The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients

Background: Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. Methods: Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. Results: Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0-171.2] to 180.0 [135.4-227.9] mmHg and the ventilatory ratio from 1.73 [1.33-2.25] to 1.96 [1.61-2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01-1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01-1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93-1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). Conclusions: Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation

Papel de la proteína de adhesión sináptica neurexina 1 en autismo

1 página. IX Jornadas Andaluzas Salud Investiga. Cádiz 20-22 octubre, 2010.El Trastorno del Espectro Autista (TEA) es un conjunto de síndromes del desarrollo que se caracterizan por déficit en la interacción social, comunicación restringida y comportamientos estereotipados. Hasta un 70% de los casos están asociados a retraso mental. La mayor parte de los casos de TEA se enmarcan dentro de las enfermedades complejas, causadas por la combinación de alelos de susceptibilidad y factores ambientales. Se han identificado mutaciones y variaciones estructurales en genes que codifican proteínas sinápticas, como las neurexinas, que podrían incrementar el riesgo a desarrollar la enfermedad. Los objetivos de nuestro estudio son entender el mecanismo de acción de neurexina-1 beta (NRXN1β) en el desarrollo del TEA.Peer reviewe

Mutations affecting synaptic levels of neurexin-1ß in autism and mental retardation

The identification of mutations in genes encoding proteins of the synaptic neurexin–neuroligin pathway in different neurodevelopmental disorders, including autism and mental retardation, has suggested the presence of a shared underlying mechanism. A few mutations have been described so far and for most of them the biological consequences are unknown. To further explore the role of the NRXN1β gene in neurodevelopmental disorders, we have sequenced the coding exons of the gene in 86 cases with autism and mental retardation and 200 controls and performed expression analysis of DNA variants identified in patients. We report the identification of four novel independent mutations that affect nearby positions in two regions of the gene/protein: i) sequences important for protein translation initiation, c.− 3G>T within the Kozak sequence, and c.3G>T (p.Met1), at the initiation codon; and ii) the juxtamembrane region of the extracellular domain, p.Arg375Gln and p.Gly378Ser. These mutations cosegregate with different psychiatric disorders other than autism and mental retardation, such as psychosis and attention-deficit/hyperactivity disorder. We provide experimental evidence for the use of an alternative translation initiation codon for c.− 3G>T and p.Met1 mutations and reduced synaptic levels of neurexin-1β protein resulting from p.Met1 and p.Arg375Gln. The data reported here support a role for synaptic defects of neurexin-1β in neurodevelopmental disorders.The authors gratefully thank the participation of patients and their families; Dr. S. Sommer for providing the sequences of PCR primers; Dr. P. Scheiffele for helpful comments; R.J. Meléndez-Cadenas for excellent technical assistance; and Dr. Miguel Lucas for support. This work was funded by grants from the Instituto de Salud Carlos III (ISCIII; PI081446 to F.G.S.) and Junta de Andalucía (P07-CVI-02943 to F.G.S., P07-CVI-0270 to A.M-M. and P06-CVI-02392). R.J.C-G. is a recipient of a fellowship from ISCIII (FI08/00730).Peer Reviewe

Report from the Killer-cell Immunoglobulin-like Receptors (KIR) component of the 17th International HLA and Immunogenetics Workshop

The goals of the KIR component of the 17th International HLA and Immunogenetics Workshop (IHIW) were to encourage and educate researchers to begin analyzing KIR at allelic resolution, and to survey the nature and extent of KIR allelic diversity across human populations. To represent worldwide diversity, we analyzed 1269 individuals from ten populations, focusing on the most polymorphic KIR genes, which express receptors having three immunoglobulin (Ig)-like domains (KIR3DL1/S1, KIR3DL2 and KIR3DL3). We identified 13 novel alleles of KIR3DL1/S1, 13 of KIR3DL2 and 18 of KIR3DL3. Previously identified alleles, corresponding to 33 alleles of KIR3DL1/S1, 38 of KIR3DL2, and 43 of KIR3DL3, represented over 90% of the observed allele frequencies for these genes. In total we observed 37 KIR3DL1/S1 allotypes, 40 for KIR3DL2 and 44 for KIR3DL3. As KIR allotype diversity can affect NK cell function, this demonstrates potential for high functional diversity worldwide. Allelic variation further diversifies KIR haplotypes. We determined KIR3DL3 ∼ KIR3DL1/S1 ∼ KIR3DL2 haplotypes from five of the studied populations, and observed multiple population-specific haplotypes in each. This included 234 distinct haplotypes in European Americans, 191 in Ugandans, 35 in Papuans, 95 in Egyptians and 86 in Spanish populations. For another 35 populations, encompassing 642,105 individuals we focused on KIR3DL2 and identified another 375 novel alleles, with approximately half of them observed in more than one individual. The KIR allelic level data gathered from this project represents the most comprehensive summary of global KIR allelic diversity to date, and continued analysis will improve understanding of KIR allelic polymorphism in global populations. Further, the wealth of new data gathered in the course of this workshop component highlights the value of collaborative, community-based efforts in immunogenetics research, exemplified by the IHIW

Report from the Killer-cell Immunoglobulin-like Receptors (KIR) component of the 17th International HLA and Immunogenetics Workshop.

The goals of the KIR component of the 17th International HLA and Immunogenetics Workshop (IHIW) were to encourage and educate researchers to begin analyzing KIR at allelic resolution, and to survey the nature and extent of KIR allelic diversity across human populations. To represent worldwide diversity, we analyzed 1269 individuals from ten populations, focusing on the most polymorphic KIR genes, which express receptors having three immunoglobulin (Ig)-like domains (KIR3DL1/S1, KIR3DL2 and KIR3DL3). We identified 13 novel alleles of KIR3DL1/S1, 13 of KIR3DL2 and 18 of KIR3DL3. Previously identified alleles, corresponding to 33 alleles of KIR3DL1/S1, 38 of KIR3DL2, and 43 of KIR3DL3, represented over 90% of the observed allele frequencies for these genes. In total we observed 37 KIR3DL1/S1 allotypes, 40 for KIR3DL2 and 44 for KIR3DL3. As KIR allotype diversity can affect NK cell function, this demonstrates potential for high functional diversity worldwide. Allelic variation further diversifies KIR haplotypes. We determined KIR3DL3 ∼ KIR3DL1/S1 ∼ KIR3DL2 haplotypes from five of the studied populations, and observed multiple population-specific haplotypes in each. This included 234 distinct haplotypes in European Americans, 191 in Ugandans, 35 in Papuans, 95 in Egyptians and 86 in Spanish populations. For another 35 populations, encompassing 642,105 individuals we focused on KIR3DL2 and identified another 375 novel alleles, with approximately half of them observed in more than one individual. The KIR allelic level data gathered from this project represents the most comprehensive summary of global KIR allelic diversity to date, and continued analysis will improve understanding of KIR allelic polymorphism in global populations. Further, the wealth of new data gathered in the course of this workshop component highlights the value of collaborative, community-based efforts in immunogenetics research, exemplified by the IHIW

Nutrient loading of forest tree seedlings to promote stress resistance and field performance:a Mediterranean perspective

The planting environment of Mediterranean areas is highly challenging as summer drought and winter frost jeopardize survival, and soil infertility limits establishment success. We review the potential for seedling nutrient loading to alleviate these post-planting stresses. A growing body of evidence indicates that nitrogen (N) rich seedlings have improved field performance in Mediterranean environments, due to their ability to grow new roots rapidly and out-compete weeds. In addition, frost resistance during hardening is crucial for relatively cold inland nurseries; recent research shows a positive relationship between N and shoot frost resistance though a knowledge gap exists regarding the influence of nutrition on root frost resistance. Some new evidence also implicates phosphorus as an important driver of seedling response in the Mediterranean due to its influence on root growth and physiology. Nutrient status influences other functional attributes critical to survival in Mediterranean areas, such as drought tolerance, root hydraulic conductivity, and mycorrhization. In light of the apparent benefits of high nutrient reserves for seedling performance in Mediterranean areas, we also review techniques for nursery nutrient loading. Exponential fertilization can be applied when species’ growth patterns match this application regime. However, many Mediterranean species exhibit episodic growth indicating that constant or fall fertilization could be more effective in reaching loading. In particular, late-season fertilization has shown good potential to avert nutrient dilution in the fall and increase frost resistance. Several needs for future research are identified, with special emphasis on the necessity to match fertilization regimes to species ecological traits and planting conditions