Subclinical myopathy in patients with colorectal cancer: clinical-pathological characterization and search for tissue markers

Skeletal muscle in patients with cancer undergoes many morphological changes due to immuno-inflammatory factors of tumor origin or treatment.T he latest event of these changes is cancer cachexia. Aim of the study is to identify myopathic features in skeletal muscle biopsies from weight stable patients with colorectal cancer and without cachexia or asthenia / weakness, that could possibly provide new diagnostic and prognostic cancer biomarkers. Morphometric analyses and immunohistochemical studies were performed on intraoperative muscle biopsies from patients with colorectal cancer and from weight stable patients undergoing surgery for benign non-inflammatory conditions. A rectus abdominis biopsy was taken in all patients and controls.A correlation between histopathologic findings and clinical characteristics, circulating inflammatory biomarkers and markers of muscle necrosis,surgery data and cancer phenotype were investigated.. Forty four patients (21male/23 female) and 17 controls (6 male/11 female) (p=NS) were studied. In cancer patients’biopsies we observed asubclinical myopathy characterized by an abnormal distribution of myonuclei, which are localized inside the myofiber rather than at the periphery, and by the presence of regenerating muscle fibers. The percentage of myofibers with internalized nuclei is significantly higher in patients (median= 9%, IQR= 3.7-18.8) than in controls (median= 2.7%, IQR= 1.7-3.2) ( p=0.0002). In patients we observed an inverse correlation between the number of centronucleated fibers and the presence of node metastasis (N+)(ρ)=-0.64 (p=0.002). Patients affected with colorectal cancer display early sign of a myopathy, characterized by centronucleated and regenerating myofibers. This myopathy appears to be associated with an early stage of neoplasia and it could be an adaptive response of muscle to cancer. We hope a future application of these findings as a possible early diagnostic and prognostic biomarker of neoplasia

Jugendliche und IT-Kompetenzen: Zwischen Digital Natives und wirksamen Fertigkeiten

Il confronto generazionale nell’ambito delle tecnologie digitali e stato fortemente segnato dal concetto di "nativo digitale", che contrappone le nuove generazioni ai piu anziani ?immigrati digitali?. Diversi studi confutano queste tesi, o quantomeno le mettono in discussione, anche se il dibattito e ancora aperto. L’indagine ICILS offre dati solidi per approfondire il rapporto tra giovani e tecnologie, in particolare contestualizzandolo in un contesto geografico e sociale puntuale nel quale le istituzioni scolastiche non hanno finora assunto un ruolo importante e definito. Questo studio cerca di rispondere alle seguenti domande: Quali caratteristiche del Sistema educativo favoriscono lo sviluppo di competenze digitali? Esiste una relazione tra eta di inizio dell’uso delle tecnologie, frequenza d’uso e tipologia d’uso e le competenze digitali nei diversi ambiti? In conclusione si cerca di aprire la riflessione al ruolo della scuola e delle politiche educative nell’uso dei dispositivi digitali e di internet da parte degli allievi. (DIPF/Orig.)Generationsbeschreibungen zum Umgang mit digitalen Technologien wurden seit Jahren vom Konzept so genannter “digital natives” geprägt. Im Gegensatz dazu wurden etwas ältere Menschen der vorangehenden Generationen als “digital immigrants” bezeichnet. Auch wenn verschiedene Studien solche Zuschreibungen kritisieren, hält sich diese Differenzierung in gegenwärtigen Diskussion. Die ICIL-Studie bietet relevante Daten, um das Verhältnis von Heranwachsenden und ihrem Umgang mit neuen medialen Technologien besser verstehen zu können. Unsere Analyse fokussiert auf ein geographisch bzw. soziostrukturell ausgewähltes Gebiet, wo die schulischen Institutionen bisher keine Leitungsrolle übernommen haben. In diesem Kontext versucht die vorliegende Untersuchung, folgende Fragen zu beantworten: Welche Eigenschaften des Schulsystems fördern die Entwicklung von Kompetenzen im Bereich Medien und Informatik? Lassen sich zwischen dem Alter der Erstnutzung, der Nutzungsfrequenz, der Art der Nutzung von digitalen Medien, und den digitalen Kompetenzen von Lernenden Zusammenhänge finden? Die Diskussion versucht Überlegungen zur Rolle der Schule und der Schulpolitik zur Nutzung von digitalen Geräten und dem Internet durch Jugendliche darzulegen. (DIPF/Orig.

Transbilayer dynamics of phospholipids in the plasma membrane of the <em>Leishmania</em> genus

Protozoans of the Leishmania genus are the etiological agents of a wide spectrum of diseases commonly known as leishmaniases. Lipid organization of the plasma membrane of the parasite may mimic the lipid organization of mammalian apoptotic cells and play a role in phagocytosis and parasite survival in the mammal host. Here, we analyzed the phospholipid dynamics in the plasma membrane of both the L. (Leishmania) and the L. (Viannia) subgenera. We found that the activity and substrate specificity of the inward translocation machinery varied between Leishmania species. The differences in activity of inward phospholipid transport correlated with the different sensitivities of the various species towards the alkyl-phospholipid analogue miltefosine. Furthermore, all species exhibited a phospholipid scramblase activity in their plasma membranes upon stimulation with calcium ionophores. However, binding of annexin V to the parasite surface was only detected for a subpopulation of parasites during the stationary growth phase and only marginally enhanced by scramblase activation

2023 On-site Padua Days on Muscle and Mobiliy Medicine: Call for speakers

The winter of 2022 approaches with the need to finalize our plans for next year. This is urgent for the 2023 Meeting of the Padua Days of Muscle and Mobility Medicine (Pdm3) to be held March 29th to April 1st, 2023 at the Hotel Petrarca in the Thermae of Euganean Hills (Padua), Italy. A preliminary Pdm3 Program is almost ready with sessions, organzers and keynote speakers, but ther is still rooms for many interesting and interested young speakers. Some of the Pdm3 sessions dedicated to molecular and cellular myology are organized by old Pdm3 Friends, but there will also be interesting new entries, including those for Rehabilitation Sessions. No doubt that 2023 Pdm3 will attract old friends, but topics of a few sessions are at the frontiers of Translational Myology and new entries are most warmly acknowledged. This is true for both basic myology research, which include beside traditional MiRNA the new entry of the LNC-RNA and the “dark side of the genome”. As to rehabilitation topics, beside the old friends of the “LBI workshop on muscle rehabilitation - from mouse to elderly”, new entries are sessions on Muscle Fascia, Muscle Rehabilitation in Dentistry (that will organize also a Practical Course) and the session on “European Medical Thermalism and FEMTEC” that will also offer a practical Course. We hope that by January 20th, 2023 many old and new friends will send their abstracts to fill an half-empty program and then by May 1st, 2023 they submit Communications to EJTM that deserve them to increase the 2023 EJTM Impact Factor

Electrical stimulation counteracts muscle atrophy associated with aging in humans

Functional and structural muscle decline is a major problem during aging. Our goal was to improve in old subjects quadriceps m. force and mobility functional performances (stair test, chair rise test, timed up and go test) with neuromuscular electrical stimulation (9 weeks, 2-3times/week, 20-30 minutes per session). Furthermore we performed histological and biological molecular analyses of vastus lateralis m. biopsies. Our findings demonstrate that electrical stimulation significantly improved mobility functional performancies and muscle histological characteristics and molecular markers

Program with last minute abstracts of the Padua Days on Muscle and Mobility Medicine, 27 February – 2 March, 2024 (2024Pdm3)

During the 2023 Padua Days on Muscle and Mobility Medicine the 2024 meeting was scheduled from 28 February to 2 March 2024 (2024Pdm3). During autumn 2023 the program was expanded with Scientific Sessions which will take place over five days (in 2024 this includes February 29), starting from the afternoon of 27 February 2024 in the Conference Rooms of the Hotel Petrarca, Thermae of Euganean Hills (Padua), Italy. As per consolidated tradition, the second day will take place in Padua, for the occasion in the Sala San Luca of the Monastery of Santa Giustina in Prato della Valle, Padua, Italy. Confirming the attractiveness of the Padua Days on Muscle and Mobility Medicine, over 100 titles were accepted until 15 December 2023 (many more than expected), forcing the organization of parallel sessions on both 1 and 2 March 2024. The five days will include lectures and oral presentations of scientists and clinicians from Argentina, Austria, Belgium, Brazil, Bulgaria, Canada, Denmark, Egypt, France, Germany, Iceland, Ireland, Italy, Romania, Russia, Slovenia, Switzerland, UK and USA. Only Australia, China, India and Japan are missing from this edition. But we are confident that authors from those countries who publish articles in the PAGEpress: European Journal of Translational Myology (EJTM: 2022 ESCI Clarivate's Impact Factor: 2.2; SCOPUS Cite Score: 3.2) will decide to join us in the coming years. Together with the program established by 31 January 2024, the abstracts will circulate during the meeting only in the electronic version of the EJTM Issue 34 (1) 2024. See you soon in person at the Hotel Petrarca in Montegrotto Terme, Padua, for the inauguration scheduled the afternoon of 27 February 2024 or on-line for free via Zoom. Send us your email address if you are not traditional participants listed in Pdm3 and EJTM address books

Toll-Like Receptor and miRNA-let-7e Expression Alter the Inflammatory Response in Leishmania amazonensis-Infected Macrophages

Parasite recognition by Toll-like receptors (TLRs) contributes to macrophage activation and subsequent control of Leishmania infection through the coordinated production of pro-inflammatory and microbicidal effector molecules. The modulation of microRNA (miRNA) expression by Leishmania infection potentially mediates the post-transcriptional regulation of the expression of genes involved in leishmanicidal activity. Here, the contribution of TLR signaling to the miRNA profile and gene expression was evaluated in Leishmania amazonensis-infected murine macrophages. The infectivity of L. amazonensis was higher in murine bone marrow-derived macrophages from mice knockout for myeloid differentiation factor 88 (MyD88−/−), TLR2 (TLR2−/−), or TLR4 (TLR4−/−) than wild type C57BL/6 (WT). L. amazonensis infection of WT macrophages modulated the expression of 32% of the miRNAs analyzed, while 50% were upregulated. The absence of MyD88, TLR2, and TLR4 altered the percentage of miRNAs modulated during L. amazonensis infection, including the downregulation of let-7e expression. Moreover, the absence of signals mediated by MyD88, TLR2, or TLR4 reduced nitric oxide synthase 2 (Nos2) mRNA expression during infection. Indeed, the inhibition of let-7e increased levels of the Nos2 mRNA and NOS2 (or iNOS) protein and nitric oxide (NO) production in L. amazonensis-infected macrophages (4–24 h). The absence of TLR2 and inhibition of let-7e increased the expression of the arginase 1 (Arg1) mRNA but did not alter the protein level during infection. However, higher levels of the L-arginine transporters Cat2B and Cat1 were detected in the absence of Myd88 signaling during infection but were not altered following let-7e inhibition. The inhibition of let-7e impacted the global expression of genes in the TLR pathway by upregulating the expression of recognition and adaptors molecules, such as Tlr6, Tlr9, Ly96, Tirap, Traf 6, Ticam1, Tollip, Casp8, Map3k1, Mapk8, Nfkbib, Nfkbil1, Ppara, Mapk8ip3, Hspd1, and Ube2n, as well as immunomodulators, such as Ptgs2/Cox2, Csf 2, Csf 3, Ifnb1, Il6ra, and Ilr1, impacting NOS2 expression, NO production and parasite infectiveness. In conclusion, L. amazonensis infection alters the TLR signaling pathways by modulating the expression of miRNAs in macrophages to subvert the host immune responses