IL-10-producing B cells, also known as regulatory B cells (Bregs), play a key role in controlling autoimmunity. In this study, we report that chimeric mice specifically lacking IL-10-producing B ...cells (IL-10(-/-)B cell) developed an exacerbated arthritis compared with chimeric wild-type (WT) B cell mice. A significant decrease in the absolute numbers of Foxp3 regulatory T cells (Tregs), in their expression level of Foxp3, and a marked increase in inflammatory Th1 and Th17 cells were detected in IL-10(-/-) B cell mice compared with WT B cell mice. Reconstitution of arthritic B cell deficient (μMT) mice with different B cell subsets revealed that the ability to modulate Treg frequencies in vivo is exclusively restricted to transitional 2 marginal zone precursor Bregs. Moreover, transfer of WT transitional 2 marginal zone precursor Bregs to arthritic IL-10(-/-) mice increased Foxp3(+) Tregs and reduced Th1 and Th17 cell frequencies to levels measured in arthritic WT mice and inhibited inflammation. In vitro, IL-10(+/+) B cells established longer contact times with arthritogenic CD4(+)CD25(-) T cells compared with IL-10(-/-) B cells in response to Ag stimulation, and using the same culture conditions, we observed upregulation of Foxp3 on CD4(+) T cells. Thus, IL-10-producing B cells restrain inflammation by promoting differentiation of immunoregulatory over proinflammatory T cells.
•Electrophoretic protein pattern and haematology are studied in horse after EHV-1/EHV-4 vaccine•Vaccine was associated with protein fractions and leukocyte population modulation•Vaccine do not alter ...the overall health status of horses
Protection against infectious diseases can be obtained with vaccines generating immunogenic response through a combination of humoral and cellular immunity. In this study haematological and serum protein electrophoretic profiles of horses vaccinated against herpesvirus 1 (EHV-1) and 4 (EHV-4) were evaluated. Blood samples were collected from 16 horses before (T0), after 24h, 48h, 72h, 1st week, 2nd week and 3rd week (T1I, T2I, T3I, T7I, T14I and T21I) from the first EHV vaccine-dose administration as well as before (TPREII), and after 24h, 48h, 72h, 1st week, 2nd week, 3rd week and 4th week (T1II, T2II, T3II, T7II, T14II, T21II and T28II) from the EHV vaccine-booster. Total leukocyte values increased at T1I, T1II, T3II and T28II compared to T0 (P < .01). Higher lymphocytes and lower neutrophils values were found after first vaccine-dose and vaccine-booster administration compared to the T0 (P < .01). Monocytes showed higher values at T14II than T0 (P < .01). Higher serum values of total proteins, α1-, α-2-, β1-, β2- and γ-globulins were found in horses after first vaccine-dose and vaccine-booster administration (P < .01). Gathered results suggest that horses vaccinated against EHV1 and EHV-4 exhibited a dynamic change of WBC, lymphocytes, neutrophils and monocytes. Moreover, the analysis of serum electrophoresis pattern suggested that EHV vaccination induced the development of inflammation and antibody response in vaccinated horses as highlighted by the increase of α-, β- and γ-globulin fractions. These changes probably reflect the systemic immunological adaptation of animals to EHV vaccine.
The evaluation of conventional and biofunctional sperm parameters is of fundamental importance for assessing male reproductive function. Among these, sperm motility is one of the most important ...parameters. Indeed, asthenozoospermia is a frequent cause of male infertility. Sperm motility depends on mitochondrial function and the measurement of mitochondrial membrane potential (MMP) better accounts for the function of this intracellular organelle. On the basis of these premises, the present study assessed whether the MMP predicts sperm motility at 4 h in patients with low or normal MMP. To accomplish this, 31 men were enrolled. Sperm analysis was conducted according to the WHO 2010 criteria. Particular attention was paid to the evaluation of MMP after liquefaction (T0) using JC-1 staining by flow cytometry. Sperm total and progressive motility were measured at T0 and after 4 h from seminal fluid collection (T4). Patients were divided into two groups based on their sperm mitochondrial function at T0. Group A (n = 18) was composed of men with normal mitochondrial function since they had a percentage of spermatozoa with low MMP (L-MMP) below the normal reference value of our laboratory (<36.5%). In contrast, group B (n = 13) was made up of men with impaired sperm mitochondrial function (L-MMP > 36.5%). Group A had a slight but not significant reduction in total and progressive sperm motility at T4 compared with the values recorded at T0. In contrast, patients in group B showed a significant decline in both total and progressive sperm motility at T4 compared with T0 (p < 0.05). The results of this study showed that worse mitochondrial function, assessed by staining with JC1, is associated with a significant decline in sperm motility over time. These findings may be of clinical relevance in programs of assisted reproduction techniques. Based on our knowledge, there is no other evidence in the literature that has shown this relationship in healthy men with low MMP of idiopathic etiology, but normozoospermics according to the WHO 2010 criteria.
To evaluate the predominant human adenovirus (HAdV) species and types associated with pediatric respiratory infections, nasopharyngeal swabs were collected from otherwise healthy children attending ...an emergency room in Milan, Italy, due to a respiratory tract infection from January 1 to February 28 of two subsequent years, 2013 and 2014. The HAdVs were detected using a respiratory virus panel fast assay (xTAG RVP FAST v2) and with a HAdV-specific real-time polymerase chain reaction; their nucleotides were sequenced, and they were tested for positive selection. Among 307 nasopharyngeal samples, 61 (19.9%) tested positive for HAdV. HAdV was the only virus detected in 31/61 (50.8%) cases, whereas it was found in association with one other virus in 25 (41.0%) cases and with two or more viruses in 5 (8.2%) cases. Human Enterovirus/human rhinovirus and respiratory syncytial virus were the most common co-infecting viral agents and were found in 12 (19.7%) and 7 (11.5%) samples, respectively. Overall, the HAdV strain sequences analyzed were highly conserved. In comparison to HAdV-negative children, those infected with HAdV had a reduced frequency of lower respiratory tract involvement (36.1% vs 55.2%; p = 0.007), wheezing (0.0% vs 12.5%; p = 0.004), and hospitalization (27.9% vs 56.1%; p<0.001). Antibiotic therapy and white blood cell counts were more frequently prescribed (91.9% vs 57.1%; p = 0.04) and higher (17,244 ± 7,737 vs 9,565 ± 3,211 cells/μL; p = 0.04), respectively, in children infected by HAdV-C than among those infected by HAdV-B. On the contrary, those infected by HAdV-B had more frequently lower respiratory tract involvement (57.1% vs 29.7%) but difference did not reach statistical significant (p = 0.21). Children with high viral load were absent from child care attendance for a longer period of time (14.5 ± 7.5 vs 5.5 ± 3.2 days; p = 0.002) and had higher C reactive protein levels (41.3 ± 78.5 vs 5.4 ± 9.6 μg/dL; p = 0.03). This study has shown that HAdV infections are diagnosed more commonly than usually thought and that HAdVs are stable infectious agents that do not frequently cause severe diseases. A trend toward more complex disease in cases due to HAdV species C and in those with higher viral load was demonstrated. However, further studies are needed to clarify factors contributing to disease severity to understand how to develop adequate preventive and therapeutic measures.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
For the estimation of the soil organic carbon stocks, bulk density (BD) is a fundamental parameter but measured data are usually not available especially when dealing with legacy soil data. It is ...possible to estimate BD by applying pedotransfer function (PTF). We applied different estimation methods with the aim to define a suitable PTF for BD of arable land for the Mediterranean Basin, which has peculiar climate features that may influence the soil carbon sequestration. To improve the existing BD estimation methods, we used a set of public climatic and topographic data along with the soil texture and organic carbon data. The present work consisted of the following steps: i) development of three PTFs models separately for top (0–0.4 m) and subsoil (0.4–1.2 m), ii) a 10-fold cross-validation, iii) model transferability using an external dataset derived from published data.
The development of the new PTFs was based on the training dataset consisting of World Soil Information Service (WoSIS) soil profile data, climatic data from WorldClim at 1 km spatial resolution and Shuttle Radar Topography Mission (SRTM) digital elevation model at 30 m spatial resolution.
The three PTFs models were developed using: Multiple Linear Regression stepwise (MLR-S), Multiple Linear Regression backward stepwise (MLR-BS), and Artificial Neural Network (ANN).
The predictions of the newly developed PTFs were compared with the BD calculated using the PTF proposed by Manrique and Jones (MJ) and the modelled BD derived from the global SoilGrids dataset.
For the topsoil training dataset (N = 129), MLR-S, MLR-BS and ANN had a R2 0.35, 0.58 and 0.86, respectively. For the model transferability, the three PTFs applied to the external topsoil dataset (N = 59), achieved R2 values of 0.06, 0.03 and 0.41. For the subsoil training dataset (N = 180), MLR-S, MLR-BS and ANN the R2 values were 0.36, 0.46 and 0.83, respectively. When applied to the external subsoil dataset (N = 29), the R2 values were 0.05, 0.06 and 0.41. The cross-validation for both top and subsoil dataset, resulted in an intermediate performance compared to calibration and validation with the external dataset. The new ANN PTF outperformed MLR-S, MLR-BS, MJ and SoilGrids approaches for estimating BD. Further improvements may be achieved by additionally considering the time of sampling, agricultural soil management and cultivation practices in predictive models.
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•Three PTFs were developed to calculate bulk density of arable top- and subsoil.•WoSIS, WorldClim, and topographic data of the Mediterranean Basin were used.•Model transferability of the three new PTFs was validated with external dataset.•Topsoil ANN-PTF had R2 of 0.89 in training and 0.45 in model transferability.•ANN-PTF outperformed the commonly employed PTF by Manrique and Jones.
Nonalcoholic fatty liver disease (NAFLD) represents the hepatic manifestation of metabolic syndrome and may evolve into hepatocellular carcinoma (HCC). Only scanty clinical information is available ...on HCC in NAFLD. The aim of this multicenter observational prospective study was to assess the clinical features of patients with NAFLD‐related HCC (NAFLD‐HCC) and to compare them to those of hepatitis C virus (HCV)‐related HCC. A total of 756 patients with either NAFLD (145) or HCV‐related chronic liver disease (611) were enrolled in secondary care Italian centers. Survival was modeled according to clinical parameters, lead‐time bias, and propensity analysis. Compared to HCV, HCC in NAFLD patients had a larger volume, showed more often an infiltrative pattern, and was detected outside specific surveillance. Cirrhosis was present in only about 50% of NAFLD‐HCC patients, in contrast to the near totality of HCV‐HCC. Regardless of tumor stage, survival was significantly shorter (P = 0.017) in patients with NAFLD‐HCC, 25.5 months (95% confidence interval 21.9‐29.1), than in those with HCV‐HCC, 33.7 months (95% confidence interval 31.9‐35.4). To eliminate possible confounders, a propensity score analysis was performed, which showed no more significant difference between the two groups. Additionally, analysis of patients within Milan criteria submitted to curative treatments did not show any difference in survival between NAFLD‐HCC and HCV‐HCC (respectively, 38.6 versus 41.0 months, P = nonsignificant) Conclusions: NAFLD‐HCC is more often detected at a later tumor stage and could arise also in the absence of cirrhosis, but after patient matching, it has a similar survival rate compared to HCV infection; a future challenge will be to identify patients with NAFLD who require more stringent surveillance in order to offer the most timely and effective treatment. (Hepatology 2016;63:827–838)
Digital health (DH) is nowadays fundamental for physicians. Despite the improvement of information and communications technology (ICT), Italian medical doctors' (MDs) education system seems ...inadequate in this area. Moreover, due to the COVID-19 pandemic, societies are waking up to their limitations. The aim of this paper is to analyze the Italian status quo in DH.
The Italian Young Medical Doctors Association (Segretariato Italiano Giovani Medici - SIGM) proposed a web-based survey to assess DH awareness and previous knowledge among young doctors. Investigated areas were: big data, -omics technology and predictive models, artificial intelligence (AI), internet of things, telemedicine, social media, blockchain and clinical-data storage.
A total of 362 participants answered to the survey. Only 13% had experience in big data during clinical or research activities, 13% in -omics technology and predictive models, 13% in AI, 6% had experience in internet of things, 22% experienced at least one telemedicine tool and 23% of the participants declared that during their clinical activities data collection was paper-driven.
Three categories of MDs, high-tech, low-tech and no-tech, can be identified from the survey-based investigation. Our survey's results indicate an urgent need for integration of pre- and post-graduation training in digital health to provide adequate medical education.
microRNAs (miRNAs) are emerging as relevant molecules in cancer development and progression. MiRNAs add a post-transcriptional level of control to the regulation of gene expression. The deregulation ...of miRNA expression results in changing the molecular circuitry in which miRNAs are involved, leading to alterations of cell fate determination. In this review, we describe the miRNAs that are emerging as innovative molecular biomarkers from liquid biopsies, not only for diagnosis, but also for post-surgery management in cancer. We focus our attention on renal cell carcinoma, in particular highlighting the crucial role of circulating miRNAs in clear cell renal cell carcinoma (ccRCC) management. In addition, the functional deregulation of miRNA expression in ccRCC is also discussed, to underline the contribution of miRNAs to ccRCC development and progression, which may be relevant for the identification and design of innovative clinical strategies against this tumor.
Avian metapneumovirus (aMPV) economically affects the global poultry industry causing respiratory and reproductive disorders. Considering the paucity of data on aMPV occurrence in European ...free-ranging avifauna, a molecular survey was conducted on wild birds of 23 species belonging to the orders Anseriformes, Charadriiformes or Passeriformes, captured alive and sampled in Northeast Italy as part of the national avian influenza virus (AIV) surveillance activities. A total of 492 oropharyngeal swabs, collected from 2007-2010, all AIV-negative, were screened from aMPV by subtype-specific qRT-PCR. An aMPV-C strain, named aMPV/C/IT/Wigeon/758/07, was found in a wintering young Eurasian wigeon (Mareca penelope) sampled in November 2007. The matrix, fusion, and attachment glycoprotein genes of the detected strain were subsequently amplified by specific independent RT-PCRs, then sequenced, and compared in a phylogenetic framework with known aMPV homologous sequences retrieved from GenBank. Close genetic relationships were found between the aMPV/C/IT/Wigeon/758/07 strain and subtype C Eurasian lineage strains isolated in the late 1990s in French domestic ducks, suggesting epidemiological links. Eurasian wigeons are medium/long-range migrant dabbling ducks that move along the Black Sea/Mediterranean flyway; our finding might, therefore, be related to migratory bridges between countries. To our knowledge, this is the first molecular evidence of the occurrence of aMPV subtype C in Italy and backdates the aMPV-C circulation to 2007. Moreover, the results suggest the susceptibility of Eurasian wigeons to aMPV. Broader investigations are needed to assess the role of wild ducks and the significance of the wildfowl/poultry interface in aMPV-C epidemiology.
RESEARCH HIGHLIGHTS
Wild birds live-captured in Italy were tested for aMPV detection and characterization.
aMPV-C Eurasian lineage was found for the first time in a wintering Eurasian wigeon.
Migratory birds could be involved in the aMPV epidemiology.
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