Suppression of IRAK1 or IRAK4 catalytic activity, but not type1 IFN signaling, prevents lupus nephritis in mice expressing a ubiquitin binding-defective mutant of ABIN1

Polymorphisms in the TNIP1 gene encoding A20-binding inhibitor of NF-κB1 (ABIN1) predispose to lupus and other autoimmune diseases in at least eight different human populations. We found previously that knock-in mice expressing a ubiquitin-binding-defective mutant of ABIN1 (ABIN1[D485N]) develop autoimmunity as they age and succumb to a disease resembling lupus nephritis in humans. Here we report that Flt3-derived dendritic cells from these mice overproduced Type1 IFNs upon stimulation with ligands that activate TLR7 or TLR9. However, crossing the ABIN1[D485N] mice to IFNAR1 knock-out mice that do not express the α-subunit of the Type1 IFN receptor, did not prevent splenomegaly, the appearance of high serum levels of auto-antibodies and other Igs, or liver inflammation, and only reduced kidney inflammation modestly. In contrast, crossing the ABIN1[D485N] mice to knock-in mice expressing catalytically inactive mutants of IRAK1 or IRAK4 prevented splenomegaly, autoimmunity, liver and kidney inflammation. Our results support the notion that IRAK1 and/or IRAK4 are attractive targets for the development of drugs to prevent, and perhaps treat, lupus nephritis and other auto-inflammatory diseases caused by decreased ability of ABIN1 or other proteins to restrict the strength of MyD88 signaling

Positive airway pressure longer than 24 h is associated with histopathological volutrauma in severe COVID-19 pneumonia—an ESGFOR based narrative case-control review

SARS-CoV-2; Post-mortem microbiology; VolutraumaSARS-CoV-2; Microbiología post mortem; VolutraumaSARS-CoV-2; Microbiologia post mortem; VolutraumaBackground and Objective: A thorough understanding of the pathogenic mechanisms elicited by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) still requires further research. Until recently, only a restricted number of autopsies have been performed, therefore limiting the accurate knowledge of the lung injury associated with SARS-CoV-2. A multidisciplinary European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group of Forensic and Post-mortem Microbiology-ESGFOR team conducted a non-systematic narrative literature review among coronavirus 2019 disease (COVID-19) pneumonia cases assessing the histopathological (HP) effects of positive airways pressure. HP lung features were recorded and compared between mechanically ventilated (>24 hours) and control (ventilation <24 hours) patients. A logistic regression analysis was performed to identify associations between mechanical ventilation (MV) and HP findings. Methods: A PubMed and MEDLINE search was conducted in order to identify studies published between March 1st 2020 and June 30th 2021. Key Content and Findings: Seventy patients (median age: 69 years) from 24 studies were analysed, among whom 38 (54.2%) underwent MV longer than 24 hours. Overall, main HP features were: diffuse alveolar damage (DAD) in 53 (75.7%), fibrosis (interstitial/intra-alveolar) in 43 (61.4%), vascular damage—including thrombosis/emboli- in 41 (58.5%), and endotheliitis in only 8 (11.4%) patients. Association of DAD, fibrosis and vascular damage was detected in 30 (42.8%) patients. Multivariate analysis, adjusted by age and gender, identified MV >24 hours as an independent variable associated with DAD (OR =5.40, 95% CI: 1.48–19.62), fibrosis (OR =3.88, 95% CI: 1.25–12.08), vascular damage (OR =5.49, 95% CI: 1.78–16.95) and association of DAD plus fibrosis plus vascular damage (OR =6.99, 95% CI: 2.04–23.97). Conclusions: We identified that patients mechanically ventilated >24 hours had a significantly higher rate of pulmonary injury on histopathology independently of age and gender. Our findings emphasize the importance of maintaining a protective ventilator strategy when subjects with COVID-19 pneumonia undergo intubation

Paradoxical effects of Worrisome Thoughts Suppression: the influence of depressive mood

Thought suppression increases the persistence of unwanted idiosyncratic worries thoughts when individuals try to suppress them. The failure of suppression may contribute to the development and maintenance of emotional disorders. Depressive people seem particulary prone to engage in unsuccessful mental control strategies such as thought suppression. Worry has been reported to be elevated in depressed individuals and a dysphoric mood may also contribute for the failure of suppression. No studies examine, however, the suppression of worisome thoughts in individuals with depressive symptoms. To investigate the suppression effects of worrisome thoughts, 46 participants were selected according to the cut-off score of a depressive symptomatology scale and they were divided in two groups (subclinical and nonclinical group). All the individuals took part in an experimental paradigm of thought suppression. The results of the mixed factorial analysis of variance revealed an increased frequency of worrisome thoughts during the suppression phase on depending of the depressive symptoms. These findings confirm that depressive mood can reduce the success of suppression.info:eu-repo/semantics/publishedVersio

Estimates of Pandemic Influenza Vaccine Effectiveness in Europe, 2009–2010: Results of Influenza Monitoring Vaccine Effectiveness in Europe (I-MOVE) Multicentre Case-Control Study

Results from a European multicentre case-control study reported by Marta Valenciano and colleagues suggest good protection by the pandemic monovalent H1N1 vaccine against pH1N1 and no effect of the 2009–2010 seasonal influenza vaccine on H1N1

Placental microbial–metabolite profiles and inflammatory mechanisms associated with preterm birth

There is growing emphasis on the potential significance of the placental microbiome and microbiome–metabolite interactions in immune responses and subsequent pregnancy outcome, especially in relation to preterm birth (PTB). This review discusses in detail the pathomechanisms of placental inflammatory responses and the resultant maternal–fetal allograft rejection in both microbial-induced and sterile conditions. It also highlights some potential placental-associated predictive markers of PTB for future investigation. The existence of a placental microbiome remains debatable. Therefore, an overview of our current understanding of the state and role of the placental microbiome (if it exists) and metabolome in human pregnancy is also provided. We critical evaluate the evidence for a placental microbiome, discuss its functional capacity through the elaborated metabolic products and also describe the consequent and more established fetomaternal inflammatory responses that stimulate the pathway to preterm premature rupture of membranes, preterm labour and spontaneous PTB

Persistent High Burden of Invasive Pneumococcal Disease in South African HIV-Infected Adults in the Era of an Antiretroviral Treatment Program

Highly active antiretroviral treatment (HAART) programs have been associated with declines in the burden of invasive pneumococcal disease (IPD) in industrialized countries. The aim of this study was to evaluate trends in IPD hospitalizations in HIV-infected adults in Soweto, South Africa, associated with up-scaling of the HAART program from 2003 to 2008.Laboratory-confirmed IPD cases were identified from 2003 through 2008 through an existing surveillance program. The period 2003-04 was designated as the early-HAART era, 2005-06 as the intermediate-HAART era and 2007-08 as the established-HAART era. The incidence of IPD was compared between the early-HAART and established-HAART eras in HIV-infected and-uninfected individuals.A total of 2,567 IPD cases among individuals older than 18 years were reported from 2003 through 2008. Overall incidence of IPD (per 100,000) did not change during the study period in HIV-infected adults (207.4 cases in the early-HAART and 214.0 cases in the established-HAART era; p = 0.55). IPD incidence, actually increased 1.16-fold (95% CI: 1.01; 1.62) in HIV-infected females between the early-and established-HAART eras (212.1 cases and 246.2 cases, respectively; p = 0.03). The incidence of IPD remained unchanged in HIV-uninfected adults across the three time periods.Despite a stable prevalence of HIV and the increased roll-out of HAART for treatment of AIDS patients in our setting, the burden of IPD has not decreased among HIV-infected adults. The study indicates a need for ongoing monitoring of disease and HAART program effectiveness to reduce opportunistic infections in African adults with HIV/AIDS, as well as the need to consider alternate strategies including pneumococcal conjugate vaccine immunization for the prevention of IPD in HIV-infected adults

Impacts of authenticity, degree of adaptation and cultural contrast on travellers’ memorable gastronomy experiences

Gastronomy is an essential component of the travel experience and isbecoming one of the “best things to do” in many destinations.Impressions gained from local food coupled with tourists’ attitudes can influence the living experience. This paper analyses the extent to whichthe perceived authenticity of local food, the degree of adaptation andcultural contrast determine memorable tourist experiences. Moreover, itproposes the moderating effect of searching for authenticity andadaptation ability. Results from a sample of international tourists whotried a typical dish support the positive effect of authenticity and culturalcontrast on the perceived experience, whereas product adaptationreduces the perception of authenticity and cultural contrast. Authenticityhas a greater effect on experience perception when actively sought bytourists, and individuals are less influenced by cultural contrast whenthey are unable to adapt to different cultures