Roche (Italy)

Sewage sludge ash (SSA) can be exploited for phosphorus recovery, as it contains about 5-15% of this element by mass. However, residual waste remains and requires valorization to avoid disposal costs. This study investigates fluidized bed mono-combusted ash from sewage treatment for water remediation within a circular economy framework. Acid treatment, primarily applied for phosphorus extraction and recovery, was here followed by the valorization of the residual ash as an adsorbent, since this step simultaneously increases porosity and surface area. Characterization by SEM, BET, XRD, ICP-OES and pHPZC provided insights into structural and chemical changes in SSA and its activated form (ASSA). Results showed complete phosphorus removal, surface area increase from 1.51 to 16.18m2/g, and compositional phase modifications. Batch adsorption experiments were performed on solutions mono-contaminated with four anionic organic dyes bearing sulphonate groups and methylene blue as a representative cationic dye. ASSA resulted in being much more effective in the removal of the anionic dyes, with the adsorption efficiency gap increasing at higher contaminants' concentrations, while no significant difference was observed in the adsorption of methylene blue. Isotherms and kinetics of the decontamination processes allowed elucidating the adsorption mechanisms, which differ for different dyes and in some cases between SSA and ASSA. Sustainability analysis, using the ESCAPE tool, indicates that the produced adsorber may be competitive with activated carbons in terms of overall environmental impact, despite its lower adsorption efficiency. The successful regeneration and reuse of ASSA is contingent upon the types and levels of contaminants present.

4552 Background: Although the genomic landscape of mccRCC has been already documented in the literature, previous clinico-genomic studies have been constrained by small sample sizes, or a narrow focus on specific genes. In this large-scale study, we aimed at investigating the real-world frequency and co-occurrence of genomic alterations (GAs) detected in mccRCC samples. Methods: This study used the nationwide (US-based) de-identified FH-FMI CGDB. The de-identified data originated from approximately 280 US cancer clinics (~800 sites of care). Eligible patients (pts) were adults diagnosed with mccRCC, with FH-EHR records between January 1, 2011 and December 31, 2022. GAs were identified in the same time span via comprehensive genomic profiling using FMI tests on tumor tissue and blood samples. Co-occurrence and mutual exclusivity were assessed using Fisher's exact test, with multiple testing correction. Clustering analysis was performed on the gene network graph derived from significant interactions. Results: Out of 1,409 pts with renal cell carcinoma, 923 (65.5%) mccRCC were considered, with a median age at the diagnosis of metastatic disease of 61 years (IQR: 54-69). The majority were male (70.3%) and white (71.1%). Nearly 89% (822) received systemic therapy, with a median number of 2 treatment lines (IQR: 1-4). A total of 958 samples were sequenced, of which 92.2% were performed on tissue, and 7.8% on blood. GAs (81.1% short variant, 17.1% copy number variant, and 1.8% rearrangement) were found in 246 different genes, with a median number of mutated genes per pts of 3 (IQR: 2-5), while in 22 (2.4%) pts, no GAs were detected. VHL (69.7%), PBRM1 (39.9%), SETD2 (24.2%), CDKN2A (19.0%), BAP1 (15.6%), CDKN2B(14.8%), TP53 (14.1%), KDM5C (13.5%), PTEN (11.2%), and TERT (8.7%) were the top-10 mutated genes. Tumor Mutational Burden (TMB) was evaluated in 639 tissue samples, with a median value of 2.6 mut/Mb; 1.6% only of the tumors studied had high TMB. Out of the 796 samples examined for microsatellite instability (MSI), only 0.6% harbored MSI-intermediate, and none showed MSI-high. Co-occurrence analysis revealed 32 significant gene interactions. CDKN2A/B were significantly associated with MTAP, BAP1, and NF2, while PBRM1 was enriched with VHL, SETD2, KDM5C, and MTOR. TSC1co-occurred with TERT, TP53, and VHL.Three clusters of co-occurring genes were identified: (1) VHL, SETD2, PBRM1, KDM5C, MTOR, and NFE2L2; (2) TP53, TSC1, and TERT; (3) CDKN2A, CDKN2B, BAP1, NF2, MTAP, and ARID1A. Mutually exclusive patterns were observed between cluster 1 and cluster 3 genes. Notably, BAP1 was mutually exclusive with PBRM1. Conclusions: This is the largest analysis of the genomic landscape of mccRCC. We identified 3 clusters of co-occurring genes, whose prognostic/predictive value will be object of future research.

Fermented milks are a source of bioactive peptides with different potential benefits on human health and may be considered as functional foods. Sheep milk and fermented milk have been collected and a biochemical characterization, by a proteomic approach, GC/MS and microtiter plate assay methods, have been conducted to evaluate their peptide, fatty acid and aromatic profile, and to assess potential health promoting effects. Furthermore, a comparison between sheep-fermented milk (SFM) made with commercial starter cultures and YoAlp®, a sheep-fermented milk obtained using local strains of lactic acid bacteria, has been performed. Peptide’s profile comparison shows a higher number of amino acidic frequencies using autochthonous starter cultures than commercial ones. Among these peptides, 20.78% and 29.87%, respectively, are supposed to be potentially bioactive. Furthermore, in both products, the fatty acid profile was similar to that of origin sheep milk, and concerning aromatic profile, YoAlp® shows yogurt typical aromatic assets. Considering bioactivity, ACE inhibitor activity is high for both samples. Similar values, as expected by peptide profile analysis, have been obtained. Even in the case of antioxidant capacity, peptide profile bioactivity prediction has been confirmed by the assay showing a DPPH inhibition higher for SFM than for YoAlp®, but this difference is not statistically significant. Local strains of lactic acid bacteria seem to work as well as the commercial, preserving biodiversity and typicality. However, further analyses are needed to understand microbial proteolytic activities and to investigate gastric digestion resistance of bioactive peptides.

Abstract Background The burden of severe haemophilia A (HA) has been studied extensively owing to the higher bleeding frequency and associated treatment requirements, leaving a clear unmet need for research focused on the burden of mild and moderate HA. Aims This study sought to characterise the clinical and psychosocial burden of mild and moderate HA in the Italian cohort of the CHESS II study. Methods This was a retrospective analysis of clinical and psychosocial outcomes in a cohort of male adults (≥18 years old) with mild or moderate HA who participated in the cross-sectional CHESS II study (October 2019-November 2020). Treatment patterns, acute and chronic clinical outcomes and mental health indicators were collected via physician-completed forms. Psychosocial outcomes related to impact of HA on social activities, exercise, opportunities, and lifestyle were collected via a participant self-complete questionnaire. All results were reported descriptively. Results A total of 113 people with haemophilia A (PwHA) were included, 79 (70%) with moderate HA and 34 (30%) with mild HA, with mean age of 41.4 and 36.6 years, respectively. No one in the sample was receiving a prophylaxis at the time of data capture, with factor VIII use in the 12 months prior reported in 30% and 29% of moderate and mild PwHA, respectively. Ninety-one PwHA (81%) experienced ≥1 bleeding event in the preceding 12 months. People with moderate HA had higher mean annual bleed rate (2.9 vs. 1.1, respectively) and higher prevalence of chronic pain (74% vs. 35%), anxiety (20% vs. 12%), and/or depression (15% vs. 3%). Target joints were reported in 22% and 12% of moderate and mild PwHA, and problem joints in 51% and 12%, respectively. Of 113 participants, 44 (39%) completed the self-complete form (moderate HA, 57%; mild HA, 43%). Overall, 40% vs. 10% of those with moderate vs mild HA reported reducing or giving up social activities, 44% vs. 21% reducing or giving up exercise, 36% vs. 26% missing out on opportunities, and 48% vs. 26% reported HA impacted their lifestyle. Conclusion Moderate PwHA from the Italian CHESS II cohort appeared to have greater clinical morbidity and lifestyle impact than mild PwHA. Psychosocial outcomes were also worse among moderate PwHA, but significant burden was also observed among mild PwHA. These findings, and the absence of prophylactic treatment in the sample examined, highlight that improving management for potentially undertreated mild/moderate PwHA may aid the avoidance long-term clinical morbidity and negative psychosocial impact.

Background: Functional beverages are ordinary foods with components or ingredients able to provide specific health effects other than purely nutritional effect. Aim: This study aims to formulate a new functional beverage obtained from the recovery of YoAlp® whey, a bovine fermented milk obtained using autochthonous starter cultures, added with Renetta Canada/Golden Delicious-Raspberry (YWL), Renetta Canada-Aronia (YWA) and Ravèntse (YWR) fruit juices to improve the functionality of the beverage. Methods: Microbiological analysis and chemical characterization, by a proteomic approach and spectrophotometric microassay, have been conducted on beverages to investigate the expected shelf-life and potential health promoting effects. Results: The microbiological assessment confirmed the safety of the beverages and the probiotic bacteria vitality over a shelf life of seven days. Biochemical analysis performed highlight the presence of different bioactive peptides (ACE inhibitory and antioxidant), and the betacasomorphin 9 (BCM-9), marker of A2 variant of β-casein typically present in Aosta Valley cattle breeds. Moreover, high amounts of total polyphenols, which concur to the antioxidant activity values observed, have been found. Furthermore, ACE inhibitory activity is well correlated to the bioactive peptides detected. Finally, a consumer test confirmed the YoAlp® whey-based beverages appreciation. Conclusions: The production of these beverages could represent a huge opportunity for Aosta Valley’s farms to increase their income and competitiveness, creating a circular economy by recovering a by-product like whey and following sustainability and healthy trends, which are driving the food sector.

PurposeA remote platform for diabetes care (Roche Diabetes® Care Platform, RDCP) has been developed that allows combined face-to-face consultations and remote patient monitoring (RPM).MethodsA dedicated flowchart is proposed as a clinical approach to help healthcare professionals in the appropriate interpretation of structured self-monitoring blood glucose data, as visualized on the RDCP during the visits, and in the optimal management of patients using the integrated RDCP-RPM tools.ResultsThe platform organizes patterns in different blocks: (i) hypoglycemia; (ii) hyperglycemia; (iii) blood glucose variability; (iv) treatment adherence, which identifies a possible individual pattern according to glycemic control challenges, potential causal factors, and behavioral type patterns. The flowchart proposed for use of the RDCP-RPM is self-explanatory and entails 3 steps: (1) evaluation of quality and quantity of self-monitoring blood glucose data; (2) pattern analysis; (3) personalized suggestions and therapy changes.ConclusionThe main aim of the remote treatment flowchart proposed is to support healthcare professionals in the identification of hypoglycemic and hyperglycemic patterns using the RDCP regardless of the HbA1c value and ongoing treatment, which however, become crucial in combination with pattern analysis in the therapeutical choice.