Evaluation of dental demands and needs of people experiencing homelessness in the city of Rome, Italy.

OBJECTIVE: Poor oral health and oral diseases are common among people experiencing homelessness. The aim of this study was to evaluate the dental demands and needs of a population of homeless persons in the city of Rome, Italy. PATIENTS AND METHODS: The clinical records of 165 homeless patients admitted between October 2020 and October 2021 to the dental service of the Primary Care Services of the Eleemosynaria Apostolica, Vatican City, were retrospectively reviewed. The service employed dentists to evaluate dental needs and oral conditions in patients experiencing homelessness. The main dental and oral pathological conditions were noted. RESULTS: One hundred and sixty-five records of homeless patients were included in the study. The sample consisted in 138 males (76.97%) and 27 females (23.03%) with a mean age of 46.9 years (range 7-85 years). Acute tooth pain was reported by 132 (80%) patients, 42 (25.45%) had edentulism or missing teeth and 18 (10.91%) patients had oral lesions. Both dental and oral pathologies were intercepted and managed in secondary healthcare facilities. CONCLUSIONS: Given the specific peculiarities of this vulnerable population, it is important to implement strategies that facilitate the access of persons experiencing homelessness to dental evaluation with a preventive and curative perspective.

SARS-CoV-2 infection prevalence in people experiencing homelessness.

OBJECTIVE: People experiencing homelessness have peculiar characteristics that make them more vulnerable to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) transmission and to more serious forms of Coronavirus Disease 19 (COVID-19). The aim of this study was to evaluate the prevalence of SARS-CoV-2 infection in the homeless population assisted by the primary care services of the Eleemosynaria Apostolica, Vatican City. PATIENTS AND METHODS: Persons experiencing homelessness and the volunteers assisting them were tested for COVID-19 through PCR and antigen rapid test between October 1st, 2020, and June 5th, 2021, in the clinical facilities of the Eleemosynaria Apostolica. RESULTS: A total of 1665 subjects from 96 different countries in five continents were included in the study; age range was 1-90 years. Overall, 2315 COVID-19 tests through nasopharyngeal swab were performed; 1052 Polymerase Chain Reaction (PCR) tests and 1263 antigen rapid tests. Nearly 40% of the subjects underwent both tests (n=650, 39.04%), 402 were tested with PCR test only (24.14%) and 613 with antigen test only (36.8%). PCR tests were negative in 966 cases and positive in 86 (8.17%), while antigen tests were negative in 1205 cases and positive in 58 (4.59%). The number of positive cases varied over time, with a drastic increase during the winter months of 2020 and a progressive decrease over 2021. Among positive cases, 24.41% were symptomatic; symptoms included fever, breathing difficulties, anosmia/hyposmia, cough, headache, and diarrhea. CONCLUSIONS: This study reported an overall prevalence of SARS-CoV-2 infection in our sample slightly above 8%. Additional data on viral genome through sequencing of SARS-CoV-2 in positive cases are of utmost importance to help identify variants and implement specific infection control measures.

Cetacean presence and distribution in the central Mediterranean Sea and potential risks deriving from plastic pollution.

The Sardinian and Sicilian Channels are considered hotspots of biodiversity and key ecological passages between Mediterranean sub-basins, but with significant knowledge gaps about marine mammal presence and potential threats they face. Using data collected between 2013 and 2019 along fixed transects, inter and intra-annual cetacean index of abundance was assessed. Habitat suitability, seasonal hot spots, and risk exposure for plastic were performed using the Kernel analysis and the Biomod2 R-package. 661 sightings of 8 cetacean species were recorded, with bottlenose and striped dolphins as the most sighted species. The north-eastern pelagic sector, the coastal waters and areas near ridges resulted the most suitable habitats for these species. The risk analysis identified the Tunis, Palermo, and Castellammare gulfs and the Egadi Island as areas of particular risk of plastic exposure. The study represents a great improvement for cetacean knowledge in this region and contributes to the development of effective conservation strategies.

Acceptance of COVID-19 vaccine among persons experiencing homelessness in the City of Rome, Italy.

OBJECTIVE: Vulnerable populations are being more severely impacted by the ongoing pandemic, and the recent release of vaccines for Coronavirus Disease 19 (COVID-19) may offer them protection. The aim of this study was to investigate the willingness of homeless persons to be vaccinated against COVID-19; secondary aims were to analyze the immunization coverage for other conditions. PATIENTS AND METHODS: The acceptance of COVID-19 vaccine and immunization coverage for other conditions were investigated through a form in 112 persons experiencing homelessness referring to the primary care medical services of the Eleemosynaria Apostolica, Holy See. RESULTS: Most subjects, with a male preponderance, were willing to be vaccinated against COVID-19 (64.3%), 3.6% were unsure and 32.1% preferred not to be vaccinated. When answering questions on the immunization coverage for tuberculosis and hepatitis A and B, most subjects reported not to be vaccinated (48.2%, 56.2% and 55.3%, respectively) or did not know (33%, 28.6% and 27.7%). CONCLUSIONS: A significant portion of our sample declared to be willing to be vaccinated against COVID-19. It would be auspicious that the recent statements from several countries on the importance to extend COVID-19 vaccination to fragile populations be followed by the distribution of the vaccine to these populations.

Health and social conditions of children living in disadvantaged neighborhoods in the city of Rome, Italy.

OBJECTIVE: The number of children living in socio-economically disadvantaged neighborhoods in developed countries is constantly growing, resulting in important implications for children's development, physical and psychological health and increased future disparities. In this study, we explored several key elements of children living in poor neighborhoods, such as demographic characteristics, access to public health assistance and school, and availability of housing and basic hygienic conditions. PATIENTS AND METHODS: The study included 711 children aged 0-17 years referring to primary care services in the suburbs of the city of Rome, Italy. RESULTS: Most children were born in Italy, while almost none of their parents were. Nearly 60% of the children did not have access to basic pediatric care, causing possible misdiagnosis and delayed treatment for acute and chronic conditions. A smaller percentage of the children did not have access to basic housing (8%) and hygienic facilities, such as heating, running water, and refrigerator (3.2%), leading to malnutrition, isolation and poor physical and psychological development. CONCLUSIONS: This study confirms a critical condition for children living in disadvantaged neighborhoods, whose vulnerability is further worsened by the limited access to paediatric health assistance and, in some cases, to basic facilities with a severe impact on their physical and psychological development.

Analysis of resorbable mesh implants in short-term human muscular fascia cultures: a pilot study.

PURPOSE: Alteration in fascial tissue collagen composition represents a key factor in hernia etiology and recurrence. Both resorbable and non-resorbable meshes for hernia repair are currently used in the surgical setting. However, no study has investigated so far the role of different implant materials on collagen deposition and tissue remodeling in human fascia. The aim of the present study was to develop a novel ex vivo model of human soft tissue repair mesh implant, and to test its suitability to investigate the effects of different materials on tissue remodeling and collagen composition. METHODS: Resorbable poly-4-hydroxybutyrate and non-resorbable polypropylene mesh implants were embedded in human abdominal fascia samples, mimicking common surgical procedures. Calcein-AM/Propidium Iodide vital staining was used to assess tissue vitality. Tissue morphology was evaluated using Mallory trichrome and hematoxylin and eosin staining. Collagen type I and III expression was determined through immunostaining semi-quantification by color deconvolution. All analyses were performed after 54 days of culture. RESULTS: The established ex vivo model showed good viability at 54 days of culture, confirming both culture method feasibility and implants biocompatibility. Both mesh implants induced a disorganization of collagen fibers pattern. A statistically significantly higher collagen I/III ratio was detected in fascial tissue samples cultured with resorbable implants compared to either non-resorbable implants or meshes-free controls. CONCLUSION: We developed a novel ex vivo model and provided evidence that resorbable polyhydroxybutyrate meshes display better biomechanical properties suitable for proper restoration in surgical hernia repair.

hERG1 and CA IX expression are associated with disease recurrence in surgically resected clear cell renal carcinoma.

BACKGROUND: In search of novel prognostic biomarkers for clear cell renal carcinoma (ccRCC), we analysed the expression of several proteins related to angiogenesis and hypoxia. METHODS: A monocentric study on 30 consecutive surgical samples from surgically-treated ccRCC patients with a 10-year follow up was performed. The following proteins were analysed by immunohistochemistry: Vascular Endothelial Growth Factor- A (VEGF-A), Platelet-Derived Growth Factor ß Receptor (PDGFRß), VEGF-receptor 1 (Flt1), VEGF-receptor 2 (KDR), Glucose Transporter 1 (GLUT1), Carbonic anhydrase IX (CA-IX) and the hERG1 potassium channel. Data were analysed in conjunction with the clinico-pathological characteristics of the patients and follow up. RESULTS: All the proteins were expressed in the samples, with statistically significant associations of VEGF-A with PDGFRß and Flt1 and hERG1 with CA IX. Notably, hERG1 and CAIX co-immunoprecipitated in primary ccRCC samples and survival analysis showed that the positivity for hERG1 and CA IX had a negative impact on Recurrence Free Survival (RFS) at the univariate analysis. At the multivariate analysis only hERG1 maintained its statistically significant negative impact. CONCLUSIONS: hERG1 expression can be exploited to predict recurrence in surgically-treated ccRCC patients. hERG1 channels form a multiprotein complex with the pH regulator CA IX in primary ccRCC samples their potential use as therapeutic target might be suggested.

PtI2(DACH), the iodido analogue of oxaliplatin as a candidate for colorectal cancer treatment: chemical and biological features.

Colorectal cancer (CRC) is a global health problem being the fourth most common cause of death due to cancer worldwide. Oxaliplatin plays a key role in current CRC treatment but shows serious drawbacks, such as a high systemic toxicity and the frequent insurgence of Pt resistance. In search of novel and more efficacious Pt-based drugs for CRC treatment, we synthesized and characterised PtI2(DACH), an oxaliplatin analogue. PtI2(DACH) was obtained through the replacement of bidentate oxalate with two iodides. PtI2(DACH) turned out to be more lipophilic than oxaliplatin, a fact that led to an enhancement of its cellular uptake. In contrast to oxaliplatin, PtI2(DACH) showed a scarce reactivity towards model proteins, while maintaining affinity for a standard DNA oligo. Notably, PtI2(DACH) induced cytotoxicities roughly comparable to those of oxaliplatin in three representative CRC cell lines. Moreover, it was able to trigger cell apoptosis, to an extent even better than cisplatin and oxaliplatin. Overall, a rather promising picture emerges for this novel Pt drug that merits, in our opinion, a deeper and more extensive preclinical evaluation.

Seasonal characterisation of maritime traffic and the relationship with cetacean presence in the Western Mediterranean Sea.

Seasonal maritime traffic was investigated in relation to cetaceans, through direct observations (July 2013-June 2015) along three fixed transects in Western Mediterranean. Visually obtained vessel abundance was compared with Automatic Identification System data to explore if the two methods provided different results. Traffic intensity and composition were characterised by seasons and vessel categories. Finally, cetacean presence was investigated in relation to traffic by measuring the difference of vessel abundance in the presence and absence of animal sightings. Results showed that visual sampling was consistent with AIS data, providing more information on small-medium vessels. Traffic was more intense and diverse in Spring/Summer, and the highest vessel abundance and seasonal variations in composition emerged for inshore subareas. The difference of traffic in the presence and absence of cetaceans was higher in most offshore subareas in Spring/Summer, verified for B. physalus and S. coeruleoalba; in inshore waters, mostly occupied by T. truncatus, no significant differences emerged.

Water-soluble Ru(II)- and Ru(III)-halide-PTA complexes (PTA=1,3,5-triaza-7-phosphaadamantane): Chemical and biological properties.

Four structurally related Ru(II)-halide-PTA complexes, of general formula trans- or cis-[Ru(PTA)4X2] (PTA=1,3,5-triaza-7-phosphaadamantane, X=Cl (1, 2), Br (3, 4), were prepared and characterized. Whereas compounds 1 and 2 are known, the corresponding bromo derivatives 3 and 4 are new. The Ru(III)-PTA compound trans-[RuCl4(PTAH)2]Cl (5, PTAH=PTA protonated at one N atom), structurally similar to the well-known Ru(III) anticancer drug candidates (Na)trans-[RuCl4(ind)2] (NKP-1339, ind=indazole) and (Him)trans-[RuCl4(dmso-S)(im)] (NAMI-A, im=imidazole), was also prepared and similarly investigated. Notably, the presence of PTA confers to all complexes an appreciable solubility in aqueous solutions at physiological pH. The chemical behavior of compounds 1-5 in water and in physiological buffer, their interactions with two model proteins - cytochrome c and ribonuclease A - as well as with a single strand oligonucleotide (5'-CGCGCG-3'), and their in vitro cytotoxicity against a human colon cancer cell line (HCT-116) and a myeloid leukemia (FLG 29.1) were investigated. Upon dissolution in the buffer, sequential halide replacement by water molecules was observed for complexes 1-4, with relatively slow kinetics, whereas the Ru(III) complex 5 is more inert. All tested compounds manifested moderate antiproliferative properties, the cis compounds 2 and 4 being slightly more active than the trans ones (1 and 3). Mass spectrometry experiments evidenced that all complexes exhibit a far higher reactivity towards the reference oligonucleotide than towards model proteins. The chemical and biological profiles of compounds 1-5 are compared to those of established ruthenium drug candidates in clinical development.

Cetacean response to summer maritime traffic in the Western Mediterranean Sea.

Maritime traffic is one of many anthropogenic pressures threatening the marine environment. This study was specifically designed to investigate the relationship between vessels presence and cetacean sightings in the high sea areas of the Western Mediterranean Sea region. We recorded and compared the total number of vessels in the presence and absence of cetacean sightings using data gathered during the summer season (2009-2013) along six fixed transects repeatedly surveyed. In locations with cetacean sightings (N = 2667), nautical traffic was significantly lower, by 20%, compared to random locations where no sightings occurred (N = 1226): all cetacean species, except bottlenose dolphin, were generally observed in locations with lower vessel abundance. In different areas the species showed variable results likely influenced by a combination of biological and local environmental factors. The approach of this research helped create, for the first time, a wide vision of the different responses of animals towards a common pressure.

hERG1 channels drive tumour malignancy and may serve as prognostic factor in pancreatic ductal adenocarcinoma.

BACKGROUND: hERG1 channels are aberrantly expressed in human cancers. The expression, functional role and clinical significance of hERG1 channels in pancreatic ductal adenocarcinoma (PDAC) is lacking. METHODS: hERG1 expression was tested in PDAC primary samples assembled as tissue microarray by immunohistochemistry using an anti-hERG1 monoclonal antibody (α-hERG1-MoAb). The functional role of hERG1 was studied in PDAC cell lines and primary cultures. ERG1 expression during PDAC progression was studied in Pdx-1-Cre,LSL-Kras(G12D/+),LSL-Trp53(R175H/+) transgenic (KPC) mice. ERG1 expression in vivo was determined by optical imaging using Alexa-680-labelled α-hERG1-MoAb. RESULTS: (i) hERG1 was expressed at high levels in 59% of primary PDAC; (ii) hERG1 blockade decreased PDAC cell growth and migration; (iii) hERG1 was physically and functionally linked to the Epidermal Growth Factor-Receptor pathway; (iv) in transgenic mice, ERG1 was expressed in PanIN lesions, reaching high expression levels in PDAC; (v) PDAC patients whose primary tumour showed high hERG1 expression had a worse prognosis; (vi) the α-hERG1-MoAb could detect PDAC in vivo. CONCLUSIONS: hERG1 regulates PDAC malignancy and its expression, once validated in a larger cohort also comprising of late-stage, non-surgically resected cases, may be exploited for diagnostic and prognostic purposes in PDAC either ex vivo or in vivo.

Optical measurement of the effect of electric fields on the nuclear spin coherence of rare-earth ions in solids.

We show that the coherence properties of the nuclear spin states of rare-earth ions in solids can be manipulated by small applied electric fields. This was done by measuring the Stark effect on the nuclear quadrupole transitions of (151)Eu in Y(2)SiO(5) (YSO) using a combination of Raman heterodyne optical detection and Stark modulated quadrupole echoes to achieve high sensitivity. The measured Stark coefficients were 0.42 and 1.0 Hz cm/V for the two quadrupole transitions at 34.54 and 46.20 MHz, respectively. The long decoherence time of the nuclear spin states (25 ms) allowed us to make the measurements in very low electric fields of ∼ 10 V/cm, which produced 100% modulation of the nuclear spin echo, and to measure Stark shifts of ∼ 1 Hz or 20 ppm of the inhomogeneous linewidth.

Glutamine depletion by crisantaspase hinders the growth of human hepatocellular carcinoma xenografts.

BACKGROUND: A subset of human hepatocellular carcinomas (HCC) exhibit mutations of ß-catenin gene CTNNB1 and overexpress Glutamine synthetase (GS). The CTNNB1-mutated HCC cell line HepG2 is sensitive to glutamine starvation induced in vitro with the antileukemic drug Crisantaspase and the GS inhibitor methionine-L-sulfoximine (MSO). METHODS: Immunodeficient mice with subcutaneous xenografts of the CTNNB1-mutated HCC cell lines HepG2 and HC-AFW1 were treated with Crisantaspase and/or MSO, and tumour growth was monitored. At the end of treatment, tumour weight and histology were assessed. Serum and tissue amino acids were determined by HPLC. Gene and protein expression were estimated with RT-PCR and western blot and GS activity with a colorimetric method. mTOR activity was evaluated from the phosphorylation of p70S6K1. RESULTS: Crisantaspase and MSO depleted serum glutamine, lowered glutamine in liver and tumour tissue, and inhibited liver GS activity. HepG2 tumour growth was significantly reduced by either Crisantaspase or MSO, and completely suppressed by the combined treatment. The combined treatment was also effective against xenografts of the HC-AFW1 cell line, which is Crisantaspase resistant in vitro. CONCLUSIONS: The combination of Crisantaspase and MSO reduces glutamine supply to CTNNB1-mutated HCC xenografts and hinders their growth.

VEGF-A clinical significance in gastric cancers: immunohistochemical analysis of a wide Italian cohort.

PURPOSE: The clinical significance of VEGF-A expression in gastric cancer (GC) has been reported with contradicting results. We analyzed the expression and clinical significance of VEGF-A in a wide Italian cohort of GC specimens. METHODS: VEGF-A expression was tested by immunohistochemistry in 507 patients with GC of all clinical stages. The impact of VEGF-A on overall survival (OS) was evaluated in conjunction with clinical and pathological parameters. RESULTS: In the Italian cohort we studied VEGF-A was not an independent prognostic factor neither at the univariate nor at multivariate analysis. CONCLUSIONS: Although frequently expressed, in our study VEGF-A was not able to discriminate between groups of patients with different risk.

Targeting ion channels in leukemias: a new challenge for treatment.

Leukemias, as other cancers, bear several genetic alterations of tumor-related genes, such as point mutations, translocations, epigenetic modifications, often accompanied by gene amplification or inactivation. The identification of tumor-related genes provides considerable insight into the biology of leukemias and opens the way to more specific pharmacological treatments. These genes comprise several ion channels and pumps, as the transport mechanisms associated with volume control, proliferation and apoptosis are often altered in cancers. In leukemic cells, such changes are observed as early as the stem cell stage. Ion channels can regulate other malignant features, such as lack of differentiation, increased migratory and invasive phenotype and chemoresistance. The role of certain voltage-gated K(+) channels, such as K(v)11.1 (also known as hERG1) can be largely attributed to modulation of cell adhesion to the extracellular matrix (ECM). K(v)11.1 exerts pleiotropic regulatory effects by forming multiprotein membrane complexes with integrin receptors in both acute myeloid leukemias (AML) and acute lymphoblastic leukemias (ALL). By recruiting growth factor and chemokine receptors, these complexes form signaling hubs that control neoplastic progression. Work in mice shows that blocking K(v)11.1 has a protective effect in acute leukemias. Ion channels are most promising targets for anti-leukemic therapy, because of their accessibility from the extracellular side and the thorough understanding of their pharmacology. In ALL cells, K(v)11.1 inhibitors abrogate the protective effect of bone marrow stromal cells and enhance the cytotoxicity of some common antileukemic drugs. Hence, ion channel modulators could overcome chemoresistance in acute leukemias, a major hindrance to therapeutic success.

A physiologic comparison of proportional assist ventilation with load-adjustable gain factors (PAV+) versus pressure support ventilation (PSV).

PURPOSE: To compare patient-ventilator interaction during PSV and PAV+ in patients that are difficult to wean. METHODS: This was a physiologic study involving 11 patients. During three consecutive trials (PSV first trial--PSV1, followed by PAV+, followed by a second PSV trial--PSV2, with the same settings as PSV1) we evaluated mechanical and patient respiratory pattern; inspiratory effort from excursion Pdi (swing(Pdi)), and pressure-time products of the transdiaphragmatic (PTPdi) pressures. Inspiratory (delay(trinsp)) and expiratory (delay(trexp)) trigger delays, time of synchrony (time(syn)), and asynchrony index (AI) were assessed. RESULTS: Compared to PAV+, during PSV trials, the mechanical inspiratory time (Ti(flow)) was significantly longer than patient inspiratory time (Ti(pat)) (p < 0.05); Ti(pat) showed a prolongation between PSV1 and PAV+, significant comparing PAV+ and PSV2 (p < 0.05). PAV+ significantly reduced delay(trexp) (p < 0.001). The portion of tidal volume (VT) delivered in phase with Ti(pat) (VT(pat)/VT(mecc)) was significantly higher during PAV+ (p < 0.01). The time of synchrony was significantly longer during PAV+ than during PSV (p < 0.001). During PSV 5 patients out of 11 showed an AI greater than 10%, whereas the AI was nil during PAV+. CONCLUSION: PAV+ improves patient-ventilator interaction, significantly reducing the incidence of end-expiratory asynchrony and increasing the time of synchrony.