Candida albicans infections have become increasingly recognised as being biofilm related. Recent studies have shown that there is a relationship between biofilm formation and poor clinical outcomes in patients infected with biofilm proficient strains. Here we have investigated a panel of clinical isolates in an attempt to evaluate their phenotypic and transcriptional properties in an attempt to differentiate and define levels of biofilm formation.

Skin malignant melanoma (MM) is an aggressive cancer with an increasing incidence with limited therapies in advanced stages. Tumor-associated macrophages (TAMs) are the major immune constituent of the MM microenvironment and contribute toward its prognosis. TAMs’ characterization and localization in human cancer is important to understand cancer progression and to identify molecular personalized therapies. M2 TAMs in stage I–II MMs are associated with worse prognostic parameters. A comprehensive M1-macrophage and M2-macrophage intratumoral localization and quantification in all stages of skin MMs is documented here with its clinical significance. To highlight immune pathways and possible early indicators of MM progression, we evaluated the number of M1 and M2 TAMs and intratumoral distribution in a large series of skin MMs. CD68 double immunostaining with MRP8–14 or inducible nitric oxide synthase (M1 macrophages) and with CD163 or CD204 (M2 macrophages) was performed in 94 stage I–IV skin MMs with a long duration of follow-up. The accumulation and distribution of M1 and M2 TAMs in intratumoral nests, stroma, and at the invasive front was correlated with clinicopathological variables. Since the early stage of MMs, M1 intratumoral macrophages were fewer than the M2 population; their recruitment was rapidly and progressively overwhelmed by an increase in M2 TAMs during MM progression. Independent of their intratumoral distribution, the accumulation of both M1 and M2 TAMs is associated with poor prognostic indicators and patients’ survival. M1-recruited macrophages shift to the M2 phenotype early in MM development, possibly induced by high inducible nitric oxide synthase intratumoral increase peculiarly occurring since the initial MM stages. M2-recruited TAMs overwhelm M1 accumulation in all stages of MM progression, thus favoring neoplastic growth and dissemination. Independent of their intratumoral distribution, the prevalent accumulation of M2 TAMs in MM is statistically confirmed to be a poor indicator of patients’ outcome and a potential target of immune therapies.

Objective: HIV-infected individuals with incomplete CD4⁺ T-cell recovery upon combination antiretroviral therapy (cART) display high levels of immune activation and microbial translocation. However, whether a link exists between gut damage and poor immunological reconstitution remains unknown. Design: Cross-sectional study of the gastrointestinal tract in late cART-treated HIV-infected individuals: 15 immunological nonresponders (CD4⁺ <350 cells/μl and/or delta CD4⁺ change from baseline 350 cells/μl and/or delta CD4⁺ change from baseline >30%). Methods: We assessed gut structure (junctional complex proteins in ileum and colon) and function (small intestine permeability/damage and microbial translocation parameters). The composition of the fecal microbiome and the size of the HIV reservoir in the gut and peripheral blood were investigated as possible mechanisms underlying mucosal impairment. Results: Markers of intestinal permeability, damage, systemic inflammation, and microbial translocation were comparable in all study individuals, yet the expression of junctional complex proteins in gut biopsies was significantly lower in HIV-infected patients with incomplete CD4⁺ restoration and negatively correlated with markers of CD4⁺ reconstitution. Electron microscopy revealed dilated intercellular spaces in individuals lacking immunological response to cART, yet not in patients displaying CD4⁺ T-cell recovery. Analysis of the fecal microbiome revealed an overall outgrowth of Bacteroides–Prevotella spp. with no differences according to CD4⁺ T-cell reconstitution. Interestingly, HIV reservoirs in peripheral CD4⁺ T cells and intestinal tissue negatively correlated with immune recovery. Conclusion: These observations establish gut damage and the size of the HIV reservoir as features of deficient immunological response to cART and provide new elements for interventional strategies in this setting.

Aims: A considerable proportion of patients affected by coronavirus respiratory disease (COVID-19) develop cardiac injury. The viral impact in cardiomyocytes deserves, however, further investigations, especially in asymptomatic patients. Methods: We investigated for SARS-CoV-2 presence and activity in heart tissues of six consecutive COVID-19 patients deceased from respiratory failure showing no signs of cardiac involvement and with no history of heart disease. Cardiac autopsy samples were collected within 2 h after death, and then analysed by digital PCR, Western blot, immunohistochemistry, immunofluorescence, RNAScope, and transmission electron microscopy assays. Results: The presence of SARS-CoV-2 into cardiomyocytes was invariably detected in all assays. A variable pattern of cardiomyocyte injury was observed, spanning from absence of cell death and subcellular alterations hallmarks, to intracellular oedema and sarcomere ruptures. In addition, we found active viral transcription in cardiomyocytes, by detecting both sense and antisense SARS-CoV-2 spike RNA. Conclusions: In this autopsy analysis of patients with no clinical signs of cardiac involvement, the presence of SARS-CoV-2 in cardiomyocytes has been detected, determining variable patterns of intracellular damage. These findings suggest the need for cardiologic surveillance in surviving COVID-19 patients not displaying a cardiac phenotype.