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BACKGROUND COVID-19 increases the risk of acute cardiovascular diseases (CVDs), including acute coronary syndrome (ACS), acute pulmonary embolism (APE), and acute myocarditis (AMyo). The actual impact of CVDs on mortality of patients with COVID-19 remains unknown. This study aimed to determine whether CVDs influence the course of COVID-19 pneumonia and if they can be easily detected by using common tests and examinations. MATERIAL AND METHODS Data of 249 consecutive patients with COVID-19 hospitalized in a dedicated cardiology department were analyzed. On admission, clinical status, biomarkers, computed tomography, and bedside echocardiography were performed. RESULTS D-dimer level predicted APE (AUC=0.850 95% CI [0.765; 0.935], P<0.001) with sensitivity of 69.4% and specificity of 96.2% for a level of 4968.0 ng/mL, and NT-proBNP predicted AMyo (AUC=0.692 95% CI [0.502; 0.883], P=0.004) and showed sensitivity of 54.5%, with specificity of 86.5% for the cut-off point of 8970 pg/mL. Troponin T levels were not useful for diagnostic differentiation between CVDs. An extent of lung involvement predicted mortality (OR=1.03 95% CI [1.01;1.04] for 1% increase, P<0.001). After adjusting for lung involvement, ACS increased mortality, compared with COVID-19 pneumonia only (OR=5.27 95% CI [1.76; 16.38] P=0.003), while APE and AMyo did not affect risk for death. CONCLUSIONS D-dimer and NT-proBNP, but not troponin T, are useful in differentiating CVDs in patients with COVID-19. ACS with COVID-19 increased in-hospital mortality independently from extent of lung involvement, while coexisting APE or AMyo did not.
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Síndrome Coronariana Aguda , COVID-19 , Doenças Cardiovasculares , Produtos de Degradação da Fibrina e do Fibrinogênio , Peptídeo Natriurético Encefálico , Embolia Pulmonar , Humanos , COVID-19/complicações , COVID-19/mortalidade , COVID-19/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Idoso , Embolia Pulmonar/diagnóstico , Síndrome Coronariana Aguda/complicações , Síndrome Coronariana Aguda/diagnóstico , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , SARS-CoV-2 , Biomarcadores/sangue , Miocardite , Ecocardiografia/métodos , Doença Aguda , Encaminhamento e Consulta , Troponina T/sangueRESUMO
BACKGROUND: The European bison (Bison bonasus) is a near threatened species and requires health monitoring. The aim of the present study was to determine the prevalence of antibodies to pathogens known to cause respiratory and digestive illness in ruminants. RESULTS: In the studied 328 European bison, the highest seroprevalence was observed for Bovine herpesvirus-1 (BoHV-1) (50.27%), Bovine Coronavirus (BCoV) (26.36%), and Bluetongue Virus (BTV) (12.83%). For Mycoplasma bovis strains and Bovine Viral Diarrhea Virus (BVDV), positive results were rare. Interestingly, a higher prevalence of BTV antibodies was noted in the northeastern populations and older animals. CONCLUSIONS: Our findings indicate that the Polish European bison population appears to have considerable contact with BoHV-1; however, this does not appear to be of great significance, as clinical symptoms and post-mortem lesions are rarely noted in Polish European bison population. The high seroprevalence of BTV in the north-east of Poland is an ongoing trend, also noted in previous studies. It is possible that European bison may perpetuate the virus in this region. This is the first report of antibodies for BCoV in European bison.
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Bison , Herpesvirus Bovino 1 , Animais , Polônia/epidemiologia , Estudos Soroepidemiológicos , Anticorpos Antivirais , Sistema DigestórioRESUMO
Electrophysiological recordings of neuronal activity show spontaneous and task-dependent changes in their frequency-domain power spectra. These changes are conventionally interpreted as modulations in the amplitude of underlying oscillations. However, this overlooks the possibility of underlying transient spectral 'bursts' or events whose dynamics can map to changes in trial-average spectral power in numerous ways. Under this emerging perspective, a key challenge is to perform burst detection, i.e. to characterise single-trial transient spectral events, in a principled manner. Here, we describe how transient spectral events can be operationalised and estimated using Hidden Markov Models (HMMs). The HMM overcomes a number of the limitations of the standard amplitude-thresholding approach to burst detection; in that it is able to concurrently detect different types of bursts, each with distinct spectral content, without the need to predefine frequency bands of interest, and does so with less dependence on a priori threshold specification. We describe how the HMM can be used for burst detection and illustrate its benefits on simulated data. Finally, we apply this method to empirical data to detect multiple burst types in a task-MEG dataset, and illustrate how we can compute burst metrics, such as the task-evoked timecourse of burst duration.
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Eletrofisiologia/métodos , Neurônios/fisiologia , Fenômenos Eletrofisiológicos , Humanos , Cadeias de Markov , Modelos NeurológicosRESUMO
OBJECTIVES: Maternal pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) have a meaningful impact on pregnancy and perinatal outcomes. The first aim of the study was to analyze the association between pre-pregnancy BMI and the prevalence of small for gestational age (SGA) and large for gestational age (LGA) outcomes. The second aim was to assess the relation- ship between pre-pregnancy BMI combined with gestational weight gain (GWG) and the prevalence of SGA and LGA measurements. MATERIAL AND METHODS: The retrospective cohort study was conducted at Jagiellonian University Hospital in Cracow, Po- land from 2016 to 2017. During this time there were 2,123 deliveries. Patients with chronic diseases, multiple pregnancies, fetal defects and incomplete data were excluded. Finally, 474 cases were enrolled. Patients were divided into BMI groups (underweight, normal, overweight and obese) and into GWG groups (inadequate, adequate, excessive). Relationships between maternal BMI, GWG and newborn weight were examined. RESULTS: There was no statistically significant association between maternal pre-pregnancy BMI and prevalence of SGA measurements. However, underweight women with inadequate GWG showed a higher risk to bear SGA babies (OR 5.2, 95% CI 1.57-17.18). Obese women with adequate GWG had higher risk of bearing LGA newborns (OR 5.48, 95% CI 1.15-26.13). High BMI correlated with excessive GWG (overweight: OR 3.0, 95% CI 1.84-3.87; obese OR 2.45, 95% CI 1.1-5.48). CONCLUSIONS: There is a considerable risk of giving birth to a SGA newborn for underweight women with inadequate GWG. There is a statistically significant association between maternal obesity and LGA outcomes. Our study shows that redefining the risks of abnormal neonatal weight considering both pre-pregnancy BMI and gestational weight gain can be useful in providing effective prevention during pregnancy.
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Peso ao Nascer/fisiologia , Índice de Massa Corporal , Ganho de Peso na Gestação/fisiologia , Gravidez/estatística & dados numéricos , Adulto , Feminino , Humanos , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Estudos RetrospectivosRESUMO
INTRODUCTION: Induction of labor is an intervention in the obstetrics, which aim is to achieve cervical ripening and stimulate contractions of uterus before beginning of labor. The purpose of our study was to evaluate efficacy of combinations of vaginal misoprostol, intracervical dinoprostone and Foley catheter at term with regard to mode of delivery and rate of emergency C-sections due to birth asphyxia. MATERIAL AND METHODS: 403 singleton pregnant women, who underwent pharmacological labor induction at term, were reviewed. Patients were divided into 2 main cohorts due to beginning of induction algorithm: vaginal misoprostol (66) or intracervical dinoprostone (337) consisting of 3 subgroups - PGE2 alone (184), PGE2+Foley catheter (125), PGE2+Foley catheter+PGE1 (28). RESULTS: Comparison of maternal age, presence of cervical dilation and parity revealed no major differences between cohorts. Effectiveness of labor induction with misoprostol, dinoprostone and dinoprostone followed by Foley catheter were respectively 90.9%, 51.3%, and 82.8%. Addition of PGE1 was effective in 83% of patients with negative response to PGE2 followed by Foley catheter. ere was no statistically significant difference in rate of C-sections between dinoprostone and misoprostol cohorts, C-section due to birth asphyxia were insignificantly more frequent in PGE1 than in PGE2 cohort. Efficacy in the subgroup administered only dinoprostone was significantly higher in 40th than in 41th (p = 0.016). CONCLUSIONS: Intracervical dinoprostone seems to be safer, but less effective in labor induction than vaginal misoprostol. Following PGE2 by other methods increased efficacy of induction in this cohort.
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Cateterismo/métodos , Dinoprostona/administração & dosagem , Trabalho de Parto Induzido/métodos , Misoprostol/administração & dosagem , Resultado da Gravidez , Adulto , Estudos de Casos e Controles , Colo do Útero/efeitos dos fármacos , Cesárea/métodos , Feminino , Humanos , Gravidez , Resultado do Tratamento , Adulto JovemRESUMO
Beta and gamma oscillations are the dominant oscillatory activity in the human motor cortex (M1). However, their physiological basis and precise functional significance remain poorly understood. Here, we used transcranial magnetic stimulation (TMS) to examine the physiological basis and behavioral relevance of driving beta and gamma oscillatory activity in the human M1 using transcranial alternating current stimulation (tACS). tACS was applied using a sham-controlled crossover design at individualized intensity for 20 min and TMS was performed at rest (before, during, and after tACS) and during movement preparation (before and after tACS). We demonstrated that driving gamma frequency oscillations using tACS led to a significant, duration-dependent decrease in local resting-state GABAA inhibition, as quantified by short interval intracortical inhibition. The magnitude of this effect was positively correlated with the magnitude of GABAA decrease during movement preparation, when gamma activity in motor circuitry is known to increase. In addition, gamma tACS-induced change in GABAA inhibition was closely related to performance in a motor learning task such that subjects who demonstrated a greater increase in GABAA inhibition also showed faster short-term learning. The findings presented here contribute to our understanding of the neurophysiological basis of motor rhythms and suggest that tACS may have similar physiological effects to endogenously driven local oscillatory activity. Moreover, the ability to modulate local interneuronal circuits by tACS in a behaviorally relevant manner provides a basis for tACS as a putative therapeutic intervention.SIGNIFICANCE STATEMENT Gamma oscillations have a vital role in motor control. Using a combined tACS-TMS approach, we demonstrate that driving gamma frequency oscillations modulates GABAA inhibition in the human motor cortex. Moreover, there is a clear relationship between the change in magnitude of GABAA inhibition induced by tACS and the magnitude of GABAA inhibition observed during task-related synchronization of oscillations in inhibitory interneuronal circuits, supporting the hypothesis that tACS engages endogenous oscillatory circuits. We also show that an individual's physiological response to tACS is closely related to their ability to learn a motor task. These findings contribute to our understanding of the neurophysiological basis of motor rhythms and their behavioral relevance and offer the possibility of developing tACS as a therapeutic tool.
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Comportamento/fisiologia , Córtex Motor/fisiologia , Receptores de GABA-A/fisiologia , Estimulação Transcraniana por Corrente Contínua , Estimulação Magnética Transcraniana , Adulto , Estudos Cross-Over , Eletromiografia , Potencial Evocado Motor/fisiologia , Feminino , Humanos , Interneurônios/fisiologia , Aprendizagem/fisiologia , Magnetoencefalografia , Masculino , Desempenho Psicomotor/fisiologia , Tempo de Reação/fisiologia , Adulto JovemRESUMO
Skewing of the human oral microbiome causes dysbiosis and preponderance of bacteria such as Porphyromonas gingivalis, the main etiological agent of periodontitis. P. gingivalis secretes proteolytic gingipains (Kgp and RgpA/B) as zymogens inhibited by a pro-domain that is removed during extracellular activation. Unraveling the molecular mechanism of Kgp zymogenicity is essential to design inhibitors blocking its activity. Here, we found that the isolated 209-residue Kgp pro-domain is a boomerang-shaped all-ß protein similar to the RgpB pro-domain. Using composite structural information of Kgp and RgpB, we derived a plausible homology model and mechanism of Kgp-regulating zymogenicity. Accordingly, the pro-domain would laterally attach to the catalytic moiety in Kgp and block the active site through an exposed inhibitory loop. This loop features a lysine (Lys129) likely occupying the S1 specificity pocket and exerting latency. Lys129 mutation to glutamate or arginine led to misfolded protein that was degraded in vivo Mutation to alanine gave milder effects but still strongly diminished proteolytic activity, without affecting the subcellular location of the enzyme. Accordingly, the interactions of Lys129 within the S1 pocket are also essential for correct folding. Uniquely for gingipains, the isolated Kgp pro-domain dimerized through an interface, which partially overlapped with that between the catalytic moiety and the pro-domain within the zymogen, i.e. both complexes are mutually exclusive. Thus, pro-domain dimerization, together with partial rearrangement of the active site upon activation, explains the lack of inhibition of the pro-domain in trans. Our results reveal that the specific latency mechanism of Kgp differs from those of Rgps.
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Adesinas Bacterianas/química , Cisteína Endopeptidases/química , Precursores Enzimáticos/química , Porphyromonas gingivalis/enzimologia , Porphyromonas gingivalis/patogenicidade , Fatores de Virulência/química , Adesinas Bacterianas/genética , Adesinas Bacterianas/metabolismo , Infecções por Bacteroidaceae/enzimologia , Infecções por Bacteroidaceae/genética , Cisteína Endopeptidases/genética , Cisteína Endopeptidases/metabolismo , Precursores Enzimáticos/genética , Precursores Enzimáticos/metabolismo , Cisteína Endopeptidases Gingipaínas , Gengivite/enzimologia , Gengivite/genética , Humanos , Microbiota , Boca/microbiologia , Porphyromonas gingivalis/genética , Domínios Proteicos , Multimerização Proteica , Relação Estrutura-Atividade , Fatores de Virulência/metabolismoRESUMO
Air breathing is an essential motor function for vertebrates living on land. The rhythm that drives breathing is generated within the central nervous system and relayed via specialised subsets of spinal motor neurons to muscles that regulate lung volume. In mammals, a key respiratory muscle is the diaphragm, which is innervated by motor neurons in the phrenic nucleus. Remarkably, relatively little is known about how this crucial subtype of motor neuron is generated during embryogenesis. Here, we used direct differentiation of motor neurons from mouse embryonic stem cells as a tool to identify genes that direct phrenic neuron identity. We find that three determinants, Pou3f1, Hoxa5 and Notch, act in combination to promote a phrenic neuron molecular identity. We show that Notch signalling induces Pou3f1 in developing motor neurons in vitro and in vivo. This suggests that the phrenic neuron lineage is established through a local source of Notch ligand at mid-cervical levels. Furthermore, we find that the cadherins Pcdh10, which is regulated by Pou3f1 and Hoxa5, and Cdh10, which is controlled by Pou3f1, are both mediators of like-like clustering of motor neuron cell bodies. This specific Pcdh10/Cdh10 activity might provide the means by which phrenic neurons are assembled into a distinct nucleus. Our study provides a framework for understanding how phrenic neuron identity is conferred and will help to generate this rare and inaccessible yet vital neuronal subtype directly from pluripotent stem cells, thus facilitating subsequent functional investigations.
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Caderinas/metabolismo , Células-Tronco Embrionárias/citologia , Neurônios Motores/citologia , Fator 6 de Transcrição de Octâmero/metabolismo , Nervo Frênico/embriologia , Transdução de Sinais/fisiologia , Animais , Diferenciação Celular/fisiologia , Diafragma/inervação , Citometria de Fluxo , Proteínas de Homeodomínio/metabolismo , Camundongos , Neurônios Motores/fisiologia , Fosfoproteínas/metabolismo , Nervo Frênico/citologia , Protocaderinas , Reação em Cadeia da Polimerase em Tempo Real , Receptores Notch/metabolismo , Transdução de Sinais/genética , Fatores de Transcrição , TranscriptomaRESUMO
The human motor cortex has a tendency to resonant activity at about 20 Hz so stimulation should more readily entrain neuronal populations at this frequency. We investigated whether and how different interneuronal circuits contribute to such resonance by using transcranial magnetic stimulation (TMS) during transcranial alternating current stimulation (tACS) at motor (20 Hz) and a nonmotor resonance frequency (7 Hz). We tested different TMS interneuronal protocols and triggered TMS pulses at different tACS phases. The effect of cholinergic short-latency afferent inhibition (SAI) was abolished by 20 Hz tACS, linking cortical beta activity to sensorimotor integration. However, this effect occurred regardless of the tACS phase. In contrast, 20 Hz tACS selectively modulated MEP size according to the phase of tACS during single pulse, GABAAergic short-interval intracortical inhibition (SICI) and glutamatergic intracortical facilitation (ICF). For SICI this phase effect was more marked during 20 Hz stimulation. Phase modulation of SICI also depended on whether or not spontaneous beta activity occurred at ~20 Hz, supporting an interaction effect between tACS and underlying circuit resonances. The present study provides in vivo evidence linking cortical beta activity to sensorimotor integration, and for beta oscillations in motor cortex being promoted by resonance in GABAAergic interneuronal circuits.
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Ritmo beta/fisiologia , Neurônios Colinérgicos/fisiologia , Interneurônios/fisiologia , Córtex Motor/fisiologia , Inibição Neural/fisiologia , Adulto , Estimulação Elétrica , Eletromiografia , Potenciais Somatossensoriais Evocados/fisiologia , Feminino , Humanos , Masculino , Nervo Mediano/fisiologia , Processamento de Sinais Assistido por Computador , Método Simples-Cego , Estimulação Transcraniana por Corrente Contínua , Estimulação Magnética Transcraniana , Punho/fisiologia , Adulto JovemRESUMO
OBJECTIVES: The aim of the study was to assess the level of implementation of recommendations of the Ministry of Health regarding infectious disease screening during pregnancy. MATERIAL AND METHODS: The study included 477 patients who were admitted to the delivery room between December 2015 and February 2016. Data on screening test results were collected based on medical records covering the period before the admission. RESULTS: The Human Immunodeficiency Virus (HIV) screening was conducted in 410 (86%). 460 (96%) of patients were screened for Hepatitis B Virus (HBV) and 427 (89.5%) for Hepatitis C Virus (HCV). Syphilis screening covered 465 (97.5%) of patients. Immunoglobulin M (IgM) titer against Rubella Virus (RV) was assessed in 218 (45%) patients and immunoglobulin G (IgG) in 319 (66.9%). Screening for Toxoplasma gondii based on assessment of IgM titer was conducted in 440 (92%) patients while IgG titter was assessed in 413 (86.6%). 343 (71.9%) patients had obtained vaginal swabs for Group B Streptococci (GBS) while the anal swabs were taken only from 268 (56.2%) patients. CONCLUSIONS: Coverage of screening for syphilis and HBV was similar to the countries with highest prevalence of conducting such screening, on the other hand RV screening place as among countries with lowest prevalence. There is an increasing trend in conducting HIV screening. Screening for HCV and toxoplasmosis is at satisfactory level and Poland is one of a few European countries offering such screening. The screening for GBS is insufficient which result in excessive use of intrapartum antibiotic prophylaxis.
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Doenças Transmissíveis/diagnóstico , Programas de Rastreamento/estatística & dados numéricos , Complicações Infecciosas na Gravidez/diagnóstico , Cuidado Pré-Natal/estatística & dados numéricos , Adulto , Doenças Transmissíveis/imunologia , União Europeia , Feminino , Infecções por HIV/diagnóstico , Hepatite B/diagnóstico , Hepatite B/imunologia , Hepatite C/diagnóstico , Hepatite C/imunologia , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Polônia , Gravidez , Complicações Infecciosas na Gravidez/imunologia , Rubéola (Sarampo Alemão)/diagnóstico , Rubéola (Sarampo Alemão)/imunologia , Vírus da Rubéola/imunologia , Testes Sorológicos , Infecções Estreptocócicas/diagnóstico , Streptococcus agalactiae , Sífilis/diagnóstico , Toxoplasma/imunologia , Toxoplasmose/diagnóstico , Toxoplasmose/imunologiaRESUMO
It is estimated that each year more than 2 million people suffer from diarrheal diseases, resulting from the consumption of contaminated meat. Foodborne infections are most frequently caused by small Gram-negative rods Campylobacter. The hosts of these bacteria are mainly birds wherein they are part of the normal intestinal flora. During the commercial slaughter, there is a likelihood of contamination of carcasses by the bacteria found in the intestinal content. In Europe, up to 90% of poultry flocks can be a reservoir of the pathogen. According to the European Food Safety Authority report from 2015, the number of reported and confirmed cases of human campylobacteriosis exceeds 200 thousands per year, and such trend remains at constant level for several years. The occurrence of growing antibiotic resistance in bacteria forces the limitation of antibiotic use in the animal production. Therefore, the European Union allows only using stringent preventive and hygienic treatment on farms. Achieving Campylobacter free chickens using these methods is possible, but difficult to implement and expensive. Utilization of bacterial viruses - bacteriophages, can be a path to provide the hygienic conditions of poultry production and food processing. Formulations applied in the food protection should contain strictly lytic bacteriophages, be non-pyrogenic and retain long lasting biological activity. Currently, on the market there are available commercial bacteriophage preparations for agricultural use, but neither includes phages against Campylobacter. However, papers on the application of bacteriophages against Campylobacter in chickens and poultry products were published in the last few years. In accordance with the estimates, 2-logarithm reduction of Campylobacter in poultry carcases will contribute to the 30-fold reduction in the incidence of campylobacteriosis in humans. Research on bacteriophages against Campylobacter have cognitive and economic importance. The paper presents current state of research on bacteriophages targeted against Campylobacter.
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Autosomal dominant polycystic kidney disease (ADPKD) is one of most common inherited renal diseases. It is estimated that very early onset ADPKD affects even 2% patients. The purpose of this article is to provide a comprehensive review of genetics, prenatal diagnosis and prognosis in very early onset autosomal dominant polycystic kidney disease.
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Rim Policístico Autossômico Dominante/diagnóstico , Diagnóstico Pré-Natal , Feminino , Aconselhamento Genético , Humanos , Rim Policístico Autossômico Dominante/genética , Gravidez , Diagnóstico Pré-Natal/métodos , PrognósticoRESUMO
PURPOSE. To investigate the expression of innate immunity components and cytokines in the gastric mucosa among H. pylori infected and uninfected children. Materials and Methods. Biopsies of the antral gastric mucosa from children with dyspeptic symptoms were evaluated. Gene expressions of innate immunity receptors and cytokines were measured by quantitative real-time PCR. The protein expression of selected molecules was tested by immunohistochemistry. RESULTS. H. pylori infection did not lead to a significant upregulation of MyD88, TLR2, TLR4, CD14, TREM1, and TREM2 mRNA expression but instead resulted in high mRNA expression of IL-6, IL-10, IFN-γ, TNF-α, and CD163. H. pylori cagA(+) infection was associated with higher IL-6 and IL-10 mRNA expression, as compared to cagA(-) strains. H. pylori infected children showed increased IFN-γ and TNF-α protein levels. IFN-γ mRNA expression correlated with both H. pylori density of colonization and lymphocytic infiltration in the gastric mucosa, whereas TNF-α protein expression correlated with bacterial density. CONCLUSION. H. pylori infection in children was characterized by (a) Th1 expression profile, (b) lack of mRNA overexpression of natural immunity receptors, and (c) strong anti-inflammatory activities in the gastric mucosa, possibly resulting from increased activity of anti-inflammatory M2 macrophages. This may explain the mildly inflammatory gastric inflammation often observed among H. pylori infected children.
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Citocinas/metabolismo , Mucosa Gástrica/imunologia , Infecções por Helicobacter/imunologia , Imunidade Inata , Adolescente , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Criança , Dispepsia/imunologia , Endoscopia , Feminino , Mucosa Gástrica/microbiologia , Regulação da Expressão Gênica , Genótipo , Helicobacter pylori , Humanos , Imuno-Histoquímica , Inflamação/imunologia , Interferon gama/imunologia , Interleucina-10/imunologia , Linfócitos/imunologia , Masculino , Fator 88 de Diferenciação Mieloide/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Receptores de Superfície Celular/metabolismo , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/imunologiaRESUMO
Interferons are a family of proteins that are released by a variety of cells in response to infections caused by viruses. Currently, we distinguish three types of interferons. They are classified based on the nucleotide sequence, interaction with specific receptors, chromosomal location, structure and physicochemical properties. The following interferons are classified as type I: α, ß, ω, κ, ε, ζ, τ, δ, ν. They are recognized and bound by a receptor formed by two peptides, IFN-αR1 and IFN-αR2. Representative of type II interferons is interferon-γ. It binds to a receptor composed of chains IFNGR-1 and IFNGR-2. The recently classified type III interferons comprise IFN-λ1, IFN-λ2, and IFN-λ3. They act on receptors formed by λR1 IFN-and IL-10R2 subunits. A high level of antiviral protection is achieved by IFN-α, IFN-ß and IFN-λ. Antiviral activity of interferons is based on the induction and regulation of innate and acquired immune mechanisms. By binding to transmembrane receptors, IFN interacts with target cells mainly by activating the JAK/STAT, but also other signaling pathways. This leads to induction and activation of many antiviral agents, such as protein kinase RNA-activated (PKR), ribonuclease 2-5A pathway, and Mx proteins, as well as numerous apoptotic pathways. As a result of the protective effect of interferons, the virus binding to cells and viral particles penetration into cells is stopped, and the release of the nucleocapsid from an envelope is suppressed. Disruption of transcription and translation processes of the structural proteins prevents the formation of virions or budding of viruses, and as a result degradation of the viral mRNA; the started processes inhibit the chain synthesis of viral proteins and therefore further stimulate the immune system cells.
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Interferons/química , Interferons/imunologia , Ativação Metabólica/imunologia , Animais , Antivirais/farmacologia , Apoptose/fisiologia , Humanos , Interferon-alfa/química , Interferon-alfa/imunologia , Interferon gama/química , Interferon gama/imunologia , Interferons/classificação , Substâncias Protetoras/metabolismo , RNA Viral/metabolismo , Transdução de Sinais/fisiologia , Proteínas Virais/química , Proteínas Virais/metabolismoRESUMO
Introduction: Pain assessment in horses presents a significant challenge due to their nonverbal nature and their tendency to conceal signs of discomfort in the presence of potential threats, including humans. Therefore, this study aimed to identify pain-associated behaviors amenable to automated AI-based detection in video recordings. Additionally, it sought to determine correlations between pain intensity and behavioral and postural parameters by analyzing factors such as time budgets, weight shifting, and unstable resting. The ultimate goal is to facilitate the development of AI-based quantitative tools for pain assessment in horses. Materials and methods: A cohort of 20 horses (mean age 15 ± 8) admitted to a university equine hospital underwent 24-h video recording. Behaviors were manually scored and retrospectively analyzed using Loopy® software. Three pain groups were established based on the Pain Score Vetmeduni Vienna : pain-free (P0), mild to moderate pain (P1), and severe pain (P2). Results: Weight shifting emerged as a reliable indicator for discriminating between painful and pain-free horses, with significant differences observed between pain groups (p < 0.001) and before and after administration of analgesia. Additionally, severely painful horses (P2 group) exhibited lower frequencies of feeding and resting standing per hour compared to pain-free horses, while displaying a higher frequency of unstable resting per hour. Discussion: The significant differences observed in these parameters between pain groups offer promising prospects for AI-based analysis and automated pain assessment in equine medicine. Further investigation is imperative to establish precise thresholds. Leveraging such technology has the potential to enable more effective pain detection and management in horses, ultimately enhancing welfare and informing clinical decision-making in equine medicine.
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INTRODUCTION: Alexander disease (AxD) is a rare neurodegenerative condition that represents the group of leukodystrophies. The disease is caused by GFAP mutation. Symptoms usually occur in the infantile age with macrocephaly, developmental deterioration, progressive quadriparesis, and seizures as the most characteristic features. In this case report, we provide a detailed clinical description of the neonatal type of AxD. METHOD: Next-Generation Sequencing (NGS), including a panel of 49 genes related to Early Infantile Epileptic Encephalopathy (EIEE), was carried out, and then Whole Exome Sequencing (WES) was performed on the proband's DNA extracted from blood. CASE DESCRIPTION: In the first weeks of life, the child presented with signs of increased intracranial pressure, which led to ventriculoperitoneal shunt implementation. Recurrent focal-onset motor seizures with secondary generalization occurred despite phenobarbital treatment. Therapy was modified with multiple anti-seizure medications. In MRI contrast-enhanced lesions in basal ganglia, midbrain and cortico-spinal tracts were observed. During the diagnostic process, GLUT-1 deficiency, lysosomal storage disorders, organic acidurias, and fatty acid oxidation defects were excluded. The NGS panel of EIEE revealed no abnormalities. In WES analysis, GFAP missense heterozygous variant NM_002055.5: c.1187C>T, p.(Thr396Ile) was detected, confirming the diagnosis of AxD. CONCLUSION: AxD should be considered in the differential diagnosis in all neonates with progressive, intractable seizures accompanied by macrocephaly.
Assuntos
Doença de Alexander , Doenças Ósseas , Doenças Desmielinizantes , Epilepsia Resistente a Medicamentos , Hiponatremia , Doenças por Armazenamento dos Lisossomos , Megalencefalia , Espasmos Infantis , Criança , Recém-Nascido , Humanos , Doença de Alexander/genética , Doença de Alexander/patologia , Proteína Glial Fibrilar Ácida/genética , Megalencefalia/genéticaRESUMO
Invasive vagus nerve stimulation has been demonstrated to be an effective treatment in major depressive episodes. Recently, a novel non-invasive method of stimulating the vagus nerve on the outer canal of the ear has been proposed. In healthy subjects, a prominent fMRI BOLD signal deactivation in the limbic system was found. The present pilot study investigates the effects of this novel technique of auricular transcutaneous electric nerve stimulation in depressed patients for the first time. A total of 37 patients suffering from major depression were included in two randomized sham controlled add-on studies. Patients were stimulated five times a week on a daily basis for the duration of 2 weeks. On days 0 and 14, the Hamilton Depression Rating Scale (HAMD) and the Beck Depression Inventory (BDI) were assessed. In contrast to sham-treated patients, electrically stimulated persons showed a significantly better outcome in the BDI. Mean decrease in the active treatment group was 12.6 (SD 6.0) points compared to 4.4 (SD 9.9) points in the sham group. HAMD score did not change significantly in the two groups. An antidepressant effect of a new transcutaneous auricular nerve stimulation technique has been shown for the first time in this controlled pilot study. Regarding the limitations of psychometric testing, the risk of unblinding for technical reasons, and the small sample size, further studies are necessary to confirm the present results and verify the practicability of tVNS in clinical fields.
Assuntos
Depressão/terapia , Estimulação Elétrica Nervosa Transcutânea/métodos , Nervo Vago/fisiologia , Adulto , Idoso , Antidepressivos/uso terapêutico , Encéfalo/irrigação sanguínea , Encéfalo/fisiopatologia , Depressão/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Escalas de Graduação Psiquiátrica , Estatísticas não Paramétricas , Estimulação Elétrica Nervosa Transcutânea/instrumentaçãoRESUMO
Drug-eluting stents (DES) demonstrated superior efficacy when compared to bare metal stents and plain-old balloon angioplasty and are nowadays used in almost all percutaneous revascularization procedures. The design of the stent platforms is constantly improving to maximize its efficacy and safety. Constant development of DES includes adoption of new materials used for scaffold production, new design types, improved overexpansion abilities, new polymers coating and, finally, improved antiproliferative agents. Especially nowadays, with the immense number of available DES platforms, it is crucial to understand how different aspects of stents impact the effect of their implantation, as subtle differences between various stent platforms could impact the most important issue-clinical outcomes. This review discusses the current status of coronary stents and the impact of stent material, strut design and coating techniques on cardiovascular outcomes.
RESUMO
Mycobacterial infections are significant issues in zoo animals, influencing animal welfare, conservation efforts, and the zoonotic potential of pathogens. Although tuberculosis is recognised to be highly dangerous, paratuberculosis can also lead to animal losses and is potentially dangerous for humans. The aim of the current study was to confirm whether Mycobacterium avium spp. paratuberculosis (MAP) infections are currently present in zoos in Poland. Faeces samples (n = 131) were collected from different animal species from eight zoos in Poland. The faeces were decontaminated and inoculated into Herrold's Egg Yolk Media. The species was determined using commercial DNA testing. The IS900 was checked using RT-PCR. The culture was positive in seven samples: five with M. avium, one with Mycobacterium fortiatum, and one without any identified Mycobacterium species. RT-PCR confirmed MAP genetic material in nine animals. Our findings represent the first confirmation of MAP in bongo (Tragelaphus eurycerus), indicating that it is present in Polish zoological gardens. Fortunately, the disease can be monitored more easily due to recent legislation (the Animal Health Law).
RESUMO
COQ8A-ataxia is a mitochondrial disease in which a defect in coenzyme Q10 synthesis leads to dysfunction of the respiratory chain. The disease is usually present as childhood-onset progressive ataxia with developmental regression and cerebellar atrophy. However, due to variable phenotype, it may be hard to distinguish from other mitochondrial diseases and a wide spectrum of childhood-onset cerebellar ataxia. COQ8A-ataxia is a potentially treatable condition with the supplementation of coenzyme Q10 as a main therapy; however, even 50% may not respond to the treatment. In this study we review the clinical manifestation and management of COQ8A-ataxia, focusing on current knowledge of coenzyme Q10 supplementation and approach to further therapies. Moreover, the case of a 22-month-old girl with cerebellar ataxia and developmental regression will be presented.