A laboratory test based on determination of cytokine profiles: a promising assay to identify exposition to contact allergens and predict the clinical outcome in occupational allergic contact dermatitis

BACKGROUND: Para-phenylenediamine (PPD) is the main allergen causing adverse reactions to hair dyes and a frequent cause of occupational-related skin sensitization among hairdressers and beauticians. The immunologic mechanism of the disease relies on the production of inflammatory cytokines by allergen-specific T cells, while regulatory T cells are thought to down-modulate the allergic response. This study was aimed at investigating the expression of effector or regulatory cytokines in exposed subjects in order to verify whether different cytokine profiles might predict distinct clinical outcomes. Peripheral blood mononuclear cells (PBMC) from 21 subjects occupationally exposed or not (10) to PPD were kept in short term cultures in the presence of optimized concentrations of NiSO4 × 6H2O or PPD. The production of IFN-γ and IL-10 elicited by antigens were analyzed by the ELISpot assay. RESULTS: The presence of IFN-γ responses toward PPD was significantly correlated with a positive patch test (P = 0.002) and allergic symptoms, while IL10 responses were invariably found in PPD-exposed but clinically asymptomatic subjects with negative patch testing. We found concordance between the different cytokine profiles and patch test results. No false-positive results were found for the different cytokine profiles induced by PPD, resulting in 100% specificity. The sensitivity of the test was 87.5% (95% CI 65.9-100.0) with an overall test accuracy of 93.3%. Although larger prospective-retrospective studies are necessary to validate the predictive potential of the test, the negative and positive predicted values for PPD in this study were NPV = 87.5% and PPV = 100%, respectively. CONCLUSIONS: These data indicate that distinct cytokine profiles are associated with different clinical manifestations. The test, which is based on a simple and rapid profiling of cytokine responses by T lymphocytes against allergens, has proven to be a promising laboratory tool, useful for both the identification of previous contact with allergens and the etiologic diagnosis of contact allergies as well as capable of predicting the clinical outcome (development of an allergic or tolerant response)

Anal cytological abnormalities and epidemiological correlates among men who have sex with men at risk for HIV-1 infection

BACKGROUND: The incidence of anal cancer, a Human Papillomavirus (HPV)-related neoplasia, has been increasing in recent decades, mainly in men who have sex with men (MSM). Cytological changes of the anal epithelium induced by HPV can be detected through an anal pap smear. This study aimed to evaluate the prevalence and epidemiological correlates of anal cytological abnormalities among relatively young MSM at risk for HIV-1 infection, to help clarify whether or not this population deserves further investigation to assess the presence of anal cancer precursor lesions. METHODS: MSM were recruited among attendees of a large STI clinic for a HIV-1 screening program. Anal samples, collected with a Dracon swab in PreservCyt, were used both for liquid-based cytology and HPV testing by the Linear Array HPV Genotyping Test. Data regarding socio-demographic characteristics and sexual behavior were collected in face-to-face interviews. RESULTS: A total of 346 MSM were recruited (median age 32 years). Overall, 72.5% of the individuals had an anal HPV infection, with 56.1% of them being infected by oncogenic HPV genotypes. Anal cytological abnormalities were found in 29.8% of the cases (16.7% ASC-US and 13.1% L-SIL). Presence of ASC-US+ was strongly associated with infection by any HPV type (OR=4.21, 95% CI: 1.97-9.23), and particularly by HPV 16 and/or 18 (OR=5.62, 95% CI: 2.33-13.81). A higher proportion of ASC-US+ was found in older MSM, in those with a higher number of lifetime partners and in those with a history of ano-genital warts. However, none of these variables or the others analyzed showed any significant association with abnormal cytological findings. CONCLUSIONS: The presence of anal cytological abnormalities in about one third of the recruited MSM and their strong association with HPV infection, in particular that caused by HPV 16 and/or 18, might provide a further complement to the data that now support the introduction of HPV vaccination among MSM to protect them from the development of HPV-associated diseases. Additional studies are needed to determine whether and how screening for anal cancer precursor lesions should be performed in younger MSM

Evaluation of Anti-Candida Activity of Vitis vinifera L. Seed Extracts Obtained from Wine and Table Cultivars

For the first time, grape seed extracts (GSEs), obtained from wine and table cultivars of Vitis vinifera L., cultured in experimental fields of Lazio and Puglia regions of Italy and grown in different agronomic conditions, have been tested on 43 Candida species strains.We demonstrated a significant correlation between the content of the flavan-3-ols in GSEs extracts, with a polymerization degree 654, and anti-Candida activity.Moreover, we demonstrated thatGSEs, obtained from plants cultured with reduced irrigation, showed a content of polymeric flavan-3-ols >250mg/gwith geometric mean MICvalues between 5.7 and 20.2 mg/L against Candida albicans reference strains. GSE, showing 573mg/g of polymeric flavan-3-ols, has been tested in an experimental murine model of vaginal candidiasis by using noninvasive in vivo imaging technique. The results pointed out a significant inhibition of Candida albicans load 5 days after challenge.These findings indicate that GSEs with high content of polymeric flavan-3-ols can be used in mucosal infection as vaginal candidiasis

Relative effectiveness of a 2nd booster dose of COVID-19 mRNA vaccine up to four months post administration in individuals aged 80 years or more in Italy. A retrospective matched cohort study

Several countries started a 2nd booster COVID-19 vaccination campaign targeting the elderly population, but evidence around its effectiveness is still scarce. This study aims to estimate the relative effectiveness of a 2nd booster dose of COVID-19 mRNA vaccine in the population aged >= 80 years in Italy, during predominant circulation of the Omicron BA.2 and BA.5 subvariants. We linked routine data from the national vaccination registry and the COVID-19 surveillance system. On each day between 11 April and 6 August 2022, we matched 1:1, according to several demographic and clinical characteristics, individuals who received the 2nd booster vaccine dose with individuals who received the 1st booster vaccine dose at least 120 days earlier. We used the Kaplan-Meier method to compare the risks of SARS-CoV-2 infection and severe COVID-19 (hospitalisation or death) between the two groups, calculating the relative vaccine effectiveness (RVE) as (1 - risk ratio)X100. Based on the analysis of 831,555 matched pairs, we found that a 2nd booster dose of mRNA vaccine, 14-118 days post administration, was moderately effective in preventing SARS-CoV-2 infection compared to a 1st booster dose administered at least 120 days earlier [14.3 %, 95 % confidence interval (CI): 2.2-20.2]. RVE decreased from 28.5 % (95 % CI: 24.7-32.1) in the time-interval 14-28 days to 7.6 % (95 % CI: -14.1 to 18.3) in the time-interval 56-118 days. However, RVE against severe COVID19 was higher (34.0 %, 95 % CI: 23.4-42.7), decreasing from 43.2 % (95 % CI: 30.6-54.9) to 27.2 % (95 % CI: 8.3-42.9) over the same time span. Although RVE against SARS-CoV-2 infection was much reduced 2-4 months after a 2nd booster dose, RVE against severe COVID-19 was about 30 %, even during prevalent circulation of the Omicron BA.5 subvariant. The cost-benefit of a 3rd booster dose for the elderly people who received the 2nd booster dose at least four months earlier should be carefully evaluated

Effectiveness of mRNA vaccines and waning of protection against SARS-CoV-2 infection and severe covid-19 during predominant circulation of the delta variant in Italy. Retrospective cohort study

Objectives: To estimate the effectiveness of mRNA vaccines against SARS-CoV-2 infection and severe covid-19 at different time after vaccination. Design: Retrospective cohort study. Setting: Italy, 27 December 2020 to 7 November 2021. Participants: 33 250 344 people aged ≥16 years who received a first dose of BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine and did not have a previous diagnosis of SARS-CoV-2 infection. Main outcome measures: SARS-CoV-2 infection and severe covid-19 (admission to hospital or death). Data were divided by weekly time intervals after vaccination. Incidence rate ratios at different time intervals were estimated by multilevel negative binomial models with robust variance estimator. Sex, age group, brand of vaccine, priority risk category, and regional weekly incidence in the general population were included as covariates. Geographic region was included as a random effect. Adjusted vaccine effectiveness was calculated as (1-IRR)×100, where IRR=incidence rate ratio, with the time interval 0-14 days after the first dose of vaccine as the reference. Results: During the epidemic phase when the delta variant was the predominant strain of the SARS-CoV-2 virus, vaccine effectiveness against SARS-CoV-2 infection significantly decreased (P<0.001) from 82% (95% confidence interval 80% to 84%) at 3-4 weeks after the second dose of vaccine to 33% (27% to 39%) at 27-30 weeks after the second dose. In the same time intervals, vaccine effectiveness against severe covid-19 also decreased (P<0.001), although to a lesser extent, from 96% (95% to 97%) to 80% (76% to 83%). High risk people (vaccine effectiveness -6%, -28% to 12%), those aged ≥80 years (11%, -15% to 31%), and those aged 60-79 years (2%, -11% to 14%) did not seem to be protected against infection at 27-30 weeks after the second dose of vaccine. Conclusions: The results support the vaccination campaigns targeting high risk people, those aged ≥60 years, and healthcare workers to receive a booster dose of vaccine six months after the primary vaccination cycle. The results also suggest that timing the booster dose earlier than six months after the primary vaccination cycle and extending the offer of the booster dose to the wider eligible population might be warranted

Evaluation of humoral and cellular response to four vaccines against COVID-19 in different age groups: A longitudinal study

To date there has been limited head-to-head evaluation of immune responses to different types of COVID-19 vaccines. A real-world population-based longitudinal study was designed with the aim to define the magnitude and duration of immunity induced by each of four different COVID-19 vaccines available in Italy at the time of this study. Overall, 2497 individuals were enrolled at time of their first vaccination (T0). Vaccine-specific antibody responses induced over time by Comirnaty, Spikevax, Vaxzevria, Janssen Ad26.COV2.S and heterologous vaccination were compared up to six months after immunization. On a subset of Comirnaty vaccinees, serology data were correlated with the ability to neutralize a reference SARS-CoV-2 B strain, as well as Delta AY.4 and Omicron BA.1. The frequency of SARS-CoV-2-specific CD4+ T cells, CD8+ T cells, and memory B cells induced by the four different vaccines was assessed six months after the immunization. We found that mRNA vaccines are stronger inducer of anti-Spike IgG and B-memory cell responses. Humoral immune responses are lower in frail elderly subjects. Neutralization of the Delta AY.4 and Omicron BA.1 variants is severely impaired, especially in older individuals. Most vaccinees display a vaccine-specific T-cell memory six months after the vaccination. By describing the immunological response during the first phase of COVID-19 vaccination campaign in different cohorts and considering several aspects of the immunological response, this study allowed to collect key information that could facilitate the implementation of effective prevention and control measures against SARS-CoV-2

Impatto della vaccinazione e della pregressa diagnosi sul rischio di infezione e di malattia severa associata a SARS-CoV-2. Un’analisi dei casi diagnosticati nel mese di ottobre 2022

In Italia, l’epidemia di infezioni da SARS-CoV-2 nel corso del 2022 è stata influenzata dalla predominanza della variante Omicron, caratterizzata da alta trasmissibilità, e dalla progressiva eliminazione di quasi tutte le misure non farmacologiche di prevenzione. La combinazione di questi due elementi ha determinato una notevole circolazione virale di SARS-CoV-2 con oltre 24,5 milioni di casi da inizio epidemia. Dato l’alto numero di persone che ha superato almeno una infezione da SARS-CoV-2 e l’alta copertura vaccinale nella popolazione è necessario stimare il ruolo protettivo dell’immunità associata sia al vaccino che all’infezione pregressa nel prevenire l’infezione e la malattia severa da COVID-19. Il presente rapporto fornisce una stima del rischio di infezione e di malattia grave, per il mese di ottobre 2022, sulla base della vaccinazione e della precedente infezione. La massima protezione contro la diagnosi di infezione da SARS-CoV-2 e la malattia severa si realizza attraverso una immunità ibrida (l’effetto combinato della vaccinazione e della pregressa infezione) mentre livelli di rischio più alto si riscontrano sempre tra le persone non vaccinate e senza una precedente diagnosi di infezione. A parità di fascia di età e di pregressa infezione, si osserva una tendenza alla riduzione del rischio di malattia severa associata alla vaccinazione, in particolare se recente

JN.1 variants circulating in Italy from October 2023 to April 2024: genetic diversity and immune recognition

Background: The continuous emergence of SARS-CoV-2 variants and subvariants poses significant public health challenges. The latest designated subvariant JN.1, with all its descendants, shows more than 30 mutations in the spike gene. JN.1 has raised concerns due to its genomic diversity and its potential to enhance transmissibility and immune evasion. This study aims to analyse the molecular characteristics of JN.1-related lineages (JN.1*) identified in Italy from October 2023 to April 2024 and to evaluate the neutralization activity against JN.1 of a subsample of sera from individuals vaccinated with XBB.1.5 mRNA. Methods: The genomic diversity of the spike gene of 794 JN.1* strain was evaluated and phylogenetic analysis was conducted to compare the distance to XBB.1.5. Moreover, serum neutralization assays were performed on a subsample of 19 healthcare workers (HCWs) vaccinated with the monovalent XBB.1.5 mRNA booster to assess neutralizing capacity against JN.1. Results: Sequence analysis displayed high spike variability between JN.1* and phylogenetic investigation confirmed a substantial differentiation between JN.1* and XBB.1.5 spike regions with 29 shared mutations, of which 17 were located within the RBD region. Pre-booster neutralization activity against JN.1 was observed in 42% of HCWs sera, increasing significantly post-booster, with all HCWs showing neutralization capacity three months after vaccination. A significant correlation was found between anti-trimeric Spike IgG levels and neutralizing titers against JN.1. Conclusions: The study highlights the variability of JN.1* in Italy. Results on a subsample of sera from HCWs vaccinated with XBB.1.5 mRNA booster vaccine suggested enhanced neutralization activity against JN.1

Social and genetic diversity in first farmers of central Europe

The Linearbandkeramik (LBK) Neolithic communities were the first to spread farming across large parts of Europe. We report genome-wide data for 250 individuals: 178 individuals from whole-cemetery surveys of the Alföld Linearbankeramik Culture eastern LBK site of Polgár-Ferenci-hát, the western LBK site of Nitra Horné Krškany and the western LBK settlement and massacre site of Asparn-Schletz, as well as 48 LBK individuals from 16 other sites and 24 earlier Körös and Starčevo individuals from 17 more sites. Here we show a systematically higher percentage of western hunter-gatherer ancestry in eastern than in western LBK sites, showing that these two distinct LBK groups had different genetic trajectories. We find evidence for patrilocality, with more structure across sites in the male than in the female lines and a higher rate of within-site relatives for males. At Asparn-Schletz we find almost no relatives, showing that the massacred individuals were from a large population, not a small community