ACAS: Always Connected, Always Secure

There is no place where safety is more important than in the home. Research has shown that home security systems are effective in deterring burglars; additionally, these security systems allow residents to monitor their property at all times, even while they are away. More and more of these home security devices rely on a stable Internet connection and cannot provide functionality without it. ACAS is a system that helps keep smart devices connected to the Internet, even in the event of a home internet outage. ACAS includes a programmable router that can connect to multiple Internet sources, which sets it apart from other routers on the market. ACAS can connect to two or more Internet sources at a time and then broadcast a wireless Internet signal that one’s smart security devices (and any other device) can connect to. The router uses one Internet source at a time to provide a wireless signal for all devices to connect to it, but in the case that the Internet source goes down for any reason, ACAS automatically switches to one of the other Internet sources connected to it. This provides a reliable backup and keeps devices connected to the Internet as long as one of the multiple Internet sources connected to the router is up and running. Our system also includes a web application that provides the ability to configure some aspects of the router and obtain up-to-date statistics about the workings of the router itself. Users can check the network speed of the Internet connection and choose which of the multiple Internet sources is the main Internet source at any given time

Interferons in immunity to chlamydia pneumoniae

The cytokine IFN-gamma is the architect behind an amazing immunological program of host resistance to intracellular bacterial and protozoan infections. IFN-gamma activates macrophages, making them into inhospitable habitats for parasites attempting to grow inside them. The family of obligate intracellular Gram-negative bacteria Chlamydia is an example of such pathogens. The overall aim of this thesis was to unravel resistance to infection with the human respiratory pathogen C. pneumoniae. Specific focus was placed on innate immune responses to C. pneumoniae and the regulation and role of IFN-gamma in the outcome of infection. An experimental mouse model of lung infection and a macrophage model of in vitro infection were used for this purpose. A protective role for infection-induced IFN-gamma in restricting C. pneumoniae growth in vivo was observed, though IFN-gamma was not required for resolution of infection. IL-12 and/or IL-23 was a necessary but not an absolute requirement for expression of IFN-gamma. IFN-gamma-dependent protection was in part mediated by iNOS expression. TNF-alpha, known to be synergistic with IFN-gamma, was not required for restricting Chlamydial growth. Innate immune cells in the lung constituted an important source of IFN-gamma and were essential for restricting C. pneumoniae growth and for containment of bacteria in the lungs. However, NK cells were not implicated in such protective IFN-gamma release. On the other hand, lung macrophages isolated from C.pneumoniae-infected mice expressed IFN-gamma. Moreover, bone marrow-derived macrophages (BMMphi) conferred upon transfer to RAG-1-/-/IFN-gamma-/-mice, enhanced resistance to C. pneumoniae infection via their ability to release IFN-gamma. Innate IFN-gamma was however not required for protection conferred by CD4+ or CD8+ T cells. Innate and T cell-derived IFN-gamma are also non-redundant (complementary) in protesting mice against C. pneumoniae. C. pneumoniae-infected BMMphi also expressed IFN-gamma in vitro. Such IFN-gamma release was IL-12independent but required instead IFN-alpha/beta and restricted Chlamydial growth. IFN-alpha/beta, and not IFNgamma, was required for iNOS-mediated protection in BMMphi. The molecular details of BMMphi-derived IFNgamma expression revealed a TLR4-MyD88-dependent pathway of IFN-alpha and IFN-gamma induction. Also surprising was the presente of a TLR4- and MyD88-independent, infection-induced NF-kappaB activation and proinflammatory cytokine expression. Phosphorylation of STAT1 during infection was IFN-alpha/beta-dependent, and necessary for increased IFN-gamma expression and for restricting Chlamydial growth. Expression of IFN-gamma and restriction of C. pneumoniae growth also required NF-kappaB activation, but such activation was independent of IFN-alpha/beta, revealing a dual pathway of C.pneumoniae-induced IFN-gamma expression in BMMphi: a TLR4-MyD88-IFNalpha/beta-STAT1 -dependent pathway, and a TLR4-independent pathway leading to NF-kappaB activation. IFN-alpha/beta was also protective in vivo by cooperating with IFN-gamma for activation of STAT1, which was required for restricting Chlamydial growth. Different from the in vitro situation, IFN-gamma was sufficient on its own for this effect and did not require IFN-alpha/beta for its expression. In summary, IFN-gamma is important for restricting C. pneumoniae growth. Innate IFN-gamma is protective both in lungs and in BMMphi. IFN-alpha/beta are pivotal in regulating protective responses in BMMphi, including IFNgamma release, but are dispensable for IFN-gamma expression and protection in vivo. This discrepancy may be a qualitative feature in C. pneumoniae pattern recognition by different cell types; lung cells convey the generation of protective, IL-12-driven responses, while IFN-alpha/beta-driven protection in BMMphi is essential

Mannose-Binding Lectin Regulates Host Resistance and Pathology during Experimental Infection with Trypanosoma cruzi

Mannose-binding lectin (MBL) is a humoral pattern-recognition molecule important for host defense. Although recent genetic studies suggest an involvement of MBL/MASP2-associated pathways in Chagas’ disease, it is currently unknown whether MBL plays a role in host resistance to the intracellular protozoan Trypanosoma cruzi, the causative agent of Chagas’ disease. In this study we employed MBL−/− mice to assess the role of MBL in resistance to experimental infection with T. cruzi. T. cruzi infection enhanced tissue expression of MBL both at the mRNA and protein level. Similarly, symptomatic acute Chagas’ disease patients displayed increased serum concentrations of MBL compared to patients with indeterminate, asymptomatic forms of the disease. Furthermore, increased parasite loads in the blood and/or tissue were observed in MBL−/− mice compared to WT controls. This was associated with reduced systemic levels of IL-12/23p40 in MBL−/− mice. Importantly, MBL−/− mice infected with a cardiotropic strain of T. cruzi displayed increased myocarditis and cardiac fibrosis compared to WT controls. The latter was accompanied by elevated hydroxyproline content and mRNA levels of collagen-1 and -6 in the heart. These observations point to a previously unappreciated role for MBL in regulating host resistance and cardiac inflammation during infection with a major human pathogen

Immunogenicity and Safety of Anti-SARS-CoV-2 mRNA Vaccines in a Cohort of Patients with Hereditary Angioedema

Many factors may trigger hereditary angioedema (HAE) attacks. This study aims to gain insights into the benefits and potential risks of COVID-19 vaccination in HAE patients, focusing particularly on the possibility of triggering attacks. We enrolled 31 patients with HAE undergoing two doses of the SARS-CoV-2 mRNA Comirnaty-BioNTech/Pfizer vaccine. To evaluate the possible influence of the vaccine on disease control and attack frequency, we administered the angioedema control test (AECT) 4-week version before (T0), 21 days after the first dose (T1), and between 21 and 28 days after the second dose (T2). Despite 5 patients (16.1%) experiencing attacks within 72 h of the first dose administration, no significant variation in attack frequency was observed before and after vaccination [F(2,60) = 0.123; p = 0.799]. In addition, patients reported higher AECT scores at T1 and T2 compared to T0 [F(2,44) = 6.541; p < 0.05; post hoc p < 0.05)], indicating that the disease was rather more controlled after vaccinations than in the previous period. All patients showed a positive serological response to the vaccine without significant differences from healthy controls (U = 162; p = 0.062). These observations suggest that the vaccine administration is safe and effective in HAE patients

Detection and isolation of airborne SARS-CoV-2 in a hospital setting

Transmission mechanisms for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are incompletely understood. In particular, aerosol transmission remains unclear, with viral detection in air and demonstration of its infection potential being actively investigated. To this end, we employed a novel electrostatic collector to sample air from rooms occupied by COVID-19 patients in a major Swedish hospital. Electrostatic air sampling in conjunction with extraction-free, reverse-transcriptase polymerase chain reaction (hid-RT-PCR) enabled detection of SARS-CoV-2 in air from patient rooms (9/22; 41%) and adjoining anterooms (10/22; 45%). Detection with hid-RT-PCR was concomitant with viral RNA presence on the surface of exhaust ventilation channels in patients and anterooms more than 2 m from the COVID-19 patient. Importantly, it was possible to detect active SARS-CoV-2 particles from room air, with a total of 496 plaque-forming units (PFUs) being isolated, establishing the presence of infectious, airborne SARS-CoV-2 in rooms occupied by COVID-19 patients. Our results support circulation of SARS-CoV-2 via aerosols and urge the revision of existing infection control frameworks to include airborne transmission

Association between Food Intake, Clinical and Metabolic Markers and DNA Damage in Older Subjects

Abstract The use of DNA damage as marker of oxidative stress, metabolic dysfunction and age-related diseases is debated. The present study aimed at assessing the level of DNA damage (evaluated as DNA strand-breaks, endogenous and oxidatively-induced DNA damage) in a group of older subjects with intestinal permeability enrolled within the MaPLE (Gut and Blood Microbiomics for Studying the Effect of a Polyphenol-Rich Dietary Pattern on Intestinal Permeability in the Elderly) intervention trial, to evaluate its association with clinical, metabolic and dietary markers. DNA damage in peripheral blood mononuclear cells was assessed by the comet assay in 49 older subjects participating in the study. Clinical and metabolic markers, markers of inflammation, vascular function and intestinal permeability were determined in serum. Food intake was estimated by weighted food diaries. On the whole, a trend towards higher levels of DNA damage was observed in men compared to women (p = 0.071). A positive association between DNA damage and clinical/metabolic markers (e.g., uric acid, lipid profile) and an inverse association with dietary markers (e.g., vitamin C, E, B6, folates) were found and differed based on sex. By considering the importance of DNA stability during aging, the results obtained on sex differences and the potential role of dietary and metabolic factors on DNA damage underline the need for further investigations in a larger group of older adults to confirm the associations found and to promote preventive strategies

A 6 day course of liposomal amphotericin B in the treatment of infantile visceral leishmaniasis: the Italian experience

OBJECTIVES: To evaluate in a retrospective analysis the efficacy and safety of a 6 day course of liposomal amphotericin B (L-AmB) in infantile cases of Mediterranean visceral leishmaniasis (VL) diagnosed over a 10 year period in Italy. PATIENTS AND METHODS: Patients included were diagnosed as having VL consecutively admitted from December 1992 to December 2001 at four main referral children's hospitals in Italy and treated with six intravenous doses of 3 mg/kg L-AmB given on days 1-5 and 10 (a total dose of 18 mg/kg). Demographic data, nutritional status, underlying diseases, clinical and laboratory findings, and therapy outcome were considered. RESULTS: A total of 164 HIV-negative children (median age 1.6 years; range 4 months to 14 years) were enrolled. All patients were initially cured by the given treatment, and did not present adverse events related to drug infusion. Seven patients (4.3%) had a clinical and parasitological relapse 3-15 months after therapy. All relapses were successfully retreated with 3 mg/kg L-AmB for 10 consecutive days (a total dose of 30 mg/kg). CONCLUSIONS: This study highlights the efficacy (>95%) and safety of the six dose L-AmB regimen and validates it as a first-line treatment for Mediterranean VL in children

Role of anti-osteopontin antibodies in multiple sclerosis and experimental autoimmune encephalomyelitis

Osteopontin (OPN) is highly expressed in demyelinating lesions in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). OPN is cleaved by thrombin into N- (OPN-N) and C-terminal (OPN-C) fragments with different ligands and functions. In EAE, administering recombinant OPN induces relapses, whereas treatment with anti-OPN antibodies ameliorates the disease. Anti-OPN autoantibodies (autoAbs) are spontaneously produced during EAE but have never been detected in MS. The aim of the study was to evaluate anti-OPN autoAbs in the serum of MS patients, correlate them with disease course, and recapitulate the human findings in EAE. We performed ELISA in the serum of 122 patients collected cross-sectionally, and 50 patients with relapsing-remitting (RR) disease collected at diagnosis and followed longitudinally for 10 years. In the cross-sectional patients, the autoAb levels were higher in the RR patients than in the primary- and secondary-progressive MS and healthy control groups, and they were highest in the initial stages of the disease. In the longitudinal group, the levels at diagnosis directly correlated with the number of relapses during the following 10 years. Moreover, in patients with active disease, who underwent disease-modifying treatments, autoAbs were higher than in untreated patients and were associated with low MS severity score. The autoAb displayed neutralizing activity and mainly recognized OPN-C rather than OPN-N. To confirm the clinical effect of these autoAbs in vivo, EAE was induced using myelin oligodendrocyte glycoprotein MOG35-55 in C57BL/6 mice pre-vaccinated with ovalbumin (OVA)-linked OPN or OVA alone. We then evaluated the titer of antibodies to OPN, the clinical scores and in vitro cytokine secretion by spleen lymphocytes. Vaccination significantly induced antibodies against OPN during EAE, decreased disease severity, and the protective effect was correlated with decreased T cell secretion of interleukin 17 and interferon-\u3b3 ex vivo. The best effect was obtained with OPN-C, which induced significantly faster and more complete remission than other OPN vaccines. In conclusion, these data suggest that production of anti-OPN autoAbs may favor remission in both MS and EAE. Novel strategies boosting their levels, such as vaccination or passive immunization, may be proposed as a future strategy in personalized MS therapy

Covid-19 And Rheumatic Autoimmune Systemic Diseases: Role of Pre-Existing Lung Involvement and Ongoing Treatments

The Covid-19 pandemic may have a deleterious impact on patients with autoimmune systemic diseases (ASD) due to their deep immune-system alterations