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BACKGROUND: The morbidity burden of respiratory syncytial virus (RSV) in infants extends beyond hospitalization. Defining the RSV burden before implementing prophylaxis programs is essential for evaluating any potential impact on short- to mid-term morbidity and the utilization of primary healthcare (PHC) and emergency services (ES). We established this reference data using a population-based cohort approach. METHODS: Infants hospitalized for RSV from January 2016 to March 2023 were matched with non-hospitalized ones based on birthdate and sex. We defined the exposure as severe RSV hospitalization. The main study outcomes were as follows: (1) PHC and ES visits for RSV, categorized using the International Classification of Primary Care codes, (2) prescriptions for respiratory airway obstructive disease, and (3) antibacterial prescriptions. Participants were followed up from 30 days before hospitalization for severe RSV until the outcome occurrence or end of the study. Adjusted incidence rate ratios (IRRs) of the outcomes along with their 95% confidence intervals (CI) were estimated using Poisson regression models. Stratified analyses by type of PHC visit (nurse, pediatrician, or pharmacy) and follow-up period were undertaken. We defined mid-term outcomes as those taking place up to 24 months of follow-up period. RESULTS: The study included 6626 children (3313 RSV-hospitalized; 3313 non-hospitalized) with a median follow-up of 53.7 months (IQR = 27.9, 69.4). After a 3-month follow-up, severe RSV was associated with a considerable increase in PHC visits for wheezing/asthma (IRR = 4.31, 95% CI: 3.84-4.84), lower respiratory infections (IRR = 4.91, 95% CI: 4.34-5.58), and bronchiolitis (IRR = 4.68, 95% CI: 2.93-7.65). Severe RSV was also associated with more PHC visits for the pediatrician (IRR = 2.00, 95% CI: 1.96-2.05), nurse (IRR = 1.89, 95% CI: 1.75-1.92), hospital emergency (IRR = 2.39, 95% CI: 2.17-2.63), primary healthcare emergency (IRR: 1.54, 95% CI: 1.31-1.82), as well as with important increase in prescriptions for obstructive airway diseases (IRR = 5.98, 95% CI: 5.43-6.60) and antibacterials (IRR = 4.02, 95% CI: 3.38-4.81). All findings remained substantial until 2 years of post-infection. CONCLUSIONS: Severe RSV infection in infants significantly increases short- to mid-term respiratory morbidity leading to an escalation in healthcare utilization (PHC/ES attendance) and medication prescriptions for up to 2 years afterward. Our approach could be useful in assessing the impact and cost-effectiveness of RSV prevention programs.
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Hospitalização , Atenção Primária à Saúde , Infecções por Vírus Respiratório Sincicial , Humanos , Infecções por Vírus Respiratório Sincicial/epidemiologia , Lactente , Masculino , Feminino , Atenção Primária à Saúde/estatística & dados numéricos , Estudos Longitudinais , Espanha/epidemiologia , Hospitalização/estatística & dados numéricos , Recém-Nascido , Incidência , Vírus Sincicial Respiratório Humano , Morbidade , Efeitos Psicossociais da DoençaRESUMO
Coronavirus Disease-19 (COVID-19) symptoms range from mild to severe illness; the cause for this differential response to infection remains unknown. Unravelling the immune mechanisms acting at different levels of the colonization process might be key to understand these differences. We carried out a multi-tissue (nasal, buccal and blood; n = 156) gene expression analysis of immune-related genes from patients affected by different COVID-19 severities, and healthy controls through the nCounter technology. Mild and asymptomatic cases showed a powerful innate antiviral response in nasal epithelium, characterized by activation of interferon (IFN) pathway and downstream cascades, successfully controlling the infection at local level. In contrast, weak macrophage/monocyte driven innate antiviral response and lack of IFN signalling activity were present in severe cases. Consequently, oral mucosa from severe patients showed signals of viral activity, cell arresting and viral dissemination to the lower respiratory tract, which ultimately could explain the exacerbated innate immune response and impaired adaptative immune responses observed at systemic level. Results from saliva transcriptome suggest that the buccal cavity might play a key role in SARS-CoV-2 infection and dissemination in patients with worse prognosis. Co-expression network analysis adds further support to these findings, by detecting modules specifically correlated with severity involved in the abovementioned biological routes; this analysis also provides new candidate genes that might be tested as biomarkers in future studies. We also found tissue specific severity-related signatures mainly represented by genes involved in the innate immune system and cytokine/chemokine signalling. Local immune response could be key to determine the course of the systemic response and thus COVID-19 severity. Our findings provide a framework to investigate severity host gene biomarkers and pathways that might be relevant to diagnosis, prognosis, and therapy.
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COVID-19 , Antivirais , Biomarcadores , COVID-19/genética , Perfilação da Expressão Gênica/métodos , Humanos , Imunidade Inata/genética , Mucosa Nasal , SARS-CoV-2RESUMO
BACKGROUND: Research on the effectiveness of COVID-19 booster-based vaccine schedule is ongoing and real-world data on vaccine effectiveness (VE) in comorbid patients are limited. We aimed to estimate booster dose VE against SARS-CoV-2 infection and COVID-19 severity in the general population and in comorbid patients. METHOD: A retrospective test-negative control study was undertaken in Galicia-Spain (December 2020-November 2021). VE and 95% confidence interval (CI) were estimated using multivariate logistic regression models. RESULTS: 1,512,415 (94.13%) negative and 94,334 (5.87%) positive SARS-CoV-2 test results were included. A booster dose of COVID-19 vaccine is associated with substantially higher protection against SARS-CoV-2 infection than vaccination without a booster [VEboosted = 87% (95%CI: 83%; 89%); VEnon-boosted = 66% (95%CI: 65%; 67%)]. The high VE was observed in all ages, but was more pronounced in subjects older than 65 years. VE against COVID-19 severity was analyzed in a mixed population of boosted and non-boosted individuals and considerable protection was obtained [VE: hospitalization = 72% (95%CI: 68%; 75%); intensive care unit administration = 83% (95%CI: 78%; 88%), in-hospital mortality = 66% (95%CI: 53%; 75%)]. Boosted comorbid patients are more protected against SARS-CoV-2 infection than those who were non-boosted. This was observed in a wide range of major diseases including cancer (81% versus 54%), chronic obstructive pulmonary disease (84% versus 61%), diabetes (84% versus 65%), hypertension (82% versus 65%) and obesity (91% versus 67%), among others. CONCLUSIONS: A booster dose of COVID-19 vaccine increases the protection against SARS-CoV-2 infection and COVID-19 severity in the general population and in comorbid patients.
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Vacinas contra COVID-19 , COVID-19 , Idoso , COVID-19/epidemiologia , COVID-19/prevenção & controle , Humanos , Imunização Secundária , Estudos Retrospectivos , SARS-CoV-2 , Espanha/epidemiologiaRESUMO
Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infections in children. By the age of 1 year, 60%-70% of children have been infected by RSV. In addition, early-life RSV infection is associated with the development of recurrent wheezing and asthma in infancy and childhood. The need for precise epidemiologic data regarding RSV as a worldwide pathogen has been growing steadily as novel RSV therapeutics are reaching the final stages of development. To optimize the prevention, diagnosis, and treatment of RSV infection in a timely manner, knowledge about the differences in the timing of the RSV epidemics worldwide is needed. Previous analyses, based on literature reviews of individual reports obtained from medical databases, have failed to provide global country seasonality patterns. Until recently, only certain countries have been recording RSV incidence through their own surveillance systems. This analysis was based on national RSV surveillance reports and medical databases from 27 countries worldwide. This is the first study to use original-source, high-quality surveillance data to establish a global, robust, and homogeneous report on global country-specific RSV seasonality.
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Saúde Global , Infecções por Vírus Respiratório Sincicial/epidemiologia , Estações do Ano , HumanosRESUMO
Nirsevimab has been recently licensed for universal RSV prophylaxis in infants. NIRSE-GAL is a three-year population-based study initiated in Galicia in September 2023. It aims to evaluate nirsevimab effectiveness against RSV-related hospitalizations lower respiratory tract infections (LRTI), severe RSV, all-cause LRTI, and all-cause hospitalization. NIRSE-GAL also aims to estimate nirsevimab impact on primary healthcare use in the short and mid-term, children's wheezing and asthma, and medical prescriptions for RSV. The immunization campaigns will be scheduled based on the expected start week for the RSV season and will last the whole season. Immunization will be offered to: i) infants born during the campaign (seasonal), ii) infants < 6 months at the start of the campaign (catch-up), and iii) infants with high-risk factors, aged 6-24 months at the start of the campaign (high-risk). The follow-up period will start: i) the immunization date for all immunized infants, ii) the start of the campaign, for the non-immunized catch-up or high-risk groups, or iii) the birthdate for the non-immunized seasonal group. Infants will be followed up until outcome occurrence, death, or end of study. Nirsevimab effectiveness will be estimated using Poisson and Cox regression models. Sensitivity and stratified analyses will be undertaken. The number of averted cases and the number needed to immunize will be estimated. Immunization failure and nirsevimab safety will be monitored. NIRSE-GAL was approved by the ethics committee of Galicia (CEIC 2023-377) and registered in ClinicalTrials.gov (ID: NCT06180993). Findings will be mainly shared via peer-reviewed publications and scientific conferences.
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Antivirais , Hospitalização , Infecções por Vírus Respiratório Sincicial , Humanos , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Lactente , Hospitalização/estatística & dados numéricos , Antivirais/uso terapêutico , Antivirais/administração & dosagem , Vírus Sincicial Respiratório Humano/imunologia , Feminino , Masculino , Infecções Respiratórias/prevenção & controle , Programas de Imunização , Recém-Nascido , Pré-Escolar , Palivizumab/uso terapêutico , Palivizumab/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagemRESUMO
After the use of facemasks, other isolation measures enacted during the SARS-CoV-2 pandemic were lifted, respiratory pathogens, such as RSV, reappeared, but until the November 2023 WHO alert for China, M. pneumoniae had virtually disappeared. After observing a similar reappearance in our hospital, a retrospective analysis of the number of positive M. pneumoniae tests. Between 2018 and December 2023, 1619 PCR tests were ordered and 43 (2.6%) of them were positive. Two outbreaks, one in 2018 and one in 2023, accounted for the majority of cases. Tests were usually ordered in an outpatient setting (53.54%, n = 23) and most of them were paediatric patients with a mean age (sd) of 10.2 (6.2) years. As for the severity of the cases, in the 2018 outbreak, of 15 children who tested positive, 53.3% (n = 8) were admitted to the ward and 6.7% (n = 1) at the intensive care unit. Whereas in 2023, 2 patients were tested in the ward (10.5%) and one in the intensive care unit (5.2%) from a total of 19 patients. The positive rate in 2023 was significantly higher in comparison with years 2020, 2021 and 2022 and significantly lower in comparison with 2018 (P-value=0.003). The outbreak in late 2023 can be explained by the seasonality of Mycoplasma pneumonia alone, which has shown outbreaks every 3-5 years, and it does not appear to be more severe than the previous one.
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Mycoplasma pneumoniae , Pneumonia por Mycoplasma , Humanos , Criança , Mycoplasma pneumoniae/genética , Espanha/epidemiologia , Estudos Retrospectivos , Pneumonia por Mycoplasma/epidemiologia , China/epidemiologiaRESUMO
Extensive literature has explored the beneficial effects of music in age-related cognitive disorders (ACD), but limited knowledge exists regarding its impact on gene expression. We analyzed transcriptomes of ACD patients and healthy controls, pre-post a music session (n = 60), and main genes/pathways were compared to those dysregulated in mild cognitive impairment (MCI) and Alzheimer's disease (AD) as revealed by a multi-cohort study (n = 1269 MCI/AD and controls). Music was associated with 2.3 times more whole-genome gene expression, particularly on neurodegeneration-related genes, in ACD than in controls. Co-expressed gene-modules and pathways analysis demonstrated that music impacted autophagy, vesicle and endosome organization, biological processes commonly dysregulated in MCI/AD. Notably, the data indicated a strong negative correlation between musically-modified genes/pathways in ACD and those dysregulated in MCI/AD. These findings highlight the compensatory effect of music on genes/biological processes affected in MCI/AD, providing insights into the molecular mechanisms underlying the benefits of music on these disorders.
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Doença de Alzheimer , Transtornos Cognitivos , Disfunção Cognitiva , Música , Humanos , Música/psicologia , Estudos de Coortes , Disfunção Cognitiva/genética , Disfunção Cognitiva/psicologia , Doença de Alzheimer/genética , Doença de Alzheimer/psicologia , Expressão GênicaRESUMO
Investigating vaccine effectiveness (VE) in real-world conditions is crucial, especially its variation across different settings and populations. We undertook a test-negative control study in Galicia (Northwest Spain) to assess BNT162b2 effectiveness against acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection as well as COVID-19 associated hospitalization, intensive care unit (ICU) admission and mortality. A total of 44,401 positive and 817,025 negative SARS-CoV-2 test results belonging to adults were included. Adjusted odds ratios of vaccination and their 95% confidence interval (CI) were estimated using multivariate logistic-regression models. BNT162b2 showed high effectiveness in reducing SARS-CoV-2 infections in all age categories, reaching maximum VE ≥ 14 days after administering the second dose [18-64 years: VE = 92.9% (95%CI: 90.2-95.1); 65-79 years: VE = 85.8% (95%CI: 77.3-91.9), and ≥80 years: VE = 91.4% (95%CI: 87.9-94.1)]. BNT162b2 also demonstrated effectiveness in preventing COVID-19 hospitalization for all age categories, with VE more pronounced for those aged ≥80 years [VE = 60.0% (95%CI: 49.4-68.3)]. Moreover, there was a considerable reduction in ICU admission [VE = 88.0% (95%CI: 74.6-95.8)] and mortality [VE = 38.0% (95%CI: 15.9-55.4)] in the overall population. BNT162b2 showed substantial protection against SARS-CoV-2 infections and COVID-19 severity. Our findings would prove useful for systematic reviews and meta-analysis on COVID-19 VE.
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Vacina BNT162 , COVID-19 , Adulto , COVID-19/epidemiologia , COVID-19/prevenção & controle , Humanos , SARS-CoV-2 , Espanha/epidemiologia , Revisões Sistemáticas como Assunto , Eficácia de VacinasRESUMO
Background: Emerging evidence indicates a potential role for monocytes in COVID-19 immunopathology. We investigated two soluble markers of monocyte activation, sCD14 and sCD163, in COVID-19 patients, with the aim of characterizing their potential role in monocyte-macrophage disease immunopathology. To the best of our knowledge, this is the first study of its kind. Methods: Fifty-nine SARS-Cov-2 positive hospitalized patients, classified according to ICU or non-ICU admission requirement, were prospectively recruited and analyzed by ELISA for levels of sCD14 and sCD163, along with other laboratory parameters, and compared to a healthy control group. Results: sCD14 and sCD163 levels were significantly higher among COVID-19 patients, independently of ICU admission requirement, compared to the control group. We found a significant correlation between sCD14 levels and other inflammatory markers, particularly Interleukin-6, in the non-ICU patients group. sCD163 showed a moderate positive correlation with the time lapsed from admission to sampling, independently of severity group. Treatment with corticoids showed an interference with sCD14 levels, whereas hydroxychloroquine and tocilizumab did not. Conclusions: Monocyte-macrophage activation markers are increased and correlate with other inflammatory markers in SARS-Cov-2 infection, in association to hospital admission. These data suggest a preponderant role for monocyte-macrophage activation in the development of immunopathology of COVID-19 patients.
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Antígenos CD , Antígenos de Diferenciação Mielomonocítica , Betacoronavirus , Infecções por Coronavirus , Receptores de Lipopolissacarídeos , Pandemias , Pneumonia Viral , Receptores de Superfície Celular , Corticosteroides/administração & dosagem , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Antígenos CD/sangue , Antígenos CD/imunologia , Antígenos de Diferenciação Mielomonocítica/sangue , Antígenos de Diferenciação Mielomonocítica/imunologia , Betacoronavirus/imunologia , Betacoronavirus/metabolismo , COVID-19 , Infecções por Coronavirus/sangue , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Feminino , Humanos , Hidroxicloroquina/administração & dosagem , Unidades de Terapia Intensiva , Interleucina-6/sangue , Interleucina-6/imunologia , Receptores de Lipopolissacarídeos/sangue , Receptores de Lipopolissacarídeos/imunologia , Ativação de Macrófagos , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Monócitos/patologia , Admissão do Paciente , Pneumonia Viral/sangue , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Receptores de Superfície Celular/sangue , Receptores de Superfície Celular/imunologia , SARS-CoV-2 , Fatores de TempoRESUMO
Invasive meningococcal disease (IMD) is a major public health concern because of its high case fatality, long-term morbidity, and potential to course with outbreaks. IMD caused by Nesseira meningitidis serogroup B has been predominant in different regions of the world like Europe and only recently broadly protective vaccines against B serogroup have become available. Two protein-based vaccines, namely 4CMenB (Bexsero®) and rLP2086 (Trumenba®) are currently licensed for use in different countries against MenB disease. These vaccines came from a novel technology on vaccine design (or antigen selection) using highly specific antigen targets identified through whole-genome sequence analysis. Moreover, it has the potential to confer protection against non-B meningococcus and against other Neisserial species such as gonococcus. Real-world data on the vaccine-use are rapidly accumulating from the UK and other countries which used the vaccine for control of outbreak or as part of routine immunization program, reiterating its safety and efficacy. Additional data on real-life effectiveness, long-term immunity, and eventual herd effects, including estimates on vaccine impact for cost-effectiveness assessment are further needed. Given the predominance of MenB in Europe and other parts of the world, these new vaccines are crucial for the prevention and public health control of the disease, and should be considered.
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INTRODUCTION: The introduction of pneumococcal conjugate vaccines (PCVs) in the routine immunization program has resulted in a significant decline in invasive pneumococcal diseases (IPD) around the world. Preterm infants are a special group at a high risk of invasive infection by encapsulated bacteria. However, their slow growth accrual and prolonged hospital stay frequently lead to delays in immunization, which contributes to their risk for severe infections. Areas covered: Authors reviewed the published immunogenicity and safety of the use of PCVs in preterm infants. Expert opinion: PCVs are safe and effective for use in low birth weight and in-hospital preterm infants. Local and systemic reactions are similar for both term and preterm populations. Reports were inconsistent on the risk of apnea, therefore hospitalized extremely premature infants should be kept under observation for at least 48 h after immunization.
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Recém-Nascido Prematuro , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/administração & dosagem , Humanos , Imunização/métodos , Programas de Imunização , Imunogenicidade da Vacina , Recém-Nascido , Vacinas Pneumocócicas/efeitos adversos , Vacinas Pneumocócicas/imunologia , Vacinas Conjugadas/administração & dosagemRESUMO
INTRODUCTION: Salivary glands are known immune effector sites and considered to be part of the whole mucosal immune system. The aim of the present study was to assess the salivary immune response to rotavirus (RV) infection through the analysis of the cytokine immune profile in saliva. MATERIAL AND METHODS: A prospective comparative study of serial saliva samples from 27 RV-infected patients (sampled upon admission to the hospital during acute phase and at convalescence-i.e. at least three months after recovery) and 36 healthy controls was performed. Concentrations of 11 salivary cytokines (IFN-γ, IFN-α2, IL-1ß, IL-6, IL-8, IL-10, IL-15, IL12p70, TNF-α, IFN-λ1, IL-22) were determined. Cytokine levels were compared between healthy controls acute infection and convalescence. The correlation between clinical data and salivary cytokine profile in infected children was assessed. RESULTS: The salivary cytokine profile changes significantly in response to acute RV infection. In RV-infected patients, IL-22 levels were increased in the acute phase with respect to convalescence (P-value < 0.001). Comparisons between infected and control group showed significant differences in salivary IFN-α2, IL-1ß, IL-6, IL-8, IL-10 and IL-22. Although acute-phase levels of IL-12, IL-10, IL-6 and IFN-γ showed nominal association with Vesikari's severity, this trend did not reach statistical significance after multiple test adjustment. CONCLUSIONS: RV infection induces a host salivary immune response, indicating that immune mucosal response to RV infection is not confined to the intestinal mucosa. Our data point to a whole mucosal implication in the RV infection as a result of the integrative mucosal immune response, and suggest the salivary gland as effector site for RV infection.
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Imunidade nas Mucosas/imunologia , Infecções por Rotavirus/imunologia , Glândulas Salivares/fisiologia , Pré-Escolar , Citocinas/análise , Feminino , Humanos , Imunidade nas Mucosas/fisiologia , Lactente , Recém-Nascido , Interleucinas/análise , Enteropatias , Mucosa Intestinal/química , Intestinos/química , Masculino , Mucosa Bucal/química , Estudos Prospectivos , Rotavirus/patogenicidade , Infecções por Rotavirus/virologia , Saliva/química , Glândulas Salivares/virologia , Interleucina 22RESUMO
Complexation of sertaconazole (SN) with hydroxypropyl-beta-cyclodextrin (HP-beta-CD) was characterized by phase-solubility diagram measurements and isothermal calorimetry (ITC) in aqueous medium, and by differential scanning calorimetry (DSC), Raman spectroscopy and X-ray diffractometry in solid state. The strongest interaction was observed at pH 1.2, at which two different 1:1 complexes can be formed depending on the hydrophobic ring of the drug involved in the process. At pH 5.8 and 7.4 the likelihood of 1:2 stoichiometry increases as a consequence of the simultaneous complexation of the nonprotonized imidazolyl and the dichlorophenyl groups. In the presence of 20% HP-beta-CD, SN solubility is enhanced by a factor of 116, 107, and 5 at pH 1.2, 5.8, and 7.4, respectively. Complexation enthalpy recorded by ITC showed the same tendency which confirms the practical interest of this technique for fast screening of the potential of CDs as drug solubilizers. Solubility and dissolution rate of the drug from compacts prepared with freeze-dried complexes were significantly greater than those obtained with SN powder or compacts made with physical blends.
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Química Farmacêutica/métodos , Imidazóis/análise , Imidazóis/química , Tiofenos/análise , Tiofenos/química , beta-Ciclodextrinas/análise , beta-Ciclodextrinas/química , 2-Hidroxipropil-beta-Ciclodextrina , Calorimetria/métodos , Solubilidade , Titulometria/métodosRESUMO
The mechanisms of rotavirus (RV) infection have been analyzed from different angles but the way in which RV modifies the transcriptome of the host is still unknown. Whole transcriptome shotgun sequencing of peripheral blood samples was used to reveal patterns of expression from the genome of RV-infected patients. RV provokes global changes in the transcriptome of infected cells, involving an over-expression of genes involved in cell cycle and chromatin condensation. While interferon IFI27 was hyper-activated, interferon type II was not suggesting that RV has developed mechanisms to evade the innate response by host cells after virus infection. Most interesting was the inhibition of genes of the glycophorins A and B (GYPA/B) family, which are the major sialoglycoproteins of the human erythrocyte membrane and receptor of several viruses for host invasion. RV infection induces a complex and global response in the host. The strong inhibition of glycophorins suggests a novel defense mechanism of the host to prevent viral infection, inhibiting the expression of receptors used by the virus for infection. The present results add further support to the systemic nature of RV infection.
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Regulação da Expressão Gênica , Glicoforinas/genética , Interações Hospedeiro-Patógeno/genética , Infecções por Rotavirus/genética , Infecções por Rotavirus/virologia , Rotavirus , Estudos de Casos e Controles , Pré-Escolar , Análise por Conglomerados , Resistência à Doença/genética , Resistência à Doença/imunologia , Regulação para Baixo , Feminino , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Sequenciamento de Nucleotídeos em Larga Escala , Interações Hospedeiro-Patógeno/imunologia , Humanos , Lactente , Masculino , Família Multigênica , Infecções por Rotavirus/diagnóstico , Infecções por Rotavirus/imunologia , TranscriptomaRESUMO
BACKGROUND AND AIMS: A properly validated scoring system allowing objective categorization of infants with acute respiratory infections (ARIs), avoiding the need for in-person assessment and that could also be used by non-health professionals is currently not available. We aimed to develop a new clinical assessment scale meeting these specifications. METHODS: We designed a clinical scale (ReSVinet scale) based on seven parameters (feeding intolerance, medical intervention, respiratory difficulty, respiratory frequency, apnoea, general condition, fever) that were assigned different values (from 0 to 3) for a total of 20 points.170 children under two years of age with ARI were assessed independently by three pediatricians using this scale. Parents also evaluated their offspring with an adapted version of the scale in a subset of 61 cases. The scale was tested for internal consistency (Cronbach's alpha), Pearson correlation coefficient for the items in the scale, inter-observer reliability (kappa index) and floor-ceiling effect. RESULTS: Internal consistency was good for all the observers, with the lowest Cronbach's alpha being 0.72. There was a strong correlation between the investigators (r-value ranged 0.76-0.83) and also between the results obtained by the parents and the investigators(r = 0.73). Light's kappa for the observations of the three investigators was 0.74. Weighted kappa in the group evaluated by the parents was 0.73. The final score was correlated with length of hospital stay, PICU admission and Wood-Downes Score. CONCLUSIONS: The ReSVinet scale may be useful and reliable in the evaluation of infants with ARI, particularly acute bronchiolitis, even with data obtained from medical records and when employed by parents. Although further studies are necessary, ReSVinet scale already complies with more score validation criteria than the vast majority of the alternatives currently available and used in the clinical practice.
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Infecções Respiratórias/diagnóstico , Inquéritos e Questionários , Doença Aguda , Estudos de Coortes , Humanos , Lactente , Pais , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Rotavirus vaccine (RV) might reduce the risk of hospitalization due to childhood seizures (CS). We aimed to identify and assess variations in the incidence of hospitalizations for CS among children <5 years of age before and after RV introduction. METHODS: Annual hospitalization rates for any kind of CS, before and after RV introduction in 2007, were calculated using the official surveillance system for hospitalization data. RESULTS: Our study cohort totaled 6149 children <5 years of age admitted to the hospital between 2003 and 2013 with any kind of CS (780.3* + 779.0* + 333.2* + 345* ICD-9-CM code). The annual hospitalization rates for any kind of CS in children <5 years of age were correlated with RV coverage (r = -0.673; P = 0.033) and rotavirus acute gastroenteritis admission rates (ρ = 0.506; P = 0.001), with decrease rates ranging from 16.2% (95% confidence interval: 8.3-23.5%) in 2007 to 34.0% (27.3-40.1%) in 2010, as compared with the median rate of the pre-vaccination period (2003 to 2006). Similarly, for convulsions (780.3*ICD-9-CM code), the decrease seen in children <5 years of age was significantly correlated with the increase in RV coverage (r = -0.747; P = 0.013) and rotavirus acute gastroenteritis admission rates (ρ = 0.543; P < 0.001), with decrease rates ranging from 18.7% (9.6-26.8%) in 2007 to 42.5% (35.3-48.9%) in 2012. Significant results were also obtained for infants <12 months and infants 1-2 years of age. In the remaining age groups or diagnostic categories analyzed, changes were either not significant or not related to vaccination changes or rotavirus acute gastroenteritis admission rates. CONCLUSIONS: Our results show that rotavirus vaccination may have a significant impact in the decrease in seizure-related hospitalizations in childhood. This additional benefit of rotavirus vaccination seems more marked in the youngest infants.
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Hospitalização/tendências , Vacinas contra Rotavirus/administração & dosagem , Vacinas contra Rotavirus/imunologia , Convulsões/epidemiologia , Convulsões/prevenção & controle , Vacinação/estatística & dados numéricos , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Estudos RetrospectivosRESUMO
This paper reports on the effect of beta-cyclodextrin (beta-CD) and hydroxypropyl-beta-cyclodextrin (HP-beta-CD) on the diffusion and the release behavior of diclofenac sodium and sulphamethizole from HPMC K4M gels and matrix tablets. The gels were prepared with 0.5-2.0% polymer and different drug/CD mole ratios, and their viscosity, cloud point and drug diffusion coefficients were estimated. No differences in cloud point were observed. The viscosity of the gels strongly depended on HPMC proportions (from 0.7 to 100 mPa.s), which affected to a lesser extent the resistance to the diffusion of the drugs (D values from 60 x 10(-6) to 5 x 10(-6) cm(2)/s). The influence of CD on diffusion was particularly evident in gels prepared with polymer proportions above its entanglement concentration, 2.0% HPMC K4M. In these systems, while high drug/CD proportions enhanced the diffusivity preventing polymer/drug hydrophobic interactions, low drug/CD ratios hindered it. An excess of free CD, especially the bulky HP-beta-CD, made the diffusion of the complexes in the relatively low mesh size 2% polymer network more difficult. In the case of tablets, CD plays an additional role as dissolution rate promoter. To evaluate to what extent the balance between the increase in dissolution rate and the decrease in diffusion rate induced by CD determines drug release, matrix tablets were prepared by direct compression of 100 mg drug and 400 mg polymer/CD/lactose blends, whose composition was chosen following a simplex centroid design. A higher CD/lactose ratio significantly increased the release rate of hydrophobic drugs (sulphamethizole), but decreased the release rate of hydrophilic drugs (diclofenac sodium), indicating the predominance of a different contribution depending on the hydrophilicity of the drug. Therefore, the use of CD derivatives may be particularly useful to modulate drug release from HPMC gels and matrix tablets; the influence of these additives being dependent on the nature of the drug and on the molecular size and hydrophilic character of the CD used.
Assuntos
Ciclodextrinas/química , Ciclodextrinas/farmacocinética , Metilcelulose/química , Metilcelulose/farmacocinética , Géis , Derivados da Hipromelose , Metilcelulose/análogos & derivados , Solubilidade/efeitos dos fármacos , Comprimidos com Revestimento EntéricoRESUMO
Cross-linking of hydroxypropyl-beta-cyclodextrin (HP beta CD) with ethyleneglycol diglycidylether (EGDE) in carbopol dispersions enabled the synthesis of cyclodextrin hydrogels with domains of interpenetrating acrylic microgels (micro-scale-IPNs) in a single step under mild conditions. As carbopol proportion increased, the hardness and compressibility of the ms-IPNs decreased, but their bioadhesion force and pH-responsiveness rose. Control HP beta CD hydrogel and ms-IPNs were loaded with estradiol and ketoconazole by immersion in drug suspensions, some of which were autoclaved to enhance (up to a 50%) drug/cyclodextrin affinity. ms-IPNs prepared with 0.8% or 1.0% carbopol showed the highest loading due to their greater swelling degree and, consequently, mesh size. The total loading of the ms-IPNs greatly exceeded (up to 200-fold) the amount dissolved in their aqueous phase, which highlights the main role of drug complexation with the cross-linked cyclodextrins. The affinity of the drug for HP beta CD sustained the release for several days; the rate being also dependent on carbopol content and on pH of the medium. Therefore, an adequate design of the HP beta CD/carbopol ms-IPNs provides a single material with tunable mechanical properties, in which the complexation ability of cyclodextrins is combined with the bioadhesive and pH-responsive properties of carbopol. The ms-IPNs are potentially useful as vehicles of relatively hydrophobic substances.
Assuntos
Ciclodextrinas/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Microesferas , Polivinil/administração & dosagem , Resinas Acrílicas , Reagentes de Ligações Cruzadas/administração & dosagem , Reagentes de Ligações Cruzadas/química , Ciclodextrinas/química , Polivinil/químicaRESUMO
PURPOSE: The goal of the study is to develop new hydrogels based on cyclodextrins cross-linked with ethyleneglycol diglycidylether (EGDE) under mild conditions, to be used as carriers of amphiphilic drugs. Also, it aims to characterize the cross-linking and the drug loading and release processes. METHODS: The cross-linking of hydroxypropyl-beta-cyclodextrin (HPbetaCD) with EGDE, in the absence or presence of hydroxypropylmethylcellulose (HPMC) Methocel K4M, was optimized applying oscillatory rheometry and Fourier transform infrared. Hydrogels were characterized regarding swelling in water, ability to load diclofenac, and release after different drying treatments. RESULTS: Solutions of HPbetaCD (14.28%), without or with HPMC (0.2-1.0%), provided firm and transparent hydrogels after cross-linking with EGDE (14.28%), in which around two thirds of the OH groups were cross-linked. The incorporation of HPMC progressively reduced the gel time and the swelling degree of hydrogels. HPbetaCD hydrogels efficiently loaded diclofenac and sustained the release for several hours. The presence of HPMC slowed the release from swollen hydrogels, but promoted it from hydrogels dried before the loading and also before the release. CONCLUSIONS: HPbetaCD hydrogels with good mechanical properties and tunable loading and release ability can be obtained by direct cross-linking with EGDE.