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Biagio Pinchera, Emanuela Zappulo, Antonio Riccardo Buonomo, Maria Rosaria Cotugno, Giovanni Di Filippo, Francesco Borrelli, Simona Mercinelli, Riccardo Villari, Ivan Gentile Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples “Federico II”, Naples, ItalyCorrespondence: Biagio Pinchera, Email biapin89@virgilio.itBackground: HCV-related liver disease is an important cause of morbidity and mortality in patients with HIV infection. It is well known that the response rates to HCV therapy are similar between HCV-monoinfected patients and HIV-HV coinfected ones. The aim of this study was to evaluate the impact of HCV eradication on CD4 + T cell count in a population of HIV-HCV coinfected patients.Materials and Methods: We enrolled patients with HIV-HCV coinfection attending the Infectious Diseases Unit of the A.O.U. Federico II of Naples, from January 2016 to February 2019, treated with ART (AntiRetroviral Therapy) and DAAs (Direct Antiviral Agents). For each patient, we evaluated HIV and HCV viral load and CD4+ T cell count before starting therapy with DAAs, by SVR12 time and by SVR48 time. Fibrosis was evaluated by the mean of Fibroscan®.Results: Fifty-two patients were enrolled, 40 males. Fibrosis score was F0-F3 in 15 patients and cirrhosis in the remaining 11 (all in Child-Pugh class A). All had been receiving ART, and all were treated with DAAs. Only patient who had not achieved HIV viral suppression for non-compliance also experienced a relapse of HCV infection after the end of DAAs. In all patients, we observed that the CD4+ T cell count at baseline did not show significant variations compared to SVR12 and SVR48 time. We also assessed CD4 count in relation to HIV categories and stage of liver disease, see Table 1. Also, based on the assessments of the subclasses considered, there were no significant changes in the CD4 + T cell count.Conclusion: Our study shows that HCV viral eradication obtained with DAAs in patients with HIV-HCV coinfection is not associated with significant changes in the CD4 + T cell count, regardless of CDC category and stage of liver disease.Keywords: HCV, HIV, fibrosis, cirrhosis, DAAs, CD4+ T cell, coinfection

Ivan Gentile,1 Antonio Riccardo Buonomo,1 Emanuela Zappulo,1 Giuseppina Minei,1 Filomena Morisco,2 Francesco Borrelli,1 Nicola Coppola,3 Guglielmo Borgia1 1Section of Infectious Diseases, 2Section of Gastroenterology, Department of Clinical Medicine and Surgery, University of Naples Federico II, 3Section of Infectious Diseases, Department of Mental Health and Public Medicine, Second University of Naples, Naples, Italy Abstract: According to the World Health Organization, approximately 150 million people worldwide are chronic carriers of hepatitis C virus (HCV). HCV infection can evolve into cirrhosis of the liver and its complications, which are ultimately responsible for more than 350,000 deaths every year. Antiviral therapy, when successful, is able to decrease the rate of progression and increase survival. Two types of therapies are currently available, ie, interferon-based therapies and interferon-free ones. The latter have several advantages in terms of safety and tolerability, and could be used even in the most advanced stages of the disease. However, their use is restricted to some viral genotypes (genotype 2 and 3) and they are expensive. Several molecules are in an advanced phase of development. This review deals with the pharmacokinetics, pharmacodynamics, tolerability, and safety of asunaprevir, an inhibitor of HCV nonstructural 3 protease. Asunaprevir exerts optimal in vitro activity particularly against HCV genotypes 1 and 4, and its pharmacokinetic profile enables twice daily administration. The drawback of asunaprevir, and of all protease inhibitors, is its low barrier to resistance. Consequently, it is used in association with other drugs to prevent resistance. Specifically, when combined with daclatasvir, an NS5A inhibitor, asunaprevir results in a very high rate of viral eradication in both treatment-naïve and treatment-experienced patients, with a sustained virological response rate of 80%–90%. Tolerability is fair; in fact, asunaprevir is associated with a transient increase in aminotransferase levels, which is mild in most cases. In conclusion, asunaprevir is a good candidate component of interferon-free combinations and may revolutionize the treatment of chronic HCV infection in the near future. Keywords: NS3, interferon, ribavirin, interferon-free, daclatasvir, sofosbuvir

Liquid biopsy is a valuable emerging alternative to tissue biopsy with great potential in the noninvasive early diagnostics of cancer. Liquid biopsy based on single cell analysis can be a powerful approach to identify circulating tumor cells (CTCs) in the bloodstream and could provide new opportunities to be implemented in routine screening programs. Since CTCs are very rare, the accurate classification based on high-throughput and highly informative microscopy methods should minimize the false negative rates. Here, we show that holographic flow cytometry is a valuable instrument to obtain quantitative phase-contrast maps as input data for artificial intelligence (AI)-based classifiers. We tackle the problem of discriminating between A2780 ovarian cancer cells and THP1 monocyte cells based on the phase-contrast images obtained in flow cytometry mode. We compare conventional machine learning analysis and deep learning architectures in the non-ideal case of having a dataset with unbalanced populations for the AI training step. The results show the capacity of AI-aided holographic flow cytometry to discriminate between the two cell lines and highlight the important role played by the phase-contrast signature of the cells to guarantee accurate classification. [ABSTRACT FROM AUTHOR]

Abstract Chronic use of anthraquinone laxatives has been blamed for the induction of habituation and the development of colonic cancer, but there are no definitive studies which have demonstrated this. [...]

Abstract Bacopa monniera (BM), a traditional Ayurvedic medicine, used for centuries as a memory enhancing, anti-inflammatory, analgesic, antipyretic, sedative and antiepileptic agent. The plant, plant extract and isolated bacosides (the [...]

Summary The effect of an ethanolic extract of propolis, with and without CAPE, and some of its components on cyclooxygenase (COX-1 and COX-2) activity in J774 macrophages has been investigated. [...]

Gold standard imaging modalities in biological field are based on fluorescence signals providing high specificity and high resolution. Recently, Fluorescence Microscopy has been combined with microfluidics to develop instrumentations called Imaging Flow Cytometers, high-throughput tools that supply bright-field, darkfield and multiple-channels fluorescence images of each single cell passing in the Field Of View (FOV). Nevertheless, Fluorescence Microscopy has some drawbacks as phototoxicity, photobleaching, expensive costs for sample preparations and also the a-priori knowledge of the tags to be used. For these reasons label-free imaging methods greatly increase in the recent years as the Quantitative Phase Imaging (QPI) technologies for microscopy. One of the optical techniques to achieve QPI is Digital Holography. DH in microscopy has several advantages such as the possibility to numerically scan the focal distance, a properties that open to the integration of DH in microfluidics. Indeed DH combined with microfluidic circuits allows to image particles or cells flowing into the FOV at different depths. Here the capabilities of label-free single-cell imaging by DH are presented and their implications on next future biomedical applications discussed. Static or in-flow configurations will be showed describing recent results and perspectives also in combination with Artificial Intelligence architectures for future applications in biomedical and clinical fields.

Byline: P. Falcone, F. Borrelli, H.E. Tseng, J. Asgari, D. Hrovat We present and discuss an in-vehicle experimental validation of an integrated steering and braking Model Predictive Control (MPC) algorithm. The experimental results are obtained in autonomous path following tests, where the vehicle autonomously performs a double-lane change manoeuvre by simultaneously coordinating the front steering and the braking torques at the four wheels. The manoeuvres are performed at high speed on slippery surfaces to operate close to the vehicle stability limits. Experimental tests of double-lane change manoeuvres at 70 kph are shown and complex countersteering manoeuvres are presented and discussed.

Byline: F. Borrelli, P. Falcone, T. Keviczky, J. Asgari, D. Hrovat In this paper, a novel approach to autonomous steering systems is presented. A model predictive control (MPC) scheme is designed in order to stabilise a vehicle along a desired path while fulfilling its physical constraints. Simulation results show the benefits of the systematic control methodology used. In particular we show how very effective steering manoeuvres are obtained as a result of the MPC feedback policy. Moreover, we highlight the trade off between the vehicle speed and the required preview on the desired path in order to stabilise the vehicle. The paper concludes with highlights on future research and on the necessary steps for experimental validation of the approach.

BackgroundThe COVID-19 pandemic has significantly impacted the management of solid organ transplant recipients and on clinical evolution in post-transplantation. Little is known on the impact of SARS-CoV-2 infection in these patients. The severity and lethality of this disease in solid organ transplant patients are higher thanin the general population. This study aims to describe clinical characteristics of SARS-CoV-2 infection in solid organ transplant recipients followed in our center.MethodsIn this observational study, we enrolled all kidney transplant recipientsattending the A.O.U. Federico II of Naples from March 2020 to January 2021. For each patient we evaluated the epidemiological and clinical characteristics as well as outcome.ResultsWe enrolled 369 kidney transplant patients (229, male, 62%). Of these, 51 (13.8%) acquired SARS-CoV-2 infection and 29 showed symptomatic disease. Of the 51 patients with the infection, 48 (94.11%) had at least one comorbidity and such comorbidities did not constitute a risk factor for a more severe disease. Hospitalization was necessary for 7 (13.7%) patients. Of these, 2 required low-flow oxygen supplementation, 3 non-invasive/high flow ventilation and 2 invasive ventilation. Finally, 2 patients died.ConclusionsOur study shows a lower mortality and hospitalization rate compared to figures available in the literature (4% vs. 13–30% and 14% vs. 32–100%, respectively). Furthermore, the comorbidities examined (hypertension, dyslipidemia, and diabetes) did not constitute a risk factor for a more severe disease condition in this patient category. Further studies with larger sample size are necessary to confirm these data.

Common variable immune deficiency (CVID) is the most frequent primary immunodeficiency in adults. In CVID, the prevalence of gastrointestinal manifestations ranges between 2 and 50% with a complication-related morbidity second only to that of the respiratory tract. In some cases, clinical and endoscopic features are undistinguishable from those of inflammatory bowel disease (IBD). We describe the case of a 28-year-old man in which a diagnosis of Crohn's disease was firstly suspected. Subsequently, a diagnosis of Crohn's-like disease in a patient with CVID was made and a replacement therapy with human normal immunoglobulin intravenously was started. Unfortunately, serum IgG levels remained below 2.0 g/l in pre-infusional controls with persistence of gastrointestinal symptoms and malnutrition despite anti-inflammatory therapy (mesalazine, corticosteroids). Then, the patient began treatment with human normal immunoglobulins administered subcutaneously. The follow-up visits showed a progressive increase in serum IgG. Moreover, the patient reported improvement of gastrointestinal symptoms with reduction of diarrhoea, and laboratory tests showed a progressive and significant improvement. We confirm that therapy with subcutaneously administered immunoglobulins is safe and effective. In addition, our observations indicate that, for patients with CVID and enteropathic complications, replacement therapy with subcutaneous IgG may be the treatment of choice. [ABSTRACT FROM AUTHOR]

Izzo AA, Di Carlo G, Borrelli F, Ernst E. Int J Cardiol 2005:98:1-14. Use of herbal medicines among patients under cardiovascular pharmacotherapy is widespread. In this paper, we have reviewed [...]

We report an unusual case of endobronchial primary large B-cell Non Hodgkin Lymphoma in a HIV-infected patient in the course of effective Highly Active Antiretroviral Therapy (HAART). Diagnosis of large B-cell NHL was obtained by fibreoptic bronchoscopy (FOB) biopsies. Three cycles of R-CHOP chemotherapy (rituximab, vincristine, cyclophosphamide, hydroxydaunorubicin, prednisone) was performed and clinical and radiological remission was obtained after 3 cycles of therapy. [ABSTRACT FROM AUTHOR]

Background and Purpose: Allyl isothiocyanate (AITC, mustard oil), a constituent of many common cruciferous vegetables (Brassicaceae), activates transient receptor potential of ankyrin type-1 (TRPA1) channels, claimed to regulate gastrointestinal contractility. In this study, we have investigated the effect of AITC on intestinal motility.Experimental Approach: Effects of AITC were investigated in vivo on upper gastrointestinal transit in mice and in mouse isolated ileum [contractions induced by electrical field stimulation (EFS), acetylcholine and spontaneous contractility]. The contractor activity of AITC was studied in mouse isolated colon. The ability of TRPA1 channel antagonists to block AITC-induced elevation of intracellular Ca(2+) [Ca(2+)](i) was assessed in HEK293 cells transfected with rat TRPA1 channels.Key Results: AITC increased [Ca(2+)](i) in HEK293 cells, reduced ileal contractility (acetylcholine-, EFS-induced contractions and spontaneous contractility), but contracted the isolated colon. Gentamicin and camphor (non-selective TRPA1 channel antagonists), HC-030031 and AP18 (selective TRPA1 channel agonists) inhibited AITC-induced effects in HEK293 cells but not in the ileum or colon. AITC-induced contractions were reduced by tetrodotoxin and strongly reduced by nifedipine, cyclopiazonic acid and ryanodine. In vivo, AITC reduced (following i.p. administration) or increased (following intragastric administration) upper gastrointestinal transit in mice These effects were not affected by HC-030031.Conclusion and Implications: AITC, depending, in vitro, on the regions of gut examined and, in vivo, on the route of administration, exerted both stimulatory and inhibitory effects on intestinal motility, which were not sensitive to TRPA1 channel antagonists. The proposition that TRPA1 channels are the primary targets for AITC to induce contraction should be revised. [ABSTRACT FROM AUTHOR]

Background and Purpose: Salvinorin A, the active component of the hallucinogenic herb Salvia divinorum, inhibits intestinal motility through activation of kappa-opioid receptors (KORs). However, this compound may have target(s) other than the KORs in the inflamed gut. Because intestinal inflammation upregulates cannabinoid receptors and endogenous cannabinoids, in the present study we investigated the possible involvement of the endogenous cannabinoid system in salvinorin A-induced delay in motility in the inflamed gut.Experimental Approach: Motility in vivo was measured by evaluating the distribution of a fluorescent marker along the small intestine; intestinal inflammation was induced by the irritant croton oil; direct or indirect activity at cannabinoid receptors was evaluated by means of binding, enzymic and cellular uptake assays.Key Results: Salvinorin A as well as the KOR agonist U-50488 reduced motility in croton oil treated mice. The inhibitory effect of both salvinorin A and U-50488 was counteracted by the KOR antagonist nor-binaltorphimine and by the cannabinoid CB(1) receptor antagonist rimonabant. Rimonabant, however, did not counteract the inhibitory effect of salvinorin A on motility in control mice. Binding experiments showed very weak affinity of salvinorin A for cannabinoid CB(1) and CB(2) and no inhibitory effect on 2-arachidonoylglycerol and anandamide hydrolysis and cellular uptake.Conclusions and Implications: The inhibitory effect of salvinorin A on motility reveals a functional interaction between cannabinoid CB(1) receptors and KORs in the inflamed--but not in the normal--gut in vivo. [ABSTRACT FROM AUTHOR]

: Gastrointestinal cancer is one of the leading causes of cancer mortality in the world. Therefore, numerous efforts are being made to find chemoprotective substances able to reduce its incidence. Amongst these, green tea, one of the most popular beverages world-wide, has been reported to provide protective effects against gastrointestinal cancer. : To critically evaluate all epidemiological studies reporting an association between green tea consumption and a reduced risk of gastrointestinal cancer. : Epidemiological studies of green tea consumption in relation to gastrointestinal cancer or preneoplastic lesions were identified through computerized literature searches using the following databases: Medline (Pubmed), Embase, Amed, CISCOM, Phytobase and Cochrane Library. Only epidemiological studies indicating the type of tea (green tea) and the site of either cancer or precancerous lesions (stomach or intestine) were included. No language restrictions were imposed. : Twenty-one epidemiological investigations met our inclusion/exclusion criteria. : These studies seemed to suggest a protective effect of green tea on adenomatous polyps and chronic atrophic gastritis formations. By contrast, there was no clear epidemiological evidence to support the suggestion that green tea plays a role in the prevention of stomach and intestinal cancer. [ABSTRACT FROM AUTHOR]

Background: Constitutive cyclooxygenase‐1 enzyme synthesizes prostaglandins which are thought to play an important role in the functional integrity of the stomach gastric mucosa. Recently, it was shown that cyclooxygenase‐1 deficient mutant mice did not develop spontaneous gastric pathology and appear less sensitive to indomethacin‐induced gastric damage. Aim: To investigate gastric acid secretion in cyclooxygenase‐1 deficient mutant mice. Methods: The basal and histamine or isobutyl methylxanthine‐stimulated acid secretion in stomachs of cyclooxygenase‐1 deficient homozygous mice and the effect of indomethacin was compared with that of heterozygous and wild‐type mice using isolated lumen perfused mouse stomachs, in organ baths, monitored by pH‐electrodes. Results: There was no significant difference in the basal or histamine stimulated gastric acid secretion between wild‐type or heterozygous or homozygous mice. However, isobutyl methylxanthine was more potent in the cyclooxygenase‐1 deficient and heterozygous mice than in wild‐type mice. Indomethacin, at concentrations below 1 mM, had no effect on either basal or histamine stimulated acid secretion in any of the mice populations. Conclusion: Gastric acid secretion is maintained without prostaglandin involvement in cyclooxygenase‐1 deficient mice. The finding that basal and histamine‐stimulated gastric acid secretion was similar in the cyclooxygenase‐1 deficient, compared to wild‐type mice is consistent with the lack of spontaneous gastric pathology in the cyclooxygenase‐1 deficient mice. [ABSTRACT FROM AUTHOR]

Current evidence suggests that aberrant crypt foci (ACF) can be used to evaluate agents for their potential colon carcinogenic activity. The aim of the present study was to determine whether senna pod extract (SE) itself induces ACF and tumors in the rat colon or increases the development of ACF and tumors induced by azoxymethane (AOM). A daily administration of SE 10 mg/kg by mouth for 13-28 weeks produced a weak laxative effect but did not itself cause the appearance of ACF or tumors. The numbers of ACF and tumors induced by AOM were, however, increased by a dose of SE (100 mg/kg) able to induce chronic diarrhea over three months. These results suggest that SE does not cause the appearance of ACF or tumors in the rat colon nor does it have a promoting effect when given to rats at a dose that produces laxation (10 mg/kg), whereas a diarrhogenic dose (100 mg/kg) increases the appearance of tumors induced by AOM. [ABSTRACT FROM AUTHOR]

It has been established that follicle stimulating hormone (FSH) circulates in the bloodstream as a heterogeneous population of molecules. Individual FSH isoforms, while displaying identical amino acid sequences, differ in their extent of post-translational modification. As a result of these variations, the FSH isoforms exhibit differences in overall charge, degree of sialic acid or sulphate incorporation, receptor binding affinity and plasma half-life. Taking advantage of the fact that these forms can be separated from each other on the basis of their charge, we have evaluated in rats the metabolic clearance rates of the acidic [with an isoelectric point (pI) ≤ISOdia≤ 4.8] and the less acidic (pI > 4.8) isoforms of recombinant human FSH (rhFSH) obtained after chromatofocusing. The less acidic isoform group was found to have a faster clearance from the circulation in rats as compared with the acidic isoform group. This finding is in agreement with the lower bioactivity in vivo (as determined by the Steelman–Pohley assay) of the less acidic isoform group, compared with the acidic one. The mass spectra of the two groups of isoforms showed a difference in the sialic acid content thus highlighting the importance of these residues on the in-vivo activity of FSH. Conversely, when the two groups of isoforms were tested in vitro by using the Y1 human FSH receptor (Y1 hFSHR) assay and a reporter gene assay, no significant differences in the biological activities between these preparations were detected when test concentrations were based on mass. [ABSTRACT FROM PUBLISHER]