Evaluation of antifungal spectrum of Cupferron against Candida albicans.

Candida albicans is an opportunistic yeast accounting for about 50-90 % of all cases of candidiasis in humans, ranging from superficial to systemic potentially life-threatening infections. The presence of several virulence factors, including biofilm, hyphal transition, and proteolytic enzymes production, worsens the fungal infections burden on healthcare system resources. Hence, developing new bioactive compounds with antifungal activity is a pressing urgence for the scientific community. In this perspective, we evaluated the anti-Candida potential of the N-Nitroso-N-phenylhydroxylamine ammonium salt (cupferron) against standard and clinical C. albicans strains. Firstly, the in vitro cytotoxicity of cupferron was checked in the range 400-12.5 µg/mL against human microglial cells (HMC-3). Secondly, its antifungal spectrum was explored via disk diffusion test, broth-microdilution method, and time-killing curve analysis, validating the obtained results through scanning electron microscopy (SEM) observations. Additionally, we evaluated the cupferron impact on the main virulence determinants of Candida albicans. At non-toxic concentrations (100-12.5 µg/mL), the compound exerted interesting anti-Candida activity, registering a minimum inhibitory concentration (MIC) between 50 and 100 µg/mL against the tested strains, with a fungistatic effect until 100 µg/mL. Furthermore, cupferron was able to counteract fungal virulence at MIC and sub-MIC values (50-12.5 µg/mL). These findings may propose cupferron as a new potential antifungal option for the treatment of Candida albicans infections.

The antiherpetic and anti-inflammatory activity of the frog-derived peptide Hylin-a1.

AIM: The high incidence of virus-related infections and the large diffusion of drug-resistant pathogens stimulate the search and identification of new antiviral agents with a broad spectrum of action. Antivirals can be designed to act on a single target by interfering with a specific step in the viral lifecycle. On the contrary, antiviral peptides (AVPs) are known for acting on a wide range of viruses, with a diversified mechanism of action targeting virus and/or host cell. In the present study, we evaluated the antiviral potential of the peptide Hylin-a1 secreted by the frog Hypsiobas albopunctatus against members of the Herpesviridae family. METHODS AND RESULTS: The inhibitory capacity of the peptide was evaluated in vitro by plaque assays in order to understand the possible mechanism of action. The results were also confirmed by real-time PCR and Western blot evaluating the expression of viral genes. Hylin-a1 acts to block the herpetic infection interfering at the early stages of both herpes simplex virus type 1 (HSV-1) and type 2 infection. Its mechanism is mainly directed on the membrane, probably by damaging the viral envelope. The same effect was also observed against HSV-1 strains resistant to acyclovir. CONCLUSIONS: The data presented in this study, such as the increased activity of the peptide when combined to acyclovir, a weak hemolytic profile, an anti-inflammatory effect, and a tolerable half-life in serum, indicates Hylin-a1 as a novel antiherpetic molecule with promising potential in the clinical setting.

Cupferron impairs the growth and virulence of Escherichia coli clinical isolates.

AIMS: Multidrug resistance is a worrying problem worldwide. The lack of readily available drugs to counter nosocomial infections requires the need for new interventional strategies. Drug repurposing represents a valid alternative to using commercial molecules as antimicrobial agents in a short time and with low costs. Contextually, the present study focused on the antibacterial potential of the ammonium salt N-nitroso-N-phenylhydroxylamine (Cupferron), evaluating the ability to inhibit microbial growth and influence the main virulence factors. METHODS AND RESULTS: Cupferron cytotoxicity was checked via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and hemolysis assays. The antimicrobial activity was assessed through the Kirby-Bauer disk diffusion test, broth microdilution method, and time-killing kinetics. Furthermore, the impact on different stages of the biofilm life cycle, catalase, swimming, and swarming motility was estimated via MTT and crystal violet (CV) assay, H2O2 sensitivity, and motility tests, respectively. Cupferron exhibited <15% cytotoxicity at 200 µg/mL concentration. The 90% bacterial growth inhibitory concentrations (MIC90) values recorded after 24 hours of exposure were 200 and 100 µg/mL for multidrug-resistant (MDR) and sensitive strains, respectively, exerting a bacteriostatic action. Cupferron-treated bacteria showed increased susceptibility to biofilm production, oxidative stress, and impaired bacterial motility in a dose-dependent manner. CONCLUSIONS: In the new antimicrobial compounds active research scenario, the results indicated that Cupferron could be an interesting candidate for tackling Escherichia coli infections.

Axillary artery aneurysms in pediatric patients: A narrative review.

OBJECTIVES: Axillary artery aneurysms in children are rare and multifactorial. The presenting clinical picture can range from an incidental discovery to threatening symptoms, including loss of extremity function. With the present study we aim to give a comprehensive review of the existing literature focusing on the etiology and management of this rare but threatening pathology. METHOD: A comprehensive review was made in a multi-staged manner. All identified studies have been categorized based on the type of lesions (true or false aneurysm) and their etiologies. RESULTS: The treatments differ from the extension of the lesions and from the etiology. CONCLUSIONS: Open surgery repair with great saphenous vein is still the best long-term approach, but even endovascular, embolization, or conservative management can be considered.

Color stability of resin-based composites: Staining procedures with liquids-A narrative review.

OBJECTIVE: The objective of this study was to review the experimental staining procedures performed in in-vitro studies for evaluating color stability of resin-based composites used for direct restorations. OVERVIEW: A review was performed with the purpose to identify in vitro procedures carried out to establish staining and color stability of resin-based composites used for direct restorations. A literature search was performed on four online databases (PubMed, Scopus, Embase and Web of Science) for articles published from January 1st 2001 till March 20th 2021, using a combination of free words and Medical Subject Headings (MESH) terms: "Composite Resins" AND "Color Stability" OR "Staining." Two reviewers screened titles and/or abstracts of 1728 unique studies. In total, 208 studies were selected for full-text reading, from which 178 were included in the review. The assessed variables were specimen dimensions, shape, and surface finishing; time before immersion; staining media type, dwell time, temperature and renewal interval; type of composite; color and translucency assessment parameters and measuring system. One hundred and seventy-eight articles analyzed color stability with staining liquids. Coffee was the most used staining medium (n = 102), followed by tea (n = 61), and red wine (n = 55). A disc-shaped specimen was used in most studies (n = 170) with a 2 mm thickness (n = 116). Spectrophotometers were the most used color assessment devices (n = 154), followed by colorimeters (n = 17). Color differences were quantified with ΔE (n = 154), ΔE00 (n = 23). Acceptability and or perceptibility thresholds were also taken into consideration (n = 126). CONCLUSIONS: The large variety of staining procedure suggests the need for standardization. CLINICAL SIGNIFICANCE: Aesthetic failure due to discoloration is a relevant clinical problem. Evaluating benefits and drawbacks of resin based composites artificial staining procedures will improve to predict materials clinical performances.

[The new territorial configuration of L'Aquila (Central Italy) after the 2009 earthquake and places and behaviours changes of everyday life]. / La riconfigurazione territoriale dell'Aquila dopo il sisma del 2009 e il cambiamento dei luoghi e dei comportamenti della quotidianità.

Since 2010, the Cartolab Laboratory research team (Department of Human Studies, University of L'Aquila) has been investigating the social geography in the post-earthquake period through the analysis of the territorial changes and new sociospatial configurations occurred in the everyday life of the L'Aquila inhabitants. Accordingly, this paper aims to describe the principal results of researches concentrating on the use of leisure time and leisure places in the post-disaster period in L'Aquila. The paper uses an action-research/participating- participatory (RAPP) methodology. The paper presents the monitored changes occurred in leisure time and places, and compares them with the conditions before the earthquake. Primary data have been retrieved by surveys and interviews. Results indicate that acceleration of fragmentation and dispersion of inhabitants are the main characteristics of the new sociospatial configuration in the post-disaster period in L'Aquila.

Limosilactobacillus reuteri DSM 17938 relieves inflammation, endoplasmic reticulum stress, and autophagy in hippocampus of western diet-fed rats by modulation of systemic inflammation.

The consumption of western diets, high in fats and sugars, is a crucial contributor to brain molecular alterations, cognitive dysfunction and neurodegenerative diseases. Therefore, a mandatory challenge is the individuation of strategies capable of preventing diet-induced impairment of brain physiology. A promising strategy might consist in the administration of probiotics that are known to influence brain function via the gut-brain axis. In this study, we explored whether Limosilactobacillus reuteri DSM 17938 (L. reuteri)-based approach can counteract diet-induced neuroinflammation, endoplasmic reticulum stress (ERS), and autophagy in hippocampus, an area involved in learning and memory, in rat fed a high fat and fructose diet. The western diet induced a microbiota reshaping, but L. reuteri neither modulated this change, nor the plasma levels of short-chain fatty acids. Interestingly, pro-inflammatory signaling pathway activation (increased NFkB phosphorylation, raised amounts of toll-like receptor-4, tumor necrosis factor-alpha, interleukin-6, GFAP, and Haptoglobin), as well as activation of ERS (increased PERK and eif2α phosphorylation, higher C/EBP-homologous protein amounts) and autophagy (increased beclin, P62-sequestosome-1, and LC3 II) was revealed in hippocampus of western diet fed rats. All these hippocampal alterations were prevented by L. reuteri administration, showing for the first time a neuroprotective role of this specific probiotic strain, mainly attributable to its ability to regulate western diet-induced metabolic endotoxemia and systemic inflammation, as decreased levels of lipopolysaccharide, plasma cytokines, and adipokines were also found. Therapeutic strategies based on the use of L. reuteri DSM17938 could be beneficial in reversing metabolic syndrome-mediated brain dysfunction and cognitive decline.

Color Stability of Polymer-Based Composite CAD/CAM Blocks: A Systematic Review.

BACKGROUND: This systematic review aims to evaluate the color stability of resin composite CAD/CAM blocks (CCB) when submitted to staining solutions. METHODS: A systematic search was performed on different databases (Embase, Medline, Scopus, Web of Science). Search terms were: 'polymer infiltrated', 'polymer-based', 'resin nanoceramic', 'resin ceramic', 'hybrid composite', 'hybrid ceramic', 'composite ceramic', 'resin infiltrated', 'CAD-CAM', 'CAD/CAM', 'color stability', 'staining', 'staining susceptibility', 'color change', 'color difference'. INCLUSION CRITERIA: in vitro articles published in the English language until 18 September 2022 without initial time restriction evaluating the color stability of CCB when submitted to staining solutions. EXCLUSION CRITERIA: studies investigating color change induced by smoke or whitening treatments; studies not including a clinical evaluation of the results using the thresholds for color perceptibility and acceptability. Risk of bias assessment using the QUIN tool. FINDINGS: Out of the 378 initially retrieved articles, 19 were included in this review. They investigated 17 different CCBs and different artificial staining by liquid protocols, including coffee, red wine, tea, and cola. CCBs exceeded clinical acceptability thresholds for color shift in 18 out of 19 studies, with a significantly higher color stability than conventional hybrid resin-based composites (RBCs), and a significantly lower color stability than ceramic materials. The identified differences in CCBs in color stability can be attributed to the material's composition, but also to the heterogeneity of staining procedures. Interpretation and clinical implication: Clinicians should be aware that, although to a lower degree when compared to RBCs used in direct or indirect procedures, CCBs undergo color changes to a higher degree in comparison to ceramic materials.

Melittin-Related Peptides Interfere with Sandfly Fever Naples Virus Infection by Interacting with Heparan Sulphate.

Emerging viruses pose an important global public health challenge, and early action is needed to control their spread. The Bunyaviridae family contains a great number of arboviruses which are potentially pathogenic for humans. For example, phleboviruses affect a large range of hosts, including humans and animals. Some infections usually have an asymptomatic course, but others lead to severe complications, such as Toscana virus, which is able to cause meningitis and encephalitis. Unfortunately, to date, no vaccines or antiviral treatments have been found. In the present study, we evaluated the effect of melittin-related peptides, namely the frog-derived RV-23 and AR-23, on sandfly fever Naples virus infection in vitro. Both peptides exhibited a strong antiviral activity by targeting the viral particles and blocking the virus-cell interaction. Their action was directed to an early phase of SFNV infection, in particular at viral adsorption on host cells, by interfering with the binding of common glycosaminoglycan receptors. Given the better antimicrobial behavior of AR-23 and RV-23 compared to melittin in terms of selectivity, our studies expand our understanding of the potential of these peptides as antimicrobials and stimulate further investigations in the direction of novel antiviral strategies against phlebovirus infection.

Duplication at 19q13.32q13.33 Segregating with Neuropsychiatric Phenotype in a Three-Generation Family: Towards the Definition of a Critical Region.

Chromosomal submicroscopic imbalances represent well-known causes of neurodevelopmental disorders. In some cases, these can cause specific autosomal dominant syndromes, with high-to-complete penetrance and de novo occurrence of the variant. In other cases, they result in non-syndromic neurodevelopmental disorders, often acting as moderate-penetrance risk factors, possibly inherited from unaffected parents. We describe a three-generation family with non-syndromic neuropsychiatric features segregating with a novel 19q13.32q13.33 microduplication. The propositus was a 28-month-old male ascertained for psychomotor delay, with no dysmorphic features or malformations. His mother had Attention-Deficit/Hyperactivity Disorder and a learning disability. The maternal uncle had an intellectual disability. Chromosomal microarray analysis identified a 969 kb 19q13.32q13.33 microduplication in the proband. The variant segregated in the mother, the uncle, and the maternal grandmother of the proband, who also presented neuropsychiatric disorders. Fragile-X Syndrome testing was negative. Exome Sequencing did not identify Pathogenic/Likely Pathogenic variants. Imbalances involving 19q13.32 and 19q13.33 are associated with neurodevelopmental delay. A review of the reported microduplications allowed to propose BICRA (MIM *605690) and KPTN (MIM *615620) as candidates for the neurodevelopmental delay susceptibility in 19q13.32q13.33 copy number gains. The peculiarities of this case are the small extension of the duplication, the three-generation segregation, and the full penetrance of the phenotype.

Lavandula austroapennina: Assessment of the Antiviral Activity of Lipophilic Extracts from Its Organs.

In a framework aimed at the recovery and enhancement of medicinal plants endemic to the territory of the Cilento and Vallo di Diano National Park, Lavandula austroapennina N.G. Passal., Tundis and Upson has aroused interest. An insight into the chemical composition of the corolla, calyx, leaf, stem, and root organs was carried out following ultrasound-assisted maceration in n-hexane. The obtained lipophilic extracts were explored using ultra-high-performance chromatography coupled to high-resolution mass spectrometry (UHPLC-ESI-QqTOF-MS/MS). The extracts from the different organs varied in their relative content of fatty acids, ursanes, and oleanane-type triterpenes. In particular, the oleanolic acid content appeared to increase in the order of corolla < leaf < stem. An MTT assay was performed to verify the possible cytotoxicity of the organ extracts of L. austroapennina at a concentration ranging from 12.5 to 400 µg/mL on the Vero CCL-81 cell line. Antiviral activity against herpes simplex virus type 1 (HSV-1), alpha human coronavirus 229E (HCoV-229E), and poliovirus type 1 (PV-1) was evaluated via a plaque reduction assay in the same cellular model. All the extracts did not show cytotoxic effects after 2 and 24 h exposure times, and the antiviral efficacy was particularly important for the stem extract, capable of completely inhibiting the tested viruses at low doses. The antiviral activity in a non-enveloped virus PV-1 allowed the assertion that the extracts from the organs of L. austroapennina, and especially the stem extract, interfered directly with the viral envelope. This study underlines how much knowledge of a territory's medicinal plant heritage is a harbinger of promising discoveries in the health field.

Oreoch-1: A Peptide from Oreochromis niloticus as a Potential Tool against Staphylococci.

Staphylococci, including Staphylococcus aureus and Staphylococcus epidermidis, are important human pathogens associated with potentially life-threatening infections. Their great biofilm-producing ability and the development of resistance mechanisms often account for therapeutic failure. Hence, the scientific community has devoted intensive efforts to the development of antimicrobial compounds active against both planktonic and sessile bacterial populations. Contextually, antimicrobial peptides (AMPs) are natural peptides produced by the innate immunity of every organism, representing a potential new therapeutic solution against human microbial pathogens. Our work focused on the in vitro activity of Oreoch-1, an AMP from the gills of Nile tilapia (Oreochromis niloticus), against standard and clinical S. aureus and S. epidermidis strains. Firstly, the cytotoxicity profile of Oreoch-1 was determined in human colon carcinoma cells. Secondly, its antibacterial spectrum was explored against staphylococcal strains to set up the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC). Our results highlighted an antibacterial activity in the range 6.25-25 µM, with a general bacteriostatic effect. Therefore, the biofilm-inhibitory property was assessed against S. aureus ATCC 25923 and S. epidermidis ATCC 35984, indicating a significant reduction in S. aureus biomass at sub-MIC concentrations. Overall, our study indicates Oreoch-1 as a promising new therapeutic weapon against staphylococcal infections.

Prenatal Exome Sequencing: Background, Current Practice and Future Perspectives-A Systematic Review.

The introduction of Next Generation Sequencing (NGS) technologies has exerted a significant impact on prenatal diagnosis. Prenatal Exome Sequencing (pES) is performed with increasing frequency in fetuses with structural anomalies and negative chromosomal analysis. The actual diagnostic value varies extensively, and the role of incidental/secondary or inconclusive findings and negative results has not been fully ascertained. We performed a systematic literature review to evaluate the diagnostic yield, as well as inconclusive and negative-result rates of pES. Papers were divided in two groups. The former includes fetuses presenting structural anomalies, regardless the involved organ; the latter focuses on specific class anomalies. Available findings on non-informative or negative results were gathered as well. In the first group, the weighted average diagnostic yield resulted 19%, and inconclusive finding rate 12%. In the second group, the percentages were extremely variable due to differences in sample sizes and inclusion criteria, which constitute major determinants of pES efficiency. Diagnostic pES availability and its application have a pivotal role in prenatal diagnosis, though more homogeneity in access criteria and a consensus on clinical management of controversial information management is envisageable to reach widespread use in the near future.

The ontogeny of fidgety movements from 4 to 20weeks post-term age in healthy full-term infants.

BACKGROUND: Fidgety movements (FMs) are an early accurate marker for normal development. AIM: The study assessed the ontogeny of normal FMs from 4 to 20weeks post-term age (PTA). STUDY DESIGN: Longitudinal prospective study of healthy full-term infants video recorded every second week from birth to 20weeks PTA. SUBJECTS: 21 full-term newborns were enrolled. OUTCOME MEASURES: Temporal organization, amplitude, character, predominance in proximal and/or distal parts of the body and the presence of FMs in fingers and wrists were independently scored by three observers. RESULTS: From 4 to 10weeks PTA, FMs were sporadic, becoming intermittent in 1-2weeks; they occurred in the proximal parts, with larger and jerkier movements in the following period. From 11 to 16weeks PTA FMs became smaller in amplitude and slower in speed, they were present in all body parts and were more continual than before. Rotational movements in wrists and ankles and finger movements with open hands appeared. From 17 to 20weeks PTA, FMs became more discontinuous and disappeared at 18-20weeks PTA. CONCLUSIONS: Developmental course of FMs was seen between 4 and 20weeks PTA with changes in temporal organization, amplitude, speed and body parts involved. The best time for scoring FMs is between 12 and 16weeks PTA.