RESUMEN
The formation of dynamic protein filaments contributes to various biological functions by clustering individual molecules together and enhancing their binding to ligands. We report such a propensity for the BTB domains of certain proteins from the ZBTB family, a large eukaryotic transcription factor family implicated in differentiation and cancer. Working with Xenopus laevis and human proteins, we solved the crystal structures of filaments formed by dimers of the BTB domains of ZBTB8A and ZBTB18 and demonstrated concentration-dependent higher-order assemblies of these dimers in solution. In cells, the BTB-domain filamentation supports clustering of full-length human ZBTB8A and ZBTB18 into dynamic nuclear foci and contributes to the ZBTB18-mediated repression of a reporter gene. The BTB domains of up to 21 human ZBTB family members and two related proteins, NACC1 and NACC2, are predicted to behave in a similar manner. Our results suggest that filamentation is a more common feature of transcription factors than is currently appreciated.
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Dominio BTB-POZ , Factores de Transcripción , Proteínas de Xenopus , Animales , Humanos , Núcleo Celular/metabolismo , Núcleo Celular/genética , Cristalografía por Rayos X , Células HEK293 , Modelos Moleculares , Unión Proteica , Multimerización de Proteína , Proteínas Represoras/metabolismo , Proteínas Represoras/genética , Proteínas Represoras/química , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Xenopus laevis , Proteínas de Xenopus/genética , Proteínas de Xenopus/metabolismo , Proteínas de Xenopus/químicaRESUMEN
Light plays an essential role in a variety of physiological processes, including vision, mood, and glucose homeostasis. However, the intricate relationship between light and an animal's feeding behavior has remained elusive. Here, we found that light exposure suppresses food intake, whereas darkness amplifies it in male mice. Interestingly, this phenomenon extends its reach to diurnal male Nile grass rats and healthy humans. We further show that lateral habenula (LHb) neurons in mice respond to light exposure, which in turn activates 5-HT neurons in the dorsal Raphe nucleus (DRN). Activation of the LHbâ5-HTDRN circuit in mice blunts darkness-induced hyperphagia, while inhibition of the circuit prevents light-induced anorexia. Together, we discovered a light-responsive neural circuit that relays the environmental light signals to regulate feeding behavior in mice.
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Conducta Alimentaria , Habénula , Luz , Animales , Masculino , Ratones , Habénula/fisiología , Conducta Alimentaria/fisiología , Núcleo Dorsal del Rafe/fisiología , Humanos , Ratones Endogámicos C57BL , Ingestión de Alimentos/fisiología , Vías Nerviosas/fisiología , Ratas , Neuronas Serotoninérgicas/fisiología , Red Nerviosa/fisiología , OscuridadRESUMEN
The aim of the study was to determine the presence of human papillomavirus (HPV) in patients with intractable plantar keratosis (IPK) by comparing the histopathological findings of biopsies. A prospective, observational, and concordance study was carried out. Three different specimens were taken from each IPK. A first punch was sent for histopathological examination, and a second punch and a superficial skin scraping were both sent for HPV polymerase chain reaction (PCR) and type determination. A total of 51 patients were included. From the histopathological examination, it was determined that 35 (68.6%) samples were diagnosed as warts and 16 (31.3%) as keratosis. However, the presence of HPV was confirmed by PCR in 49 (96.1%) and in 42 (82.4%) samples obtained by punch and superficial scraping, respectively. In the 49 PCR-positive samples, the most common HPV types were HPV1, HPV2, HPV27, HPV57, and HPV65, accounting for 81.6% of the samples. In conclusion, this study demonstrates that HPV infection and IPK lesions are very closely related. Although we cannot confirm that HPV is the cause of the development of IPK, the high prevalence of HPV observed in these lesions calls for a change to the procedures for managing IPK.
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Queratosis , Infecciones por Papillomavirus , Verrugas , Humanos , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/epidemiología , Virus del Papiloma Humano , Estudios Prospectivos , Verrugas/epidemiología , Papillomaviridae/genética , ADN Viral/genética , ADN Viral/análisisRESUMEN
Chile had a violent military coup (1973-1990) that resulted in 3,000 victims declared detained, missing or killed; many are still missing and unidentified. Currently, the Human Rights Unit of the Forensic Medical Service in Chile applies globally recognised forensic anthropological approaches, but many of these methods have not been validated in a Chilean sample. As current research has demonstrated population-specificity with extant methods, the present study aims to validate sex estimation methods in a Chilean population and thereafter establish population-specific equations. A sample of 265 os coxae of known age and sex of adult Chileans from the Santiago Subactual Osteology Collection were analysed. Visual assessment and scoring of the pelvic traits were performed in accordance with the Phenice (1969) and Klales et al. (2012) methods. The accuracy of Phenice (1969) in the Chilean sample was 96.98%, with a sex bias of 7.68%. Klales et al. (2012) achieved 87.17% accuracy with a sex bias of -15.39%. Although both methods showed acceptable classification accuracy, the associated sex bias values are unacceptable in forensic practice. Therefore, six univariate and eight multivariate predictive models were formulated for the Chilean population. The most accurate univariate model was the ventral arc at 96.6%, with a sex bias of 5.2%. Classification accuracy using all traits was 97.0%, with a sex bias of 7.7%. This study provides Chilean practitioners a population-specific morphoscopic standard with associated classification probabilities acceptable to accomplish legal admissibility requirements in human rights and criminal cases specific to the second half of the 20th century.
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Antropología Forense , Determinación del Sexo por el Esqueleto , Humanos , Chile , Determinación del Sexo por el Esqueleto/métodos , Masculino , Femenino , Antropología Forense/métodos , Adulto , Persona de Mediana Edad , Adulto Joven , Anciano , Huesos Pélvicos/anatomía & histología , Hueso Púbico/anatomía & histologíaRESUMEN
The glucocorticoid (GC) receptor (GR) is essential for normal development and in the initiation of inflammation. Healthy GRdim/dim mice with reduced dimerization propensity due to a point mutation (A465T) at the dimer interface of the GR DNA-binding domain (DBD) (here GRD/D) have previously helped to define the functions of GR monomers and dimers. Since GRD/D retains residual dimerization capacity, here we generated the dimer-nullifying double mutant GRD+L/D+L mice, featuring an additional mutation (I634A) in the ligand-binding domain (LBD) of GR. These mice are perinatally lethal, as are GRL/L mice (these mice have the I634A mutation but not the A465T mutation), displaying improper lung and skin formation. Using embryonic fibroblasts, high and low doses of dexamethasone (Dex), nuclear translocation assays, RNAseq, dimerization assays, and ligand-binding assays (and Kd values), we found that the lethal phenotype in these mice is due to insufficient ligand binding. These data suggest there is some correlation between GR dimerization potential and ligand affinity. We conclude that even a mutation as subtle as I634A, at a position not directly involved in ligand interactions sensu stricto, can still influence ligand binding and have a lethal outcome.
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Dexametasona , Mutación Puntual , Receptores de Glucocorticoides , Animales , Dexametasona/farmacología , Glucocorticoides/farmacología , Ligandos , Ratones , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismoRESUMEN
BACKGROUND & AIMS: Early-onset colorectal cancer (EOCRC) is a distinct clinical and molecular entity with poor survival outcomes compared with late-onset CRC. Although the incidence of EOCRC is rising, current CRC screening strategies have several limitations in diagnostic performance for EOCRC. In view of this clinical challenge, novel and robust biomarkers for detection of EOCRC are necessary. The aim of this study was to develop a circulating micro RNA (miRNA) signature for the diagnosis of patients with EOCRC. METHODS: A systematic discovery approach by analyzing a large, publicly available, noncoding RNA expression profiling dataset (GSE115513) was used. A panel of miRNAs was identified, which was subsequently validated in blood samples from patients with EOCRC in 2 independent cohorts (n = 149) compared with controls (n = 110) and pre/postoperative plasma specimens (n = 22) using quantitative reverse-transcription polymerase chain reaction assays. RESULTS: In the discovery phase, 4 miRNAs were found to be expressed in blood samples. A combination signature of these 4 miRNAs (miR-193a-5p, miR-210, miR-513a-5p, and miR-628-3p) yielded an area under the curve of 0.92 (95% confidence interval, 0.85-0.96) for identification of EOCRC in the training cohort. The miRNA panel performance was then confirmed in an independent validation cohort (area under the curve, 0.88; 95% confidence interval, 0.82-0.93). Moreover, the miRNA panel robustly identified patients with early-stage EOCRC (P < .001). The decreased expression of miRNAs in postsurgery plasma specimens indicated their tumor specificity. CONCLUSIONS: Our novel miRNA signature for the diagnosis of EOCRC has the potential to identify patients with EOCRC with high accuracy for clinical application in the noninvasive diagnosis of EOCRC.
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MicroARN Circulante , Neoplasias Colorrectales , MicroARNs , Humanos , Biomarcadores de Tumor/genética , Curva ROC , MicroARNs/genética , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/genética , Biopsia Líquida , Perfilación de la Expresión GénicaRESUMEN
BACKGROUND: Satellite cells are tissue-specific stem cells primarily responsible for the regenerative capacity of skeletal muscle. Satellite cell function and maintenance are regulated by extrinsic and intrinsic mechanisms, including the ubiquitin-proteasome system, which is key for maintaining protein homeostasis. In this context, it has been shown that ubiquitin-ligase NEDD4-1 targets the transcription factor PAX7 for proteasome-dependent degradation, promoting muscle differentiation in vitro. Nonetheless, whether NEDD4-1 is required for satellite cell function in regenerating muscle remains to be determined. RESULTS: Using conditional gene ablation, we show that NEDD4-1 loss, specifically in the satellite cell population, impairs muscle regeneration resulting in a significant reduction of whole-muscle size. At the cellular level, NEDD4-1-null muscle progenitors exhibit a significant decrease in the ability to proliferate and differentiate, contributing to the formation of myofibers with reduced diameter. CONCLUSIONS: These results indicate that NEDD4-1 expression is critical for proper muscle regeneration in vivo and suggest that it may control satellite cell function at multiple levels.
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Músculo Esquelético , Complejo de la Endopetidasa Proteasomal , Complejo de la Endopetidasa Proteasomal/metabolismo , Proliferación Celular/fisiología , Músculo Esquelético/metabolismo , Células Madre , Diferenciación Celular , Ubiquitinas/metabolismo , Desarrollo de Músculos/fisiología , Factor de Transcripción PAX7/genética , Factor de Transcripción PAX7/metabolismoRESUMEN
OBJECTIVE: To determine the frequency of oral squamous cell carcinoma (OSCC) associated or not with oral potentially malignant disorders (OPMD), and the epidemiological profile and traditional risk factors in Latin America. METHODS: A retrospective observational study was conducted in 17 Latin American centres. There were included cases of OSCC, analysing age, gender, OSCC and their association with previous OPMD. Clinicopathological variables were retrieved. The condition of sequential-OSCC versus OSCC-de novo (OSCC-dn) was analysed concerning the aforementioned variables. Quantitative variables were analysed using Student's t-test, and qualitative variables with chi-square. RESULTS: In total, 2705 OSCC were included with a mean age of 62.8 years old. 55.8% were men. 53.75% of the patients were smokers and 38% were common drinkers. The lateral tongue border was the most affected site (24.65%). There were regional variations in OPMD, being leukoplakia the most frequent. Of the overall 2705 OSCC cases, 81.4% corresponded to OSCC-dn, while s-OSCC were 18.6%. Regarding lip vermillion SCC, 35.7% corresponded to de novo lip SCC and 64.3% were associated with previous OPMD. CONCLUSIONS: In Latin America, OSCC-dn seems to be more frequent with regional variations of some clinical and histopathological features. Further prospective studies are needed to analyse this phenomenon.
RESUMEN
Adenovirus minor coat protein VI contains a membrane-disrupting peptide that is inactive when VI is bound to hexon trimers. Protein VI must be released during entry to ensure endosome escape. Hexon:VI stoichiometry has been uncertain, and only fragments of VI have been identified in the virion structure. Recent findings suggest an unexpected relationship between VI and the major core protein, VII. According to the high-resolution structure of the mature virion, VI and VII may compete for the same binding site in hexon; and noninfectious human adenovirus type 5 particles assembled in the absence of VII (Ad5-VII-) are deficient in proteolytic maturation of protein VI and endosome escape. Here we show that Ad5-VII- particles are trapped in the endosome because they fail to increase VI exposure during entry. This failure was not due to increased particle stability, because capsid disruption happened at lower thermal or mechanical stress in Ad5-VII- compared to wild-type (Ad5-wt) particles. Cryoelectron microscopy difference maps indicated that VII can occupy the same binding pocket as VI in all hexon monomers, strongly arguing for binding competition. In the Ad5-VII- map, density corresponding to the immature amino-terminal region of VI indicates that in the absence of VII the lytic peptide is trapped inside the hexon cavity, and clarifies the hexon:VI stoichiometry conundrum. We propose a model where dynamic competition between proteins VI and VII for hexon binding facilitates the complete maturation of VI, and is responsible for releasing the lytic protein from the hexon cavity during entry and stepwise uncoating.
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Adenovirus Humanos/metabolismo , Proteínas de la Nucleocápside/metabolismo , Ensamble de Virus , Internalización del Virus , Adenovirus Humanos/genética , Adenovirus Humanos/ultraestructura , Microscopía por Crioelectrón , Humanos , Proteínas de la Nucleocápside/química , Proteínas de la Nucleocápside/genética , Unión Proteica , Dominios ProteicosRESUMEN
Previous studies have reported the potential emission of nail dust to the indoor air of the podiatrist's workplace during nail drilling procedures. The main objective of this study was to analyse the fungal bioaerosol present in the indoor air of podiatry rooms, including during the nail drilling procedure. Seventeen private clinics were sampled in Madrid during spring and summer. The most prevalent filamentous fungi detected were Cladosporium spp. and Penicillium spp. in both seasons. The presence of Trichophyton rubrum and Trichophyton interdigitale was reported in samples during the drilling procedures, establishing a positive association with the clinical suspicion of onychomycosis (p = 0.002) and the utilization of aspiration systems (p=0.04). The present study concludes that airborne fungal concentrations in podiatrist's clinics are consistent with national and international guidance. Occupational exposure to dermatophytes may briefly occur during definite periods across the daily activity despite the use of dust aspiration systems.
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Contaminación del Aire Interior , Exposición Profesional , Hongos , Exposición Profesional/análisis , Lugar de Trabajo , Polvo/análisis , Microbiología del Aire , Contaminación del Aire Interior/análisisRESUMEN
BACKGROUND: Commensal Neisseria species (spp). represent an important reservoir of antimicrobial resistance genes for pathogenic Neisseria spp. In this systematic review, we aimed to assess the antimicrobial susceptibility of commensal Neisseria spp. and how this has evolved over time. We also aimed to assess if commensal Neisseria spp. showed intrinsic resistance to four antimicrobials - penicillin, azithromycin, ceftriaxone and ciprofloxacin. METHODS: Pubmed and Google Scholar were searched following the PRISMA guidelines. Articles reporting MICs of commensal Neisseria spp. were included according to inclusion/exclusion criteria, and the quality of the articles was assessed using a pre-designed tool. Individual and summary measures of penicillin, azithromycin, ceftriaxone and ciprofloxacin MICs were collected. Additional data was sought to perform a comparison between the MICs of pathogenic and commensal Neisseria spp. RESULTS: A total of 15 studies met our criteria.We found no evidence of intrinsic AMR in commensal Neisseria spp. We did find evidence of an increasing trend in MICs of commensal Neisseria spp. over time for all antimicrobials assessed. These findings were similar in various countries. Eight additional studies were included to compare pathogenic and commensal Neisseria spp. CONCLUSION: The MICs of commensal Neisseria spp. appear to be increasing in multiple countries. Surveillance of MICs in commensals could be used as an early warning system for antimicrobial resistance emergence in pathogens. Our findings underline the need for antibiotic stewardship interventions, particularly in populations with high antimicrobial consumption.
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Antibacterianos , Gonorrea , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Ceftriaxona/farmacología , Ciprofloxacina/farmacología , Farmacorresistencia Bacteriana , Gonorrea/tratamiento farmacológico , Gonorrea/epidemiología , Humanos , Pruebas de Sensibilidad Microbiana , Neisseria , Neisseria gonorrhoeae/genéticaRESUMEN
BACKGROUND: The ongoing coronavirus 2019 disease (COVID-19) pandemic strained medical systems worldwide. We report on the impact on pediatric oncology care in Latin American (LATAM) during its first year. METHOD: Four cross-sectional surveys were electronically distributed among pediatric onco-hematologists in April/June/October 2020, and April/2021 through the Latin American Society of Pediatric Oncology (SLAOP) email list and St Jude Global regional partners. RESULTS: Four hundred fifty-three pediatric onco-hematologists from 20 countries responded to the first survey, with subsequent surveys response rates above 85%. More than 95% of participants reported that treatment continued without interruption for new and active ongoing patients, though with disruptions in treatment availability. During the first three surveys, respondents reported suspensions of outpatient procedures (54.2%), a decrease in oncologic surgeries (43.6%), radiotherapy (28.4%), stem cell transplants (SCT) (69.3%), and surveillance consultations (81.2%). Logistic regression analysis showed that at the beginning of the first wave, participants from countries with healthcare expenditure below 7% were more likely to report a decrease in outpatient procedures (odds ratio [OR]: 1.84, 95% CI: 1.19-2.8), surgeries (OR: 3, 95% CI: 1.9-4.6) and radiotherapy (OR: 6, 95% CI: 3.5-10.4). Suspension of surveillance consultations was higher in countries with COVID-19 case fatality rates above 2% (OR: 3, 95% CI: 1.4-6.2) and SCT suspensions in countries with COVID-19 incidence rate above 100 cases per 100,000 (OR: 3.48, 95% CI: 1.6-7.45). Paradoxically, at the beginning of the second wave with COVID-19 cases rising exponentially, most participants reported improvements in cancer services availability. CONCLUSION: Our data show the medium-term collateral effects of the pandemic on pediatric oncology care in LATAM, which might help delineate oncology care delivery amid current and future challenges posed by the pandemic.
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COVID-19 , Neoplasias , COVID-19/epidemiología , Niño , Estudios Transversales , Humanos , América Latina/epidemiología , Neoplasias/epidemiología , Neoplasias/terapia , Pandemias , SuspensionesRESUMEN
OBJECTIVES: The SARS-CoV-2 virus continues wreaking worldwide havoc on health and between March and August 2020, the first outbreak of COVID-19 hit Chile. The pregnant population is especially vulnerable to infection. Studies have been published that associate socioeconomic status, overcrowding, and poverty with a higher prevalence of SARS-CoV-2 infection. There are few studies about the development of this pandemic in Latin American countries so far. This study seeks to show the prevalence and sociodemographic and perinatal characteristics in pregnant women at the time of delivery, comparing both groups with positive and negative COVID-19 PCR results. METHODS: A prospective, cross-sectional study of pregnant women who delivered at the San Juan de Dios Hospital in Santiago between April 15, 2020 and June 15, 2020. Analysis of epidemiological, sociodemographic, obstetric, perinatal and sociodemographic data of patients with positive and negative COVID-19 PCR results. RESULTS: There were 701 patients included in the study. The prevalence of those with a positive COVID-19 PCR was 9.7% and 67.7% being asymptomatic. Pre-term delivery was significantly higher in the group of positive patients (23.5%) vs. negative patients (8.7%), which was not the same rate as with cesarean sections (C-sections). A 13.2% of patients required management of the pathology in the Critical Care Unit (CCU) and there were no cases of maternal or fetal deaths. We found no significant difference between both groups when analyzing socioeconomic variables, though we noted a trend of greater overcrowding among the group of patients with infection. CONCLUSIONS: The majority of pregnant patients with SARS-CoV-2 infection are asymptomatic. COVID-19 increases the rate of premature births, but this rate is not same with C-sections. Sociodemographic conditions and overcrowding do not show a higher infection rate in a homogeneous population in relation to the economic, social and demographic level.
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COVID-19/epidemiología , Hospitales Públicos/estadística & datos numéricos , Complicaciones Infecciosas del Embarazo/epidemiología , Adolescente , Adulto , Chile/epidemiología , Estudios Epidemiológicos , Femenino , Humanos , Persona de Mediana Edad , Embarazo , Prevalencia , Factores Sociodemográficos , Adulto JovenRESUMEN
Following pathogen infection, plants have developed diverse mechanisms that direct their immune systems towards more robust induction of defense responses against recurrent environmental stresses. The induced resistances could be inherited by the progenies, rendering them more tolerant to stressful events. Although within-generational induction of tolerance to abiotic stress is a well-documented phenomenon in virus-infected plants, the transgenerational inheritance of tolerance to abiotic stresses in their progenies has not been explored. Here, we show that infection of Nicotiana benthamiana plants by Potato virus X (PVX) and by a chimeric Plum pox virus (PPV) expressing the P25 pathogenicity protein of PVX (PPV-P25), but not by PPV, conferred tolerance to both salt and osmotic stresses to the progeny, which correlated with the level of virulence of the pathogen. This transgenerational tolerance to abiotic stresses in the progeny was partially sustained even if the plants experience a virus-free generation. Moreover, progenies from a Dicer-like3 mutant mimicked the enhanced tolerance to abiotic stress observed in progenies of PVX-infected wild-type plants. This phenotype was shown irrespective of whether Dicer-like3 parents were infected, suggesting the involvement of 24-nt small interfering RNAs in the transgenerational tolerance to abiotic stress induced by virus infection. RNAseq analysis supported the upregulation of genes related to protein folding and response to stress in the progeny of PVX-infected plants. From an environmental point of view, the significance of virus-induced transgenerational tolerance to abiotic stress could be questionable, as its induction was offset by major reproductive costs arising from a detrimental effect on seed production.
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Virus Eruptivo de la Ciruela , Potexvirus , Presión Osmótica , Virus Eruptivo de la Ciruela/genética , Potexvirus/genética , Nicotiana , Cloruro de Sodio/farmacología , Estrés Fisiológico/genética , Regulación de la Expresión Génica de las Plantas , Plantas Modificadas Genéticamente/fisiología , Proteínas de Plantas/genéticaRESUMEN
Systemic inflammatory response syndrome (SIRS) is a severe condition characterized by systemic inflammation, which may lead to multiple organ failure, shock and death. SIRS is common in burn patients, pancreatitis and sepsis. SIRS is often accompanied by intestinal dysbiosis. However, the mechanism, role and details of microbiome alterations during the early phase of acute SIRS are not completely understood. The current study aimed to characterize the dynamic alterations of both the intestinal and respiratory microbiome at two timepoints during the early phase of acute SIRS (4 and 8 h after LPS) and link these to the host response in a mouse model of a LPS-induced lethal SIRS. Acute SIRS had no effect on the microbiome in the large intestine but induced a rapid dysbiosis in the small intestine, which resembled the microbiome alterations commonly observed in SIRS patients. Later in the disease progression, a dysbiosis of the respiratory microbiome was observed, which was associated with the MMP9 expression in the lungs. Although similar bacteria were increased in both the lung and the small intestine, no evidence for a gut-lung translocation was observed. Gut dysbiosis is commonly observed in diseases involving inflammation in the gut. However, whether the inflammatory response associated with SIRS and sepsis can directly cause gut dysbiosis was still unclear. In the current study we provide evidence that a LPS-induced SIRS can directly cause dysbiosis of the small intestinal and respiratory microbiome.
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Endotoxemia , Microbioma Gastrointestinal , Sepsis , Animales , Disbiosis/microbiología , Endotoxemia/complicaciones , Inflamación/metabolismo , Lipopolisacáridos/toxicidad , Metaloproteinasa 9 de la Matriz , Ratones , Sepsis/complicacionesRESUMEN
The benefit of autologous platelet-rich plasma (PRP) treatment is still under discussion. Variations in PRP products, consequence of the lack of a standardised protocol for the multitude of commercially available blood separation systems and the lack of knowledge of the optimal composition of PRP or its suitability for the proposed indication are some of the reasons behind clinical inconsistencies. The impact of inter-subject variability in PRP has received less attention in comparison. The purpose of this study was to determine the inter-subject variability, based on age, in the concentrates prepared by a new blood concentration system. Twenty-six healthy volunteers of both genders (29-93 years) were enrolled. Whole blood (WB) was collected from each participant to prepare PRP using the Easy PRP kit. Platelets and white blood cells (WBC) from WB and PRP were analysed after split population by age; patients younger than 65 years (n = 13) and patients ≥65 years old (n = 13). Among the demographic characteristics tested, only age was significantly different between the groups. Cell capture efficiency of the system was specific for each type of blood cell and identical for both age groups. Platelets and WBC in PRP were higher than in WB (P < .001). In WB, platelets and WBC concentrations were significantly lower in older group (P ≤ .035). These differences persisted in the prepared PRP (P ≤ .004). The ageing of population has a strong influence on the haematocrit and therefore on the composition of PRP. Because the efficiency of blood separator system seems to be constant across individuals, the inter-subject haematocrit variability based on age could be used as a predictor of resulting PRP. The clinical application of PRP should be restricted to the specific cell capture capacity of the different commercial devices.
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Plaquetas , Plasma Rico en Plaquetas , Anciano , Femenino , Voluntarios Sanos , Humanos , Recuento de Leucocitos , Leucocitos , MasculinoRESUMEN
BACKGROUND: Patients with myasthenia gravis (MG) may be particularly vulnerable during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic due to risk of worsening disease during infection, potential adverse impacts of coronavirus disease 2019 (COVID-19) treatments on neuromuscular transmission, and a limited ability to fight off infection related to immunosuppressive treatments. Our goal is to understand how patients are experiencing the COVID-19 pandemic, including where they receive relevant information, how it has affected medical care, and what measures they use to protect themselves. METHODS: This is a prospective online survey study at large academic practice. All patients with a neuromuscular junction disorder diagnosis code in the Duke Health System were invited to participate. RESULTS: One thousand eight hundred and forty eight patients were approached to participate and 75 completed the survey between 16 April 2020 and 28 May 2020. The most frequently used information sources were non-presidential federal government (75%), state government (57%), local healthcare provider (37%), and television news (36%). Non-presidential federal government (80%), local healthcare providers (55%), state government (33%), and patient support organizations (29%) were considered the most trusted information sources. Thirty-three (44%) of survey responders had attended a telemedicine visit. Patients were taking recommended precautions during the pandemic and remained very concerned (69%) about COVID-19. Generalized Anxiety Disorder-7 scores were moderate-severe in 20% of responders. CONCLUSIONS: Healthcare providers, the government, and patient organizations play a critical role in communicating with the MG patient community. Use of targeted messaging strategies by these groups to convey accurate information may increase effectiveness and lead to more informed patients with reduced anxiety.
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COVID-19 , Conocimientos, Actitudes y Práctica en Salud , Miastenia Gravis , Anciano , Estudios de Cohortes , Gobierno Federal , Femenino , Desinfección de las Manos , Personal de Salud , Humanos , Masculino , Máscaras , Persona de Mediana Edad , Cuestionario de Salud del Paciente , Distanciamiento Físico , Estudios Prospectivos , SARS-CoV-2 , Gobierno Estatal , Encuestas y Cuestionarios , Telemedicina , Televisión , Estados UnidosRESUMEN
BACKGROUND: The immunopathology of autoimmune seronegative myasthenia gravis (SN MG) is poorly understood. Our objective was to determine immune profiles associated with a diagnosis of SN MG. METHODS: We performed high-dimensional flow cytometry on blood samples from SN MG patients (N = 68), healthy controls (N = 46), and acetylcholine receptor antibody (AChR+) MG patients (N = 27). We compared 12 immune cell subsets in SN MG to controls using logistic modeling via a discovery-replication design. An exploratory analysis fit a multinomial model comparing AChR+ MG and controls to SN MG. RESULTS: An increase in CD19+ CD20- CD38hi plasmablast frequencies was associated with lower odds of being a SN MG case in both the discovery and replication analyses (discovery P-value = .0003, replication P-value = .0021). Interleukin (IL) -21 producing helper T cell frequencies were associated with a diagnosis of AChR+ MG (P = .004). CONCLUSIONS: Reduced plasmablast frequencies are strongly associated with a SN MG diagnosis and may be a useful diagnostic biomarker in the future.
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Autoanticuerpos/sangre , Miastenia Gravis/sangre , Células Plasmáticas/citología , Receptores Colinérgicos/sangre , Adulto , Anciano , Biomarcadores/sangre , Femenino , Citometría de Flujo/métodos , Humanos , Masculino , Persona de Mediana Edad , Miastenia Gravis/diagnóstico , Receptores Colinérgicos/inmunología , Adulto JovenRESUMEN
Microbial communities live on macroalgal surfaces. The identity and abundance of the bacteria making these epiphytic communities depend on the macroalgal host and the environmental conditions. Macroalgae rely on epiphytic bacteria for basic functions (spore settlement, morphogenesis, growth, and protection against pathogens). However, these marine bacterial-macroalgal associations are still poorly understood for macroalgae inhabiting the Colombian Caribbean. This study aimed at characterizing the epiphytic bacterial community from macroalgae of the species Ulva lactuca growing in La Punta de la Loma (Santa Marta, Colombia). We conducted a 16S rRNA gene sequencing-based study of these microbial communities sampled twice a year between 2014 and 2016. Within these communities, the Proteobacteria, Bacterioidetes, Cyanobacteria, Deinococcus-Thermus and Actinobacteria were the most abundant phyla. At low taxonomic levels, we found high variability among epiphytic bacteria from U. lactuca and bacterial communities associated with macroalgae from Germany and Australia. We observed differences in the bacterial community composition across years driven by abundance shifts of Rhodobacteraceae Hyphomonadaceae, and Flavobacteriaceae, probably caused by an increase of seawater temperature. Our results support the need for functional studies of the microbiota associated with U. lactuca, a common macroalga in the Colombian Caribbean Sea.
Asunto(s)
Algas Marinas , Ulva , Bacterias/genética , Región del Caribe , Colombia , ARN Ribosómico 16S/genética , Agua de MarRESUMEN
Some viruses package dsDNA together with large amounts of positively charged proteins, thought to help condense the genome inside the capsid with no evidence. Further, this role is not clear because these viruses have typically lower packing fractions than viruses encapsidating naked dsDNA. In addition, it has recently been shown that the major adenovirus condensing protein (polypeptide VII) is dispensable for genome encapsidation. Here, we study the morphology and mechanics of adenovirus particles with (Ad5-wt) and without (Ad5-VII-) protein VII. Ad5-VII- particles are stiffer than Ad5-wt, but DNA-counterions revert this difference, indicating that VII screens repulsive DNA-DNA interactions. Consequently, its absence results in increased internal pressure. The core is slightly more ordered in the absence of VII and diffuses faster out of Ad5-VII- than Ad5-wt fractured particles. In Ad5-wt unpacked cores, dsDNA associates in bundles interspersed with VII-DNA clusters. These results indicate that protein VII condenses the adenovirus genome by combining direct clustering and promotion of bridging by other core proteins. This condensation modulates the virion internal pressure and DNA release from disrupted particles, which could be crucial to keep the genome protected inside the semi-disrupted capsid while traveling to the nuclear pore.