SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Decision Making and Fibromyalgia: A Systematic Review

Decision making (DM) is the ability to choose among multiple options, considering external and internal variables and identifying potential paths of action that need to be assessed. Some brain areas involved in decision making are also implicated in pain processing, such as in fibromyalgia (FM). FM is a syndrome characterized by chronic widespread musculoskeletal pain and cognitive difficulties. We conducted a systematic review with the aim of identifying articles that evaluated DM in people with fibromyalgia, highlighting the main assessment tools. This work was conducted according to the PRISMA statement by consulting six online databases and providing a quality assessment of each search that met the inclusion criteria. In line with the limited interest in this in the scientific landscape to date, we found nine studies that evaluated the performance of DM in patients with FM; furthermore, we discovered that only certain types of DM were tested. The importance of our work lies in shedding light on a cognitive ability that is often undervalued in the scientific landscape but essential in everyday life. This review can serve as a starting point for further studies to clarify the relationship between DM and FM, improving understanding of the topic

The leader peptide of a human rec. MnSOD as molecular carrier which delivers high amounts of cisplatin into tumor cells inducing a fast apoptosis in vitro

The leader peptide of a recombinant MnSOD (rMnSOD-Lp) constitutes the carrier that allows rMnSOD to penetrate tumor cells. A synthetic preparation of rMnSOD-Lp was \u2076\u2078Ga labeled (rMnSOD-Lp- \u2076\u2078Ga) and injected into animals bearing spontaneous mammary cancers, followed by PET examinations, which demonstrated unambiguously the tumor sites in all the animals, suggesting that if rMnSOD-Lp was able to transport the radioisotope into tumor cells, it would also be able to deliver cytotoxic molecules. The rMnSOD-Lp was, therefore, conjugated to cisplatin (rMnSOD-Lp-CC) and added to cultured tumor cells. Equal concentrations of cisplatin were used for the tests. After treating the ovarian cancer cells with 11.1 \u3bcg of cisplatin alone, analysis by atomic absorbance spectrophotometry was able to detect only 6 ng of platinum, whereas when the same cells were treated with the same amount of cisplatin conjugated to leader peptide rMnSOD, 387 ng of platinum were detected, i.e., an amount 80 times greater. Only the tumor cells died following treatment with rMnSOD-Lp-CC; molecular analysis revealed that its addition generated an increasing expression of Erk-2 and Bax products, which could be inhibited only by a selective MAP/ERK kinase inhibitor (PD98059), revealing that rMnSOD-Lp-CC has an apoptotic function, exactly as occurs when using the cisplatin alone. Data are statistically significant and indicate that by using rMnSOD-Lp-CC, the cisplatin can be transformed from an agent with antireplicative activity into a specific and selective antitumor molecule, increasing its therapeutic index. We think that rMnSOD-Lp-CC deserves to be considered as a new antitumor agent

Equilibrium studies of new bis-hydroxypyrone derivatives with Fe3+, Al3+, Cu2+ and Zn2+

This paper presents an easy and low cost synthesis of chelating agents for potential medical and environmental applications, and the evaluation of the stability of their complexes with Fe3+, Al3+, Cu2+ and Zn2+. In the last years, we synthesized and characterized effective iron chelators based on two kojic acid units joined by different linkers in position 6. In this study, we preserved kojic acid (a cheap and non-toxic molecule) as the basic unit but joined the two kojic acid units through ethylene diamine, propylene diamine and butylene diamine by reacting them with the OH groups in position 2. The different anchoring position of the linker, as well as the linker length, can affect both protonation and complex formation equilibria. A thorough study of the protonation and complex formation equilibria of the three ligands toward the metal ions is presented based on combined potentiometric and spectroscopic studies, and 1H NMR. The obtained results allow remarking that the orientation of the oxygen atoms in the kojic acid units, related to the anchoring position of the linker, strongly affects the protonation constants, while the chelating ability is practically unaffected. The trivalent metal ions form stable complexes with a 2:3 metal to ligand stoichiometry through the oxygen donor atoms of the ligands, whereas divalent metal ions form binuclear complexes for which the nitrogen atoms from the linker might be involved in the coordination sphere. The stability of the complexes decreases with linker length, and the selectivity of the ligands toward metal ions grows in the order Zn2+ < Cu2+ < Al3+ < Fe3+

Changes in surgicaL behaviOrs dUring the CoviD-19 pandemic. The SICE CLOUD19 Study

BACKGROUND: The spread of the SARS-CoV2 virus, which causes COVID-19 disease, profoundly impacted the surgical community. Recommendations have been published to manage patients needing surgery during the COVID-19 pandemic. This survey, under the aegis of the Italian Society of Endoscopic Surgery, aims to analyze how Italian surgeons have changed their practice during the pandemic.METHODS: The authors designed an online survey that was circulated for completion to the Italian departments of general surgery registered in the Italian Ministry of Health database in December 2020. Questions were divided into three sections: hospital organization, screening policies, and safety profile of the surgical operation. The investigation periods were divided into the Italian pandemic phases I (March-May 2020), II (June-September 2020), and III (October-December 2020).RESULTS: Of 447 invited departments, 226 answered the survey. Most hospitals were treating both COVID-19-positive and -negative patients. The reduction in effective beds dedicated to surgical activity was significant, affecting 59% of the responding units. 12.4% of the respondents in phase I, 2.6% in phase II, and 7.7% in phase III reported that their surgical unit had been closed. 51.4%, 23.5%, and 47.8% of the respondents had at least one colleague reassigned to non-surgical COVID-19 activities during the three phases. There has been a reduction in elective (>200 procedures: 2.1%, 20.6% and 9.9% in the three phases, respectively) and emergency (<20 procedures: 43.3%, 27.1%, 36.5% in the three phases, respectively) surgical activity. The use of laparoscopy also had a setback in phase I (25.8% performed less than 20% of elective procedures through laparoscopy). 60.6% of the respondents used a smoke evacuation device during laparoscopy in phase I, 61.6% in phase II, and 64.2% in phase III. Almost all responders (82.8% vs. 93.2% vs. 92.7%) in each analyzed period did not modify or reduce the use of high-energy devices.CONCLUSION: This survey offers three faithful snapshots of how the surgical community has reacted to the COVID-19 pandemic during its three phases. The significant reduction in surgical activity indicates that better health policies and more evidence-based guidelines are needed to make up for lost time and surgery not performed during the pandemic

COVID-19 Host Genetics Initiative. A first update on mapping the human genetic architecture of COVID-19

The COVID-19 pandemic continues to pose a major public health threat, especially in countries with low vaccination rates. To better understand the biological underpinnings of SARS-CoV-2 infection and COVID-19 severity, we formed the COVID-19 Host Genetics Initiative1. Here we present a genome-wide association study meta-analysis of up to 125,584 cases and over 2.5 million control individuals across 60 studies from 25 countries, adding 11 genome-wide significant loci compared with those previously identified2. Genes at new loci, including SFTPD, MUC5B and ACE2, reveal compelling insights regarding disease susceptibility and severity.</p