Bioaccessibility and Antioxidant Capacity of Grape Seed and Grape Skin Phenolic Compounds After Simulated In Vitro Gastrointestinal Digestion.

Grapes present recognized beneficial effects on human health due to their polyphenolic composition. The grape overproduction together with the wine sales down and the world socioeconomic situation makes the wine grape valorization a promising strategy to give an added-value to this natural product. The objective of the present work was to study the influence of in vitro gastrointestinal digestion on antioxidant capacity and polyphenolic profile of skin and seed extracts of different grape varieties (Tempranillo, Graciano, Maturana tinta and Hondarrabi zuri). After in vitro gastrointestinal digestion, total phenolic content (TPC) of seed polyphenolic extracts decreased significantly for all the varieties. The highest decrease was for Tempranillo going from 108 ± 9 to 50 ± 3 mg / g dry matter (dm). This variety also showed the highest decrease of 90% in antioxidant capacity. However, for all the skin polyphenolic extracts there was an increase in TPC. The highest variation was also for Tempranillo. It varied from 10.1 ± 0.8 to 55.1 ± 0.9 mg / g dm. Among red varieties Tempranillo skin polyphenolic extract showed the lowest undigested anthocyanin content but the highest bioaccessibility index (BI) of 77%. For flavanols, flavonols and procyanidins the seed polyphenolic extracts showed a BI at the intestinal phase between 11% for (+)-epicatechin gallate to 130% procyanidin A2. The results of this study suggest that grape skin extracts and grape seed extracts are a reliable source of bioaccessible antioxidant polyphenols, to be used for the development of antioxidant supplements with specific functionalities depending on the grape variety.

SBRT-SG-01: final results of a prospective multicenter study on stereotactic body radiotherapy for liver metastases.

OBJECTIVE: This study aimed to assess the efficacy and tolerability of stereotactic body radiation therapy (SBRT) for the treatment of liver metastases. METHODS: Patients with up to 5 liver metastases were enrolled in this prospective multicenter study and underwent SBRT. Efficacy outcomes included in-field local control (LC), progression-free survival (PFS), and overall survival (OS). Acute and late toxicities were evaluated using CTCAE v.4.0. RESULTS: A total of 52 patients with 105 liver metastases were treated between 2015 and 2018. The most common primary tumor was colorectal cancer (72% of cases). Liver metastases were synchronous with the primary tumor diagnosis in 24 patients (46.2%), and 21 patients (40.4%) presented with other extrahepatic oligometastases. All patients underwent intensity-modulated radiation therapy (IMRT)/volumetric-modulated arc therapy (VMAT) with image-guided radiation therapy (IGRT) and respiratory gating, and a minimum biologically effective dose (BED10Gy) of 100 Gy was delivered to all lesions. With a median follow-up of 23.1 months (range: 13.4-30.9 months) since liver SBRT, the median actuarial local progression-free survival (local-PFS) was not reached. The actuarial in-field LC rates were 84.9% and 78.4% at 24 and 48 months, respectively. The median actuarial liver-PFS and distant-PFS were 11 and 10.8 months, respectively. The actuarial median overall survival (OS) was 27.7 months from SBRT and 52.5 months from metastases diagnosis. Patients with lesion diameter ≤ 5 cm had significantly better median liver-PFS (p = 0.006) and OS (p = 0.018). No acute or late toxicities of grade ≥ 3 were observed. CONCLUSIONS: This prospective multicenter study confirms that liver SBRT is an effective alternative for the treatment of liver metastases, demonstrating high rates of local control and survival while maintaining a low toxicity profile.

Ultra-hypofractionated one-week locoregional radiotherapy for patients with early breast cancer: Acute toxicity results.

Purpose: Moderate hypofractionated radiotherapy is the standard of care for all patients with breast cancer, irrespective of stage or prior treatments. While extreme hypofractionation is accepted for early-stage tumours, its application in irradiating locoregional lymph nodes remains controversial. Materials and methods: A prospective registry analysis from July 2020 to September 2023 included 276 patients with early-stage breast cancer treated with one-week ultra-hypofractionation (UHF) at 26 Gy in 5 fractions on the whole breast (58.3 %) or thoracic wall (41.7 %) and ipsilateral regional lymph nodes and simultaneous integrated boost (58.3 %). Primary endpoint was assessment of acute adverse events (AEs). Secondarily, onset of early-delayed toxicity was assessed. A minimum 6-month follow-up was required for assessing potential treatment-related early-delayed complications. Acute or late complications attributable to treatment were assessed at inclusion using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 criteria. Results: With a median follow-up of 19 months (range 1-49 months), 159 (57.6 %) patients reported AEs, predominantly grade (G) 1 (n = 139, 50.4 %) and G2 (n = 20, 7.8 %). Skin acute toxicity was common (G1/2: 134, G3: 14), while breast oedema occurred in 10 patients (G1: 9, G2: 1), and 15.9 % reported breast pain (G1: 42, G2: 2). Ipsilateral arm oedema was observed in 1.8 % patients. For patients with a follow-up beyond 6 months (n = 213), 23.4 % patients reported G1/G2 skin AEs, 8.8 % had G1/G2 breast/chest wall oedema, and 8.9 % experienced arm lymphedema. There were no cases of brachial plexopathy or G3 toxicity in this group of patients. Conclusions: One-week UHF adjuvant locoregional radiation is well-tolerated, displaying low-toxicity profiles comparable to other studies using similar irradiation schedules.

Moderate hypofractionated radiation therapy and pathologic response for soft tissue sarcomas (STS) of limbs and trunk: experience from a tertiary cancer center.

BACKGROUND: Preoperative radiation therapy following by limb-sparing or conservative surgery is a standard approach for limb and trunk STS. Data supporting hypofractionated radiotherapy schedules are scarce albeit biological sensitivity of STS to radiation would justify it. We sought to evaluate the impact of moderate hypofractionation on pathologic response and its influence on oncologic outcomes. MATERIAL AND METHODS: From October 2018 to January 2023, 18 patients with limb or trunk STS underwent preoperative radiotherapy at a median dose of 52.5 Gy (range 49.5-60 Gy) in 15 fractions of 3.5 Gy (3.3-4 Gy) with or without neoadjuvant chemotherapy. A favorable pathologic response (fPR) was considered as ≥ 90% tumor necrosis on specimen examination. RESULTS: All patients completed planned preoperative radiotherapy. Eleven patients (61.1%) achieved a fPR, and 7 patients (36.8%) a complete pathologic response with total disappearance of tumor cells. Nine patients (47%) developed grade 1-2 acute skin toxicity, and 7 patients (38.8%) had wound complications on follow-up. With a median follow-up of 14 months (range 1-40), no cases of local relapse were observed, and actuarial 3-year overall survival (OS) and distant metastases-free survival (DMFS) are 87% and 76.4%, respectively. In the univariate analysis, the presence of a favorable pathologic response (fPR) was associated with improved 3-year OS (100% vs. 56.03%, p = 0.058) and 3-year DMFS (86.91% vs. 31.46%, p = 0.002). Moreover, both complete or partial RECIST response and radiological stabilization of the tumor lesion showed a significant association with higher rates of 3-year distant metastasis-free survival (DMFS) (83% vs. 83% vs. 56%, p < 0.001) and 3-year overall survival (OS) (100% vs. 80% vs. 0, p = 0.002). CONCLUSIONS: Preoperative moderate hypofractionated radiation treatment for STS is feasible and well tolerated and associates encouraging rates of pathologic response that could have a favorable impact on final outcomes.

Highlights of FDA Oncology Approvals in 2023: Bispecific T-cell Engagers, Pediatric Indications, and Inclusive Drug Development.

SUMMARY: Cancer drug development remained robust in 2023. Highlights of U.S. drug approvals this year include new immunotherapies and targeted drug development in adult and pediatric patients as well as patients with rare diseases.

Real-World Outcomes in Patients with Metastatic Colorectal Cancer in Spain: The RWD-ACROSS Study.

The retrospective, observational RWD-ACROSS study analyzed disease characteristics, systemic treatment, and survival in patients with metastatic colorectal cancer (mCRC) in Spain. In total, 2002 patients were enrolled (mean age 65.3 years; 62.7% male). Overall median overall survival (OS) was 26.72 months, and was longer in patients with left-sided tumors (28.85 vs. 21.04 months (right-sided tumors); p < 0.0001) and in patients receiving first-line anti-epidermal growth factor receptor (EGFR) treatment (31.21 vs. 26.75 (anti-vascular endothelial growth factor (VEGF) treatment) and 24.45 months (chemotherapy); p = 0.002). Overall median progression-free survival (PFS) was 10.72 months and was longer in patients with left-sided tumors (11.24 vs. 9.31 months (right-sided tumors); p < 0.0001), and in patients receiving either first-line anti-EGFR or anti-VEGF (12.13 and 12.00 vs. 8.98 months (chemotherapy); p < 0.001). PFS was longer with anti-VEGF treatment in patients with right-sided tumors and wild-type RAS (11.24 vs. 8.78 (anti-EGFR) and 7.83 months (chemotherapy); p = 0.025). Both anti-EGFR and anti-VEGF produced longer PFS in patients with left-sided tumors and wild-type RAS than chemotherapy alone (12.39 and 13.14 vs. 9.83 months; p = 0.011). In patients with left-sided tumors and mutant RAS, anti-VEGF produced a longer PFS than chemotherapy alone (12.36 vs. 9.34 months; p = 0.001). In Spain, wild-type RAS or left-sided mCRC tumors are predictive of longer survival times.

Efficacy of Protein Baits with Fipronil to Control Vespa velutina nigrithorax (Lepeletier, 1836) in Apiaries.

The yellow-legged hornet (Vespa velutina nigrithorax), outside its natural range, has become a major threat to domestic bees. Several control methods have been used to fight against V. velutina, but the results achieved are not satisfactory. The use of protein baits with biocides has shown to be an effective method to control invasive wasp populations, but they have not been used to control V. velutina. Thus, the efficacy of protein baits containing fipronil to reduce the presence of hornets in apiaries was evaluated in this study. After laboratory determination of the optimal efficacy of a protein bait at a 0.01% concentration of fipronil, field trials were conducted involving 222 beekeepers. The data reported by the 90 beekeepers who completed the requested questionnaire demonstrated that in the groups of apiaries with the highest pressure of hornets (groups with 10-30 and >30 hornets), there was a significant decrease in the presence of V. velutina, lasting at least two weeks. The reduction in the number of hornets was positively correlated with bait consumption, and bait consumption was positively correlated with the number of hornets present at the time of treatment. Although the method used has shown good efficacy and the concentration of fipronil used was very low; possible negative effects on the environment should also be evaluated.

Circulating NPTX2 methylation as a non-invasive biomarker for prognosis and monitoring of metastatic pancreatic cancer.

BACKGROUND: Pancreatic cancer is the most lethal cancer with a dismal prognosis mainly due to diagnosis at advanced stage and ineffective treatments. CA19-9 levels and computed tomography (CT) imaging are the main standard criteria for evaluating disease progression and treatment response. In this study we explored liquid biopsy-based epigenetic biomarkers for prognosis and monitoring disease in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). METHODS: Plasma samples were collected from 44 mPDAC patients at the time of diagnosis, and in 15 of them, additional samples were obtained during follow-up of the disease. After cell-free DNA (cfDNA), isolation circulating levels of methylated NPTX2, SPARC, BMP3, SFRP1 and TFPI2 genes were measured using digital droplet PCR (ddPCR). BEAMing technique was performed for quantitation of RAS mutations in cfDNA, and CA19-9 was measured using standard techniques. RESULTS: NPTX2 was the most highly and frequently methylated gene in cfDNA samples from mPDAC patients. Higher circulating NPTX2 methylation levels at diagnosis were associated with poor prognosis and efficiently stratified patients for prediction of overall survival (6.06% cut-off, p = 0.0067). Dynamics of circulating NPTX2 methylation levels correlated with disease progression and response to therapy and predicted better than CA19-9 the evolution of disease in mPDAC patients. Remarkably, in many cases the disease progression detected by CT scan was anticipated by an increase in circulating NPTX2 methylation levels. CONCLUSIONS: Our study supports circulating NPTX2 methylation levels as a promising liquid biopsy-based clinical tool for non-invasive prognosis, monitoring disease evolution and response to treatment in mPDAC patients.

Acute skin toxicity of ultra-hypofractionated whole breast radiotherapy with simultaneous integrated boost for early breast cancer.

Background: Whole-breast irradiation (WBI) after breast conserving surgery (BCS) is indicated to improve loco-regional control and survival. Former studies showed that addition of tumor bed boost in all age groups significantly improved local control although no apparent impact on overall survival but with an increased risk of worse cosmetic outcome. Even though shortened regimens in 3 weeks are considered the standard, recent studies have shown the non-inferiority of a treatment regimen of 5 fractions in one-week in both locoregional control and toxicity profile, although simultaneous integrated boost (SIB) in this setting has been scarcely studied. Materials and Methods: From March-2020 to March-2022, 383 patients with early breast cancer diagnosis and a median age of 56 years-old (range 30-99)were included in a prospective registry of ultra-hypofractionated WBI up to a total dose of 26 Gy in 5.2 Gy/fraction with a SIB of 29 Gy in 5.8 Gy/fraction in 272 patients (71%), 30-31 Gy in 6-6.2 Gy/fraction in 111 patients (29%) with close/focally affected margins. Radiation treatment was delivered by conformal 3-D technique in 366 patients (95%), VMAT in 16patients (4%) and conformal 3-D with deep inspiration breath hold (DIBH) in 4patients (1%). Ninety-three per cent of patients received endocrine therapy and 43% systemic or targeted chemotherapy. Development of acute skin complications was retrospectively reviewed. Results: With a median follow-up of 18 months (range 7-31), all patients are alive without evidence of local, regional or distant relapse. Acute tolerance was acceptable, with null o mild toxicity: 182 (48%) and 15 (4%) patients developed skin toxicity grade 1 and 2 respectively; 9 (2%) and 2 (0.5%) patients breast edema grade 1and 2 respectively. No other acute toxicities were observed. We also evaluated development of early delayed complications and observed grade 1 breast edema in 6 patients (2%); grade 1 hyperpigmentation in 20 patients (5%); and grade 1 and 2 breast induration underneath boost region in 10(3%) and 2 patients (0.5%) respectively. We found a statistically significant correlation between the median PTVWBI and presence of skin toxicity (p = 0.028) as well as a significant correlation between late hyperpigmentation with the median PTVBOOST (p = 0.007) and the ratio PTVBOOST/PTVWBI (p = 0.042). Conclusion: Ultra-hypofractionated WBI + SIB in 5 fractions over one-week is feasible and well tolerated, although longer follow-up is necessary to confirm these results.

Standard Hypercaloric, Hyperproteic vs. Leucine-Enriched Oral Supplements in Patients with Cancer-Induced Sarcopenia, a Randomized Clinical Trial.

(1) Background: Malnutrition frequently affects patients with cancer, and it negatively impacts treatment tolerance, clinical outcomes and survival. Thus, appropriate nutritional screening and early nutrition support are extremely recommended. Currently, a significant number of oral supplements (OS) are commercially available; despite this, there is a lack of evidence for recommending specific OS, including leucine-enriched OS, for nutritional support in patients with cancer. (2) Aim: To compare the clinical evolution of patients with cancer (undergoing systemic treatment) that received standard hypercaloric, whey protein-based hyperproteic oral supplements vs. hypercaloric, hyperproteic leucine-enriched OS using a novel morphofunctional nutritional evaluation. (3) Patients and methods: This paper details an open-label, controlled clinical study in which patients were randomly assigned to receive nutritional treatment with whey protein-based hyperproteic oral supplements (control group) vs. hypercaloric, hyperproteic leucine-enriched OS (intervention group) during a twelve-week period. Forty-six patients were included; epidemiological, clinical, anthropometric, ultrasound (muscle echography of the rectus femoris muscle of the quadriceps and abdominal adipose tissue) and biochemical evaluation were performed. All patients received additional supplementation with vitamin D. (4) Results: Nutritional parameters (including bioimpedance, anthropometric, ultrasound and biochemical variables) of all included patients remained stable after the nutritional intervention. Extracellular mass tended to increase in the patients that received the leucine-enriched formula. Functionality (evaluated through the stand-up test) improved in both groups (p < 0.001). Prealbumin, transferrin levels and superficial adipose tissue increased in the control group (p < 0.05), while self-reported quality of life improved in all the evaluated patients (p < 0.001). (5) Conclusions: Nutritional support with hypercaloric, hyperproteic (with whey protein) OS and vitamin D supplementation were associated with the maintenance of body composition and improvements in functionality and in quality of life in the patients with cancer undergoing systemic treatment. No significant benefits were observed when a leucine-enriched formula was used.

The Frequency of Specific KRAS Mutations, and Their Impact on Treatment Choice and Survival, in Patients With Metastatic Colorectal Cancer.

BACKGROUND: Patients with metastatic colorectal cancer (mCRC) and KRAS mutations have a poor prognosis, seemingly dependent on the location of the mutation. This multicenter, retrospective, cohort study assessed the frequency and prognostic value of specific KRAS mutation codon locations in mCRC patients, and survival outcomes in relation to treatment. MATERIALS AND METHODS: Data from mCRC patients treated in 10 Spanish hospitals between January 2011 and December 2015 were analyzed. The main objective was to investigate (1) the impact of KRAS mutation location on overall survival (OS), and (2) the effect of targeted treatment plus metastasectomy and primary tumor location on OS in patients with KRAS mutations. RESULTS: The KRAS mutation location was known for 337/2002 patients. Of these, 177 patients received chemotherapy only, 155 received bevacizumab plus chemotherapy, and 5 received anti-epidermal growth factor receptor therapy plus chemotherapy; 94 patients underwent surgery. The most frequent KRAS mutation locations were G12A (33.8%), G12D (21.4%), and G12V (21.4%). Compared with other locations, patients with a G12S mutation had the shortest median OS (10.3 [95% CI, 2.5-18.0] months). OS was longer in patients who underwent surgery versus those who did not, with a trend toward prolonged survival with bevacizumab (median OS 26.7 [95% CI, 21.8-31.7] months) versus chemotherapy alone (median OS 23.2 [95% CI, 19.4-27.0] months). CONCLUSION: These findings confirm that KRAS mutation location may predict survival outcomes in patients with mCRC, and suggest that pre-/post-operative bevacizumab plus metastasectomy provides survival benefits in patients with KRAS mutations.

Stereotactic body radiation therapy (SBRT) for spinal metastases: 12 years of a single center experience.

OBJECTIVE: To assess the clinical outcomes of patients with spine metastases treated with SBRT at our institution. MATERIALS AND METHODS: Patients with spine metastases treated with SBRT (1 fraction/18 Gy or 5 fractions/7 Gy) during the last 12 years have been analyzed. All patients were simulated supine in a vacuum cushion or with a shoulder mask. CT scans and MRI image registration were performed. Contouring was based on International Spine-Radiosurgery-Consortium-Consensus-Guidelines. Highly conformal-techniques (IMRT/VMAT) were used for treatment planning. Intra and interfraction (CBCT or X-Ray-ExacTrac) verification were mandatory. RESULTS: From February 2010 to January 2022, 129 patients with spinal metastases were treated with SBRT [1 fraction/18 Gy (75%) or 5 fractions/7 Gy] (25%). For patients with painful metastases (74/129:57%), 100% experienced an improvement in pain after SBRT. With a median follow-up of 14.2 months (average 22.9; range 0.5-140) 6 patients (4.6%) experienced local relapse. Local progression-free survival was different, considering metastases's location (p < 0.04). The 1, 2 and 3 years overall survival (OS) were 91.2%, 85.1% and 83.2%, respectively. Overall survival was significantly better for patients with spine metastases of breast and prostate cancers compared to other tumors (p < 0.05) and significantly worse when visceral metastases were present (p < 0.05), when patients were metastatic de novo (p < 0.05), and in those patients receiving single fraction SBRT (p: 0.01). CONCLUSIONS: According to our experience, SBRT for patients with spinal metastases was effective in terms of local control and useful to reach pain relief. Regarding the intent of the treatment, an adequate selection of patients is essential to propose this ablative approach.

Behaviour of Vespa velutina nigrithorax (Hymenoptera: Vespidae) under Controlled Environmental Conditions.

From its introduction in Europe, Vespa velutina nigrithorax has become an invasive species, since it is a predator of native fruits and insects, most of the latter being honeybees. Despite the knowledge on the life cycle of this hornet, Asian hornet behaviour is not well understood, since in vivo studies on this species are quite difficult to perform. In this work, an observational study of the behaviour of this invasive species in captivity has been carried out. Two secondary and one embryo nests were caught and kept under controlled environmental conditions, up to 13 weeks for the secondary nest and 6 weeks for the embryo nest. Captivity adaptation, defence against perturbations, evolution of the colony and overwintering were the different behaviours studied. The study has shown the importance of avoiding disturbances to the nest from the beginning of the experiments, since they tend to destroy the colony. The aggressive behaviour observed in the embryo nest was lower than in the secondary nests. Results of this research will allow obtaining additional information on this species, which is crucial to develop effective control methods.

Primary Chemoradiotherapy Treatment (PCRT) for HER2+ and Triple Negative Breast Cancer Patients: A Feasible Combination.

Primary systemic treatment (PST) downsizes the tumor and improves pathological response. The aim of this study is to analyze the feasibility and tolerance of primary concurrent radio−chemotherapy (PCRT) in breast cancer patients. Patients with localized TN/HER2+ tumors were enrolled in this prospective study. Radiation was delivered concomitantly during the first 3 weeks of chemotherapy, and it was based on a 15 fractions scheme, 40.5 Gy/2.7 Gy per fraction to whole breast and nodal levels I-IV. Chemotherapy (CT) was based on Pertuzumab−Trastuzumab−Paclitaxel followed by anthracyclines in HER2+ and CBDCA-Paclitaxel followed by anthracyclines in TN breast cancers patients. A total of 58 patients were enrolled; 25 patients (43%) were TN and 33 patients HER2+ (57%). With a median follow-up of 24.2 months, 56 patients completed PCRT and surgery. A total of 35 patients (87.5%) achieved >90% loss of invasive carcinoma cells in the surgical specimen. The 70.8% and the 53.1% of patients with TN and HER-2+ subtype, respectively, achieved complete pathological response (pCR). This is the first study of concurrent neoadjuvant treatment in breast cancer in which three strategies were applied simultaneously: fractionation of RT (radiotherapy) in 15 sessions, adjustment of CT to tumor phenotype and local planning by PET. The pCR rates are encouraging.

HPLC-(Q)-TOF-MS-Based Study of Plasma Metabolic Profile Differences Associated with Age in Pediatric Population Using an Animal Model.

A deep knowledge about the biological development of children is essential for appropriate drug administration and dosage in pediatrics. In this sense, the best approximation to study organ maturation is the analysis of tissue samples, but it requires invasive methods. For this reason, surrogate matrices should be explored. Among them, plasma emerges as a potential alternative since it represents a snapshot of global organ metabolism. In this work, plasma metabolic profiles from piglets of different ages (newborns, infants, and children) obtained by HPLC-(Q)-TOF-MS at positive and negative ionization modes were studied. Improved clustering within groups was achieved using multiblock principal component analysis compared to classical principal component analysis. Furthermore, the separation observed among groups was better resolved by using partial least squares-discriminant analysis, which was validated by bootstrapping and permutation testing. Thanks to univariate analysis, 13 metabolites in positive and 21 in negative ionization modes were found to be significant to discriminate the three groups of piglets. From these features, an acylcarnitine and eight glycerophospholipids were annotated and identified as metabolites of interest. The findings indicate that there is a relevant change with age in lipid metabolism in which lysophosphatidylcholines and lysophoshatidylethanolamines play an important role.

SEOM-GETTHI clinical guideline for the practical management of molecular platforms (2021).

The improvement of molecular alterations in cancer as well as the development of technology has allowed us to bring closer to clinical practice the determination of molecular alterations in the diagnosis and treatment of cancer. The use of multidetermination platforms is spreading in most Spanish hospitals. The objective of these clinical practice guides is to review their usefulness, and establish usage guidelines that guide their incorporation into clinical practice.

Low toxicity deep eutectic solvent-based ferrofluid for the determination of UV filters in environmental waters by stir bar dispersive liquid microextraction.

In this work, a low toxicity deep eutectic solvent-based ferrofluid is presented for the first time as magnetic fluid to be used as an efficient solvent in liquid-based microextraction techniques. This ferrofluid is made of a hydrophobic deep eutectic solvent, composed by menthol and thymol in a 1:5 molar ratio as carrier solvent, and oleic acid-coated cobalt ferrite (CoFe2O4@oleic acid) magnetic nanoparticles. This material was characterized via magnetism measurement, scanning electron microscopy, infrared spectroscopy and density measurement. The determination of UV filters in environmental water samples was selected as model analytical application to test the extraction performance of this new ferrofluid by employing stir bar dispersive liquid microextraction, prior to liquid chromatography-tandem mass spectrometry analysis. The response surface methodology was used as a multivariate optimization method for extraction step. Under the optimized conditions, good analytical features were obtained, such as low limits of detection between 7 and 83 ng L-1, good repeatability (relative standard deviations, RSD (%) below 15%), enrichment factors between 46 and 101 and relative recoveries between 80 and 117%, proving the good extraction capability of this ferrofluid. Finally, the method was successfully applied to three environmental waters (beach and river waters), finding trace amounts of the target UV filters. The presented low toxicity deep eutectic solvent-based ferrofluid results to be a good alternative to conventional solvents used in liquid-phase microextraction techniques.

Aspergillus fumigatus Fumagillin Contributes to Host Cell Damage.

The activity of fumagillin, a mycotoxin produced by Aspergillus fumigatus, has not been studied in depth. In this study, we used a commercial fumagillin on cultures of two cell types (A549 pneumocytes and RAW 264.7 macrophages). This toxin joins its target, MetAP2 protein, inside cells and, as a result, significantly reduces the electron chain activity, the migration, and the proliferation ability on the A549 cells, or affects the viability and proliferation ability of the RAW 264.7 macrophages. However, the toxin stimulates the germination and double branch hypha production of fungal cultures, pointing out an intrinsic resistant mechanism to fumagillin of fungal strains. In this study, we also used a fumagillin non-producer A. fumigatus strain (∆fmaA) as well as its complemented strain (∆fmaA::fmaA) and we tested the fumagillin secretion of the fungal strains using an Ultra High-Performance Liquid Chromatography (UHPLC) method. Furthermore, fumagillin seems to protect the fungus against phagocytosis in vitro, and during in vivo studies using infection of immunosuppressed mice, a lower fungal burden in the lungs of mice infected with the ∆fmaA mutant was demonstrated.

Exploring the Decomposition Products of 1,3,3,3-Tetrafluoropropene and Perfluoro-(3-methylbutan-2-one) Gas Mixtures in Medium-Voltage Electrical Switchgear as Alternatives to SF6.

In this work, binary and ternary gas mixtures of 1,3,3,3-tetrafluoropropene, HFO-1234ze(E), and perfluoro-(3-methylbutan-2-one), CF3C(O)CF(CF3)2, with CO2 and synthetic air, are presented as alternatives to SF6 in medium-voltage electrical equipment. They were used in four medium-voltage switchgear cubicles replacing SF6 gas, and after a period of time, under permanent 30 kV AC voltage, gas mixture samples were extracted and analyzed on the same day using a validated methodology based on gas chromatography (GC) coupled to mass spectrometry (MS) and thermal conductivity (TCD). CF4 (tetrafluoromethane), C2F6 (hexafluoroethane), C3F6 (hexafluoropropylene), C3HF7 (1,1,1,2,2,3,3-heptafluoropropane), CH2F2 (difluoromethane), and the cis and trans-C3H2F4 (1,3,3,3-tetrafluoropropene) have been identified as decomposition products in these gas mixtures. In addition, a quantity of water has been observed, as well as CO in one of the cubicles. The most abundant decomposition products identified in gas mixture samples (C3HF7 and C3F6) together with water and CO content have been quantified using commercial gas mixture reference standards. The toxicity and global warming of the analyzed compounds are evaluated to determine the most adequate gas mixture among those studied as a candidate to substitute SF6.

Radiation therapy with curative intention in men with de novo metastatic prostate carcinoma: shoot'em all!

BACKGROUND: About 5% of prostate cancer cases are metastatic at diagnoses. Radiotherapy of both primary tumor and secondary lesions can be, in addition to systemic treatments, a radical alternative for selected patients. MATERIALS AND METHODS: Patients with de novo prostate carcinoma with bone or lymph node metastases were retrospectively reviewed. All patients received moderate hypofractionated IMRT/VMAT up to 63 Gy in 21 daily fractions of 3 Gy to prostate and metastases with neoadjuvant and concurrent androgen deprivation therapy (ADT). According to known advances some patients also received abiraterone, enzalutamide, or docetaxel. RESULTS: Between 2015-2020, we attended 26 prostate cancer patients (median age 69.5 years, range 52-84) with simultaneous oligometastases [mean 2.1 metastases, median 1.5 metastases (range 1-6)]. Eighteen patients (69%) presented lymph node metastases, 4 (15.5%) bone metastases and 4 (15.5%) both lymph node and bone metastases. With a median follow-up of 15.5 months (range 3-65 months), 16 patients (62%) are alive and tumor free while 10 (38%) are alive with tumor. Four patients (17%) developed tumor progression, out of irradiated area in all cases, with a median time to progression of 43.5 months (range 27-56 months). Actuarial progression-free survival (PFS) rates at 12 and 24 months were 94.1% and 84.7%, respectively. No grade > 2 acute or late complications were recorded. CONCLUSIONS: Simultaneous directed radical hypofractionated radiation therapy for prostate and metastases is feasible, well tolerated and achieves an acceptable PFS rate. However, further studies with longer follow-up are necessary to definitively address these observations.