Functional associations between polymorphic regions of the human 3'IgH locus and COVID-19 disease.

PURPOSE: The pandemic diffusion of Coronavirus Disease 2019 (COVID-19) has highlighted significant gender-related differences in disease severity. Despite several hypotheses being proposed, how the genetic background of COVID-19 patients might impact clinical outcomes remains largely unknown. METHODS: We collected blood samples from 192 COVID-19 patients (115 men, 77 women, mean age 67 ± 19 years) admitted between March and June 2020 at two different hospital centers in Italy, and determined the allelic distribution of nine Single Nucleotide Polymorphisms (SNPs), located at the 3'Regulatory Region (3'RR)-1 in the immunoglobulin (Ig) heavy chain locus, including *1 and *2 alleles of polymorphic hs1.2 enhancer region. RESULTS: In COVID-19 patients, the genotyped SNPs exhibited strong Linkage Disequilibrium and produced 7 specific haplotypes, associated to different degrees of disease severity, including the occurrence of pneumonia. Additionally, the allele *2, which comprises a DNA binding site for the Estrogen receptor alpha (ERα) in the polymorphic enhancer hs1.2 of 3'RR-1, was significantly enriched in women with a less severe disease. CONCLUSIONS: These findings document genetic variants associated to individual clinical severity of COVID-19 disease. Most specifically, a novel genetic protective factor was identified that might explain the sex-related differences in immune response to Sars-COV-2 infection in humans.

An innovative autonomous robotic system for on-site detection of heavy metal pollution plumes in surface water.

Smart monitoring has been studied and developed in recent years to create faster, cheaper, and more user-friendly on-site methods. The present study describes an innovative technology for investigative monitoring of heavy metal pollution (Cu and Pb) in surface water. It is composed of an autonomous surface vehicle capable of semiautonomous driving and equipped with a microfluidic device for detection of heavy metals. Detection is based on the method of square wave anodic stripping voltammetry using carbon-based screen-printed electrodes (SPEs). The focus of this work was to validate the ability of the integrated system to perform on-site detection of heavy metal pollution plumes in river catchments. This scenario was simulated in laboratory experiments. The main performance characteristics of the system, which was evaluated based on ISO 15839 were measurement bias (Pb 75%, Cu 65%), reproducibility (in terms of relative standard deviation: Pb 11-18%, Cu 6-10%) and the limit of detection (4 µg/L for Pb and 7 µg/L for Cu). The lowest detectable change (LDC), which is an important performance characteristic for this application, was estimated to be 4-5 µg/L for Pb and 6-7 µg/L for Cu. The life span of an SPE averaged 39 measurements per day, which is considered sufficient for intended monitoring campaigns. This work demonstrated the suitability of the integrated system for on-site detection of Pb and Cu emissions from large and medium urban areas discharging into small water bodies.

Mesothelioma in Familial Mediterranean Fever With Colchicine Intolerance: A Case Report and Literature Review.

A 65-year-old Italian physician affected by Familial Mediterranean fever (FMF) was hospitalized due to progressive abdominal enlargement, which had begun 6 months before admission. Physical examination revealed ascites and bilateral leg edema. Abdominal CT scan showed ascitic fluid and extensive multiple peritoneal implants; peritoneal CT-guided biopsy revealed an epithelial-type malignant mesothelioma. The patient's past medical history revealed recurrent episodes of abdominal pain and fever from the age of 2. Clinical diagnosis of FMF was suspected at the age of 25, while genetic analysis, performed at the age of 50, confirmed homozygosity for the M694I mutation in the MEFV gene. Treatment with the first line FMF drug colchicine was started and stopped several times because of worsened leukopenia. The patient in fact had a history of asymptomatic leukopenia/lymphopenia from an early age; the intake of colchicine aggravated his pre-existing problem until the definitive suspension of the drug. As for second-line drugs, canakinumab was first prescribed, but due to prescription issues, it was not possible to be administered. When he was given anakinra, there was a worsening of leukopenia leading to septic fever. Systematic literature review indicates that, in most cases, recurrent peritoneal inflammation results in benign peritoneal fibrosis or less commonly in encapsulating peritonitis. There are only a few reported cases of recurrent peritoneal inflammation progressing from FMF to peritoneal mesothelioma (MST). In such cases, intolerance to colchicine or its erratic intake may lead to long-term recurrent inflammation, which usually precedes the development of the tumor, while pre-existing leukopenia, as in our patient, could also be a factor promoting or accelerating the tumor progression. In conclusion, we suggest that in the presence of intolerance or resistance to colchicine, interleukin (IL)-1 inhibition could suppress peritoneal inflammation and prevent MSTs.

[Lipomatosis of interatrial septum and supraventricular arrhythmias]. / Lipomatosi del setto interatriale e aritmie sopraventricolari.

Lipomatosis of interatrial septum is a rare benign disorder characterized by fat accumulation into interatrial septum. It may cause atrial arrhythmias and hemodynamic complications. For this reason, it should be considered in differential diagnosis of other cardiac masses. We report the typical case of lipomatosis of interatrial septum and atrial flutter.