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Abstract Epilepsy affects 1% of the general population and 30% of patients are resistant to antiepileptic drugs. Although optogenetics is an efficient antiepileptic strategy, the difficulty of illuminating deep brain areas poses translational challenges. Thus, the search of alternative light sources is strongly needed. Here, we develop pH-sensitive inhibitory luminopsin (pHIL), a closed-loop chemo-optogenetic nanomachine composed of a luciferase-based light generator, a fluorescent sensor of intracellular pH (E2GFP), and an optogenetic actuator (halorhodopsin) for silencing neuronal activity. Stimulated by coelenterazine, pHIL experiences bioluminescence resonance energy transfer between luciferase and E2GFP which, under conditions of acidic pH, activates halorhodopsin. In primary neurons, pHIL senses the intracellular pH drop associated with hyperactivity and optogenetically aborts paroxysmal activity elicited by the administration of convulsants. The expression of pHIL in hippocampal pyramidal neurons is effective in decreasing duration and increasing latency of pilocarpine-induced tonic-clonic seizures upon in vivo coelenterazine administration, without affecting higher brain functions. The same treatment is effective in markedly decreasing seizure manifestations in a murine model of genetic epilepsy. The results indicate that pHIL represents a potentially promising closed-loop chemo-optogenetic strategy to treat drug-refractory epilepsy.

Multiple myeloma (MM) progression is closely dependent on cells in the bone marrow (BM) microenvironment, including fibroblasts (FBs) and immune cells. In their BM niche, MM cells adhere to FBs sustaining immune evasion, drug resistance and the undetectable endurance of tumor cells known as minimal residual disease (MRD). Here, we describe the novel bi-specific designed ankyrin repeat protein (DARPin) α-FAPx4–1BB (MP0310) with FAP-dependent 4–1BB agonistic activity. The α-FAPx4–1BB DARPin simultaneously binds to FAP and 4–1BB overexpressed by activated FBs and immune cells, respectively. Although flow cytometry analysis showed that T and NK cells from MM patients were not activated and did not express 4–1BB, stimulation with daratumumab or elotuzumab, monoclonal antibodies (mAbs) currently used for the treatment of MM, significantly upregulated 4–1BB both in vitro and in MM patients following mAb-based therapy. The mAb-induced 4–1BB overexpression allowed the engagement of α-FAPx4–1BB that acted as a bridge between FAP+FBs and 4–1BB+NK cells. Therefore, α-FAPx4–1BB enhanced both the adhesion of daratumumab-treated NK cells on FBs as well as their activation by improving release of CD107a and perforin, hence MM cell killing via antibody-mediated cell cytotoxicity (ADCC). Interestingly, α-FAPx4–1BB significantly potentiated daratumumab-mediated ADCC in the presence of FBs, suggesting that it may overcome the BM FBs’ immunosuppressive effect. Overall, we speculate that treatment with α-FAPx4–1BB may represent a valuable strategy to improve mAb-induced NK cell activity fostering MRD negativity in MM patients through the eradication of latent MRD cells.

Abstract Green chemistry and engineering seek for maximizing efficiency and minimizing negative impacts on the environment and human health in chemical production processes. Driven by advances in the principles of environment protection and sustainability, these fields are expected to greatly contribute to achieving sustainable development goals. To this end, many studies have been conducted to develop new approaches within green chemistry and engineering. The Advances in Green Chemistry and Engineering Collection at Scientific Reports aims at gathering the latest research on developing and implementing the principles of green chemistry and engineering.

The conversion of levulinic acid (LA) into alkyl levulinates is highly significant due to the wide range of applications for these products, including their use as fuel additives, solvents, and fragrances. In order to meet the growing need for environmentally friendly chemical production, this study takes a circular economy approach by upcycling a common urban waste, i.e., pine needles, to synthesize a robust heterogeneous acid catalyst, subsequently used to efficiently upgrade LA into levulinates. By utilizing a single-step procedure under mild operating conditions, the resulting PiNe–SO3H catalyst demonstrated good performances and flexibility in synthesizing diverse bio-derived levulinates. In fact, the catalyst showed an exceptionally broad range of applicability, resulting in isolated yields ranging from ̴ 46% to ̴ 93%, which is an unprecedented achievement. The catalyst's ability to be reused was tested, revealing remarkable performance for up to 10 consecutive cycles with negligible loss in efficiency. Additionally, a significant focus was directed towards developing a method that minimizes waste during the isolation process. This involved optimizing reaction conditions and rationalizing work-up procedures, resulting in low Environmental factor (E-factor) values ranging from 1.2 to 8.9. To comprehensively assess the overall environmental sustainability of the process, various additional green metrics were calculated, and the Ecoscale tool was employed as well. Furthermore, mechanistic investigations elucidated the favored reaction pathway, underscoring that, under the optimized conditions, the prevailing mechanism entails direct esterification, as opposed to the generation of a pseudo-ester intermediate.

Soil microorganisms play a crucial role in maintaining soil fertility sensu lato. Sustainable soil management aims to make the soil environment more hospitable increasing microorganism diversity and complexity by means of the minimal disturbance of soil and inputs of organic material. This results in the effective functioning of agricultural systems, better crop productivity, and a reduction in environmental impacts. A study was carried out to evaluate the effects of the long-term application (more than 15 years) of sustainable practices versus conventional ones on soil microbial biomass activity and its functional diversity within different Mediterranean commercial fruit orchards located in Southern Italy. A preliminary survey—performed using the electromagnetic induction technique (EMI)—guided the collection of representative soil samples by reducing the spatial heterogeneity of soil microorganisms. Soil management practices, based on no tillage and the recycling of organic materials of different origins and quality produced within the orchard, increased soil organic carbon, telluric microorganisms activity and their functional diversity compared to ‘non-conservative’ management methods such as continuous tillage. In addition, the rational use of the orchard-inside organic matter (natural/seeded grass cover and pruning material) allowed it to virtuously transform from useless waste into precious resources, eliminating the logistical and economic constraints for their disposal. The simultaneous use of different types of soil management strategies aimed at soil conservation reinforced the positive effects on the microbiological indicators of soil quality rather than the application of a single strategy. This study provides the opportunity to represent what could be the possible evolution of tilled orchards towards more balanced soil conditions when subjected to conservative practices, offering a reference model for fruit growers and technicians who want to improve the stability and the resiliency of their agrosystems.

The advent of immunotherapy and antibody–drug conjugates (ADCs) have revolutionized breast cancer treatment, offering new hope to patients. However, challenges, such as resistance and limited efficacy in certain cases, remain. Recently, the combination of these therapies has emerged as a promising approach to address these challenges. ADCs play a crucial role by delivering cytotoxic agents directly to breast cancer cells, minimizing damage to healthy tissue and enhancing the tumor-killing effect. Concurrently, immunotherapies harness the body’s immune system to recognize and eliminate cancer cells. This integration offers potential to overcome resistance mechanisms and significantly improve therapeutic outcomes. This review explores the rationale behind combining immunotherapies with ADCs, recent advances in this field, and the potential implications for breast cancer treatment.

Hydrothermal carbonization (HTC) serves as a sustainable method to transform pine needle waste into nitrogen-doped (N-doped) hydrochars. The primary focus is on evaluating these hydrochars as catalytic electrodes for the oxygen reduction reaction (ORR) and carbon dioxide reduction reaction (CO2RR), which are pivotal processes with significant environmental implications. Hydrochars were synthesized by varying the parameters such as nitrogen loading, temperature, and residence time. These materials were then thoroughly characterized using diverse analytical techniques, including elemental analysis, density measurements, BET surface area analysis, and spectroscopies like Raman, FTIR, and XPS, along with optical and scanning electron microscopies. The subsequent electrochemical assessment involved preparing electrocatalytic inks by combining hydrochars with an anion exchange ionomer (AEI) to leverage their synergistic effects. To the best of our knowledge, there are no previous reports on catalytic electrodes that simultaneously incorporate both a hydrochar and AEI. Evaluation metrics such as current densities, onset and half-wave potentials, and Koutecky–Levich and Tafel plots provided insights into their electrocatalytic performances. Notably, hydrochars synthesized at 230 °C exhibited an onset potential of 0.92 V vs. RHE, marking the highest reported value for a hydrochar. They also facilitated the exchange of four electrons at 0.26 V vs. RHE in the ORR. Additionally, the CO2RR yielded valuable C2 products like acetaldehyde and acetate. These findings highlight the remarkable electrocatalytic activity of the optimized hydrochars, which could be attributed, at least in part, to their optimal porosity.

By exploiting the combined use of a heterogeneous recyclable palladium(II)-bis(N-heterocyclic carbene) catalyst and cyclopentyl methyl ether (CPME) as a convenient recoverable safer reaction medium, an effective waste-minimized approach has been developed for the intramolecular Pd-catalyzed C(sp3)-H activation of methyl pyrrole derivatives. This synthetic tools has allowed to access condensed N-heterocycles generally endowed with biological activities and representatively are the core motif of complex molecules such as Mitomycines and Tylophorines. The heterogeneous catalytic system could be recovered and reused up to representative five runs without any loss in efficiency. The target products (19 examples) have been obtained selectively and with excellent isolated yields up to 93%. The approach leads to the definition of a protocol with a very good E-factor (21) which is much lower (up to 98%) than those of comparable literature examples. Other green metrics have been calculated and the data collected demonstrate that our newly developed protocol is very promising in terms of its environmental impact profile.

Prostate cancer (PC) is the most common type of tumor in men. In the early stage of the disease, it is sensitive to androgen deprivation therapy. In patients with metastatic castration-sensitive prostate cancer (mHSPC), chemotherapy and second-generation androgen receptor therapy have led to increased survival. However, despite advances in the management of mHSPC, castration resistance is unavoidable and many patients develop metastatic castration-resistant disease (mCRPC). In the past few decades, immunotherapy has dramatically changed the oncology landscape and has increased the survival rate of many types of cancer. However, immunotherapy in prostate cancer has not yet given the revolutionary results it has in other types of tumors. Research into new treatments is very important for patients with mCRPC because of its poor prognosis. In this review, we focus on the reasons for the apparent intrinsic resistance of prostate cancer to immunotherapy, the possibilities for overcoming this resistance, and the clinical evidence and new therapeutic perspectives regarding immunotherapy in prostate cancer with a look toward the future.

IntroductionDelayed discharge represents the difficulty in proceeding with discharge of patients who do not have any further benefit from prolonged stay. A quota of this problem is related to organizational issues. In the Lazio region in Italy, a macro service re-organization in on the way, with a network of hospital and territorial centers engaged in structuring in- and out- of hospital patient pathways, with a special focus on intermediate care structures. Purpose of this study is to quantify the burden of delayed discharge on a single hospital structure, in order to estimate costs and occurrence of potential resource misplacement.Material and methodsObservational Retrospective study conducted at the Santo Spirito Hospital in Rome, Italy. Observation period ranged from 1/09/2022, when the local database was instituted, to 1/03/2023 (6 months). Data from admissions records was anonymously collected. Data linkage with administrative local hospital database was performed in order to identify the date a discharge request was fired for each admission. Surgical discharges and Intensive Care Unit (ICU) discharges were excluded from this study. A Poisson hierarchical regression model was employed to investigate for the role of ward, Severity of Disease (SoD) and Risk of Mortality (RoM) on elongation of discharge time.Results1222 medical ward admissions were recorded in the timeframe. 16% of them were considered as subject to potentially elongated stay, and a mean Delay in discharge of 6.3 days (SD 7.9) was observed.Discussion and conclusionsDelayed discharge may cause a "bottleneck" in admissions and result in overcrowded Emergency Department, overall poor performance, and increase in overall costs. A consisted proportion of available beds can get inappropriately occupied, and this inflates both direct and indirect costs. Clinical conditions on admission are not a good predictor of delay in discharge, and the root causes of this phenomenon likely lie in organizational issues (on structure\system level) and social issues (on patient's level).

Abstract In this study, Brillouin and Raman micro-Spectroscopy (BRamS) and Machine Learning were used to set-up a new diagnostic tool for Osteoarthritis (OA), potentially extendible to other musculoskeletal diseases. OA is a degenerative pathology, causing the onset of chronic pain due to cartilage disruption. Despite this, it is often diagnosed late and the radiological assessment during the routine examination may fail to recognize the threshold beyond which pharmacological treatment is no longer sufficient and prosthetic replacement is required. Here, femoral head resections of OA-affected patients were analyzed by BRamS, looking for distinctive mechanical and chemical markers of the progressive degeneration degree, and the result was compared to standard assignment via histological staining. The procedure was optimized for diagnostic prediction by using a machine learning algorithm and reducing the time required for measurements, paving the way for possible future in vivo characterization of the articular surface through endoscopic probes during arthroscopy.

Background: Wearable cardioverter-defibrillators (WCDs) are currently used in patients at temporarily heightened risk for sudden cardiac death (SCD) who are temporarily unable to receive an implantable cardioverter-defibrillator (ICD). WCD can safely record and terminate life-threatening arrhythmias through a non-invasive electrode-based system. The current clinical indications for WCD use are varied and keep evolving as experience with this technology increases. Methods: We reviewed and explored the data behind indications for WCD use and discuss its usefulness in congenital heart disease (CHD) patients. Results: We considered 8 consecutive patients (mean age 35.25 years, range 18–51 years, average duration of WCD use 4 months, range 3–6 months) with complex CHD, in which a WCD was used between June 2018 and January 2022. No sustained ventricular arrhythmias requiring shocks were recorded in the observation period. No inappropriate shocks were recorded. All the patients showed a good compliance and a very high mean wear time per day (21.2 ± 1 h a day). Four patients implanted a permanent device (3 CRT-D, 1 ICD), three underwent cardiac surgery at the end of the WCD period and one is still on the waiting list for the operation. Conclusions: Larger trial could confirm the possible conceivable benefit from an extended use of the WCD in certain populations with complex CHD as in our case series, especially in patients with life-treating ventricular arrhythmias waiting for surgery for residual cardiac defects or in the early phases following the surgical/hemodynamic interventions, patients with tachycardiomyopathy expected to improve after the arrhythmias are removed and patients awaiting implantation of an ICD at high risk due to active infection.

The brewing industry plays a significant role in producing a substantial annual volume of by-products, which contributes to the global accumulation of food waste. The primary by-product generated is brewer’s spent grain (BSG), a lignocellulosic biomass rich in proteins, fiber, and moisture content. Leveraging biorefining and valorization techniques for BSG represents a promising strategy to enhance sustainability, resilience, and circularity within the brewing chain. To date, most studies have focused on extracting proteins from BSG. Yet, it is crucial to note that the fiber part of BSG also holds considerable potential for biorefining processes. This study introduces a novel sequential extraction method designed to integrally recover the major components of BSG. Notably, it introduces a reactive extraction approach that enables the simultaneous extraction and tuneable functionalization of the hemicellulose component. Additionally, the study assesses the utility of the attenuated total reflection–Fourier transform infrared (ATR-FTIR) spectroscopy as a user-friendly tool to monitor and evaluate the effectiveness of the fractionation process. This spectroscopic technique can provide valuable insights into the changes and composition of BSG throughout the extraction process.

Abstract The pathophysiology of heart failure with preserved ejection fraction (HFpEF) is a matter of investigation and its diagnosis remains challenging. Although the mechanisms that are responsible for the development of HFpEF are not fully understood, it is well known that nearly 80% of patients with HFpEF have concomitant hypertension. We investigated whether early biochemical alterations were detectable during HFpEF progression in salt-induced hypertensive rats, using Fourier-transformed infrared (FTIR) and Raman spectroscopic techniques as a new diagnostic approach. Greater protein content and, specifically, greater collagen deposition were observed in the left atrium and right ventricle of hypertensive rats, together with altered metabolism of myocytes. Additionally, Raman spectra indicated a conformational change, or different degree of phosphorylation/methylation, in tyrosine-rich proteins. A correlation was found between tyrosine content and cardiac fibrosis of both right and left ventricles. Microcalcifications were detected in the left and right atria of control animals, with a progressive augmentation from six to 22 weeks. A further increase occurred in the left ventricle and right atrium of 22-week salt-fed animals, and a positive correlation was shown between the mineral deposits and the cardiac size of the left ventricle. Overall, FTIR and Raman techniques proved to be sensitive to early biochemical changes in HFpEF and preceded clinical humoral and imaging markers.

This paper aims to provide an evaluation of the environmental and economic aspects of strawberry cultivation in the Campania and Basilicata regions of Southern Italy, and to consider the effects on strawberry productivity following compost tea (CT) application. Eight strawberry-growing systems were tested. To this end, compost tea production and characterization were described; a quantitative analysis of the strawberries’ yield was performed, and environmental impact per ha and per kg of strawberries was estimated using the life cycle assessment methodology. To compare the profitability of the systems analyzed, the gross profit of the farmers was calculated, also considering the social cost of pollution. One of the two organic systems analyzed, using solarization for soil disinfestation, biological fight for pest control, and corrugated boxes as packaging recycled at the end-of-life, was the most sustainable system with carbon credits. At the same time, organic crops are not always the most sustainable and profitable systems if significant irrigation and fertigation interventions are carried out, as in another organic system analyzed. Plastic materials and zinc structures were the most impacting items in almost all analyzed systems. The use of a CT with an elevated number of beneficial microorganisms with a high suppressive action allowed to obtain a good increase of the yield, in both systems that used it, and to have a higher gross profit. On the other hand, the validity of this technique was strongly linked to the finding of high-quality green compost.

Obstruction of the superior vena cava represents an under-recognized cause of chylothorax in the adult population. Our case report describes the successful conservative management of chylothorax due to bilateral superior vena cava obstruction in an adult patient with complex congenital heart disease. (Level of Difficulty: Beginner.)

Extracellular vesicles (EVs) have emerged as important players in cell-to-cell communication within the bone marrow (BM) of multiple myeloma (MM) patients, where they mediate several tumor-associated processes. Here, we investigate the contribution of fibroblasts-derived EVs (FBEVs) in supporting BM angiogenesis. We demonstrate that FBEVs’ cargo contains several angiogenic cytokines (i.e., VEGF, HGF, and ANG-1) that promote an early over-angiogenic effect independent from EVs uptake. Interestingly, co-culture of endothelial cells from MM patients (MMECs) with FBEVs for 1 or 6 h activates the VEGF/VEGFR2, HGF/HGFR, and ANG-1/Tie2 axis, as well as the mTORC2 and Wnt/β-catenin pathways, suggesting that the early over-angiogenic effect is a cytokine-mediated process. FBEVs internalization occurs after longer exposure of MMECs to FBEVs (24 h) and induces a late over-angiogenic effect by increasing MMECs migration, chemotaxis, metalloproteases release, and capillarogenesis. FBEVs uptake activates mTORC1, MAPK, SRC, and STAT pathways that promote the release of pro-angiogenic cytokines, further supporting the pro-angiogenic milieu. Overall, our results demonstrate that FBEVs foster MM angiogenesis through dual time-related uptake-independent and uptake-dependent mechanisms that activate different intracellular pathways and transcriptional programs, providing the rationale for designing novel anti-angiogenic strategies.

Abstract Background Hereditary angioedema associated to C1 inhibitor deficiency (C1-INH-HAE) is a pathological condition characterized by episodes of subcutaneous swelling and it is frequently associated with discomfort and social impairment of the patients, due to the anxiety experienced for an unpreventable manifestation of an attack during daily life. In children increased level of stress and alexithymia have been associated to C1-INH-HAE, and the latter correlated also with the severity of the disease. We hypothesized that the involvement of psychological issues may impact on the severity of C1-INH-HAE in adult patients as well, interfering with their ability to engage with the management of the disease. Methods 28 adult patients with C1-INH-HAE were evaluated for clinical (C1-INH-HAE Severity Score) and psychological factors (alexithymia, emotion regulation, stress, patient health engagement, general severity index) by means of validated questionnaires. Results Mean age (standard deviation [SD]) was 45 (11) years and time from diagnosis was 20 (12) years. The mean C1-INH-HAE severity score was 6.4. Alexithymia was absent in 22 (78%) patients. Moderate and high stress levels were present in 17 (61%) and 4 (14%) patients, respectively. Moderate-high discomfort was experienced by 9 (36%) patients and a discomfort beyond the clinical attention threshold was shown by 3 (12%) patients. Stress correlated with patient health engagement and with psychological discomfort. Conclusions In C1-INH-HAE, patients health engagement and moderate-high psychological discomfort are linked with stress but not with the severity of the disease or alexithymia. A better patient health engagement may be a target for psychological intervention in clinics to ameliorate the stress perceived by C1-INH-HAE patients.

Salt inhibitors have been receiving increasing attention as potential innovative systems to counteract salt damage by preventing crystallisation of the salts within the natural stone structure—and related disruptive action—of built heritage. Especially, we focus on biomass-derived inhibitor systems featuring complete solubility in water or alcohol and intrinsic non-toxicity. Moving from the promising results obtained, the present study aims to develop research concerning the possibility of rationalizing the collected data sets and making them amenable to statistical analysis. This paper reports on an exploratory application of one of the most powerful methods in chemometrics, i.e., principal component analysis (PCA), in this area. It will be seen that this method is a promising tool to extract information from a series of tests to optimize them and to reduce the level of “noise” present in the data collected, i.e., unnecessary information or experimental errors, and to suggest new directions.

Protein-losing enteropathy (PLE) represents a rare but severe and potentially life-threatening complication following Fontan operation in patients with a functional single ventricle. PLE is characterized by enteric protein loss, leading to devastating multiorgan involvement with increased morbidity and mortality. In spite of remarkable advances in the care of congenital heart disease in recent years, treatment of PLE is still one of the most challenging tasks due to limited understanding of the underlying mechanisms and lack of high-quality evidence from large scale, controlled studies to test the real efficacy of the several treatment strategies, which have been proposed. For this reason, we herewith aim to discuss the pathogenesis and diagnosis of PLE in Fontan patients as well as provide a comprehensive overview on potential advantages and disadvantages of the currently available therapeutic strategies, in order to propose a stepwise approach for the management of this unique condition.

Summary: Huntington's disease (HD) is an autosomal dominant disorder with progressive motor dysfunction and cognitive decline. The disease is caused by a CAG repeat expansion in the IT15 gene, which elongates a polyglutamine stretch of the HD protein, Huntingtin. No therapeutic treatments are available, and new pharmacological targets are needed. Retrotransposons are transposable elements (TEs) that represent 40% and 30% of the human and Drosophila genomes and replicate through an RNA intermediate. Mounting evidence suggests that mammalian TEs are active during neurogenesis and may be involved in diseases of the nervous system. Here we show that TE expression and mobilization are increased in a Drosophila melanogaster HD model. By inhibiting TE mobilization with Reverse Transcriptase inhibitors, polyQ-dependent eye neurodegeneration and genome instability in larval brains are rescued and fly lifespan is increased. These results suggest that TE activation may be involved in polyQ-induced neurotoxicity and a potential pharmacological target.

Background: real-world data on COVID-19 vaccine safety, immunogenicity and acceptance in adults with congenital heart disease (ACHD) are lacking. Methods: ACHD patients who were offered COVID-19 vaccination from January to June 2021 were included. Data on adverse events, on patients’ attitude towards vaccination and antispike IgG titre were retrospectively collected. A group of healthy individuals with similar age and sex undergoing vaccination was included for comparison. Results: 208 patients followed in a single ACHD tertiary centre (33.3 [26–45] years, 54% male) received COVID-19 vaccine, 65% vaccinated at our institution: 199 (96%) received Pfizer–BioNTech BNT162b2 vaccine, 4 (2%) Moderna-1273 and 5 (2%) AstraZeneca–ChAdOx1. Median follow-up after vaccination was 79 [57–96] days. No major adverse event was reported and the incidence of minor events was not different between ACHD patients and the control group. One patient was diagnosed with acute pericarditis. There were two deaths unrelated to the vaccine during follow-up. Three (1.5%) vaccinated patients tested positive for COVID-19. Antispike IgG titre, available in 159 (76%) patients, was 1334 [600–3401] BAU/ml, not significantly different from the control group (p=0.2). One patient with Fontan failure was seronegative. Advanced physiological stage was associated with lower antibody response, independently from previous viral exposure (p

Exposure to artificial radio frequency electromagnetic fields (RF-EMFs) has greatly increased in recent years, thus promoting a growing scientific and social interest in deepening the biological impact of EMFs on living organisms. The current legislation governing the exposure to RF-EMFs is based exclusively on their thermal effects, without considering the possible non-thermal adverse health effects from long term exposure to EMFs. In this study we investigated the biological non-thermal effects of low-level indoor exposure to RF-EMFs produced by WiFi wireless technologies, using Drosophila melanogaster as the model system. Flies were exposed to 2.4 GHz radiofrequency in a Transverse Electromagnetic (TEM) cell device to ensure homogenous controlled fields. Signals were continuously monitored during the experiments and regulated at non thermal levels. The results of this study demonstrate that WiFi electromagnetic radiation causes extensive heterochromatin decondensation and thus a general loss of transposable elements epigenetic silencing in both germinal and neural tissues. Moreover, our findings provide evidence that WiFi related radiofrequency electromagnetic fields can induce reactive oxygen species (ROS) accumulation, genomic instability, and behavioural abnormalities. Finally, we demonstrate that WiFi radiation can synergize with RasV12 to drive tumor progression and invasion. All together, these data indicate that radiofrequency radiation emitted from WiFi devices could exert genotoxic effects in Drosophila and set the stage to further explore the biological effects of WiFi electromagnetic radiation on living organisms.

Agriculture, and the related food systems, represents one of the sectors that use most of the available water resources and is responsible for a large part of the greenhouse gases increase in Earth’s atmosphere. The aim of the present research was to estimate the three dimensions of sustainability—identified by the 2030 Agenda—of the olive oil supply chain in a typical production area within Campania Region (South Italy), through the analysis of seven different olive oil systems: four certified as organic, two of which irrigated (BIO1, BIO2, BIO-IRR1, BIO-IRR2); two integrated (INT1, INT2); and one hobbyist (HOBB). The novelty of the research was the broad-spectrum sustainability evaluation of these systems, through the estimation of their water and carbon footprints, and some economic and social aspects, to classify them in sustainability classes. So, the Life Cycle Thinking approach was used to quantify the environmental impacts and the social issues, as well as the costs of production of 1 litre of packed oil produced. Environmental impacts were assessed thought the life cycle assessment methodology, with a focus on the global warming and the water footprint, using the SimaPro 9.0 software and Hoekstra methodology, respectively. The cost production evaluation was performed by the life cycle costing methodology, while a primordial approach of social sustainability estimation was built identifying the stakeholders involved and suitable impact categories. Results showed that, per litre of oil, HOBB and BIO2 were the systems that emitted less CO2 eq (0.73 and 1.50 kg, respectively); BIO-IRR1 and BIO1 were the systems with the smallest water footprint (2.97 and 3.65 m3, respectively); HOBB and BIO1 were the systems with the lowest production costs (3.11 and 3.87 €, respectively). From a social point of view, INT1 and INT2 were the most pro-social systems. Overall, BIO1 was in absolute the most sustainable system under the various aspects considered. Hence the need to spread more and more (a) organic production methods, characterized by the use of self-produced fertilizers (on-farm compost); (b) more efficient machines use, for saving fuel; (c) balanced nitrogen fertilization to lower the water footprint.

This paper aimed to analyse and compare the environmental and energy sustainability of two orchards (peach versus kiwifruit) located in Southern Italy using Life Cycle Thinking. To this end, anthropogenic energy, CO2 emissions, biogenic energy and carbon gains were also considered through Life Cycle Assessment methodology and Energy Analysis. The C–CO2 balance was calculated as the difference between total C–CO2 stored in soil and trees, at the end of their life cycles, and orchards Carbon Footprint (CF). The results showed that the production of 1 kg of peaches caused minor impacts, especially with reference to CF (0.124 kg CO2 eq against 0.145 for kiwifruit), while it required 1.56 MJ of energy against 1.32 MJ for kiwifruit. In both orchards the main sources of direct CO2 emissions came from fuel combustion, nitrous oxide release by crop residue decomposition, and nitrogenous fertilizer distribution. Nevertheless, both orchards had sustainable environmental and energy results. Despite the management of the orchards releasing CO2 and consuming energy, they showed a significant capacity to store CO2 and energy, proving to be virtuous systems. This research can give useful indications for farmers, farmer associations, technicians, and stakeholders to improve orchard management efficiency. The net balance approach seems to be an adequate strategy, allowing best estimation of environmental impacts and guiding farmer decisions towards more sustainable alternatives.

Addition of organic amendments (OAs) could be a means to sequester carbon (C) in soils. However, the efficiency of C sequestration depends on how OAs evolve in the soil. A field study was installed in arid soil to which was added one of five OAs – olive husk-based compost (CM), palm leaf-based compost (CP), crushed olive pruning (GW), fresh olive mill wastewater (OMW) or fermented ovine manure (OM) – at an equivalent fixed level of 350 g of C/m2. C and N mineralization were followed for 112 days by measuring the evolution of released CO2 and mineral N evolution. The results showed that CM and CP did not disturb soil respiration, with a very low CO2 emission or almost no respiration for the CM, while CO2 release reached 7.6 g of CO2/m2 for GW and OMW. Soil organic carbon (SOC) was sustainably improved by 0.54% and 0.50%, respectively, for CM and CP. N mineralization showed no significant difference between amended and untreated soils. Based on these results, compost amendment was the most efficient for C sequestration to enhance soil fertility and consequently reduce the rate of CO2 emission.

Background: Implantable cardioverter defibrillators (ICD) are widely accepted therapy in congenital heart disease (CHD) patients at risk of life-threatening ventricular arrhythmias or sudden cardiac death (SCD). Initial experience with subcutaneous ICD (S-ICD) systems has shown a high efficacy. However, the use of S-ICD in complex ACHD (adult congenital heart disease) implies some specific considerations, as the safety for these patients in unknown and recommendations among physicians may vary widely. Methods: We review the data and studied the indications for S-ICD in complex ACHD and discuss its usefulness in clinical practice. Results: From a large cohort of 297 patients enrolled in the S-ICD “Monaldi care” registry, that encompass all the patients implanted in the Monaldi Hospital of Naples, we considered 14 consecutive complex ACHD patients (aged 35.9 ± 16.7 years) who underwent S-ICD implant from February 2015 to June 2020. Mean follow-up was 23 ± 19.5 months. All the patients showed a good compliance to the device system with no complications (infections or skin erosions). Four patients (1 M/3F aged 38.2 ± 11.3) were listed for heart transplantation (HTX). Two of these underwent HTX, one died for refractory heart failure (HF) and one is still on the waiting list. Conclusions: There might be a conceivable benefit from an extended use of the S-ICD in selected patients with CHD, especially in those with life-treating ventricular arrhythmias and complex anatomy or patients awaiting HTX. S-ICD appears to be a safe alternative to a transvenous system when a transvenous ICD cannot be implanted and pacing is not required.