83 research outputs found
Corrigendum to âSphingolipids as Mediators in the Crosstalk between Microbiota and Intestinal Cells: Implications for Inflammatory Bowel Diseaseâ
Sphingolipids as Mediators in the Crosstalk between Microbiota and Intestinal Cells: Implications for Inflammatory Bowel Disease
Failing to Make Ends Meet: The Broad Clinical Spectrum of DNA Ligase IV Deficiency. Case Series and Review of the Literature
DNA repair defects are inborn errors of immunity that result in increased apoptosis and oncogenesis. DNA Ligase 4-deficient patients suffer from a wide range of clinical manifestations since early in life, including: microcephaly, dysmorphic facial features, growth failure, developmental delay, mental retardation; hip dysplasia, and other skeletal malformations; as well as a severe combined immunodeficiency, radiosensitivity, and progressive bone marrow failure; or, they may present later in life with hematological neoplasias that respond catastrophically to chemo- and radiotherapy; or, they could be asymptomatic. We describe the clinical, laboratory, and genetic features of five Mexican patients with LIG4 deficiency, together with a review of 36 other patients available in PubMed Medline. Four out of five of our patients are dead from lymphoma or bone marrow failure, with severe infection and massive bleeding; the fifth patient is asymptomatic despite a persistent CD4+ lymphopenia. Most patients reported in the literature are microcephalic females with growth failure, sinopulmonary infections, hypogammaglobulinemia, very low B-cells, and radiosensitivity; while bone marrow failure and malignancy may develop at a later age. Dysmorphic facial features, congenital hip dysplasia, chronic liver disease, gradual pancytopenia, lymphoma or leukemia, thrombocytopenia, and gastrointestinal bleeding have been reported as well. Most mutations are compound heterozygous, and all of them are hypomorphic, with two common truncating mutations accounting for the majority of patients. Stem-cell transplantation after reduced intensity conditioning regimes may be curative
Controlo quĂmico de infestantes
Uma planta Ă© considerada infestante quando nasce espontaneamente num local e momento indesejados, podendo interferir negativamente com a cultura instalada.
As infestantes competem com as culturas para o espaço, a luz, ågua e nutrientes, podendo atrasar e prejudicar as operaçÔes de colheita, depreciar o produto final e assegurarem a reinfestação nas culturas seguintes.
Dado o modo de propagação diferenciado das diversas espĂ©cies de infestantes, com as anuais a propagarem-se por semente e as perenes ou vivazes a assegurarem a sua propagação atravĂ©s de ĂłrgĂŁos vegetativos (rizomas, bolbos, tubĂ©rculos, etc.), assim, tambĂ©m o seu controlo quer quĂmico, quer mecĂąnico terĂĄ que ser diferenciado, ou seja, para controlar infestantes anuais serĂĄ suficiente destruir a sua parte aĂ©rea, enquanto para controlar infestantes perenes teremos que destruir os seus ĂłrgĂŁos reprodutivos.
O controlo de infestantes poderĂĄ ser quĂmico, atravĂ©s da utilização de herbicidas, ou mecĂąnico pela utilização de alfaias agrĂcolas, tais como a charrua de aivecas, a charrua de discos, a grade de discos, o escarificador e a fresa. Quando a tĂ©cnica utilizada na instalação das culturas Ă© a sementeira directa, o controlo das infestantes terĂĄ que ser obrigatoriamente quĂmico, enquanto se o recurso Ă mobilização do solo for a tĂ©cnica mais utilizada (sistema de mobilização tradicional ou sistema de mobilização reduzida), o controlo das infestantes tanto poderĂĄ ser quĂmico como mecĂąnico.
Neste trabalho iremos abordar apenas, o controlo quĂmico de infestantes
Emergence of methicillin resistance predates the clinical use of antibiotics
The discovery of antibiotics more than 80 years ago has led to considerable improvements in human and animal health. Although antibiotic resistance in environmental bacteria is ancient, resistance in human pathogens is thought to be a modern phenomenon that is driven by the clinical use of antibiotics(1). Here we show that particular lineages of methicillin-resistant Staphylococcus aureus-a notorious human pathogen-appeared in European hedgehogs in the pre-antibiotic era. Subsequently, these lineages spread within the local hedgehog populations and between hedgehogs and secondary hosts, including livestock and humans. We also demonstrate that the hedgehog dermatophyte Trichophyton erinacei produces two beta-lactam antibiotics that provide a natural selective environment in which methicillin-resistant S. aureus isolates have an advantage over susceptible isolates. Together, these results suggest that methicillin resistance emerged in the pre-antibiotic era as a co-evolutionary adaptation of S. aureus to the colonization of dermatophyte-infected hedgehogs. The evolution of clinically relevant antibiotic-resistance genes in wild animals and the connectivity of natural, agricultural and human ecosystems demonstrate that the use of a One Health approach is critical for our understanding and management of antibiotic resistance, which is one of the biggest threats to global health, food security and development
Jardins per a la salut
Facultat de FarmĂ cia, Universitat de Barcelona. Ensenyament: Grau de FarmĂ cia. Assignatura: BotĂ nica farmacĂšutica. Curs: 2014-2015. Coordinadors: Joan Simon, CĂšsar BlanchĂ© i Maria Bosch.Els materials que aquĂ es presenten sĂłn el recull de les fitxes botĂ niques de 128 espĂšcies presents en el JardĂ Ferran Soldevila de lâEdifici HistĂČric de la UB. Els treballs han estat realitzats manera individual per part dels estudiants dels grups M-3 i T-1 de lâassignatura BotĂ nica FarmacĂšutica durant els mesos de febrer a maig del curs 2014-15 com a resultat final del Projecte dâInnovaciĂł Docent «Jardins per a la salut: aprenentatge servei a BotĂ nica farmacĂšutica» (codi 2014PID-UB/054). Tots els treballs sâhan dut a terme a travĂ©s de la plataforma de GoogleDocs i han estat tutoritzats pels professors de lâassignatura. Lâobjectiu principal de lâactivitat ha estat fomentar lâaprenentatge autĂČnom i col·laboratiu en BotĂ nica farmacĂšutica. TambĂ© sâha pretĂšs motivar els estudiants a travĂ©s del retorn de part del seu esforç a la societat a travĂ©s dâuna experiĂšncia dâAprenentatge-Servei, deixant disponible finalment el treball dels estudiants per a poder ser consultable a travĂ©s dâuna Web pĂșblica amb la possibilitat de poder-ho fer in-situ en el propi jardĂ mitjançant codis QR amb un smartphone
Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-Ï auto-Abs in children
We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-alpha 2 in 10 patients: IFN-alpha 2 only in three, IFN-alpha 2 plus IFN-omega in five, and IFN-alpha 2, IFN-omega plus IFN-beta in two; IFN-omega only in nine patients). Seven children (3.8%) had Abs neutralizing at least 10 ng/ml of one IFN, whereas the other 12 (6.6%) had Abs neutralizing only 100 pg/ml. The auto-Abs neutralized both unglycosylated and glycosylated IFNs. We also detected auto-Abs neutralizing 100 pg/ml IFN-alpha 2 in 4 of 2,267 uninfected children (0.2%) and auto-Abs neutralizing IFN-omega in 45 children (2%). The odds ratios (ORs) for life-threatening COVID-19 pneumonia were, therefore, higher for auto-Abs neutralizing IFN-alpha 2 only (OR [95% CI] = 67.6 [5.7-9,196.6]) than for auto-Abs neutralizing IFN-. only (OR [95% CI] = 2.6 [1.2-5.3]). ORs were also higher for auto-Abs neutralizing high concentrations (OR [95% CI] = 12.9 [4.6-35.9]) than for those neutralizing low concentrations (OR [95% CI] = 5.5 [3.1-9.6]) of IFN-omega and/or IFN-alpha 2
Autoantibodies against type I IFNs in patients with critical influenza pneumonia
In an international cohort of 279 patients with hypoxemic influenza pneumonia, we identified 13 patients (4.6%) with autoantibodies neutralizing IFN-alpha and/or -omega, which were previously reported to underlie 15% cases of life-threatening COVID-19 pneumonia and one third of severe adverse reactions to live-attenuated yellow fever vaccine. Autoantibodies neutralizing type I interferons (IFNs) can underlie critical COVID-19 pneumonia and yellow fever vaccine disease. We report here on 13 patients harboring autoantibodies neutralizing IFN-alpha 2 alone (five patients) or with IFN-omega (eight patients) from a cohort of 279 patients (4.7%) aged 6-73 yr with critical influenza pneumonia. Nine and four patients had antibodies neutralizing high and low concentrations, respectively, of IFN-alpha 2, and six and two patients had antibodies neutralizing high and low concentrations, respectively, of IFN-omega. The patients' autoantibodies increased influenza A virus replication in both A549 cells and reconstituted human airway epithelia. The prevalence of these antibodies was significantly higher than that in the general population for patients 70 yr of age (3.1 vs. 4.4%, P = 0.68). The risk of critical influenza was highest in patients with antibodies neutralizing high concentrations of both IFN-alpha 2 and IFN-omega (OR = 11.7, P = 1.3 x 10(-5)), especially those <70 yr old (OR = 139.9, P = 3.1 x 10(-10)). We also identified 10 patients in additional influenza patient cohorts. Autoantibodies neutralizing type I IFNs account for similar to 5% of cases of life-threatening influenza pneumonia in patients <70 yr old
Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs
Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population
X-linked agammaglobulinemia (XLA) : Phenotype, diagnosis, and therapeutic challenges around the world
Background: X-linked agammaglobulinemia is an inherited immunodeficiency recognized since 1952. In spite of seven decades of experience, there is still a limited understanding of regional differences in presentation and complications. This study was designed by the Primary Immunodeficiencies Committee of the World Allergy Organization to better understand regional needs, challenges and unique patient features. Methods: A survey instrument was designed by the Primary Immunodeficiencies Committee of the World Allergy Organization to collect both structured and semi-structured data on X-linked agammaglobulinemia. The survey was sent to 54 centers around the world chosen on the basis of World Allergy Organization participation and/or registration in the European Society for Immunodeficiencies. There were 40 centers that responded, comprising 32 countries. Results: This study reports on 783 patients from 40 centers around the world. Problems with diagnosis are highlighted by the reported delays in diagnosis>24 months in 34% of patients and the lack of genetic studies in 39% of centers Two infections exhibited regional variation. Vaccine-associated paralytic poliomyelitis was seen only in countries with live polio vaccination and two centers reported mycobacteria. High rates of morbidity were reported. Acute and chronic lung diseases accounted for 41% of the deaths. Unusual complications such as inflammatory bowel disease and large granular lymphocyte disease, among others were specifically enumerated, and while individually uncommon, they were collectively seen in 20.3% of patients. These data suggest that a broad range of both inflammatory, infectious, and autoimmune conditions can occur in patients. The breadth of complications and lack of data on management subsequently appeared as a significant challenge reported by centers. Survival above 20 years of age was lowest in Africa (22%) and reached above 70% in Australia, Europe and the Americas. Centers were asked to report their challenges and responses (n = 116) emphasized the difficulties in access to immunoglobulin products (16%) and reflected the ongoing need for education of both patients and referring physicians. Conclusions: This is the largest study of patients with X-linked agammaglobulinemia and emphasizes the continued morbidity and mortality of XLA despite progress in diagnosis and treatment. It presents a world view of the successes and challenges for patients and physicians alike. A pivotal finding is the need for education of physicians regarding typical symptoms suggesting a possible diagnosis of X-linked agammaglobulinemia and sharing of best practices for the less common complications.Peer reviewe
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