Enforcing the positive charge of N-termini enhances membrane interaction and antitumor activity of bovine seminal ribonuclease

AbstractBinding to cell membrane, followed by translocation into the cytosol and RNA degradation, is a necessary requirement to convert a ribonuclease into a cytotoxin for malignant tumor cells. In this paper, we investigate the membrane binding attitude of bovine seminal ribonuclease (BS-RNase) and its variant G38K-BS-RNase, bearing an enforced cluster of positive charges at the N-termini surface. By using a combination of biophysical techniques, including CD, SPR and ESR, we find for the two proteins a common, two-step mechanism of interaction with synthetic liposomes, an initial binding to the bilayer surface, driven by electrostatic interactions, followed by a shallow penetration in the lipid core. Protein binding effectively perturbs lipid packing and dynamics. Remarkably, the higher G38K-BS-RNase membrane interacting capability well correlates with its increased cytotoxicity for tumor cells. Overall, these studies shed light on the mechanism of membrane binding and perturbation, proving definitely the importance of electrostatic interactions in the cytotoxic activity of BS-RNase, and provide a rational basis to design proteins with anticancer potential

Impact of anxiety, apathy and reduced functional autonomy on perceived quality of life in Parkinson's disease

Introduction Parkinson's disease (PD) is characterized by a wide spectrum of non-motor symptoms that may impact negatively on the activities of the patient's daily life and reduce Health-related quality of life (HRQoL). The present study explored the impact of specific non-motor symptoms on the HRQoL in PD. Methods Eighty-four outpatients underwent the Montreal Cognitive Assessment (MoCA) assessing global functioning and several questionnaires to assess depression, apathy, impulse control disorders (ICD), anxiety, anhedonia and functional impact of cognitive impairment. The perceived QoL was assessed by Parkinson's Disease Questionnaire (PDQ-8). The PD sample was divided into patients with high and low HRQoL around the median of PDQ-8 and compared on clinical features, cognitive and neuropsychiatric variables. A linear regression analysis, in which the global functioning, apathy, depression, anxiety, anhedonia, ICD and the functional autonomy scores were entered as independent variables and PDQ-8 score as dependent variable, was applied. Results Patients with lower HRQoL were more depressed, apathetic, anxious and showed more severe reduction of functional autonomy and global functioning than patients with high HRQoL. The regression analysis revealed that higher level of anxiety, executive apathy and more reduced functional autonomy were significantly associated with higher score on PDQ-8. Conclusions The finding indicated that anxiety, apathy associated with impaired planning, attention and organization (i.e., executive apathy evaluated by the Dimensional Apathy Scale) and reduced functional autonomy contribute significantly to reduce the HRQoL in PD. Therefore, early identification and management of these neuropsychiatric symptoms should be relevant to preserve HRQoL in PD

HIV rapid test in a community setting as a strategy to improve access to HIV testing: data from a multicentre experience in Italy

4,000 new HIV diagnoses and approximately 800 AIDS cases are still reported annually in Italy. Improving public awareness and bringing out HIV-undiagnosed individuals are keystones to progress towards the control of the HIV epidemic. For this purpose, the Open HIV TEST project was organized and delivered by the Italian NGO Anlaids, together with local infectious diseases specialists, in order to provide free access to HIV testing outside the healthcare setting. Between October 2017 and February 2019 six Open HIV TEST initiatives were delivered in six Italian cities (3 northern cities, 1 central and 2 southern cities). In all, 581 people were tested: the overall prevalence of HIV test reactivity was 0.7%. Participants were also asked about previous screenings and about their satisfaction with the initiative: previous HIV screening due to pregnancy or surgical procedures was reported mainly by participants in northern centres (p<0.001); finally, the initiative was considered useful and noteworthy by 99% of participants. Prevalence of HIV test reactivity in our experience was in line with national data. Our experience suggests that active testing and counselling strategies in community settings should be recommended and institutionalized by local health authorities in line with the 90-90-90 global strategy

Exploring the DNA2-PNA heterotriplex formation in targeting the Bcl-2 gene promoter: A structural insight by physico-chemical and microsecond-scale MD investigation

Peptide Nucleic Acids (PNAs) represent a promising tool for gene modulation in anticancer treatment. The uncharged peptidyl backbone and the resistance to chemical and enzymatic degradation make PNAs highly advantageous to form stable hybrid complexes with complementary DNA and RNA strands, providing higher stability than the corresponding natural analogues. Our and other groups’ research has successfully shown that tailored PNA sequences can effectively downregulate the expression of human oncogenes using antigene, antisense, or anti-miRNA approaches. Specifically, we identified a seven bases-long PNA sequence, complementary to the longer loop of the main G-quadruplex structure formed by the bcl2midG4 promoter sequence, capable of downregulating the expression of the antiapoptotic Bcl-2 protein and enhancing the anticancer activity of an oncolytic adenovirus. Here, we extended the length of the PNA probe with the aim of including the double-stranded Bcl-2 promoter among the targets of the PNA probe. Our investigation primarily focused on the structural aspects of the resulting DNA2-PNA heterotriplex that were determined by employing conventional and accelerated microsecond-scale molecular dynamics simulations and chemical-physical analysis. Additionally, we conducted preliminary biological experiments using cytotoxicity assays on human A549 and MDA-MB-436 adenocarcinoma cell lines, employing the oncolytic adenovirus delivery strategy

Rassegna storica salernitana. N.s. A.11, n.1(1994)

La Società Salernitana di Storia Patria aderisce al progetto EleA e autorizza la pubblicazione del fascicoloN.S., A. 11, n.1(1994): Galdi, A., Un'altra questione di agiografia salernitana: i santi martiri Fortunato, Caio e Ante, P. 7 ; Currò, C., Vicende storiche della chiesa di S. Salvatore de Fondaco in Salerno, P. 39 ; Pisapia, A., La difesa locale a Cava de' Tirreni nella prima età moderna, P. 75 ; Sirago, M., Il porto di Salerno nel «sistema» portuale del regno meridionale in età moderna (1503-1806), P. 103 ; Parrella, R., Burocrati e società locale nel Mezzogiorno liberale: la Sottoprefettura di Campagna (1861-1913), P. 153 ; Gallo, I., Ancora su Francesco Brandileone, P. 213 ; Palmieri, S., Galante, M., Per una storiagrafia che dialoghi. A proposito di libro recente sul Principato longobardo di un Salerno, P. 225 ; Amarotta, A.R., Medioevo sepolto a Salerno: le aree di S. Sofia e S. Grammazio, P. 243 ; Travaini, L., Un follaro di Marino Sebastos, duca di Amalfi (1096-1100)?, P. 261 ; De Gregorio, V., Un nuovo osservatorio sulla bibliologia italiana, P. 267 ; Incarnato, G., Su una discutibile interpretazione della Rivoluzione napoletana del 1799, P. 299 ; Musi, A., Donato Cosimato e la storia salernitana, P. 277 ; D'Arienzo, V., La storia a un bivio. Il momento delle scelte, P. 305 ; Falanga, L., Sulle ali dell'aquila imperiale: l'arte a Napoli nel periodo asburgico, P. 309.Sul recto del frontespizio: fasc. 21 della Nuova Serie (annata LIV dalla fondazione

Low-Wage Agricultural Migrant Workers in Apulian Ghettos, Italy: General Health Conditions Assessment and HIV Screening

Background: Approximately 500,000 migrants work in the agricultural sector in Italy. Many of them live in shantytowns, wrongly called “ghettos”, far away from city centers, with no water, proper hygienic conditions or health services. The aim of this study is to assess general health conditions and HIV prevalence by giving hygienic and sanitary sustenance. Methods: Between June 2019 and February 2020, we performed a screening campaign for HIV–diabetes–hypertension, involving migrants living in three Apulian establishments: ghetto Pista, “Sankara House” and “Arena House”. Results: Overall, 321 migrants were enrolled in the study. In the medical screening, one HIV test resulted positive. Hypertension was found in 12% of the migrants visited, diabetes in 2% and TB symptoms in 17%. Among others symptoms explored, muscle and joint pain/fatigue resulted in being the most frequent, and was reported by 34% of the migrants, followed by cough (10%). Significant predictors of muscle and joint pain/fatigue were: low BMI values (OR = 1.32; 95% CI 1.19–1.99), the absence of education (OR = 1.85; 95% CI 1.02–2.95), being employed with a regular contract (OR = 2.64; 95% CI 2.39–2.83) and living in the ghettos since >12 months (OR = 1.74; 95% CI 1.24–2.21). Conclusions: Our experience suggests that, in this population, the health condition is mainly linked to the specific working activities in the agricultural fields, as well as to the hygienic and living conditions, and that all of this is due to the lack of social protection in their life and job

Low-Wage Agricultural Migrant Workers in Apulian Ghettos, Italy: General Health Conditions Assessment and HIV Screening

Background: Approximately 500,000 migrants work in the agricultural sector in Italy. Many of them live in shantytowns, wrongly called “ghettos”, far away from city centers, with no water, proper hygienic conditions or health services. The aim of this study is to assess general health conditions and HIV prevalence by giving hygienic and sanitary sustenance. Methods: Between June 2019 and February 2020, we performed a screening campaign for HIV–diabetes–hypertension, involving migrants living in three Apulian establishments: ghetto Pista, “Sankara House” and “Arena House”. Results: Overall, 321 migrants were enrolled in the study. In the medical screening, one HIV test resulted positive. Hypertension was found in 12% of the migrants visited, diabetes in 2% and TB symptoms in 17%. Among others symptoms explored, muscle and joint pain/fatigue resulted in being the most frequent, and was reported by 34% of the migrants, followed by cough (10%). Significant predictors of muscle and joint pain/fatigue were: low BMI values (OR = 1.32; 95% CI 1.19–1.99), the absence of education (OR = 1.85; 95% CI 1.02–2.95), being employed with a regular contract (OR = 2.64; 95% CI 2.39–2.83) and living in the ghettos since >12 months (OR = 1.74; 95% CI 1.24–2.21). Conclusions: Our experience suggests that, in this population, the health condition is mainly linked to the specific working activities in the agricultural fields, as well as to the hygienic and living conditions, and that all of this is due to the lack of social protection in their life and job

Rassegna storica salernitana. N.s. A.11, n.2(1994)

La Società Salernitana di Storia Patria aderisce al progetto EleA e autorizza la pubblicazione del fascicoloN.s. A.11, n.2(1994): Spinelli, E., La Certosa di Padula: gli scribi e i libri (secc.XIV-XVI), P. 5 ; Senatore, F., Il Principato di Salerno durante la guerra dei baroni (1460-63). Dai carteggi diplomatici al «De bello Neapolitano», P. 29 ; Esposito, L.G., I Domenicani a Salerno in una relazione del 1650, P. 115 ; Musi, A., Le piccole e medie città nella storia moderna del Mezzogiorno continentale, P. 145 ; Pelizzari, M.R., Per una storia della quotidianità: vita di piazza nel Mezzogiorno moderno, P. 165 ; Avino, L., La cappella della Purificazione. Lavori in marmo perla Cattedrale di Salerno nel sec. XVIII, P. 185 ; Gallo, I., Eros nell'antica Pompei, P. 203 ; Delogu, P., La conquista dell'Italia Meridionale come ideologiastoriografica, P. 211 ; Chiappinelli, L., Spigolature dialettali e toponomastiche, P. 223 ; Currò, C., Storia curiosa del Quattrocento ebolitano, P. 229 ; Boni, V., Su una raffigurazione di Salerno nella cartografiadi Piri Reis, P. 237 ; Bruno, L., Prerrolini a Salerno, P. 243 ; Galasso, G., L'inquietudine nella storia, P. 249 ; Esposito P., Il Convegno lucreriano di Sarno (25 e 26 febbraio 1994), P. 261 ; Falanga, L., La rivincita di Paolo De Matteis, P. 265 ; De Vita, A., Il Convegno di studi su «Enzio Cetrangolo: poesia e traduzione» (Vallo della Lucania, 3 ottobre 1994), P. 273 ; Pisapia, A., Il territorio de «La cava» prima e dopo la Bolla di Bonifacio IX (1394): pròfilo giuridico, economico, civile e religioso,(Cava dei Tirreni 6-8 ottobre 1994), P. 277 ; Currò, C., Geronimo Seripando e la Chiesa del suo tempo (nel V centenario della nascita) (Salerno 14-15 ottobre 1994), P. 281 ; D'Episcopo, F., La rivolta delle acque, P. 287.Sul recto del frontespizio: fasc. 22 della Nuova Serie (annata LIV dalla fondazione

Rassegna storica salernitana. N.s. A.12, n.1(1995)

La Società Salernitana di Storia Patria aderisce al progetto EleA e autorizza la pubblicazione del fascicoloN.S., A. 12, 1(1995): Cammarano A., Riflessi di latinità nella toponomastica dell'Agro Picentino, P. 9 ; Colapietra R., Uomini e cose del Regno di Napoli nell'operadi Torquato Tasso, P. 67 ; Achille Mango A., Gli Intrichi d'Amore, P. 145 ; D'Arienzo V., Alcuni aspetti dello Jus prohibendi del sale nel Regno di Napoli. La dogana del sale di Salerno tra XVI e XVIII secolo, P. 151 ; Musi A., La comunità greca di Napoli in età moderna, P. 185 ; Baldi A., “L'epitaffio” di Ponte Surdolo Cava de' Tirreni, P. 203 ; Addeo G., La stampa periodica della Repubblica partenopea:«Il Vero Repubblicano», P. 217 ; Zileri Dal Verme A., Il reclutamento dell'esercito napoletano durante il decennio napoleonico, P. 231 ; Sirago M., Il porto di Salerno nel «sistema» portuale del Regno meridionale in età moderna (1806-1861), P.285 ; Chiappinelli L., Spigolature dialettali e toponomastiche II, P.313 ; Currò C., Ancora sui tre Martiri Salernitani: alcune considerazioni, P. 319 ; Garzillo F., I Padri Osservanti, il culto e la Confraternita di S. Bernardino a Salerno: precisazioni storiche, P.335 ; Rossi L., Considerazioni sulla storiografia cilentana del Novecento, P. 347 ; Quagliariello E., Ricordo di Domenico Rea, P. 353 ; Gallo I., Pasolini a Salerno e la traduzione dell'Orestea, P. 359 ; Lorenzo Falanga L., I tesori dei D'Avalos (Mostra e Catalogo: Napoli, Castel Sant'Elmo), P.369 ; Di Guglielmo N., Il convegno nazionale di studi su «Francesco Tedesco e la politica nell'età giolittiana», P.375 ; Salvatore A., «Memoria delle origini e ibridazioni storico-culturali. Un secolo di migrazioni nel Vallo di Diano e nel Cilento», P.383.Sul recto del frontespizio: fasc. 23 della Nuova Serie (annata LV dalla fondazione

HIV-HCV Incidence in Low-Wage Agricultural Migrant Workers Living in Ghettos in Apulia Region, Italy: A Multicenter Cross Sectional Study

Migrant populations are more susceptible to viral hepatitis and HIV due to the epidemiology from their country of origin or their social vulnerability when they arrive in Europe. The aims of the study are to explore the incidence of HIV and HCV in low-wage agricultural migrant workers and their knowledge, attitude, and practice with regard to HIV and HCV, as well as their sexual behaviour and risk factors. As part of the mobile clinic services, we performed a screening campaign for HIV-HCV involving migrants living in three Apulian establishments. Results: Between January 2020 and April 2021, 309 migrants (n. 272, 88% male, mean age 28.5 years) were enrolled in the study. Most of the migrants interviewed (n = 297, 96%) reported a stopover in Libya during their trip to Italy. Only 0.9% (n. 3) of migrants reported having been tested for HCV, while 30.7% (n. 95) reported being tested for HIV. Furthermore, screening tests found four migrants (1.3%) to be HIV positive and nine (2.9%) to be HCV positive. The median knowledge score was 1 (IQR 0-3; maximum score: 6 points) for HCV and 3 (IQR 1-4; maximum score: 7 points) for HIV and low use of condoms was 5% (n. 16), while more than 95% show an attitude score of 5 (IQR 5-6; maximum score:6 points) on HIV-HCV education campaigns. In a multivariate analysis, being male (OR = 1.72; 95% CI 1.28–1.92), being single (OR = 1.63; 95% CI 1.20–2.03), being of low educational status (OR = 2.09; 95% CI 1.29–2.21), living in shantytowns for >12 months (OR = 1.95; 95% CI 1.25–2.55), and originating from the African continent (OR = 1.43; 95% CI 1.28–2.01) are significant predictors of poor knowledge on HCV. Our data show low knowledge, especially of HCV, confirming migrants as a population with a higher risk of infection. To develop education programmes, integrated care and screening among migrants could be an effective strategy, considering the high attitude toward these items shown in our study