The polymorphism L412F in TLR3 inhibits autophagy and is a marker of severe COVID-19 in males

The polymorphism L412F in TLR3 has been associated with several infectious diseases. However, the mechanism underlying this association is still unexplored. Here, we show that the L412F polymorphism in TLR3 is a marker of severity in COVID-19. This association increases in the sub-cohort of males. Impaired macroautophagy/autophagy and reduced TNF/TNFα production was demonstrated in HEK293 cells transfected with TLR3L412F-encoding plasmid and stimulated with specific agonist poly(I:C). A statistically significant reduced survival at 28 days was shown in L412F COVID-19 patients treated with the autophagy-inhibitor hydroxychloroquine (p = 0.038). An increased frequency of autoimmune disorders such as co-morbidity was found in L412F COVID-19 males with specific class II HLA haplotypes prone to autoantigen presentation. Our analyses indicate that L412F polymorphism makes males at risk of severe COVID-19 and provides a rationale for reinterpreting clinical trials considering autophagy pathways. Abbreviations: AP: autophagosome; AUC: area under the curve; BafA1: bafilomycin A1; COVID-19: coronavirus disease-2019; HCQ: hydroxychloroquine; RAP: rapamycin; ROC: receiver operating characteristic; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; TLR: toll like receptor; TNF/TNF-α: tumor necrosis factor

I toscani dell'Ottocento

I toscani dell'Ottocento / Pietro Pancrazi. - Firenze : Bemporad, stampa 1924 Dedica manoscritta a Erminia Bodrero: alla signorina Erminia Bodrero / in devoto omaggio / e per la comune simpatia / a questi bravi veneti scrittori / [...] Pancrazi / giugno 927 https://galileodiscovery.unipd.it/discovery/fulldisplay?context=L&vid=39UPD_INST:VU1&search_scope=MyInst_and_CI&tab=Everything&docid=alma99000994208020604

CT colonography with rectal iodine tagging: Feasibility and comparison with oral tagging in a colorectal cancer screening population

PURPOSE: To evaluate feasibility, diagnostic performance, patient acceptance, and overall examination time of CT colonography (CTC) performed through rectal administration of iodinated contrast material. MATERIALS AND METHODS: Six-hundred asymptomatic subjects (male:female=270:330; mean 63 years) undergoing CTC for colorectal cancer screening on an individual basis were consecutively enrolled in the study. Out of them, 503 patients (group 1) underwent CTC with rectal tagging, of which 55 had a total of 77 colonic lesions. The remaining 97 patients (group 2) were randomly selected to receive CTC with oral tagging of which 15 had a total of 20 colonic lesions. CTC findings were compared with optical colonoscopy, and per-segment image quality was visually assessed using a semi-quantitative score (1=poor, 2=adequate, 3=excellent). In 70/600 patients (11.7%), CTC was performed twice with both types of tagging over a 5-year follow-up cancer screening program. In this subgroup, patient acceptance was rated via phone interview two weeks after CTC using a semi-quantitative scale (1=poor, 2=fair, 3=average, 4=good, 5=excellent). RESULTS: Mean per-polyp sensitivity, specificity, positive and negative predictive values of CTC with rectal vs oral tagging were 96.1% (CI95% 85.4÷99.3%) vs 89.4% (CI95% 65.4÷98.1%), 95.3% (CI95% 90.7÷97.8%) vs 95.8% (CI95% 87.6÷98.9%), 86.0% (CI95% 73.6÷93.3) vs 85.0% (CI95% 61.1÷96.0%), and 98.8% (CI95% 95.3÷99.8%) vs 97.2% (CI95% 89.4÷99.5%), respectively (p>0.05). Polyp detection rates were not statistically different between groups 1 and 2 (p>0.05). Overall examination time was significantly shorter with rectal than with oral tagging (18.3±3.5 vs 215.6±10.3 minutes, respectively; p<0.0001). CONCLUSIONS: Rectal iodine tagging can be an effective alternative to oral tagging for CTC with the advantages of greater patient acceptance and lower overall examination time

CT colonography with rectal iodine tagging: Feasibility and comparison with oral tagging in a colorectal cancer screening population

PURPOSE: To evaluate feasibility, diagnostic performance, patient acceptance, and overall examination time of CT colonography (CTC) performed through rectal administration of iodinated contrast material. MATERIALS AND METHODS: Six-hundred asymptomatic subjects (male:female=270:330; mean 63 years) undergoing CTC for colorectal cancer screening on an individual basis were consecutively enrolled in the study. Out of them, 503 patients (group 1) underwent CTC with rectal tagging, of which 55 had a total of 77 colonic lesions. The remaining 97 patients (group 2) were randomly selected to receive CTC with oral tagging of which 15 had a total of 20 colonic lesions. CTC findings were compared with optical colonoscopy, and per-segment image quality was visually assessed using a semi-quantitative score (1=poor, 2=adequate, 3=excellent). In 70/600 patients (11.7%), CTC was performed twice with both types of tagging over a 5-year follow-up cancer screening program. In this subgroup, patient acceptance was rated via phone interview two weeks after CTC using a semi-quantitative scale (1=poor, 2=fair, 3=average, 4=good, 5=excellent). RESULTS: Mean per-polyp sensitivity, specificity, positive and negative predictive values of CTC with rectal vs oral tagging were 96.1% (CI95% 85.4÷99.3%) vs 89.4% (CI95% 65.4÷98.1%), 95.3% (CI95% 90.7÷97.8%) vs 95.8% (CI95% 87.6÷98.9%), 86.0% (CI95% 73.6÷93.3) vs 85.0% (CI95% 61.1÷96.0%), and 98.8% (CI95% 95.3÷99.8%) vs 97.2% (CI95% 89.4÷99.5%), respectively (p>0.05). Polyp detection rates were not statistically different between groups 1 and 2 (p>0.05). Overall examination time was significantly shorter with rectal than with oral tagging (18.3±3.5 vs 215.6±10.3 minutes, respectively; p<0.0001). CONCLUSIONS: Rectal iodine tagging can be an effective alternative to oral tagging for CTC with the advantages of greater patient acceptance and lower overall examination time

Teleconsultations for mental health: Recommendations from a Delphi panel

Introduction: The use of teleconsultations for mental health has drastically increased since 2020 due to the Covid19 pandemic. In the present paper, we aimed to analyze the advantages and disadvantages of teleconsultations for mental health compared to face-to-face consultations, and to provide recommendations in this domain. Methods: The recommendations were gathered using a Delphi methodology. The expert panel (N = 21) included professionals from the health and ICT domains. They answered questions via two rounds of web surveys, and then discussed the results in a plenary meeting. Some of the questions were also shared with non-experts (N = 104). Results: Both the experts and the non-experts with teleconsultation experience reported a general satisfaction concerning teleconsultations. A SWOT analysis revealed several strengths and opportunities of teleconsultations for mental health, but also several weaknesses and threats. The experts provided a set of practical recommendations for the preparation and organization of teleconsultations for mental health. Discussion: Teleconsultations for mental health have the potential to allow access to care for patients in remote and isolated areas. Thus, their use will unlikely be discontinued after the end of the pandemic. In this context, we suggest that the collaboration among clinicians, researchers, and interface designers is crucial to improve usability and user experience for both clinicians and patients. The importance of teaching teleconsultation skills and informing the public on the features of teleconsultations (e.g., data privacy/security) is also highlighted

Mapping the human genetic architecture of COVID-19

The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3–7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease

Mapping the human genetic architecture of COVID-19

The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3,4,5,6,7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease