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Background: Few studies investigated the immune response to SARS-CoV-2 vaccine in patients with multiple sclerosis (pwMS) treated with natalizumab (NTZ) and found a short-term efficient humoral response; however, there are no studies assessing the levels of SARS-CoV-2 IgG antibodies in pwMS treated with NTZ over time. Methods: Humoral immune response to BNT162b2 mRNA COVID-19 vaccine was assessed in a group of 26 pwMS on NTZ up to 6months after a full COVID-19 vaccination cycle and compared it with 43 age- and sex-matched group of HC. Serum samples were collected before the first dose (T0), and 4 weeks (T1) and 6months (T2) after the first dose of BNT162b2 mRNA COVID-19 vaccine. The LIAISON® SARS-CoV-2 TrimericS-IgG assay (DiaSorin-S.p.A.) was employed for the detection of IgG antibodies to SARS-CoV-2 spike protein (cutoff for positive IgG antibodies: 33.8 BAU/mL). Results: At T1 and T2, both groups showed an efficient humoral response to BNT162b2 mRNA COVID-19 vaccine. A significant reduction of IgG antibodies to SARS-CoV-2 spike protein was detected at T2 both in pwMS and in HC, but SARS-CoV-2 IgG antibodies were still above the cutoff limit in all participants. Conclusions: pwMS on NTZ develop and maintain a long-term humoral response after a full COVID-19 vaccination cycle comparable to their healthy peers, and these findings are relevant for clinicians called to counsel about COVID-19 mRNA vaccine timing and booster doses in pwMS treated with NTZ.

Real-world clinical data suggest an attenuated short-term humoral response to SARS-CoV-2 vaccines in patients with multiple sclerosis (pwMS) receiving high efficacy (HE) disease modifying therapies (DMTs) such as Ocrelizumab (OCR) and Fingolimod (FNG). Long-term humoral response in pwMS treated with these HE-DMTs has been poorly investigated. The aim of our study was to explore: i) the humoral response up to six months after a full cycle of the BNT162b2 mRNA Covid-19 vaccine in pwMS treated with OCR and FNG and to compare it to age- and sex-matched healthy controls (HCs); ii) the relationship between humoral response and clinical and immunological characteristics of the studied population.Serum samples were collected from HCs and pwMS treated with OCR or FNG at the following time points: before BNT162b2 mRNA Covid-19 vaccine (T0), and 4 (T1), 8 (T2), 16 (T3) and 24 (T4) weeks after the first dose. Sera were stored at -20 °C and tested for the quantitative detection of IgG antibodies to SARS-CoV-2 trimeric spike protein (Anti-TSP IgG) expressed in binding antibody units (BAU). At T1 neutralizing antibodies (NAbs) titres were assessed. The relationship between Anti-TSP IgG at each time-point and clinical and laboratoristic analyses were analysed by the Spearman correlation coefficient.47 HCs and 50 pwMS (28 on OCR and 22 on FNG) were included in the study. All HCs mounted a positive humoral response at T1 and preserved it up to six months. At T1 only 57.1% pwMS on OCR (p 0.001 compared with HCs) and 40.9% on FNG (p 0.001) had a positive humoral response at T1, with only 39.3% and 27.3% maintaining a positive response at sixth months (T4), respectively. A strong positive correlation was observed between Nabs titres and Anti-TSP IgG at T1 (rho 0.87, p 0.0001) with NAbs titres significantly higher in HCs compared with pwMS on OCR and FNG (p0.0001). We also found a strong positive correlation between time-window since last OCR infusion and anti-TSP IgG titres at all time-points (T1 rho=0.58, p = 0.001; T2 rho=0.59, p = 0.001; T3 rho=0.53, p = 0.004; T4 rho=0.47, p = 0.01). In the FNG group we observed a significant correlation between the humoral response measured from T1 to T4 and: i) treatment duration (T1: rho -0.65, p = 0.001; T2: rho -0.8 p0.001; T3: rho -0.72, p=0.001; T4: rho -0.67, p0.001), ii) disease duration (T1: rho -0.5, p = 0.017; T2: rho -0.6, p = 0.003; T3: rho -0.58, p = 0.005; T4: rho -0.57, p = 0.006), and iii) baseline total lymphocyte count (T1: rho 0.37, p = 0.08; T2: rho 0.45, p = 0.03; T3: rho 0.43, p = 0.04; T4: rho 0.45, p = 0.03).Our long-term data show a weakened and short-lasting humoral response to SARS-CoV-2 mRNA vaccine in pwMS treated with OCR and FNG when compared with HCs. MS neurologists should take into account the time elapsed since the last infusion for pwMS on OCR, and the lymphocyte count as well as the disease and treatment duration for those on FNG when called to counsel such pwMS regarding the vaccination with the SARS-CoV-2 mRNA vaccine.

Background The assessment of the safety and the humoral response to a third booster dose of the BNT162b2 mRNA COVID-19 vaccine is relevant in patients with Multiple Sclerosis (pwMS) treated with Ocrelizumab (OCR) or Fingolimod (FNG). Methods Serum samples were collected from Healthy controls (HCs) and pwMS treated with OCR or FNG at the following time-points: before the first of two vaccine doses (T0); 8 (T1), 16 (T2), 24 (T3) weeks after the first dose; within 8 weeks before (T0b) and after (T1b) the booster dose. IgG antibodies to SARS-CoV-2 trimeric spike protein (Anti-TSP IgG) were quantified and expressed as binding antibody units (BAU)/mL. Results 40 HCs, 28 pwMS on OCR and 19 on FNG were included. At T0b 12 (42.9%) pwMS on OCR and 6 (31.6%) on FNG were still positive while, at T1b 16 (57.14%) pwMS on OCR and 16 (84.2%) on FNG, passed the threshold of positivity. The increase of Anti-TSP IgG levels at T1b was higher for: (i) HCs with respect to OCR (p p = 0.032) groups; (ii) pwMS on FNG compared with pwMS on OCR (p Conclusions The third booster dose of BNT162b2 mRNA vaccine to OCR- and FNG-treated pwMS revives the humoral response, independently of any clinical variable, and manifests a good safety and tolerability profile.

To investigate clinical outcomes, radiation exposure and procedural costs associated with percutaneous varicocoele embolization using coils and sclerosing agents (SAs) in a cohort of young-adult men.Data from consecutive men treated with percutaneous varicocoele embolization using coils and SA between 2017 and 2021 were analyzed. The allocation was based on a change of policy occurred in June 2020 with the substitution of coils with SA (before and after study). Semen analysis values were based on 2010 WHO reference criteria. Anatomic variants of gonadal veins were categorized according to Jargiello et al. Intraoperative radiation dose and procedural costs were collected for each patient. Descriptive statistics and linear regression models were used to describe the association between clinical parameters with procedural costs and radiation exposure.One hundred sixteen men were included, of whom 76 (65.5%) received coils, and 40 (34.5%) received SA. Baseline characteristics of the two study groups did not differ. A type 3 Jargiello anatomic variation of left gonadal vein was found in 45.7% of cases. Radiation dose was lower in the SA group as compared to the coils one (13.2 [7-43] vs. 19.8 [12-57] Gy/cmSA and coils for varicocoele embolization are equally safe and effective. The use of SA was associated with lower radiation exposure and procedural costs than coils. These results should be considered in terms of public health cost and patient's safety.

Introduction Obstruction of the lacrimal drainage represents a common ophthalmologic issue. The blockage may interest any level of the lacrimal drainage pathway, and it is important to find the site of obstruction to plan the most appropriate treatment. In this study, findings from magnetic resonance (MR) dacryocystography were compared with findings from endoscopic and surgical procedures to evaluate the accuracy of MR dacryocystography in localizing the site of nasolacrimal duct obstruction. Methods We enrolled twenty-one patients with clinical suspicion of nasolacrimal duct obstruction who underwent dacryoendoscopy and surgery. MR dacryocystography was performed with a heavily T2-weighted fast spin echo sequence in the coronal planes. Before the MRI was performed, a sterile 0.9% NaCl solution was administered into both conjunctival sacs. For each examination, two independent readers (with 8 and 10 years of experience in head and neck imaging) evaluated both heavily 3D space T2-weighted and STIR sequences. Results Stenosis/obstruction of nasolacrimal duct or lacrimal sac was diagnosed in all 21 patients who underwent MRI dacryocystography. In particular, the site of the obstruction was classified as lacrimal sac in 12 (57%) patients, nasolacrimal duct in 6 (29%) patients, and canaliculi in 3 (14%) patients by both readers. By comparison with the evidence resulting from the endoscopy, there were differences between MRI dacryocystography and dacryoendoscopy in the evaluation of the obstruction’s site in three patients, with an overall accuracy of 85.7%. Conclusion MR dacryocystography allows a non-invasive evaluation of the lacrimal drainage pathway, valid for the planning of the most appropriate treatment.

Objectives: Several concerns regard the immunogenicity of SARS-CoV-2 vaccines in people with multiple sclerosis (pwMS), since the majority of them is treated with immunomodulating/immunosuppressive disease modifying therapies. Here we report the first data on the humoral response to mRNA SARS-CoV-2 vaccine in a case series of 4 pwMS treated with ocrelizumab (OCR) as compared to a group of healthy subjects (HS). Methods: We collected serum samples at 0, 14, 21 days after the first dose and 7 days after the second dose of BNT162b2-mRNA-Covid-19 vaccine from 55 health-care workers and 4 relapsing pwMS on OCR, with no history of Covid-19 infection. Sera were tested using the LIAISON®SARS-CoV-2 TrimericS-IgG assay (DiaSorin-S.p.A.) for the detection of IgG antibodies to SARS-CoV-2 spike protein. The anti-spike IgGtiters were expressed in Binding Antibody Units (BAU), an international standard unit. Results: At baseline all subjects were negative for anti-spike IgG. Seven days after the second dose of vaccine all HS mounted a significant humoral response (geometric mean 2010.4 BAU/mL C.I. 95% 1512.7-2672) while the 4 pwMS showed a lower response (range

Healthcare workers are at an increased risk of contracting Mycobacterium tuberculosis infection. Tuberculin skin test (TST) and interferon gamma release assay (IGRA) represent the available tests most used for the diagnosis of latent tuberculosis infection (LTBI). Different borderline zones have been proposed for defining conversions and reversions to improve the interpretation of the IGRA test results as part of serial testing. From 2012 to 2017, 5468 health students of an Italian University Hospital were screened for tuberculosis infection through the execution of the TST and, in case of positivity, of the QuantiFERON-TB&reg, Gold In-Tube assay (QFT&ndash, GIT). The QFT&ndash, GIT is considered &ldquo, borderline&rdquo, with values from 0.35 to 0.99 IU/mL. Among the students who performed the QFT&ndash, GIT assay, 27 subjects presented a range of values defined as borderline. The QFT&ndash, GIT was repeated after 90 days on 19 subjects with borderline values and showed a negativization of the values in 14 students and a positive conversion in three cases, while for two students, a borderline value was also found for the second test, with a 74% regression of the borderline cases. The introduction of QuantiFERON borderline values is a useful assessment tool to bring out LTBI case candidates for chemoprophylaxis.

The objective of this work was to provide an update information on HPV age/genotype distribution by retrospectively analyzing a cohort of women living in the metropolitan area of Naples.From January 2011 to December 2017, cervical scrape specimens from 1265 women, with abnormal cytological indication, were tested for HPV DNA. The presence and the viral genotypes were assessed by the Linear Array HPV genotyping test for the detection of 37 anogenital HPV-DNA genotypes.The overall prevalence of HPV infections was of 44.5% (95% CI 41.77-47.24). Among HR-HPV types, HPV-16 was the most common identified genotype, followed by HPV-31, -66, -59 and -51. As concern LR-HPV, HPV-53 resulted the most prevalent. Stratifying the study population by age, the total HPV infections showed a peak in younger women aged23 years (58.5%), with a significative decrease by age (23-29 years, 54%; ≥ 30 years, 38.2%) (p 0.001).We provided an HPV epidemiological analysis, highlighting the need to implement vaccination programmes and preventative screening strategies.

Aims: The objective of this work was to study the distribution of hepatitis C virus (HCV) genotypes and subtypes from 2010 to 2015 in 1,221 anti-HCV/HCV-RNA-positive specimens from patients living in the metropolitan area of Naples, since HCV genotypes and subtypes remain cornerstones in the management of chronic HCV infection even in the directly acting antivirals era. Methods: The study was carried out on 1,221 anti-HCV/HCV-RNA-positive plasma samples collected between April 2010 and December 2015. Results: Of the 1,221 patients enrolled, 633 (51.9%) were males and 588 (48.1%) were females, with a mean age of 60 ± 13 (SD) years. The most frequent HCV genotype observed was genotype 1 (68.1%; 1b in 55.3% and 1a in 9.5%); HCV genotype 2 was found in 289 samples (23.67%), genotype 3 in 6.47%, genotype 4 in only 19 samples, and only 2 samples were classified as genotype 5. The mean age of the patients with genotype 1a or 3 was lower (51 ± 12 and 49 ± 12 years, respectively) than those with genotype 1b (62 ± 11, p < 0.0001 for both) or 2 (62 ± 14, p < 0.0001 for both). Conclusions: The data from the present study suggest that HCV genotype 1b remains the most prevalent in this area, followed by genotype 2, 1a, and 3a.

Background: Photodynamic therapy (PDT) involves the use of a photosensitizing agent, which may require metabolic synthesis (i.e. a prodrug), followed by light activation. Numerous studies have advanced PDT as a means for treating bacteria, fungi and viruses. In this study, the photoinactivation of Herpes simplex virus type 1 (HSV-1) in human keratinocytes using 5-aminolaevulinic acid (5-ALA) was investigated. Methods: HaCat cells were infected with HSV-1 and treated with 5-ALA to verify its antiviral effect during the stages of adsorption and penetration to host cells. Immunoblot analysis was used to estimate the effect of ALA–PDT on the production of viral proteins glycoprotein D (gD), infected cell proteins (ICP) 27 and virion protein (VP) 16. We also investigated whether the effect of ALA–PDT was associated with a cellular apoptotic mechanism through DNA fragmentation and the study of p53, PARP and caspase-3 protein expression. Results: While the treatment of ALA–PDT after the viral adsorption period reduced HSV-1 replication by about 70%, it did not act on the virus in the first phase of infection. The viral proteins' expressions were reduced by ALA–PDT treatments. There was no evidence of ALA–PDT-induced apoptosis. Conclusion: Our data suggest that the target of photoinactivation appears to be viral replication and not a cellular response.

Background: The incidence of typhoid fever and shigellosis parallels that of malaria, so many individuals who are on antimalarial drugs can be found in areas where these diseases are widespread. We investigated the effect of quinine sulfate on the growth and invasion of Salmonella typhimurium and Shigella flexneri M90T to determine whether people on antimalarials can have secondary gain from some protection against typhoid fever and shigellosis. Methods: The effect of 50 and 100 μM quinine sulfate on the invasive ability of Salmonella typhimurium and Shigella flexneri M90T into human colon adenocarcinoma-2 (Caco-2) cells was studied during the infection period. The invasive efficiency was expressed as the number of viable internalized bacteria by counting the colony-forming units. Results: The invasive ability of Salmonella typhimurium and Shigella flexneri M90T was significantly inhibited by 50 and 100 μM quinine sulfate in a dose-dependent manner (for Salmonella typhimurium) when the drug was added to Caco-2 cell monolayers during the infection period. Conclusions: Since so many people who are on antimalarial drugs visit and inhabit areas that are endemic to typhoid fever and Shigella infection, a study on the influence of these drugs on the disease is long overdue. Our data indicate that quinine sulfate interferes with the invasion and internalization of Salmonella typhimurium and Shigella flexneri M90T into host cells. Further studies on additional strains/serotypes with other newer antimalarials at various concentrations are needed to verify this effect of quinine sulfate and to draw conclusions on its significance in vivo.

This study investigated the effect of various structural components of Gram-positive (lipotheichoic acid and protein A) and Gram-negative (porins and lipopolysaccharide) bacteria on human dermal fibroblasts. Fibroblasts are important effector cells which have a potential role in augmenting the inflammatory response in various diseases. In this study we present a profile of TNF-alpha, IL-6 and IL-8, the expression of intercellular adhesion molecules (ICAM-1) and the activation of transcriptional nuclear factor NF-kB and AP-1 in human dermal fibroblasts stimulated by bacterial surface components. Compared to the controls, increased ICAM-1, IL-6 and IL-8 gene expression after stimulation of LPS and porins at 2 and 4 h was more evident than that obtained following stimulation of LTA and PA. Gene expression was also associated with the production of cytokine proteins in culture supernatants. TNF-alpha gene expression remained undetectable. Moreover, LPS and porin treatments determined IkBalpha phosphorylation and degradation in human dermal fibroblasts and the subsequent activation of nuclear factors NF-kB and AP-1. These data suggest the importance of such stimuli in the first step of the inflammatory process, as well as the important role played by fibroblasts in skin inflammatory disease.

Objective Human papillomavirus (HPV) has been recognized as the major etiologic agent of cervical squamous cell carcinoma. However, it has been demonstrated that HPV infection is usually a self-limited process and does not lead to significant epithelial lesions or cancer. Recent data indicate that persistent high-risk HPV (HR-HPV) infections have a significantly increased risk of developing incident high-grade cervical intraepithelial neoplasia and cervical cancer. Our aim, therefore, was to assess whether there exist HPV genotypes whose persistence can be considered powerful surrogates of a progressive disease. We retrospectively selected all patients with a negative cytological diagnosis or with atypical squamous cells of undetermined significance, with a positive test for HR-HPV, different from HPV types 16 and 18, and assessed the significance of the risk of progression based on the persistence of the specific HR-HPV. Materials and methods We retrospectively queried the database of our Colposcopy Clinic for all patients with a negative cytological diagnosis or with atypical squamous cells of undetermined significance and a positive test for HR-HPV, and we calculated the incidence of progression to lesions greater than or equal to low-grade squamous intraepithelial lesions after 6 months, according to the HPV type. Results A progression rate of 48.27% was found in patients tested positive for HPV-31 (Group 1), 38.46% in patients tested positive for HPV-45 (Group 2), and 5.73% in patients tested positive for HPV types other than HPV-16, HPV-18, HPV-31, and HPV-45 (Group 3). Conclusion Our data demonstrate that the persistence of HPV-31 and HPV-45 is strongly associated with the occurrence of squamous intraepithelial lesion.

Some species of Candida are opportunistic pathogens that can cause disease in a host immunocompromised by underlying local or systemic pathological processes. C. albicans is the species most often associated with oral lesions, but other species of Candida, including C. glabrata, C. tropicalis and C. parapsilosis, have also been isolated in the saliva of subjects with and without candidiasis. In the present study we evaluated the host defence mechanisms induced by Candida albicans and other Candida species in monocytes and oral epithelial cells in order to establish the existence of a species-specific cellular response. Our results indicated that, during Candida species infection, the epithelial cells actively participate in the host defence by producing antimicrobial peptides and proinflammatory cytokines. Moreover, in infections caused by Candida tropicalis and Candida glabrata, the host defence may be strengthened by the release of perforin and granzyme by polymorphonuclear leukocytes recruited at the site of infection. Copyright © by BIOLIFE, s.a.s.

The chemical investigation of an Indonesian specimen of Theonella swinhoei afforded four aurantosides, one of which, aurantoside J (5), is a new compound. The structure of this metabolite, exhibiting the unprecedented N-α-glycosidic linkage between the pentose and the tetramate units, has been determined through detailed spectroscopic analysis. The four obtained aurantosides have been tested against five fungal strains (four Candida and one Fusarium) responsible of invasive infections in immuno-compromised patients. The non-cytotoxic aurantoside I (4) was the single compound to show an excellent potency against all the tested strains, thus providing valuable insights about the antifungal potential of this class of compounds and the structure-activity relationships.

BACKGROUND: As some of the many patients who receive antimalarials for the treatment of noninfective inflammatory diseases (lupus erythematosus, collagen vascular diseases, rheumatoid arthritis, and others) are also immunosuppressed because of their disease and/or treatments, and may have concomitant bacterial infections, we investigated the effect of these drugs on the growth and invasion of several bacteria that are commonly associated with skin and soft tissue infections to determine whether they could protect against such conditions and obviate the need for an additional antibiotic drug. METHODS: The effect of quinine sulfate (QS) at concentrations of 50 and 100 microm on the entry process of Enterobacter agglomerans, Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae into Caco-2 cells was studied during the infection period. The invasive efficiency was expressed as the number of viable internalized bacteria obtained by counting the colony-forming units (CFUs). RESULTS: The invasive ability of E. agglomerans and S. aureus was significantly inhibited by 50 and 100 microm QS in a dose-dependent manner when the drug was added to Caco-2 cell monolayers during the infection period; however, QS had no significant effect on the internalization of P. aeruginosa or K. pneumoniae. DISCUSSION AND CONCLUSIONS: Antimalarial drugs are currently widely used to treat patients with autoimmune dermatologic and rheumatologic diseases, and have also been recently proposed as additional therapy for patients with human immunodeficiency virus (HIV) infection. These patients, who are often immunocompromised, may receive a secondary advantage from these antimalarials, which may provide some protection against staphylococci (amongst the most important human pathogens causing many superficial and systemic infections) and E. agglomerans.

Oral candisosis is an heterogeneous group of diseases, caused by different species of Candida fungus. The incidence of drug-resistant species is increasing dramatically; furthermore, in recent years higher incidences of non-albicans and antimycotic-resistant species of Candida have been reported, thus increasing necessity of a non-antibiotic agent, which should be both highly effective and safe. It has been showed that the main polyphenolic component of green tea, epigallocatechin-gallate (EGCG), has antibacterial activity; recently, it has been reported its antifungal activity too. We tested the effectiveness of a 0.20% EGCG (TEAVIGO ®) gel, a non-pharmaceutical product suitable for oral in vivo use, on four species of Candida yeast (C.albicans, C.parapsilosis, C.tropicalis, C.glabrata), evaluating its antifungal activity and its capacity to inhibit biofilm formation. The EGCG gel showed a remarkable activity against C. parapsilosis and C. tropicalis. This preliminary study confirms EGCG effectiveness on fungi; for this reason, a product with such a low concentration of EGCG could be used with no side-effect for every-day oral hygiene. Anyway, mechanisms of antifungal activity of EGCG are not comprehended and need further studies to better understand the reasons of some Candida species' resistance. Copyright © by BIOLIFE, s.a.s.