The influence of acute lifestyle changes on NAFLD evolution in a multicentre cohort: a matter of body composition.

BACKGROUND: Unhealthy lifestyles represent a key element fueling Non-alcoholic fatty liver disease (NAFLD) onset and worsening. We aimed to evaluate the effects of forced acute lifestyle changes on NAFLD evolution. METHODS: 187 NAFLD patients were followed two years pre- and two years during the lockdown social restrictions in three Italian medical centers. For each patient, biochemical, clinical, non-invasive liver fibrosis, nutritional, and body composition data were collected. RESULTS: An increase in fats and carbohydrate intake associated with impaired weekly physical activity during the lockdown was demonstrated as well as an increase in body mass index and waist-hip-ratio (p < 0.0001 for all). Total cholesterol, low-density lipoprotein, high-density lipoprotein, triglycerides, glucose, insulin, homeostatic model assessment for insulin resistance, and transaminases worsened during the lockdown (glucose: p = 0.0007; p < 0.0001 for the others). Moreover, NAFLD fibrosis score, liver stiffness, and controlled attenuation parameter were also impaired during the same period (p < 0.0001 for all). The bioelectrical impedance analysis (BIA) evidenced an increase of fat mass (FM), and a reduction of free fat mass (FFM) and body cell mass (BCM) (p < 0.0001 for all). The lockdown overall hepatocellular carcinoma (HCC) and Milan-out HCC occurrence revealed Hazard Ratio (HR): 2.398, 95% Confidence Interval (CI):1.16-5, p = 0.02, and HR:5.931, CI:2-17.6, p = 0.008 respectively. A liver disease stage and comorbidities independent association between both the assessed outcomes and body composition analysis in terms of mean values and variation (T1-T2 Δ) was demonstrated. CONCLUSIONS: The acute lifestyle changes impacted NAFLD evolution via body composition modifications negatively influencing the HCC occurrence.

Profiling the patient with inflammatory bowel disease in the relationship between physical activity and partner/social network status: A post hoc patient-tailored analysis of the "BE-FIT-IBD" study.

INTRODUCTION: Normal quality of life is an ultimate target in the therapeutic approach to inflammatory bowel diseases (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC) in the context of which regular physical activity (PA) is often a chimeric parameter that is not standardized in terms of quality/quantity. The study aimed to profile a sample of IBD patients about the relationship between PA-partner status and social network support. PATIENTS AND METHODS: A post hoc analysis of the "BE-FIT-IBD" study was set up by stratifying the data of PA with that of partner status and the support that the patient's social network (i.e., relatives, friends) provided in inciting the patient to practice regular PA. RESULTS: In the 219 patients included, there was a greater tendency for patients with stable partners to view the risk of reactivation/worsening of IBD as a barrier to conducting regular PA (p<0.0001). Single patients considered PA more as a protective factor (p=0.045). Patients without a PA-supporting social network retained IBD-related treatment as a PA barrier (p=0.016) and PA as a risk for IBD complications (p=0.01), with less confidence that PA could improve the course of IBD (p<0.001). Rectal syndrome was an IBD-related barrier more represented in patients with PA-deterring social network (p<0.0001). CONCLUSIONS: These factors are potential targets for recovering the IBD patient's adherence to regular PA.

Systemic Oxidative Balance Reflects the Liver Disease Progression Status for Primary Biliary Cholangitis (Pbc): The Narcissus Fountain.

Biological antioxidant potential (BAP) and Reactive Oxygen Metabolites (dROMs) are two tests complementarily assessing systemic oxidative statuses (SOSs) that are never applied in chronic liver disorders (CLDs). We enrolled 41 ursodeoxycholic acid (UDCA)-naïve Primary Biliary Cholangitis (PBC) patients [age: 58.61 ± 11.26 years; females (F): 39], 40 patients with metabolic-dysfunction-associated steatotic livers (age: 54.30 ± 11.21; F: 20), 52 patients with HBV (age: 52.40 ± 8.22; F: 34), 50 patients with (age: 56.44 ± 7.79, F: 29), and 10 controls (age: 52.50 ± 9.64; F: 7). Liver fibrosis and the steatosis severity were determined using transient elastography, and the SOS was balanced using d-ROMs and the BAP test. The gene expressions of superoxide dismutase (SOD1; SOD2) and glutathione peroxidase (GPx1) were evaluated using real-time PCR in advanced fibrosis (AF: F3F4) in patients with PBC. In contrast to other CLDs, in PBC the dROMs and BAP levels were, respectively, directly and inversely correlated with hepatic fibrosis (dROMs, R: 0.883; BAP, R: -0.882) and steatosis (dROMs, R: 0.954; BAP, R: -0931) severity (p < 0.0001 all). Patients with PBC also revealed a progressively increasing trend of d-ROMs (F0-F2 vs. F3: p = 0.0008; F3 vs. F4: p = 0.04) and reduction in BAP levels (F0-F2 vs. F3: p = 0.0007; F3 vs. F4 p = 0.04) according to the worsening of liver fibrosis. In AF-PBC, the SOD1, SOD2, and GPx1 expressions were significantly downregulated in patients presenting SOS imbalance (SOD1, p = 0.02; SOD2, p = 0.03; GPx1, p = 0.02). SOS disequilibrium represents a leitmotiv in patients with PBC, perfectly reflecting their liver disease progression status.

Environmental bisphenol A exposure triggers trained immunity-related pathways in monocytes.

Introduction: Trained Immunity represents a novel revolutionary concept of the immunological response involving innate immune cells. Bisphenol A is a well-known endocrine disrupter, widely disseminated worldwide and accumulated in the human body. Due to the increased interest regarding the effects of plastic-derived compounds on the immune system, our purpose was to explore whether BPA was able to induce trained immunity in human primary monocytes in vitro using low environmental concentrations. Materials and methods: We extracted BPA from the serum of 10 healthy individuals through a liquid-liquid extraction followed by a solid phase extraction and measured the concentration using an HPLC system coupled to a triple quadrupole mass spectrometer. In parallel, monocytes were isolated from whole blood and acutely stimulated or trained with BPA at three different concentrations (1 nM, 10 nM, 20 nM). Pro- and anti-inflammatory cytokines (IL-1ß, TNF-α, IL-6, and IL-10) production were assessed after 24 hours of acute stimulation and after Lipopolysaccharide (LPS) rechallenge. A comprehensive overview of the metabolic changes after BPA acute stimulation and trained immunity induction was assessed through extracellular lactate measurements, Seahorse XFb metabolic flux analysis and ROS production. Results: Monocytes primed with BPA showed increased pro- and anti-inflammatory cytokine responses upon restimulation, sustained by the modulation of the immunometabolic circuits. Moreover, we proved the non-toxic effect of BPA at each experimental concentration by performing an MTT assay. Additionally, correlation analysis were performed between pro- and anti-inflammatory cytokines production after LPS acute stimulation or BPA-mediated trained immunity and BPA serum concentrations showing a significant association between TNF-α and BPA circulating levels. Discussion: Overall, this study pointed out for the first time the immunological effects of an environmental chemical and plastic-derived compound in the induction of trained immunity in a healthy cohort.

Role of Non-Coding RNAs in Hepatocellular Carcinoma Progression: From Classic to Novel Clinicopathogenetic Implications.

Hepatocellular carcinoma (HCC) is a predominant malignancy with increasing incidences and mortalities worldwide. In Western countries, the progressive affirmation of Non-alcoholic Fatty Liver Disease (NAFLD) as the main chronic liver disorder in which HCC occurrence is appreciable even in non-cirrhotic stages, constitutes a real health emergency. In light of this, a further comprehension of molecular pathways supporting HCC onset and progression represents a current research challenge to achieve more tailored prognostic models and appropriate therapeutic approaches. RNA non-coding transcripts (ncRNAs) are involved in the regulation of several cancer-related processes, including HCC. When dysregulated, these molecules, conventionally classified as "small ncRNAs" (sncRNAs) and "long ncRNAs" (lncRNAs) have been reported to markedly influence HCC-related progression mechanisms. In this review, we describe the main dysregulated ncRNAs and the relative molecular pathways involved in HCC progression, analyzing their implications in certain etiologically related contexts, and their applicability in clinical practice as novel diagnostic, prognostic, and therapeutic tools. Finally, given the growing evidence supporting the immune system response, the oxidative stress-regulated mechanisms, and the gut microbiota composition as relevant emerging elements mutually influencing liver-cancerogenesis processes, we investigate the relationship of ncRNAs with this triad, shedding light on novel pathogenetic frontiers of HCC progression.

Hericium erinaceus, in combination with natural flavonoid/alkaloid and B3/B8 vitamins, can improve inflammatory burden in Inflammatory bowel diseases tissue: an ex vivo study.

Hericium erinaceus, berberine, and quercetin are effective in experimental colitis. It is unknown whether they can ameliorate inflammatory bowel diseases in humans. This ex vivo study aimed to evaluate the anti-inflammatory potential of a nutraceutical compound of HBQ-Complex® (H. erinaceus, berberine, and quercetin), biotin, and niacin in inflammatory bowel disease patients. Tissue specimens were obtained either from Normal-Appearing Mucosa (NAM) or from Inflamed Mucosa (IM) in 20 patients with inflammatory bowel disease. mRNA and protein expression of COX-2, IL-10, and TNF-α were determined in NAM and IM biopsy samples (T0). IM samples were then incubated in HBQ-Complex® (with the addition of niacin and biotin), and COX-2, IL-10, and TNF-α tissue levels were evaluated at 120 minutes (T1) and 180 minutes (T2). Incubation with this compound resulted in a progressive decrease in gene and protein COX-2 and TNF-α expression at T1/T2 in the IM. IL-10 showed an opposite trend, with a progressive increase of mRNA and protein expression over the same time window. HBQ-Complex® (with the addition of niacin and biotin) decreased the expression of proinflammatory cytokines at the mRNA and protein levels in IBD tissue. On the contrary, mRNA and protein expression of the anti-inflammatory cytokine IL-10 showed a progressive increase.

Prevalence and Distribution of High- and Low- Risk HPV Genotypes in Women Living in the Metropolitan Area of Naples: A Recent Update.

INTRODUCTION: Human papillomavirus (HPV) can infect both male and female genitals, skin, and mucous membranes, causing benign or malignant lesions. HPV is a common sexually transmitted infection and it is the main cause of cervical cancer. The present retrospective study updated the previously published data on HPV genotypes distribution among women living in Naples. MATERIALS AND METHODS: In this study, 502 cervical scrape specimens were collected from women with abnormal cytological indication and analyzed for HPV DNA identification by Linear Array HPV genotyping test. RESULTS: The HPV infection rate was 24.1%. HPV-16 (14.6%) was the most representative HR-HPV genotypes, followed by HPV-31 (13.8%), -18 (9.2%), and HPV-51 (8.5%). In addition, HPV-42 (16.4%) was the most prevalent genotype among LR-HPV  genotypes (low-risk human papillomavirus). It was also found that women at the age group of 23-29 years (42.5%) were at the highest risk of HPV infection. It was found that the HPV-16 frequency decreased, but HPV-31 and -18 frequency increased a little. The LR HPV-53 frequency decreased, leaving the first place for abundance to the LR HPV-42. HPV-6 frequency did not change. LR HPV -11 was no more present. Merging <23 and 23-29 age classes into one class followed the same result. CONCLUSION: HPV prevalence declined in comparison to the previous data. A frequency variation was recorded for several genotypes in this study.  Data can be useful to implement the preventative strategies and to promote HPV vaccination.

Sponge Whirl-Pak Sampling Method and Droplet Digital RT-PCR Assay for Monitoring of SARS-CoV-2 on Surfaces in Public and Working Environments.

The SARS-CoV-2 can spread directly via saliva, respiratory aerosols and droplets, and indirectly by contact through contaminated objects and/or surfaces and by air. In the context of COVID-19 fomites can be an important vehicle of virus transmission and contribute to infection risk in public environments. The aim of the study was to analyze through surface sampling (sponge method) the presence of SARS-CoV-2 in public and working environments, in order to evaluate the risk for virus transmission. Seventy-seven environmental samples were taken using sterile sponges in 17 animal farms, 4 public transport buses, 1 supermarket and 1 hotel receptive structure. Furthermore, 246 and 93 swab samples were taken in the farms from animals and from workers, respectively. SARS-CoV-2 detection was conducted by real-time RT-PCR and by digital droplet RT-PCR (dd RT-PCR) using RdRp, gene E and gene N as targets. None of the human and animal swab samples were positive for SARS-CoV-2, while detection was achieved in 20 of the 77 sponge samples (26%) using dd RT-PCR. Traces of the RdRp gene, gene E and gene N were found in 17/77 samples (22%, average concentration 31.2 g.c./cm2, range 5.6 to 132 g.c./cm2), 8/77 samples (10%, average concentration 15.1 g.c./cm2, range 6 to 36 g.c./cm2), and in 1/77 (1%, concentration 7.2 g.c./cm2). Higher detection rates were associated with sampling in animal farms and on public transport buses (32% and 30%) compared to the supermarket (21%) and the hotel (no detection). The result of the study suggests that the risk of contamination of surfaces with SARS-CoV-2 increases in environments in which sanitation strategies are not suitable and/or in highly frequented locations, such as public transportation. Considering the analytical methods, the dd RT-PCR was the only approach achieving detection of SARS-CoV-2 traces in environmental samples. Thus, dd RT-PCR emerges as a reliable tool for sensitive SARS-CoV-2 detection.

Assessment of Saliva Specimens' Reliability for COVID-19 Surveillance.

The aim of the present study is to assess saliva as a reliable specimen for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection by real-time reverse transcription-PCR (RT-PCR), especially in community mass screening programs. The performance analysis considered 1,221 total samples [nasopharyngeal (NP) swabs and corresponding saliva], tested by means of a reference diagnostic real-time RT-PCR assay. Conflicting results were further investigated with a second, more sensitive, reference assay. Analysis of agreement showed a good concordance (95.82%), with a k coefficient value of.74 (p < 0.001); moreover, a follow-up analysis revealed the presence of viral gene targets in saliva samples at the time point the corresponding NP swabs turned negative. Data obtained prove the reliability of this alternative biofluid for SARS-CoV-2 detection in real-time RT-PCR. Considering the role of saliva in the coronavirus disease 2019 (COVID-19) transmission and pathogenesis, and the advantages in the use of salivary diagnostics, the present validation supports the use of saliva as an optimal choice in large-scale population screening and monitoring of the SARS-CoV-2 virus.

An observational study of a cohort of citizens receiving the AZD1222 vaccine against SARS-CoV-2.

In this retrospective study, a cohort of 67 subjects vaccinated with AZD1222 was retrospectively observed. Consistently with published findings, no serious adverse event was reported, and all adverse events reported (fever, muscle ache and/or pain in the site of injection) had resolved by day 8. Of note, some citizens were prescribed low-dose aspirin and even heparin for thrombosis prevention. We also found variations in laboratory test results (full blood count and chemistry) on day 1 compared with day 8. Physicians should be aware that no prevention therapy for thrombosis is currently recommended, given the very low incidence of this side effect. Additional studies are warranted to interpret our findings.

No detection of SARS-CoV-2 in animals exposed to infected keepers: results of a COVID-19 surveillance program.

SARS-CoV-2, the causative agent of the COVID-19 pandemic, has rarely been associated with transmission from humans to animals (reverse zoonotic transmission). In this retrospective study, the authors reviewed data obtained from 236 animals, including buffaloes, goats/sheep, horses, carrier pigeons, rabbits, hens, snakes, pigs and cows that were screened for SARS-CoV-2 infection because they had been in contact with their SARS-CoV-2-positive breeder for at least 2 weeks. None of the tested animals were found to be positive. The authors' findings suggest that the risk of reverse zoonotic transmission among bred animals and SARS-CoV-2-positive breeders is very low or nonexistent. Additional studies are warranted.

Seroprevalence of SARS-CoV-2 Assessed by Four Chemiluminescence Immunoassays and One Immunocromatography Test for SARS-Cov-2.

The onset of the new SARS-CoV-2 coronavirus encouraged the development of new serologic tests that could be additional and complementary to real-time RT-PCR-based assays. In such a context, the study of performances of available tests is urgently needed, as their use has just been initiated for seroprevalence assessment. The aim of this study was to compare four chemiluminescence immunoassays and one immunochromatography test for SARS-Cov-2 antibodies for the evaluation of the degree of diffusion of SARS-CoV-2 infection in Salerno Province (Campania Region, Italy). A total of 3,185 specimens from citizens were tested for anti-SARS-CoV-2 antibodies as part of a screening program. Four automated immunoassays (Abbott and Liaison SARS-CoV-2 CLIA IgG and Roche and Siemens SARS-CoV-2 CLIA IgM/IgG/IgA assays) and one lateral flow immunoassay (LFIA Technogenetics IgG-IgM COVID-19) were used. Seroprevalence in the entire cohort was 2.41, 2.10, 1.82, and 1.85% according to the Liaison IgG, Abbott IgG, Siemens, and Roche total Ig tests, respectively. When we explored the agreement among the rapid tests and the serologic assays, we reported good agreement for Abbott, Siemens, and Roche (Cohen's Kappa coefficient 0.69, 0.67, and 0.67, respectively), whereas we found moderate agreement for Liaison (Cohen's kappa coefficient 0.58). Our study showed that Abbott and Liaison SARS-CoV-2 CLIA IgG, Roche and Siemens SARS-CoV-2 CLIA IgM/IgG/IgA assays, and LFIA Technogenetics IgG-IgM COVID-19 have good agreement in seroprevalence assessment. In addition, our findings indicate that the prevalence of IgG and total Ig antibodies against SARS-CoV-2 at the time of the study was as low as around 3%, likely explaining the amplitude of the current second wave.

Seroprevalence of SARS-CoV-2-specific antibodies in the town of Ariano Irpino (Avellino, Campania, Italy): a population-based study.

The Italian municipality of Ariano Irpino (Avellino, Campania, Italy) was locked down by the regional authorities from March until April 2020 after several citizens tested positive for SARS coronavirus 2 (SARS-CoV-2). A serological mass screening campaign targeting the Ariano Irpino population using the Roche Cobas Elecsys anti-SARS-CoV-2 assay was organized by the Zoo-Prophylactic Institute of Southern Italy (Portici, Italy) and conducted in cooperation with the Local Health Unit (Azienda Sanitaria Locale - ASL - Avellino, Avellino, Italy), the Department of Public Health of University Federico II (Naples, Italy) and Department of Health Services of Azienda Ospedaliera dei Colli-Cotugno and Monaldi Hospital (Naples, Italy) in May 2020. A total of 13,218 asymptomatic individuals were reviewed in this analysis. A total of 738 citizens tested positive for anti-SARS-CoV-2 antibodies (398 females, 340 males). The overall prevalence in the sample was 5.6% (95% CI: 5.2-6.0). Among seropositive citizens, 101 cases tested positive on RT-PCR (0.76% of the overall population). Among citizens aged 14-18, 18-65 and >65 years, the seroprevalence was equal to 6.1 (95% CI: 4.1-8.7), 5.6 (95% CI: 5.1-6.1) and 4% (95% CI: 3.3-4.8), respectively. In the pediatric cohort (<14 years old), seroprevalence was 13% (95% CI: 10.2-16.2). A serological-based screening strategy could be a cost-effective public health intervention to tackle the COVID-19 pandemic.

Durability of Humoral Immune Responses to SARS-CoV-2 in Citizens of Ariano Irpino (Campania, Italy): A Longitudinal Observational Study With an 11.5-Month Follow-Up.

As of November 17, 2021, SARS-CoV-2 (Severe Acute Respiratory Syndrome CoronaVirus 2), the causative agent of COVID-19 (COronaVIrus Disease 19), has infected ~250 million people worldwide, causing around five million deaths. Titers of anti-SARS-CoV-2 neutralizing antibodies were relatively stable for at least 9 months in a population-based study conducted in Wuhan, China, both in symptomatic and in asymptomatic individuals. In the mass screening campaign conducted in the town of Ariano Irpino (Avellino, Italy) in May, 2020, 5.7% (95% CI: 5.3-6-1) of the 13,444 asymptomatic citizens screened were positive for anti-nucleocapsid antibodies against SARS-CoV-2. Among these, 422 citizens were re-tested for anti SARS-CoV-2 antibodies in January, 2021 and/or in April, 2021 and enrolled in this longitudinal observational study. Median (interquartile range) age of the study cohort was 46 years (29-59), with 47 (11.1%) participants of minor age, while 217 (51.4%) participants were females. There was no evidence of re-infection in any of the subjects included. Presence of anti-nuclear antibodies antibodies (Elecysis, Roche) was reported in 95.7 and 93.7% of evaluable participants in January and April, 2021. Multiple logistic regression analysis used to explore associations between age, sex and seroprevalence showed that adults vs. minors had significantly lower odds of having anti-S1 antibodies (Biorad) both in January, 2021 and in April, 2021. Our findings showed that antibodies remained detectable at least 11.5 months after infection in >90% of never symptomatic cases. Further investigation is required to establish duration of immunity against SARS-CoV-2.

Modulation of the cytokine profile in Caco-2 cells by faecal lactobacilli and bifidobacteria from individuals with distinct dietary habits.

Enterocytes are actively involved in the defense against pathogens and they limit penetration of commensal microbes into tissues. They also have an important role in gut immunity as enterocytes confer mucosal dendritic cell specialisation. On the other hand, the microbiota is directly involved in the development and modulation of the intestinal immune system. Particularly, lactobacilli and bifidobacteria play a primary role in shaping the immune response. We further explored this issue by evaluating whether functional differences in Caco-2 cells could characterise faecal populations of lactobacilli (155 samples) and bifidobacteria (110 samples) isolated from three dietary cohorts (omnivores, ovo-lacto-vegetarians and vegans) recruited at four Italian centres (Turin, Parma, Bologna and Bari). According to our findings, tested bacteria were unable to modulate expression of IL-8, IL-10, TGF-ß or thymic stromal lymphopoietin (TSLP) cytokines in unstimulated Caco-2 cells. Conversely, in phorbol 12-myristate 13-acetate and ionomycin (PMA/Io) stimulated Caco-2 cells, lactobacilli from the omnivorous group and all bifidobacteria significantly down-regulated IL-8. Notably, both genera also lowered the TSLP expression in stimulated Caco-2 cells, regardless of the diet regimen. By further examining these data on the basis of geographical origin, we found that lactobacilli from the vegetarian group recruited in Bari, significantly up-regulated this cytokine. In conclusion, we highlighted a peculiar immune-modulatory activity profile for lactobacilli on enterocytes undergoing a stimulatory signal, which was associated with a specific dietary habit. Furthermore, the geographical area had a significant impact on the inflammatory potential of members of the Lactobacillus genus.