New clinical insight in amyotrophic lateral sclerosis and innovative clinical development from the non-profit repurposing trial of the old drug guanabenz.

Drug repurposing is considered a valid approach to accelerate therapeutic solutions for rare diseases. However, it is not as widely applied as it could be, due to several barriers that discourage both industry and academic institutions from pursuing this path. Herein we present the case of an academic multicentre study that considered the repurposing of the old drug guanabenz as a therapeutic strategy in amyotrophic lateral sclerosis.

The positive impact on translational research of Fondazione italiana di ricerca per la Sclerosi Laterale Amiotrofica (AriSLA), a non-profit foundation focused on amyotrophic lateral sclerosis. Convergence of ex-ante evaluation and ex-post outcomes when goals are set upfront.

Charities investing on rare disease research greatly contribute to generate ground-breaking knowledge with the clear goal of finding a cure for their condition of interest. Although the amount of their investments may be relatively small compared to major funders, the advocacy groups' clear mission promotes innovative research and aggregates highly motivated and mission-oriented scientists. Here, we illustrate the case of Fondazione italiana di ricerca per la Sclerosi Laterale Amiotrofica (AriSLA), the main Italian funding agency entirely dedicated to amyotrophic lateral sclerosis research.

The mental health toll of COVID-19: significant increase in admissions to ICU for voluntary self-inflicted injuries after the beginning of the pandemic.

Background: COVID-19 outbreak deeply impacted on mental health, with high rate of psychological distress in healthcare professionals, patients and general population. Current literature on trauma showed no increase in ICU admissions for deliberate self-inflicted injuries in the first weeks after the beginning of COVID-19.

Objectives: We tested the hypothesis that self-inflicted injuries/harms of any method requiring ICU admission increased in the year following COVID-19 outbreak.

A retrospective analysis of the hemolysis occurrence during extracorporeal membrane oxygenation in a single center.

Introduction: Extracorporeal membrane oxygenation (ECMO)-associated hemolysis still represents a serious complication. The present study aimed to investigate those predictive factors, such as flow rates, the use of anticoagulants, and circuit connected dialysis, that might play a pivotal role in hemolysis in adult patients.

Methods: This is a retrospective single-center case series of 35 consecutive adult patients undergoing veno-venous ECMO support at our center between April 2014 and February 2020.

Closed-aperture unbounded acoustics experimentation using multidimensional deconvolution.

In physical acoustic laboratories, wave propagation experiments often suffer from unwanted reflections at the boundaries of the experimental setup. We propose using multidimensional deconvolution (MDD) to post-process recorded experimental data such that the scattering imprint related to the domain boundary is completely removed and only the Green's functions associated with a scattering object of interest are obtained. The application of the MDD method requires in/out wavefield separation of data recorded along a closed surface surrounding the object of interest, and we propose a decomposition method to separate such data for arbitrary curved surfaces.

Mind-Mindedness and Parenting Stress: A Cross-Sectional Study in a Cohort of Mothers of 3-Month-Old Full-Term and Preterm Infants.

The preterm birth of a child is a sudden event that can disturb the overall family system and its functioning. Many studies have been conducted with the aim of exploring how and the degree to which this event affects the early mother-infant dyadic relationship and maternal well-being, with often mixed findings. The present study investigates the combined effect of preterm birth and parenting stress on mind-mindedness, a parenting dimension that captures how parents represent and treat their children as separate individuals with their own mental states and activities.

Impact of lower limb movement on the hemodynamics of femoropopliteal arteries: A computational study.

Femoropopliteal arteries (FPAs) are subjected to a wide range of deformations, mainly determined by leg movement. FPAs are often affected by atherosclerotic plaque development, presumably influenced by the biomechanics of surrounding tissues. Although abnormal hemodynamics in FPAs appears to be an important factor in driving plaque development, to date it has been investigated in few studies, in which the leg was modeled in either fixed straight or bent configuration.

Comparing the different response of PNS and CNS injured neurons to mesenchymal stem cell treatment.

Mesenchymal stem cells (MSCs) are adult bone marrow-derived stem cells actually proposed indifferently for the therapy of neurological diseases of both the Central (CNS) and the Peripheral Nervous System (PNS), as a panacea able to treat so many different diseases by their immunomodulatory ability and supportive action on neuronal survival. However, the identification of the exact mechanism of MSC action in the different diseases, although mandatory to define their real and concrete utility, is still lacking. Moreover, CNS and PNS neurons present many different biological properties, and it is still unclear if they respond in the same manner not only to MSC treatment, but also to injuries.

Seven Years Cognitive Functioning and Early Assessment in Extremely Low Birth Weight Children.

Infants born preterm are at high risk for the onset of cognitive dysfunctions at school age. The aim of this study was to investigate the association between early neurodevelopmental assessment and the risk of adverse cognitive outcome in extremely low birth weight children. We enrolled all newborns (January 2002 - April 2007) consecutively admitted to our Institution, with a birthweight < 1000 g.

Human Mesenchymal Stem Cells Protect Dorsal Root Ganglia from the Neurotoxic Effect of Cisplatin.

Background/aim: Peripheral neurotoxicity is a dose-limiting factor of many chemotherapeutic agents, including cisplatin. Mesenchymal stem cells are promising for the treatment of several neurological disorders, and our aim was to verify the neuroprotective potential of human mesenchymal stem cells (hMSCs) on dorsal root ganglia (DRG) exposed to cisplatin.

Materials And Methods: DRG were exposed to different cisplatin concentrations and then co-cultured with hMSCs or with hMSC-conditioned medium.

Neurobasal medium toxicity on mature cortical neurons.

Neurobasal medium (NBM) is a widely used medium for neuronal cultures, originally formulated to support survival of rat hippocampal neurons, but then optimized for several other neuronal subtypes. In the present study, the toxic effect of NBM on long-term cortical neuron cultures has been reported and investigated. A significant neuronal cell loss was observed 24 h after the total medium change performed at days in vitro 10.

Elastodynamic Green's function retrieval through single-sided Marchenko inverse scattering.

The solution of the inverse scattering problem for the one-dimensional Schrödinger equation is given by the Marchenko equation. Recently, a Marchenko-type equation has been derived for three-dimensional (3D) acoustic wave fields, whose solution has been shown to recover the Green's functions from points within the medium to its exterior, using only single-sided scattered data. Here we extend this approach to 3D vectorial wave fields that satisfy the elastodynamic wave equation and recover Green's functions from points interior to an elastic, solid-state medium from purely external and one-sided measurements.

A double mechanism for the mesenchymal stem cells' positive effect on pancreatic islets.

The clinical usability of pancreatic islet transplantation for the treatment of type I diabetes, despite some encouraging results, is currently hampered by the short lifespan of the transplanted tissue. In vivo studies have demonstrated that co-transplantation of Mesenchymal Stem Cells (MSCs) with transplanted pancreatic islets is more effective with respect to pancreatic islets alone in ensuring glycemia control in diabetic rats, but the molecular mechanisms of this action are still unclear. The aim of this study was to elucidate the molecular mechanisms of the positive effect of MSCs on pancreatic islet functionality by setting up direct, indirect and mixed co-cultures.

Undifferentiated MSCs are able to myelinate DRG neuron processes through p75.

Over the last few years the therapeutic approach to demyelinating diseases has radically changed, strategies having been developed aimed at partnering the classic symptomatic treatments with the most advanced regenerative medicine tools. At first, the transplantation of myelinogenic cells, Schwann cells or oligodendrocytes was suggested, but the considerable technical difficulties, (poor availability, difficulties in harvesting and culturing, and the problem of rejection in the event of non-autologous sources), shifted attention towards more versatile cellular types, such as Mesenchymal Stem Cells (MSCs). Recent studies have already demonstrate both in vitro and in vivo that glially-primed MSCs (through exposure to chemical cocktails) have myelogenic abilities.

Mesenchymal stem cells support dorsal root ganglion neurons survival by inhibiting the metalloproteinase pathway.

The positive effect of adult undifferentiated mesenchymal stem cells (MSCs) on neuronal survival has already been reported, although the mechanisms by which MSCs exert their effect are still a matter of debate. Here we have demonstrated that MSCs are able to prolong the survival of dorsal root ganglion (DRG) neurons mainly by inhibiting some proteolytic enzymes, and in particular the pathway of metalloproteinases (MMPs), a family of proteins that are involved in many neuronal processes, including survival. The inhibition of MMPs was both direct, by acting on MT-MMP1, and indirect, by acting on those proteins that regulate MMPs' activation, such as Timp-1 and Sparc.

NGF protects dorsal root ganglion neurons from oxaliplatin by modulating JNK/Sapk and ERK1/2.

The involvement of the Mitogen-Activated Protein Kinases (MAPKs) family in platinum derivative-induced peripheral neuropathy has already been demonstrated. In particular, it has been evidenced that in Dorsal Root Ganglion (DRG) neurons prolonged exposure to oxaliplatin (OHP) induces early activation of p38 and ERK1/2, which mediate neuronal apoptosis, while the neuroprotective action of JNK/Sapk is downregulated by the drug treatment. In this study, the exposure of OHP-treated neurons to a neuroprotective stimulus, represented by a high dose of NGF, counteracts OHP-induced neuronal mortality.

Role of MAPKs in platinum-induced neuronal apoptosis.

An unsolved question is how platinum derivatives used for solid cancer therapy cause peripheral neuropathy in patients and apoptosis in "in vitro" models of chemotherapy-induced peripheral neuropathy. DRG neurons from E15 rat embryos were treated with toxic doses of oxaliplatin or cisplatin. Here, the role of MAPKs in neuronal apoptosis was studied.

Adult mesenchymal stem cells support cisplatin-treated dorsal root ganglion survival.

Mesenchymal stem cells (MSCs) have been found to be useful in the management of different models of neurological diseases. In the present study, we tested the possible protective effect of MSCs on sensory dorsal root ganglia (DRG) explants exposed to the toxic effect of CDDP, a widely used anticancer drug. DRG explants cultured on a collagen layer and exposed to NGF for 2h (differentiating neurons) or for 5 days (fully differentiated neurons) were treated with CDDP and subsequently co-cultured with MSCs.

The effects of an early developmental mother-child intervention program on neurodevelopment outcome in very low birth weight infants: a pilot study.

Background: Several studies report increased minor neurodevelopment dysfunctions in children born very low birth weight (VLBW). Usefulness of preventive early intervention programs to improve neurodevelopment outcome of VLBW infants is still under investigation.

Aims: To evaluate the effects of an early post-discharge developmental mother-child intervention program on neurodevelopment outcome at 36 months in VLBW infants.

Comparison of A-mode ultrasound and computed tomography: detection of secretion in maxillary and frontal sinuses in ventilated patients.

Objective: To study the accuracy of A-mode ultrasonography (A-MU) in detecting secretion in maxillary and frontal sinuses in critically ill, intubated patients undergoing mechanical ventilation.

Design: Open study in mechanically ventilated, comatose patients.

Setting: Medical-surgical intensive care unit in the General Hospital of Rovigo.

[Well-differentiated acinic cell carcinoma of the parotid].

Well-differentiated acinic-cell carcinoma of parotid gland. The authors report a case of well-differentiated acinic-cell carcinoma of the parotid gland with an important lymphoid component, whereas in the aspiration a diagnosis of adenolymphoma was made. In our case cytologic examination showed an abundant cellularity, consisting mostly of lymphocytes.

A novel class of cholinergic agents structurally related to 2-morpholinol.

A series of esters and ethers of N-alkylmorpholin-2-ols, and their methiodides, which can be considered cyclic analogues of acetylcholine, were synthesized. The amines were obtained by acylation or etherification of morpholinols with the appropriate acyl chlorides and alcohols. All compounds were tested for their ability to interact with the muscarinic receptor M2 (guinea-pig atria) or M3 (rat ileum and urinary bladder) subtype.