Studies for the Conservation and Valorisation of the Archaeological Rock Heritage of Calascibetta in Sicily, Italy

Abstract. The rock settlement of Vallone Canalotto, which stands in the valleys surrounding the town of Calascibetta – about three kilometres north from Enna, Sicily, Italy – testify to a widespread population of the area from prehistoric times up to the Middle Ages, probably linked to the agricultural and pastoral exploitation of its fertile land. This valuable heritage, dug into very soft limestone banks, is now threatened by significant erosion and disruption phenomena, which, in the absence of adequate safeguarding and maintenance actions, will lead to a progressive loss of material and the consequent collapse of some portions, making the documentable traces more and more paltry. The archaeological complex demonstrates the continuity of the funerary use from the remotest ages to the early Christian era, as testified by the excavation of rupestrian columbaria. In the early medieval period, small rural communities used the hypogeal structures for residential and religious purposes. In the present work, integrated procedures have been put in place for the 3D documentation of these artefacts, whose effectiveness has already been tested by the same team in other Sicilian rock sites. The research aims at the knowledge and cataloguing of places, which are important for the Island's history but to date only marginally explored. It intends to stimulate and plan adequate conservation and enhancement activities. To improve the attendance of the sites, design proposals have been developed to guarantee greater accessibility to the archaeological areas and their understanding by visitors

Expression of the Antimicrobial Peptide Piscidin 1 and Neuropeptides in Fish Gill and Skin: A Potential Participation in Neuro-Immune Interaction

Antimicrobial peptides (AMPs) are found widespread in nature and possess antimicrobial and immunomodulatory activities. Due to their multifunctional properties, these peptides are a focus of growing body of interest and have been characterized in several fish species. Due to their similarities in amino-acid composition and amphipathic design, it has been suggested that neuropeptides may be directly involved in the innate immune response against pathogen intruders. In this review, we report the molecular characterization of the fish-specific AMP piscidin1, the production of an antibody raised against this peptide and the immunohistochemical identification of this peptide and enkephalins in the neuroepithelial cells (NECs) in the gill of several teleost fish species living in different habitats. In spite of the abundant literature on Piscidin1, the biological role of this peptide in fish visceral organs remains poorly explored, as well as the role of the neuropeptides in neuroimmune interaction in fish. The NECs, by their role as sensors of hypoxia changes in the external environments, in combination with their endocrine nature and secretion of immunomodulatory substances would influence various types of immune cells that contain piscidin, such as mast cells and eosinophils, both showing interaction with the nervous system. The discovery of piscidins in the gill and skin, their diversity and their role in the regulation of immune response will lead to better selection of these immunomodulatory molecules as drug targets to retain antimicrobial barrier function and for aquaculture therapy in the future.Expression of the Antimicrobial Peptide Piscidin 1 and Neuropeptides in Fish Gill and Skin: A Potential Participation in Neuro-Immune InteractionpublishedVersio

Immunogenicity and safety after the third dose of BNT162b2 anti-SARS-CoV-2 vaccine in patients with solid tumors on active treatment: a prospective cohort study

Background: Although a full course of coronavirus disease 2019 (COVID-19) vaccine is effective in cancer patients, the duration of the protection and the efficacy of a booster dose against the new variants remain unknown. We prospectively evaluated the immunogenicity of the third dose of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) BNT162b2 messenger RNA vaccine in cancer patients undergoing active treatment. Patients and methods: Patients with solid cancer, vaccinated with a booster dose during active treatment, were enrolled in this study. Patients were classified into SARS-CoV-2 naïve (without previous COVID-19 infection) and SARS-CoV-2 experienced (with previous COVID-19 infection). Neutralizing antibody (NT Ab) titer and total anti-Spike immunoglobulin G (IgG) concentration were quantified in serum. Heparinized whole blood samples were used for SARS-CoV-2 Interferon Gamma Release Assay (IGRA). The primary endpoint was to assess the increase of IgG antibody level between baseline and 3 weeks after the booster. Results: One hundred and forty-two consecutive patients were recruited. In SARS-CoV-2-naïve subjects, the median level of IgG was 157 BAU/ml [interquartile range (IQR) 62-423 BAU/ml] at T0 and reached a median of 2080 BAU/ml (IQR 2080-2080 BAU/ml) at 3 weeks after booster administration (T1; P < 0.0001). A median 16-fold increase of SARS-CoV-2 NT Ab titer (IQR 4-32) was observed in naïve subjects (from median 20, IQR 10-40, to median 640, IQR 160-640; P < 0.0001). Median interferon-γ level at T1 was significantly higher than that measured at T0 in SARS-CoV-2-naïve subjects (P = 0.0049) but not in SARS-CoV-2-experienced patients. The median level of SARS-CoV-2 NT Abs was 32-fold lower against Omicron compared to the wild-type strain (P = 0.0004) and 12-fold lower compared to the Delta strain (P = 0.0110). Conclusions: The third dose is able to trigger both the humoral and the cell-mediated immune response in cancer patients on active treatment. Our preliminary data about the neutralization of the SARS-CoV-2 vaccine against variants of concern seem to confirm the lower vaccine activity

Analysis of the humoral and cellular immune response after a full course of BNT162b2 anti-SARS-CoV-2 vaccine in cancer patients treated with PD-1/PD-L1 inhibitors with or without chemotherapy: an update after 6 months of follow-up

Background: The durability of immunogenicity of SARS-CoV-2 vaccination in cancer patients remains to be elucidated. We prospectively evaluated the immunogenicity of the vaccine in triggering both the humoral and the cell-mediated immune response in cancer patients treated with anti-programmed cell death protein 1/programmed death-ligand 1 with or without chemotherapy 6 months after BNT162b2 vaccine. Patients and methods: In the previous study, 88 patients were enrolled, whereas the analyses below refer to the 60 patients still on immunotherapy at the time of the follow-up. According to previous SARS-CoV-2 exposure, patients were classified as SARS-CoV-2-naive (without previous SARS-CoV-2 exposure) and SARS-CoV-2-experienced (with previous SARS-CoV-2 infection). Neutralizing antibody (NT Ab) titer against the B.1.1 strain and total anti-spike immunoglobulin G concentration were quantified in serum samples. The enzyme-linked immunosorbent spot assay was used for quantification of anti-spike interferon-γ (IFN-γ)-producing cells/106 peripheral blood mononuclear cells. Fifty patients (83.0%) were on immunotherapy alone, whereas 10 patients (7%) were on chemo-immunotherapy. We analyzed separately patients on immunotherapy and patients on chemo-immunotherapy. Results: The median T-cell response at 6 months was significantly lower than that measured at 3 weeks after vaccination [50 interquartile range (IQR) 20-118.8 versus 175 IQR 67.5-371.3 IFN-γ-producing cells/106 peripheral blood mononuclear cells; P < 0.0001]. The median reduction of immunoglobulin G concentration was 88% in SARS-CoV-2-naive subjects and 2.1% in SARS-CoV-2-experienced subjects. SARS-CoV-2 NT Ab titer was maintained in SARS-CoV-2-experienced subjects, whereas a significant decrease was observed in SARS-CoV-2-naive subjects (from median 1 : 160, IQR 1 : 40-1 : 640 to median 1 : 20, IQR 1 : 10-1 : 40; P < 0.0001). A weak correlation was observed between SARS-CoV-2 NT Ab titer and spike-specific IFN-γ-producing cells at both 6 months and 3 weeks after vaccination (r = 0.467; P = 0.0002 and r = 0.428; P = 0.0006, respectively). Conclusions: Our work highlights a reduction in the immune response in cancer patients, particularly in SARS-CoV-2-naive subjects. Our data support administering a third dose of COVID-19 vaccine to cancer patients treated with programmed cell death protein 1/programmed death-ligand 1 inhibitors

Localization of Acetylcholine, Alpha 7-NAChR and the Antimicrobial Peptide Piscidin 1 in the Macrophages of Fish Gut: Evidence for a Cholinergic System, Diverse Macrophage Populations and Polarization of Immune Responses

20 pages, 9 figures, 2 tables.-- Data Availability Statement: Not applicableThe recognition and elimination of invading pathogens are vital for host survival. Macrophages play a central role in host protection and cells functionally reminiscent of vertebrate macrophages are present in all multicellular organisms. A pattern responsible for bacterial recognition found on the surface of macrophages is CD14. These cells possess a repertoire of antimicrobial molecules stored in their granules and lysosomes. Polarization states observed in mammalian macrophages termed M1 and M2 also likely exist in fish macrophages. Markers for macrophage subtypes are slowly but definitively emerging in fish species. In the present study cell markers such as CD14, acetylcholine, alpha 7 acetylcholine nicotinic receptor (nAChR) subtype, the inducible nitric oxidase synthase (iNOS), and the antimicrobial peptide piscidin 1 are reported for the first time in the intestinal macrophages of both catfish Heteropneustes fossilis (Bloch, 1794) and the African bonytongue Heterotis niloticus (Cuvier, 1829) along the anterior and the posterior axis and the concentric muscle layers. Many antimicrobial effector responses of vertebrate macrophages including respiratory burst and NO induction are similar across the diverse animal taxa. Antibodies against calbindin coupled with ones to VAChT and tubulin revealed the localization of myenteric and submucosal plexuses, which are made up of enteric neurons, glial cells, and nerves near macrophages. Current studies allow for the elucidation of multiple roles of macrophages in disease models providing an insight into their in vivo function in fishPeer reviewe

The noise-lovers: cultures of speech and sound in second-century Rome

This chapter provides an examination of an ideal of the ‘deliberate speaker’, who aims to reflect time, thought, and study in his speech. In the Roman Empire, words became a vital tool for creating and defending in-groups, and orators and authors in both Latin and Greek alleged, by contrast, that their enemies produced babbling noise rather than articulate speech. In this chapter, the ideal of the deliberate speaker is explored through the works of two very different contemporaries: the African-born Roman orator Fronto and the Syrian Christian apologist Tatian. Despite moving in very different circles, Fronto and Tatian both express their identity and authority through an expertise in words, in strikingly similar ways. The chapter ends with a call for scholars of the Roman Empire to create categories of analysis that move across different cultural and linguistic groups. If we do not, we risk merely replicating the parochialism and insularity of our sources.Accepted manuscrip

Switching to Intravenous Methadone in Advanced Cancer Patients: A Retrospective Analysis

Context: Information about opioid switching to intravenous methadone is lacking. Objectives: The aim of this study was to assess the outcome of opioid switching to intravenous methadone (IV-ME) in patients admitted to an acute supportive/palliative care unit (ASPCU). The secondary outcome was to assess the conversion ratio from IV-ME to oral methadone at time of hospital discharge. Methods: We retrieved from the pharmacy registry the list of patients who were prescribed IV-ME during their ASPCU admission for a period of 47 months. Poor analgesia with previous opioids and/or adverse effects were the main indications for opioid switching. IV-ME was titrated until acceptable analgesia was achieved. The effective dose was multiplied by three to establish the intravenous daily dose, given as a continuous infusion. Doses were then changed according to the clinical needs. Once the patient was stabilized, IV-ME dose was converted to oral methadone, by using an initial ratio of 1:1.2. Further dose changes were made according to clinical needs until stabilization, before patients' discharge. Information about patients' characteristics, pain scores on the Edmonton Symptom Assessment Scale (ESAS), Memorial Delirium Assessment Scale (MDAS), Cut-down, Annoyed, Guilty, Eye-opener (CAGE) questionnaire, previous opioids and their doses, expressed as oral morphine equivalents (OME), were recorded. The effective bolus of IV-ME, initial daily infusion rate, and oral methadone doses were assessed, and conversion ratios calculated. Results: Forty-one patients were taken into consideration for the study. The mean effective bolus of IV-ME titrated for achieving acceptable analgesia was 9 mg (range 5-15 mg). The mean daily continuous infusion rate of IV-ME was 27.6 mg/day (SD 21). The mean daily dose of oral methadone at time of discharge was 46.8 mg/day (SD 43). Discharge occurred within a median of seven days (range 6-9) after admission. Previous opioid (OME)/IV-ME, oral-IV-ME, and previous opioid (OME)/oral methadone were 6.25, 1.7, and 3.7, respectively. Conclusion: IV-ME dose titration followed by intravenous infusion allowed a rapid pain control in few minutes in patients with severe pain intensity, not responsive to previous opioids. Conversion to oral route was successful and facilitated home discharge. Further studies should be performed to confirm these preliminary results

Rapid Titration With Intravenous Oxycodone for Severe Cancer Pain and Oral Conversion Ratio

to assess a dose titration with intravenous oxycodone to achieve rapid pain relief of cancer pain of severe intensity. The second objective was to provide a conversion ratio with the oral route

Maddalena Opioid Switching Score (MOSS) in patients with cancer pain

Evaluation of opioid switching (OS) for cancer pain has not been properly assessed. The aim of this study was to assess an integrated score (Maddalena Opioid Switching Score, MOSS) as a simple and repeatable tool to evaluate the outcomes of OS, facilitating the interpretation and comparison of studies, and information exchange among researchers. The integrated score took into account pain intensity, intensity of opioid-related symptoms, and cognitive function by using an authors' formula. Physical and psychological symptoms were evaluated by Edmonton Symptom Assessment Scale (ESAS) and patient global impression (PGI) by the minimal clinically important difference (MCID).One-hundred-six patients were analyzed. Ninety-five patients were switched successfully, and eleven patients underwent a further OS and/or alternative procedure. MOSS significantly decreased after OS and was highly correlated to PGI of improvement (P&lt;0.0005). In patients with unsuccessful OS, no significant changes in MOSS and PGI were observed. A significant reduction in ESAS items intensity was observed after OS.MOSS resulted to be a sensitive instrument for measuring the clinical improvement produced by OS

Characteristics of Untreated Cancer Patients Admitted to an Acute Supportive/Palliative Care Unit

Backgrund. The characteristics of patients who had never received anticancer treatments at admission of an acute supportive palliative care unit (ASPCU) have never been explored.Measures. From a consecutive sample of 422 advanced cancer patients, 62 patients with no previous anticancer therapy were selected and compared with a random sample of patients who had received anticancer treatments. Age, gender, primary tumor, Karnofsky status, characteristics of admission, the level of education, economic status, awareness of disease, the presence of cachexia, and comorbidities and palliative prognostic score, symptom intensity, opioid drugs used at admission, reasons for admission to APSCU were recorded in both groups. At time of discharge, ESAS and analgesic drugs used were recorded again. Discharge modalities were also recorded. One month after the end of recruitment period (the last patient enrollment), a follow-up was performed by phone contacts with relatives to assess survival at three months after discharge.Outcomes. Patients without previous anticancer therapy (14.7%) were mainly admitted to ASPCU for a low Karnofsky level and high symptom burden, often waiting for or needing a histological diagnosis to make a decision for the next therapeutic steps. This group of patients were older (P&lt;0.0005), more frequently males (P=0.007), and had more comorbidities (P&lt;0.0005) in comparison with treated patients. Twenty-four per cent of these patients started chemotherapy subsequently. Treatment-naive patients had a higher level of symptom burden, which was less responsive to a comprehensive palliative and more frequently died within three months in comparison with treated patients.Discussion. Treatment-naive patients showed a higher level of symptom burden, which was less responsive to a comprehen-sive palliative treatment. In addition they more frequently died within three months in comparison with treated patients. J Pain Symptom Manage 2023;65:e677-e682. (c) 2023 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved