Functional characterization of the riboflavin-overproducing and dextran-producing Weissella cibaria BAL3C-5 C120T strain for the development of biofortified plant-based beverages.

Riboflavin (vitamin B2) is essential for human beings and it has to be provided by healthy nutrition. The use of fermentation with riboflavin-overproducing lactic acid bacteria (LAB) represents an ideal strategy to generate, by in situ biofortification, functional drinks. These beverages can positively contribute to consumer health and address nutritional deficiencies. In the present work, the functional capabilities of Weissella cibaria BAL3C-5 C120T for riboflavin-overproduction and dextran-production during fermentation of oat-, rice-, soybean- and almond-based drinks have been evaluated. It was confirmed that the strain was capable of producing riboflavin and dextran in the analysed drinks. This property was especially pronounced in the oat-based drink, where after 24 h of fermentation the strain was able to increase riboflavin and dextran levels up to 3.4 mg/L and 3.2 g/L, respectively. Moreover, under optimized conditions the strain was able to enrich the fermented oat-based drinks with the prebiotic oligosaccharide panose (up to 6.6 g/L). In addition, in the oat-based drinks BAL3C-5 C120T showed a good pH-lowering ability (from 7.0 to 3.8) as well as a high 80 % cell viability after one month of storage. Rheological analysis of the resulting fermented oat-based beverages revealed a thixotropic structure related to a gel-like behaviour which was not observed in the non-fermented control drinks. In summary, these results confirmed the unique characteristics of W. cibaria BAL3C-5 C120T strain for the development of biofortified and functional plant-based beverages with improved nutritional and rheological properties. Analysis of the BAL3C-5 C120T strain survival under gastrointestinal conditions and its autoaggregation properties, also indicated its potential use as a probiotic delivered in an oat-based fermented beverage. In this context, this study also promotes the utilization of W. cibaria species in health and food industries where it has not yet been used as a starter or adjunct culture.

SEOM clinical guidelines on venous thromboembolism (VTE) and cancer (2023).

The Spanish Society of Medical Oncology (SEOM) last published clinical guidelines on venous thromboembolism (VTE) and cancer in 2019, with a partial update in 2020. In this new update to the guidelines, SEOM seeks to incorporate recent evidence, based on a critical review of the literature, to provide practical current recommendations for the prophylactic and therapeutic management of VTE in patients with cancer. Special clinical situations whose management and/or choice of currently recommended therapeutic options (low-molecular-weight heparins [LMWHs] or direct-acting oral anticoagulants [DOACs]) is controversial are included.

The role of emotion regulation through mindfulness in oncological patients: A pilot study.

BACKGROUND: Traditional MBSR or MBTC programs do not delve deeply enough into emotional regulation, which is especially relevant in oncological patients. The aim of this study was to analyze the benefits of a mindfulness-based emotion regulation program in adult oncological patients. METHOD: Psycho-oncologists from the AECC developed a mindfulness-based emotion regulation program. The Five Facet Mindfulness Questionnaire (FFMQ), Trait Meta-Mood Scale (TMMS), and Hospital Anxiety and Depression Scale (HADS) were administered before and after the program. A single-group pre-post test design with repeated measures was employed, utilizing the General Linear Model. RESULTS: Ninety-seven adult cancer patients completed the pre- and post-program assessments. Statistically significant improvements were observed in all FFMQ subscales, increased clarity of emotional discrimination, mood repair, and statistically significant reductions in anxiety and depressive symptoms. CONCLUSIONS: Regardless of the phase of the disease, the results of this study suggest that emotional regulation may improve and anxiety and depressive symptomatology decrease after a mindfulness-based emotion regulation program in oncological patients.

Real-world dosing patterns of regorafenib for patients with metastatic colorectal cancer in Spain: the RE-SEARCH study.

PURPOSE: To describe the dosing patterns of regorafenib in a real-world population of patients with metastatic colorectal cancer (mCRC) in a routine clinical practice setting in Spain, focusing on the starting dose of regorafenib. METHODS: An observational, retrospective, multicenter study that included patients ≥ 18 years old who had histologically documented mCRC and who had initiated treatment with regorafenib since January 2017. Post hoc categorization of dosing patterns revealed the following: initial dose < 160 mg and dose escalation, initial dose < 160 mg and maintenance, initial dose equal to 160 mg and maintenance, and initial dose equal to 160 mg and dose reduction. RESULTS: Most patients (152/241, 63.8%) initiated treatment with regorafenib at doses < 160 mg. There was large variation in the starting dose of regorafenib over time: in 2017, most patients (59%) initiated regorafenib at a dose of 160 mg, this proportion decreased to 6% in 2021. There were no significant differences in the median progression-free survival according to the regorafenib dose patterns during the first two cycles. The proportion of patients who reported at least one adverse event (AE), had a grade 3-4 AE or had an AE leading to dose reduction was greater in the group of patients who received an initial dose equal to 160 and reduction. CONCLUSIONS: Our results indicate that physicians in Spain have gradually adopted a dose-escalation approach during cycle 1, which is a common practice for starting treatment with a reduced dose (< 160 mg/day), a strategy that seems to improve tolerability while maintaining efficacy. TRIAL REGISTRATION: Not applicable.

Global Variation in Escherichia coli mcr-1 Genes and Plasmids from Animal and Human Genomes Following Colistin Usage Restrictions in Livestock.

Antimicrobial resistance (AMR) is a significant global health threat, with multidrug-resistant (MDR) bacterial clones becoming a major concern. Polymyxins, especially colistin, have reemerged as last-resort treatments for MDR Gram-negative infections. However, colistin use in livestock has spread mobile colistin resistance (mcr) genes, notably mcr-1, impacting human health. In consequence, its livestock use was banned in 2017, originating a natural experiment to study bacterial adaptation. The aim of this work was to analyse the changes in the mcr-1 genetic background after colistin restriction across the world. This study analyses 3163 Escherichia coli genomes with the mcr-1 gene from human and livestock hosts, mainly from Asia (n = 2621) and Europe (n = 359). Genetic characterisation identifies IncI2 (40.4%), IncX4 (26.7%), and multidrug-resistant IncHI2 (18.8%) as the most common plasmids carrying mcr-1. There were differences in plasmids between continents, with IncX4 (56.6%) being the most common in Europe, while IncI2 (44.8%) was predominant in Asia. Promoter variants related to reduced fitness costs and ISApl1 showed a distinct pattern of association that appears to be associated with adaptation to colistin restriction, which differed between continents. Thus, after the colistin ban, Europe saw a shift to specialised mcr-1 plasmids as IncX4, while ISApl1 decreased in Asia due to changes in the prevalence of the distinct promoter variants. These analyses illustrate the evolution of mcr-1 adaptation following colistin use restrictions and the need for region-specific strategies against AMR following colistin restrictions.

AMBER: A Device for Hand Motor and Cognitive Rehabilitation-Development and Proof of Concept.

Stroke survivors usually exhibit concurrent motor and cognitive impairment. Historically, rehabilitation strategies post-stroke occur separately in terms of motor and cognitive functions. However, recent studies show that hand motor interventions can have a positive impact on cognitive recovery. In this work, we introduce AMBER (portAble and Modular device for comprehensive Brain Evaluation and Rehabilitation), a new device developed for the evaluation and rehabilitation of both hand motor function and cognition simultaneously. AMBER is a simple, portable, ergonomic and cheap device based on Force Sensitive Resistors, in which every finger interaction is recorded to provide information about finger strength, processing speed, and memory status. This paper presents the requirements of the device and the design of the system. In addition, a pilot study was conducted with 36 healthy individuals using the evaluation module of the device to assess its psychometric properties, as test-retest reliability and measurement error. Its validity was also evaluated comparing its measurements with three different gold standards for strength, processing speed and memory. The device showed good test-retest reliability for strength (ICC =0.741-0.852), reaction time (ICC =0.715 - 0.900) and memory (ICC =0.556-0.885). These measures were correlated with their corresponding gold standards (r =0.780-890). AMBER shows great potential to impact hand rehabilitation, offering therapists a valid, reliable and versatile tool to comprehensively assess patients. With ongoing advancements and refinements, it has the opportunity to significantly impact rehabilitation practices and improve patient outcomes.

Scn1a haploinsufficiency in the prefrontal cortex engages to cognitive impairment and depressive phenotype.

Altered development and function of the prefrontal cortex (PFC) during adolescence is implicated in the origin of mental disorders. Deficits in the GABAergic system prominently contribute to these alterations. Nav1.1 is a voltage-gated Na+ channel critical for normal GABAergic activity. Here, we studied the role of Nav1.1 in PFC function and its potential relationship with the aetiology of mental disorders. Dysfunction of Nav1.1 activity in the medial PFC (mPFC) of adolescent mice enhanced the local excitation/inhibition ratio, resulting in epileptic activity, cognitive deficits and depressive-like behaviour in adulthood, along with a gene expression profile linked to major depressive disorder (MDD). Additionally, it reduced extracellular serotonin concentration in the dorsal raphe nucleus and brain-derived neurotrophic factor expression in the hippocampus, two MDD-related brain areas beyond the PFC. We also observed alterations in oscillatory activity and impaired hippocampal-mPFC coherence during sleep. Finally, we found reduced expression levels of SCN1A, the gene encoding Nav1.1, in post-mortem PFC samples from human MDD subjects. Collectively, our results provide a novel mechanistic framework linking adolescence-specific alterations in Nav1.1 function in the PFC to the pathogenesis of epilepsy and comorbidities such as cognitive impairment and depressive disorders.

Dual-language testing improves bilinguals' verbal scores.

Objective: Research demonstrates that college educated, English language dominant bilinguals underperform relative to English speaking monolinguals on tests of verbal ability. We investigated whether accepting responses in their two languages would reveal improved performance in bilinguals, and whether such improvement would be of sufficient magnitude to demonstrate the same performance level as monolinguals. Method: Participants were college students attending the same university. Spanish-English bilinguals were compared to English speaking monolinguals on the Bilingual Verbal Ability Tests (BVAT), which include Picture Vocabulary, Oral Vocabulary, and Verbal Analogies. Results: When given the opportunity to respond in Spanish to items failed in English, bilinguals obtained significantly higher scores on all three subtests, and their performance matched that of monolinguals on Oral Vocabulary and Verbal Analogies. Conclusion: An "either-language" scoring approach may enable optimal measurement of verbal abilities in bilinguals. We provide normative data for use in applying the either-language scoring approach on subtests of the BVAT. We discuss the findings in the context of clinical assessment.

Rechallenge with Anti-EGFR Treatment in RAS/BRAF wt Metastatic Colorectal Cancer (mCRC) in Real Clinical Practice: Experience of the GITuD Group.

BACKGROUND: There are few third- and fourth-line therapeutic options for metastatic colorectal cancer (mCRC). In RAS/BRAF wild-type (wt) mCRC previously treated with anti-epidermal growth factor receptor (anti-EGFR) (first-line) and relapsed after a good response, retreatment with anti-EGFR (rechallenge) emerges as a therapeutic alternative. OBJECTIVE: The aim was to show the activity and safety of anti-EGFR rechallenge in RAS/BRAF wt mCRC in real-world practice. PATIENTS AND METHODS: A multicenter, retrospective, observational study (six hospitals of the Galician Group of Research in Digestive Tumors) was conducted. Adult patients with RAS/BRAF wt mCRC, evaluated by liquid biopsy, were included. They received anti-EGFR rechallenge (cetuximab, panitumumab) as monotherapy, or combined with chemotherapy, in third- or subsequent lines. Efficacy (overall response rate [ORR], disease control rate [DCR], overall survival [OS], and progression-free survival [PFS]) and safety (incidence of adverse events [AEs]) were assessed. RESULTS: Thirty-one patients were analyzed. Rechallenge (median 6 cycles [range 1-27], mainly cetuximab [80.7%]), started at a median anti-EGFR-free time of 18.4 months (1.7-37.5 months) after two (38.7%) or more (61.3%) lines of treatment; 64.5% of patients received a full dose. Median OS and PFS were 9.8 months (95% confidence interval [CI] 8.2-11.4) and 2.6 months (95% CI 1.7-3.4), respectively. ORR was 10%, and DCR was 30%. The most common AEs were diarrhea (35.5%), anemia (29%), emesis (6.4%), and neutropenia (6.4%); < 5% grade ≥ 3; 48.4% of patients reported anti-EGFR-related skin toxicity (grade > 1). Hypomagnesemia required supplements in 29% of patients. Dose delays (≥ 3 days) and reduction (≥ 20%) were reported in 11 (35.5%) and seven patients (22.6%), respectively. CONCLUSIONS: In RAS/BRAF wt mCRC patients, an anti-EGFR rechallenge provides a feasible therapeutic option with clinical benefit (survival) and a manageable safety profile.

Sequential RAS mutations evaluation in cell-free DNA of patients with tissue RAS wild-type metastatic colorectal cancer: the PERSEIDA (Cohort 2) study.

PURPOSE: RAS (KRAS/NRAS) mutational status on a tumor biopsy is mandatory to guide the best treatment in metastatic colorectal cancer (mCRC). Determining the RAS mutational status by tumor-tissue biopsy is essential in guiding the optimal treatment decision for mCRC. RAS mutations are negative predictive factors for the use of EGFR monoclonal antibodies. Cell-free DNA (cfDNA) analysis enables minimally invasive monitoring of tumor evolution. METHODS/PATIENTS: PERSEIDA was an observational, prospective study assessing cfDNA RAS, BRAF and EGFR mutations (using Idylla™) in first-line mCRC, RAS wild-type (baseline tumor-tissue biopsy) patients (cohort 2). Plasma samples were collected before first-line treatment, after 20 ± 2 weeks, and at disease progression. RESULTS: 117 patients were included (103 received panitumumab + chemotherapy as first-line treatment). At baseline, 7 (6.8%) patients had RAS mutations, 4 (3.9%) BRAF mutations and no EGFR mutations were detected (cfDNA, panitumumab + chemotherapy subpopulation [panitumumab + Ch]). The baseline RAS mutational status concordance between tissue and liquid biopsies was 94.0% (93.2%, panitumumab + Ch). At 20 weeks, only one patient in the study (included in the panitumumab + Ch) had an emerging cfDNA RAS mutation. No emerging BRAF or EGFR mutations were reported. At disease progression, 6 patients had emergent mutations not present at baseline (RAS conversion rate: 13.3% [6/45]; 15.0% [6/40], panitumumab + Ch). CONCLUSIONS: The concordance rate between liquid and solid biopsies at baseline was very high, as previously reported, while our results suggest a considerable emergence of RAS mutations during disease progression. Thus, the dynamics of the genomic landscape in ctDNA may provide relevant information for the management of mCRC patients.