Metagenetic and Volatilomic Approaches to Elucidate the Effect of Lactiplantibacillus plantarum Starter Cultures on Sicilian Table Olives

The present study aimed to evaluate the effect of selected Lactiplantibacillus plantarum strains on both microbiota composition and volatile organic compound profile of Sicilian table olives. Two mixed cultures, named O1 and O2, were set up for pilot-plan scale fermentations at 5% of NaCl. Uninoculated table olives at 5 and 8% (C5 and C8) of salt were used as control. The fermentation process was monitored until 80 days through a dual approach, which included both classical microbiological and 16S amplicon-based sequencing and volatilomics analyses. Compared with control samples (C5 and C8), experimental samples, inoculated with starter cultures (O1 and O2), exhibited a faster acidification with a more pronounced drop in pH. Metagenetics data revealed significant differences of microbiota composition among samples, highlighting the dominance of lactobacilli in both experimental samples; a high occurrence of Enterobacter genus only in control samples with 5% of NaCl; and the presence of Bacteroides, Faecalibacterium, Klebsiella, and Raoultella genera only in control samples with 8% of NaCl. Furthermore, microbiota composition dynamics, through the fermentation process, significantly affected the volatile organic compounds of the final products, whereas no compounds involved in off-odors metabolites were detected in all samples investigated. In conclusion, the addition of the proposed starter cultures and the use of low concentrations of sodium chloride positively affected the microbiota and volatile organic compounds, ensuring the microbiological safety and the pleasant flavors of the final product

Targeting PI3K/AKT/mTOR Pathway in Breast Cancer: From Biology to Clinical Challenges

Breast cancer (BC) is the most common women cancer and cause of cancer death. Despite decades of scientific progress in BC treatments, the clinical benefit of new drugs is modest in several cases. The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway mutations are frequent in BC (20-40%) and are significant causes of aggressive tumor behavior, as well as treatment resistance. Improving knowledge of the PI3K/AKT/mTOR pathway is an urgent need. This review aims to highlight the central role of PI3K-mTORC1/C2 mutations in the different BC subtypes, in terms of clinical outcomes and treatment efficacy. The broad base of knowledge in tumor biology is a key point for personalized BC therapy in the precision medicine era

T-DM1 efficacy in trastuzumab-pertuzumab pre-treated HER2 positive metastatic breast cancer patients: a meta-analysis.

Background: Current guidelines consider T-DM1 the standard 2nd line therapy for HER2 positive metastatic breast cancer (MBC) patients following trastuzumab (T) + pertuzumab (P) and taxane 1st line treatment. Despite this, there are no prospective studies supporting this sequence. Methods: We performed a meta-analysis using real world data to determine the efficacy of T-DM1 after 1st line TP in HER2 positive MBC patients. We used a random-effect model to find differences in the rate of 1-year progression free survival (PFS) between TP pre-treated population and the EMILIA phase III pivotal trial. Results: Seven studies were eligible. The meta-analysis showed a combined 1-year PFS risk difference for T-DM1 efficacy after TP in 2nd or more lines of -0.122, with lower and upper limits of -0.253 and 0.010, respectively (p = 0.07), with low heterogeneity among studies (I2 0.01%, p = 0.836). Considering the four studies on T-DM1 in 2nd line setting, 1-year PFS risk was -0.034 (95% CI -0.207 - 0,139; p = 0.701) (I2 0.01%, p = 0.91). Conclusion: Overall, the efficacy of T-DM1 after TP seems to be similar to that previously reported in the EMILIA trial. In the second line setting, data are not mature enough to confirm T-DM1 efficacy in TP pre-treated population

Saccharomyces hybrids as a tool for improving the quality of Moscato di Siracusa DOC wine

The study aimed to evaluate four Saccharomyces cerevisiae strains, one intraspecific S. cerevisiae hybrid, and five interspecific S. cerevisiae×S. uvarum hybrids with respect to the quality of Moscato di Siracusa DOC wine by comparing them with a commercial Saccharomyces cerevisiae strain. Most of the interspecific hybrids maintained volatile acidity (VA) at very low levels, produced high concentrations of glycerol, malic and succinic acid, and yielded the highest concentration of positive sensory attributes. On the basis of the results of these experimental fermentation trials, a real opportunity to produce special wines employing S. cerevisiae×S. uvarum hybrids is proposed.The study aimed to evaluate four Saccharomyces cerevisiae strains, one intraspecific S. cerevisiae hybrid, and five interspecific S. Cerevisiae×S. uvarum hybrids with respect to the quality of Moscato di Siracusa DOC wine by comparing them with a commercial Saccharomyces cerevisiae strain.Most of the interspecific hybrids maintained volatile acidity (VA) at very low levels, producedhigh concentrations of glycerol, malic and succinic acid, and yielded the highest concentrationof positive sensory attributes.On the basis of the results of these experimental fermentation trials, a real opportunity to producespecial wines employing S. cerevisiae×S. uvarum hybrids is proposed

Effects of different stress parameters on growth and on oleuropein-degrading abilities of lactiplantibacillus plantarum strains selected as tailored starter cultures for naturally table olives

The use of β-glucosidase positive strains, as tailored-starter cultures for table olives fermentation, is a useful biotechnological tool applied to accelerate the debittering process. Nowadays, strains belonging to Lactiplantibacillus plantarum species are selected for their high versatility and tolerance to stress conditions. The present study investigated the effect of different stress factors (pH, temperature and NaCl) on growth and on oleuropein-degrading abilities of selected L. plantarum strains. In addition, the presence of the beta-glucosidase gene was investigated by applying a PCR based approach. Results revealed that, overall, the performances of the tested strains appeared to be robust toward the different stressors. However, the temperature of 16 °C significantly affected the growth performance of the strains both singularly and in combination with other stressing factors since it prolongs the latency phase and reduces the maximum growth rate of strains. Similarly, the oleuropein degradation was mainly affected by the low temperature, especially in presence of low salt content. Despite all strains displayed the ability to reduce the oleuropein content, the beta-glucosidase gene was detected in five out of the nine selected strains, demonstrating that the ability to hydrolyze the oleuropein is not closely related to the presence of beta-glucosidase. Data of the present study suggest that is extremely important to test the technological performances of strains at process conditions in order to achieve a good selection of tailored starter cultures for table olives

Predictive factors for relapse in triple-negative breast cancer patients without pathological complete response after neoadjuvant chemotherapy

IntroductionTriple-negative breast cancer (TNBC) patients who do not obtain pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) present higher rate of relapse and worse overall survival. Risk factors for relapse in this subset of patients are poorly characterized. This study aimed to identify the predictive factors for relapse in TNBC patients without pCR after NACT. MethodsWomen with TNBC treated with NACT from January 2008 to May 2020 at the Modena Cancer Center were included in the analysis. In patients without pCR, univariate and multivariable Cox analyses were used to determine factors predictive of relapse. ResultsWe identified 142 patients with a median follow-up of 55 months. After NACT, 62 patients obtained pCR (43.9%). Young age at diagnosis (<50 years) and high Ki-67 (20%) were signi!cantly associated with pCR. Lack of pCR after NACT resulted in worse 5-year event-free survival (EFS) and overall survival (OS). Factors independently predicting EFS in patients without pCR were the presence of multifocal disease [hazard ratio (HR), 3.77; 95% CI, 1.45-9.61; p=0.005] and residual cancer burden (RCB) III (HR, 3.04; 95% CI, 1.09-9.9; p=0.04). Neither germline BRCA status nor HER2-low expression were associated with relapse. DiscussionThese data can be used to stratify patients and potentially guide treatment decision-making, identifying appropriate candidates for treatment intensi!cation especially in neo-/adjuvant setting

Effectiveness of perampanel as the only add-on: Retrospective, multicenter, observational real-life study on epilepsy patients

Objective: Perampanel (PER) is indicated as adjunctive antiseizure medication (ASM) in adolescents and adults with epilepsy. Data from clinical trials show good efficacy and tolerability, while limited information is available on the routine clinical use of PER, especially when used as only add-on treatment. Methods: We performed an observational, retrospective, multicenter study on people with focal or generalized epilepsy aged >12 years, consecutively recruited from 52 Italian epilepsy centers. All patients received PER as the only add-on treatment to a background ASM according to standard clinical practice. Retention rate, seizure frequency, and adverse events were recorded at 3, 6, and 12 months after PER introduction. Subanalyses by early or late use of PER and by concomitant ASM were also conducted. Results: Five hundred and three patients were included (age 36.5 ± 19.9 years). Eighty-one percent had focal epilepsy. Overall, the retention rate was very high in the whole group (89% at 12 months) according with efficacy measures. No major differences were observed in the subanalyses, although patients who used PER as early add-on, as compared with late add-on, more often reached early seizure freedom at 3-month follow-up (66% vs 53%, P =.05). Treatment-emergent adverse events occurred in 25%, far less commonly than in PER randomized trials. Significance: This study confirms the good efficacy and safety of PER for focal or generalized epilepsy in real-life conditions. We provide robust data about its effectiveness as only add-on treatment even in patients with a long-standing history of epilepsy and previously treated with many ASMs

Sustained seizure freedom with adjunctive brivaracetam in patients with focal onset seizures

The maintenance of seizure control over time is a clinical priority in patients with epilepsy. The aim of this study was to assess the sustained seizure frequency reduction with adjunctive brivaracetam (BRV) in real-world practice. Patients with focal epilepsy prescribed add-on BRV were identified. Study outcomes included sustained seizure freedom and sustained seizure response, defined as a 100% and a ≥50% reduction in baseline seizure frequency that continued without interruption and without BRV withdrawal through the 12-month follow-up. Nine hundred ninety-four patients with a median age of 45 (interquartile range = 32–56) years were included. During the 1-year study period, sustained seizure freedom was achieved by 142 (14.3%) patients, of whom 72 (50.7%) were seizure-free from Day 1 of BRV treatment. Sustained seizure freedom was maintained for ≥6, ≥9, and 12 months by 14.3%, 11.9%, and 7.2% of patients from the study cohort. Sustained seizure response was reached by 383 (38.5%) patients; 236 of 383 (61.6%) achieved sustained ≥50% reduction in seizure frequency by Day 1, 94 of 383 (24.5%) by Month 4, and 53 of 383 (13.8%) by Month 7 up to Month 12. Adjunctive BRV was associated with sustained seizure frequency reduction from the first day of treatment in a subset of patients with uncontrolled focal epilepsy