could be prevented by active promotion of nutritional advice and physical activity, implementing virtual activities associated with regular mass promotion campaigns.

9.
J Rural Stud ; 95: 533-543, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36246736

RESUMEN

California agricultural workers are predominately Latino/a, are medically underserved, and reside in larger households, placing them at elevated COVID-19 risk at work and at home. While some research has examined COVID-19 among agricultural workers in the interior of the United States, little research exists on experiences of COVID-19 along the US-Mexico border. Grounded in resilience thinking, this study aims to understand how agricultural workers navigated their heightened risk to COVID-19 at work and at home, and made use of available resources in the context of a bi-national community. Our study utilized qualitative interviews with 12 agricultural workers to understanding the COVID-19 experiences of resident and daily migrant agricultural workers in Imperial County, California, located along the US-Mexico border. Findings suggest that agricultural workers faced significant impacts and risks at work (work stoppages, stress about bringing COVID-19 home to family) and at home (contracting COVID-19, loss of friends and family, and mental health challenges). Agricultural workers and their employers often implemented COVID-19 precautions such as social distancing measures, personal protective equipment, hand washing and hand sanitizers, and isolation. Many agricultural workers did access testing resources on either side of the US-Mexico border and worked with US-based Spanish-speaking community-based organizations to register for vaccine appointments. To better support agricultural workers and their employers in the future, we recommend the following: 1. Prioritize agricultural workplace conditions to increase agricultural worker physical and mental health, 2. Extend public health services into agricultural work sites of transit and the workplace, and 3. Lastly, trusted Spanish-speaking community-based organizations can play a critical role in public health outreach.

10.
Diabetes Metab Res Rev ; 37(1): e3359, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32500584

RESUMEN

AIM: To identify new transcriptomic alterations in pancreatic islets associated with metabolic dysfunctions in people with prediabetes (PD)/type 2 diabetes (T2D). MATERIALS AND METHODS: We collected information from public data repositories T2D related microarray datasets from pancreatic islets. We identified Differential Expressed Genes (DEGs) in non-diabetic (ND) vs people with T2D in each study. To identify relevant DEGs in T2D, we selected those that varied consistently in the different studies for further meta-analysis and functional enrichment analysis. DEGs were also evaluated at the PD stage. RESULTS: A total of seven microarray datasets were collected and analysed to find the DEGs in each study and meta-analysis was performed with 245 ND and 96 T2D cases. We identified 55 transcriptional alterations potentially associated with specific metabolic dysfunctions in T2D. Meta-analysis showed that 87% of transcripts identified as DEGs (48 out of 55) were confirmed as having statistically significant up- or down-modulation in T2D compared to ND. Notably, nine of these DEGs have not been previously reported as dysregulated in pancreatic islets from people with T2D. Consistently, the most significantly enriched pathways were related to the metabolism and/or development/maintenance of ß-cells. Eighteen of the 48 selected DEGs (38%) showed an altered expression in islets from people with PD. CONCLUSIONS: These results provide new evidence to interpret the pathogenesis of T2D and the transition from PD to T2D. Further studies are necessary to validate its potential use for the development/implementation of efficient new strategies for the prevention, diagnosis/prognosis and treatment of T2D.


Asunto(s)
Diabetes Mellitus Tipo 2 , Estado Prediabético , Transcriptoma , Diabetes Mellitus Tipo 2/genética , Perfilación de la Expresión Génica , Humanos , Islotes Pancreáticos , Estado Prediabético/genética , Transcriptoma/genética
11.
Biochem J ; 477(17): 3131-3145, 2020 09 18.
Artículo en Inglés | MEDLINE | ID: mdl-32766732

RESUMEN

The Hedgehog-regulated transcription factors GLI1 and GLI2 play overlapping roles in development and disease; however, the mechanisms underlying their interplay remain elusive. We report for the first time that GLI1 and GLI2 physically and functionally interact in cancer cells. GLI1 and GLI2 were shown to co-immunoprecipitate in PANC1 pancreatic cancer cells and RMS13 rhabdomyosarcoma cells. Mapping analysis demonstrated that the zinc finger domains of both proteins are required for their heteromerization. RNAi knockdown of either GLI1 or GLI2 inhibited expression of many well-characterized GLI target genes (BCL2, MYCN, PTCH2, IL7 and CCND1) in PANC1 cells, whereas PTCH1 expression was only inhibited by GLI1 depletion. qPCR screening of a large set of putative canonical and non-canonical Hedgehog/GLI targets identified further genes (e.g. E2F1, BMP1, CDK2) strongly down-regulated by GLI1 and/or GLI2 depletion in PANC1 cells, and demonstrated that ANO1, AQP1 and SOCS1 are up-regulated by knockdown of either GLI1 or GLI2. Chromatin immunoprecipitation showed that GLI1 and GLI2 occupied the same regions at the BCL2, MYCN and CCND1 promoters. Furthermore, depletion of GLI1 inhibited GLI2 occupancy at these promoters, suggesting that GLI1/GLI2 interaction is required for the recruitment of GLI2 to these sites. Together, these findings indicate that GLI1 and GLI2 co-ordinately regulate the transcription of some genes, and provide mechanistic insight into the roles of GLI proteins in carcinogenesis.


Asunto(s)
Regulación Neoplásica de la Expresión Génica , Proteínas Hedgehog/metabolismo , Proteínas Nucleares/metabolismo , Neoplasias Pancreáticas/metabolismo , Rabdomiosarcoma/metabolismo , Proteína con Dedos de Zinc GLI1/metabolismo , Proteína Gli2 con Dedos de Zinc/metabolismo , Línea Celular Tumoral , Proteínas Hedgehog/genética , Humanos , Proteínas Nucleares/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Multimerización de Proteína , Rabdomiosarcoma/genética , Rabdomiosarcoma/patología , Proteína con Dedos de Zinc GLI1/genética , Proteína Gli2 con Dedos de Zinc/genética
12.
Molecules ; 26(19)2021 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-34641342

RESUMEN

Methylphenidate is a powerful central nervous system stimulant with a high potential for abuse in horse racing. The detection of methylphenidate use is of interest to horse racing authorities for both prior to and during competition. The use of hair as an alternative sampling matrix for equine anti-doping has increased as the number of detectable compounds has expanded. Our laboratory developed a liquid chromatography-high-resolution mass spectrometry method to detect the presence of methylphenidate in submitted samples. Briefly, hair was decontaminated, cut, and pulverized prior to liquid-liquid extraction in basic conditions before introduction to the LC-MS system. Instrumental analysis was conducted using a Thermo Q Exactive mass spectrometer using parallel reaction monitoring using a stepped collision energy to obtain sufficient product ions for qualitative identification. The method was validated and limits of quantitation, linearity, matrix effects, recovery, accuracy, and precision were determined. The method has been applied to confirm the presence of methylphenidate in official samples submitted by racing authorities.


Asunto(s)
Cabello/química , Extracción Líquido-Líquido/métodos , Metilfenidato/análisis , Animales , Cromatografía Liquida , Caballos , Espectrometría de Masas , Detección de Abuso de Sustancias/veterinaria
13.
Medicina (Kaunas) ; 58(1)2021 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-35056315

RESUMEN

Background and Objectives: The work was aimed to determine the chronological sequence of events triggered by a fructose-rich diet (FRD) (10% w/v in the drinking water) in normal rats. Material and Methods: Serum parameters, liver and islet markers of metabolism, inflammation and oxidative stress were determined weekly for 21 days. Results: At the end of the first week, rats fed with a FRD showed an early increase in circulating triglycerides, fat liver deposit, and enzymatic activity of liver glucokinase and glucose-6-phosphate dehydrogenase (G6P-DH). After two weeks of such a diet, liver glucose-6-phosphatase (G6Pase) activity and liver oxidative stress markers were significantly increased. Liver sterol regulatory element-binding protein 1c (SREBP1c) mRNA also increased in the second week while their target genes fatty acid synthase (FAS) and glycerol-3-phosphate dehydrogenase (GPAT) enhanced their expression at the third week. Liver and pancreatic inflammation markers also enhanced their gene expression in the last week of treatment. Whereas both control and FRD rats remained normoglycemic throughout the entire period of treatment, blood insulin levels were significantly higher in FRD animals at the third week, thereby evidencing an insulin-resistant state (higher HOMA-IR, HOMA-B and HIS indexes). Pancreatic islets isolated from rats fed with a FRD for 3 weeks also increased glucose-induced insulin secretion (8.3 and 16.7 mM). Conclusions: FRD induces asynchronous changes involving early hypertriglyceridemia together with intrahepatic lipid deposit and metabolic disturbances from week one, followed by enhanced liver oxidative stress, liver and pancreas inflammation, pancreatic ß-cell dysfunction, and peripheral insulin-resistance registered at the third week. Knowledge of time-course adaptation mechanisms involved in our rat model could be helpful in developing appropriate strategies to prevent the progression from prediabetes to Type 2 diabetes (T2D) triggered by unhealthy diets.


Asunto(s)
Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Animales , Dieta , Fructosa/efectos adversos , Ratas , Ratas Wistar
14.
Gac Med Mex ; 157(4): 436-442, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-35133349

RESUMEN

The pandemic of SARS-CoV-2 infection, which causes COVID-19, has deeply affected health systems and has had a significant impact on families, communities and nations. A comprehensive response strategy requires, in addition to epidemiological, scientific and technical considerations, for human suffering associated with disease, vulnerability and death not to be forgotten. Palliative care for people with suspicion or diagnosis of COVID-19 with serious evolution, and their families should also be a key part of organized actions that help alleviate suffering and improve quality of life by controlling symptoms, addressing psychological, emotional, social and spiritual needs, support for advanced care planning and its goals, end-of-life care, as well as support in complex decision-making and ethical problems, among others. Recommendations are provided for offering palliative care in COVID-19 pandemic context.


La pandemia de infección por SARS-CoV-2, la cual es causada por COVID-19, ha afectado profundamente a los sistemas de salud y ha ocasionado un enorme impacto en las familias, las comunidades y las naciones. La estrategia de respuesta integral requiere que además de las consideraciones epidemiológicas, científicas y técnicas, no se olvide el sufrimiento humano asociado a la enfermedad, la vulnerabilidad y la muerte. La atención paliativa a personas con sospecha o diagnóstico de COVID-19 con evolución grave y sus familias debe ser también parte clave de la acción organizada que ayude al alivio del sufrimiento y mejore la calidad de vida mediante el control de los síntomas, el abordaje de las necesidades psicológicas, sociales y espirituales, el apoyo para la planificación de la atención avanzada y la articulación de los objetivos de la misma, el cuidado de la persona en la fase final de la vida, así como el soporte ante la toma de decisiones complejas y problemas éticos, entre otros. Se ofrecen recomendaciones para brindar los cuidados paliativos en el contexto de la pandemia de COVID-19.


Asunto(s)
COVID-19 , Humanos , Cuidados Paliativos , Pandemias , Calidad de Vida , SARS-CoV-2
15.
J Phys Chem A ; 124(44): 9222-9236, 2020 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-33086016

RESUMEN

The addition of NO2 to Group IV (MO2)n and Group VI (MO3)n (n = 1-3) nanoclusters was studied using both density functional theory (DFT) and coupled cluster theory (CCSD(T)). The structures and overall binding energetics were predicted for Lewis acid-base addition without transfer of spin (a physisorption-type process) and the formation of either cluster-ONO (HONO-like or bidentate bonding) or NO3- formation where for both the spin is transferred to the metal oxide clusters (a chemisorption-type process). Only chemisorption of NO2 is predicted to be thermodynamically allowed at temperatures ≥298 K for Group IV (MO2)n clusters with the formation of surface chemisorbed NO2 being by far the most energetically favorable. The ligand binding energies (LBEs) for physisorption and chemisorption on the TiO2 nanoclusters are consistent with computational studies of the bulk solids. Chemisorption is only predicted to occur for (CrO3)n clusters in the form of a terminal nitrate containing species whereas the larger chemisorbed nitrate structures for (MoO3)n and (WO3)n were found to be metastable and unlikely to form in any appreciable amount at temperatures of 298 K and higher. NO2 is predicted to only be capable of physisorbing to (MoO3)n and (WO3)n at lower temperatures and therefore unlikely to bind NO2 at temperatures ≥298 K. Correlations between the (MO3)nNO2 ligand bond energies and the chemical properties of the parent (MO3)n clusters (Lewis acidity, ionization potentials, excitation energies, and M = O/M-O bond strengths) are described.

16.
Inj Prev ; 26(2): 191-193, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32019771

RESUMEN

The current study documents homicide trends in Honduras from 2008 to 2018. Specifically, this study describes demographics of homicide victims and incident profiles (ie, weapons) using homicide data from the Honduras National Police and census data from the National Institute of Statistics. A total of 58 543 homicide incidents were analysed. Results indicated that the homicide rate in Honduras increased from 2008 to 2011 and decreased substantially after 2011. In addition, the male homicide victimisation rate was significantly higher than the female homicide victimisation rate across the entire time period, with the highest rate for males aged 30-44 (233.4 per 100 000 population). Firearms were the weapons used most frequently in homicides (80.3%). Implications of the findings are discussed in light of public safety in Honduras.


Asunto(s)
Violencia/estadística & datos numéricos , Heridas y Lesiones/etiología , Adolescente , Adulto , Distribución por Edad , Causas de Muerte/tendencias , Femenino , Armas de Fuego/estadística & datos numéricos , Honduras/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Vigilancia de la Población/métodos , Distribución por Sexo , Heridas y Lesiones/epidemiología
17.
Int J Mol Sci ; 21(2)2020 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-31936668

RESUMEN

Ezrin, a member of the ERM (ezrin/radixin/moesin) family of proteins, serves as a crosslinker between the plasma membrane and the actin cytoskeleton. By doing so, it provides structural links to strengthen the connection between the cell cortex and the plasma membrane, acting also as a signal transducer in multiple pathways during migration, proliferation, and endocytosis. In this study, we investigated the role of ezrin phosphorylation and its intracellular localization on cell motility, cytoskeleton organization, and cell stiffness, using fluorescence live-cell imaging, image quantification, and atomic force microscopy (AFM). Our results show that cells expressing constitutively active ezrin T567D (phosphomimetic) migrate faster and in a more directional manner, especially when ezrin accumulates at the cell rear. Similarly, image quantification results reveal that transfection with ezrin T567D alters the cell's gross morphology and decreases cortical stiffness. In contrast, constitutively inactive ezrin T567A accumulates around the nucleus, and although it does not impair cell migration, it leads to a significant buildup of actin fibers, a decrease in nuclear volume, and an increase in cytoskeletal stiffness. Finally, cell transfection with the dominant negative ezrin FERM domain induces significant morphological and nuclear changes and affects actin, microtubules, and the intermediate filament vimentin, resulting in cytoskeletal fibers that are longer, thicker, and more aligned. Collectively, our results suggest that ezrin's phosphorylation state and its intracellular localization plays a pivotal role in cell migration, modulating also biophysical properties, such as membrane-cortex linkage, cytoskeletal and nuclear organization, and the mechanical properties of cells.


Asunto(s)
Movimiento Celular , Proteínas del Citoesqueleto/metabolismo , Citoesqueleto/metabolismo , Fosfotreonina/metabolismo , Citoesqueleto de Actina/metabolismo , Animales , Fenómenos Biomecánicos , Núcleo Celular/metabolismo , Forma del Núcleo Celular , Proteínas del Citoesqueleto/genética , Ratones , Mutación/genética , Células 3T3 NIH , Fosforilación , Tubulina (Proteína)/metabolismo , Vimentina/metabolismo
18.
J Stroke Cerebrovasc Dis ; 29(4): 104691, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32067853

RESUMEN

BACKGROUND AND PURPOSE: Acute ischemic stroke (AIS) severity and clinical course are less known in direct oral anticoagulants (DOAC) users. We aimed to explore the outcome of AIS in patients pretreated with vitamin-K-antagonists (VKA) and DOAC. METHODS: A retrospective study was performed. Patients pretreated with oral anticoagulants (OAC) for nonvalvular atrial fibrillation admitted for AIS in a stroke unit between 2016-01-01 and 2018-08-31 were included. The primary endpoint was mortality during the hospital stay, and secondary endpoints were neurologic improvement at stroke unit discharge and good functional outcome 90 days after AIS. RESULTS: A total of 156 patients were included (83 on VKA and 73 on DOAC). Stroke severity (defined by NIHSS on admission) was comparable in both groups (AVK 13.0 [4.0-20.0] versus DOAC 11.0 [4.0-17.0], P = .435). Infratherapeutic levels and/or inappropriate low dose of OAC was also similar between groups (P = .152) and was not associated with stroke severity (P = .631) or mortality (P = .788). VKA (OR 12.616, P = .035, 95%CI 1.19-133.64) and PH2 hemorrhagic transformation (OR 7.516, P = .024, 95%CI 1.31-43.20) were associated with higher mortality in multivariate analysis. Higher stroke severity (OR .101, P < .001, 95%CI .037-.279) and VKA usage (OR .212, P = .003, 95%CI .08-.58) were associated with worse functional outcome at 3 months. Reperfusion therapy was significantly associated with neurologic improvement during stroke unit stay (OR 3.969, P = .009, 95%CI 1.42-11.11) but not with the functional outcome (P = .063). CONCLUSIONS: Nonvalvular atrial fibrillation patients pretreated with DOAC admitted for AIS had a better outcome when compared to VKA, although stroke severity was similar between groups.


Asunto(s)
Anticoagulantes/administración & dosificación , Antitrombinas/administración & dosificación , Fibrilación Atrial/tratamiento farmacológico , Isquemia Encefálica/etiología , Accidente Cerebrovascular/etiología , Vitamina K/antagonistas & inhibidores , Administración Oral , Anciano , Anciano de 80 o más Años , Anticoagulantes/efectos adversos , Antitrombinas/efectos adversos , Fibrilación Atrial/complicaciones , Fibrilación Atrial/diagnóstico , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/mortalidad , Isquemia Encefálica/terapia , Evaluación de la Discapacidad , Femenino , Mortalidad Hospitalaria , Humanos , Masculino , Recuperación de la Función , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la Enfermedad , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/mortalidad , Accidente Cerebrovascular/terapia , Factores de Tiempo , Resultado del Tratamiento
19.
Yale J Biol Med ; 93(3): 429-432, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32874149

RESUMEN

On September 20 of 2017, Hurricane Maria made landfall in Puerto Rico as a strong category 4 hurricane with destructive winds and flooding. Everyone suffered in the aftermath of the hurricane due to overwhelming destruction and lack of available resources. For medical students, these conditions were intensified due to their duty as first responders, academic responsibilities from medical school, personal losses, and financial difficulties. Despite the hardships, these students learned lessons and found solutions to overcome their challenges. The objective of this article is to portray the situations that medical students confronted and offer suggestions on how medical students and academic institutions can prepare for future natural disasters.


Asunto(s)
Facultades de Medicina , Estudiantes de Medicina , Tormentas Ciclónicas , Humanos , Puerto Rico , Facultades de Medicina/organización & administración , Estudiantes de Medicina/psicología
20.
J Phys Chem A ; 123(46): 10169-10183, 2019 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-31618023

RESUMEN

We have performed an extensive computational investigation of the potential energy surfaces for the reactions of SOx (x = 2 or 3) with H2S and H2O in the gas phase and in aqueous solution at the CCSD(T)/CBS level of theory plus a self-consistent reaction field approach. Formation of a gas-phase H2SO4 from the hydrolysis of SO3 at lower temperatures requires the presence of additional water molecules. When additional waters are introduced, the barrier for H2SO4 formation is significantly reduced, and a barrierless transition occurs with only three excess waters as well as in aqueous solution. In a mixture of H2O, H2S, and SO3, formation of H2S2O3 has a lower barrier in the gas phase than does the formation of H2SO4. In aqueous solution, no barrier is predicted, and both are likely to be formed. Introduction of an additional water to the SO3 + H2S reaction results in a decrease in barrier height, nearly identical to the ∼18 kcal/mol catalytic effect of the first additional water in SO3 hydrolysis, with the barrier for H2S2O3 formation disappearing altogether in aqueous solution. Formation of H2SO3 by the way of SO2 hydrolysis is unlikely. Excess waters reduce the barrier for SO2 hydrolysis; however, the overall endothermicity is increased as waters are added. The formation of H2S2O2 from SO2 and H2S via an isostructural pathway to SO2 hydrolysis is unlikely, with additional water molecules resulting in a small increase in the overall endothermicity and a catalytic effect smaller than that observed for the SO3 reactions. The results of this work have implications pertaining to the formation of H2SO4, H2S2O3, H2SO3, and H2S2O2 in the atmospheres of Earth and Venus. These results also question the existence of H2S2O2 as an intermediate in the Claus process.

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