RESUMO
BACKGROUND: In September 2015, the four-component, protein-based meningococcal serogroup B vaccine (4CMenB; Bexsero) became available for private purchase in Spain. METHODS: We conducted a nationwide matched case-control study to assess the effectiveness of 4CMenB in preventing invasive meningococcal disease in children. The study included all laboratory-confirmed cases of invasive meningococcal disease in children younger than 60 months of age between October 5, 2015, and October 6, 2019, in Spain. Each case patient was matched with four controls according to date of birth and province. 4CMenB vaccination status of the case patients and controls was compared with the use of multivariate conditional logistic regression. RESULTS: We compared 306 case patients (243 [79.4%] with serogroup B disease) with 1224 controls. A total of 35 case patients (11.4%) and 298 controls (24.3%) had received at least one dose of 4CMenB. The effectiveness of complete vaccination with 4CMenB (defined as receipt of at least 2 doses, administered in accordance with the manufacturer's recommendations) was 76% (95% confidence interval [CI], 57 to 87) against invasive meningococcal disease caused by any serogroup, and partial vaccination was 54% (95% CI, 18 to 74) effective. Complete vaccination resulted in an effectiveness of 71% (95% CI, 45 to 85) against meningococcal serogroup B disease. Vaccine effectiveness with at least one dose of 4CMenB was 64% (95% CI, 41 to 78) against serogroup B disease and 82% (95% CI, 21 to 96) against non-serogroup B disease. With the use of the genetic Meningococcal Antigen Typing System, serogroup B strains that were expected to be covered by 4CMenB were detected in 44 case patients, none of whom had been vaccinated. CONCLUSIONS: Complete vaccination with 4CMenB was found to be effective in preventing invasive disease by serogroup B and non-serogroup B meningococci in children younger than 5 years of age.
Assuntos
Infecções Meningocócicas , Vacinas Meningocócicas , Neisseria meningitidis Sorogrupo B , Criança , Humanos , Lactente , Estudos de Casos e Controles , Infecções Meningocócicas/microbiologia , Infecções Meningocócicas/prevenção & controle , Vacinas Meningocócicas/uso terapêutico , Neisseria meningitidis , EspanhaRESUMO
The target of the rapamycin (TOR) signaling pathway plays a negative role in controlling virulence in phytopathogenic fungi. However, the actual targets involved in virulence are currently unknown. Using the corn smut fungus Ustilago maydis, we tried to address the effects of the ectopic activation of TOR on virulence. We obtained gain-of-function mutations in the Rheb GTPase, one of the conserved TOR kinase regulators. We have found that unscheduled activation of Rheb resulted in the alteration of the proper localization of the pheromone receptor, Pra1, and thereby pheromone insensitivity. Since pheromone signaling triggers virulence in Ustilaginales, we believe that the Rheb-induced pheromone blindness was responsible for the associated lack of virulence. Strikingly, although these effects required the concourse of the Rsp5 ubiquitin ligase and the Art3 α-arrestin, the TOR kinase was not involved. Several eukaryotic organisms have shown that Rheb transmits environmental information through TOR-dependent and -independent pathways. Therefore, our results expand the range of signaling manners at which environmental conditions could impinge on the virulence of phytopathogenic fungi.
Assuntos
Ustilago , Ustilago/genética , Feromônios/metabolismo , Proteína Enriquecida em Homólogo de Ras do Encéfalo/genética , Proteína Enriquecida em Homólogo de Ras do Encéfalo/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Zea mays/metabolismo , Fungos/metabolismo , Cegueira , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismoRESUMO
In nature, multiple stress factors occur simultaneously. The screening of natural diversity panels and subsequent Genome-Wide Association Studies (GWAS) is a powerful approach to identify genetic components of various stress responses. Here, the nutritional status variation of a set of 270 natural accessions of Arabidopsis thaliana grown on a natural saline-carbonated soil is evaluated. We report significant natural variation on leaf Na (LNa) and Fe (LFe) concentrations in the studied accessions. Allelic variation in the NINJA and YUC8 genes is associated with LNa diversity, and variation in the ALA3 is associated with LFe diversity. The allelic variation detected in these three genes leads to changes in their mRNA expression and correlates with plant differential growth performance when plants are exposed to alkaline salinity treatment under hydroponic conditions. We propose that YUC8 and NINJA expression patters regulate auxin and jasmonic signaling pathways affecting plant tolerance to alkaline salinity. Finally, we describe an impairment in growth and leaf Fe acquisition associated with differences in root expression of ALA3, encoding a phospholipid translocase active in plasma membrane and the trans Golgi network which directly interacts with proteins essential for the trafficking of PIN auxin transporters, reinforcing the role of phytohormonal processes in regulating ion homeostasis under alkaline salinity.
Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Estudo de Associação Genômica Ampla , Homeostase , Ácidos Indolacéticos/metabolismo , Salinidade , Estresse Salino/genética , Sódio/metabolismo , Folhas de PlantaRESUMO
BACKGROUND: With more than 7500 cases reported since April 2022, Spain has experienced the highest incidence of mpox in Europe. From 12 July onward, the modified vaccinia Ankara-Bavaria Nordic (MVA-BN) smallpox vaccine was offered as pre-exposure prophylaxis for those receiving pre-exposure prophylaxis for human immunodeficiency virus (HIV-PrEP). Our aim was to assess the effectiveness of 1 dose of MVA-BN vaccine as pre-exposure prophylaxis against mpox virus (MPXV) infection in persons on HIV-PrEP. METHODS: National retrospective cohort study between 12 July and 12 December 2022. Individuals aged ≥18 years receiving HIV-PrEP as of 12 July with no previous MPXV infection or vaccination were eligible. Each day, we matched individuals receiving a first dose of vaccine and unvaccinated controls of the same age and region. We used a Kaplan-Meier estimator, calculated risk ratios (RR) and vaccine effectiveness (VE = [1 - RR]x100). RESULTS: We included 5660 matched pairs, with a median follow-up of 62 days (interquartile range, 24-97). Mpox cumulative incidence was 5.6 per 1000 (25 cases) in unvaccinated and 3.5 per 1000 (18 cases) in vaccinated. No effect was found during days 0-6 post-vaccination (VE, -38.3; 95% confidence interval [CI], -332.7 to 46.4), but VE was 65% at ≥7 days (95% CI, 22.9 to 88.0) and 79% at ≥14 days (95% CI, 33.3 to 100.0) post-vaccination. CONCLUSIONS: One dose of MVA-BN vaccine offered protection against mpox in most-at-risk population shortly after the vaccination. Further studies need to assess the VE of a second dose and the duration of protection over time.
Assuntos
Infecções por HIV , Mpox , Vacinas , Vacínia , Humanos , Adolescente , Adulto , Vacínia/prevenção & controle , Estudos de Coortes , Estudos Retrospectivos , Vaccinia virus , Vacinação , Monkeypox virus , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controleRESUMO
AbstractInfectious disease dynamics operate across biological scales: pathogens replicate within hosts but transmit among populations. Functional changes in the pathogen-host interaction thus generate cascading effects across organizational scales. We investigated within-host dynamics and among-host transmission of three strains (SAT-1, -2, -3) of foot-and-mouth disease viruses (FMDVs) in their wildlife host, African buffalo. We combined data on viral dynamics and host immune responses with mathematical models to ask the following questions: How do viral and immune dynamics vary among strains? Which viral and immune parameters determine viral fitness within hosts? And how do within-host dynamics relate to virus transmission? Our data reveal contrasting within-host dynamics among viral strains, with SAT-2 eliciting more rapid and effective immune responses than SAT-1 and SAT-3. Within-host viral fitness was overwhelmingly determined by variation among hosts in immune response activation rates but not by variation among individual hosts in viral growth rate. Our analyses investigating across-scale linkages indicate that viral replication rate in the host correlates with transmission rates among buffalo and that adaptive immune activation rate determines the infectious period. These parameters define the virus's relative basic reproductive number (â0), suggesting that viral invasion potential may be predictable from within-host dynamics.
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Búfalos , Vírus da Febre Aftosa , Febre Aftosa , Animais , Búfalos/virologia , Vírus da Febre Aftosa/imunologia , Vírus da Febre Aftosa/crescimento & desenvolvimento , Febre Aftosa/transmissão , Febre Aftosa/virologia , Febre Aftosa/imunologia , Interações Hospedeiro-Patógeno/imunologia , Replicação Viral , Modelos BiológicosRESUMO
Previous studies have shown after the resolution of acute infection and viraemia, foot-and-mouth disease virus (FMDV) capsid proteins and/or genome are localised in the light zone of germinal centres of lymphoid tissue in cattle and African buffalo. The pattern of staining for FMDV proteins was consistent with the virus binding to follicular dendritic cells (FDCs). We have now demonstrated a similar pattern of FMDV protein staining in mouse spleens after acute infection and showed FMDV proteins are colocalised with FDCs. Blocking antigen binding to complement receptor type 2 and 1 (CR2/CR1) prior to infection with FMDV significantly reduced the detection of viral proteins on FDCs and FMDV genomic RNA in spleen samples. Blocking the receptors prior to infection also significantly reduced neutralising antibody titres, through significant reduction in their avidity to the FMDV capsid. Therefore, the binding of FMDV to FDCs and sustained induction of neutralising antibody responses are dependent on FMDV binding to CR2/CR1 in mice.
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Vírus da Febre Aftosa , Febre Aftosa , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais/metabolismo , Proteínas do Capsídeo/metabolismo , Bovinos , Células Dendríticas Foliculares/metabolismo , Vírus da Febre Aftosa/genética , Centro Germinativo , Camundongos , Receptores de Complemento/metabolismoRESUMO
This review sought to assess the efficacy, effectiveness and safety of high-dose inactivated influenza vaccines (HD-IIV) for the prevention of laboratory-confirmed influenza in individuals aged 18 years or older. A systematic literature search was conducted in electronic databases and grey literature sources up to 7 February 2020. Randomised controlled trials (RCTs) and non-randomised studies of interventions (NRSIs) were included. The search returned 28,846 records, of which 36 studies were included. HD-IIV was shown to have higher relative vaccine efficacy in preventing influenza compared with standard-dose influenza vaccines (SD-IIV3) in older adults (Vaccine effectiveness (VE) = 24%, 95% CI 10-37, one RCT). One NRSI demonstrated significant effect for HD-IIV3 against influenza B (VE = 89%, 95% CI 47-100), but not for influenza A(H3N2) (VE = 22%, 95% CI -82 to 66) when compared with no vaccination in older adults. HD-IIV3 showed significant relative effect compared with SD-IIV3 for influenza-related hospitalisation (VE = 11.8%, 95% CI 6.4-17.0, two NRSIs), influenza- or pneumonia-related hospitalisation (VE = 13.7%, 95% CI 9.5-17.7, three NRSIs), influenza-related hospital encounters (VE = 13.1%, 95% CI 8.4-17.7, five NRSIs), and influenza-related office visits (VE = 3.5%, 95% CI 1.5-5.5, two NRSIs). For safety, HD-IIV were associated with significantly higher rates of local and systemic adverse events compared with SD-IIV (combined local reactions, pain at injection site, swelling, induration, headache, chills and malaise). From limited data, compared with SD-IIV, HD-IIV were found to be more effective in the prevention of laboratory-confirmed influenza, for a range of proxy outcome measures, and associated with more adverse events.
Assuntos
Vacinas contra Influenza , Influenza Humana , Adolescente , Idoso , Humanos , Influenza Humana/prevenção & controle , Estações do Ano , Vacinação/efeitos adversos , Vacinas de Produtos Inativados/efeitos adversosRESUMO
The most effective means of preventing seasonal influenza is through strain-specific vaccination. In this study, we investigated the efficacy, effectiveness and safety of cell-based trivalent and quadrivalent influenza vaccines. A systematic literature search was conducted in electronic databases and grey literature sources up to 7 February 2020. Randomised controlled trials (RCTs) and non-randomised studies of interventions (NRSIs) were eligible for inclusion. Two reviewers independently screened, extracted data and assessed the risk of bias of included studies. Certainty of evidence for key outcomes was assessed using the GRADE methodology. The search returned 28,846 records, of which 868 full-text articles were assessed for relevance. Of these, 19 studies met the inclusion criteria. No relative efficacy data were identified for the direct comparison of cell-based vaccines compared with traditional vaccines (egg-based). Efficacy data were available comparing cell-based trivalent influenza vaccines with placebo in adults (aged 18-49 years). Overall vaccine efficacy was 70% against any influenza subtype (95% CI 61%-77%, two RCTS), 82% against influenza A(H1N1) (95% CI 71%-89%, 2 RCTs), 72% against influenza A(H3N2) (95% CI 39%-87%, 2 RCTs) and 52% against influenza B (95% CI 30%-68%, 2 RCTs). Limited and heterogeneous data were presented for effectiveness when compared with no vaccination. One NRSI compared cell-based trivalent and quadrivalent vaccination with traditional trivalent and quadrivalent vaccination, finding a small but significant difference in favour of cell-based vaccines for influenza-related hospitalisation, hospital encounters and physician office visits. The safety profile of cell-based trivalent vaccines was comparable to traditional trivalent influenza vaccines. Compared with placebo, cell-based trivalent influenza vaccines have demonstrated greater efficacy in adults aged 18-49 years. Overall cell-based vaccines are well-tolerated in adults, however, evidence regarding the effectiveness of these vaccines compared with traditional seasonal influenza vaccines is limited.
Assuntos
Vacinas contra Influenza , Influenza Humana , Adolescente , Adulto , Humanos , Hospitalização , Estações do Ano , VacinaçãoRESUMO
The assessment of body fat of children in primary care requires consideration of the dynamic changes in height, weight, lean mass, and fat mass during childhood growth. To achieve this, we aim to develop a predictive equation based on anthropometric values, with optimal diagnostic utility. This is a cross-sectional observational study, involving schoolgoers aged 11-17 years in the Vigo metropolitan area. Out of 10,747 individuals, 577 were randomly recruited. VARIABLES: age, sex, ethnicity/country of origin, weight, height, 8 skinfolds, 3 diameters, 7 perimeters, and 85% percentile of body fat mass as the gold standard. Generalized additive regression was selected by cross-validation and compared using receiver operating characteristic curves (ROC curves). Sensitivity, specificity, positive and negative predictive values, true positive and true negative values, false positive and false negative values, accuracy, and positive and negative likelihood ratios were calculated. Two models were identified. The optimal model includes sex, weight, height, leg perimeter, and arm perimeter, with sensitivity of 0.93 (0.83-1.00), specificity of 0.91 (0.83-0.96), accuracy of 0.91 (0.84-0.96), and area under the curve (AUC) of 0.957 (0.928-0.986). The second model includes sex, age, and body mass index, with sensitivity of 0.93 (0.81-1.00), specificity of 0.90 (0.80-0.97), accuracy of 0.90 (0.82-0.96), and an AUC of 0.944 (0.903-0.984). CONCLUSION: Two predictive models, with the 85th percentile of fat mass as the gold standard, built with basic anthropometric measures, show very high diagnostic utility parameters. Their calculation is facilitated by a complementary online calculator. WHAT IS KNOWN: ⢠In routine clinical practice, mainly in primary care, BMI is used to determine overweight and obesity. This index has its weaknesses in the assessment of children. WHAT IS NEW: ⢠We provide a calculator whose validated algorithm, through the determination of fat mass by impedanciometry, makes it possible to determine the risk of overweight and obesity in the community setting, through anthropometric measurements, providing a new practical, accessible and reliable model that improves the classification of overweight and obesity in children with respect to that obtained by determining BMI.
Assuntos
Obesidade Infantil , Humanos , Adolescente , Criança , Masculino , Feminino , Estudos Transversais , Espanha/epidemiologia , Obesidade Infantil/diagnóstico , Obesidade Infantil/epidemiologia , Índice de Massa Corporal , Curva ROC , Medição de Risco/métodos , Sensibilidade e Especificidade , Antropometria/métodosRESUMO
BACKGROUND: A French intersociety consensus on behalf the Société Française de Médecine Vasculaire and the Société de Chirurgie Vasculaire et Endovasculaire was proposed in 2021 for the management of patients with lower extremity peripheral artery disease (LEAD). Recent studies have been published and an update of this consensus about the management of low-density lipoprotein cholesterol (LDLc) and hypertriglyceridemia was required. METHODS: A steering committee of 12 vascular physicians and surgeons defined questions of interest about LDLc and hypertriglyceridemia management. A French expert panel voted the proposals. Consensus was considered to have been achieved if more than 80% of the responses corresponded to either "Agreement" or "Disagreement". RESULTS: Among the 56 experts who were asked to participate, 46 (82%) accepted. After the first round of the Delphi procedure, the 4 proposals reached consensus. The following suggestions and recommendations were approved: 1. For LEAD patients treated by the highest tolerated statin dose ± ezetimibe and who have an LDLc ≥0.70 g/L, we recommend adding a proprotein convertase subtilisin/kexin type 9 inhibitor. 2. For LEAD patients treated by statin and who have elevated triglyceride level between ≥150 mg/dL and ≤500 mg/dL, we suggest adding Icosapent Ethyl. 3. Before adding Icosapent Ethyl in LEAD patients treated with statin, we suggest looking for symptoms that may suggest atrial fibrillation. 4. For LEAD patients treated by Icosapent Ethyl and who have symptoms that suggest atrial fibrillation, we recommend performing an electrocardiogram. CONCLUSIONS: This update will help clinicians to improve LEAD patient management.
Assuntos
Fibrilação Atrial , Cardiologia , Inibidores de Hidroximetilglutaril-CoA Redutases , Hipertrigliceridemia , Doença Arterial Periférica , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , LDL-Colesterol , Consenso , Resultado do Tratamento , Hipertrigliceridemia/complicações , Hipertrigliceridemia/diagnóstico , Hipertrigliceridemia/tratamento farmacológico , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/cirurgiaRESUMO
The monoclonal antibody nirsevimab was at least 70% effective in preventing hospitalisations in infants with lower respiratory tract infections (LRTI) positive for respiratory syncytial virus (RSV) in Spain (Oct 2023-Jan 2024), where a universal immunisation programme began late September (coverage range: 79-99%). High protection was confirmed by two methodological designs (screening and test-negative) in a multicentre active surveillance in nine hospitals in three regions. No protection against RSV-negative LRTI-hospitalisations was shown. These interim results could guide public-health decision-making.
Assuntos
Anticorpos Monoclonais Humanizados , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Infecções Respiratórias , Lactente , Humanos , Espanha/epidemiologia , Antivirais/uso terapêutico , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Infecções por Vírus Respiratório Sincicial/epidemiologia , Hospitalização , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/prevenção & controle , Infecções Respiratórias/epidemiologia , HospitaisRESUMO
PURPOSE: Drug-induced sleep endoscopy (DISE) is commonly performed in patients suffering obstructive sleep apnea (OSA) with continuous positive airway pressure (CPAP) intolerance. We aimed to evaluate the effects of adding CPAP to DISE to provide understanding of the reason of its failure and better guidance in future therapeutic decisions. METHODS: A retrospective observational descriptive study was conducted on CPAP-intolerant patients with moderate-severe OSA. DISE was used to evaluate upper airway collapsibility, and CPAP was tested to better describe anatomical sites of obstruction and to measure the opening pharyngeal pressure. RESULTS: Sample size consisted of 38 patients with a mean age of 49 ± 9 years. Mean BMI was 28.4 ± 2.4 kg/m2, mean apnea-hypopnea index (AHI) was 35.4 events per hour ± 20.1, and mean saturation under 90% (TSat90) was 14.5%. In DISE we found a collapse at Velum in 92% of patients, at Oropharyngeal level in 89%, at tongue in 42%, and at epiglottis in 36%. In the subgroup of patients with clinical failure with CPAP, we observed 100% of epiglottic collapse and 50% of tongue obstruction. In this specific population, we recommended personalized surgery and myofunctional therapy. CONCLUSION: DISE-CPAP is a useful tool to select the treatment that better fits to each patient taking care all information available. It improves our ability to prescribe a multilevel treatment with an exhaustive topographic evaluation of upper airway collapsibility that complements CPAP classic titration, and it can be helpful to distinguish better candidates for surgery, myofunctional therapy or CPAP.
Assuntos
Pressão Positiva Contínua nas Vias Aéreas , Endoscopia , Apneia Obstrutiva do Sono , Humanos , Pressão Positiva Contínua nas Vias Aéreas/métodos , Apneia Obstrutiva do Sono/terapia , Apneia Obstrutiva do Sono/fisiopatologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Masculino , Feminino , Endoscopia/métodos , Adulto , Obstrução das Vias Respiratórias/terapia , Obstrução das Vias Respiratórias/fisiopatologia , PolissonografiaRESUMO
PURPOSE: To evaluate the influence of viewing the Olfatín Project video on the assessment of school LAIV-associated pain in three and four-year-old children through the Wong Baker Faces® pain classification scale. DESIGN AND METHODS: A three-arm randomized multicenter clinical trial with a placebo control group was carried out. The main variable measured was pain, assessed through the score on the Wong Baker Faces® Pain Rating Scale. There were a total population of 4591 children three and four-year-olds (born in 2019 and 2020) and who attended the 1st and 2nd year of early childhood education. Before the school vaccination, researchers randomly assigned participant schools corresponding to each of the basic health areas to each of the three study groups: Olfatín's video viewing, a control video viewing not related to influenza and no video viewing. RESULTS: No significant differences according to sex, age or the minor's grade according to the assigned intervention were detected. 72.3% of those vaccinated assigned a 0 from the Wong Baker Faces® scale: 75.4% of those who watched Olfatín's video, 68.3% for those in Drilo's group and 72.8% for those who didn't watch any video, but without significant differences (p = 0.08). There were no significant differences either stratifying by sex. CONCLUSION: LAIV is a painless vaccine for children, which has to be taken into account by the health authorities when planning the pediatric influenza vaccination campaign. PRACTICE IMPLICATIONS: Olfatín's cartoon video can be used by professionals to create a greater experience for children and therefore a better acceptance.
RESUMO
A novel rare mutation in the pore region of Nav1.5 channels (p.L889V) has been found in three unrelated Spanish families that produces quite diverse phenotypic manifestations (Brugada syndrome, conduction disease, dilated cardiomyopathy, sinus node dysfunction, etc.) with variable penetrance among families. We clinically characterized the carriers and recorded the Na+ current (INa) generated by p.L889V and native (WT) Nav1.5 channels, alone or in combination, to obtain further insight into the genotypic-phenotypic relationships in patients carrying SCN5A mutations and in the molecular determinants of the Nav1.5 channel function. The variant produced a strong dominant negative effect (DNE) since the peak INa generated by p.L889V channels expressed in Chinese hamster ovary cells, either alone (-69.4 ± 9.0 pA/pF) or in combination with WT (-62.2 ± 14.6 pA/pF), was significantly (n ≥ 17, p < 0.05) reduced compared to that generated by WT channels alone (-199.1 ± 44.1 pA/pF). The mutation shifted the voltage dependence of channel activation and inactivation to depolarized potentials, did not modify the density of the late component of INa, slightly decreased the peak window current, accelerated the recovery from fast and slow inactivation, and slowed the induction kinetics of slow inactivation, decreasing the fraction of channels entering this inactivated state. The membrane expression of p.L889V channels was low, and in silico molecular experiments demonstrated profound alterations in the disposition of the pore region of the mutated channels. Despite the mutation producing a marked DNE and reduction in the INa and being located in a critical domain of the channel, its penetrance and expressivity are quite variable among the carriers. Our results reinforce the argument that the incomplete penetrance and phenotypic variability of SCN5A loss-of-function mutations are the result of a combination of multiple factors, making it difficult to predict their expressivity in the carriers despite the combination of clinical, genetic, and functional studies.
Assuntos
Cricetulus , Canal de Sódio Disparado por Voltagem NAV1.5 , Linhagem , Penetrância , Canal de Sódio Disparado por Voltagem NAV1.5/genética , Canal de Sódio Disparado por Voltagem NAV1.5/metabolismo , Humanos , Animais , Células CHO , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Espanha , Mutação com Perda de Função , Fenótipo , MutaçãoRESUMO
Nitrate pollution in aquifers is a global concern. Spain has developed a national strategy to recover nitrate polluted aquifers aligned with the European Union (EU) policies, specifically through the water planning under the EU Water Framework Directive. River basin management plans use PATRICAL model results to define the maximum nitrogen surplus in each polluted aquifer for the first time. The maximum nitrogen surplus allows to reach the good status in each aquifer and the model provides the number of years required. Around 30% of the aquifers in Spain is currently heavily polluted by nitrates. Model results show that 90% of these aquifers can be recovered in next 6-12 years by increasing nitrogen use efficiency and reducing nitrogen losses around 50%, which is in line with the EU Farm to Fork Strategy. The remaining aquifers require additional reductions to achieve the good status. In Spain this increase in nitrogen efficiency can be obtained with different measures including 30% reduction of current fertilization.
Assuntos
Água Subterrânea , Poluentes Químicos da Água , Espanha , Nitratos/análise , Nitrogênio/análise , Poluentes Químicos da Água/análise , Monitoramento Ambiental/métodos , Abastecimento de Água , ÁguaRESUMO
An automated system for acquiring microscopic-resolution radiographic images of biological samples was developed. Mass-produced, low-cost, and easily automated components were used, such as Commercial-Off-The-Self CMOS image sensors (CIS), stepper motors, and control boards based on Arduino and RaspberryPi. System configuration, imaging protocols, and Image processing (filtering and stitching) were defined to obtain high-resolution images and for successful computational image reconstruction. Radiographic images were obtained for animal samples including the widely used animal models zebrafish (Danio rerio) and the fruit-fly (Drosophila melanogaster), as well as other small animal samples. The use of phosphotungstic acid (PTA) as a contrast agent was also studied. Radiographic images with resolutions of up to (7±0.6)µm were obtained, making this system comparable to commercial ones. This work constitutes a starting point for the development of more complex systems such as X-ray attenuation micro-tomography systems based on low-cost off-the-shelf technology. It will also bring the possibility to expand the studies that can be carried out with small animal models at many institutions (mostly those working on tight budgets), particularly those on the effects of ionizing radiation and absorption of heavy metal contaminants in animal tissues.
Assuntos
Drosophila melanogaster , Peixe-Zebra , Animais , Raios X , Radiografia , Processamento de Imagem Assistida por Computador/métodosRESUMO
Writing as we know it today is a relatively new development in the cultural history of humanity. More current still is the massiveness of the literacy of the population. Since the origins of psychiatry, writing has been an inherent part of it in the medical literature, but it has also been a tool applied in practice in various formats, both for diagnostic and therapeutic purposes. However, compared to the classic communication tools, such as speech, and in child psychiatry, also play and drawing, writing seems to have been relegated. In this bibliographical research, that would not have precedents of its kind, a historical overview of the subject was carried out from the emergence of psychiatry as a specialty to the present day; where events such as the World Wars, the evolution of the concept of disability or the COVID-19 pandemic seem to have played a key role in delimiting variables that characterize at least three historical periods and presuming a fourth in full gestation. The technological support with which it is written and the use and format given to writing were the main variables of the different periods. Being a time of very high demand in Mental Health, challenging in its accessibility and the massive use of writing from information technologies, this research would represent a significant contribution to the development of writing as a tool for the practice of psychiatry and mental health.
La escritura como la conocemos hoy en día es un desarrollo relativamente nuevo en la historia cultural de la humanidad. Más actual aún es la masividad de la alfabetización de la población. Desde los orígenes de la psiquiatría, la escritura forma parte inherente de ésta en la bibliografía médica pero también como una herramienta aplicada en la práctica en diversos formatos, tanto con fines diagnósticos como terapéuticos. No obstante, frente a las herramientas clásicas de comunicación, como el habla, y en la psiquiatría infantil, también el juego y el dibujo, la escritura parece haber sido relegada. En esta investigación bibliográfica, que no tendría antecedentes en su tipo, se realizó un recorrido histórico de la temática desde el surgimiento de la psiquiatría como especialidad hasta nuestros días; donde hechos como las Guerras Mundiales, la evolución del concepto de discapacidad o la pandemia por COVID-19 parecen haber jugado un papel clave para delimitar variables que caracterizan, al menos, tres períodos históricos y presumir un cuarto en plena gestación. El soporte tecnológico con el que se escribe y el uso y formato dado a la escritura resultaron las principales variables de los distintos períodos. Siendo ésta una época de muy alta demanda en Salud Mental, desafiante en su accesibilidad y la masividad en el uso de la escritura a partir de tecnologías de la información, esta investigación representaría un aporte significativo al desarrollo de la escritura como herramienta para la práctica de la psiquiatría y la salud mental.
Assuntos
Saúde Mental , Psiquiatria , Redação , Estudos RetrospectivosRESUMO
Carbonate-rich soils limit plant performance and crop production. Previously, local adaptation to carbonated soils was detected in wild Arabidopsis thaliana accessions, allowing the selection of two demes with contrasting phenotypes: A1 (carbonate tolerant, c+) and T6 (carbonate sensitive, c-). Here, A1(c+) and T6(c - ) seedlings were grown hydroponically under control (pH 5.9) and bicarbonate conditions (10 mM NaHCO3 , pH 8.3) to obtain ionomic profiles and conduct transcriptomic analysis. In parallel, A1(c+) and T6(c - ) parental lines and their progeny were cultivated on carbonated soil to evaluate fitness and segregation patterns. To understand the genetic architecture beyond the contrasted phenotypes, a bulk segregant analysis sequencing (BSA-Seq) was performed. Transcriptomics revealed 208 root and 2503 leaf differentially expressed genes in A1(c+) versus T6(c - ) comparison under bicarbonate stress, mainly involved in iron, nitrogen and carbon metabolism, hormones and glycosylates biosynthesis. Based on A1(c+) and T6(c - ) genome contrasts and BSA-Seq analysis, 69 genes were associated with carbonate tolerance. Comparative analysis of genomics and transcriptomics discovered a final set of 18 genes involved in bicarbonate stress responses that may have relevant roles in soil carbonate tolerance.
Assuntos
Bicarbonatos , Solo , Bicarbonatos/metabolismo , Carbonatos/metabolismo , Perfilação da Expressão Gênica , Genômica , Regulação da Expressão Gênica de PlantasRESUMO
Decades of extensive efforts on marine collagen extraction and characterization allowed to recognize the unique and excellent characteristics of marine collagen offering advantages over that obtained from terrestrial sources. However, not all marine collagens have the same biochemical characteristics; understanding those at molecular and supramolecular level, is crucial for optimal design of applications. One relevant aspect of collagen characterization is the analysis of its different subunits (α-chains) and their intermolecular cross-links (ß- and γ-components), which ultimately determine the specific functions of a particular collagen. Collagens from a teleost and an elasmobranch species were analyzed to understand the influence of their subunit composition and intermolecular crosslinking pattern on their different physicochemical behaviour. For comparative purposes a commercial mammal collagen was included in the study. Although electrophoretic profiles showed the typical composition of type I collagen for hake, blue shark and calf collagen, molar ratios of their α-chains were different indicating a different degree of dimerization of their α2-chains with implications in the presence of a different crosslinking degree pattern. Electrophoresis, amino acid composition, hydrophobicity (RP-HPLC) and molecular weight analysis (GPC-HPLC) results, besides a peptide mapping and an antioxidant activity study of the resultant peptides, would help to understand the role of different subunit collagen composition and different crosslinking pattern in the conformation of a differential quaternary supramolecular structure within different species and its biofunctional implications. The experiments developed would allow to progress in the valorization potential of fish discards and byproducts to explore commercial uses of collagens from marine origin.
Assuntos
Colágeno , Gadiformes , Animais , Aminoácidos , Cromatografia Líquida de Alta Pressão , Dimerização , MamíferosRESUMO
The microwave detection capability of GaN-based asymmetric planar nanodiodes (so-called Self-Switching Diode, SSD, due to its non-linearity) has been characterized in a wide temperature range, from 70 K up to 300 K. At low temperature, microwave measurements reveal an enhancement of the responsivity at frequencies below 1 GHz, which, together with a pronounced hysteresis in the DC curves, indicate a significant influence of the surface states. This leads to a significant variability and non-repeatability which needs to be reduced since it degrades the accuracy of the detection. For this sake, the RF characterization was repeated after applying a positive/negative voltage able to fill/empty the surface states in order to have a well-established preconditioned state. As a consequence of the positive pre-soak bias, a significant enhancement of the measured responsivity, with a × 10 increase at low temperature. The RF detection measurements after such preconditioning contains a time dependence induced by the slow discharge mechanism of the traps, so that the improved responsivity remains even after 100s of seconds. On the other hand, a negative voltage pre-soak benefits the discharge process, thus suppressing the low frequency dispersion and the important variability of the detection without the pre-conditioning step. We also show that the relation between the voltage and current responsivities in each case allows to explain the impact of the surface charges in terms of the device impedance.