The impact of the COVID-19 pandemic on healthcare-associated infections in intensive care unit patients: a retrospective cohort study.

BACKGROUND: During the intensive care units' (ICUs) reorganization that was forced by the COVID-19 emergency, attention to traditional infection control measures may have been reduced. Nevertheless, evidence on the effect of the COVID-19 pandemic on healthcare-associated infections (HAIs) is still limited and mixed. In this study, we estimated the pandemic impact on HAI incidence and investigated the HAI type occurring in COVID-19 patients. METHODS: Patients admitted to the main ICU of the Umberto I teaching hospital of Rome from March 1st and April 4th 2020 were compared with patients hospitalized in 2019. We assessed the association of risk factors and time-to-first event through multivariable Fine and Grey's regression models, that consider the competitive risk of death on the development of HAI (Model 1) or device related-HAI (dr-HAI, Model 2) and provide estimates of the sub-distribution hazard ratio (SHR) and its associated confidence interval (CI). A subgroup analysis was performed on the 2020 cohort. RESULTS: Data from 104 patients were retrieved. Overall, 59 HAIs were recorded, 32 of which occurred in the COVID-19 group. Patients admitted in 2020 were found to be positively associated with both HAI and dr-HAI onset (SHR: 2.66, 95% CI 1.31-5.38, and SHR: 10.0, 95% CI 1.84-54.41, respectively). Despite being not confirmed at the multivariable analysis, a greater proportion of dr-HAIs seemed to occur in COVID-19 patients, especially ventilator-associated pneumonia, and catheter-related urinary tract infections. CONCLUSIONS: We observed an increase in the incidence of patients with HAIs, especially dr-HAIs, mainly sustained by COVID-19 patients. A greater susceptibility of these patients to device-related infections was hypothesized, but further studies are needed.

A survey on knowledge and awareness on the issue "microplastics": a pilot study on a sample of future public health professionals.

BACKGROUND: Microplastics pollution represents a global public health concern. Since the greatest amount of microplastics are of anthropogenic origin, one of the most relevant strategies to reduce microplastics pollution is to raise awareness among the population and this is even more important for all those involved in public health prevention interventions. The aim of this study was to assess the level of knowledge and awareness on microplastics of a samples of future healthcare workers. STUDY DESIGN: A cross-sectional study was performed on 151 university students in the field of Public Health, both pre- and post-graduate, attending the Sapienza University of Rome courses. METHODS: A questionnaire consisting of three sections was administered to the participants. The first section assessed knowledge and awareness on microplastics, the second consisted of an informative brochure on microplastics, the third evaluated the awareness after reading the brochure, and interventions considered useful to manage microplastics pollution. RESULTS: About 25% of participants had never heard of microplastics. The scores on knowledge about microplastics were low, and differences between the investigated courses were not statistically significant (p-Value=0.134). Internet was the main source of information on microplastics, while the scores describing concern about the investigated issue resulted always higher after reading the informative brochure respect to before reading. CONCLUSIONS: The lack of knowledge about microplastics pollution highlights that future public health workers should be better informed and, therefore, able to transfer essential information to the population. Increasing general population's knowledge and awareness would increase risk perception and make all individuals more active actors for reducing microplastics pollution.

In vivo characterization of Zirconia Toughened Alumina material: a comparative animal study.

The development of a new chromia-doped Zirconia Toughened Alumina (ZTA) material was previously reported as displaying mechanical properties suitable for implants with load bearing applications, such as orthopaedic and dental implants. This type of biomaterial is expected to be in contact with living tissues for a long period of time and its long-term toxicity must be carefully evaluated. In this study the suitability of this ZTA material as a candidate biomaterial for orthopaedic implants and dental devices was further investigated in vivo in comparison to alumina and zirconia, which are currently used in orthopaedic and dental surgery. Cylinders of the materials were implanted in vivo in white rabbits, and local and systemic tissue reactions were analyzed at different time intervals after surgery. Radiologic examinations displayed the absence of radiolucence around cylinders and no signs of implant loosening up to twelve months. No tumours developed in the animals either locally (at the site of implantation), or systemically in the peripheral organs. The results obtained suggest that this new ZTA material does not display any long term pathogenic effect in vivo. These findings extend our previous observations on the biocompatibility and the absence of any long-term carcinogenic effect in vitro of this material which displays interesting properties for biomedical applications. In conclusion, we report the in vivo characterization of a new chromia-doped ZTA material and confirm its suitability as a candidate biomaterial for orthopaedic implants and dental devices since it does not give any local nor systemic toxicity even after a long period of time after implantation.

Development of a new zirconia-toughened alumina: promising mechanical properties and absence of in vitro carcinogenicity.

High purity alumina as well as zirconia ceramics have been widely used as orthopaedic implant biomaterials and dental devices displaying optimal, but sometimes exclusive, mechanical properties. In order to combine the advantages of alumina and zirconia ceramic materials different types of composites have been developed in which either zirconia is dispersed in an alumina matrix or vice versa. Orthopaedic and dental implant biomaterials are expected to be in contact with living tissues for a long period of time and their long term toxicity must be carefully evaluated. In this study we report the development of a high performance chromia-doped zirconia toughened alumina (ZTA) material which displays promising mechanical properties in terms of hardness, strength and fracture toughness that make it suitable for prosthesis even for small joints. The long-term biocompatibility of this material was also evaluated, mainly in terms of DNA damage, mutagenicity and cancerogenetic potential in mammalian cells. The results obtained suggest that this new ZTA material does not display any longterm carcinogenic effect and it is suitable for biomedical applications from a cancerogenetic point of view. In conclusion, we report the development of a new chromia-doped ZTA material with interesting properties, both from a mechanical and a biocompatibility point of view which warrant further studies on its suitability as a candidate biomaterial for orthopaedic implants and dental devices.

Evidence for the role of neurogenic inflammation components in trypsin-elicited scratching behaviour in mice.

BACKGROUND AND PURPOSE: We investigated the mechanisms underlying the pruritogenic response induced by trypsin in mice, to assess the relevance of neurogenic inflammation components in this response. EXPERIMENTAL APPROACH: Itching was induced by an intradermal injection of trypsin in the mouse neck. The animals were observed for 40 min and their scratching behaviour was quantified. KEY RESULTS: Trypsin-induced itching was blocked by the lima bean trypsin inhibitor, the selective proteinase-activated receptor-2 (PAR-2) antagonist FSLLRY and PAR-2 receptor desensitization. An important involvement of mast cells was observed, as chronic pretreatment with the mast cell degranulator compound 48/80 or the mast cell stabilizer disodium cromoglycate prevented scratching. Also, trypsin response was inhibited by the selective COX-2 inhibitor celecoxib and by the selective kinin B2 (FR173657) and B1 (SSR240612) receptor antagonists. Moreover, an essential role for the mediators of neurogenic inflammation was established, as the selective NK1 (FK888), NK3 (SR142801) and calcitonin gene-related peptide (CGRP(8-37) fragment) receptor antagonists inhibited trypsin-induced itching. Similarly, blockade of transient receptor potential vanilloid 1 (TRPV1) receptors by the selective TRPV1 receptor antagonist SB366791, or by genetic deletion of TRPV1 receptor reduced this behaviour in mice. C-fibre desensitization showed a very similar result. CONCLUSIONS AND IMPLICATIONS: Trypsin intradermal injection proved to be a reproducible model for the study of itching and the involvement of PAR-2 receptors. Also, trypsin-induced itching seems to be widely dependent on neurogenic inflammation, with a role for TRPV1 receptors. In addition, several other mediators located in the sensory nerves and skin also seem to contribute to this process.

Identification of 14 new glucokinase mutations and description of the clinical profile of 42 MODY-2 families.

Mutations in glucokinase are associated with defects in insulin secretion and hepatic glycogen synthesis resulting in mild chronic hyperglycaemia, impaired glucose tolerance or diabetes mellitus. We screened members of 35 families with features of maturity-onset diabetes of the young for mutations in the glucokinase gene and found 16 different mutations. They included 14 new mutations in the glucokinase gene: 9 missense mutations (A53S, G80A, H137R, T168P, M210T, C213R, V226M, S336L and V367M); 2 nonsense mutations (E248X and S360X); a deletion of one nucleotide resulting in a frameshift (V401del1); a substitution of a conserved nucleotide at a splice acceptor site (L122-1G-->T); and a 10 base pair deletion that removed the GT of the splice donor site and the following eight nucleotides (K161 + 2del10). In addition, we found two previously identified mutations: R186X and G261R. Study of 260 subjects with glucokinase-deficient hyperglycaemia from 42 families with 36 different GCK mutations made it possible to define the clinical profile of this subtype of non-insulin-dependent diabetes mellitus (NIDDM). Hyperglycaemia due to glucokinase deficiency is often mild (fewer than 50% of subjects have overt diabetes) and is evident during the early years of life. Despite the long duration of hyperglycaemia, glucokinase-deficient subjects have a low prevalence of micro- and macro-vascular complications of diabetes. Obesity, arterial hypertension and dyslipidaemia are also uncommon in this form of NIDDM.

Effect of mutations on the sensitivity of human beta-cell glucokinase to liver regulatory protein.

Human beta-cell glucokinase and its liver counterpart displayed a half-saturating concentration of glucose (S0.5) of about 8 mmol/l and a Hill coefficient of 1.7, and were as sensitive to inhibition by the rat liver regulatory protein as the rat liver enzyme. These results indicate that the N-terminal region of glucokinase, which differs among these three enzymes, is not implicated in the recognition of the regulatory protein. They also suggest that the regulatory protein, or a related protein, could modulate the affinity of glucokinase for glucose in beta cells. We have also tested the effect of several mutations, many of which are implicated in maturity onset diabetes of the young. The mutations affected the affinity for glucose and for the regulatory protein to different degrees, indicating that the binding site for these molecules is different. An Asp158 Ala mutation, found in the expression plasmid previously thought to encode the wild-type enzyme, increased the affinity for glucose by about 2.5-fold without changing the affinity for the regulatory protein. The mutations that were found to decrease the affinity for the regulatory protein (Asn166 Arg. Val203 Ala, Asn204 Gln, Lys414 Ala) clustered in the hinge region of glucokinase and nearby in the large and small domains. These results are in agreement with the concept that part of the binding site for the regulatory protein is situated in the hinge region of this enzyme.

Electroencephalographic consequences of sodium dehydrocholate-induced blood-brain barrier disruption: Part 2. Generation and propagation of spike activity after the topical application of sodium dehydrocholate.

Sodium dehydrocholate was applied topically to the right hemispheric cortex of eight rats and the electrocorticogram was monitored from both the treated cortex and the homotopic cortex of the contralateral hemisphere. All animals developed blood-brain barrier (BBB) disruption in the treated cortex as evidenced by cortical staining with systemically administered Evans blue dye. Spike activity developed in three of eight animals after the topical application of dehydrocholate. The subsequent intravenous injection of sodium dehydrocholate provoked spike activity in both hemispheres in all eight animals. Dependent and independent spike activity was recorded in the nondisrupted hemisphere. The intravenous administration of gamma-aminobutyric acid (GABA) resulted in alterations in spike activity in four of five animals because of penetration of the GABA through the altered BBB. These findings demonstrate that sodium dehydrocholate can result in increased BBB permeability when applied directly to the cortical surface. Spike activity subsequent to the topical application of dehydrocholate can be enhanced by systemic loading with dehydrocholate. Spike activity occurring over the nontreated cortex (secondary focus) represents interhemispheric propagation of spike activity from the disrupted hemisphere (primary focus). The lack of Evans blue staining in the actively discharging secondary focus suggests that spike activity does not account for the increases in BBB permeability observed with dehydrocholate treatment.

Effect of intracarotid etoposide on opening the blood-brain barrier.

The effect of an intracarotid artery infusion of etoposide on blood-brain barrier (BBB) integrity was investigated in a rat model system. The external carotid arteries of Sprague-Dawley rats were catheterized in a retrograde manner. Etoposide in a dose range from 3.0 mg/kg to 22.5 mg/kg was infused into the internal carotid artery by this technique. BBB disruption was evaluated qualitatively by the appearance in the infused hemisphere of the systemically administered dye Evans blue and quantitatively by the ratio of counts of the technetium-labeled chelate of diethylenetriaminepentaacetic acid (99mTc-DTPA) in the infused to the noninfused hemisphere. Evidence of increased BBB permeability was seen at all doses of etoposide. Degree of BBB disruption increased with increasing doses of etoposide. The intracarotid infusion and subsequent BBB disruption were well tolerated. Further clinical trials employing the intracarotid administration of etoposide should be cognizant of the potential for BBB disruption.