Current emerging SARS-CoV-2 pandemic: Potential direct/indirect negative impacts of virus persistence and related therapeutic drugs on the aquatic compartments.

The purpose of the present work is to provide a complete overview of possible direct/indirect implications on the quality of aquatic compartments due to the recent SARS-CoV-2 outbreak. With this aim, the environmental impacts are mainly related to i) the virus persistence in sewage and wastewaters, and ii) possible fate in aquatic compartments of drugs tested and administered to SARS-CoV-2 infected patients. Because SARS-CoV-2 spread is very recent, and there is a lack of specific studies on this strain, the virus persistence in wastewaters, the parameters influencing the persistence, as well as the detection methodologies are referenced to the general coronaviruses group. However, the present detailed report of up-to-date knowledge on this topic can provide a useful source for further studies focusing on more deepened investigations of SARS-CoV-2 behaviour in the environment. Such a perspective is significant not only for the control of virus diffusion but also represents a crucial point for the identification of produced alteration to the environmental quality.

Contraception during Coronavirus-Covid 19 pandemia. Recommendations of the Board of the Italian Society of Contraception.

Purpose: The Italian Society of Contraception identified as one of its priorities the need to give recommendations on management of contraception during Coronavirus-Covid 19 pandemiaMaterials and methods: A concise communication was produced which summarises in an easy-to-read format suitable for clinicians the management of the different contraceptives mostly used. Information how to manage contraception in different conditions is presented.Results: Women may, in general, continue to use either intrauterine and or hormonal contraceptives. The use of condom should be added to any hormonal contraceptive, when the contraceptive efficacy is reduced or when women stop the contraceptive method.Conclusion: At the present time, during the Coronavirus-Covid 19 pandemia, no data contraindicate the use of intrauterine or hormonal contraceptives. Conversely the use of an appropriate contraception is advocate to prevent unintended pregnancies.

Acquired neuromyotonia in thymoma-associated myasthenia gravis: a clinical and serological study.

BACKGROUND AND PURPOSE: Acquired neuromyotonia can occur in patients with thymoma, alone or in association with myasthenia gravis (MG), but the clinical prognostic significance of such comorbidity is largely unknown. The clinico-pathological features were investigated along with the occurrence of neuromyotonia as predictors of tumour recurrence in patients with thymoma-associated myasthenia. METHODS: A total number of 268 patients with thymomatous MG were studied retrospectively. Patients with symptoms of spontaneous muscle overactivity were selected for autoantibody testing using immunohistology for neuronal cell-surface proteins and cell-based assays for contactin-associated protein 2 (CASPR2), leucine-rich glioma inactivated 1 (LGI1), glycine receptor and Netrin-1 receptor antibodies. Neuromyotonia was diagnosed according to the presence of typical electromyography abnormalities and/or autoantibodies against LGI1/CASPR2. RESULTS: Overall, 33/268 (12%) MG patients had a thymoma recurrence. Five/268 (2%) had neuromyotonia, four with typical autoantibodies, including LGI1 (n = 1), CASPR2 (n = 1) or both (n = 2). Three patients had Netrin-1 receptor antibodies, two with neuromyotonia and concomitant CASPR2+LGI1 antibodies and one with spontaneous muscle overactivity without electromyography evidence of neuromyotonia. Thymoma recurrence was more frequent in those with (4/5, 80%) than in those without (28/263, 10%, P < 0.001) neuromyotonia. Neuromyotonia preceded the recurrence in 4/5 patients. In univariate analysis, predictors of thymoma recurrence were age at thymectomy [odds ratio (OR) 0.95, 95% confidence interval (CI) 0.93-0.97], Masaoka stage ≥IIb (OR 10.73, 95% CI 2.38-48.36) and neuromyotonia (OR 41.78, 95% CI 4.71-370.58). CONCLUSIONS: De novo occurrence of neuromyotonia in MG patients with previous thymomas is a rare event and may herald tumour recurrence. Neuronal autoantibodies can be helpful to assess the diagnosis. These observations provide pragmatic risk stratification for tumour vigilance in patients with thymomatous MG.

Contraceptive use and sexual function: a comparison of Italian female medical students and women attending family planning services.

Objectives: The aims of the study were to understand how education relates to contraceptive choice and how sexual function can vary in relation to the use of a contraceptive method.Methods: We surveyed female medical students and women attending a family planning service (FPS) in Italy. Participants completed an online questionnaire which asked for information on sociodemographics, lifestyle, sexuality and contraceptive use and also included items of the Female Sexual Function Index (FSFI).Results: The questionnaire was completed by 413 women (362 students and 51 women attending the FPS) between the ages of 18 and 30 years. FSFI scores revealed a lower risk of sexual dysfunction among women in the control group who did not use oral hormonal contraception. The differences in FSFI total scores between the two study groups, when subdivided by the primary contraceptive method used, was statistically significant (p < 0.005). Women using the vaginal ring had the lowest risk of sexual dysfunction, compared with all other women, and had a positive sexual function profile. In particular, the highest FSFI domain scores were lubrication, orgasm and satisfaction, also among the control group. Expensive contraception, such as long-acting reversible contraception, was not preferred by this young population, even though such methods are more contemporary and manageable. Compared with controls, students had lower compliance with contraception and a negative attitude towards voluntary termination of pregnancy.Conclusion: Despite their scientific knowledge, Italian female medical students were found to need sexual and contraceptive assistance. A woman's sexual function responds to her awareness of her body and varies in relation to how she is guided in her contraceptive choice. Contraceptive counselling is an excellent means to improve female sexuality.

Polymicrobial antibiofilm activity of the membranotropic peptide gH625 and its analogue.

This work illustrates a new role for the membranotropic peptide gH625 and its derivative gH625-GCGKKK in impairing formation of polymicrobial biofilms. Mixed biofilms composed of Candida and bacterial species cause frequently infections and failure of medical silicone devices and also show a major drug resistance than single-species biofilms. Inhibition and eradication of biofilms were evaluated by complementary methods: XTT-reduction, and crystal violet staining (CV). Our results indicate that gH625-GCGKKKK, better than the native peptide, strongly inhibited formation of mixed biofilms of clinical isolates of C. tropicalis/S. marcescens and C. tropicalis/S. aureus and reduced the biofilm architecture, interfering with cell adhesion and polymeric matrix, as well as eradicated the long-term polymicrobial biofilms on silicone surface.

Pazopanib in advanced vascular sarcomas: an EORTC Soft Tissue and Bone Sarcoma Group (STBSG) retrospective analysis.

BACKGROUND: Pazopanib is a multitargeted tyrosine kinase inhibitor approved for the treatment of patients with selective subtypes of advanced soft tissue sarcoma (STS) who have previously received standard chemotherapy including anthracyclines. Data on the efficacy in vascular sarcomas are limited. The main objective of this study was to investigate the activity of pazopanib in vascular sarcomas. PATIENTS AND METHODS: A retrospective study of patients with advanced vascular sarcomas, including angiosarcoma (AS), epithelioid hemangioendothelioma (HE) and intimal sarcoma (IS) treated with pazopanib in real life practice at EORTC centers as well as patients treated within the EORTC phase II and III clinical trials (62043/62072) was performed. Patient and tumor characteristics were collected. Response was assessed according to RECIST 1.1. and survival analysis was performed. RESULTS: Fifty-two patients were identified, 40 (76.9%), 10 (19.2%) and two (3.8%) with AS, HE and IS, respectively. The response rate was eight (20%), two (20%) and two (100%) in the AS, HE and IS subtypes, respectively. There was no significant difference in response rate between cutaneous and non-cutaneous AS and similarly between radiation-associated and non-radiation-associated AS. Median progression-free survival (PFS) and median overall survival (OS; from commencing pazopanib) were three months (95% CI 2.1-4.4) and 9.9 months (95% CI 6.5-11.3) in AS, respectively. CONCLUSION: The activity of pazopanib in AS is comparable to its reported activity in other STS subtypes. In this study, the activity of pazopanib was similar in cutaneous/non-cutaneous and in radiation/non-radiation-associated AS. In addition, pazopanib showed promising activity in HE and IS, worthy of further evaluation.

Emerging Concern from Short-Term Textile Leaching: A Preliminary Ecotoxicological Survey.

Textile dyes and their residues gained growing attention worldwide. Textile industry is a strong water consumer potentially releasing xenobiotics from washing and rinsing procedures during finishing processes. On a decentralised basis, also final consumers generate textile waste streams. Thus, a procedure simulating home washing with tap water screened cotton textiles leachates (n = 28) considering physico-chemical (COD, BOD5, and UV absorbance) and ecotoxicological data (Daphnia magna, Pseudokirchneriella subcapitata and Lepidium sativum). Results evidenced that: (i) leachates presented low biodegradability levels; (ii) toxicity in more than half leachates presented slight acute or acute effects; (iii) the remaining leachates presented "no effect" suggesting the use of green dyes/additives, and/or well established finishing processes; (iv) no specific correlations were found between traditional physico-chemical and ecotoxicological data. Further investigations will be necessary to identify textile residues, and their potential interactions with simulated human sweat in order to evidence potential adverse effects on human health.

Electrochemotherapy in the Treatment of Cutaneous Metastases from Breast Cancer: A Multicenter Cohort Analysis.

BACKGROUND: The management of breast cancer (BC) skin metastases represents a therapeutic challenge. Electrochemotherapy (ECT) combines the administration of bleomycin with temporary permeabilization induced by locally administered electric pulses. Preliminary experience with ECT in BC patients is encouraging. METHODS: A total of 125 patients with BC skin metastases who underwent ECT between 2010 and 2013 were enrolled onto a multicenter retrospective cohort study. The treatment was administered following the European Standard Operative Procedures of Electrochemotherapy. Tumor response was clinically assessed adapting the Response Evaluation Criteria in Solid Tumors, and toxicity was evaluated according to Common Terminology Criteria for Adverse Events 4.0. Cox regression analysis was used to identify predictive factors. RESULTS: Response was evaluable in 113 patients for 214 tumors (median 1 per patient, range 1-3). The overall response rate after 2 months was 90.2 %, while the complete response (CR) rate was 58.4 %. In multivariate analysis, small tumor size (P < 0.001), absence of visceral metastases (P = 0.001), estrogen receptor positivity (P = 0.016), and low Ki-67 index (P = 0.024) were significantly associated with CR. In the first 48 h, 10.4 % of patients reported severe skin pain. Dermatologic toxicity included grade 3 skin ulceration (8.0 %) and grade 2 skin hyperpigmentation (8.8 %). Tumor 1-year local progression-free survival was 86.2 % (95 % confidence interval 79.3-93.8) and 96.4 % (95 % confidence interval 91.6-100) in the subgroup of those with CR. CONCLUSIONS: In this study, small tumor size, absence of visceral metastases, estrogen receptor positivity, and low Ki-67 index were predictors of CR after ECT. Patients who experienced CR had durable local control. ECT represents a valuable skin-directed therapy for selected patients with BC.

Degradation and toxicity assessment of the nonionic surfactant Triton™ X-45 by the peroxymonosulfate/UV-C process.

The degradation and mineralization of the nonionic surfactant octylphenol ethoxylate (OPEO), commercially known as Triton™ X-45, by the peroxymonosulfate (PMS)/UV-C process were investigated. Three different toxicity tests (Daphnia magna, Vibrio fischeri and Pseudokirchneriella subcapitata) as well as the Yeast Estrogen Screen (YES) bioassay were undertaken to evaluate the potential toxic and estrogenic effects of OPEO and its oxidation products. OPEO removal was very fast and complete after 7 min via PMS/UV-C treatment under the investigated reaction conditions (OPEO = 20 mg L(-1) (47 µM); TOC = 12 mg L(-1); PMS = 2.5 mM; initial reaction pH = 6.5; applied UV-C dose = 21 Wh L(-1)). TOC removal also proceeded rapidly; a gradual decrease was observed resulting in an overall TOC removal of 84%. The toxic responses of PMS/UV-C treated OPEO solutions varied according to the test organism used in the bioassay. Daphnia magna was found to be most sensitive to aqueous OPEO, whereas Pseudokirchneriella subcapitata appeared to be the least sensitive one. Daphnia magna and Vibrio fischeri tests revealed that the inhibitory effect of OPEO decreased significantly during the course of treatment. On the other hand, PMS/UV-C oxidation products exhibited a high toxic effect towards Pseudokirchneriella subcapitata (around 60%). YES test results underlined the need for improving the PMS/UV-C treatment performance to remove the estrogenic activity of OPEO and its oxidation products.

An assessment of contamination of the Fusaro Lagoon (Campania Province, southern Italy) by trace metals.

The Fusaro Lagoon is a shallow lagoon, located in SW Italy, largely influenced in the last decades by several anthropic impacts. The study examined the pollution status of the lagoon, during year 2011-2012 at nine sampling stations with the aim to find out proper measurements of water lagoon restoration. Concentrations of heavy metals (HMs) (aluminium [Al], barium [Ba], cadmium [Cd], copper [Cu], iron [Fe], manganese [Mn], vanadium [V] and zinc [Zn]) were examined in water, sediments and specimens of the ascidian Ciona intestinalis sp. A. Low levels of dissolved oxygen concentration were detected at many stations, with mean values of 5.2-6.4 mg L(-1). The redox potential of surface waters was also low, -2.7 to 50.7 mV. Sediments possessed high organic matter content, 17.7-29.4%. In sediments, the mean Zn level, 251.4 mg kg(-1), was about sixfold higher than that recorded in year 2000 (38.5 mg kg(-1)) and considerably higher than that recorded in 2007 (191 mg kg(-1)). The mean levels of Cd were outstandingly high, with a mean value of 70.5 mg kg(-1), about 30- and 50-fold higher than those determined in 2000 and 2007, respectively. Cadmium (Cd), Cu and nickel (Ni) appeared in excess with respect to most current guidelines, reaching significant pollution levels. C. intestinalis sp. A was detected only at few stations, with metals accumulated preferentially in the body in respect to the tunic, from 1.2 times for Zn (178 mg kg(-1)) to 4.0 times for V (304 mg kg(-1)). Data suggests the necessity of an immediate action of eco-compatible interventions for environmental restoration.

Acetylcholinesterase inhibitors are ineffective in MuSK-antibody positive myasthenia gravis: Results of a study on 202 patients.

BACKGROUND: Myasthenia gravis (MG) with MuSK antibodies (MuSK-MG) represents a distinct subtype with different responses to treatments compared to patients with AChR antibodies, especially in terms of tolerance to acetylcholinesterase inhibitors (AChEI). However, AChEI are often used as first line symptomatic treatment in MuSK-MG, despite reports that they are poorly tolerated, seldom effective or even deleterious. METHODS: We analyzed demographic, clinical and therapeutic responses and side-effects in the large cohort of 202 MuSK-MG patients cared for at the MG Clinic of Azienda Ospedaliero-Universitaria Pisana. RESULTS: 165 patients had received AChEI at first evaluation. Only 7/165 patients (4.2%) reported an initial clinical benefit. Conversely, 76.9% of patients reported at least one side effect, most commonly neuromuscular hyperexcitability (68.4%), gastrointestinal (53.9%) and neurovegetative (35.8%) disturbances. 56 (33.9%) patients reported a concomitant worsening of muscle weakness and twelve patients (7.3%) suffered a cholinergic crisis. According to these patients, the severity of cholinergic side effects was greater at higher doses of AChEI, but side effects occurred regardless of the dose administered and ceased once the drug was discontinued. CONCLUSIONS: This is the largest population of MuSK-MG patients reported for perceived responsiveness and tolerance to AChEI treatment. Our obervations strongly suggest avoiding this treatment in MuSK-MG.

Efficacy and safety of ipilimumab in patients with pre-treated, uveal melanoma.

BACKGROUND: Patients with advanced uveal melanoma have a poor prognosis and limited treatment options. Ipilimumab is approved for pre-treated adult patients with advanced melanoma. However, because previous clinical trials with ipilimumab have excluded patients with uveal melanoma, data in this patient population are limited. PATIENTS AND METHODS: Pre-treated patients with advanced uveal melanoma received ipilimumab 3 mg/kg through an expanded access programme, every 3 weeks for four doses. Tumour assessments were conducted at baseline and after completion of treatment and patients were monitored throughout for adverse events. RESULTS: Among 82 assessable patients, 4 (5%) had an immune-related objective response and 24 (29%) had immune-related stable disease lasting ≥3 months for an immune-related disease control rate of 34%. With a median follow-up of 5.6 months, median overall survival (OS) was 6.0 months and median progression-free survival (PFS) was 3.6 months. The 1-year rates of OS and PFS were 31% and 11%, respectively. The safety profile of ipilimumab was similar to that in patients with cutaneous melanoma. CONCLUSIONS: These data suggest ipilimumab 3 mg/kg is a feasible option in pre-treated patients with metastatic uveal melanoma. Evidence of disease control and a 1-year survival rate of 31% indicate the need for further investigation in randomised, controlled trials to determine the optimal timing and use of ipilimumab in this patient population.

A holistic picture of spatial distribution of river polluting loads in a highly anthropized area.

For many years, there has been a debate on the polluting loads affecting the Gulf of Naples, one of Italy's most spectacular and iconic landscape. The wide territory bordering the Gulf includes the Sarno river basin (SRB) managed by the Southern Apennines River Basin District Authority in the framework of Unit of Management Sarno (UoM-Sarno). The paper investigated the anthropogenic pressures and their spatial distribution in the UoM-Sarno, revealing as SRB represents a hotspot of pollution mainly due to the high population density and widespread hydro-demanding activities which are responsible of high organic and eutrophication loads. The pollution sources, variably distributed on the area, and potentially conveyed to the wastewater treatment plants (WWTPs) located into SRB, were estimated considering the WWTPs treatment capacity as well. Results revealed a holistic picture of UoM-Sarno area allowing to establish the priorities of the interventions aimed at safeguarding the coastal marine resources. In particular, 2590 tons BOD/year were directly discharged into the Gulf of Naples due to the missing of sewers, and other 10,600 tons BOD/year are potentially discharged in the Sarno river reaching the sea, considering the contribution of population, industrial activity, and livestock.

Multigenerational tests on Daphnia spp.: a vision and new perspectives.

Multigenerational toxicity testing is a valuable tool for understanding the long-term effects of contaminants on aquatic organisms. This review focuses on the use of multigenerational tests with Daphnia, a widely used model organism in aquatic toxicological studies. The review highlights the importance of studying multiple generations to assess Daphnia spp. reproductive, growth, and physiological responses to various contaminants. We discuss the outcomes of multigenerational tests involving different contaminants, including nanoparticles, pesticides, and pharmaceuticals. The results reveal that multigenerational exposure can lead to transgenerational effects, where the impacts of contaminants are observed in subsequent generations even after the initial exposure has ceased. These transgenerational effects often manifest as reproduction, growth, and development alterations. Furthermore, we emphasize the need for standardized protocols in multigenerational testing to ensure comparability and reproducibility of results across studies. We also discuss the implications of multigenerational testing for ecological risk assessment, as it provides a more realistic representation of the long-term effects of contaminants on populations and ecosystems. Overall, this review highlights the significance of multigenerational tests with Daphnia in advancing our understanding of the ecological impacts of contaminants. Such tests provide valuable insights into the potential risks associated with long-term exposure to pollutants and contribute to the development of effective mitigation strategies for aquatic ecosystems.

Environmental microbial contamination in dental setting: a local experience.

INTRODUCTION: Patients and operators are exposed during dental practice to an infective risk, which derives especially from microorganisms suspended in aerosols. Environmental microbiological monitoring in dental settings represents a good instrument to detect critical situations. METHODS: In order to investigate environmental microbial contamination level in a local reality, we analyzed water, air and surfaces samples of a community-based dental facility by using protocol and threshold values proposed in a recent multicenter study carried out by the Italian Society of Hygiene, Preventive Medicine and Public Health (S.It.I.) working group "Hygiene in Dentistry". Microbial contamination was assessed in the same room for 4 non-consecutive weeks during all the five working days, before and at the end of the daily activity. Air was sampled also during clinical activity, through both active and passive sampling systems. RESULTS: Contamination of water showed a decrease during activities, while a decrease in air contamination was registered only at the end of the day. Passive sampling values resulted more often above threshold values adopted. At the same time, surfaces contamination increases at the end of the activity. It seems that in the dental clinic analyzed microbial buildup represents the higher critical element. No differences have been registered among the different days of the week. DISCUSSION: Our study highlights the need to improve disinfection procedures and air treatment systems in the considered environment. Microbiological monitoring could represent an important element to detect the presence of risk factors and to adopt control measures.

Central nervous system failure in melanoma patients: results of a randomised, multicentre phase 3 study of temozolomide- and dacarbazine- based regimens.

BACKGROUND: This study compared the central nervous system (CNS) metastasis incidence between a temozolomide- and a dacarbazine-based regimen in untreated stage IV melanoma patients. METHODS: A total of 150 patients were randomly assigned to receive either oral temozolomide (200 mg m(-2) per day; days 1-5) or intravenous dacarbazine (800 mg m(-2); day 1), in combination with intravenous cisplatin (75 mg m(-2); day 1) and subcutaneous interleukin-2 (3 MU twice daily; days 9-18), every 28 days (CTI and CDI). RESULTS: A total of 149 patients were eligible for an intention-to-treat analysis (CTI: n=74, CDI: n=75). The 1-year cumulative CNS incidence failure was 20.6% for CTI and 31.1% for CDI (P=0.22). In all 24 patients in CTI (32%) and 34 (45%) in CDI developed CNS metastases; 31 patients died of early systemic progression, before CNS evaluation. Median survival time was 8.4 months in the CTI and 8.7 in the CDI arm; in patients with CNS metastases the median survival time was 13.5 months in the CTI and 11.5 in the CDI arm. No difference in toxicity was observed between the two arms. CONCLUSION: The incidence of CNS failures in metastatic melanoma was not significantly reduced and the clinical course was not modified substituting a dacarbazine-based regimen with a temozolomide-based regimen. Patients who developed CNS metastases did not have a worse prognosis than patients progressing in other sites and should not be excluded from new investigational studies.

Comparison of in situ sediment remediation amendments: Risk perspectives from species sensitivity distribution.

Contaminated sediment is a major issue for aquatic environments, but attention must be kept even during remediation activities that can negatively affect resident biota especially when applied in situ. For the first time, the species sensitivity distribution (SSD) approach was applied to amendments used for in situ sediment remediation considering 39 papers including both freshwater (F) and saltwater (S) effect data (i.e. n = 17 only F, n = 19 only S, and n = 3 both F and S). Toxicity data related to the application of activated carbon (AC), nano-Zero-Valent-Iron (nZVI), apatite (A), organoclay (OC) and zeolite (Z) were collected and analyzed. SSD curves were constructed by lognormal model providing comprehensive comparisons of the sensitivities of different species to the relative testing methods. Results indicated that Bacteria were the most sensitive group of testing organisms, while Crustaceans were the less sensitive. The hazardous concentration for 5% of the affected species (HC5) were derived to determine the concentration protecting 95% of the species. OC, A and Z presented both acute and chronic toxicity. The HC5 values in descending order are: AC (4.79 g/L) > nZVI (0.02 g/L) > OC, A and Z (1.77E-04 g/L). AC and nZVI can be considered safer than OC, A and Z in sediment remediation activities, even if in situ long-term effects remained still underexplored.