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The Mediterranean area is one of the major global producers of agricultural food. However, along the entire supply chain—from farming to food distribution and consumption—food waste represents a significant fraction. Additionally, plant waste residues generated during the cultivation of specific fruits and vegetables must also be considered. This heterogeneous biomass is a valuable source of bioactive compounds and materials that can be transformed into high-performance functional products. By analyzing technical and scientific literature, this review identifies extraction, composite production, and bioconversion as the main strategies for valorizing agricultural by-products and waste. The advantages of these approaches as well as efficiency gains through digitalization are discussed, along with their potential applications in the Mediterranean region to support new research activities and bioeconomic initiatives. Moreover, the review highlights the challenges and disadvantages associated with waste valorization, providing a critical comparison of different studies to offer a comprehensive perspective on the topic. The objective of this review is to evaluate the potential of agricultural waste valorization, identifying effective strategies while also considering their limitations, to contribute to the development of sustainable and innovative solutions in Mediterranean bioeconomy.

ObjectiveOn the one hand, trends in average height in adulthood mirror changes in living standard and health status of a population and its subgroups; on the other hand, height in general, as well as the loss of height in older age in particular, are associated in different ways with outcomes for health. For these aspects, there is hardly any information for Switzerland based on representative and measured body height data.DesignRepeated cross-sectional survey study.SettingFully anonymised data from the representative population-based Geneva Bus Santé Study between 2005 and 2017 were analysed.MethodsData from N=8686 study participants were used in the trend analysis. Height was measured and sociodemographic information and self-rated health was collected via questionnaires. Follow-up (mean: 7.1 years) measurements from N=2112 participants were available to assess height loss after age 50.ResultsWomen were, on average, 166.2 cm (SD 6.5) tall and men 179.2 cm (SD 6.5). Among men and women, higher socioeconomic status was associated with taller average height. The flattening of the increase in height from the 1970s birth years appears to begin earlier in the subgroup with the highest education level. The tallest average height was measured for men and women from Central and Northern Europe, the shortest for South America and Asia. The likelihood that participants rated their health as ‘very good’ increased with greater body height. The follow-up data show that men lost −0.11 cm per follow-up year (95% CI −0.12 to −0.10), women −0.17 cm (95% CI −0.18 to 0.15).ConclusionsThe association of height and health status is currently understudied. Monitoring changes in average body height may indicate disparities in different subgroups of populations. Based on our study and a growing literature, we think that the multifaceted role of body height should be better considered in clinical practice.

The Arctic is changing rapidly due to the amplification of global temperature trends, causing profound impacts on the ice sheet in Greenland, glaciers, frozen ground, ecosystems, and societies. Here, we focus on impacts that atmospheric circulation causes in addition to the climate warming trends. We combine time series of glacier mass balance from temporal satellite gravimetry measurements (GRACE/GRACE-FO; 2002–2023), active layer thickness in permafrost areas from ESA’s Climate Change Initiative remote sensing and modelling product (2003–2019), and field measurements of the Circumpolar Active Layer Monitoring Network (2002–2023). Despite regional and system-related complexities, we identify robust covariations between these observations, which vary asynchronously between neighbouring regions and synchronously in regions antipodal to the North Pole. We reveal a close connection with dominant modes of atmosphere circulation, controlling about 75% of the common pan-Arctic impact variability (2002–2022), also affecting the Greenland Ice Sheet. We emphasize that it is necessary to consider such atmospheric driving patterns when projecting impacts, particularly caused by extremes, in an increasingly warmer Arctic.

ObjectivePerianal fistulas in Crohn’s disease (CD) are associated with a high burden of illness and their treatment is challenging. Recent data indicate promising short-term efficacy of bone marrow-derived mesenchymal stromal cell (bmMSC) therapy. The aim of this case series is to gather more information on the long-term effectiveness and safety.MethodsBetween 2013 and 2017, bmMSCs were administered under compassionate use to patients at a university hospital in Germany, as no stem cell therapy was approved at the time. Inclusion criteria were inactive CD (Harvey-Bradshaw Index <5) without proctitis, at least one treatment-refractory perianal fistula (with or without rectovaginal additional fistulas) and prior tumour necrosis factor-alpha inhibitor and/or surgical exposure. After curettage of the fistula tract, patients received repeated intrafistular injections with up to 300 million bmMSCs. We retrospectively analysed patient records to assess disease course, clinical fistula remission and radiological activity using the modified van Assche index.ResultsSix female patients with a total of 13 fistulas (9 trans-sphincteric, 2 extrasphincteric and 2 rectovaginal) underwent bmMSC application. Median radiological and clinical long-term follow-up was 80 months (range 44–98 months) after first local bmMSC injection. 8 of 13 fistulas (62%) exhibited complete closure. For rectovaginal fistulas, long-term remission (98 months) was 50% (1 of 2). Pelvic MRI showed a decrease in modified Van Assche index from baseline to long-term follow-up. No immediate adverse events related to bmMSC injections were observed. One patient was diagnosed with a local adenocarcinoma of the rectum 106 months after first bmMSC injection. MRI control 11 months prior showed complete fistula remission. The tumour exhibited a female karyotype, while bmMSC had been derived from a male volunteer.ConclusionIn this analysis, 62% of complex perianal and 50% of rectovaginal fistulas showed long-term remission up to 8 years post–bmMSC therapy. Further real-world data are needed.

Background and Aims Pyoderma gangrenosum (PG) is a rare but challenging extraintestinal manifestation (EIM) of inflammatory bowel disease (IBD), affecting 6–48% of IBD patients. This retrospective study analyzes affected patients and evaluates therapeutic strategies for both IBD remission and PG resolution. METHODS A multicenter retrospective analysis was conducted on patients with IBD and PG in 8 tertiary centers in Germany and Austria. Demographic data, prior therapies, surgeries, treatment of PG were collected, and treatment responses assessed. RESULTS The cohort included 50 patients (median age: 43 years; 68% female). Crohn’s disease (CD) was present in 58%, ulcerative colitis (UC) in 42%. Fifty percent of patients had prior surgery, 68% having an intestinal stoma. 48% were experienced to biologic therapy, predominantly anti-TNF therapy (83%). PG mainly affected the lower extremities (52%) and peristomal areas (24%). Systemic steroids were used in 52% of patients and led to PG resolution in only 12%. Anti-TNF therapy was the main approach, used in 68% of patients, with resolution achieved in 80%. Calcineurin inhibitors were given to 26% of patients and induced resolution in 38%. Three of six non-responders were successfully switched to infliximab. Overall PG resolution was achieved in 80%, correlating with IBD remission in 78%. The median time to PG resolution was five months. CONCLUSION Anti-TNF therapy was an effective treatment for PG in IBD patients, even in those with prior non-response to calcineurin inhibitors. Systemic steroids showed low response rates. PG healing mostly aligned with IBD remission, underlining the need for tailored long-term therapy.

Purpose Immunogenicity is a major reason for secondary loss of response to infliximab (IFX). Recent work suggested potentially lower immunogenicity of subcutaneous (SC) compared to intravenous (IV) IFX. However, it is unknown whether re-exposure to IFX SC after secondary loss of response and immunogenicity to its intravenous formulation is safe and effective. Methods In a retrospective cohort study conducted at two medical centers, patients with clinically (Harvey-Bradshaw Index ≥ 5) and/or biochemically (fecal calprotectin > 250 µg/g) active Crohn’s disease (CD) and previous immunogenic failure of IFX IV underwent exposure to IFX SC. Harvey-Bradshaw Index, fecal calprotectin, IFX serum concentration, and anti-drug antibodies were assessed until month 12. Results Twenty CD patients were included. The majority of patients (90%) had previous treatment with three or more biologics. Fifteen (75%) and ten (50%) of 20 patients continued IFX SC treatment until months 6 and 12, respectively. No immediate hypersensitivity reactions were observed. Two patients discontinued IFX SC treatment because of delayed hypersensitivity at week 2 and week 4. IFX serum concentrations increased from baseline to month 12, while anti-drug antibody levels decreased. Combined clinical and biochemical remission at month 12 was observed in seven of 20 patients (35%). Conclusion Subcutaneous infliximab treatment of Crohn’s disease patients with previous immunogenic failure of intravenous infliximab was well tolerated and effective in a cohort of patients with refractory Crohn’s disease.

Background Naturalistic developmental behavioural interventions (NDBI) have been shown to improve autism-specific symptoms in young children with Autism Spectrum Disorder (ASD). NDBI approaches, such as the ASD-specific Frankfurt Early Intervention Programme for ASD (A-FFIP), are based on ASD-specific developmental and learning aspects. A-FFIP is a low-intensity intervention which can easily be implemented in the local health care/social welfare system. The aim of the present study is to establish 1-year efficacy of the manualised early intervention programme A-FFIP in toddlers and preschool children with ASD. It is hypothesised that A-FFIP will result in improved ASD-specific symptoms compared to early intervention as usual (EIAU). Child- and family-specific secondary outcomes, as well as moderators and mediators of outcome, will be explored. Methods/design A prospective, multi-centre, parallel-group, randomised controlled, phase-III trial comparing A-FFIP versus EIAU. A total of 134 children (A-FFIP: 67, EIAU: 67) aged 24–66 months at baseline assessment meeting the criteria for ASD ( DSM-5 ) will be included. The primary outcome is the absolute change of the total score of the Brief Observation of Social Communication Change (BOSCC-AT) between baseline (T2) and 1-year follow-up (T6). The treatment effect will be tested, adjusted for relevant covariates applying a mixed model for repeated measures. Secondary outcomes are BOSCC social communication and repetitive-behaviour scores, single ASD symptoms, language, cognition, psychopathology, parental well-being and family quality of life. Predictors, moderators and mediating mechanisms will be explored. Discussion If efficacy of the manualised A-FFIP early intervention is established, the current study has the potential to change clinical practice strongly towards the implementation of a low-intensity, evidence-based, natural early intervention in ASD. Early intervention in ASD requires specialist training, which subsequently needs to be developed or included into current training curricula. Trial registration German Registry for Clinical Trials (Deutscher Register Klinischer Studien, DRKS); ID: 00016330. Retrospectively registered on 4 January 2019. URL: https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00016330 .

Contrast-enhanced whole-body computed tomography (also called “pan-scanning”) is considered to be a conclusive diagnostic tool for major trauma. We sought to determine the accuracy of this method, focusing on the reliability of negative results. Between July 2006 and December 2008, a total of 982 patients with suspected severe injuries underwent single-pass pan-scanning at a metropolitan trauma centre. The findings of the scan were independently evaluated by two reviewers who analyzed the injuries to five body regions and compared the results to a synopsis of hospital charts, subsequent imaging and interventional procedures. We calculated the sensitivity and specificity of the pan-scan for each body region, and we assessed the residual risk of missed injuries that required surgery or critical care. A total of 1756 injuries were detected in the 982 patients scanned. Of these, 360 patients had an Injury Severity Score greater than 15. The median length of follow-up was 39 (interquartile range 7–490) days, and 474 patients underwent a definitive reference test. The sensitivity of the initial pan-scan was 84.6% for head and neck injuries, 79.6% for facial injuries, 86.7% for thoracic injuries, 85.7% for abdominal injuries and 86.2% for pelvic injuries. Specificity was 98.9% for head and neck injuries, 99.1% for facial injuries, 98.9% for thoracic injuries, 97.5% for abdominal injuries and 99.8% for pelvic injuries. In total, 62 patients had 70 missed injuries, indicating a residual risk of 6.3% (95% confidence interval 4.9%–8.0%). We found that the positive results of trauma pan-scans are conclusive but negative results require subsequent confirmation. The pan-scan algorithms reduce, but do not eliminate, the risk of missed injuries, and they should not replace close monitoring and clinical follow-up of patients with major trauma.

Adenoviral infections are a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT) in pediatric patients. Adoptive transfer of donor-derived human adenovirus (HAdV)-specific T-cells represents a promising treatment option. However, the difficulty in identifying and selecting rare HAdV-specific T-cells, and the short time span between patients at high risk for invasive infection and viremia are major limitations. We therefore developed an IL-15-driven 6 to 12 day short-term protocol for in vitro detection of HAdV-specific T cells, as revealed by known MHC class I multimers and a newly identified adenoviral CD8 T-cell epitope derived from the E1A protein for the frequent HLA-type A*02∶01 and IFN-γ. Using this novel and improved diagnostic approach we observed a correlation between adenoviral load and reconstitution of CD8(+) and CD4(+) HAdV-specific T-cells including central memory cells in HSCT-patients. Adaption of the 12-day protocol to good manufacturing practice conditions resulted in a 2.6-log (mean) expansion of HAdV-specific T-cells displaying high cytolytic activity (4-fold) compared to controls and low or absent alloreactivity. Similar protocols successfully identified and rapidly expanded CMV-, EBV-, and BKV-specific T-cells. Our approach provides a powerful clinical-grade convertible tool for rapid and cost-effective detection and enrichment of multiple virus-specific T-cells that may facilitate broad clinical application.

Recent findings suggest an implication of the gut microbiome in Parkinson's disease (PD) patients. PD onset and progression has also been linked with various environmental factors such as physical activity, exposure to pesticides, head injury, nicotine, and dietary factors. In this study, we used a mouse model, overexpressing the complete human SNCA gene (SNCA-TG mice) modeling familial and sporadic forms of PD to study whether environmental conditions such as standard vs. enriched environment changes the gut microbiome and influences disease progression. We performed 16S rRNA DNA sequencing on fecal samples for microbiome analysis and studied fecal inflammatory calprotectin from the colon of control and SNCA-TG mice kept under standard environment (SE) and enriched environment (EE) conditions. The overall composition of the gut microbiota was not changed in SNCA-TG mice compared with WT in EE with respect to SE. However, individual gut bacteria at genus level such as Lactobacillus sp. was a significant changed in the SNCA-TG mice. EE significantly reduced colon fecal inflammatory calprotectin protein in WT and SNCA-TG EE compared to SE. Moreover, EE reduces the pro-inflammatory cytokines in the feces and inflammation inducing genes in the colon. Our data suggest that an enriched social environment has a positive effect on the induction of SNCA mediated inflammation in the intestine and by modulating anti-inflammatory gut bacteria.Recent findings suggest an implication of the gut microbiome in Parkinson's disease (PD) patients. PD onset and progression has also been linked with various environmental factors such as physical activity, exposure to pesticides, head injury, nicotine, and dietary factors. In this study, we used a mouse model, overexpressing the complete human SNCA gene (SNCA-TG mice) modeling familial and sporadic forms of PD to study whether environmental conditions such as standard vs. enriched environment changes the gut microbiome and influences disease progression. We performed 16S rRNA DNA sequencing on fecal samples for microbiome analysis and studied fecal inflammatory calprotectin from the colon of control and SNCA-TG mice kept under standard environment (SE) and enriched environment (EE) conditions. The overall composition of the gut microbiota was not changed in SNCA-TG mice compared with WT in EE with respect to SE. However, individual gut bacteria at genus level such as Lactobacillus sp. was a significant changed in the SNCA-TG mice. EE significantly reduced colon fecal inflammatory calprotectin protein in WT and SNCA-TG EE compared to SE. Moreover, EE reduces the pro-inflammatory cytokines in the feces and inflammation inducing genes in the colon. Our data suggest that an enriched social environment has a positive effect on the induction of SNCA mediated inflammation in the intestine and by modulating anti-inflammatory gut bacteria.