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2.
Sci Rep ; 14(1): 10477, 2024 05 07.
Artículo en Inglés | MEDLINE | ID: mdl-38714743

RESUMEN

Endothelial glycocalyx (eGC) covers the inner surface of the vessels and plays a role in vascular homeostasis. Syndecan is considered the "backbone" of this structure. Several studies have shown eGC shedding in sepsis and its involvement in organ dysfunction. Matrix metalloproteinases (MMP) contribute to eGC shedding through their ability for syndecan-1 cleavage. This study aimed to investigate if doxycycline, a potent MMP inhibitor, could protect against eGC shedding in lipopolysaccharide (LPS)-induced sepsis and if it could interrupt the vascular hyperpermeability, neutrophil transmigration, and microvascular impairment. Rats that received pretreatment with doxycycline before LPS displayed ultrastructural preservation of the eGC observed using transmission electronic microscopy of the lung and heart. In addition, these animals exhibited lower serum syndecan-1 levels, a biomarker of eGC injury, and lower perfused boundary region (PBR) in the mesenteric video capillaroscopy, which is inversely related to the eGC thickness compared with rats that only received LPS. Furthermore, this study revealed that doxycycline decreased sepsis-related vascular hyperpermeability in the lung and heart, reduced neutrophil transmigration in the peritoneal lavage and inside the lungs, and improved some microvascular parameters. These findings suggest that doxycycline protects against LPS-induced eGC shedding, and it could reduce vascular hyperpermeability, neutrophils transmigration, and microvascular impairment.


Asunto(s)
Doxiciclina , Glicocálix , Lipopolisacáridos , Sepsis , Glicocálix/metabolismo , Glicocálix/efectos de los fármacos , Animales , Sepsis/tratamiento farmacológico , Sepsis/metabolismo , Doxiciclina/farmacología , Ratas , Masculino , Permeabilidad Capilar/efectos de los fármacos , Pulmón/patología , Pulmón/metabolismo , Pulmón/efectos de los fármacos , Sindecano-1/metabolismo , Ratas Wistar , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/metabolismo , Endotelio Vascular/patología , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Neutrófilos/metabolismo , Neutrófilos/efectos de los fármacos , Inhibidores de la Metaloproteinasa de la Matriz/farmacología
3.
Microvasc Res ; 154: 104683, 2024 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-38522507

RESUMEN

BACKGROUND: Microvascular dysfunction plays a central role in organ dysfunction during septic shock. Endothelial glycocalyx (eGC) damage could contribute to impaired microcirculation. The aim was to assess whether several eGC-damaged biomarkers are associated with microvascular dysfunction in resuscitated septic shock patients. METHODS: This cross-sectional study included resuscitated septic shock patients (N = 31), and a group of healthy individuals (N = 20). The eGC damage biomarkers measured were syndecan-1 (SDC-1), soluble CD44 (CD44s), hyaluronic acid (HYAL) in blood sample; sulfated glycosaminoglycans (GAGs) in urine sample; and thrombomodulin (TBML) in blood sample as biomarker of endothelial cell damage. Microcirculation was assessed through sublingual videocapillaroscopy using the GlycoCheck™, which estimated the perfused vascular density (PVD); the perfused boundary region (PBR), an inverse parameter of the eGC thickness; and the microvascular health score (MVHS). We defined a low MVHS (<50th percentile in septic patients) as a surrogate for more impaired microvascular function. RESULTS: The SDC-1, CD44s, TBML and GAGs levels were correlated with impaired microvascular parameters (PVD of vessels with diameter < 10 µm, MVHS and flow-adjusted PBR); p < 0.05 for all comparisons, except for GAGs and flow-adjusted PBR. The SDC-1 [78 ng/mL (interquartile range (IQR) 45-336) vs. 48 ng/mL (IQR 9-85); p = 0.052], CD44s [796ρg/mL (IQR 512-1995) vs. 526ρg/mL (IQR 287-750); p = 0.036], TBML [734ρg/mL (IQR 237-2396) vs. 95ρg/mL (IQR 63-475); p = 0.012] and GAGs levels [0.42 ρg/mg (IQR 0.04-1.40) vs. 0.07 ρg/mg (IQR 0.02-0.20); p = 0.024]; were higher in septic patients with more impaired sublingual microvascular function (low MVHS vs. high MVHS). CONCLUSION: SDC-1, CD44s, TBML and GAGs levels were associated with impaired microvascular function in resuscitated septic shock patients.

4.
BMJ Open ; 14(2): e076629, 2024 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-38367970

RESUMEN

INTRODUCTION: Weight-related stigma (WS) has been associated with adverse psychosocial and physical health effects. Despite the relationship between WS and allostatic load, there are no integrative reviews of this association. This scoping review aims to provide a comprehensive overview of the relationship between allostatic load biomarkers associated with WS by identifying gaps in this topic and proposing recommendations for future research. METHODS AND ANALYSIS: This protocol was guided by the methodological framework of Arksey and O'Malley and the Joanna Briggs Institute (JBI). The research questions were based on the population-concept-context framework. Studies in adults diagnosed as overweight or obese, exposed to WS and assessing the association between WS and biomarkers of allostatic load will be included. A search will be conducted in Medline (Ovid), PsycINFO (Ovid), Scopus (Elsevier), Cochrane Library (Wiley) and Google Scholar. The search strategy will be conducted in three stages, based on the JBI recommendation with the MESH terms "Social Stigma," "Weight Prejudice," "Biomarkers," "Allostasis," "Adults" and related terms. Data extraction will be done with a template adapted from JBI. The search strategy and selection process results will be presented in a flow chart and summarised in the text. The main results will be presented in a descriptive synthesis. ETHICS AND DISSEMINATION: Ethics review and approval are not required. The results will be disseminated through peer-reviewed publications, conferences, congresses or symposia.


Asunto(s)
Alostasis , Prejuicio de Peso , Adulto , Humanos , Academias e Institutos , MEDLINE , Biomarcadores , Proyectos de Investigación , Literatura de Revisión como Asunto
5.
Comp Immunol Microbiol Infect Dis ; 104: 102094, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38035481

RESUMEN

The non-human primate (NHP) Leontopithecus rosalia is an endangered species native of Brazil and lives in forest fragments with different levels of contact with humans (natural, private and urban). Other NHPs - Callithrix spp. - were introduced by humans and co-exist and interact with the native species in these forests. To evaluate if living in or close to human-modified environments could constitute a risk for L. rosalia, we compared the prevalence, genetic background, antibiotic susceptibility and virulence gene content of staphylococci collected from the native and the introduced species from different forest fragments. We found that presence in human-dominated environments increased the colonization rate of L. rosalia with Mammaliicoccus sciuri (former Staphylococcus sciuri) from 18 % to 85 % (p = 0.0001) and of Callithrix spp with Staphylococcus aureus from 6 % to 100 % (p = 0.0001). According to molecular typing data obtained differences probably resulted from dissemination of these bacterial species from the invader NHP species and from humans. Changes in microbiota were paralleled by an increase in the prevalence of Panton-Valentine Leukocidin gene and in resistance to beta-lactams, macrolides and/or lincosamides as exposure to human environment increased. In particular, erythromycin resistance in S. aureus from Callithrix spp. increased from 0 % to 50 % and resistance rate to at least one antibiotic in coagulase-negative staphylococci species from L. rosalia increased from 13 % to 56 % (p = 0.0003). Our results showed that contact of native animal species with human-created environments increased the content of antimicrobial resistant and pathogenic bacteria on their commensal microbiota, which ultimately can impact on their health. IMPORTANCE: Endangered animal species are vulnerable to environmental alterations and human activities have been repeatedly identified as factors driving drastic changes in the natural landscape. It is extremely important to monitor changes in the environment surrounding protected species, because this could lead to early detection of any potential threats. In this study, we found that the contact of L. rosalia - a protected non-human primate from Brazil - with human environments is related to changes in their commensal microbiota. These included an increase in the number of pathogenic and antibiotic resistant bacteria, which have a higher potential to cause infections that are more difficult to treat. We provided evidence for the harmful impact human contact has on L. rosalia. Also, our results suggest that monitoring of commensal microbiota of protected animal species might be a useful way of sensing the risks of protected species to human exposure.


Asunto(s)
Antibacterianos , Infecciones Estafilocócicas , Animales , Humanos , Antibacterianos/farmacología , Staphylococcus aureus/genética , Brasil/epidemiología , Callithrix , Farmacorresistencia Bacteriana , Infecciones Estafilocócicas/epidemiología , Infecciones Estafilocócicas/veterinaria , Infecciones Estafilocócicas/microbiología , Pruebas de Sensibilidad Microbiana/veterinaria
6.
Maturitas ; 180: 107873, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37995422

RESUMEN

OBJECTIVE: To study sociodemographic and clinical factors associated with the long-COVID-19 syndrome among women living in Latin American countries using undirected and directed methods. METHOD: We studied 347 patients with COVID-19 (confirmed by polymerase chain reaction) living in nine Latin American countries between May 2021 and July 2022, including 70 premenopausal, 48 perimenopausal, and 229 postmenopausal women. We compared the sociodemographic and general health information of women with (n = 164) and without (n = 183) the long-COVID-19 syndrome. They also completed the Connor-Davidson Resilience Scale, the Fear of COVID-19 Scale, the Jenkins Sleep Scale, and the Menopause Rating Scale to define the minimum set of variables for adjustment. We designed a directed acyclic graph (DAG) to identify factors related to the long-COVID-19 syndrome. Data were submitted to categorical logistic regression analyses. Results are reported as means and standard deviations or ß-coefficients and 95 % confidence intervals. RESULTS: Women with long-COVID-19 syndrome had a poor lifestyle, severe menopause symptoms, hypertension, insomnia, depression, anxiety, chronic diseases/conditions, risk of hospitalization, sleep disturbance, and low menopause-related quality of life compared to women without the syndrome. The DAG identified the following long-COVID-19 covariates: age, obesity, anxiety, depression, cancer, lifestyle, smoking, and menstrual status. A multivariable logistic model with these covariates indicated that anxiety is the only factor to be significantly associated with long-COVID-19 syndrome, whereas other covariates were confounding factors. There was no significant influence of menopausal status on the long-COVID-19 syndrome. CONCLUSION: Among factors selected by the DAG, only anxiety was significantly associated with the long-COVID-19. There was no significant influence of the menopause status on the long-COVID-19 syndrome in the studied population.


Asunto(s)
COVID-19 , Pruebas Psicológicas , Calidad de Vida , Femenino , Humanos , América Latina/epidemiología , Síndrome Post Agudo de COVID-19 , Depresión/epidemiología , Depresión/complicaciones , COVID-19/epidemiología , Menopausia , Ansiedad/epidemiología , Resiliencia Psicológica
7.
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1535949

RESUMEN

Introduction: Anal squamous cell carcinoma is rare, but its incidence and mortality have been increasing globally; 90% of cases are related to human papillomavirus (HPV) infection(1,2). Patients with inflammatory bowel disease (IBD) have a higher risk of infection with this virus; an incidence of 5.5 per 100,000 patients has been identified in the IBD group compared to 1.8 in the non-IBD group(3). Materials and methods: A descriptive case series study was conducted with 21 patients with IBD and no perianal symptoms between January and July 2022 at the Institute of Coloproctology in Medellín. They underwent anal cytology, HPV genotyping, and high-resolution anoscopy after explanation and acceptance of the procedure. If lesions were found, ablative treatment was performed. Results: 23% of this cohort had low-grade squamous lesions, while 14.2% had high-grade lesions with dysplasia changes during anoscopy. Besides, 90.4% had positive HPV genotyping, of which 76.1% were high-grade. Conclusions: Our study suggests that this series of patients with IBD behaves as a high-risk group for developing premalignant lesions in association with HPV. High-resolution anoscopy is a cost-effective, painless, and affordable method that, in expert hands, may impact the diagnosis and management of premalignant lesions and decrease the incidence of anal cancer in patients with IBD.


Introducción: El carcinoma anal de células escamosas es raro, pero su incidencia y mortalidad han ido en aumento globalmente. El 90% de los casos están relacionados con la infección por el virus del papiloma humano (VPH)1,2 y los pacientes con enfermedad inflamatoria intestinal (EII) tienen un mayor riesgo de infección por este virus; se ha identificado una incidencia de 5,5 por 100.000 pacientes en el grupo de EII frente a 1,8 en el grupo sin EII3. Metodología: Se realizó un estudio descriptivo de serie de casos en el que se incluyó a 21 pacientes con EII, sin síntomas perianales, entre enero y julio de 2022 en el Instituto de Coloproctología de Medellín, a quienes se les realizó citología anal, genotipificación del VPH y anoscopia de alta resolución, previa explicación y aceptación del procedimiento. Si se encontraban lesiones, se realizaba tratamiento ablativo. Resultados: El 23% de esta cohorte tenía lesiones escamosas de bajo grado, mientras que el 14,2% presentaba lesiones de alto grado con cambios de displasia al momento de la anoscopia. El 90,4% tenían genotipificación positiva para VPH, de los cuales el 76,1% eran de alto grado. Conclusiones: Nuestro estudio sugiere que esta serie de pacientes con EII se comporta como un grupo de alto riesgo para desarrollar lesiones premalignas en asociación con el VPH. La anoscopia de alta resolución es un método rentable, indoloro y asequible que, en manos expertas, puede impactar el diagnóstico y manejo de lesiones premalignas y disminuir la incidencia de cáncer anal en pacientes con EII.

9.
Sci Rep ; 13(1): 15679, 2023 09 21.
Artículo en Inglés | MEDLINE | ID: mdl-37735195

RESUMEN

Gut microbiome disruptions may lead to adverse effects on wildlife fitness and viability, thus maintaining host microbiota biodiversity needs to become an integral part of wildlife conservation. The highly-endangered callitrichid golden lion tamarin (GLT-Leontopithecus rosalia) is a rare conservation success, but allochthonous callitrichid marmosets (Callithrix) serve as principle ecological GLT threats. However, incorporation of microbiome approaches to GLT conservation is impeded by limited gut microbiome studies of Brazilian primates. Here, we carried out analysis of gut metagenomic pools from 114 individuals of wild and captive GLTs and marmosets. More specifically, we analyzed the bacterial component of ultra filtered samples originally collected as part of a virome profiling study. The major findings of this study are consistent with previous studies in showing that Bifidobacterium, a bacterial species important for the metabolism of tree gums consumed by callitrichids, is an important component of the callitrichid gut microbiome - although GTLs and marmosets were enriched for different species of Bifidobacterium. Additionally, the composition of GLT and marmoset gut microbiota is sensitive to host environmental factors. Overall, our data expand baseline gut microbiome data for callitrichids to allow for the development of new tools to improve their management and conservation.


Asunto(s)
Callithrix , Microbioma Gastrointestinal , Humanos , Animales , Bifidobacterium , Callitrichinae
10.
Mol Ther ; 31(9): 2767-2782, 2023 09 06.
Artículo en Inglés | MEDLINE | ID: mdl-37481701

RESUMEN

The AAV9 gene therapy vector presented in this study is safe in mice and non-human primates and highly efficacious without causing overexpression toxicity, a major challenge for clinical translation of Rett syndrome gene therapy vectors to date. Our team designed a new truncated methyl-CpG-binding protein 2 (MECP2) promoter allowing widespread expression of MECP2 in mice and non-human primates after a single injection into the cerebrospinal fluid without causing overexpression symptoms up to 18 months after injection. Additionally, this new vector is highly efficacious at lower doses compared with previous constructs as demonstrated in extensive efficacy studies performed by two independent laboratories in two different Rett syndrome mouse models carrying either a knockout or one of the most frequent human mutations of Mecp2. Overall, data from this multicenter study highlight the efficacy and safety of this gene therapy construct, making it a promising candidate for first-in-human studies to treat Rett syndrome.


Asunto(s)
Síndrome de Rett , Humanos , Ratones , Animales , Síndrome de Rett/genética , Síndrome de Rett/terapia , Síndrome de Rett/metabolismo , Primates/genética , Terapia Genética , Mutación
11.
Photobiomodul Photomed Laser Surg ; 41(6): 277-282, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37335619

RESUMEN

Objective: This study analyzed the histological and immunohistochemical changes in hair follicles submitted to epilation with light-emitting diode (LED). Background: The use of specific wavelengths of LED leads to the absorption of photons by chromophore tissues, enabling different photophysical and photochemical events, bringing therapeutic benefits such as removing body hair. Methods: The sample included five participants, with phototypes II-V, divided into two groups. The volunteers received a session of epilation with the Holonyak® device on the pubic region and right groin, whereas the contralateral side was kept as a control. An energy of 10 J and a cooling temperature of -5°C were used, after which the pain provoked by the equipment was questioned using the analogue pain scale. After 45 days, the punching procedure was performed in the region where skin samples were taken for histological and immunohistochemical analysis. Results: For all phototypes, in the treated area, the follicles and sebaceous glands were in a stage of involution, showing perifollicular inflammatory infiltrate with changes suggestive of apoptosis. The apoptosis process was confirmed by the increase in markers cytokeratin-18 and cleaved caspase 3, in addition to the reduced expression of Blc-2, and the lower cell proliferation (Ki67), reinforcing the action of LED based on the definite involution and resorption of the follicle, through macrophages (CD68) triggered by the inflammatory process. Conclusions: The preliminary results of this study found relevant histological changes and immunohistochemical markers in the epilation process, which may indicate the efficacy of LED in permanent hair removal.


Asunto(s)
Remoción del Cabello , Humanos , Remoción del Cabello/métodos , Proyectos Piloto , Piel , Folículo Piloso
12.
Hacia promoc. salud ; 28(1)jun. 2023.
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1534519

RESUMEN

An analytical observational study was conducted to investigate the association between knowledge of COVID-19 in the general population of Mexico and sociodemographic variables of interest. A total of 758 adults between 18 and 74 years old (M = 37.3 SD = 12.6), of which 88.9% had higher education and 33.2% were health care workers, participated in an online questionnaire assessing disease knowledge and the COVID-5 item Fear Scale, which was adapted by the research team. The proportion of individuals with high knowledge about COVID-19 was found to be 41.0%. Participants with higher education and healthcare professionals demonstrated higher knowledge scores in comparison to those with primary and secondary education, as well as non-healthcare professionals (PR=1.25, 95%CI 1.05-1.48). In conclusion, that people with higher education and healthcare workers exhibited better knowledge scores regarding the disease, while high knowledge about COVID-19 was only associated with being a health professional.


Se realizó un estudio observacional analítico con el objetivo de explorar la asociación entre el conocimiento que tiene la población general de México sobre COVID-19 y las variables sociodemográficas de interés. Un total de 758 adultos entre 18 y 74 años (M=37,3 DE=12,6), 88,9% con educación superior y 33,2% trabajadores de la salud, diligenciaron un cuestionario en línea sobre conocimientos la enfermedad y la Escala de Temor a COVID-5, adaptada por el equipo de investigación. La proporción de conocimientos altos sobre COVID-19 fue del 41,0%. Las personas con educación superior y los profesionales de la salud presentaron puntajes de conocimientos altos en comparación con los que tenían primaria y secundaria y con los que no pertenecían al gremio de la salud RP = 1,25 IC 95% (1,05 - 1,48). Se concluye que las personas con escolaridad superior y los profesionales de la salud tienen mejores puntajes de conocimientos sobre la enfermedad, mientras que el conocimiento alto sobre COVID-19 solo se asoció con ser profesional de la salud.


Foi realizado um estudo observacional analítico com o objetivo de explorar a associação entre o conhecimento que tem a população geral de México sobre COVID-19 e as variáveis sociodemográficas de interesse. Um total de 758 adultos entre 18 e 74 anos (M=37,3 DE=12,6), 88,9% com ensino superior e 33,2% trabalhadores da saúde, responderam um questionário on-line sobre conhecimentos a doença e a Escala de Temor a COVID-5, adaptada pela equipe de pesquisa. A proporção de conhecimentos altos sobre COVID-19 foi do 41,0%. As pessoas com educação superior e os profissionais da saúde apresentaram pontuação de conhecimentos altos em comparação com os que tinham ensino básico e ensino médio e com os que não pertenciam aos profissionais da saúde RP = 1,25 IC 95% (1,05 - 1,48). Concluise que as pessoas com educação superior e os profissionais da saúde têm melhor pontuação de conhecimentos sobre a doença, enquanto que o conhecimento alto sobre COVID-19 só se associou com ser professional da saúde.

13.
Medicina (Ribeirao Preto, Online) ; 56(1)abr. 2023. ilus, tab
Artículo en Portugués | LILACS | ID: biblio-1442404

RESUMEN

Objetivo: Relatar a experiência e a percepção dos profissionais de enfermagem com a utilização de simulação in situnão anunciada de parada cardiorrespiratória (PCR) em ritmo de fibrilação ventricular no ambiente intra-hospitalar. Métodos: Manequim (Laerdal®) de alta fidelidade foi colocado no leito de isolamento de uma Unidade Coronariana que dispõe de central de monitoramento, sem o conhecimento dos profissionais de enfermagem que estavam assumindo o plantão. Um técnico de enfermagem do turno anterior de trabalho passou o caso como um paciente fictício recém-admitido com infarto agudo do miocárdio. Após a passagem do plantão, modificou-se o ritmo cardíaco do manequim de ritmo sinusal para fibrilação ventricular. Registrou-se o tempo (em minutos e segundos) desde a modificação do ritmo até algum profissional da enfermagem desencadear uma ação efetiva relacionada ao fato. Após o profissional perceber que se tratava de um manequim, ele foi orientado a desencadear as intervenções adequadas como se fosse um paciente real. Após o final da simulação, um questionário para avaliação da percepção desses profissionais em relação à atividade foi aplicado. Resultado: Quinze profissionais participaram da simulação in situ. O tempo para reação foi 28 segundos no turno diurno, dois minutos e seis segundos no turno vespertino e quatro minutos e três segundos no período noturno. Todos profissionais (100%) reconheceram a importância do treinamento, todos (100%) acharam que este treinamento aumenta a segurança do profissional e do paciente, a maioria (90%) achou que pode melhorar a comunicação entre a equipe, e todos (100%) acharam que atividades como esta deveriam ser repetidas. Conclusão: A simulação in situ parece ser uma alternativa viável para o treinamento dos profissionais de enfermagem no atendimento inicial da PCR em um hospital de emergência brasileiro. Esta atividade foi avaliada positivamente pelos participantes (AU).


Objective: Report the experience and perception of nursing professionals with an unannounced in-situ simulation of cardiopulmonary arrest (CPA) in ventricular fibrillation in an in-hospital environment. Methods: A high-fidelity mannequin (Laerdal®) was placed on the isolation bed of a Coronary Care Unit with a monitoring center without the knowledge of the nursing professionals taking over the shift. A nurse technician from the previous shift was told to report the case as a fictitious newly admitted patient with acute myocardial infarction. After the care transition, the cardiac rhythm was changed from sinus rhythm to ventricular fibrillation. The time was recorded (in minutes and seconds) from the onset of ventricular fibrillation until a nursing professional triggered an effective action. After the professionals realized it was a mannequin, they were instructed to initiate the appropriate interventions as if the mannequin were an actual patient. After the end of the simulation, a questionnaire was used to assess the professionals' perception of the activity. Results: Fifteen professionals participated in this in-situ simulation. The reaction time was 28 seconds on the morning shift, two minutes and six seconds on the afternoon shift, and four minutes and three seconds on the night shift. All professionals (100%) recognized the importance of this training, and all thought it increased professional and patient safety. Most participants (90%) thought it could improve communication among the team. All professionals (100%) felt that such activities should be repeated. Conclusion: In-situ simulation is a feasible alternative to train nursing professionals in the initial CPA management in a Brazilian emergency hospital. Participants positively evaluated this activity (AU).


Asunto(s)
Humanos , Fibrilación Ventricular , Educación en Salud , Infarto del Miocardio/terapia
14.
Gene Ther ; 30(6): 487-502, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36631545

RESUMEN

Fabry disease is an X-linked lysosomal storage disorder caused by loss of alpha-galactosidase A (α-Gal A) activity and is characterized by progressive accumulation of glycosphingolipids in multiple cells and tissues. FLT190, an investigational gene therapy, is currently being evaluated in a Phase 1/2 clinical trial in patients with Fabry disease (NCT04040049). FLT190 consists of a potent, synthetic capsid (AAVS3) containing an expression cassette with a codon-optimized human GLA cDNA under the control of a liver-specific promoter FRE1 (AAV2/S3-FRE1-GLAco). For mouse studies FLT190 genome was pseudotyped with AAV8 for efficient transduction. Preclinical studies in a murine model of Fabry disease (Gla-deficient mice), and non-human primates (NHPs) showed dose-dependent increases in plasma α-Gal A with steady-state observed 2 weeks following a single intravenous dose. In Fabry mice, AAV8-FLT190 treatment resulted in clearance of globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3) in plasma, urine, kidney, and heart; electron microscopy analyses confirmed reductions in storage inclusion bodies in kidney and heart. In NHPs, α-Gal A expression was consistent with the levels of hGLA mRNA in liver, and no FLT190-related toxicities or adverse events were observed. Taken together, these studies demonstrate preclinical proof-of-concept of liver-directed gene therapy with FLT190 for the treatment of Fabry disease.


Asunto(s)
Enfermedad de Fabry , Terapia Genética , Animales , Humanos , Ratones , Células Cultivadas , Enfermedad de Fabry/genética , Enfermedad de Fabry/terapia , Fibroblastos , Vectores Genéticos , Hígado/metabolismo , alfa-Galactosidasa/genética , alfa-Galactosidasa/metabolismo
15.
Virus Res ; 325: 199017, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36565815

RESUMEN

Viral metagenomics has contributed enormously to the characterization of a wide range of viruses infecting animals of all phyla in the last decades. Among Neotropical primates, especially those introduced, knowledge about viral diversity remains poorly studied. Therefore, using metagenomics based on virus enrichment, we explored the viral microbiota present in the feces of introduced common marmosets (Callithrix sp.) in three locations from the Silva Jardim region in the State of Rio de Janeiro, Brazil. Fecal samples were collected from nine marmosets, pooled into three sample pools, and sequenced on Illumina MiSeq platform. Sequence reads were analyzed using a viral metagenomic analysis pipeline and two novel insect viruses belonging to the Parvoviridae and Baculoviridae families were identified. The complete genome of a densovirus (Parvoviridae family) of 5,309 nucleotides (nt) was obtained. The NS1 and VP1 proteins share lower than 32% sequence identity with the corresponding proteins of known members of the subfamily Densovirinae. Phylogenetic analysis suggests that this virus represents a new genus, provisionally named Afoambidensovirus due to its discovery in the Brazilian Atlantic Forest. The novel species received the name Afoambidensovirus incertum 1. The complete circular genome of a baculovirus of 107,191 nt was also obtained, showing 60.8% sequence identity with the most closely related member of the Baculoviridae family. Phylogenetic analysis suggests that this virus represents a new species in the Betabaculovirus genus, provisionally named Betabaculovirus incertum 1. In addition, sequences from several families of arthropods in the three pools evaluated were characterized (contigs ranging from 244 to 6,750 nt), corroborating the presence of possible insect hosts with which these new viruses may be associated. Our study expands the knowledge about two viral families known to infect insects, an important component of the marmosets' diet. This identification in hosts' feces samples demonstrates one of the many uses of this type of data and could serve as a basis for future research characterizing viruses in wildlife using noninvasive samples.


Asunto(s)
Callithrix , Virus , Animales , Callithrix/genética , Brasil , Filogenia , Viroma , Metagenómica , Virus/genética , Dieta , Genoma Viral
16.
Menopause ; 30(2): 165-173, 2023 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-36477574

RESUMEN

OBJECTIVE: The aim of this study was to assess resilience, fear of COVID-19, sleep disorders, and menopause-related symptoms after the acute phase of COVID-19 in middle-aged women with positive reverse transcription-polymerase chain reaction and noninfected women. METHODS: This is a cross-sectional, analytical study of climacteric women from 9 Latin American countries, aged 40-64 years, attending a routine health checkup. We evaluated clinical characteristics and used the Connor-Davidson Resilience Scale, the Fear of COVID-19 Scale, the Jenkins Sleep Scale, and the Menopause Rating Scale to evaluate their health. RESULTS: A total of 1,238 women were studied, including 304 who were positive for COVID-19 reverse transcription-polymerase chain reaction. The median (interquartile range) age was 53 (12) years; years of studies, 16 (6); body mass index, 25.6 (5.1) kg/m 2 ; and time since first COVID-19 symptom, 8 (6) months. COVID-19 patients reported fatigability (18.8%), joint and muscular discomfort (14.1%), and anosmia (9.5%). They had a significantly lower resilience score (26.87 ± 8.94 vs 29.94 ± 6.65), higher Fear of COVID-19 score (17.55 ± 7.44 vs 15.61 ± 6.34), and a higher Jenkins Scale score (6.10 ± 5.70 vs 5.09 ± 5.32) compared with control women. A logistic regression model confirmed these results. There was not a significant difference in the total Menopause Rating Scale score, although the odds ratios for both severe menopausal symptoms (1.34; 95% confidence interval, 1.02-1.76) and the use of hypnotics were higher in women with COVID-19 (1.80; 95% confidence interval, 1.29-2.50) compared with those without infection. We found no decrease in studied outcomes between the initial 7 months versus those reported after 8 to 18 months since first COVID-19 symptoms. CONCLUSIONS: COVID-19 climacteric women have sleep disorders, lower resilience and higher fear of COVID-19.


Asunto(s)
COVID-19 , Climaterio , Trastornos del Sueño-Vigilia , Persona de Mediana Edad , Humanos , Femenino , América Latina/epidemiología , Síndrome Post Agudo de COVID-19 , Estudios Transversales , COVID-19/epidemiología , Menopausia
17.
Omega (Westport) ; 87(1): 4-19, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-34000883

RESUMEN

The study aimed to perform confirmatory factor analysis, internal consistency, gender differential item functioning, and discriminant validity of the Fear of COVID-5 Scale in emerging adult students of a university in Mexico. Confirmatory factor analysis, internal consistency (Cronbach's alpha and McDonald's omega), and gender differential item functioning were estimated (Kendall tau b correlation). The Fear of COVID-5 Scale showed a one-dimension structure (RMSEA = 0.07, CFI = 0.98, TLI = 0.96, and SRMR = 0.02), with high internal consistency (Cronbach's alpha of 0.78 and McDonald's omega of 0.81), non-gender differential item functioning (Kendall tau b between 0.07 and 0.10), and significant discriminant validity (Higher scores for fear of COVID-19 were observed in high clinical anxiety levels). In conclusion, the Fear of COVID-5 Scale presents a clear one-dimension structure similar to a previous study.


Asunto(s)
COVID-19 , Humanos , Adulto , Universidades , México , Miedo , Estudiantes , Análisis Factorial , Encuestas y Cuestionarios , Reproducibilidad de los Resultados , Psicometría
18.
J Sports Med Phys Fitness ; 63(1): 60-68, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35415999

RESUMEN

BACKGROUND: The aim of this study was to compare the hypertrophic adaptations to barbell or flywheel squat exercise added to regular in-season soccer training. METHODS: Quadriceps' (rectus femoris [RF], vastus medialis [VM] and vastus lateralis [VL]) cross-sectional area (CSA) in its portions (proximal [PROX], middle [MID], and distal [DIST]) was measured on both legs before and after a 6-week barbell (80 to 90% one-maximum repetition; N.=7) or flywheel (0.0611 to 0.0811 kg·m2; N.=7) in an U19 professional soccer team using a 3T magnetic resonance imaging. Both groups underwent 5 sets × 6 reps per session of squat separated by 3-min rest, while controlling the time under tension (within 0.5 and 0.8 s). RESULTS: The barbell squat group experienced moderate CSA increments in the VMMID and the VLDIST of the right leg (d=0.98-0.99). Additionally, the flywheel group experience large CSA increments in the RFMID, VLPROX and VLMID of the right leg (d=1.00-1.84). On average, flywheel squat training largely produced greater force during exercise compared to the barbell squat training (29.2 vs. 12.2 N·kg-1; d=5.95), whereas the barbell squat training produced moderately greater power output (10.5 vs. 9.7; d=0.52). CONCLUSIONS: Barbell squat training seems to be more effective for VM hypertrophy whereas flywheel squat triggers greater RF and VL hypertrophy as complementary to regular field-based soccer practice and competition within a short range of time (6 weeks) during the in-season. These findings can be considered also from either strength or reconditioning perspective based on the increase in the quadriceps muscles' CSA as mechanism underlying strength/power adaptations.


Asunto(s)
Entrenamiento de Fuerza , Fútbol , Humanos , Entrenamiento de Fuerza/métodos , Fuerza Muscular , Estaciones del Año , Hipertrofia , Músculo Esquelético/diagnóstico por imagen
20.
Foods ; 11(24)2022 Dec 08.
Artículo en Inglés | MEDLINE | ID: mdl-36553721

RESUMEN

Agriculture worldwide faces the need to reduce chemical pesticides and produce healthier food. In Latin America, research on the organic food sector primarily focuses on supply. Consumption analysis is crucial for providing information about customers' needs. This paper aims to analyze the Ecuadorian organic food sector, which is an interesting case for investigating the relationship between willingness to consume organic food and socioeconomic factors. To this end, 382 consumers were surveyed. The study applied a logit regression analysis to assess the role of socioeconomic factors in the willingness to consume organic food. Radar diagrams depict the percentage of respondents who checked a particular reason for choosing or refusing organic food. A cross-location comparison analysis was applied to identify differences between locations within the Central Ecuador region. Results reveal that Ecuadorian consumers' awareness rate of organic food is only 53.5%. Regarding organic food's price, 24% of consumers perceive it to be overly expensive. Based on strengthening the supervision of organic food production, various channels should be used to promote organic food consumption and facilitate the recognition of available organic food.

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