Evidence from field measurements and satellite imaging of impact of Earth rotation on Lake Iseo chemistry

During an initial field survey in 2012, we observed an unexpected asymmetry of dissolved oxygen distribution between the western and eastern side in northern Lake Iseo. Motivated by this apparent anomaly, we conducted a detailed field investigation, and we used a physical model of the northern part of the lake to understand the in- fluences that might affect the distribution of material in the northern section of the lake. These investigations sug- gested that the Earth's rotation has significant influence on the inflow of the lake's two main tributaries. In order to further crosscheck the validity of these results, we conducted a careful analysis at a synoptic scale using images acquired during thermally unstratified periods by Landsat-8 and Sentinel-2 satellites. We retrieved and post- processed a large set of images, providing conclusive evidence of the role exerted by the Earth's rotation on pol- lutant transport in Lake Iseo and of the greater environmental vulnerability of the north-west shore of this lake, where important settlements are located. Our study confirms the necessity for three-dimensional hydrodynamic models including Coriolis effect in order to effectively predict local impacts of inflows on nearshore water quality of medium-sized elongated lakes of similar scale to Lake Iseo

Fifteen-minute consultation: The prepubescent gender-diverse child: how to answer parents' questions

Parents and caregivers may seek help with different questions or concerns on how to handle the diverse gender expressions of their children. Sometimes the issue may be evident while seeking medical advice for other concerns. Because of the many uncertainties around this topic, clinicians need to know what to say and what can be done to provide the best possible care for gender-diverse children

Protective but Not Anticonvulsant Effects of Ghrelin and JMV-1843 in the Pilocarpine Model of Status epilepticus.

In models of status epilepticus ghrelin displays neuroprotective effects mediated by the growth hormone secretagogue-receptor 1a (GHS-R1a). This activity may be explained by anticonvulsant properties that, however, are controversial. We further investigated neuroprotection and the effects on seizures by comparing ghrelin with a more effective GHS-R1a agonist, JMV-1843. Rats were treated either with ghrelin, JMV-1843 or saline 10 min before pilocarpine, which was used to induce status epilepticus. Status epilepticus, developed in all rats, was attenuated by diazepam. No differences were observed among the various groups in the characteristics of pilocarpine-induced seizures. In saline group the area of lesion, characterized by lack of glial fibrillary acidic protein immunoreactivity, was of 0.45\ub10.07 mm2 in the hippocampal stratum lacunosum-moleculare, and was accompanied by upregulation of laminin immunostaining, and by increased endothelin-1 expression. Both ghrelin (P<0.05) and JMV-1843 (P<0.01) were able to reduce the area of loss in glial fibrillary acidic protein immunostaining. In addition, JMV-1843 counteracted (P<0.05) the changes in laminin and endothelin-1 expression, both increased in ghrelin-treated rats. JMV-1843 was able to ameliorate neuronal survival in the hilus of dentate gyrus and medial entorhinal cortex layer III (P<0.05 vs saline and ghrelin groups). These results demonstrate diverse protective effects of growth hormone secretagogues in rats exposed to status epilepticus

Chapter Mapping of the risk of coastal erosion for two case studies: Pianosa island (Tuscany) and Piscinas (Sardinia)

This study focuses on the use of remote sensing to generate coastal erosion risk maps for Pianosa Island (Tuscany) and Piscinas dune system (Sardinia). The method made use of both ancillary and satellite data (Sentinel-2), in addition to SAR images (COSMO SkyMed and Sentinel-1B). TOA radiance products were atmospherically corrected and processed using Sen2Coral and BOMBER in order to map different marine substrates and bathymetry. The coastal erosion risk maps have been generated based on these output and the results confirm that the coasts of these sites don’t have coastal erosion problems

The Color of Water from Space: A Case Study for Italian Lakes from Sentinel-2

Lakes are inestimable renewable natural resources that are under significant pressure by human activities. Monitoring lakes regularly is necessary to understand their dynamics and the drivers of these dynamics to support effective management. Remote sensing by satellite sensors offers a significant opportunity to increase the spatiotemporal coverage of environmental monitoring programs for inland waters. Lake color is a water quality attribute that can be remotely sensed and is independent of the sensor specifications and water type. In this study we used the Multispectral Imager (MSI) on two Sentinel-2 satellites to determine the color of water of 170 Italian lakes during two periods in 2017. Overall, most of the lakes appeared blue in spring and green-yellow in late summer, and in particular, we confirm a blue-water status of the largest lakes in the subalpine ecoregion. The color and its seasonality are consistent with characteristics determined by geomorphology and primary drivers of water quality. This suggests that information about the color of the lakes can contribute to synoptic assessments of the trophic status of lakes. Further ongoing research efforts are focused to extend the mapping over multiple years

EGF and IGF1 affect Sunitinib activity in BP-NEN: new putative targets beyond VEGFR?

Broncho-Pulmonary Neuroendocrine Neoplasms (BP-NENs) are neoplasms orphan of an efficient therapy. Available medical treatments derived from clinical trials are not specific for the management of this malignancy. Sunitinib is a multi-receptor tyrosine-kinases (RTKs) inhibitor that has already shown its efficacy in NENs but there are not available data about its action in BP-NENs. Therefore, our aim was to understand the effects of RTKs inhibition promoted by Sunitinib in order to evaluate new putative targets useful in malignancy treatment. Since our results underlined a role for EGFR and IGF1R in modulating Sunitinib antiproliferative action, we investigated the effects of Erlotinib, an EGFR inhibitor, and Linsitinib, an IGF1R inhibitor, in order to understand their function in regulating cells behaviour. Cell viability and caspase activation were evaluated on two immortalized human BP-NEN cell lines and primary cultures. Our results showed that after treatment with Sunitinib and/or IGF1, EGF and VEGF, the antiproliferative effect of Sunitinib was counteracted by EGF and IGF1 but not by VEGF. Therefore, we evaluated with alpha-screen technology the phosphorylated EGFR and IGF1R levels in primary cultures treated with Sunitinib and/or EGF and IGF1. Results showed a decrease of p-IGF1R after treatment with Sunitinib and an increase after co-treatment with IGF1. Then, we assessed cell viability and caspase activation on BP-NEN cell lines after treatment with Linsitinib and/or Erlotinib. Results demonstrate that these two agents have a stronger antiproliferative effect compared to Sunitinib. In conclusion, our results suggest that IGF1R and EGF1R could represent putative molecular targets in BP-NENs treatment

Short-Term Outcomes of an ESDM Intervention in Italian Children with Autism Spectrum Disorder following the COVID-19 Lockdown

The COVID-19 pandemic caused a temporary lockdown period in Italy, during which the delivery of in-person treatment for children with autism spectrum disorder (ASD) in public health services was discontinued. This occurrence represented a crucial challenge for both families and professionals. We assessed the short-term outcomes of a sample of 18 children who received an early intervention with the Early Start Denver Model (ESDM), delivered at low intensity over one year in the pre-pandemic period, after six months of interruption of in-presence treatment due to lockdown restrictions. Children who received the ESDM treatment maintained their gains in sociocommunicative skills and did not exhibit any developmental regression. Additionally, there was evidence of a decrease in the restrictive and repetitive behavior (RRB) domain. The parents, who were already familiar with the principles of the ESDM, only received telehealth support from therapists that aimed to sustain the gains already achieved. We believe that it is always helpful to support parents in their daily lives by implementing interactional and play skills with their children to integrate and consolidate the results obtained in the individual interventions conducted by experienced therapists

Pancreatic and broncho-pulmonary neuroendocrine neoplasms in vitro studies: a route from culture systems evaluation to approved and innovative therapeutic approaches

Neuroendocrine Neoplasms (NENs) are a group of malignancies arising from cells of the diffuse endocrine system. Pancreatic and broncho-pulmonary NENs (pNENs and BP-NENs, respectively) represent the two main NENs in terms of incidence and, since surgery is not possible in most of the cases, are orphan of an effective therapy. Beyond surgery, different therapeutic approaches are available for NENs management. Molecular targeted therapies gained during years growing interest and different agents have been approved for NENs treatment. In particular, Everolimus, an mTOR inhibitor, has been approved for the treatment of both pNENs and BP-NENs while Sunitinib, a multiple tyrosine kinase receptors (RTKs) inhibitor, has been approved for pNENs treatment. However, despite these agents have shown to improve progression free survival, mechanisms of acquired resistance may occur leading to the need of new approaches. Therefore, finding an effective therapy for NENs represents a crucial issue and, in this study, we tried to approach this problem in different ways. We started our work trying to identify, through the use of a pNEN cell line, the best method to culture NENs in 3D since this growth system has already demonstrated its validity with in vitro studies. The three methods taken into consideration involved different tools: a 96-well hanging drop plate, a 24-well plate with a cell repellent surface and an ultra low attachment 96-well plate with clear round bottom (ULA). Results were compared and analysed in terms of easiness/reproducibility error and have indicated ULA plates method as the best to culture NENs. Therefore, we used this method in the following parts of the study. After the assessment of the best 3D culture method, we started our investigation on BP-NENs resistance wondering whether the well-known RTKs inhibitor Sunitinib could have been effective in the treatment of BP-NENs and not only pNENs. Sunitinib showed to have an antiproliferative effect on both the BP-NENs cell lines taken into consideration. In addition, its action was counteracted by some growth factors co-tested with the drug. Thanks to these results we tested other agents, the IGF1R inhibitor Linsitinib and the EGFR inhibitor Erlotinib, in order to understand whether a drug with a more specific target could have overcome Sunitinib resistance. Results indicated that Linsitinib and Erlotinib were able to decrease cell viability despite the proliferative action promoted by growth factors and that their combination induced a strong antiproliferative effect and caspase activation. Thanks to these encouraging findings we started to investigate a complex topic: the influence of tumour microenvironment (TME) in BP-NENs behaviour and drugs resistance. Therefore, we cultured two BP-NENs cell lines in 2D and in 3D with or without the addition of a lung fibroblast cell line. Moreover, in order to pursue our aim, we evaluated the effects of a CDKs and cyclines inhibitor, Dinaciclib, on the described system comparing its action with the one displayed by Everolimus. Our preliminary results underlined the influence of fibroblasts on BP-NENs behaviour/drug sensitivity indicating Dinaciclib as an effective agent in the treatment of this malignancy. In conclusion our study provided several indications useful for NENs study, drugs resistance comprehension and malignancy management. These data are preliminary results that can be useful for further investigations in order to achieve a better NENs knowledge and more effective therapies.Le neoplasie neuroendocrine (NENs) sono un gruppo di neoplasie rare che originano dal sistema neuroendocrino diffuso. Le due principali NENs sono quelle di origine pancreatica e broncopolmonare (rispettivamente pNENs e BP-NENs) e, a tutt’oggi, non esiste ancora una terapia efficace per queste neoplasie. Il trattamento di prima scelta è la resezione chirurgica che però non è consentita nella maggior parte dei casi. Anche altre terapie vengono utilizzate per il trattamento delle NENs. Gli inibitori a bersaglio molecolare hanno richiamato un crescente interesse ed alcune molecole sono state approvate per il trattamento di questo tipo di neoplasie. In particolare, Everolimus, inibitore di mTOR, è stato approvato sia per il trattamento di NENs broncopolmonari che pancreatiche mentre Sunitinib, inibitore di recettori tirosin-chinasici, è stato approvato per il trattamento di NEN di origine pancreatica. Nonostante questi farmaci si siano rivelati efficaci nel prolungare il tempo libero da progressione di malattia, lo sviluppo di resistenza alla terapia può verificarsi anche dopo brevi periodi. La ricerca di trattamenti efficaci è quindi un punto cruciale e, in questo studio, abbiamo cercato di affrontare il problema sotto diversi punti di vista. Abbiamo iniziato il nostro studio cercando di identificare il sistema migliore per coltivare una linea di pNEN in 3D dato che questo metodo di coltura ha ampiamente dimostrato di essere efficace negli studi in vitro. Abbiamo preso in considerazione tre sistemi di coltura in 3D resi possibili dall’utilizzo di 3 piastre: piastre da 96 pozzetti con tecnologia “hanging drop”, piastre da 24 pozzetti con una superficie repellente e piastre da 96 pozzetti con un fondo “ultra low attachment” (ULA). I risultati ottenuti sono stati comparati in termini di facilità di coltura e di errore di riproducibilità indicando le piastre ULA come il metodo più efficace. Grazie a questi risultati, il metodo ULA è stato utilizzato anche nelle seguenti parti dello studio. Dopo aver individuato il miglior metodo di coltura in 3D, ci siamo domandati se il noto inibitore Sunitinib potesse essere efficace anche nel trattamento delle NENs di origine broncopolmonare. I risultati hanno indicato un effetto antiproliferativo del farmaco, contrastato dal co-trattamento con fattori di crescita. Grazie a questi risultati sono stati testati altri due inibitori, l’inibitore di IGF1R Linsitinib e l’inibitore di EGFR Erlotinib, in modo da poter comprendere se farmaci con un bersaglio molecolare più specifico possano diminuire la vitalità cellulare nonostante l’azione proliferativa fattori di crescita. I risultati hanno indicato che sia Linsitinib che Erlotinib hanno una forte azione inibitoria, nonostante il co-trattamento con fattori di crescita. Inoltre, l’azione combinata dei due farmaci è in grado di generare una forte riduzione della vitalità e una massiva attivazione caspasica. Nell’ultima parte del nostro lavoro è stata valutata l’influenza del micorambiente tumorale (TME) nel comportamento e nella resistenza ai farmaci delle NENs broncopolmonari. Due linee cellulari di BP-NEN sono state coltivate in 2D ed in 3D con o senza l’aggiunta di una linea cellulare di fibroblasti polmonari e, per poter perseguire al meglio il nostro scopo, sul sistema è stata valutata l’azione di due farmaci: Dinaciclib, inibitore di cicline e CDK, ed Everolimus. I risultati ottenuti hanno evidenziato un ruolo del TME nella sensibilità ai farmaci/sviluppo tumorale ed hanno inoltre indicato una forte azione inibitoria promossa da Dinaciclib su entrambe le linee di BP-NENs. In conclusione, in questo lavoro sono state ottenute diverse indicazioni per lo studio, la comprensione e la gestione delle NENs. Questi risultati preliminari possono pertanto porre le basi per future indagini mirate ad una maggiore conoscenza delle NENs e ad una terapia più efficace