Markers of physical functioning and neuromuscular fatigue for the post-discharge follow-up of subjects already assisted in intensive care for COVID-19 and non-communicable diseases.

L'insorgenza di malattie non trasmissibili con incidenza neuromuscolare e il prolungato ricovero in terapia intensiva comportano implicazioni negative sulla capacità funzionale e l'autonomia dei pazienti. Queste alterazioni sono causate da fattori come l'immobilità prolungata, l'infiammazione sistemica, le disfunzioni neuromuscolari e gli effetti diretti della patologia stessa. Ciò porta a fatica e debolezza muscolare, contribuendo a un significativo declino nelle abilità motorie, ostacolando il recupero e peggiorando la qualità della vita dei pazienti. Le principali disfunzioni motorie si manifestano con l’alterata deambulazione, limitando l'autonomia nelle attività quotidiane. Tali disfunzioni sono causate dalla compromissione delle vie motorie del sistema nervoso e si manifestano già durante la fase acuta della malattia, peggiorando successivamente con il suo evolversi. Tale quadro clinico è aggravato ulteriormente dalla conseguente inattività fisica, favorita dalle condizioni psicofisiche dei singoli. Di conseguenza, tutto ciò incide notevolmente sulle proprietà contrattili dei muscoli, portando ad alterazioni critiche che influenzano la capacità del sistema nervoso centrale e periferico di reclutare e modulare l'attività delle unità motorie. Date le complessità associate a queste considerazioni, diventa fondamentale identificare marcatori in grado di quantificare e caratterizzare l’alterazione della capacità funzionale e l’insorgenza della debolezza muscolare e della fatica. Ciò faciliterebbe una diagnosi precoce e, in modo cruciale, il monitoraggio continuo di tali problematiche. Pertanto, l'obiettivo primario di questa ricerca di Dottorato è identificare e analizzare marcatori in grado di supportare efficacemente gli operatori sanitari nella progettazione e nell'implementazione di approcci terapeutici personalizzati per accelerare il recupero di questi individui. Nonostante, infatti, la pratica clinica attualmente in uso negli ospedali offra continui miglioramenti, questa presenta ancora delle limitazioni. Sebbene le valutazioni attualmente impiegate riescano ad identificare la presenza di fatica e debolezza muscolare nei pazienti post-ricovero in terapia intensiva o in soggetti affetti da malattie non trasmissibili, non riescono tuttavia ad indagare a fondo su quali siano le effettive cause che innescano la perdita della forza muscolare o ad esaminare in modo esaustivo i fattori centrali e/o periferici che contribuiscono all'insorgenza della fatica. Per colmare in modo esaustivo questa lacuna, lo studio ha condotto un'ampia ricerca combinando l'elettromiografia di superficie con la capacità di generare forza muscolare in diverse condizioni patologiche, includendo attivazioni muscolari sia volontarie che indotte elettricamente. Il muscolo oggetto di studio è stato il tibiale anteriore, scelto per il suo ruolo cruciale nella biomeccanica della deambulazione e quindi fondamentale per il mantenimento dell’autonomia motoria. I risultati hanno mostrato che le variazioni nella forza e nei parametri delle unità motorie possono servire da indicatori per le alterazioni neuromuscolari e il recupero progressivo, facilitando il monitoraggio a breve e lungo termine. Questo studio ha quindi un'importanza fondamentale per le popolazioni coinvolte e può suggerire approcci più ampi per la gestione delle alterazioni neuromuscolari in diversi contesti clinici. In particolare, sottolinea l'importanza di programmi di riabilitazione personalizzati e soggettivati alle esigenze specifiche di ciascun individuo.The onset of non-communicable neuromuscular diseases and prolonged stays in the intensive care unit have deep implications for physical functioning and neuromuscular health. These repercussions arise from muscle deconditioning, systemic inflammation, and the direct impact of the pathology. Moreover, resulting fatigue and acquired muscle weakness contribute to reduced muscular performance, significantly hampering recovery and diminishing overall quality of life. The predominant motor impairments observed in these patients primarily manifest in their ability to perform correct walking, substantially limiting their independent execution of daily activities. This compromised excitability in descending motor pathways becomes evident during the acute phase of the disease and intensifies as the condition progresses chronically, exacerbated by prolonged physical inactivity. Consequently, this significantly affects the muscle's contractile properties, leading to critical alterations that influence the nervous systems' capacity to recruit and modulate the activity of motor units, the fundamental functional units responsible for planning, executing, and maintaining motor gestures. Given these considerations, it becomes crucial to identify markers that enable the quantification and characterization of physical functioning impairment, muscle weakness and fatigue. This would facilitate early diagnosis and, crucially, the ongoing monitoring of these issues. Thus, the primary goal of this PhD research is to identify and analyze markers that can effectively support healthcare practitioners in devising and delivering personalized therapeutic approaches to expedite the recovery of these individuals. The overarching objective is to optimize the current clinical practice commonly employed in hospitals. Despite ongoing refinements, these practices still exhibit limitations. While standard assessments succeed in identifying the presence of fatigue and muscle weakness in ICU patients or those afflicted by non-communicable diseases, they fall short of investigating the root causes of muscle strength deterioration or thoroughly probing the central and/or peripheral factors contributing to the emergence of pathological fatigue. To comprehensively bridge this existing gap, the study undertook an extensive exploration by measuring concurrent joint torques and surface electromyography across various pathological conditions, encompassing both voluntary and electrically induced muscle activations. The focal point was the tibialis anterior muscle, chosen for its pivotal role in gait patterns and consequential influence on individual autonomy. The presented results were mainly achieved through the decomposition of signals recorded using the High-Density Surface EMG technique. This technique enabled the analysis of individual motor units recruited during motor tasks administered to patients within the studied populations. The process of data collection and analysis revealed that variations in muscle strength values and motor unit parameters can serve as indicators of neuromuscular system alterations and progressive recovery. These factors are pivotal for subsequent follow-up procedures. Indeed, by establishing a robust framework of markers, is possible to contribute to the development of evidence-based protocols that enhance the post-discharge care of these individuals. This study is not only pivotal for these specific cohorts but also holds the potential to inform broader strategies for managing physical impairment and neuromuscular challenges in diverse clinical settings. Notably, the study highlights that hospitalization in intensive care, as well as the onset of non-communicable pathologies with high motor impact, leads to specific alterations in parameters of both central and peripheral neuromuscular pathways. This underscores the imperative for devising personalized rehabilitation regimens tailored to each patient's needs

Significance of the early Jurassic Garamilla formation in the Western Nordpatagonian Massif

By means of facial, stratigraphic, petrographic, geochemical and geochronological studies we characterize the Garamilla Formation, cropping out in the western Nordpatagonian Massif. The studies of these volcanic rocks reveal an Early Jurassic volcanic episode calc-alkaline series. Other geochemical features reveal a progressive change formed by three volcanic units that change from normal calc-alkaline to high-K 13 from an initial subduction-related volcanism to one intraplate-related volcanism. This volcanic episode is temporally and geochemically equivalent to those volcanic units located in half-grabens in several areas of the Neuquén Basin. The volcanic units were erupted in different structural designs. A portion of its depocenter was interpreted as a transtensional half-graben whereas the other exhibits a trapdoor structure. The lineament trends that bound the volcanic system were also recognised in Western Nordpatagonian Massif, and were assigned to the Gondwanide Orogenic.Fil: Benedini, Leonardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Bahia Blanca. Instituto Geológico del Sur; Argentina;Fil: Gregori, Daniel Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Bahia Blanca. Instituto Geológico del Sur; Argentina

Nanodevices for Facing New Challenges of Medical Treatments: Stimuli-Responsive Drug Delivery Systems

The administration of therapeutic agents for the treatment of diseases without inclusion in a pharmaceutical formulation has been rarely reported in the current literature. In this condition, drugs show poor biodistribution profiles, a lack of predictable therapeutic response, and possible toxicity. For overcoming this issue, delivery systems were developed to carry, release drugs that finally interact with target sites with accuracy. The advent of nanotechnology has encouraged the improvement of these devices for facing new challenges of medical treatments. Therefore, pharmaceutical formulations have evolved from dissolutions and powders towards nanosized-smart drug delivery systems. Consequently, in this review, they are shown the main applications of nanotechnology on the design and development of drug delivery devices such as niosomes, liposomes, lipid-based nanoparticles, polymeric micelles, polymer-based devices, liquid crystals-based systems, and nanocomposites; and their capability for responding to different external and/or internal stimuli and thus release their content in the specific site. Owing to the progress in drug (or another therapeutic agent) delivery system and those applied to the imaging diagnostics, a new subarea known as theranostic, have been launched. This strategy combines the diagnosis of diseases and their treatment in a one-step procedure through the application of external stimuli to a formulation that once administrated to the body can release their content for treating and also for following the progress of the disease. For that reason, theranostic therapy has also described in this text as another example of the evolution of formulations based on nanodevices.Fil: Benedini, Luciano Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; ArgentinaFil: Messina, Paula Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentin

Relating second order geometry of manifolds through projections and normal sections

We use normal sections to relate the curvature locus of regular (resp. singular corank 1) 3-manifolds in R6 (resp. R5) with regular (resp. singular corank 1) surfaces in R5 (resp. R4 ). For example, we show how to generate a Roman surface by a family of ellipses different to Steiner's way. We also study the relations between the regular and singular cases through projections. We show that there is a commutative diagram of projections and normal sections which relates the curvature loci of the different types of manifolds, and therefore, that the second order geometry of all of them is related. In particular, we define asymptotic directions for singular corank 1 3-manifolds in R5 and relate them to asymptotic directions of regular 3-manifolds in R6 and singular corank 1 surfaces in R4

The Gondwana-South America Iapetus margin evolution as recorded by Lower Paleozoic units of western Precordillera, Argentina: The Bonilla Complex, Uspallata

Terrane, accreted to Gondwana South America during Ordovician times. The Bonilla Complex, which represents the southern tip of the Precordillera, is constituted of metasedimentary rocks of internal and external platform environments. Paleocurrents inferred from sedimentary structures indicate provenance from the northeast and southeast (actual coordinates). The limestones of this complex, located in the eastern part of the outcrops, suggest evolution toward a carbonate-dominated Late Neoproterozoic to Cambrian passive margin. Mafic volcanic rocks were emplaced coevally with sedimentation, whereas ultramafic rocks were later tectonically emplaced. Chemical evidence suggests that the protolith of the metasedimentary rocks was derived from an older exhumed felsic basement belonging to an upper continental crust. The most prominent population of detrital zircons (~500- 600 Ma) from the Bonilla Complex support the hypothesis that these rocks are equivalent to those of the Sierras Pampeanas and the northern Patagonia. The most proximal source of the Pampean zircons found in the Bonilla Complex is the Sierras Pampeanas, located immediately to the east (present coordinates). The Bonilla Complex was deposited in an open marine basin considerably earlier (~50 Ma) than the supposed detachment of the Cuyania Terrane from the Ouachita embayment in the Laurentia margin. It is therefore not necessary to invoke the presence of an allochthonous terrane between the Bonilla Complex and the Gondwana margin to explain the 1 Ga zircon populations. Silurian to Devonian deformation was characterized by metamorphism and imbrication within an accretionary prism, the consequence of eastward subduction in the western margin of Gondwana. Therefore, the Bonilla Complex, as well as equivalent units in western Precordillera, was originally deposited as sediments on a continental shelf at the southwestern margin of Gondwana, covering a basement that was already part of the Gondwana continent by Neoproterozoic-Cambrian times.Fil: Gregori, Daniel Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Bahia Blanca. Instituto Geológico del Sur; Argentina;Fil: Martinez, Juan Cruz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Bahia Blanca. Instituto Geológico del Sur; Argentina;Fil: Benedini, Leonardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Bahia Blanca. Instituto Geológico del Sur; Argentina

Overview of Cellular Transplantation in Diabetes Mellitus: Focus on the Metabolic Outcome

Diabetes mellitus is a metabolic disease possible to treat via several different therapeutic approaches. Since the advent of insulin in 1922, type 1 diabetes mellitus has become a chronic treatable disease. Nonetheless, type 1 diabetes mellitus can be a devastating disease when the macro- and microangiopathic complications take place after several years of illness. Starting from the eighties, pancreas/islet transplantation has become a potential innovative treatment of diabetes mellitus. The major advantage of pancreas/islet transplantation is the restoration of c-peptide cosecretion along with insulin; the major disadvantage is the need to administer immunosuppressive drugs which are diabetogenic themselves. Islet transplantation is the progenitor of more recent forms of cellular and stem cell therapies which will be reviewed herein. Cellular therapies for diabetes mellitus are still an experimental procedure. Herein we present the actual current achievements and an outlook of close future possible advancements in the area of cellular transplantation for the cure of diabetes mellitus