Chemical skin defence in the Eastern fire-bellied toad Bombina orientalis: an ultrastructural approach to the mechanism of poison gland rehabilitation after discharge

Type I serous glands in the skin of the Eastern yellow-bellied toad Bombina orientalis released their product massively after 10-3 M nor-adrenalin (NA) stimulation, mimicking orthosympathetic control on poison emission in chemical skin defence. Features of cutaneous glands involved in this bulk discharge were observed under light and electron microscopes. Furthermore, restoration of depleted glands was followed after 1, 2 and 3 weeks, and compared with serous biosynthesis during larval gland development. Bulk discharge was caused by contraction of myoepithelial cells (mecs) encircling the secretory units. Mec compression dramatically affected the secretory unit, but parts of this syncytial cytoplasm were saved from degeneration and cooperated in gland renewal with stem cells from the gland neck. These adenoblasts underwent proliferation and secretory cytodifferentiation, until merging with the syncytium. Cytoplasm that had resumed secretory activity showed the features typical of larval gland development: the endoplasmic reticulum (rer) cisterns were aligned in close parallel arrangement and Golgi stacks released minute type I granules. Secretory rehabilitation led to increasing amounts of granule content. In the meantime, rough cisterns decreased in number and assumed the less ordered pattern described in control specimens. Data collected in the present study revealed that chemical skin defence in anurans is a multi-factorial mechanism involving specific activities: mechanical from mecs, biosynthetic from secretory syncytium and proliferative from intercalated stem cells

The role of immune suppression in COVID-19 hospitalization: clinical and epidemiological trends over three years of SARS-CoV-2 epidemic

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

Chemical skin defence in the Eastern fire-bellied toad <i>Bombina orientalis</i>: an ultrastructural approach to the mechanism of poison gland rehabilitation after discharge

Type I serous glands in the skin of the Eastern yellow-bellied toad Bombina orientalis released their product massively after 10-3 M nor-adrenalin (NA) stimulation, mimicking orthosympathetic control on poison emission in chemical skin defence. Features of cutaneous glands involved in this bulk discharge were observed under light and electron microscopes. Furthermore, restoration of depleted glands was followed after 1, 2 and 3 weeks, and compared with serous biosynthesis during larval gland development. Bulk discharge was caused by contraction of myoepithelial cells (mecs) encircling the secretory units. Mec compression dramatically affected the secretory unit, but parts of this syncytial cytoplasm were saved from degeneration and cooperated in gland renewal with stem cells from the gland neck. These adenoblasts underwent proliferation and secretory cytodifferentiation, until merging with the syncytium. Cytoplasm that had resumed secretory activity showed the features typical of larval gland development: the endoplasmic reticulum (rer) cisterns were aligned in close parallel arrangement and Golgi stacks released minute type I granules. Secretory rehabilitation led to increasing amounts of granule content. In the meantime, rough cisterns decreased in number and assumed the less ordered pattern described in control specimens. Data collected in the present study revealed that chemical skin defence in anurans is a multi-factorial mechanism involving specific activities: mechanical from mecs, biosynthetic from secretory syncytium and proliferative from intercalated stem cells

Survival and recruitment in the population ecology of the endangered Bombina pachypus (Amphibia: Anura): Supplementary Material

<p>Global amphibian decline is a subject of great conservation concern, yet often basic demographic information is absent, which prevents the understanding of population trends and the planning of effective conservation management. We analysed capture-mark-recapture data from six populations of the endangered<i> Bombina pachypus</i> in order to understand the relative contribution of survival and recruitment to population growth, and to assess if any differences exist among populations in terms of their population dynamics. We found that survival was rather high and generally constant among sites, and recruitment was low, with the exception of two single years at one site. Population growth depended on survival on all sites, except the years following high recruitment at one site. Annual population size was generally lower than 30 individuals, but in one site it was estimated to be larger than 50. Our findings suggest that juvenile survival is more important for population dynamics than recruitment from the larval to the juvenile stage. We also suggest that the low recruitment rates we recorded was a result of juvenile dispersal, and that when populations exhibited high recruitment it was due to occasional successful migration or local recruitment. This pattern could represent a way to counterbalance the risk of inbreeding in populations composed of few individuals, a common characteristic of populations of <i>B. pachypus</i>. Finally, we suggest that conservation measures for <i>B. pachypus</i> should be planned at the landscape scale, and should not be limited solely to the breeding site and its close surroundings.</p

Compensatory recruitment allows amphibian population persistence in anthropogenic habitats

International audienceHabitat anthropization is a major driver of global biodiversity decline. Although most species are negatively affected, some benefit from anthropogenic habitat modifications by showing intriguing life-history responses. For instance, increased recruitment through higher allocation to reproduction or improved performance during early-life stages could compensate for reduced adult survival, corresponding to “compensatory recruitment”. To date, evidence of compensatory recruitment in response to habitat modification is restricted to plants, limiting understanding of its importance as a response to global change. We used the yellow-bellied toad ( Bombina variegata ), an amphibian occupying a broad range of natural and anthropogenic habitats, as a model species to test for and to quantify compensatory recruitment. Using an exceptional capture–recapture dataset composed of 21,714 individuals from 67 populations across Europe, we showed that adult survival was lower, lifespan was shorter, and actuarial senescence was higher in anthropogenic habitats, especially those affected by intense human activities. Increased recruitment in anthropogenic habitats fully offset reductions in adult survival, with the consequence that population growth rate in both habitat types was similar. Our findings indicate that compensatory recruitment allows toad populations to remain viable in human-dominated habitats and might facilitate the persistence of other animal populations in such environments

Clinical characteristics and outcomes of vaccinated patients hospitalised with SARS-CoV-2 breakthrough infection: Multi-IPV, a multicentre study in Northern Italy

Background: Despite the well-known efficacy of anti-COVID-19 vaccines in preventing morbidity and mortality, several vaccinated individuals are diagnosed with SARS-CoV-2 breakthrough infection, which might require hospitalisation. This multicentre, observational, and retrospective study aimed to investigate the clinical characteristics and outcomes of vaccinated vs. non-vaccinated patients, both hospitalised with SARS-CoV-2 infection in 3 major hospitals in Northern Italy. Methods: Data collection was retrospective, and paper and electronic medical records of adult patients with a diagnosed SARS-CoV-2 infection were pseudo-anonymised and analysed. Vaccinated and non-vaccinated individuals were manually paired, using a predetermined matching criterion (similar age, gender, and date of hospitalisation). Demographic, clinical, treatment, and outcome data were compared between groups differing by vaccination status using Pearson’s Chi-square and Mann-Whitney tests. Moreover, multiple logistic regression analyses were performed to assess the impact of vaccination status on ICU admission or intra-hospital mortality. Results: Data from 360 patients were collected. Vaccinated patients presented with a higher prevalence of relevant comorbidities, like kidney replacement therapy or haematological malignancy, despite a milder clinical presentation at the first evaluation. Non-vaccinated patients required intensive care more often than their vaccinated counterparts (8.8% vs. 1.7%, p = 0.002). Contrariwise, no difference in intra-hospital mortality was observed between the two groups (19% vs. 20%, p = 0.853). These results were confirmed by multivariable logistic regressions, which showed that vaccination was significantly associated with decreased risk of ICU admission (aOR=0.172, 95%CI: 0.039–0.542, p = 0.007), but not of intra-hospital mortality (aOR=0.996, 95%CI: 0.582–1.703, p = 0.987). Conclusions: This study provides real-world data on vaccinated patients hospitalised with COVID-19 in Northern Italy. Our results suggest that COVID-19 vaccination has a protective role in individuals with higher risk profiles, especially regarding the need for ICU admission. These findings contribute to our understanding of SARS-CoV-2 infection outcomes among vaccinated individuals and emphasise the importance of vaccination in preventing severe disease, particularly in those countries with lower first-booster uptake rates

Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial

BackgroundTocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients.MethodsA multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival.ResultsIn the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6-24.0, P=0.52) and 22.4% (97.5% CI: 17.2-28.3, P&lt;0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline.ConclusionsTocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline.Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092)