Efficient dissipation of acetamiprid, metalaxyl, S-metolachlor and terbuthylazine in a full-scale free water surface constructed wetland in Bologna province, Italy: A kinetic modeling study.

The study investigated the dissipation ability of a vegetated free water surface (FWS) constructed wetland (CW) in treating pesticides-contaminated agricultural runoff/drainage water in a rural area belonging to Bologna province (Italy). The experiment simulated a 0.1% pesticide agricultural water runoff/drainage event from a 12.5-ha farm by dissolving acetamiprid, metalaxyl, S-metolachlor, and terbuthylazine in 1000 L of water and pumping it into the CW. Water and sediment samples from the CW were collected for 4 months at different time intervals to determine pesticide concentrations by multiresidue extraction and chromatography-mass spectrometry analyses. In parallel, no active compounds were detected in the CW sediments during the experimental period. Pesticides dissipation in the wetland water compartment was modeled according to best data practices by fitting the data to Single First Order (SFO), First Order Multi-Compartment (FOMC) and Double First Order in Parallel (DFOP) kinetic models. SFO (except for metalaxyl), FOMC and DFOP kinetic models adequately predicted the dissipation for the four investigated molecules, with the DFOP kinetic model that better fitted the observed data. The modeled distribution of each pesticide between biomass and water in the CW highly correlated with environmental indexes as Kow and bioconcentration factor. Computed DT50 by DFOP model were 2.169, 8.019, 1.551 and 2.047 days for acetamiprid, metalaxyl, S-metolachlor, and terbuthylazine, respectively. Although the exact degradation mechanisms of each pesticide require further study, the FWS CW was found to be effective in treating pesticides-contaminated agricultural runoff/drainage water within an acceptable time. Therefore, this technology proved to be a valuable tool for mitigating pesticides runoff occurring after intense rain events.

Enhanced Delivery of 5-Aminolevulinic Acid by Lecithin Invasomes in 3D Melanoma Cancer Model.

Photodynamic therapy (PDT) is a noninvasive therapeutic approach for the treatment of skin cancer and diseases. 5-Aminolevulinic acid is a prodrug clinically approved for PDT. Once internalized by cancer cells, it is rapidly metabolized to the photosensitizer protoporphyrin IX, which under the proper light irradiation, stimulates the deleterious reactive oxygen species (ROS) production and leads to cell death. The high hydrophilicity of 5-aminolevulinic acid limits its capability to cross the epidermis. Lipophilic derivatives of 5-aminolevulinic acid only partly improved skin penetration, thus making its incorporation into nanocarriers necessary. Here we have developed and characterized 5-aminolevulinic acid loaded invasomes made of egg lecithin, either 1,2-dilauroyl-sn-glycero-3-phosphocholine or 1,2-dioleoyl-sn-glycero-3-phosphocholine, and the terpene limonene. The obtained invasomes are highly thermostable and display a spherical morphology with an average size of 150 nm and an encapsulation efficiency of 80%; moreover, the ex vivo epidermis diffusion tests established that nanovesicles containing the terpene led to a much higher skin penetration (up to 80% in 3 h) compared to those without limonene and to the free fluorescent tracer (less than 50%). Finally, in vitro studies with 2D and 3D human cell models of melanoma proved the biocompatibility of invasomes, the enhanced intracellular transport of 5-aminolevulinic acid, its ability to generate ROS upon irradiation, and consequently, its antiproliferative effect. A simplified scaffold-based 3D skin model containing melanoma spheroids was also prepared. Considering the results obtained, we conclude that the lecithin invasomes loaded with 5-aminolevulinic acid have a good therapeutic potential and may represent an efficient tool that can be considered a valid alternative in the topical treatment of melanoma and other skin diseases.

Age-Related Properties of Aquaponics-Derived Tilapia Skin (Oreochromis niloticus): A Structural and Compositional Study.

In the last two decades, fisheries and fish industries by-products have started to be recovered for the extraction of type I collagen because of issues related to the extraction of traditional mammalian tissues. In this work, special attention has been paid to by-products from fish bred in aquaponic plants. The valorization of aquaponic fish wastes as sources of biopolymers would make the derived materials eco-friendlier and attractive in terms of profitability and cost effectiveness. Among fish species, Nile Tilapia is the second-most farmed species in the world and its skin is commonly chosen as a collagen extraction source. However, to the best of our knowledge, no studies have been carried out to investigate, in depth, the age-related differences in fish skin with the final aim of selecting the most advantageous fish size for collagen extraction. In this work, the impact of age on the structural and compositional properties of Tilapia skin was evaluated with the aim of selecting the condition that best lends itself to the extraction of type I collagen for biomedical applications, based on the known fact that the properties of the original tissue have a significant impact on those of the final product. Performed analysis showed statistically significant age-related differences. In particular, an increase in skin thickness (+110 µm) and of wavy-like collagen fiber bundle diameter (+3 µm) besides their organization variation was observed with age. Additionally, a preferred collagen molecule orientation along two specific directions was revealed, with a higher fiber orientation degree according to age. Thermal analysis registered a shift of the endothermic peak (+1.7 °C) and an increase in the enthalpy (+3.3 J/g), while mechanical properties were found to be anisotropic, with an age-dependent brittle behavior. Water (+13%) and ash (+0.6%) contents were found to be directly proportional with age, as opposed to protein (-8%) and lipid (-10%) contents. The amino acid composition revealed a decrease in the valine, leucine, isoleucine, and threonine content and an increase in proline and hydroxyproline. Lastly, fatty acids C14:0, C15:0, C16:1, C18:2n6c, C18:3n6, C18:0, C20:3n3, and C23:0 were revealed to be upregulated, while C18:1n9c was downregulated with age.

Testosterone levels and androgen receptor copy number variations in castration-resistant prostate cancer treated with abiraterone or enzalutamide.

PURPOSE: Our study aims to investigate the association between copy number of the androgen receptor (AR) and testosterone levels in metastatic castration-resistant prostate cancer (mCRPC) treated with second-generation antiandrogen therapies. MATERIALS AND METHODS: We retrospectively collected data from mCRPC treated with abiraterone acetate and enzalutamide. Serum testosterone levels were collected at baseline, at 3 months since the start of therapy and at disease progression. A cohort of cases treated with docetaxel was also used to evaluate the impact of testosterone levels. RESULTS: Patients treated with abiraterone with AR copy number aberrations and basal testosterone levels below 0.09 nmol/L had worse progression-free survival (PFS) compared to patients with no AR copy number abnormalities (8.5 vs 2.9 months, P = 0.005). No relevant differences were observed in the enzalutamide group with a PFS of 3.9 months (no AR gain) vs 2.7 months ( AR gain, P = 0.004) for patients with below 0.09 nmol/L testosterone levels. Similar results are obtained for univariate analysis for overall survival (OS). The negative prognostic role of AR copy number gain in OS for both treatment groups (25.5 vs 10.6 months, P = 0.0002 for abiraterone and 14.1 vs 8.3 months, P = 0.031 for enzalutamide) was confirmed, and it was recognized the negative prognostic impact of testosteronemia below 0.09 only for patients treated with enzalutamide (8.8 vs 42.8 months, P = 0.016). On multivariate analysis for patients treated with abiraterone, low testosterone levels below 0.09 and plasma AR gain were significantly associated with worse PFS and OS. These data are confirmed in the enzalutamide group for PFS. CONCLUSIONS: Testosterone levels and the AR copy number alterations were considered as independent prognostic factors. The results of this study show that serum testosteronemia associated with changes in copy number of AR gene could represent a noninvasive biomarker useful to identify a subgroup of patients with worse prognosis that can benefit less from second-generation antiandrogen therapies in the mCRPC setting.

SiO2 -Coated ZnO Nanoflakes Decorated with Ag Nanoparticles for Photocatalytic Water Oxidation.

Many strategies have been adopted to improve the photoinduced features of zinc oxide nanostructures for different application fields. In this work, zinc oxide has been synthesised and decorated by plasmonic metal nanoparticles to enhance its photocatalytic activity in the visible range. Furthermore, an insulating layer of SiO2 has been grown between the surface of zinc oxide nanoflakes and silver nanoparticles. A synthetic procedure that allows the accurate modulation of the insulating layer thickness in the range 5-40 nm has been developed. Evidences highlight the crucial role of the SiO2 layer in dramatically increasing photocatalytic water oxidation promoted by the nanostructure under both UV and visible illumination. An ideal thickness value of about 10 nm has been demonstrated to guarantee the plasmon-induced resonance energy-transfer process and to quench the Förster resonance energy-transfer mechanism; thus, optimising the local surface plasmon resonance effect and water oxidation properties.

Immune System and DNA Repair Defects in Ovarian Cancer: Implications for Locoregional Approaches.

In the last few years, substantial progress has been made in the treatment of ovarian cancer, with increased knowledge about the biology of the disease. Ovarian cancer is a neoplasm strongly linked to defects in DNA repair mechanisms, where deficiency in the homologous recombination (HR) system results in a better response of ovarian cancers to therapy, whether platinum-based chemotherapy, anthracyclines, or poly (ADP-ribose) polymerase (PARP) inhibitors. More recently, it has been demonstrated that different ovarian cancer histotypes may have different immunogenicity. Interestingly, defects in HR systems are associated more frequently with higher tumor infiltrating lymphocytes, providing a rationale for developing combination therapy with immune-modulating agents and PARP inhibitors. Again, locoregional therapies combining heat shock and chemotherapy delivery have been shown to induce an anticancer immune response in vitro. Thus, the potential for locoregional therapeutic approaches that may impact the immune system, perhaps in combination with immune-modulating agents or PARP inhibitors, needs to be further explored. With this premise, we reviewed the main biological and clinical data demonstrating a strict interplay between the immune system, DNA repair mechanisms, and intraperitoneal therapies in ovarian cancer, with a focus on potential future therapeutic implications.

Ethane-Bridged Bisporphyrin Conformational Changes As an Effective Analytical Tool for Nonenzymatic Detection of Urea in the Physiological Range.

Conformational switching induced in ethane-bridged bisporphyrins was used as a sensitive transduction method for revealing the presence of urea dissolved in water via nonenzymatic approach. Bisporphyrins were deposited on solid quartz slides by means of the spin-coating method. Molecular conformations of Zn and Ni monometalated bis-porphyrins were influenced by water solvated urea molecules and their fluorescence emission was modulated by the urea concentration. Absorption, fluorescence and Raman spectroscopies allowed the identification of supramolecular processes, which are responsible for host-guest interaction between the active layers and urea molecules. A high selectivity of the sensing mechanism was highlighted upon testing the spectroscopic responses of bis-porphyrin films to citrulline and glutamine used as interfering agents. Additionally, potential applicability was demonstrated by quantifying the urea concentration in real physiological samples proposing this new approach as a valuable alternative analytical procedure to the traditionally used enzymatic methods.

Oxaliplatin plus leucovorin and 5-fluorouracil (FOLFOX-4) as a salvage chemotherapy in heavily-pretreated platinum-resistant ovarian cancer.

BACKGROUND: The purpose of this study was to evaluate the clinical impact of oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX-4) chemotherapy in terms of the response rate, progression-free/overall survival (PFS/OS) and safety profile in patients with heavily pretreated recurrent epithelial ovarian cancer. METHODS: Clinical data were reviewed in 29 patients who received FOLFOX-4 as more than third-line chemotherapy, consisting of 85 mg/m2 of oxaliplatin, 200 mg/m2 of leucovorin, and bolus 400 mg/m2 on day 1 of 5-fluorouracil, followed by a 22-h infusion of 600 mg/m2 of 5-fluorouracil for 2 consecutive days every 3 weeks. We also compared the efficacy and toxicity of FOLFOX-4 with that of topotecan, a standard treatment, given at a dosage of 1.5 mg/m2 every three weeks in 26 patients. RESULTS: The median age of enrolled patients was 60 years (range 33 to 85). A median of 4 cycles (range 1-17) of FOLFOX-4 were administered. Complete response and partial response were observed in one (3.5%) and 5 (17.2.2%) patients, respectively, while stable disease was reported in 8 (27.6%) patients. Among all patients, grade 3-4 anemia, neutropenia, and thrombocytopenia were observed in 0 (0%), 5 (17.2%), and 3 (10.3%) cases, respectively. Grade 3-4 fatigue was recorded in one (3.4%) patient and diarrhea in 2 (6.9%). Median PFS and OS were 2.8 months [95% confidence interval (CI) 1.7-4.9] and 6.2 months (95% CI 2.4-14.6), respectively. No significant differences in terms of efficacy and toxicity were observed between patients receiving FOLFOX-4 and those treated with topotecan. CONCLUSIONS: The FOLFOX-4 regimen would seem to obtain similar survival rates to those of standard therapy with topotecan in platinum-resistant ovarian cancer. Further randomized trials are warranted to confirm our findings.

A Phase II Study of Everolimus Plus Oral Prednisone in Patients with Metastatic Renal Cell Cancer.

LESSONS LEARNED: The combination of everolimus and low-dose prednisone administered daily was hypothesized to prevent noninfectious pneumonitis (NIP) and mucositis, two common adverse events related to everolimus. Although mucositis was detected in only one case, all-grade NIP occurred in four of eight cases (50%), and this was considered enough to stop accrual of the study.These data suggest the need for careful monitoring of patients receiving everolimus who are treated with corticosteroids. BACKGROUND: Everolimus is standard of care in the treatment of patients affected by metastatic renal cell carcinoma (mRCC) that has progressed after at least one previous line of treatment. Stomatitis and noninfectious pneumonitis (NIP) are common adverse events (AEs) in patients treated with everolimus. Prednisone could reduce the incidence of stomatitis, and it is commonly used to treat NIP. We hypothesized that low doses of prednisone could reduce the incidence and/or the severity of everolimus-induced NIP and stomatitis. METHODS: We have conducted an open-label, single-arm, phase II trial of prednisone 5 mg b.i.d. added to everolimus 10 mg/day in patients with mRCC. We planned to evaluate the safety, tolerability, and activity of this combination in mRCC patients. We aimed to reduce incidence of drug discontinuations due to stomatitis or NIP from 25% to 10%. RESULTS: Three (38%) of the first eight patients enrolled experienced grade ≥2 pneumonitis and stopped treatment. Grade 1 stomatitis occurred in only one patient (13%). Five of eight patients experienced disease progression at the 2-month evaluation. Two patients (25%) were reported free of disease progression at 1 year of treatment. CONCLUSION: The incidence of NIP in these patients was considered too high for completing accrual of this study. These results may be of interest for investigating the pathogenesis of NIP and suggest that patients should be carefully followed if treated with chronic corticosteroids while receiving everolimus.

On-Demand Release of Hydrosoluble Drugs from a Paramagnetic Porous Collagen-Based Scaffold.

The design of a collagen scaffold containing iron oxide nanostructures capped by a TiO2 (anatase) layer is reported. The TiO2 shell is proposed to perform a dual role: 1) as an innovative and biocompatible cross-linker agent, providing binding sites to the protein moiety, through the well-known TiO2 chemical affinity towards carboxyl groups, and 2) as a protective surface layer for the paramagnetic core against oxidation. Simultaneously, the presence of the nanostructures confers to the collagen gel sensitivity to an external stimulus; that is, the application of a magnetic field. The hybrid biomaterial was demonstrated to be nontoxic and is proposed as a smart scaffold for the release of bioactive compounds on demand. The tuneable release of a model protein (myoglobin) upon application of a magnetic field was investigated. Myoglobin was loaded in the microporous material and discharge was induced by consecutive magnet applications, leading to release of the protein with high spatio-temporal and dosage control.

Malfunction of cardiac devices after radiotherapy without direct exposure to ionizing radiation: mechanisms and experimental data.

AIMS: Malfunctions of cardiac implantable electronical devices (CIED) have been described after high-energy radiation therapy even in the absence of direct exposure to ionizing radiation, due to diffusion of neutrons (n) causing soft errors in inner circuits. The purpose of the study was to analyse the effect of scattered radiation on different types and models of CIED and the possible sources of malfunctions. METHODS AND RESULTS: Fifty-nine explanted CIED were placed on an anthropomorphous phantom of tissue-equivalent material, and a high-energy photon (15 MV) radiotherapy course (total dose = 70 Gy) for prostate treatment was performed. All devices were interrogated before and after radiation. Radiation dose, the electromagnetic field, and neutron fluence at the CIED site were measured. Thirty-four pacemakers (PM) and 25 implantable cardioverter-defibrillators (ICD) were analysed. No malfunctions were detected before radiation. After radiation a software malfunction was evident in 13 (52%) ICD and 6 (18%) PM; no significant electromagnetic field or photon radiations were detected in the thoracic region. Neutron capture was demonstrated by the presence of the (198)Au((197)Au + n) or (192)Ir((191)Ir + n) isotope activation; it was significantly greater in ICD than in PM and non-significantly greater in damaged devices. A greater effect in St Jude PM (2/2 damaged), Boston (9/11), and St Jude ICD (3/6) and in older ICD models was observed; the year of production was not relevant in PM. CONCLUSION: High-energy radiation can cause different malfunctions on CIED, particularly ICD, even without direct exposure to ionizing radiation due to scattered radiation of neutrons produced by the linear accelerator.

(18)F-Fluorocholine PET/CT for early response assessment in patients with metastatic castration-resistant prostate cancer treated with enzalutamide.

PURPOSE: We investigated the role of (18)F-methylcholine (FCH) PET/CT in the early evaluation of patients with metastatic castration-resistant prostate cancer (mCRPC) treated with enzalutamide. METHODS: The study group comprised 36 patients with a median age of 72 years (range 48-90 years) who were treated with enzalutamide 160 mg once daily after at least one chemotherapeutic regimen with docetaxel. Patients were evaluated monthly for serological prostate-specific antigen (PSA) response. FCH PET/CT was performed at baseline and repeated after 3-6 weeks. Univariate and multivariate Cox regression models addressed potential predictors of progression-free survival (PFS) and overall survival (OS). RESULTS: At a median follow-up of 24.2 months (range 1.8-27.3 months), 34 patients were evaluable for early FCH PET/CT evaluation of response, and of these 17 showed progressive disease (PD) and 17 had stable disease or a partial response. A decrease in PSA level of more than 50% was observed in 21 patients. Early FCH PET/CT PD predicted radiological PD 3 months in advance of CT in 12 of 18 patients (66%) and was discordant with the decrease in PSA level in 13 patients. In 6 of these, biochemical PD was confirmed in 2 months. In multivariate analysis, only decrease in PSA level and FCH PET/CT were significant predictors of PFS (p = 0.0005 and p = 0.029, respectively), whereas decrease in PSA level alone was predictive of OS (p = 0.007). CONCLUSION: This is one of the first studies to evaluate the role of FCH PET/CT as an early predictor of outcome in mCRPC patients treated with enzalutamide. Our preliminary results suggest that the combination of FCH PET/CT and decrease in PSA level could be a valid tool to predict PFS in mCRPC patients. PSA remains the single most important prognostic factor, while FCH PET/CT does not add more information on OS beyond that obtained from PSA. Further studies in larger populations are needed to confirm these data and to clarify the role of FCH PET/CT in predicting response to enzalutamide in mCRPC patients.

Biocompatible Collagen Paramagnetic Scaffold for Controlled Drug Release.

A porous collagen-based hydrogel scaffold was prepared in the presence of iron oxide nanoparticles (NPs) and was characterized by means of infrared spectroscopy and scanning electron microscopy. The hybrid scaffold was then loaded with fluorescein sodium salt as a model compound. The release of the hydrosoluble species was triggered and accurately controlled by the application of an external magnetic field, as monitored by fluorescence spectroscopy. The biocompatibility of the proposed matrix was also tested by the MTT assay performed on 3T3 cells. Cell viability was only slightly reduced when the cells were incubated in the presence of the collagen-NP hydrogel, compared to controls. The economicity of the chemical protocol used to obtain the paramagnetic scaffolds as well as their biocompatibility and the safety of the external trigger needed to induce the drug release suggest the proposed collagen paramagnetic matrices for a number of applications including tissue engeneering and drug delivery.

Synthesis and Characterization of Collagen Scaffolds Reinforced by Eggshell Derived Hydroxyapatite for Tissue Engineering.

In this work, we synthesized porous nanohydroxyapatite/collagen composite scaffold (nHA-COL), which resemble extracellular matrices in bone and cartilage tissues. Nano hydroxyapatite (nHA) was successfully nucleated in to the collagen matrix using hen eggshell as calcium biogenic source. Porosity was evaluated by apparent and theoretical density measurement. Porosity of all scaffolds was in the range of 95-98%. XRD and TEM analyses show the purity and size of nucleated HA around 10 nm and selected area electron diffraction (SAED) analysis reveals the polycrystalline nature of nucleated HA. SEM analysis reveals (i) all the scaffolds have interconnected pores with an average pore diameter of 130 micron and (ii) aggregates of hydroxyapatite were strongly embedded in the collagen matrix for both composite scaffolds compared with pure collagen scaffold. EDS analysis shows the Ca/P stoichiometric ratio around 1.67 and FTIR reveals the chemical interaction between the collagen molecule and HA particles. The testing of mechanical properties evidenced that incorporation of HA resulted in up to a two-fold increase in compressive modulus with high reinforcement level (-7 kPa for 50HA-50COL) compared to pure collagen scaffold.

Chromogranin A is a potential prognostic marker in prostate cancer patients treated with enzalutamide.

BACKGROUND: In this retrospective study, we assessed chromogranin A (CgA) baseline value as a possible factor associated with poor prognosis in metastatic castration-resistant prostate cancer (CRPC). METHODS: Thirty-five patients with metastatic CRPC progressing after docetaxel chemotherapy treated with enzalutamide are subdivided into three groups: serum CgA level was normal when <120 ng/ml (group A, n = 10), within three times the upper normal value (UNV) when between 120 and 360 (group B, n = 17), more than three times the UNV when ≥360 ng/ml (group C, n = 8). RESULTS: No correlation was observed in three groups among CgA baseline values and PSA response rates (RR) (P = 0.4648), whereas a significative difference was associated with median progression-free survival (PFS) and overall survival (OS) among three CgA groups (P = 0.0301 and P = 0.0011, respectively). In the multivariate analysis, PSA RR (nonresponsive vs. responsive) and CgA levels (group 3 vs. groups 1 + 2) were predictors of OS (P = 0.0029 and P = 0.0025, respectively), whereas they only were not significantly correlated with PFS, even had a borderline significance (P = 0.0628 and P = 0.0772, respectively). CONCLUSIONS: In CRPC patients treated with enzalutamide, the evaluation of serum CgA levels could be an useful prognostic factor because of the strong association between CgA value more than three times the UNV and clinical outcome, independently from PSA response.

On the effect of pepsin incubation on type I collagen from horse tendon: Fine tuning of its physico-chemical and rheological properties.

Type I collagen is commonly recognized as the gold standard biomaterial for the manufacturing of medical devices for health-care related applications. In recent years, with the final aim of developing scaffolds with optimal bioactivity, even more studies focused on the influence of processing parameters on collagen properties, since processing can strongly affect the architecture of collagen at various length scales and, consequently, scaffolds macroscopic performances. The ability to finely tune scaffold properties in order to closely mimic the tissues' hierarchical features, preserving collagen's natural conformation, is actually of great interest. In this work, the effect of the pepsin-based extraction step on the material final properties was investigated. Thus, the physico-chemical properties of fibrillar type I collagens upon being extracted under various conditions were analyzed in depth. Correlations of collagen structure at the supramolecular scale with its microstructural properties were done, confirming the possibility of tuning rheological, viscoelastic and degradation properties of fibrillar type I collagen.

Impact of DCM-Causing Genetic Background on Long-Term Response to Cardiac Resynchronization Therapy.

BACKGROUND: Patients with nonischemic dilated cardiomyopathy (DCM), severe left ventricular (LV) dysfunction, and complete left bundle branch block benefit from cardiac resynchronization therapy (CRT). However, a large heterogeneity of response to CRT is described. Several predictors of response to CRT have been identified, but the role of the underlying genetic background is still poorly explored. OBJECTIVES: In the present study, the authors sought to define differences in LV remodeling and outcome prediction after CRT when stratifying patients according to the presence or absence of DCM-causing genetic background. METHODS: From our center, 74 patients with DCM subjected to CRT and available genetic testing were retrospectively enrolled. Carriers of causative monogenic variants in validated DCM-causing genes, and/or with documented family history of DCM, were classified as affected by genetically determined disease (GEN+DCM) (n = 25). Alternatively, by idiopathic dilated cardiomyopathy (idDCM) (n = 49). The primary outcome was long-term LV remodeling and prevalence of super response to CRT (evaluated at 24-48 months after CRT); the secondary outcome was heart failure-related death/heart transplant/LV assist device. RESULTS: GEN+DCM and idDCM patients were homogeneous at baseline with the exception of QRS duration, longer in idDCM. The median follow-up was 55 months. Long-term LV reverse remodeling and the prevalence of super response were significantly higher in the idDCM group (27% in idDCM vs 5% in GEN+DCM; P = 0.025). The heart failure-related death/heart transplant/LV assist device outcome occurred more frequently in patients with GEN+DCM (53% vs 24% in idDCM; P = 0.028). CONCLUSIONS: Genotyping contributes to the risk stratification of patients with DCM undergoing CRT implantation in terms of LV remodeling and outcomes.

Precision Estimation of Crop Coefficient for Maize Cultivation Using High-Resolution Satellite Imagery to Enhance Evapotranspiration Assessment in Agriculture.

The estimation of crop evapotranspiration (ETc) is crucial for irrigation water management, especially in arid regions. This can be particularly relevant in the Po Valley (Italy), where arable lands suffer from drought damages on an annual basis, causing drastic crop yield losses. This study presents a novel approach for vegetation-based estimation of crop evapotranspiration (ETc) for maize. Three years of high-resolution multispectral satellite (Sentinel-2)-based Normalized Difference Vegetation Index (NDVI), Normalized Difference Water Index (NDWI), Normalized Difference Red Edge Index (NDRE), and Leaf Area Index (LAI) time series data were used to derive crop coefficients of maize in nine plots at the Acqua Campus experimental farm of Irrigation Consortium for the Emilia Romagna Canal (CER), Italy. Since certain vegetation indices (VIs) (such as NDVI) have an exponential nature compared to the other indices, both linear and power regression models were evaluated to estimate the crop coefficient (Kc). In the context of linear regression, the correlations between Food and Agriculture Organization (FAO)-based Kc and NDWI, NDRE, NDVI, and LAI-based Kc were 0.833, 0.870, 0.886, and 0.771, respectively. Strong correlation values in the case of power regression (NDWI: 0.876, NDRE: 0.872, NDVI: 0.888, LAI: 0.746) indicated an alternative approach to provide crop coefficients for the vegetation period. The VI-based ETc values were calculated using reference evapotranspiration (ET0) and VI-based Kc. The weather station data of CER were used to calculate ET0 based on Penman-Monteith estimation. Out of the Vis, NDWI and NDVI-based ETc performed the best both in the cases of linear (NDWI RMSE: 0.43 ± 0.12; NDVI RMSE: 0.43 ± 0.095) and power (NDWI RMSE: 0.44 ± 0.116; NDVI RMSE: 0.44 ± 0.103) approaches. The findings affirm the efficacy of the developed methodology in accurately assessing the evapotranspiration rate. Consequently, it offers a more refined temporal estimation of water requirements for maize cultivation in the region.

Inherited Mutations in DNA Damage Repair Genes in Italian Men with Metastatic Prostate Cancer: Results from the Meet-URO 10 Study.

Background: The prevalence of pathogenic germline mutations in DNA damage repair (gDDR) genes in the Italian population is unknown. Objective: In this prospective multicenter cohort study, we evaluated the prevalence of gDDR alterations in the Italian population affected by metastatic prostate cancer (mPCa) and analyzed the impact on response to therapy, survival, and time to castration resistance. Design setting and participants: In an observational prospective trial, 300 consecutive Italian mPCa patients, enrolled in the Meet-Uro-10 trial from three academic Italian centers, were recruited between 2017 and 2019 and were screened for gDDR mutations in 107 genes. Outcome measurements and statistical analysis: The primary endpoint was to assess the prevalence of gDDR mutations in the Italian population of patients with mPCa. The secondary endpoints included the association of gDDR subgroups with metastatic onset, Gleason score, and time to castration resistance. Results and limitations: We identified 297 valuable patients. Forty-six patients had a pathogenic/likely pathogenic variant (15.5%, 95% confidence interval: 11.4-19.6): the more frequent was gBRCA2 found in nine cases (3%), followed by gATM in five cases (1.7%). In patients without mutations, longer median overall survival was observed with the sequence docetaxel-androgen receptor signaling inhibitor (ARSI) than with the sequence ARSI-docetaxel (87.9 vs 42 mo, p = 0.0001). In a univariate analysis, the median time to castration resistance in gDDR mutated patients was 19.8 mo, versus 23.7 mo in no mutated patients (p = 0.024). There were no associations of gDDR subgroups with metastatic onset and Gleason score ≥8. In our cohort, variants of unknown significance in gDDR genes were found in 80 patients and might have a prognostic relevance. Conclusions: The study reported the prevalence of gDDR in the Italian population. The presence of gBRCA2 mutations correlates with a shorter time to the onset of castration resistance disease. Patient summary: The prevalence of gBRCA2 in the Italian population is 3%, which is similar to that in the Spanish population, identifying similarities between people of the Western Mediterranean area.

Multicenter institutional experience of surgically resected thymic epithelial tumors (TETs): an observational report on behalf of F.O.N.I.C.A.P. (Forza Operativa Nazionale Interdisciplinare Contro il Cancro del Polmone).

BACKGROUND: This multicenter analysis evaluated patient outcome and clinical pathologic features of thymic epithelial tumors after complete surgical resection and adjuvant treatment. METHODS: Histologic classification and clinical staging were performed according to WHO classification and Masaoka staging system, respectively. RESULTS: We analyzed 62 patients, 20 (32%) of whom had myasthenia at diagnosis. Clinical and pathologic staging was as follows: 31 (50%) and 30 (48%) patients had stage I disease, 19 (30%) and 22 (35%) stage II, 5 (8%) and 3 (6%) stage III, 2 (4%) and 2 (3%) stage IVa, and 5 (8%) and 5 (8%) stage IVb, respectively. Histologic examination revealed 11 (19%) type A tumors, 19 (30%) type AB tumors, 7 (12%) type B1 tumors, 11 (17%) type B2 tumors, 11 (17%) type B3 tumors, and 3 (5%) type C tumors. Adjuvant therapies comprised chemotherapy in 3 (5%) patients and radiotherapy in 16 (26%) patients. Median follow-up was 71 months (range 1-145). DFS and OS at 48, 60, and 72 months were 89 and 89%, 86 and 97%, and 95% and 92%, respectively. Myasthenia at the onset of disease (P=0.18 for DFS; P=0.97) and tumor size>5 cm (P=0.94 for DFS; P=0.56) were not prognostic factors. CONCLUSIONS: TETs are rare and indolent tumors. Complete surgical resection followed by adjuvant therapies, such as chemotherapy and/or radiotherapy, in patients at risk of recurrence show very good DFS and OS results, even in cases with radically resected pleural-pulmonary metastases.