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Weighted Gene Co-expression Network Analysis (WGCNA) is a widely used approach for the generation of gene co-expression networks. However, networks generated with this tool usually create large modules with a large set of functional annotations hard to decipher. We have developed TGCN, a new method to create Targeted Gene Co-expression Networks. This method identifies the transcripts that best predict the trait of interest based on gene expression using a refinement of the LASSO regression. Then, it builds the co-expression modules around those transcripts. Algorithm properties were characterized using the expression of 13 brain regions from the Genotype-Tissue Expression project. When comparing our method with WGCNA, TGCN networks lead to more precise modules that have more specific and yet rich biological meaning. Then, we illustrate its applicability by creating an APP-TGCN on The Religious Orders Study and Memory and Aging Project dataset, aiming to identify the molecular pathways specifically associated with APP role in Alzheimer's disease. Main biological findings were further validated in two independent cohorts. In conclusion, we provide a new framework that serves to create targeted networks that are smaller, biologically relevant and useful in high throughput hypothesis driven research. The TGCN R package is available on Github: https://github.com/aliciagp/TGCN .
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Algoritmos , Doença de Alzheimer , Redes Reguladoras de Genes , Humanos , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Perfilação da Expressão Gênica/métodos , Encéfalo/metabolismo , Biologia Computacional/métodosRESUMO
Some patients with autism and severe intellectual disability may experience uncontrolled aggression, causing serious injury or harm to others, and the therapeutic ineffectiveness of traditional pharmacological and behavioral treatment may aggravate symptoms. Deep brain stimulation (DBS) has been tested in patients with little evidence in children and adolescents. Therefore, we analyzed the efficacy and safety of DBS in refractory aggression in pediatric subjects with autism (ASD) and severe intelligence deficit (ID).Methods A meta-analytic review of Web of Science (WOS) and Scopus articles, following Prisma criteria. A total of 555 articles were identified, but after applying the inclusion criteria, only 18 were analyzed. The review of the registries and the extraction of information was performed by 2 independent groups, to reduce the evaluator's bias. For the description of the results, pediatric patients with ASD or ID present in each registry, with an application of specialized scales (Overt aggression scale, OAS, and THE modified version of the OAS, MOAS) pre and post-DBS, with a clinical follow-up of at least 12 months, were considered valid. Clinical improvement was calculated using tests of aggressiveness. In each registry with available data and then pooling the means of all patients in the OAS and MOAS, the effect size of DBS (overall and per study) was estimated. Finally, the adapted NOS scale was applied to rate the studies' quality and level of bias.Results In the studies analyzed, 65/100 were pediatric patients, with a mean age of 16.8 years. Most of the studies were conducted in South America and Europe. In all teams, aggressive behavior was intractable, but only 9 groups (53/65) applied specialized scales to measure aggressiveness, and of these, only 51 subjects had a follow-up of at least 12 months. Thus, in 48/51 a clinical improvement of patients was estimated (94.2%), with a considerable overall effect size (OAS: d = 4.32; MOAS: d = 1.46). However, adverse effects and complications were found in 13/65 subjects undergoing DBS. The brain target with the most evidence and the fewest side effects was the posteromedial hypothalamic nuclei (pHypN). Finally, applying the adapted NOS scale, quality, and bias, only 9 studies show the best indicators.Conclusion An optimal level of efficacy was found in only half of the publications. This is mainly due to design errors and irrelevant information in the reports. We believe that DBS in intractable aggressiveness in children and adolescents with ASD and severe ID can be safe and effective if working groups apply rigorous criteria for patient selection, interdisciplinary assessments, objective scales for aggressiveness, and known surgical targets.
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Agressão , Estimulação Encefálica Profunda , Deficiência Intelectual , Humanos , Estimulação Encefálica Profunda/métodos , Criança , Deficiência Intelectual/terapia , Adolescente , Transtorno Autístico/terapia , Resultado do TratamentoRESUMO
BACKGROUND: Glass ionomers may be a good alternative to composite resin restorations in special needs patients with challenging behaviours. The present study was carried out to evaluate the restorative efficacy of glass ionomer in the occlusal cavities of permanent molars among patients with special needs after one year of follow-up. MATERIAL AND METHODS: A randomized split-mouth study was made of a cohort of patients with special needs. First and second permanent molars with occlusal caries were treated with glass ionomer, silver amalgam and composite resin. Assessments were made at 3, 6 and 12 months, using a scale based on the original code of Ryge and the USPHS criteria. RESULTS: A total of 34 patients and 102 restorations comprised the study sample. The survival rate of both the glass ionomer and silver amalgam was 100%, versus 97.1% in the case of composite resin. The glass ionomer afforded good marginal adaptation and stable color, with no fractures or secondary caries. CONCLUSIONS: The glass ionomer remained successfully for one year in the occlusal cavities of the permanent molars, with the same survival rate as silver amalgam, and better survival than composite resin, in the patients with special needs.
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Restauração Dentária Permanente , Cimentos de Ionômeros de Vidro , Humanos , Masculino , Feminino , Restauração Dentária Permanente/métodos , Adulto , Cimentos de Ionômeros de Vidro/uso terapêutico , Adulto Jovem , Cárie Dentária/terapia , Assistência Odontológica para a Pessoa com Deficiência , Pessoa de Meia-Idade , Amálgama Dentário , Adolescente , Resinas Compostas/uso terapêutico , Resinas Acrílicas , Dióxido de SilícioRESUMO
BACKGROUND: Although there are several endoscopic grading systems for chronic rhinosinusitis (CRS), they are limited in their range and applicability. We developed a SiNonasal Endoscopic Score (SiNES) that builds upon the strengths of previous systems while addressing their limitations. METHODS: The SiNES system was developed by consensus after multiple rounds of guided discussions. Face, content, and convergent validity were investigated. It was validated using an independent sample of 79 CRS individuals from two referral centres from September 2021 to February 2022. Each patient underwent a sinonasal endoscopy and filled PROM questionnaires. Three independent rhinologists graded endoscopic videos using the SiNES and modified Lund-Kennedy (MLK) scores. Inter-rater and test-retest reliability were assessed via the intraclass correlation coefficient (ICC). SiNES and MLK scores were correlated with PROMs using a Spearman correlation and canonical correlation analysis (CCA). RESULTS: The SiNES system evaluates five anatomical spaces regarding edema, discharge, and scarring. Face, content, and convergent validity were deemed satisfactory by the study authors and an independent panel of Otolaryngologists. Inter-rater reliability was excellent for the SiNES and good for the MLK score. Test-retest reliability was excellent for both systems. Total SiNES was correlated with self-reported smell loss. CONCLUSIONS: The SiNES system is an accurate and reliable grading framework applicable to all CRS subtypes. It can be utilized in clinical and research settings and improves upon previously published systems.
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Endoscopia , Rinite , Sinusite , Humanos , Sinusite/diagnóstico , Doença Crônica , Rinite/diagnóstico , Endoscopia/métodos , Reprodutibilidade dos Testes , Feminino , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Adulto , Índice de Gravidade de Doença , Seios Paranasais , RinossinusiteRESUMO
Aging can be associated with the accumulation of hypobranched glycogen molecules (polyglucosan bodies, PGBs), particularly in astrocytes of the hippocampus. While PGBs have a detrimental effect on cognition in diseases such as adult polyglucosan body disease and Lafora disease, the underlying mechanism and clinical relevance of age-related PGB accumulation remains unknown. Here, we have investigated the genetic basis and functional impact of age-related PGB accumulation in 32 fully sequenced BXD-type strains of mice which exhibit a 400-fold variation in PGB burden in 16-18 month old females. We mapped a major locus controlling PGB density in the hippocampus to chromosome 1 at 72-75 Mb (linkage of 4.9 -logP), which we defined as the Pgb1 locus. To identify potentially causal gene variants within Pgb1, we generated extensive hippocampal transcriptome datasets and identified two strong candidate genes for which mRNA correlates with PGB density-Smarcal1 and Usp37. In addition, both Smarcal1 and Usp37 contain non-synonymous allele variations likely to impact protein function. A phenome-wide association analysis highlighted a trans-regulatory effect of the Pgb1 locus on expression of Hp1bp3, a gene known to play a role in age-related changes in learning and memory. To investigate the potential impact of PGBs on cognition, we performed conditioned fear memory testing on strains displaying varying degrees of PGB burden, and a phenome-wide association scan of ~12,000 traits. Importantly, we did not find any evidence suggesting a negative impact of PGB burden on cognitive capacity. Taken together, we have identified a major modifier locus controlling PGB burden in the hippocampus and shed light on the genetic architecture and clinical relevance of this strikingly heterogeneous hippocampal phenotype.
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BACKGROUND: The global spread of Klebsiella pneumoniae ST15, causing multi-continental outbreaks, contributes to the movement of resistance genes between clones increasing the antimicrobial resistance crisis. The genomic traits providing it with the ability to outcompete other bacteria and cause epidemics remain unclear. AIM: To identify the specific genomic traits of K. pneumoniae ST15 to develop a diagnostic test. METHODS: An outbreak caused by K. pneumoniae occurred in Hospital A Coruña, Spain. Antimicrobial susceptibility analysis and molecular typing (PGFE and MLST) were performed. One isolate of each sequence type was selected for whole-genome sequencing analysis. Comparative analysis of genomes was performed using RAST. BLASTn was used to evaluate the presence of the fhaC and kpiD genes. Two hundred and ninety-four K. pneumoniae from a Spanish nationwide collection were analysed by PCR. FINDINGS: Genotyping showed that 87.5% of the isolates tested belonged to a clone with a unique PFGE pattern which corresponded to ST15. Comparative genomic analysis of the different STs enabled us to determine the specific genomic traits of K. pneumoniae ST15. Two adherence-related systems (Kpi and KpFhaB/FhaC) were specific markers of this clone. Multiplex-PCR analysis with kpiD and fhaC oligonucleotides revealed that K. pneumoniae ST15 is specifically detected with a sensitivity of 100% and a specificity of 97.76%. The PCR results showed 100% concordance with the MLST and whole-genome sequencing data. CONCLUSION: K. pneumoniae ST15 possesses specific genomic traits that could favour its dissemination. They could be used as targets to detect K. pneumoniae ST15 with high sensitivity and specificity.
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Antibacterianos , Infecções por Klebsiella , Humanos , Antibacterianos/uso terapêutico , Tipagem de Sequências Multilocus/métodos , beta-Lactamases/genética , Klebsiella pneumoniae , Infecções por Klebsiella/diagnóstico , Infecções por Klebsiella/epidemiologia , Infecções por Klebsiella/tratamento farmacológico , Reação em Cadeia da Polimerase Multiplex , Células Clonais , Testes de Sensibilidade MicrobianaRESUMO
OBJECTIVES: To determine the association between tobacco and peri-implant diseases in a sample of patients who had received implant-supported restorations in a university dental clinic. Furthermore, the study aimed to investigate patient- and implant-related variables associated with peri-implant diseases. MATERIALS AND METHODS: The present retrospective study analyzed data from 117 patients treated with implant-supported restorations from 2001 to 2013. A total of 450 implants were evaluated. Patients were selected from an electronic database, and patient- and implant-related variables were evaluated. Detailed information regarding the smoking history (i.e., smoking status, lifetime cumulative dose, duration of exposure, intensity of the habit, and smoking cessation) was recorded. The primary study outcome was peri-implant status [i.e., health (H), peri-implant mucositis (PM) and peri-implantitis (PI)]. Univariate and multinomial regression models comparing PM and PI versus peri-implant health were conducted. RESULTS: A total of 117 subjects [55 (47%) females and 62 (53%) males] with a mean age at examination of 64.2 years (SD 11.6) and rehabilitated with 450 implants were included. The average number of implants per patient was 4.6 (SD 3.3) with a mean time in function of 8.0 years (SD 1.9). Fifty-six patients (47.9%) were non-smokers, 42 (35.9%) were former-smokers, and 19 (16.2%) were current-smokers. Thirty-nine subjects (33.4%) were H, whereas 41 (35%) and 37 (31.6%) exhibited PM and PI, respectively. At implant level, the corresponding values were 142 (31.6%), 230 (51.1%) and 78 (17.3%). In the multinomial regression model, significant associations for peri-implant diseases were observed for the mean number of implants per patient (p = .016), function time (p = .048), implants placed simultaneously with guided bone regeneration (p = .016), implant surface (p = .020), keratinized mucosa at the buccal aspect (p = .032), and access to interproximal hygiene (p < .001). In addition, ever smokers >23 pack-years exhibited a significantly higher risk for peri-implantitis (p = .002). Finally, the multinomial regression analysis revealed that subjects who had stopped smoking more than 21 years before the last examination presented a significantly lower risk of peri-implant diseases than a smoking cessation of ≤21 years (p = .028). CONCLUSIONS: Smoke intensity was associated with an increased risk of the development of peri-implantitis. Moreover, the risk of peri-implant diseases might be similar in those subjects who had stopped smoking for more than 21 years with respect to never-smokers.
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Introduction: The coronavirus pandemic continues to affect the mental health of healthcare personnel in Latin America (LA). Objective: To estimate the prevalence of psychological disturbances and associated risk factors for mental health in healthcare personnel in LA during the second year of the COVID-19 pandemic. Method: This multicenter cross-sectional study included a total sample of 5437 healthcare professionals from Argentina, Bolivia, Chile, Colombia, Ecuador, and Peru. The PHQ-9, GAD-7, and a brief demographic questionnaire were used. The prevalence of anxiety and depression was estimated based on the cut-off points of the instruments. Two multivariate logistic regressions were performed. Results: A population burden of anxiety (40.1%) and depression (62.2%) was found in healthcare personnel in LA. Among professionals in Argentina (OR = 1.374; P<.001), those working in state hospitals (OR = 1.536; P<.003), frontline healthcare workers for COVID patients (OR = 1.848; P<.001), general practitioners (OR = 1.335; P<.001), and specialists (OR = 1.298; P<.001), a higher risk of experiencing mental disorders was observed. Among women, younger personnel, and administrative staff, a higher probability of experiencing anxiety and depression was identified. Conclusions: The burden of mental disorders on healthcare personnel in Latin America is alarming. Psychological support services are necessary, aimed at providing measures for professionals to develop healthy coping mechanisms that mitigate the impact of the pandemic on their well-being and facilitate post-crisis adjustment.
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In this study, we aimed to comparatively evaluate the in vitro activity of cefiderocol versus other antimicrobials against a well-characterized collection of metallo-beta-lactamase (MBL)-producing Gram-negative bacilli (MBL-GNB) isolates from hospitals in Andalusia, Spain. We recovered 232 MBL-GNB from Andalusian hospitals, including 160 Enterobacterales and 72 nonfermenting Gram-negative bacilli belonging to 44 different clones (2015 to 2020). Cefiderocol and comparator MICs were determined with commercial methods (UMIC [Bruker] and EUMDROXF [Sensititre; Thermo Fisher], respectively). EUCAST breakpoints were used for all antimicrobials tested, and CLSI also was used for cefiderocol. Control strains used were E. coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853. Cefiderocol showed potent in vitro activity against isolates tested, regardless of breakpoint (susceptibility rates, 85.3% for EUCAST versus 96.6% for CLSI, P < 0.001). MIC ranges for Enterobacterales and nonfermenting Gram-negative bacilli (NF-GNB) were ≤0.03 to 1 mg/L and 0.06 to 2 (IMP), 0.06 to 8 mg/L and 0.06 to 16 (VIM), 0.25 to 16 mg/L and 2 to 16 mg/L (NDM), respectively, and 0.25 to 8 mg/L for double MBL-producing Enterobacterales. By species, all cefiderocol-susceptible rates were over 90%, except Klebsiella oxytoca, Enterobacter cloacae, Escherichia coli, and Acinetobacter spp. Significant differences were observed comparing resistant isolates between Enterobacterales and NF-GNB by EUCAST (19.4% versus 4.2%, P < 0.01), but not by CLSI (4.4% versus 1.4%, P = 0.2). Cefiderocol was the most active antimicrobial tested. Cefiderocol showed excellent in vitro activity against MBL-GNB, especially NF-GNB; almost all isolates resistant to comparators were susceptible. IMPORTANCE This article demonstrates the efficacy of cefiderocol against a large collection of well-characterized metallo-beta-lactamase-producing isolates, some of them even producing double carbapenemases. Furthermore, cefiderocol activity is compared to other novel broad-spectrum antimicrobials with activity against carbapenemases.
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Antibacterianos , Anti-Infecciosos , Antibacterianos/farmacologia , Escherichia coli , Espanha , Bactérias Gram-Negativas , beta-Lactamases , CefiderocolRESUMO
At 17 wk of age, 1,800 Lohman brown hens were housed in 8 pens of an experimental aviary system, specifically set up for the purposes of the present study, and kept until 26 wk without or with nest lighting (lights inside the nest 1.5 h before the lighting of the installation) for training in the nest use. Then, at 27 wk, 4 combinations of nest curtains were adopted to evaluate the effects on hens' distribution, that is, nests with red (RR) or yellow (YY) curtains at all tiers; nests with red and yellow curtains at the first and second tier, respectively (RY); or nests with yellow and red curtains at the first and second tier, respectively (YR). The use of enlightened compared to dark nests at housing increased the oviposition rate (P < 0.001) and decreased the rate of broken (P < 0.001) and dirty eggs (P < 0.05) from 27 to 45 wk, while increasing the rate of eggs laid inside the nests (P < 0.001). The presence of yellow nest curtains increased the rate of hens on the floor in pens YY and YR compared to pens RR and RY (35.3 and 35.5% vs. 34.1 and 33.3%, respectively; P = 0.05) and the rate of floor eggs in pens YR (2.23% vs. 1.63 and 1.65% in pens RR and RY; P < 0.05). In pens RY, a higher rate of eggs was always found on the second tier compared to the first one with the most inhomogeneous distribution compared to pens RR, YY, and YR (+10.8 vs. +3.4, +1.9, and +4.6 percentage points of eggs laid on the second tier compared to the first one, respectively). In conclusion, nest lighting at housing trained hens to the use of nests while improving egg production in terms of quantity and quality. The use of yellow curtains on nests moved hens between the different levels of the aviary but this was not associated with an increased nest use for laying.
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Galinhas , Abrigo para Animais , Animais , Feminino , Iluminação , Criação de Animais Domésticos , Óvulo , OviposiçãoRESUMO
The suppression of the SOS response has been shown to enhance the in vitro activity of quinolones. Furthermore, Dam-dependent base methylation has an impact on susceptibility to other antimicrobials affecting DNA synthesis. Here, we investigated the interplay between these two processes, alone and in combination, in terms of antimicrobial activity. A genetic strategy was used employing single- and double-gene mutants for the SOS response (recA gene) and the Dam methylation system (dam gene) in isogenic models of Escherichia coli both susceptible and resistant to quinolones. Regarding the bacteriostatic activity of quinolones, a synergistic sensitization effect was observed when the Dam methylation system and the recA gene were suppressed. In terms of growth, after 24 h in the presence of quinolones, the Δdam ΔrecA double mutant showed no growth or delayed growth compared to the control strain. In bactericidal terms, spot tests showed that the Δdam ΔrecA double mutant was more sensitive than the ΔrecA single mutant (about 10- to 102-fold) and the wild type (about 103- to 104-fold) in both susceptible and resistant genetic backgrounds. Differences between the wild type and the Δdam ΔrecA double mutant were confirmed by time-kill assays. The suppression of both systems, in a strain with chromosomal mechanisms of quinolone resistance, prevents the evolution of resistance. This genetic and microbiological approach demonstrated the enhanced sensitization of E. coli to quinolones by dual targeting of the recA (SOS response) and Dam methylation system genes, even in a resistant strain model.
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Proteínas de Escherichia coli , Quinolonas , Escherichia coli , Antibacterianos/farmacologia , Resposta SOS em Genética , Epigenoma , Proteínas de Escherichia coli/genética , Quinolonas/farmacologia , Mutação/genéticaRESUMO
RecA inhibition could be an important strategy to combat antimicrobial resistance because of its key role in the SOS response, DNA repair and homologous recombination contributing to bacterial survival. This study evaluated the impact of RecA inactivation on heteroresistance in clinical isolates of Escherichia coli and their corresponding recA-deficient isogenic strains to multiple classes of antimicrobial agents. A high frequency (>30%) of heteroresistance was observed in this collection of clinical isolates. Deletion of the recA gene led to a marked reduction in heteroresistant subpopulations, especially against quinolones or ß-lactams. The molecular basis of heteroresistance was associated with an increase in copy number of plasmid-borne resistance genes (blaTEM-1B) or tandem gene amplifications (qnrA1). Of note, in the absence of the recA gene, the increase in copy number of resistance genes was suppressed. This makes the recA gene a promising target for combating heteroresistance.
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Escherichia coli , Quinolonas , Escherichia coli/genética , Plasmídeos/genética , Reparo do DNARESUMO
Objectives:To evaluate human-like intravenous doses of fosfomycin (8g/Q8h) and amikacin (15mg/kg/Q24h) efficacy in monotherapy and in combination against six fosfomycin-heteroresistant Escherichia coli isolates using a hollow-fiber infection model (HFIM).Materials and methods:Six fosfomycin-heteroresistant E. coli isolates (4 with strong mutator phenotype) and the control strain E. coli ATCC 25922 were used. Mutant frequencies for rifampin (100mg/L), fosfomycin (50 and 200mg/L) and amikacin (32mg/L) were determined. Fosfomycin and amikacin MICs were assessed by agar dilution (AD), gradient strip (GSA) and broth microdilution (BMD) assays. Fosfomycin and amikacin synergies were studied by checkerboard and time-kill assays at different concentrations. Fosfomycin (8g/Q8h) and amikacin (15mg/kg/Q24h) efficacy alone and in combination were assessed using a HFIM.Results:Five isolates were resistant to fosfomycin by AD and BMD, but all susceptible by GSA. All isolates were considered susceptible to amikacin. Antibiotic combinations were synergistic in two isolates and no antagonism was detected. In time-kill assays, all isolates survived under fosfomycin at 64mg/L, although, at 307mg/L, only the normomutators and two hypermutators survived. Four isolates survived under 16mg/L amikacin and none at 45mg/L. No growth was detected under combination conditions. In HFIM, fosfomycin and amikacin monotherapies failed to sterilise bacterial cultures, however, fosfomycin and amikacin combination showed a rapid eradication.Conclusions.There may be a risk of treatment failure of fosfomycin-heteroresistant E. coli isolates using either amikacin or fosfomycin in monotherapy. These results support that the combination amikacin-fosfomycin can rapidly decrease bacterial burden and prevent the emergence of resistant subpopulations against fosfomycin-heteroresistant strains.
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Background and objectives: An increase in emotional disturbances and complaints about cognitive performance has been observed in Latin American healthcare workers during the SARS-CoV-2 pandemic, which can affect attention capacity and increase the levels of stress and burnout of these professionals. The objective was to analyse subjective cognitive complaints (SCC) and associated factors in health personnel during the COVID-19 pandemic in five Latin American countries.Methods: Multicentre cross-sectional study, which included 3,738 professionals from Colombia, Chile, Argentina, Ecuador, Bolivia, and Peru. The Generalized Anxiety Disorder Scale (GAD-7) and the Patient Health Questionnaire (PHQ-9) was used to assess depression, and the Mini-Z to assess Burnout. For the SCC, an item on cognitive concerns in attention and memory was used.Results: The prevalence of cognitive complaints was 69.2%. The factors associated with a higher risk of SCC were the scores in the GAD-7, PHQ and Mini-Z, in addition to being part of the Ecuadorian health personnel.Conclusions: There is a high prevalence of SCC in health personnel, which is modulated by emotional states and stress.
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Introduction: Recent reports have shown several cases of cerebrovascular events after vaccination against COVID-19. The effects have been described mainly in women within the first two weeks of receiving the vaccine. Clinical Case: We describe here the first Colombian case of a cerebrovascular event after vaccination against COVID-19 in a 67-year-old woman with a vascular history. Four days after application of the messenger ribonucleic acid (mRNA) vaccine, she exhibited deviation of the labial commissure, ipsilateral ptosis, and limitation of march with lateralization. The event was associated with a subacute ischemic event in the right thalamus in parasagittal situation, changes in chronic ischemic microangiopathy of small vessels, and vascular crossing in the right cerebellar angle, without other alternative causes. Conclusion: The development and rapid use of vaccines has allowed the hospitalization and mortality statistics associated with COVID-19 to be reduced, but at the same time, it has generated concern about the potential side effects, generating controversy among the general population, especially in individuals with cardiovascular diseases. In our case, we provided evidence for the discussion of potential cerebrovascular events related to the application of vaccines in older people with a history of cerebrovascular diseases. This was done in order to analyze and control in subsequent studies the modulation of medical history on the likely effects of vaccination. However, despite the unavoidable side effects, the benefits of vaccination are superior.
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BACKGROUND: Recently, interest in the use of herbs and phytogenic compounds has grown because of their potential role in the production and health of livestock animals. Among these compounds, several tannins have been tested in poultry, but those from chestnut wood and grape-industry byproducts have attracted remarkable interest. Thus, the present study aimed to gain further insights into the mechanisms involved in the response to the dietary supplementation with extracts of chestnut wood or grape pomace. To this purpose, 864 broiler chickens were fed a control diet (C) or the same diet supplemented 0.2% chestnut wood (CN) extract or 0.2% grape pomace (GP) extract from hatching until commercial slaughtering (at 45 days of age) to assess their effects on performance, meat quality, jejunum immune response and whole-transcriptome profiling in both sexes at different ages (15 and 35 d). RESULTS: Final live weight and daily weight gain significantly increased (P < 0.01) in chickens fed GP diets compared to CN and C diets. The villi height was lower in chickens fed the CN diet than in those fed the C diet (P < 0.001); moreover, a lower density of CD45+ cells was observed in chickens fed the CN diet (P < 0.05) compared to those fed the C and GP diets. Genes involved in either pro- or anti-inflammatory response pathways, and antimicrobial and antioxidant responses were affected by GP and CN diets. There was no effect of the dietary treatment on meat quality. Regarding sex, in addition to a lower growth performance, females showed a lower occurrence of wooden breast (16.7% vs. 55.6%; P < 0.001) and a higher occurrence of spaghetti meat (48.6% vs. 4.17%; P < 0.001) in pectoralis major muscles after slaughtering than those in males. Based on the results of whole-transcriptome profiling, a significant activation of some molecular pathways related to immunity was observed in males compared with those of females. CONCLUSIONS: The GP supplementation improved chicken performance and promoted immune responses in the intestinal mucosa; moreover, age and sex were associated with the most relevant transcriptional changes.
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In most eukaryotes, pairing of homologous chromosomes is an essential feature of meiosis that ensures homologous recombination and segregation. However, when the pairing process begins, it is still under investigation. Contrasting data exists in Mus musculus, since both leptotene DSB-dependent and preleptotene DSB-independent mechanisms have been described. To unravel this contention, we examined homologous pairing in pre-meiotic and meiotic Mus musculus cells using a three-dimensional fluorescence in situ hybridization-based protocol, which enables the analysis of the entire karyotype using DNA painting probes. Our data establishes in an unambiguously manner that 73.83% of homologous chromosomes are already paired at premeiotic stages (spermatogonia-early preleptotene spermatocytes). The percentage of paired homologous chromosomes increases to 84.60% at mid-preleptotene-zygotene stage, reaching 100% at pachytene stage. Importantly, our results demonstrate a high percentage of homologous pairing observed before the onset of meiosis; this pairing does not occur randomly, as the percentage was higher than that observed in somatic cells (19.47%) and between nonhomologous chromosomes (41.1%). Finally, we have also observed that premeiotic homologous pairing is asynchronous and independent of the chromosome size, GC content, or presence of NOR regions.
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Meiose , Prófase Meiótica I , Animais , Camundongos , Masculino , Hibridização in Situ Fluorescente , Cariótipo , EspermatócitosRESUMO
Early diagnosis and treatment has an important impact on the morbidity and mortality of infections caused by multidrug-resistant bacteria. Multidrug-resistant gram-negative bacilli (MR-GNB) constitute the main current threat in hospitals and especially in intensive care units (ICU). The role of the microbiology laboratory is essential in providing a rapid and effective response. This review updates the microbiology laboratory procedures for the rapid detection of BGN-MR and its resistance determinants. The role of the laboratory in the surveillance and control of outbreaks caused by these bacteria, including typing techniques, is also studied. The importance of providing standardized resistance maps that allow knowing the epidemiological situation of the different units is emphasized. Finally, the importance of effective communication systems for the transmission of results and decision making in the management of patients infected by BGN-MR is reviewed.
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Infecções por Bactérias Gram-Negativas , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Bactérias Gram-Negativas , Infecções por Bactérias Gram-Negativas/diagnóstico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/epidemiologia , Humanos , Unidades de Terapia IntensivaRESUMO
A total 302 teeth (148 molars and 154 premolars) corresponding to 152 patients aged ≥18 years were evaluated for caries using the ICDAS (International Caries Detection and Assessment System), fluorescence (DD, DIAGNOdent) and electrical impedance (IMS, CarieScan PRO) systems. Fissurotomy and intraoral radiographs were used as the gold standard. Accordingly, 27.5% (n=84) of the teeth were classified as sound, while 26.9% (n=81) had enamel involvement and 45.6% (n=138) presented carious lesions reaching the dentin. Sensitivity (Se), specificity (Sp), and the area under the curve (AUC) were, respectively, 90.7%, 87.8%, and 0.954 (IMS); 92.4%, 92.7%, and 0.954 (DD); and 79.0%, 72.3%, and 0.756 (ICDAS). With regard to Se and Sp, there were significant differences between ICDAS and DD (p<0.001) and between ICDAS and IMS (p=0.01), but not between IMS and DD (p=0.07). In relation to AUC, there were significant differences between ICDAS and DD (p<0.001), and between ICDAS and IMS (p<0.001), but not between IMS and DD (p>0.05). The correlations between fissurotomy and each method were 88.7% (IMS), 89.7% (DD), and 77.1% (ICDAS). Within the limitations of this study, clinically, the electrical system is not useful for differentiating between sound teeth and truly incipient caries lesions by itself. The fluorescence or electrical systems are recommended with the ICDAS to detect carious lesions in their early stages.
Assuntos
Cárie Dentária , Espectroscopia Dielétrica , Adolescente , Adulto , Cárie Dentária/diagnóstico , Cárie Dentária/patologia , Esmalte Dentário/patologia , Fluorescência , Humanos , Dente Molar/patologia , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
The need for alternatives to antibiotic therapy due to the emergence of multidrug resistant bacteria (MDR), such as the nosocomial pathogen Acinetobacter baumannii, has led to the recovery of phage therapy. In addition, phages can be combined in cocktails to increase the host range. In this study, the evolutionary mechanism of adaptation was utilized in order to develop a phage adapted to A. baumannii, named phage Ab105-2phiΔCI404ad, from a mutant lytic phage, Ab105-2phiΔCI, previously developed by our group. The whole genome sequence of phage Ab105-2phiΔCI404ad was determined, showing that four genomic rearrangements events occurred in the tail morphogenesis module affecting the ORFs encoding the host receptor binding sites. As a consequence of the genomic rearrangements, 10 ORFs were lost and four new ORFs were obtained, all encoding tail proteins; two inverted regions were also derived from these events. The adaptation process increased the host range of the adapted phage by almost 3-fold. In addition, a depolymerase-expressing phenotype, indicated by formation of a halo, which was not observed in the ancestral phage, was obtained in 81% of the infected strains. A phage cocktail was formed by combining this phage with the A. baumannii phage vB_AbaP_B3, known to express a depolymerase. Both the individual phages and the phage cocktail showed strong antimicrobial activity against 5 clinical strains and 1 reference strain of A. baumannii tested. However, in all cases resistance to the bacterial strains was also observed. The antibiofilm activity of the individual phages and the cocktail was assayed. The phage cocktail displayed strong antibiofilm activity.