Novel Penicillin-Type Analogues Bearing a Variable Substituted 2-Azetidinone Ring at Position 6: Synthesis and Biological Evaluation

The synthesis and the biological activity of novel semi-synthetic β-lactam compounds containing an azetidinone moiety joined to the amino-nitrogen of the (+)-6-aminopenicillanic acid (6-APA) as new antibacterial agents is reported. The synthesized compounds were screened for their in vitro antimicrobial activity against a panel of Gram positive and Gram negative pathogens and environmental bacteria. Tested compounds displayed good antimicrobial activity against all tested Gram positive bacteria and for Staphylococcus aureus and Staphylococcus epidermidis antimicrobial activity resulted higher than that of the reference antibiotic. Additionally, in vitro cytotoxic screening was also carried out indicating that the compounds do not cause a cell vitality reduction effective at concentration next to and above those shown to be antimicrobial

Geographical Indications and Risks of Unsustainability Linked to “Disaffection Effects” in the Dairy Sector

This paper deals with the role of geographical indications (GI) in the dairy sector of Italy, with the purpose of highlighting eventual negative dynamics in the adhesion to the GI by the potential operators of Italy. A negative adhesion to the GI circuit shows a “disaffection effect,” and has relevant implications on sustainability on account of the role of a GI in boosting various dimensions of sustainability (economic, social, environmental). In order to verify the presence of a disaffection effect, an empirical analysis of the actors adhering to the GI dairy sector is carried out. Through the collection of secondary sources from official databases, the paper emphasises a negative trend in the adhesion to the GI dairy sector, which also reveals diversified territorial impacts. More precisely, unlike other sectors, the dairy sector reveals negative dynamics in the operators choosing to adhere to the GI circuits. The results of the analysis address some policy issues and solicit policy action to limit the disaffection effect on GI in the dairy sector

Application of the seven-factor-model of personality to an Italian preschool sample

OBJECTIVE: Advances in dimensional assessment of children in healthy and clinical populations has renewed interest in the study of temperament. Cloninger's Temperament and Character Inventory (TCI) has shown high reliability and internal consistency. Adult and adolescent versions have been translated into a number of languages and validated in cross-cultural studies worldwide. To date only one preschool-TCI-based study has been conducted in early infancy with teachers as observers. The present study is aimed to test an Italian Preschool version of the Temperament and Character Inventory (PsTCI). This is the first replication and the first validation study of TCI on preschoolers with parents as observers. METHODS: 395 preschool children, recruited from pediatric communities and day-care centres throughout Italy, participated in the study. Parents of each child enrolled in the study and completed a PsTCI about the child. Standard psychometric tests of reliability and validation were performed. RESULTS: Exploratory factor analyses demonstrated the presence of distinct domains for temperament and character. TCI dimensions had good internal consistency with Cronbach's alpha ranging values (|0.60|-|0.81|). Gender differences were found for Harm Avoidance (β=-0.186; p≤0.001) and Self-Directedness (β=-0.216; p≤0.01), and accounted for 5-35arm-38-702- of the observed variance. CONCLUSION: The present work suggests the psychological complexity of Cloninger's model and confirms its application in pre-school children from diverse environmental and cultural backgrounds. The results confirm that Cloninger's instrument for temperament and character evaluations can also be used with different observers and highlight the importance of considering cultural and demographic differences in the assessment of temperament and character in preschoolers

New simple and low-cost methods for periodic checks of Cyclone® Plus Storage Phosphor System

The recent large use of the Cyclone® Plus Storage Phosphor System, especially in European countries, as imaging system for quantification of radiochemical purity of radiopharmaceuticals raised the problem of setting the periodic controls as required by European Legislation. We described simple, low-cost methods for Cyclone® Plus quality controls, which can be useful to evaluate the performance measurement of this imaging system

Polystyrene nanoparticles internalization in human gastric adenocarcinoma cells

The increase in the use of nanoparticles, as a promising tool for drug delivery or as a food additive, raises questions about their interaction with biological systems, especially in terms of evoked responses. In this work, we evaluated the kinetics of uptake of 44 nm (NP44) and 100 nm (NP100) unmodified polystyrene nanoparticles (PS-NPs) in gastric adenocarcinoma (AGS) cells, as well as the endocytic mechanism involved, and the effect on cell viability and gene expression of genes involved in cell cycle regulation and inflammation processes. We showed that NP44 accumulate rapidly and more efficiently in the cytoplasm of AGS compared to NP100; both PS-NPs showed an energy dependent mechanism of internalization and a clathrin-mediated endocytosis pathway. Dose response treatments revealed a non-linear curve. PS-NPs also affected cell viability, inflammatory gene expression and cell morphology. NP44 strongly induced an up-regulation of IL-6 and IL-8 genes, two of the most important cytokines involved in gastric pathologies. Our study suggests that parameters such as time, size and concentration of NPs must be taken carefully into consideration during the development of drug delivery systems based on NPs and for the management of nanoparticles associated risk factors

A Case of Schizophrenia Complicated in Subacute Combined Degeneration: How Nutrition Affects Physical Health in Psychotic Patients

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Renal hemodynamic response to maximal vasodilating stimulus in healthy older subjects

Renal hemodynamic response to maximal vasodilating stimulus in healthy older subjects.BackgroundIt is still unclear whether age per se is associated with preservation of renal functional reserve, that is, of the increase in glomerular filtration rate (GFR) induced by appropriate vasodilating stimulus.MethodsTo gain insights into this issue, we evaluated the renal response to a maximal vasodilating stimulus, represented by the combined infusion of mixed amino acid solution (AA) and dopamine at renal dose (D), in 10 young subjects (median age of 30 years, range of 19 to 32) and in 11 subjects of older age (median age of 67 years, range of 65 to 76). Two further age-matched groups of young (N = 15) and older (N = 11) living kidney donors underwent renal needle biopsy immediately before nephrectomy to perform semiquantitative scoring (0 to 3) of arteriosclerosis in intrarenal arteries. All of the study subjects were nonsmokers with healthy status proven by extensive diagnostic evaluation excluding any risk factor of renal dysfunction.ResultsBasal renal plasma flow (RPF) and GFR were proportionally lower in older subjects (RPF, 361 ± 29 vs. 618 ± 34mL/min/1.73m2, P < 0.001; GFR, 79 ± 4 vs. 127 ± 5.8mL/min/1.73m2, P < 0.001). After AA + D, a significant increase of RPF and GFR was observed in both groups, but the older subjects exhibited a smaller percentage increment (RPF, 25.5 ± 4.8 vs. 42.4 ± 5.8, P < 0.05; GFR, 19.6 ± 5.7 vs. + 33.8 ± 6.4, P < 0.05). Furthermore, the maximal vasodilating stimulus was not able to restore renal hemodynamics in older subjects to the level measured in young controls at baseline. Renal vascular resistances were higher (P < 0.05) in the older subjects both at baseline (0.19 ± 0.02 vs. 0.09 ± 0.004mm Hg/mL/min) and after AA + D (0.14 ± 0.01 vs. 0.06 ± 0.004). Light microscopy examination detected the presence of a greater degree of arteriosclerosis at the level of interlobular and arcuate arteries (0.89 ± 0.15 vs. 0.45 ± 0.08) and interstitial fibrosis/tubular atrophy (1.18 ± 0.13 vs. 0.53 ± 0.13) in older than in young subjects.ConclusionsTherefore, aging has adverse effects on renal function despite the absence of any risk factor for renal disease, including chronic smoking: (1) GFR and RPF are lower, and (2) the renal response to maximal vasodilating stimulus is impaired. These aging-related alterations of renal hemodynamics are possibly due to organic lesions in renal vasculature

Safety and immunogenicity of the COVID-19 vaccine BNT162b2 for patients with breast and gynecological cancer on active anticancer therapy: Results of a prospective observational study

Background: Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are highly effective. Nevertheless, immunocompromised participants were excluded from randomized controlled clinical trials. This study evaluates the efficacy and safety of the Pfizer/BioNTech BNT162b2 (BNT162b2) vaccine in patients with breast and gynecological cancer treated with active anticancer therapy versus a control cohort of healthy participants. Methods: Immune responses to the BNT162b2 vaccine in patients with breast cancer (n = 44) or a gynecological malignancy (n = 6) on active anticancer therapy (28 on chemotherapy, mostly anthracycline- or taxane-based, and 22 on target therapy) and in a control cohort of participants without cancer (n = 67) were investigated by SARS-CoV-2 neutralizing antibody titers measured by S1-binding immunoglobulin G (IgG) concentrations assessed using the LIAISON XL tools (DiaSorin S.p.A.). Response was assessed after a second dose of the BNT162b2 vaccine administered before and at least 3 weeks after the vaccine dose. Results: Overall, 43/50 (86%) patients of the cancer cohort (74% in the breast cancer group and 100% in the gynecological malignancy group) developed IgG antibodies after the second dose of the BNT162b2 vaccine. There were no statistically significant differences in responder rates between patients treated with chemotherapy and those on target therapy. The majority of patients who received chemotherapy with or without target therapy, 21/28 (75%), developed a reliable antibody titer after a vaccine. All seven non-responder patients were undergoing an anthracycline-based regimen. Based on IgG levels (0-400 AU/ml), patients were classified as negative ('non-responders'), weakly positive, or strongly positive ('responders'). No delay in cancer therapy schedule or reported side effects were recorded after BNT162b2 vaccine administration. All healthy participants were strongly positive. Responder rates differed significantly between the two study cohorts (p < 0.001). Conclusions: Most patients develop antibody titers after the second immunization. However, given the persistence of non-responders or weak responders, additional immunization booster seems to be required, along with proactive planning in the vaccination schedule, with vaccine administration spaced out over time with respect to chemotherapy

Outcomes and Predictors of Mortality in Patients With KPC-Kp Infections Treated With Meropenem Vaborbactam: An Observational Multicenter Study

Background Meropenem-vaborbactam is a recent and promising option for the treatment of KPC-producing Klebsiella pneumoniae (KPC-Kp) infections, including those resistant to ceftazidime-avibactam.Methods We conducted a retrospective analysis of observational data from 19 Italian hospitals on use and outcomes of patients treated with meropenem-vaborbactam for at least &gt;= 24 hours for KPC-Kp infections. Crude and propensity-weighted multiple Cox regression models were performed to ascertain risk factors independently associated with 30-day mortality.Results The cohort included 342 adults with bloodstream infections (n = 172) and nonbacteremic infections (n = 170), of which 107 were lower respiratory tract infections, 30 were complicated urinary tract infections, and 33 were infections involving other sites. Most infections (62.3%) were managed with meropenem-vaborbactam monotherapy, or in combination with at least 1 other active drug (usually fosfomycin, tigecycline, or gentamicin) (37.7%). The 30-day mortality rate was 31.6% (108/342). In multiple Cox regression model, 30-day mortality was independently associated with septic shock at infection onset, Charlson comorbidity index &gt;= 3, dialysis, concomitant COVID-19, and INCREMENT score &gt;= 8. Administration of meropenem-vaborbactam within 48 hours from infection onset was a negative predictor of mortality. All predictors, except administration of meropenem-vaborbactam within 48 hours, remained significant when the multiple Cox regression model was repeated after adjustment for the propensity score for receipt of combination therapy.Conclusions Despite the limits of a retrospective study, the data derived from this multicenter cohort provide additional evidence on the efficacy of meropenem-vaborbactam in treating severe KPC-Kp infections, even when used as monotherapy