Studio dell’acquifero carsico del Cansiglio-Monte Cavallo (Alta valle Livenza, Pordenone) tramite tracciamento multiplo, monitoraggio idrochimico e idrologico

Con questo lavoro si cerca di definire, tramite l’interpretazione dei dati ottenuti da un monitoraggio idrochimico e idrologico di sorgenti e da una prova di tracciamento multiplo grotta-sorgente, la configurazione interna del Massiccio del Cansiglio-Monte Cavallo (Alta Livenza, Pordenone), uno dei maggiori complessi carsici italiani. Molinetto, Santissima e Gorgazzo sono i nomi delle tre sorgenti monitorate. Si tratta di tre grandi sorgenti, tutte posizionate sul versante orientale e sud-orientale del massiccio, le cui acque costituiscono i maggiori apporti del fiume Livenza. Sono ubicate in aree e a quote differenti, con estensioni diverse tra loro, ma tutte con soglia di permeabilità sottoposta (secondo la classificazione Civita, 1972). I dati pregressi ottenuti nei precedenti lavori in queste sorgenti come le misure di portata, il monitoraggio in continuo dei parametri fisico-chimici e i dati idrochimici e isotopici ricavati dal campionamento delle acque, sono stati ampliati con l’aggiunta dei dati del tracciamento acquisiti, fulcro del lavoro di questa tesi. Tramite l’iniezione di tre diversi traccianti artificiali in tre grotte differenti, è stato monitorato l’arrivo del tracciante alle sorgenti grazie a strumenti da campo installati, come fluorimetri e fluocaptori. La combinazione finale di pregresse analisi geochimiche, di un monitoraggio idrodinamico in continuo e di una prova di tracciamento multiplo ha infine dimostrato che le tre sorgenti hanno aree di ricarica differenti. Lo studio è finalizzato a dare un’interpretazione della configurazione del suddetto acquifero carsico. È ritenuto fondamentale studiare questa complicata tipologia di acquiferi perché, nel prossimo futuro, in previsione di carenza d’acqua dovuta a cambiamenti globali e sovrasfruttamento delle acque sotterranee nelle principali pianure urbanizzate, questi potrebbero diventare una risorsa fondamentale come serbatoio strategico di acqua ad alta qualità (Liu et al., 2017)

Efficacy and Dose of Rehabilitation Approaches for Severe Upper Limb Impairments and Disability during Early Acute and Subacute Stroke: A Systematic Review

Objective. The purpose of this study was to examine the evidence regarding the efficacy of rehabilitation approaches for improving severe upper limb impairments and activity during acute and early subacute stroke, taking into consideration the dosage of therapy. Methods. Randomized controlled trials from PubMed, Web of Science, and Scopus databases were searched by 2 independent researchers. Studies were selected if they involved active rehabilitation interventions that were conducted in the acute stage (<7 days after stroke) or the early subacute stage (>7 days–3 months after stroke), with the aim of improving severe upper limb motor impairments and disability. Data were extracted on the basis of the type and effect of rehabilitation interventions, and on the dosage (duration, frequency, session length, episode difficulty, and intensity). Study quality was assessed using the Physiotherapy Evidence Database Scale. Results. Twenty-three studies (1271 participants) with fair to good methodological quality were included. Only 3 studies were performed in the acute stage. Regardless of the type of intervention, upper limb rehabilitation was found to be beneficial for severe upper limb impairments and disability. Robotic therapy and functional electrical stimulation were identified as the most popular upper limb interventions; however, only a limited number of studies showed their superiority over a dose-matched control intervention for severe upper limb impairments in the subacute stage. A longer rehabilitation session length (<60 minutes) did not seem to have a larger impact on the magnitude of improved upper limb impairments. Conclusion. Different rehabilitation approaches seem to improve severe upper limb impairments and disability in the subacute stage after stroke; however, they are not distinctly superior to standard care or other interventions provided at the same dosage. Impact. Robotic therapy and functional electrical stimulation add variety to rehabilitation programs, but their benefit has not been shown to exceed that of standard care. Further research is necessary to identify the impact of dose (eg, intensity) on upper limb motor impairments and function, especially in the acute stage

Experimental Investigation on Spontaneously Active Hippocampal Cultures Recorded by Means of High-Density MEAs: Analysis of the Spatial Resolution Effects

Based on experiments performed with high-resolution Active Pixel Sensor microelectrode arrays (APS-MEAs) coupled with spontaneously active hippocampal cultures, this work investigates the spatial resolution effects of the neuroelectronic interface on the analysis of the recorded electrophysiological signals. The adopted methodology consists, first, in recording the spontaneous activity at the highest spatial resolution (interelectrode separation of 21 μm) from the whole array of 4096 microelectrodes. Then, the full resolution dataset is spatially downsampled in order to evaluate the effects on raster plot representation, array-wide spike rate (AWSR), mean firing rate (MFR) and mean bursting rate (MBR). Furthermore, the effects of the array-to-network relative position are evaluated by shifting a subset of equally spaced electrodes on the entire recorded area. Results highlight that MFR and MBR are particularly influenced by the spatial resolution provided by the neuroelectronic interface. On high-resolution large MEAs, such analysis better represent the time-based parameterization of the network dynamics. Finally, this work suggest interesting capabilities of high-resolution MEAs for spatial-based analysis in dense and low-dense neuronal preparation for investigating signaling at both local and global neuronal circuitries

Dose-dependent fetal complications of warfarin in pregnant women with mechanical heart valves

AbstractOBJECTIVESThe purpose of this study was to assess the incidence of warfarin fetal complications and whether they are dose-dependent.BACKGROUNDGravid patients with mechanical heart valves require long-term anticoagulant therapy. Controversy exists concerning the appropriate treatment of these patients.METHODSForty-three women on warfarin carrying out 58 pregnancies were studied. For each patient with full-term pregnancy a caesarian section was scheduled for the 38th week during brief warfarin discontinuation. Maternal and fetal complications were evaluated. Fetal complications were divided according to the warfarin dosage ≤5 mg and >5 mg necessary to keep an international normalized ratio (INR) of 2.5 to 3.5, and analyzed subsequently.RESULTSA total of 58 pregnancies were observed: 31 healthy babies (30 full term, 1 premature) and 27 fetal complications (22 spontaneous abortions, 2 warfarin embryopathies, 1 stillbirth, 1 ventricular septal defect, 1 growth retardation) were recorded. Two maternal valve thromboses occurred. No fetal or maternal bleeding was observed during caesarian sections or premature vaginal delivery. Patients whose warfarin doses during pregnancy were >5 mg had 22 fetal complications, whereas those taking a dose ≤5 mg had only five fetal complications (p = 0.0001). For an increase of the warfarin dose there was a substantially increased probability of fetal complications (p < 0.0001; ρ < 0.7316).CONCLUSIONSThere is a close dependency between warfarin dosage and fetal complications. Patients on warfarin anticoagulation may be delivered by planned caesarian section at the 38th week while briefly interrupting anticoagulation

Detection and exploitation of white lupin (Lupinus albus L.) genetic variation for seed γ-conglutin content

The seed γ-conglutin protein fraction of white lupin has particular pharmacological interest, but its industrial production is hindered by low content in the seed. This study provides an unprecedented assessment of genotypic and environmental variation for seed content and production of γ-conglutin, exploring also the ability of Near-Infrared Spectroscopy (NIRS) to predict seed γ-conglutin content. Significant (P &lt; 0.01) genetic variation for seed γ-conglutin content emerged among ten genotypes (cultivars or breeding lines) across three environments (range: 1.59-2.02 %) and five genotypes in other two environments (range: 1.47-1.80 %). Genotype variation was found also for seed protein content and γ-conglutin proportion on total protein, the latter trait having higher impact than the former on genotype variation for seed γ-conglutin content. The production of γ-conglutin per unit area was affected also by genotype yielding ability beside genotype seed γ-conglutin content. No genotype × environment interaction was detected for any γ-conglutin trait. NIRS-based prediction based on cross-validations was only moderately accurate for seed γ-conglutin content (R2 = 0.66), while being accurate for seed protein content (R2 = 0.95). In conclusion, breeding for higher seed γ-conglutin content is feasible using data from very few test sites and, to some extent, NIRS-based predictions

Modeling Skeletal Muscle Laminopathies Using Human Induced Pluripotent Stem Cells Carrying Pathogenic LMNA Mutations

Laminopathies are a clinically heterogeneous group of disorders caused by mutations in LMNA. The main proteins encoded by LMNA are Lamin A and C, which together with Lamin B1 and B2, form the nuclear lamina: a mesh-like structure located underneath the inner nuclear membrane. Laminopathies show striking tissue specificity, with subtypes affecting striated muscle, peripheral nerve, and adipose tissue, while others cause multisystem disease with accelerated aging. Although several pathogenic mechanisms have been proposed, the exact pathophysiology of laminopathies remains unclear, compounded by the rarity of these disorders and lack of easily accessible cell types to study. To overcome this limitation, we used induced pluripotent stem cells (iPSCs) from patients with skeletal muscle laminopathies such as LMNA-related congenital muscular dystrophy and limb-girdle muscular dystrophy 1B, to model disease phenotypes in vitro. iPSCs can be derived from readily accessible cell types, have unlimited proliferation potential and can be differentiated into cell types that would otherwise be difficult and invasive to obtain. iPSC lines from three skeletal muscle laminopathy patients were differentiated into inducible myogenic cells and myotubes. Disease-associated phenotypes were observed in these cells, including abnormal nuclear shape and mislocalization of nuclear lamina proteins. Nuclear abnormalities were less pronounced in monolayer cultures of terminally differentiated skeletal myotubes than in proliferating myogenic cells. Notably, skeletal myogenic differentiation of LMNA-mutant iPSCs in artificial muscle constructs improved detection of myonuclear abnormalities compared to conventional monolayer cultures across multiple pathogenic genotypes, providing a high-fidelity modeling platform for skeletal muscle laminopathies. Our results lay the foundation for future iPSC-based therapy development and screening platforms for skeletal muscle laminopathies

Targeted delivery of neutralizing anti-C5 antibody to renal endothelium prevents complement- dependent tissue damage

Complement activation is largely implicated in the pathogenesis of several clinical conditions and its therapeutic neutralization has proven effective in preventing tissue and organ damage. A problem that still needs to be solved in the therapeutic control of complement-mediated diseases is how to avoid side effects associated with chronic neutralization of the complement system, in particular, the increased risk of infections. We addressed this issue developing a strategy based on the preferential delivery of a C5 complement inhibitor to the organ involved in the pathologic process. To this end, we generated Ergidina, a neutralizing recombinant anti-C5 human antibody coupled with a cyclic-RGD peptide, with a distinctive homing property for ischemic endothelial cells and effective in controlling tissue damage in a rat model of renal ischemia/reperfusion injury (IRI). As a result of its preferential localization on renal endothelium, the molecule induced complete inhibition of complement activation at tissue level, and local protection from complement-mediated tissue damage without affecting circulating C5. The ex vivo binding of Ergidina to surgically removed kidney exposed to cold ischemia supports its therapeutic use to prevent posttransplant IRI leading to delay of graft function. Moreover, the finding that the ex vivo binding of Ergidina was not restricted to the kidney, but was also seen on ischemic heart, suggests that this RGD-targeted anti-C5 antibody may represent a useful tool to treat organs prior to transplantation. Based on this evidence, we propose preliminary data showing that Ergidina is a novel targeted drug to prevent complement activation on the endothelium of ischemic kidney

Higher 90-Day Mortality after Surgery for Hip Fractures in Patients with COVID-19: A Case-Control Study from a Single Center in Italy

The mortality of hip fracture (HF) patients is increased by concomitant COVID-19; however, evidence is limited to only short follow-up. A retrospective matched case-control study was designed with the aim to report the 90-day mortality and determine the hazard ratio (HR) of concomitant HF and COVID-19 infection. Cases were patients hospitalized for HF and diagnosed with COVID-19. Controls were patients hospitalized for HF not meeting the criteria for COVID-19 diagnosis and were individually matched with each case through a case-control (1:3) matching algorithm. A total of 89 HF patients were treated during the study period, and 14 of them were diagnosed as COVID-19 positive (overall 15.7%). Patients' demographic, clinical, and surgical characteristics were similar between case and control groups. At 90 days after surgery, 5 deaths were registered among the 14 COVID-19 cases (35.7%) and 4 among the 42 HF controls (9.5%). COVID-19-positive cases had a higher risk of mortality at 30 days (HR = 4.51; p = 0.0490) and 90 days (HR = 4.50; p = 0.025) with respect to controls. Patients with concomitant HF and COVID-19 exhibit high perioperative mortality, which reaches a plateau of nearly 30-35% after 30 to 45 days and is stable up to 90 days. The mortality risk is more than four-fold higher in patients with COVID-19

Effect of Intensive Rehabilitation Program in Thermal Water on a Group of People with Parkinson’s Disease: A Retrospective Longitudinal Study

: The main objective of this study is to test the effect of thermal aquatic exercise on motor symptoms and quality of life in people with Parkinson's Disease (PD). Fourteen participants with diagnosis of idiopathic PD completed the whole rehabilitation session and evaluation protocol (Hoehn and Yahr in OFF state: 2-3; Mini Mental State Examination &gt;24; stable pharmacological treatment in the 3 months prior participating in the study). Cognitive and motor status, functional abilities and quality of life were assessed at baseline and after an intensive rehabilitation program in thermal water (12 sessions of 45 min in a 1.4 m depth pool at 32-36 ∘C). The Mini Balance Evaluation System Test (Mini-BESTest) and the PD Quality of Life Questionnaire (PDQ-39) were considered as main outcomes. Secondary assessment measures evaluated motor symptoms and quality of life and psychological well-being. Participants kept good cognitive and functional status after treatment. Balance of all the participants significantly improved (Mini-BESTest: p&lt;0.01). The PDQ-39 significantly improved after rehabilitation (p=0.038), with significance being driven by dimensions strongly related to motor status. Thermal aquatic exercise may represent a promising rehabilitation tool to prevent the impact of motor symptoms on daily-life activities of people with PD. PDQ-39 improvement foreshows good effects of the intervention on quality of life and psychological well-being