Polyphenols: a route from bioavailability to bioactivity addressing potential health benefits to tackle human chronic diseases.

Chronic pathologies or non-communicable diseases (NCDs) include cardiovascular diseases, metabolic syndrome, neurological diseases, respiratory disorders and cancer. They are the leading global cause of human mortality and morbidity. Given their chronic nature, NCDs represent a growing social and economic burden, hence urging the need for ameliorating the existing preventive strategies, and for finding novel tackling therapies. NCDs are highly correlated with unhealthy lifestyle habits (such as high-fat and high-glucose diet, or sedentary life). In general, lifestyle approaches that might improve these habits, including dietary consumption of fresh vegetables, fruits and fibers, may contrast NCD symptoms and prolong life expectancy of affected people. Polyphenols (PPLs) are plant-derived molecules with demonstrated biological activities in humans, which include: radical scavenging and anti-oxidant activities, capability to modulate inflammation, as well as human enzymes, and even to bind nuclear receptors. For these reasons, PPLs are currently tested, both preclinically and clinically, as dietary adjuvants for the prevention and treatment of NCDs. In this review, we describe the human metabolism and bioactivity of PPLs. Also, we report what is currently known about PPLs interaction with gastro-intestinal enzymes and gut microbiota, which allows their biotransformation in many different metabolites with several biological functions. The systemic bioactivity of PPLs and the newly available PPL-delivery nanosystems are also described in detail. Finally, the up-to-date clinical studies assessing both safety and efficacy of dietary PPLs in individuals with different NCDs are hereby reported. Overall, the clinical results support the notion that PPLs from fruits, vegetables, but also from leaves or seeds extracts, are safe and show significant positive results in ameliorating symptoms and improving the whole quality of life of people with NCDs.

Role of the T2Dx magnetic resonance assay in patients with suspected bloodstream infection: a single-centre real-world experience.

BACKGROUND: T2Dx was approved by the US Food and Drug Administration for the rapid detection of a modified panel of ESKAPE bacterial species or Candida spp. causing bloodstream infection (BSI). PATIENTS AND METHODS: We performed a retrospective, observational study from January 1, 2018 to December 31, 2019 of all hospitalised patients with suspected BSI who underwent assessment using T2Dx in addition to standard blood culture (BC). T2-positive patients (cases) were compared to a matched group of patients with BSI documented only by BC (1:2 ratio) to investigate the possible impact of T2Dx on the appropriateness of empirical antimicrobial therapy and 21-day mortality. RESULTS: In total, 78 T2Dx-analysed samples (49 patients) were analysed. The T2Dx assay result was positive for18 patients and negative for 31 patients. The concordance rates of the T2Bacteria Panel and T2Candida Panel results with those of standard BC were 74.4% and 91.4%, respectively. In the matched analysis, inappropriate empiric antimicrobial therapy administration was significantly less frequent in cases than in comparators (5.5% vs. 38.8%). The 21-day mortality rate was twofold lower in cases than in comparators (22.2% vs. 44.4%), although the difference was not significant. No other analysed variables were significantly different between the two groups. CONCLUSIONS: This study illustrated that T2Dx might be associated with an increase in the appropriateness of empiric antimicrobial therapy in patients with BSI. Further studies are needed to evaluate whether the T2Dx assay can improve patient outcomes.

Virological and Clinical Outcome of DAA Containing Regimens in a Cohort of Patients in Calabria Region (Southern Italy).

Background and objectives: In Italy, Hepatitis C Virus (HCV) infections are most prevalent in people older than 50 years of age, who often experience multi-morbidities, take co-medications, and have a long history of liver disease. These characteristics could potentially affect tolerability of HCV treatments and adherence in this subgroup. After achievement of sustained virological response (SVR), retention into care is very important both to detect the onset of possible complications and prevent further infections. In this study, SVR rates and retention into care of patients treated with directly acting antivirals (DAAs) of a single-center cohort in Southern Italy were evaluated. Materials and Methods: Patients treated with directly acting antivirals from 2014 to 2018 were included. Patients were stratified by age (i.e., <65 vs. ≥65 years) and by cirrhosis presence (i.e., liver stiffness >14.6 KPa or clinical/ultrasound cirrhosis vs. absence of these criteria). Primary outcome was availability of SVR at Weeks 12-24 after the end of treatment. Inter- and intra-group comparisons were performed along the follow-up for significant laboratory parameters. Results: In total, 212 patients were treated; 184 (87%) obtained SVR after the first treatment course and 4 patients after retreatment. Twenty-two (10.4%) patients were lost to follow-up before assessment of SVR, and two patients died before the end of treatment for liver decompensation. Considering only the first treatment episode, per protocol analysis (i.e., excluding patients lost to follow-up) showed the following rates of SVR: 97% (overall), 97% (older age group), 96% (age group <65 years), 94% (cirrhotics), and 100% (non-cirrhotics). By contrast, at the intention to treat analysis (i.e., patients lost were computed as failures), SVR percentages were significantly lower for patients <65 years of age (80%) and for non-cirrhotics (85%). Conclusions: High rates of SVR were obtained. However, younger patients and those without cirrhosis displayed an apparent high risk of being lost to follow-up. This may have important implications: since those who are lost may transmit HCV in case SVR is not achieved, these subpopulations should receive appropriate counselling during treatment.

Evaluation of cardiac function by global longitudinal strain before and after treatment with sofosbuvir-based regimens in HCV infected patients.

BACKGROUND: Possible cardiotoxicity of sofosbuvir in humans has not been demonstrated yet. Also, since HCV can exert deleterious effects on hearth function, it is of interest to know whether HCV eradication provides any benefits using global longitudinal strain (GLS), a measure of left ventricular function more reliable than ejection fraction (EF). METHODS: Patients eligible for treatment with the combination therapy for HCV were invited to perform a transthoracic cardiac ultrasound at four different time points: before starting treatment, after one month, at the end of treatment and, after six month. Left ventricular function was measured with both EF and GLS. RESULTS: From March 2015 to December 2016, 82 patients were enrolled. Fifty-six percent patients were males. Mean age was 66.12 (SD: 9.25) years. About 20% patients did not present any cardiovascular risk factors or comorbidities. A worsening trend of GLS was observed. Variations were not found to be statistically significant when EF was studied along the follow-up. However, when GLS was studied, its variations were found to be statistically significant indicating a worsening effect, albeit with different trends in patients who underwent treatment for three months compared to six months. Worsening of GLS was found to be statistically significant even after adjusting for body mass index and liver fibrosis, independently from treatment duration. CONCLUSIONS: Our results showed unexpected worsening of left ventricular function when measured through GLS after HCV treatment response induced by DAAs including sofosbuvir. Although this result is not proven to be clinically significant, the safety profile of sofosbuvir-based regimens needs to be studied further.

Release of nickel and chromium in common foods during cooking in 18/10 (grade 316) stainless steel pots.

BACKGROUND: Literature data on the release of nickel and chromium from stainless steel cookware during food preparation are contrasting, have often been obtained with uncommon foods and/or procedures, and are thus not widely applicable. OBJECTIVES: To assess the release of nickel and chromium from 18/10 (grade 316) stainless steel pots in cooking conditions that are common in an urban lifestyle. METHODS: Tomato sauce and lemon marmalade were cooked for 1 h, alone or with added EDTA, in used or unused stainless steel pots from different manufacturers. Additionally, aqueous solutions at pH 2.3, 7.7 and 9 were boiled for 1 h in the same pots. Metal release was assessed with inductively coupled plasma mass spectrometry. RESULTS: The release of nickel and chromium increased with cooking/boiling time, was higher with unused pots, at low pH or with EDTA, and was sometimes remarkably different between manufacturers. In all experiments, the amounts released were below known allergy-triggering thresholds. CONCLUSIONS: Under common conditions, the use of 18/10 stainless steel pots is considered to be safe for the majority of nickel-allergic and/or chromium-allergic subjects. However, the total amount of nickel contained in foods and released from pots may exceed the individual threshold for triggering allergy, potentially causing problems for highly sensitive patients, or, conversely, contribute to induction of immunotolerance by oral low-dose exposure.

High risk of pleural plaques and parenchymal abnormalities in women living in Biancavilla (Italy).

Fluoro-edenite is a natural mineral species first isolated in Biancavilla, Sicily, used for construction of houses and roads, with health effects allegedly the same as those of asbestos. The aim of the current study was to evaluate the risks of pleural plaques and parenchymal abnormalities in women living in Biancavilla through a retrospective cross-sectional study. The evaluation pointed out a relative risk of pleural plaques of 39.67 (95% CI: 11.33-138.82) and 27.67 (95% CI: 5.43-141.00) for parenchymal abnormalities as well. These findings have prompted urge to extend the screening on the possible abnormalities of the respiratory tract to all Biancavilla's population, particularly in those aged more than 30 years.

Is hand-grip another culprit for the risk of fractures in HIV-positive patients?

Risk of bone fractures in patients with HIV infection is greater than in the general population, particularly in those co-infected with hepatitis viruses. We compared bone mineral density (BMD) and muscular strength, measured by hand grip test (HG), in HIV mono-infected and co-infected patients. T-score values were lower in HIV patients co-infected with hepatitis viruses vs. mono-infected individuals. Since no significant correlations between HG and T-scores were found, we hypothesize that these factors belong, at least in part, to independent pathways, so both should be taken into account as risks for fragility fractures. Larger prospective studies are needed to confirm this hypothesis.

CT patterns of pleuro-pulmonary damage caused by inhalation of pumice as a model of pneumoconiosis from non-fibrous amorphous silicates.

PURPOSE: The aim of this article is to correlate the radiological features of pleuro-pulmonary damage caused by inhalation of pumice (an extrusive volcanic rock classified as a non-fibrous, amorphous, complex silicate) with exposure conditions. MATERIALS AND METHODS: 36 subjects employed in the pumice quarries were evaluated for annual follow-up in a preventive medical surveillance program including spirometry, chest CT lasting from 1999 to 2014. They were only male subjects, mean age 56.92 ± 16.45 years. Subjects had worked in the quarries for an average of 25.03 ± 9.39 years. Domestic or occupational exposure to asbestos or other mineral dusts other than pumice was excluded. Subjects were also classified as smokers, former smokers and nonsmokers. RESULTS: Among the 36 workers examined, we identified four CT patterns which resulted to be dependent on exposure duration and intensity, FVC, FEV1 and FEF25-75, but not on cigarette smoking. The most common symptoms reported by clinical examination were dyspnoea, cough and asthenia. In no case it was proven an evolution of CT findings during follow-up for 10 years. CONCLUSIONS: Liparitosis, caused by pumice inhalation, can be considered a representative example of pneumoconiosis derived by amorphous silica compounds, which are extremely widespread for industrial manufacturing as well as for applicative uses, such as nano-materials. Moreover, being pumice free of quartz contamination, it can represent a disease model for exposure to pure non-fibrous silicates.

IL-17 and IL-22 serum levels in greenhouse workers exposed to pesticides.

INTRODUCTION: Altered immune function may be an indicator of increased potential for the development of immunologically based diseases such as cancer, hypersensitivity and autoimmunity. MATERIALS AND METHODS: To investigate whether Th17 and Th22 cells are targeted by pesticide exposure, we analyzed IL-17 and IL-22 serum levels in a population of 64 greenhouse workers. RESULTS AND CONCLUSION: A significant increase in IL-22 concentration was observed in serum of the exposed subjects compared to controls. These findings support the hypothesis that exposure to pesticides may reduce host defenses against infections and cancer.

Challenging clinical cases in HCV infection.

We present clinical cases, which underline some difficulties in diagnosis and treatment of hepatitis C virus (HCV) infection. Case report #1 shows a patient who avoided clinical follow-up for HCV until the development of hepatocellular carcinoma. In this patient, non-invasive procedures did not allow to make a differential diagnosis between hydatidosis and hepatocellular carcinoma but diagnosis was only made with liver biopsy.

Present, old and future strategies for anti-HCV treatment in patients infected by genotype-1: estimation of the drug costs in the Calabria Region in the era of the directly acting antivirals.

BACKGROUND: In Italy, anti-HCV drugs are provided free of charge by the National Health System. Since 2011, three drug regimens including a directly acting antiviral (DAA) are considered the gold standard for HCV treatment. However, these drugs add a significant cost (roughly €26,000) to the combination of pegylated-interferon-α/ribavirin (PEG-IFN/RBV), which before DAA represented the unique treatment. To provide the National Health System potential useful information, we estimated costs to provide anti-HCV drugs to treat a population experienced for PEG-INF/RBV. METHODS: Genotype 1 HCV mono-infected or HIV/HCV co-infected individuals who were treated with PEG-IFN/RBV between 2008 and 2013 were included. The cost to treat these patients with PEG-IFN/RBV was calculated (cost 1). We also estimated costs if we had to treat these patients with a lead-in period of PEG-INF/RBV followed by PEG-IFN/RBV and a DAA in naïves (cost 2), in addition to cost 1 plus the estimated cost to re-treat with PEG-IFN/RBV and a DAA patients who had a relapse or a non response (cost 3). Moreover, all costs were normalized by SVR. Rates of foreseen response with DAA were obtained from literature data. RESULTS: The overall study population consisted of 104 patients. The rate of sustained virological response (SVR) was 55%, while it was estimated that SVR would be obtained in 75% of patients with a lead-in period with PEG-IFN/RBV followed by a DAA combination, and in 78% if this treatment is used to re-treat experienced patients with a DAA. Drug costs associated with these treatments were: €1,214,283 for cost 1, €3,474,977 for cost 2 and €3,002,095 for cost 3. Costs per SVR achieved were: €22,284 for cost 1, €44,643 for cost 2 and €38,322 for cost 3. CONCLUSIONS: Treatments including DAAs achieve a SVR in more patients than PEG-IFN/RBV but they cost around three times more than PEG-IFN/RBV alone regimens. Also, cost per SVR is almost twofold greater than PEG-IFN/RBV regimens. Therefore, it is mandatory to implement use of DAA in clinical practice, but the National Health System should allocate adequate resources to provide drugs, which challenges sustainability. Cost reduction for anti-HCV drugs should be pursued.

Sleep disorders, stress coping strategies and neurobehavioral aspects: an outlook on the impact of covid­19 in first­year resident physicians.

The COVID-19 pandemic had a profound impact on the physical and mental health of healthcare professionals. The present study explored the relationship between sleep disorders, stress, coping strategies and neurobehavioral aspects among young physicians during the second wave of the COVID-19 pandemic. Through a multi-assessment approach, this cross-sectional study collected sociodemographic and occupational data from first-year resident doctors in southern Italy. Subjective sleep quality, chronotype, work-related stress, coping approach and mood state were assessed by administering validated questionnaires during face-to-face interviews. Among the 258 resident physicians enrolled in the study, ~25% complained of poor sleep quality, mainly male subjects [odds ratio (OR), 2.52]. Alcohol consumption resulted as a risk factor for poor sleep quality (OR, 1.97). None of the participants reported work-related stress showing, on the contrary, a high score for the vigor factor in the profile of mood state, in particular in subjects with previous working experience with COVID patients and prevention (P<0.040 and P<0.035, respectively). Women were more likely to adopt coping strategies that involved the search for social support, confirming their tendency to manage stressful situations through emotion-focused mechanisms. The set of these results represents a sight on the attitude of young physicians in their approach to facing the COVID-19 pandemic, in its second wave. The pandemic has turned the spotlight on the importance of prevention and early diagnosis of physical health and mental well-being. Further studies are performed to monitor long-term consequences on health status.

An autochthonous case of cutaneous bacillary angiomatosis not related to major immunosuppression: An emerging or overlooked disease?

Cutaneous bacillary angiomatosis (cBA) is a vascular proliferative disorder due to Bartonella henselae or Bartonella quintana that has been mostly described in people living with HIV. Since cBA is considered to be rare in hosts not affected by major immunosuppression, it could be underdiagnosed in this population. Moreover, antimicrobial treatment of cBA has been poorly validated, thus reporting experiences on this clinical entity is important. We reported a challenging and well-characterized case of an Italian 67-year-old gentleman without a history of major immunocompromizing conditions, although he was affected by conditions that can be associated with impaired immune function. The patient reported herein was diagnosed after a long time since the initiation of symptoms and was successfully treated with combined antibiotic therapy including macrolides and quinolones under the guidance of molecular test results. Physicians should consider cBA as a possible manifestation of Bartonella spp. Infection in patients not suffering from major immunocompromizing conditions. Until evidence-based guidelines are available, molecular tests together with severity and extension of the disease can be useful to personalize the type of treatment and its duration.

Antiproliferative activity of the dietary isothiocyanate erucin, a bioactive compound from cruciferous vegetables, on human prostate cancer cells.

It is becoming increasingly clear that many dietary agents, such as isothiocyanates (ITCs) from cruciferous vegetables, can retard or prevent the process of prostate carcinogenesis. Erucin (ER) is a dietary ITC, which has been recently considered a promising cancer chemopreventive phytochemical. The potential protective activity of ER against prostate cancer was investigated using prostate adenocarcinoma cells (PC3), to analyze its effects on pathways involved in cell growth regulation, such as the cyclin-dependent kinase (CDKs) inhibitor p21(WAF1/CIP1) (p21), phosphatidylinositol-3 kinase/AKT, and extracellular signal-regulated kinases (ERK)1/2 signaling pathways. We have shown for the first time that ER increases significantly p21 protein expression and ERK1/2 phosphorylation in a dose-dependent manner to inhibit PC3 cell proliferation (P ≤ 0.01). Compared to the structurally related sulforaphane, a well-studied broccoli-derived ITC, ER showed lower potency in inhibiting proliferation of PC3 cells, as well as in modulating p21 and pERK1/2 protein levels. Neither of the naturally occurring ITCs was able to affect significantly pAKT protein levels in prostate cells at all concentrations tested (0-25 µM). It is clearly important for the translation of laboratory findings to clinical approaches to investigate in animal and cell studies the molecular mechanisms by which ITCs may exert health promoting effects.

Salivary Biomarkers Analysis and Neurobehavioral Assessment in Nurses Working Rotation Shifts: A Pilot Study.

Currently, about one in five workers is employed in night shift work in Europe. Shift work including nighttime hours is essential in several activities, especially the healthcare sector. Importantly, night working may be associated with the occurrence of sleep disorders or work-related stress, both potentially augmenting the risk of errors and accidents at work. This study aims to examine the presence of neurobehavioral alterations that can be a consequence of shift working and concurrent misalignment of the sleep times and circadian rhythms. Nurses (n = 102) employed at a University Hospital located in North-Eastern Sicily, Italy, voluntarily participated in this pilot study. During medical surveillance, morning and evening salivary samples were collected, and seven psychodiagnostics questionnaires were administered to all the subjects. On one hand, the salivary levels of stress-related biomarkers (cortisol and alpha-amylase) and a circadian biomarker (melatonin) were evaluated. On the other hand, several neurobehavioral features were assessed, including depression, anxiety, work-related, and sleep issues. Interestingly, a positive relationship between salivary morning cortisol and depression scale, as well as a negative relationship between salivary morning alpha-amylase and work ability scale, were observed. Based on these results, the integration of subjective questionnaire outcomes and objective salivary biomarker quantification can help to identify workers with increased susceptibility to developing neurobehavioral alterations. This approach may contribute to ameliorating preventive strategies towards sensitive categories, such as nurses working rotation shifts.

A Rare Complication of Ascariasis: A Case of Acute Interstitial Nephritis.

Acute interstitial nephritis (AIN) due to helminths is a rare cause of acute kidney injury (AKI). Helminthiases often progresses insidiously, making diagnosis difficult. This was the case of a 72-year-old man, who presented with renal failure, itching and diarrhoea. Urinalysis revealed leukocyturia, microhaematuria and mild proteinuria. A full blood count revealed leucocytosis with eosinophilia. A stool parasitological examination revealed fertilised eggs of Ascaris lumbricoides. Tubulointerstitial nephropathy secondary to A. lumbricoides infection was suspected. A percutaneous renal biopsy was not performed since the patient refused the anti-platelet therapy discontinuation. Mebendazole, albendazole and prednisone therapy was administered. After worm eradiation and discharge, recovery from the parasitosis, absence of pruritus and eosinophilia, and progressive improvement of renal function were observed, strongly suggesting a causal relationship between Ascaris infection and AIN. Parasite infection should be considered in the differential diagnosis of unexplained renal failure because early diagnosis and treatment are necessary to avoid irreversible complications.

Touching Base with Some Mediterranean Diseases of Interest from Paradigmatic Cases at the "Magna Graecia" University Unit of Infectious Diseases: A Didascalic Review.

Among infectious diseases, zoonoses are increasing in importance worldwide, especially in the Mediterranean region. We report herein some clinical cases from a third-level hospital in Calabria region (Southern Italy) and provide a narrative review of the most relevant features of these diseases from epidemiological and clinical perspectives. Further, the pathogenic mechanisms involved in zoonotic diseases are reviewed, focusing on the mechanisms used by pathogens to elude the immune system of the host. These topics are of particular concern for individuals with primary or acquired immunodeficiency (e.g., people living with HIV, transplant recipients, patients taking immunosuppressive drugs). From the present review, it appears that diagnostic innovations and the availability of more accurate methods, together with better monitoring of the incidence and prevalence of these infections, are urgently needed to improve interventions for better preparedness and response.

Role-Playing Between Environmental Pollutants and Human Gut Microbiota: A Complex Bidirectional Interaction.

There is a growing interest in the characterization of the involvement of toxicant and pollutant exposures in the development and the progression of several diseases such as obesity, diabetes, cancer, as well as in the disruption of the immune and reproductive homeostasis. The gut microbiota is considered a pivotal player against the toxic properties of chemicals with the establishment of a dynamic bidirectional relationship, underlining the toxicological significance of this mutual interplay. In fact, several environmental chemicals have been demonstrated to affect the composition, the biodiversity of the intestinal microbiota together with the underlining modulated metabolic pathways, which may play an important role in tailoring the microbiotype of an individual. In this review, we aimed to discuss the latest updates concerning the environmental chemicals-microbiota dual interaction, toward the identification of a distinctiveness of the gut microbial community, which, in turn, may allow to adopt personalized preventive strategies to improve risk assessment for more susceptible workers.

Chronic Pesticide Exposure in Farm Workers Is Associated with the Epigenetic Modulation of hsa-miR-199a-5p.

The increasing use of pesticides in intensive agriculture has had a negative impact on human health. It was widely demonstrated how pesticides can induce different genetic and epigenetic alterations associated with the development of different diseases, including tumors and neurological disorders. Therefore, the identification of effective indicators for the prediction of harmful pesticide exposure is mandatory. In this context, the aim of the study was to evaluate the modification of hsa-miR-199a-5p expression levels in liquid biopsy samples obtained from healthy donors and farm workers with chronic exposure to pesticides. For this purpose, the high-sensitive droplet digital PCR assay (ddPCR) was used to detect variation in the expression levels of the selected microRNA (miRNA). The ddPCR analyses revealed a significant down-regulation of hsa-miR-199a-5p observed in individuals exposed to pesticides compared to control samples highlighting the good predictive value of this miRNA as demonstrated by statistical analyses. Overall, the obtained results encourage the analysis of miRNAs as predictive biomarkers of chronic pesticide exposure thus improving the current strategies for the monitoring of harmful pesticide exposure.

Work Performance, Mood and Sleep Alterations in Home Office Workers during the COVID-19 Pandemic.

The sudden burst of the COVID-19 pandemic has changed the work environment in favor of remote working, affecting the perception of work quality, satisfaction and performance. This crisis has also influenced workers' mood, sleep quality and general perception of everyday life. Our main purpose in this study was to give empirical contributions about home office workers experiencing remote working during the pandemic by assessing mood spectrum variations, sleep disturbances and the general impact of pandemic in everyday life. This cross-sectional study was performed between November and December 2020 through an online questionnaire. Participants were office workers performing remote work from workstations settled at home. The questionnaire investigated sociodemographic characteristics, health factors, perception of remote working, mood spectrum, sleep quality and pandemic context perception. The sample consisted of 94 respondents: 63 women and 31 men; the mean age was 50.4 years. Study population showed great satisfaction for remote working performance and online services for video connections. Only one third of the participants reported higher levels of irritability and loneliness and 16% of women complained of nightmares. Most of participants stated that the pandemic importantly affected daily life (85.1%). Half of female subjects with children <18 years stated that children's age influenced their work performance. Since the pandemic is still an ongoing issue, the lesson learnt is that local government actions are needed to assist home office workers through tailored programs to support families. Given the central role of women in childcare, female workers would mainly benefit from social support accordingly to their parental tasks and remote work organization.