COVID-19 Molecular Pathophysiology: Acetylation of Repurposing Drugs.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces immune-mediated type 1 interferon (IFN-1) production, the pathophysiology of which involves sterile alpha motif and histidine-aspartate domain-containing protein 1 (SAMHD1) tetramerization and the cytosolic DNA sensor cyclic-GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway. As a result, type I interferonopathies are exacerbated. Aspirin inhibits cGAS-mediated signaling through cGAS acetylation. Acetylation contributes to cGAS activity control and activates IFN-1 production and nuclear factor-κB (NF-κB) signaling via STING. Aspirin and dapsone inhibit the activation of both IFN-1 and NF-κB by targeting cGAS. We define these as anticatalytic mechanisms. It is necessary to alleviate the pathologic course and take the lag time of the odds of achieving viral clearance by day 7 to coordinate innate or adaptive immune cell reactions.

NLRP-3 Inflammasome: A Key Target, but Mostly Overlooked following SARS-CoV-2 Infection.

The last two years have shown many political and scientific debates during the current Coronavirus Disease 2019 (COVID-19) pandemic [...].

Acute Hepatitis of Unknown Origin (AHUO)-The Puzzle Ahead.

An intriguing form of hepatitis has been detected in more than a hundred children worldwide [...].

Pre-conceptional and prenatal exposure to pesticides and pediatric neuroblastoma. A meta-analysis of nine studies.

Neuroblastoma is primarily an embryonal tumor of infancy. Recently, some toxicological agents used as pesticides have been associated with an increased incidence of this tumor. We intended to determine the potential association between prenatal exposure to pesticides and the incidence of neuroblastoma in children. Studies targeting the link between neuroblastoma and pesticides were searched in PUBMED, SCOPUS, and Google Scholar from January 1, 1960, through December 2020. We performed a PRISMA-based systematic review and meta-analysis. In addition, we took into consideration the IARC evaluation on pesticides issued in recent monographs. Prenatal pesticide exposure is associated with an increased risk of neuroblastoma with an OR of 1.6 (1.1-2.3; p = 0.013), while the OR is 1.0 (0.8-1.3; p = 0.723) for pesticide exposure after birth. There is a significant association between prenatal pesticide exposure and neuroblastoma. We emphasize the IARC conclusions evaluating the carcinogenicity of diazinon, glyphosate, malathion, parathion, and tetrachlorvinphos.

Diffusion modeling of COVID-19 under lockdown.

Viral immune evasion by sequence variation is a significant barrier to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine design and coronavirus disease-2019 diffusion under lockdown are unpredictable with subsequent waves. Our group has developed a computational model rooted in physics to address this challenge, aiming to predict the fitness landscape of SARS-CoV-2 diffusion using a variant of the bidimensional Ising model (2DIMV) connected seasonally. The 2DIMV works in a closed system composed of limited interaction subjects and conditioned by only temperature changes. Markov chain Monte Carlo method shows that an increase in temperature implicates reduced virus diffusion and increased mobility, leading to increased virus diffusion.

SAMHD1 as the Potential Link Between SARS-CoV-2 Infection and Neurological Complications.

The recent pandemic of coronavirus infectious illness 2019 (COVID19) triggered by SARS-CoV-2 has rapidly spread around the globe, generating in severe events an acute, highly lethal pneumonia and death. In the past two hitherto similar CoVs, the severe acute respiratory syndrome CoV (SARS-CoV-1) and Middle East respiratory syndrome CoV (MERS-CoV) also gained universal attention as they produced clinical symptoms similar to those of SARS-CoV-2 utilizing angiotensin-converting enzyme 2 (ACE2) receptor and dipeptidyl peptidase 4 (DPP4) to go into the cells. COVID-19 may also present with overtly neurological symptoms. The proper understanding of the expression and dissemination of ACE2 in central and peripheral nerve systems is crucial to understand better the neurological morbidity caused by COVID-19. Using the STRING bioinformatic tool and references through text mining tools associated to Coronaviruses, we identified SAMHD1 as the probable link to neurological symptoms. Paralleled to the response to influenza A virus and, specifically, respiratory syncytial virus, SARS-CoV-2 evokes a response that needs robust induction of a subclass of cytokines, including the Type I and, obviously, Type III interferons as well as a few chemokines. We correlate ACE2 to the pathogenesis and neurologic complications of COVID-19 and found that SAMHD1 links to NF-κB pathway. No correlation was found with other molecules associated with Coronavirus infection, including ADAR, BST2, IRF3, IFITM3, ISG15, MX1, MX2, RNASEL, RSAD2, and VPRBP. We suggest that SAMHD1 is the molecule that may be behind the mechanisms of the neurological complications associated with COVID-19.

Low bone mineral density in HIV-positive young Italians and migrants.

BACKGROUND: Human immunodeficiency virus (HIV) infected individuals may have osteoporosis. We aimed to evaluate the bone mineral density (BMD) in naïve antiretroviral (ARV) treated HIV positive patients comparing native Italian group (ItG) to a Migrants group (MiG) upon arrival in Italy. METHODS: We conducted a cross-sectional study on 83 HIV patients less than 50 years old. We used the dual-energy X-ray absorptiometry (DXA) within six months from the HIV diagnosis. Participants were categorized as having low BMD if the femoral neck or total lumbar spine Z-score was- 2 or less. RESULTS: MiG showed low BMD more often than ItG (37.5% vs.13.6%), especially for the female gender (16.7% vs. 0.0%). A low CD4 rate (<200 cells/µl) was most often detected in MiG than ItG. In particular, we found most often male Italians with abnormal CD4 than male migrants (67.8% vs. 33.3%) and vice versa for females (30.5% vs. 66.7%). We found an abnormal bone mineral density at the lumbar site. Low BMD at the lumbar site was more frequently observed in female migrants than female Italians. Both male and female migrants had a Z-score value significantly lower than male and female Italians, respectively. By logistic regression low vitamin-D level was positively correlated to low BMD in ItG only. All data were verified and validated using a triple code identifier. CONCLUSIONS: Both DXA and vitamin-D evaluation should be offered after the diagnosis of HIV infection. Lumbar site low BMD is an initial condition of bone loss in HIV young patients, especially in female migrants. Vitamin D levels and supplementation may be considered after HIV diagnosis independently of age to improve bone health. HIGHLIGHTS: This study evaluates the frequency of bone mineral density in HIV positive patients naive to antiretroviral therapy. It compares the density of the native Italian population with that of HIV Migrants upon arrival in Italy. The results show that HIV positive migrants, even if younger than 50 years of age, are at risk for osteoporosis, especially if they are female.

Face Masks Are Beneficial Regardless of the Level of Infection in the Fight Against COVID-19.

Coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently a global pandemic that has affected over 7 million people worldwide, resulting in over 400,000 deaths. In the past 20 years, they have been several viral epidemics that were primarily transmitted by respiratory droplets. The use of face masks is proven to be effective in protecting health-care workers as they perform their duties. Still, there is limited evidence about whether the widespread use of face mask would be very useful in protecting the general population. This study aimed to conduct a review to determine if face masks would be beneficial in the general population as a means of reducing the spread of COVID-19. The widespread implementation of wearing face masks by the general population is challenging due to a variety of factors. However, the extensive use of cloth masks in conjunction with other preventative measures such as social distancing and handwashing can potentially reduce the risk of transmission of COVID-19.