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The assessment of antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is of critical importance to verify the protective efficacy of available vaccines. Hospital healthcare workers play an essential role in the care and treatment of patients and were particularly at risk of contracting the SARS-CoV-2 infection during the pandemic. The vaccination protocol introduced in our hospital protected the workers and contributed to the containment of the infection' s spread and transmission, although a reduction in vaccine efficacy against symptomatic and breakthrough infections in vaccinated individuals was observed over time. Here, we present the results of a longitudinal and prospective analysis of the anti-SARS-CoV-2 antibodies at multiple time points over a 17-month period to determine how circulating antibody levels change over time following natural infection and vaccination for SARS-CoV-2 before (T0-T4) and after the spread of the omicron variant (T5-T6), analyzing the antibody response of 232 healthy workers at the Pio XI hospital in Desio. A General Estimating Equation model indicated a significant association of the antibody response with time intervals and hospital area, independent of age and sex. Specifically, a similar pattern of antibody response was observed between the surgery and administrative departments, and a different pattern with higher peaks of average antibody response was observed in the emergency and medical departments. Furthermore, using a logistic model, we found no differences in contracting SARS-CoV-2 after the third dose based on the hospital department. Finally, analysis of antibody distribution following the spread of the omicron variant, subdividing the cohort of positive individuals into centiles, highlighted a cut-off of 550 BAU/mL and showed that subjects with antibodies below this are more susceptible to infection than those with a concentration above the established cut-off value.

Down syndrome (DS) is a complex chromosomal disorder considered as a genetically determined form of Alzheimer's disease (AD). Maintenance of brain cholesterol homeostasis is essential for brain functioning and development, and its dysregulation is associated with AD neuroinflammation and oxidative damage. Brain cholesterol imbalances also likely occur in DS, concurring with the precocious AD-like neurodegeneration. In this pilot study, we analyzed, in the brain of the Ts2Cje (Ts2) mouse model of DS, the expression of genes encoding key enzymes involved in cholesterol metabolism and of the levels of cholesterol and its main precursors and products of its metabolism (i.e., oxysterols). The results showed, in Ts2 mice compared to euploid mice, the downregulation of the transcription of the genes encoding the enzymes 3-hydroxy-3-methylglutaryl-CoA reductase and 24-dehydrocholesterol reductase, the latter originally recognized as an indicator of AD, and the consequent reduction in total cholesterol levels. Moreover, the expression of genes encoding enzymes responsible for brain cholesterol oxidation and the amounts of the resulting oxysterols were modified in Ts2 mouse brains, and the levels of cholesterol autoxidation products were increased, suggesting an exacerbation of cerebral oxidative stress. We also observed an enhanced inflammatory response in Ts2 mice, underlined by the upregulation of the transcription of the genes encoding for α-interferon and interleukin-6, two cytokines whose synthesis is increased in the brains of AD patients. Overall, these results suggest that DS and AD brains share cholesterol cycle derangements and altered oxysterol levels, which may contribute to the oxidative and inflammatory events involved in both diseases.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with a high rate of mortality in kidney transplant recipients (KTRs). Current vaccine strategies for KTRs seem to be unable to provide effective protection against coronavirus disease 2019 (COVID-19), and the occurrence of severe disease in some vaccinated KTRs suggested a lack of immunity. We initially analyzed the antibody response in a group of 32 kidney transplant recipients (KTRs) followed at the nephrology and dialysis unit of the Hospital Pio XI of Desio, ASST-Brianza, Italy. Thus, we studied the differences in antibody levels between subjects who contracted SARS-CoV-2 after the booster (8 individuals) and those who did not contract it (24 individuals). Furthermore, we verified if the antibody response was in any way associated with creatinine and eGFR levels. We observed a significant increase in the antibody response pre-booster compared to post-booster using both a Roche assay and DIAPRO assay. In the latter, through immunotyping, we highlight that the major contribution to this increase is specifically due to IgG S1 IgM S2. We observed a significant increase in IgA S1 and IgA NCP ( p = 0.045, 0.02) in the subjects who contracted SARS-CoV-2. We did not find significant associations for the p -value corrected for false discovery rate (FDR) between the antibody response to all assays and creatinine levels. This observation allows us to confirm that patients require additional vaccine boosters due to their immunocompromised status and therapy in order to protect them from infections related to viral variants. This is in line with the data reported in the literature, and it could be worthwhile to deeply explore these phenomena to better understand the role of IgA S1 and IgA NCP antibodies in SARS-CoV-2 infection.

We retrospectively analyzed the antimicrobial data of Enterobacter spp. strains isolated from hospitalized subjects and outpatients over 20 years (2000-2019). A total of 2277 non-duplicate Enterobacter spp. isolates, 1037 from outpatients (45%) and 1240 from hospitalized subjects (55%), were retrieved. Most of samples are infections of the urinary tract. Considering Enterobacter aerogenes, now classified as Klebsiella aerogenes, and Enterobacter cloacae , representing more than 90% of all isolates, except for aminoglycosides and fluroquinolones, which showed significant antibiotic decreasing trends ( p < 0.01), none of the other antimicrobial agents tested showed significant changes in both groups ( p > 0.05). Conversely, there was a significant increasing resistance trend for fosfomycin ( p < 0.01), among both community and hospital-related subjects, most probably owing to uncontrolled and improper usage. Surveillance studies on antibiotic resistance at the local and regional level are required to detect new resistance mechanisms, reduce inappropriate antimicrobial consumption, and increase the focus on antimicrobial stewardship.

Windstorms are rare in the Southern Alps, but their frequency is increasing due to climate change. This research analyzed the vegetation of two spruce forests in Camonica Valley (Northern Italy) destroyed by the Vaia storm to evaluate the vegetation responses to blowdown damage. In each study area, the normalized difference vegetation index (NDVI) was used to evaluate the change in plant cover and greenness from 2018 (before the Vaia storm) to 2021. Furthermore, floristic-vegetation data were analyzed to identify current plant communities and develop models of plant succession. The results showed that the two areas, although located in different altitudinal vegetation belts, are undergoing the same ecological processes. NDVI is increasing in both areas, and pre-disturbance values (~0.8) should be reached in less than ten years. Nevertheless, the spontaneous restoration of pre-disturbance forest communities ( Calamagrostio arundinaceae-Piceetum ) should not occur in both study areas. In fact, the two plant succession trends are characterized by pioneer and intermediate stages with young trees of Quercus petraea and Abies alba , typical of more thermophilic mature forest communities compared to pre-disturbance ones. These results could reinforce the trend of the upward shift in forest plant species and plant communities in response to environmental changes in mountain areas.

The strongest genetic risk factor for sporadic Alzheimer's disease (AD) is the presence of the ε4 allele of the apolipoprotein E (ApoE) gene, the major apolipoprotein involved in brain cholesterol homeostasis. Being astrocytes the main producers of cholesterol and ApoE in the brain, we investigated the impact of the ApoE genotype on astrocyte cholesterol homeostasis. Two mouse astrocytic cell lines expressing the human ApoE3 or ApoE4 isoform were employed. Gas chromatography-mass spectrometry (GC-MS) analysis pointed out that the levels of total cholesterol, cholesterol precursors, and various oxysterols are altered in ApoE4 astrocytes. Moreover, the gene expression analysis of more than 40 lipid-related genes by qRT-PCR showed that certain genes are up-regulated (e.g., CYP27A1) and others down-regulated (e.g., PPARγ, LXRα) in ApoE4, compared to ApoE3 astrocytes. Beyond confirming the significant reduction in the levels of PPARγ, a key transcription factor involved in the maintenance of lipid homeostasis, Western blotting showed that both intracellular and secreted ApoE levels are altered in ApoE4 astrocytes, as well as the levels of receptors and transporters involved in lipid uptake/efflux (ABCA1, LDLR, LRP1, and ApoER2). Data showed that the ApoE genotype clearly affects astrocytic cholesterol homeostasis; however, further investigation is needed to clarify the mechanisms underlying these differences and the consequences on neighboring cells. Indeed, drug development aimed at restoring cholesterol homeostasis could be a potential strategy to counteract AD.

Background: Cefiderocol is a siderophore cephalosporin that exhibits antimicrobial activity against most multi-drug resistant Gram-negative bacteria, including Enterobacterales, Pseudomonas aeruginosa , Acinetobacter baumannii , and Stenotrophomonas maltophilia ., Methods: A total of 20 multidrug-resistant A. baumannii strains were isolated from 2020 to 2021, molecularly characterized and tested to assess the in vitro antibacterial activity of cefiderocol. Thirteen strains were carbapenem-hydrolysing oxacillinase OXA-23-like producers, while seven were non-OXA-23-like producers. Minimum inhibitory concentrations (MICs) were determined by broth microdilution, considered as the gold standard method. Disk diffusion test was also carried out using iron-depleted CAMHB plates for cefiderocol., Results: Cefiderocol MICs ranged from 0.5 to 1 mg/L for OXA-23-like non-producing A. baumannii strains and from 0.25 to >32 mg/L for OXA-23-like producers, using the broth microdilution method. Cefiderocol MIC 90 was 8 mg/L. Diameter of inhibition zone of cefiderocol ranged from 18 to 25 mm for OXA-23-like non-producers and from 15 to 36 mm for OXA-23-like producers, using the diffusion disk method. A large variability and a low reproducibility were observed during the determination of diameter inhibition zone. Molecular characterization showed that all isolates presented the ISAba1 genetic element upstream the bla OXA-51. Among OXA-23-like non-producers, four were bla OXA-58 positive and two were negative for all the resistance determinants analyzed., Conclusions: Cefiderocol showed in vitro antimicrobial activity against both carbapenem-susceptible and non-susceptible A. baumannii strains, although some OXA-23-like producers were resistant. Further clinical studies are needed to consolidate the role of cefiderocol as an antibiotic against MDR A. baumannii .

The β-lactams have a central place in the antibacterial armamentarium, but the increasing resistance to these drugs, especially among Gram-negative bacteria, is becoming one of the major threats to public health worldwide. Treatment options are limited, and only a small number of novel antibiotics are in development. However, one of the responses to this threat is the combination of β-lactam antibiotics with β-lactamase inhibitors, which are successfully used in the clinic for overcoming resistance by inhibiting β-lactamases. The existing inhibitors inactivate most of class A and C serine β-lactamases, but several of class D and B (metallo-β-lactamase) are resistant. The present review provides the status and knowledge concerning current β-lactamase inhibitors and an update on research efforts to identify and develop new and more efficient β-lactamase inhibitors.