5 research outputs found
Hereditary Angioedema: Diagnosis, Management, Current State of Art and Advances
Abstract
Hereditary angioedema (HAE) is a rare, mostly inherited disorder however 25% of patients have de novo mutations. Although itâs rarity, it can be life threatening due to laryngeal involvement. Along with understanding the basis of swelling, several new treatment options aside from C1-inhibitory protein (C1-INH) replacement have been developed and are avaible on the markets. However the avaibility of approved drugs for attacks of HAE varies world wide. Treatment management requires angioedema attacks treatment, pre-procedural treatment and long term prophylaxis (LTP). C1-INH which was firstly developed and approved for on-demand treatment, pre-procedural treatment and LTP by iv route, nowadays for LTP, other developed and approved options are used by orally and sc route. Despite the new developing medications, permanent treatment such as gene therapy is needed
Elevers utĂ„tagerande beteende â Elevers och pedagogers syn pĂ„ problematiken kring ett utĂ„tagerande beteende
Denna studies syfte Ă€r att kunna förstĂ„ elevers utĂ„tagerande beteende utifrĂ„n bĂ„de lĂ€rares och elevers perspektiv. Detta genom att belysa bĂ„de elevers syn pĂ„ problematiken och lĂ€rares förhĂ„llningssĂ€tt till olika situationer som kan uppstĂ„ i mötet med elever som agerar utĂ„triktat. Detta valde vi att undersöka för det vĂ€ckte ett intresse hos oss ute pĂ„ praktiken, dĂ€r vi ofta uppmĂ€rksammade situationer med elever som ansĂ„gs vara utĂ„tagerande samt hur pedagogerna tog kontroll över dessa tillstĂ„nd. För att fĂ„ en djupare förstĂ„else för vad ett utĂ„tagerande beteende Ă€r har vi tagit upp tidigare forskning. Forskningen utgĂ„r frĂ„n tre olika perspektiv fysiologiskt, sociokulturellt och psykodynamiskt perspektiv, dĂ€r forskarna tar upp olika vinklar om hur de tror att ett utĂ„tagerande beteende uppstĂ„r.I denna studie anvĂ€nde vi oss av bĂ„de en kvantitativ och en kvalitativ metod. Framförallt valde vi att anvĂ€nda oss av enkĂ€ter med elever pĂ„ mellanstadiet i Ă„rskurs 4-6. De flesta av dessa elever gick Ă€ven pĂ„ fritidshemmet och det var 133 elever som medverkade i enkĂ€tundersökningen. Resultatet frĂ„n enkĂ€tundersökningen visar att majoriteten av eleverna valde att undvika att hamna i brĂ„k, bĂ„de med kamrater och lĂ€rare. Vi anvĂ€nde oss Ă€ven av enkĂ€ter via mail till pedagoger, dĂ€r vi fick kontakt med sex olika pedagoger som gick med pĂ„ att delta i undersökningen. Resultatet av enkĂ€terna visar att pedagogerna valde att undvika att dra slutsatser om eleverna som skulle förknippas med ett utĂ„tagerande beteende, pĂ„ grund av en önskan att undvika att befĂ€sta ett beteendemönster hos eleverna. Pedagogerna var Ă€ven överens om hur de skulle hantera situationer som kunde uppstĂ„ nĂ€r de bemötte elever som ansĂ„gs vara utĂ„tagerande. De var Ă€ven medvetna om att deras bemötande kunde pĂ„verka elevers beteende. För att kunna sĂ€tta enkĂ€terna i ett sammanhang och fĂ„ en övergripande bild av skolmiljön, sĂ„ valde vi Ă€ven att genomföra observationer som gjordes ute pĂ„ rasten, pĂ„ skolgĂ„rden och i kapprummen. Anledningen var att vi ville fĂ„ en förstĂ„else för hur eleverna agerade och uppförde sig kring sina kamrater och lĂ€rare. I vĂ„rt resultat kom vi fram till att eleverna, trots att de svarade i enkĂ€terna att de valde att undvika att hamna i konflikter, tycktes söka konflikter och brĂ„k mellan sina kamrater och lĂ€rare. Dessutom visar resultatet att flera av de konflikter som uppstod pĂ„ skolan avgjordes av hur eleverna blev bemötta â av lĂ€rare och av andra elever
Adverse COVID-19 Outcomes in Immune Deficiencies; Inequality Exists Between Subclasses.
Background Genetic deficiencies of immune system, referred to as inborn errors of immunity (IEI), serve as a valuable model to study human immune responses. In a multicenter prospective cohort, we evaluated the outcome of SARS-CoV-2 infection among IEI subjects and analyzed genetic and immune characteristics that determine adverse COVID-19 outcomes. Methods We studied 34 IEI patients (19M/15F, 12 [min: 0.6-max: 43] years) from six centers. We diagnosed COVID-19 infection by finding a positive SARS-CoV-2 PCR test (n = 25) and/or a lung tomography scoring (CORADS) >= 4 (n = 9). We recorded clinical and laboratory findings prospectively, fitted survival curves, and calculated fatality rates for the entire group and each IEI subclass. Results Nineteen patients had combined immune deficiency (CID), six with predominantly antibody deficiency (PAD), six immune dysregulation (ID), two innate immune defects, and one in the autoinflammatory class. Overall, 23.5% of cases died, with disproportionate fatality rates among different IEI categories. PAD group had a relatively favorable outcome at any age, but CIDs and IDs were particularly vulnerable. At admission, presence of dyspnea was an independent risk for COVID-related death (OR: 2.630, 95% CI; 1.198-5.776, p < .001). Concerning predictive roles of laboratory markers at admission, deceased subjects compared to survived had significantly higher CRP, procalcitonin, Troponin-T, ferritin, and total-lung-score (p = .020, p = .003, p = .014, p = .013, p = .020; respectively), and lower absolute lymphocyte count, albumin, and trough IgG (p = .012, p = .022, p = .011; respectively). Conclusion Our data disclose a highly vulnerable IEI subgroup particularly disadvantaged for COVID-19 despite their youth. Future studies should address this vulnerability and consider giving priority to these subjects in SARS-Cov-2 therapy trials
A Stk4-Foxp3-NF-kappa B p65 transcriptional complex promotes T-reg cell activation and homeostasis
The molecular programs involved in regulatory T (T-reg) cell activation and homeostasis remain incompletely understood. Here, we show that T cell receptor (TCR) signaling in T-reg cells induces the nuclear translocation of serine/threonine kinase 4 (Stk4), leading to the formation of an Stk4-NF-kappa B p65-Foxp3 complex that regulates Foxp3- and p65-dependent transcriptional programs. This complex was stabilized by Stk4-dependent phosphorylation of Foxp3 on serine-418. Stk4 deficiency in T-reg cells, either alone or in combination with its homolog Stk3, precipitated a fatal autoimmune lymphoproliferative disease in mice characterized by decreased Treg cell p65 expression and nuclear translocation, impaired NF-kappa B p65-Foxp3 complex formation, and defective Treg cell activation. In an adoptive immunotherapy model, overexpression of p65 or the phosphomimetic Foxp3S418E in Stk3/4-deficient T-reg cells ameliorated their immune regulatory defects. Our studies identify Stk4 as an essential TCR-responsive regulator of p65-Foxp3-dependent transcription that promotes T-reg cellmediated immune tolerance