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Optimizing high-productivity farming techniques trough mechanization and lower workforce input in terraced olive groves is helpful to preserve local olive oil production, reducing costs and preserving ecosystem functionality. However, efficient work organisation should be provided. Moreover, mechanization can affect environmental sustainability. In this paper operative, economic and environmental performances of four olive harvesting techniques are reported; experimentations were performed in an olive grove in the Sorrento Peninsula (NA) during 2022–2023 productive seasons. Mechanized techniques (Harvesting technique 1 and Harvesting technique 4) performed highest working capacities (159.01 kg h−1 and 200.51 kg h−1) and the lowest unitary costs (630.00 € ha−1 for Harvesting technique 2 and 840.00 € ha−1 for harvesting technique 4), whereas environmental performances were the worst (266.30 kg CO2 eq and 252.59 kg CO2 eq) due to diesel intakes. Thus, their applications are helpful, but morphological or agronomic boundaries may affect their effectiveness in other areas. Among aided methods, Harvesting technique 1 overcame Harvesting technique 3 in any aspect (91.01 kg h−1 vs 76.13 kg h−1: 1822.09 € ha−1 vs 2793.80 € ha−1; 33.01 kg CO2 eq vs 127.21 kg CO2 eq); the absence of diesel inputs in harvesting technique 1 and its superior work capacity explain the environmental impact differences. Thus, the former may be adopted in farms where slope and irregular shape hinder mechanized harvest. Life Cycle Assessment dataset may be helpful to perform similar analysis in other Italian olive oil supply chains.

Objective: The aim of our study was to evaluate the long-term efficacy and safety of mexiletine in 112 patients affected by genetically confirmed non-dystrophic myotonias. The study was performed at the Neurophysiologic Division of Fondazione Policlinico Universitario A. Gemelli Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS), Rome and the Children's Hospital Bambino Gesù, Rome.Methods: The treatment was accepted by 59 patients according to clinical severity, individual needs, and concerns about a chronic medication. Forty-three patients were affected by recessive congenita myotonia, 11 by sodium channel myotonia, and five by dominant congenital myotonia. They underwent clinical examination before and after starting therapy, and Electromyography (EMG). A number of recessive myotonia patients underwent a protocol of repetitive nerve stimulations, for detecting and quantifying the transitory weakness, and a modified version of the Timed Up and Go test, to document and quantify the gait impairment.Results: Treatment duration ranged from 1 month to 20 years and the daily dosages in adults ranged between 200 and 600 mg. No patient developed cardiac arrhythmias causing drug discontinuation. Mexiletine was suspended in 13 cases (22%); in three patients, affected by Sodium Channel myotonia, because flecainide showed better efficacy; in one patient because of a gastric cancer antecedent treatment; in four patients because of untreatable dyspepsia; and five patients considered the treatment not necessary.Conclusions: In our experience, mexiletine is very useful and not expensive. We did not observe any hazarding cardiac arrhythmias. Dyspepsia was the most frequent dose-limiting side effect.

According to the Regulation (EC) N. 141/2000 of the European Parliament and of the Council, rare diseases are life-threatening or chronically debilitating conditions, affecting no more than 5 in 10 000 persons in the European Community. It is estimated that between 6000 to 8000 distinct rare diseases affect up to 6% of the total EU population. Therefore, these conditions can be considered rare if taken individually but they affect a significant proportion of the European population when considered as a single group. Several initiatives have been undertaken at international, European and national level to tackle public health as well as research issues related to the prevention, diagnosis, treatment and surveillance of these diseases. The development of innovative and effective medical products for their diagnosis and treatment is frequently hampered by several factors, including the limited knowledge of their natural history, the difficulties in setting up clinical studies due to the limited numbers of patients affected by a specific disease, the weak interest of sponsors due to the restricted market opportunities. Therefore, incentives and other facilitations have been adopted in many parts of the world, including in the EU, in order to facilitate the development and commercialization of diagnostic tools and treatments devoted to rare diseases. This paper illustrates mainly the European initiatives and will discuss the problematic and controversial aspects surrounding orphan drugs. Finally, activities and measures adopted in Italy are presented.

The PuÁ¡n district in the southwest of the province of Buenos Aires covers an area of 6,385 km2 (2,465 mi2) and has a population of about 18,000 residing in small urban centers and rural areas where farming is the main economic activity. Owing to the absence of freshwater streams and the low level of rainfall, groundwater provides the principal source of water and is used for human and animal consumption, as well as for the growing network of supplementary irrigation. This paper gives an overview of the district's water resources by reporting on the landscape, surface runoff, and groundwater quality within the framework of six geomorphological environments. Groundwater depth, anion-cation content and principal pollutants are measured in representative samples from each geomorphological unit. Pollutants are divided into those of natural origin (arsenic-boron-fluoride) and those induced by anthropic activity. The results obtained provide a basis for the adequate planning of water management, taking into account the consequences of groundwater exploitation and the implementation of preventive measures where necessary. [ABSTRACT FROM AUTHOR]

The study investigated the application of Wastewater-Based Epidemiology (WBE) as a tool for monitoring the SARS-CoV-2 prevalence in a city in northern Italy from October 2021 to May 2023. Based on a previously used deterministic model, this study proposed a variation to account for the population characteristics and virus biodegradation in the sewer network. The model calculated virus loads and corresponding COVID-19 cases over time in different areas of the city and was validated using healthcare data while considering viral mutations, vaccinations, and testing variability. The correlation between the predicted and reported cases was high across the three waves that occurred during the period considered, demonstrating the ability of the model to predict the relevant fluctuations in the number of cases. The population characteristics did not substantially influence the predicted and reported infection rates. Conversely, biodegradation significantly reduced the virus load reaching the wastewater treatment plant, resulting in a 30% reduction in the total virus load produced in the study area. This approach can be applied to compare the virus load values across cities with different population demographics and sewer network structures, improving the comparability of the WBE data for effective surveillance and intervention strategies.

Mucopolysaccharidoses (MPSs) are lysosomal disorders with neurological involvement for which no cure exists. Here, we show that recombinant NK1 fragment of hepatocyte growth factor rescues substrate accumulation and lysosomal defects in MPS I, IIIA and IIIB patient fibroblasts. We investigated PI3K/Akt pathway, which is of crucial importance for neuronal function and survival, and demonstrate that PI3K inhibition abolishes NK1 therapeutic effects. We identified that autophagy inhibition, by Beclin1 silencing, reduces MPS IIIB phenotype and that NK1 downregulates autophagic-lysosome (ALP) gene expression, suggesting a possible contribution of autophagosome biogenesis in MPS. Indeed, metabolomic analyses revealed defects of mitochondrial activity accompanied by anaerobic metabolism and inhibition of AMP-activated protein kinase (AMPK), which acts on metabolism and autophagy, rescues lysosomal defects. These results provide insights into the molecular mechanisms of MPS IIIB physiopathology, supporting the development of new promising approaches based on autophagy inhibition and metabolic rewiring to correct lysosomal pathology in MPSs., Competing Interests: Luigi Michele Pavone has licensed compositions comprising hepatocyte growth factor or variants thereof for use in the treatment of mucopolysaccharidoses (granted Italian patent MI2014A001454)., (© 2024 The Author(s).)

Background: Lung cancer is the leading cause of death worldwide. The treatment choice for advanced stage of lung cancer may depend on histotype, performance status (PS), age, and comorbidities. In the present study, we focused on the effect of metronomic vinorelbine treatment in elderly patients with advanced unresectable non-small cell lung cancer (NSCLC)., Methods: From January 2016 to December 2016, 44 patients affected by non-small cell lung cancer referred to our oncology day hospital were progressively analyzed. The patients were treated with oral vinorelbine 30 mg x 3/wk or 40 mg x 3/wk meaning one day on and one day off. The patients were older than 60, stage IIIB or IV, ECOG PS ≥ 1, and have at least one important comorbidity (renal, hepatic, or cardiovascular disease). The schedule was based on ECOG-PS and comorbidities. The primary endpoint was progression-free survival (PFS). PFS was used to compare patients based on different scheduled dosage (30 or 40 mg x3/weekly) and age (more or less than 75 years old) as exploratory analysis. We also evaluated as secondary endpoint toxicity according to Common Toxicity Criteria Version 2.0., Results: Vinorelbine showed a good safety profile at different doses taken orally and was effective in controlling cancer progression. The median overall survival (OS) was 12 months. The disease control rate (DCR) achieved 63%. The median PFS was 9 months. A significant difference in PFS was detected comparing patients aged below with those over 75, and the HR value was 0.72 (p<0.05). Not significant was the difference between groups with different schedules., Conclusions: This study confirmed the safety profile of metronomic vinorelbine and its applicability for patients unfit for standard chemotherapies and adds the possibility of considering this type of schedule not only for very elderly patients.

Background: Influenza virus (IFV) infection is associated with increased morbidity and mortality in people with underlying lung disease. Treatment options for IFV are currently limited and antiviral resistance is a growing concern. DAS181, an inhaled antiviral with a unique mechanism of action, has shown promise in early clinical trials involving generally healthy human subjects. This study was undertaken to assess the safety and tolerability of DAS181 in individuals with underlying reactive airway disease., Methods: This was a randomized, double-blind, placebo-controlled, crossover phase 1 study of DAS181-F02. Dry particle inhaler administration of 10 mg was done on 3 consecutive days in ten adult volunteers with well-controlled asthma. The primary outcome was the frequency of adverse events (AEs), grade 1 or higher that occurred during each study period., Results: There were 280 AEs among ten evaluable subjects (56.8 % active; 43.2 % placebo); 90.7 % were grade 1. No grade 3 or higher AEs occurred. A statistically significant association between exposure to DAS181 and experiencing any AE, a grade 1 AE, or a grade 2 AE was not detected. Overall, the majority of AEs were classified as possibly related (35.7 %), unlikely related (38.9 %), or unrelated (15.4 %) to study drug administration. However, there was a statistically significant association between exposure to DAS181 and experiencing a definitely or probably related AE. Respiratory effects, including dyspnea, dry cough, and chest discomfort related to respirations, accounted for all of the definitely related AEs and one of the most common probably related AEs., Conclusions: DAS181 was safe in this small study of otherwise healthy subjects with well-controlled asthma. However, the generalizability of these results is limited by the small sample size and generally mild nature of the subjects' asthma at baseline. The increased association of respiratory events classified as probably or definitely related to DAS181 administration suggests caution may need to be employed when administering DAS181 to individuals with less stable reactive airway disease. Further investigation in a controlled setting of the safety and efficacy of DAS181 in a larger population of asthmatic subjects with varying disease activity is warranted., Trial Registration: ClinicalTrials.gov NCT01113034 Trial Registration Date: April 27, 2010.

Rheumatoid arthritis (RA) is an immune-mediated polyarthritis; currently no pathogenic agent has been identified as a disease trigger. A patient with RA, presumably caused by periodontal infection, whose remission has been observed after periodontitis treatment in absence of specific RA therapy, is reported here for the first time, to our knowledge. A 61-year-old male patient presented migrant arthritis associated with antibodies against citrullinated protein antigens positivity. The clinical features allowed to make RA diagnosis according to the 2010 European League against Rheumatism/American College of Rheumatology RA classification criteria. X-ray of the second upper molar showed chronic apical periodontitis. After its treatment, arthritis remission has been observed in the absence of specific RA therapy. It has been suggested that periodontitis may have a trigger role in RA pathogenesis. This could be explained by the enzymatic action of Porphyromonas gingivalis, probably leading to break tolerance to collagen. The identification and subsequent treatment of periodontitis should therefore be considered pivotal in RA prophylaxis and management.

The presence and spatial distribution of groundwater arsenic was evaluated in an area of approximately 6000 square kilometers that extends along the southeast border of the subhumid pampa plains of southeast Buenos Aires Province, Argentina. Groundwater constitutes the only easily exploitable source of water for the large rural and suburban population in the area, both for human consumption and for use in agricultural and livestock production. In the study area, 56.3 percent of water samples had seriously elevated arsenic levels (0.06 to 0.5 milligrams per liter [mg/L]), constituting a risk for human consumption and agricultural and livestock use. In 27.2 percent of the samples, arsenic content ranged from just below the World Health Organization-recommended maximum level of 0.01 mg/L to 0.05 mg/L. Only in 16.5 percent of the samples did the water contain no or very low concentrations. The contamination of domestic water supplies in the study area constitutes a serious water quality problem since this element has been identified as the cause of a number of health problems, including cancer.