Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

Application of infrared thermography for the analysis of rewarming in patients with cold intolerance

Cold intolerance is a serious long-term problem after injury to the ulnar and median nerves, and its pathophysiology is unclear. We investigated the use of infrared thermography for the analysis of thermoregulation after injury to peripheral nerves. Four patients with injuries to the ulnar nerve and four with injuries to the median nerve (4 12 years after injury) immersed their hands in water at 158C for 5 minutes, after which infrared pictures were taken at intervals of 2 4 minutes. The areas supplied by the injured nerves could be identified easily in the patients with symptoms of cold intolerance. At baseline temperature distribution of the hand was symmetrical, but after testing the injured side warmed up much slower. We concluded that the infrared profile of the temperature of the hand after immersion in cold water is helpful to assess thermoregulation after injury to peripheral nerves

Digital rewarming patterns after median and ulnar nerve injury

Purpose Posttraumatic cold intolerance (CI) is a frequent and important sequel after peripheral nerve injury. In this study, it is hypothesized that altered rewarming patterns after peripheral nerve injury are related to the degree of posttraumatic CI. This hypothesis is tested by quantitatively comparing rewarming patterns of the digits in controls and in median or ulnar nerve injury patients and by investigating relationships between rewarming patterns, sensory recovery, and CI. Methods Twelve median or ulnar nerve injury patients with a follow-up of 4 to 76 months after nerve repair and 13 control subjects had isolated cold stress testing of the hands. Video thermography was used to analyze and compare rewarming patterns of the injured and uninjured digits after cold stress testing. Temperature curves were analyzed by calculating the Q value as an indicator of heat transfer (temperature added during the first 10 minutes after start of active rewarming) and the maximum slope. Results Testretest reliability was 0.64 and 0.79, respectively, for the Q value and maximum slope. High Q values and maximum slopes were interpreted as the presence of active rewarming. Patients with return of active rewarming had better sensory recovery and lower Blond McIndoe Cold Intolerance Severity Scale (CISS) scores. Better sensory recovery was correlated with lower CISS scores. Conclusions Testretest reliability of cold stress testing was good, and we found a difference in rewarming patterns between erve injury patients and controls. The presence of active rewarming in the nerve injury patients was related to sensory recovery and fewer complaints of posttraumatic CI

Adults with congenital or acquired facial disfigurement: impact of appearance on social functioning

This study evaluates the impact of congenital and acquired facial disfigurement on social functioning in adults and whether this differs from adults without facial disfigurement. Moreover, the predictive value of objective and subjective appearance on social functioning is explored. Fifty-nine adults with severe congenital facial disfigurement, 59 adults with traumatically acquired facial deformities in adulthood, and 120 adults without facial disfigurement, completed the Scale for Interpersonal Behaviour, Social Avoidance and Distress Scale, and Visual Analogue Scale for facial appearance satisfaction. The impact of congenital and acquired facial disfigurement on social functioning in adults is similar and significantly differed from the reference group. The level of stress evoked by interpersonal behaviour, and social anxiety and distress were not significantly different between the groups. Only the patient's subjective appearance was a predictor of social functioning. Avoiding stress caused by stigmatization and uncertainty about reactions of others, leads to less frequent interpersonal behaviour in adults with facial disfigurement. The fact whether the deformity is congenital or acquired in adulthood has no influence on social functioning. Patient's satisfaction with facial appearance is more important than the objective severity of the deformity; in this context realistic expectations of the patient considering additional surgery are important. © 2011 European Association for Cranio-Maxillo-Facial Surgery

Prevalence of Coxiella Burnetii in Ticks After a Large Outbreak of Q Fever

Q fever has emerged as an important human and veterinary public health problem in the Netherlands with major outbreaks in three consecutive years. Goat farms are probably the prime source from which Coxiella burnetii have spread throughout the environment, infecting people living in the vicinity. Coxiella burnetii infection not only spilled over from animal husbandry to humans but could also have spread to neighbouring wildlife and pets forming novel reservoirs and consequently posing another and lingering threat to humans, companion animals and livestock. In these cases, transmission routes other than airborne spread of contaminated aerosols may become significant. Therefore, the role of ticks in the transmission of Coxiella burnetii in the current situation was investigated. A total of 1891 questing Ixodes ricinus ticks and 1086 ticks feeding on pets, wildlife and livestock were tested by a recently developed multiplex Q-PCR. All ticks were negative, except for a few ticks feeding on a herd of recently vaccinated sheep. Coxiella-positive ticks were not detected after resampling this particular herd three months later. Based on these data we conclude that the current risk of acquiring Q fever from questing ticks in the Netherlands is negligible. However, for future risk assessments, it might be relevant to sample more ticks in the vicinity of previously C. burnetii infected goat farms and to assess whether C. burnetii can be transmitted transovarially and transstadially in I. ricinus ticks

ARL2 and BART Enter Mitochondria and Bind the Adenine Nucleotide Transporter

The ADP-ribosylation factor-like 2 (ARL2) GTPase and its binding partner binder of ARL2 (BART) are ubiquitously expressed in rodent and human tissues and are most abundant in brain. Both ARL2 and BART are predominantly cytosolic, but a pool of each was found associated with mitochondria in a protease-resistant form. ARL2 was found to lack covalent N-myristoylation, present on all other members of the ARF family, thereby preserving the N-terminal amphipathic α-helix as a potential mitochondrial import sequence. An overlay assay was developed to identify binding partners for the BART·ARL2·GTP complex and revealed a specific interaction with a protein in bovine brain mitochondria. Purification and partial microsequencing identified the protein as an adenine nucleotide transporter (ANT). The overlay assay was performed on mitochondria isolated from five different tissues from either wild-type or transgenic mice deleted for ANT1. Results confirmed that ANT1 is the predominant binding partner for the BART·ARL2·GTP complex and that the structurally homologous ANT2 protein does not bind the complex. Cardiac and skeletal muscle mitochondria from ant1(−)/ant1(−) mice had increased levels of ARL2, relative to that seen in mitochondria from wild-type animals. We conclude that the amount of ARL2 in mitochondria is subject to regulation via an ANT1-sensitive pathway in muscle tissues

Is reaching 90-90-90 enough to end AIDS? Lessons from Amsterdam

Purpose of review Although cities present opportunities for infectious pathogens such as HIV to spread, public health infrastructure within these cities also provides opportunities to design effective approaches to eliminate transmission of these pathogens. The HIV Transmission Elimination AMsterdam (H-TEAM) Initiative, a consortium of relevant stakeholders involved in HIV prevention and care, designed an integrated approach to curb the HIV epidemic in Amsterdam, including providing preexposure prophylaxis (PrEP), increasing awareness of acute HIV infection, offering same-day test and treat, and improving indicator disease-driven HIV testing. Recent findings In 2013, approximately 230 people in Amsterdam were newly diagnosed with HIV, largely belonging to one of two key affected populations, namely MSM and people with a migration background. Since the start of H-TEAM in 2014, a decrease in new diagnoses was observed (130 in 2017), with an increasing proportion of MSM who had been diagnosed with a recent infection. The H-TEAM shows that a city-based concerted effort is feasible. However, major challenges remain, such as reducing the number of late HIV diagnoses, and identifying and providing appropriate services to a diminishing group of individuals who are likely the source of transmission.Immunogenetics and cellular immunology of bacterial infectious disease

Predictive Performance of Cardiovascular Disease Risk Prediction Algorithms in People Living With HIV

Immunogenetics and cellular immunology of bacterial infectious disease