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Severe acute respiratory syndrome coronavirus 2 is a recently discovered pathogen responsible of coronavirus disease 2019 (COVID-19). The immunological changes associated with this infection are largely unknown. We evaluated the peripheral blood mononuclear cells profile of 63 patients with COVID-19 at diagnosis. We also assessed the presence of association with inflammatory biomarkers and the 28-day mortality. Lymphocytopenia was present in 51 of 63 (80.9%) patients, with a median value of 720 lymphocytes/µl (IQR 520-1,135). This reduction was mirrored also on CD8+ (128 cells/µl, IQR 55-215), natural killer (67 cells/µl, IQR 35-158) and natural killer T (31 cells/µl, IQR 11-78) cells. Monocytes were preserved in total number but displayed among them a subpopulation with a higher forward and side scatter properties, composed mainly of cells with a reduced expression of both CD14 and HLA-DR. Patients who died in the 28 days from admission (N=10, 15.9%), when compared to those who did not, displayed lower mean values of CD3+ (337.4 cells/µl vs 585.9 cells/µl; p=0.028) and CD4+ cells (232.2 cells/µl vs 381.1 cells/µl; p=0.042) and an higher percentage of CD8+/CD38+/HLA-DR+ lymphocytes (13.5% vs 7.6%; p=0.026). The early phases of COVID-19 are characterized by lymphocytopenia, predominance of Th2-like lymphocytes and monocytes with altered immune profile, which include atypical mononuclear cells.

Specific immune suppression types have been associated with a greater risk of severe COVID-19 disease and death. We analyzed data from patients >17 years that were hospitalized for COVID-19 at the “Fondazione IRCCS Ca′ Granda Ospedale Maggiore Policlinico” in Milan (Lombardy, Northern Italy). The study included 1727 SARS-CoV-2-positive patients (1,131 males, median age of 65 years) hospitalized between February 2020 and November 2022. Of these, 321 (18.6%, CI: 16.8–20.4%) had at least one condition defining immune suppression. Immune suppressed subjects were more likely to have other co-morbidities (80.4% vs. 69.8%, p  < 0.001) and be vaccinated (37% vs. 12.7%, p  < 0.001). We evaluated the contribution of immune suppression to hospitalization during the various stages of the epidemic and investigated whether immune suppression contributed to severe outcomes and death, also considering the vaccination status of the patients. The proportion of immune suppressed patients among all hospitalizations (initially stable at <20%) started to increase around December 2021, and remained high (30–50%). This change coincided with an increase in the proportions of older patients and patients with co-morbidities and with a decrease in the proportion of patients with severe outcomes. Vaccinated patients showed a lower proportion of severe outcomes; among non-vaccinated patients, severe outcomes were more common in immune suppressed individuals. Immune suppression was a significant predictor of severe outcomes, after adjusting for age, sex, co-morbidities, period of hospitalization, and vaccination status (OR: 1.64; 95% CI: 1.23–2.19), while vaccination was a protective factor (OR: 0.31; 95% IC: 0.20–0.47). However, after November 2021, differences in disease outcomes between vaccinated and non-vaccinated groups (for both immune suppressed and immune competent subjects) disappeared. Since December 2021, the spread of the less virulent Omicron variant and an overall higher level of induced and/or natural immunity likely contributed to the observed shift in hospitalized patient characteristics. Nonetheless, vaccination against SARS-CoV-2, likely in combination with naturally acquired immunity, effectively reduced severe outcomes in both immune competent (73.9% vs. 48.2%, p  < 0.001) and immune suppressed (66.4% vs. 35.2%, p  < 0.001) patients, confirming previous observations about the value of the vaccine in preventing serious disease.

Aiming at understanding the source of the fluids that mineralizing within seismically active fault zones, we investigate the noble gas isotopes (i.e., helium (He), neon (Ne), and argon (Ar)) in the fluid inclusions (FIs) trapped in the calcite veins sampled along high‐angle fault zones of the Contursi hydrothermal basin, southern Italy. The latter basin lies in close vicinity of the MW = 6.9, 1980 Irpinia earthquake and exposes numerous fault scarps dissecting Mesozoic shallow‐water carbonates. The analyses of noble gases (He, Ne, Ar) are conducted to identify the origin of the volatiles circulating along the faults at the time of calcite precipitation. Then, outcomes of this discussions are compared with currently outgassing of deep‐sourced CO2 coupled to mantle‐derived He in that area, whose output is larger than those from some volcanic areas worldwide. The results indicate that He in FIs is dominated by a crustal radiogenic component (4He), and by an up to 20% of a mantle‐derived component (3He), with a highest isotopic signature of 1.38 Ra. This value is consistent with the highest percentage of mantle‐derived He associated to high‐flux CO2 gas emission in the investigated area (1.41 Ra). We propose that the variability of the He isotopic signature measured in primary FIs can result from early trapping of fluid inclusions or post trapping processes and seismic activity that modify the pristine He isotopic signature (i.e., derived from the crust and/or mantle) in groundwater along the faults during periods of background seismicity. Such investigations are fundamental to understand fluid migration in fault systems and the role of fluids in processes of earthquake nucleation. Key Points Paleofluids in the studied seismogenic fault derive from the mixing between crustal and mantle (∼20%) derived fluids The variability of the He isotopic signature registered in fluid inclusions results from either early trapping processes (due to past possible earthquakes events) or post trapping processes by addition of radiogenic 4He produced within fractured calcite veins over time (vein aging) The pristine mantle source has been active in the Irpinia area (southern Italy) for at least 1 Ma based on the post trapping process

Background. The hypermobile type of Ehlers–Danlos syndrome (hEDS) is likely the most common hereditary disorder of connective tissue mainly characterized by joint hypermobility. Patients with hEDS suffer joint pain, in particular low back pain, commonly resistant to drug therapy. The aim of this research was to evaluate a neurocognitive rehabilitation approach based not only on the motion and function recovery but also on the pain management. Methods. In this nonrandomized clinical trial, eighteen hEDS patients (4 males and 14 females) with mean age 21 years (range 13-55) were recruited and evaluated before and after three months of rehabilitation treatment. Results. The outcome scores showed significant statistical results after treatment in reducing pain symptoms (numerical rating scale, P=0.003; McGill (total score), P=0.03), fatigue (fatigue severity scale, P=0.03), fear of movement (Tampa scale, P=0.003), and pain-associated disability (Oswestry disability index, P=0.03). Conclusion. The clinical results observed in our study seem to confirm the role of a specific neurocognitive rehabilitation program in the chronic pain management in the Ehlers–Danlos syndrome; the rehabilitation treatment should be tailored on patient problems and focused not only in the recovery of movement but also on pain perception.