The rising demand for sustainable materials has increasedinterestin biodegradable plastics. The black soldier fly (BSF) is a proteinsource characterized by the ability to thrive on organic waste, rapiddevelopment, and low environmental impact. This study shows that BSFproteins can undergo amyloid-like aggregation in alkaline environments,ultimately leading to amyloid fibrils suitable as reinforcing nanofillersfor bioplastic films. The fibrillization process was monitored throughThioflavin-T (ThT) fluorescence assay and sodium dodecyl sulfate polyacrylamidegel electrophoresis (SDS-PAGE). The fibrils’ structure wasstudied by means of transmission electron microscopy (TEM) and one-dimensional/two-dimensional(1D/2D) X-ray diffraction (XRD) analyses performed on films obtainedby casting. Bioplastic films were prepared by blending fibrillizatedBSF proteins with poly­(vinyl alcohol) (PVOH) and glycerol. They exhibitedthermal weldability and mechanical and gas barrier properties in linewith those of the traditional oil- and biobased plastics used forpackaging applications. Due to the current technological interestin BSF as a bioconverter of organic matter, the BSF protein-basedmaterials presented in this work not only could help in mitigatingthe pressure arising from the accumulation of nonbiodegradable plasticsbut also provide tangible evidence about the valorization of municipalorganic waste.

Pelvic organ prolapse (POP) affects millions of women around the world, with age-standardized prevalence rates of 2769 per 100,000 women in 2021. Although it greatly affects quality of life (QoL), only 18–50% of women experiencing this issue seek medical attention, largely due to a lack of knowledge, misunderstandings about the condition, and obstacles to accessing healthcare. This narrative review explores the progression of POP management towards a focus on patient-centered care, highlighting the importance of personalized treatment strategies that prioritize patient-reported outcomes (PROs) over solely anatomical factors. The approach to treatment has transitioned from being centered on anatomy to focusing on the patient, emphasizing the relief of symptoms and enhancement in QoL. Existing research indicates that monitoring without intervention is advisable for asymptomatic patients, as long-term studies have revealed that up to 40% of women experience stable or improved prolapse over a period up to 60 months. Pessary treatment has a fitting success rate above 90% and a treatment persistence rate of 60%, providing an effective non-surgical option for management. The approach to selecting surgical treatments has progressed to prioritize sufficient apical support as a key factor for achieving lasting results. For primary POP, native tissue repair (NTR) is now recommended as the first-line surgical option. Mesh-augmented repairs are used only in certain high-risk situations, whereas sacrocolpopexy offers the best anatomical stability for particular cases, such as those involving post-hysterectomy prolapse and recurrences. Contemporary POP management involves personalized, patient-focused decision-making that emphasizes addressing symptom severity and functional objectives rather than solely aiming for anatomical precision. The evidence suggests that NTR should be the primary surgical approach, while other procedures should be reserved for specially chosen patients. Success should primarily be evaluated based on PROs instead of anatomical factors, ensuring that treatments align with each patient’s preferences and expectations while reducing complications.

As life expectancy continues to increase, age-related disorders are becoming more prevalent. Among these, vascular complications resulting from chronic inflammation are particularly concerning, as they impair angiogenesis and hinder tissue repair, both processes that heavily rely on a well-structured extracellular matrix (ECM). In this context, MicroMatrix® UBM Particulate, a skin substitute composed of collagen, laminin, and proteoglycans, appears to offer properties conducive to tissue regeneration. The aim of this study was to evaluate the regenerative potential of MicroMatrix® combined with the Secretome of human Dental Pulp Stem Cells (hDPSC-S), using the medicinal leech Hirudo verbana, a well-established model for studying wound healing, angiogenesis, and tissue regeneration. Adult leeches were injected with MicroMatrix® either suspended in FBS-free medium (CTRL) or supplemented with hDPSC-S. 1-week post-treatment, the animals were sacrificed and subjected to morphological and immunohistochemical analyses. Our findings revealed that MicroMatrix® successfully integrated into the leech body wall. Notably, when supplemented with hDPSC-S, there was a marked increase in cell infiltration, including telocytes and Hematopoietic Precursor Stem Cells, along with a significantly higher vessel density compared to CTRL. These results support the effectiveness of the cell-free device composed of MicroMatrix® and hDPSC-S, highlighting its potential as a promising strategy for regenerative therapies aimed at treating complex wounds with poor vascularization.

ImportanceThe DIPLOMA trial showed comparable radical resection rates after minimally invasive left pancreatectomy (MILP) and open left pancreatectomy (OLP) in patients with upfront resectable pancreatic cancer. Data on long-term overall survival (OS) and disease-free survival (DFS) are currently lacking, but are required before the oncological efficacy of MILP can be confirmed.ObjectiveTo determine the long-term oncological outcome, including OS and DFS, of MILP vs OLP in patients with upfront resectable left-sided pancreatic cancer in the DIPLOMA trial.Design, Setting, and ParticipantsThe randomized, patient-blinded and pathologist-blinded DIPLOMA trial was conducted between 2018 and 2021, with a follow-up duration of at least 36 months. It was a multicenter international trial that took place in 35 centers in 12 countries worldwide. Patients with upfront resectable pancreatic ductal adenocarcinoma of the body or tail of the pancreas were included.InterventionsParticipants were randomly assigned to undergo MILP (laparoscopic and robotic) or OLP. Patients were blinded for the surgical approach.Main Outcomes and MeasuresMain outcomes included OS and DFS. Other outcomes include receipt of adjuvant therapy and time to start of adjuvant therapy.ResultsBetween May 2018 and May 2021, 258 patients were randomized to the MILP (131 patients) and OLP (127 patients) groups. After a median follow-up of 38 (IQR 36-46) months, 134 patients (52%) had died and 127 patients (55%) experienced disease recurrence. OS did not differ significantly between the MILP and OLP groups (median, 32 vs 34 months; stratified hazard ratio, 1.02; 95% CI, 0.72-1.44; P = .92). Also, DFS did not significantly differ between the MILP and OLP groups (median, 21 vs 17 months; stratified hazard ratio, 0.96; 95% CI, 0.68-1.35; P = .81). Adjuvant therapy was administered in 79 patients after MILP (79 of 113 [70%]) and 79 patients after OLP (79 of 110 [72%]) (P = .63). Time to adjuvant therapy was comparable between groups (median 59 vs 56 days; P = .92).Conclusions and RelevanceIn this long-term follow-up of the randomized DIPLOMA trial in patients with upfront resectable pancreatic cancer, oncological outcomes after MILP and OLP did not differ significantly, confirming the oncological safety of MILP.Trial RegistrationInternational Standard Registered Clinical/Social Study Number Registry Identifier: ISRCTN44897265

Fibromyalgia is a chronic syndrome characterized by widespread musculoskeletal pain, fatigue, non-restorative sleep, and cognitive impairment. Its pathogenesis reflects a complex interplay between central and peripheral mechanisms, including altered pain modulation, neuroinflammation, mitochondrial dysfunction, autonomic imbalance, and genetic and epigenetic factors. Evidence from neuroimaging, omics studies, and neurophysiology supports this multifactorial model. Epidemiological updates confirm a global prevalence of 2-8%, with a strong female predominance and a significant impact on quality of life and healthcare costs. Diagnostic criteria have evolved from the 1990 American College of Rheumatology tender points to the 2010/2011 revisions and the 2016 update, improving case ascertainment but still lacking objective biomarkers. Recent omics and systems biology approaches have revealed transcriptional, proteomic, and metabolic signatures that may enable molecularly informed stratification. Therapeutic management remains multidisciplinary, combining pharmacological interventions (e.g., duloxetine, pregabalin, milnacipran) with non-pharmacological strategies such as graded aerobic exercise and cognitive behavioral therapy. Emerging approaches include drug repurposing to target neuroinflammation, mitochondrial dysfunction, and nociceptive pathways. Despite promising advances, progress is limited by small sample sizes, heterogeneous cohorts, and lack of standardization across studies. Future priorities include large-scale validation of biomarkers, integration of multi-omics with clinical phenotyping, and the design of precision-guided trials. By synthesizing mechanistic insights with clinical evidence, this review provides an updated framework for the diagnosis and management of fibromyalgia, highlighting pathways toward biomarker-guided, personalized medicine.

In this datanote we present data from 31 iRBD (idiopathic Rapid eye movement (REM) sleep Behaviour Disorder) patients followed throughout three years to assess their eventual phenoconversion to Parkinson's disease and other established neurodegenerative conditions. iRBD is a prodromal condition of neurological pathologies such as Parkinson's disease. We evaluated transcription factor mRNA levels in CD4+ T cells as predictive biomarkers of phenoconversion in iRBD, showing that among the transcription factors mRNA levels analysed, STAT1, GATA3 and FOXP3 mRNA levels may be used to predict phenoconversion. In particular, we found that CD4+ T cells from converters had higher STAT1, and lower GATA3 and FOXP3 mRNA levels. According to ROC curve analysis STAT1 levels provided a good discrimination, GATA3 levels an excellent discrimination of future converters and not-converters, while discrimination provided by FOXP3 levels was acceptable.

Paracetamol (also known as acetaminophen or N-acetyl-p-aminophenol, APAP) is the most widely used antipyretic and analgesic during pregnancy and early childhood, although its exact mechanism of action remains not fully understood. Several publications have suggested a potential association with adverse neurological or behavioural outcomes in foetal or neonatal development; however, these studies were limited by significant confounding factors. More recently, a nationwide sibling-controlled study has definitively refuted this hypothesis. Similarly, some evidence supports both the safety and the efficacy of paracetamol use in early childhood. Based on the available literature and their own clinical experience, a multidisciplinary panel of Italian experts developed a position paper addressing the safety of paracetamol exposure during pregnancy, the neonatal period and the first 1,000 days of life. Current evidence and the board’s clinical experience indicate that paracetamol is safe and should be considered the first-choice treatment in these stages of life, as highlighted and endorsed by the guidelines of leading scientific societies.

Abstract Optical frequency combs have become a key research topic in optics and photonics. A peculiar comb state is the harmonic frequency comb (HFC), where optical lines are spaced by integer multiples of the cavity’s free-spectral range. The spontaneous formation of HFCs has recently been observed in semiconductor lasers with fast gain recovery, such as Quantum Cascade Lasers (QCLs), although the underlying physical mechanism remains unclear. In this work, we provide a physical interpretation for the formation of HFCs in QCLs, based on a resonance phenomenon between an effective Rabi frequency and a mode of the laser cavity. This is corroborated by the results of the numerical integration of the effective semiconductor Maxwell-Bloch equations used to describe the multimode laser dynamics, as well as by the linear stability analysis of the continuous wave emission at threshold.